{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q15465","secondaryAccessions":["A4D247","Q75MC9"],"uniProtkbId":"SHH_HUMAN","entryAudit":{"firstPublicDate":"1999-07-15","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1996-11-01","entryVersion":255,"sequenceVersion":1},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"Reference","id":"Ref.2"}],"value":"Sonic hedgehog protein"},"shortNames":[{"value":"SHH"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"}],"value":"3.1.-.-"}]},"alternativeNames":[{"fullName":{"value":"HHG-1"}},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24522195"}],"value":"Shh unprocessed N-terminal signaling and C-terminal autoprocessing domains"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24522195"}],"value":"ShhNC"}]}],"contains":[{"recommendedName":{"fullName":{"value":"Sonic hedgehog protein N-product"},"shortNames":[{"value":"ShhN"}]},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24522195"}],"value":"Shh N-terminal processed signaling domains"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24522195"}],"value":"ShhNp"}]}]}],"flag":"Precursor"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"7590746"},{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:10848"}],"value":"SHH"}}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29995851"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"}],"value":"Precursor of sonic hedgehog, a morphogen that activates the smoothened signaling pathway, and which is essential for a variety of patterning events during development (PubMed:29954986, PubMed:29995851, PubMed:30139912, PubMed:31127104, PubMed:31548691). The C-terminal part of the precursor displays an autoproteolysis and a cholesterol transferase activity, resulting (1) in the cleavage of the full-length protein into two parts, Sonic hedgehog protein N-product and C-product (ShhN and ShhC, respectively) and (2) covalent attachment of a cholesterol moiety to the C-terminus of the newly generated ShhN (By similarity). Both autoproteolysis and a cholesterol transferase activities occur in the endoplasmic reticulum (By similarity). Following additional lipidation, ShhN acts as a morphogen, while ShhC is degraded in the endoplasmic reticulum (By similarity)"}],"commentType":"FUNCTION","molecule":"Sonic hedgehog protein"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10753901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29995851"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31555730"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24522195"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24863049"}],"value":"The dually lipidated sonic hedgehog protein N-product (ShhN) is a morphogen that activates the smoothened signaling pathway, and which is essential for a variety of patterning events during development (PubMed:10753901, PubMed:24522195, PubMed:24863049, PubMed:29995851, PubMed:30139912, PubMed:31127104, PubMed:31548691, PubMed:31555730). Acts by binding to the patched receptor (PTCH1 or PTCH2), relieving smoothened (SMO) inhibition by patched, activating the smoothened signaling pathway and transcription of target genes (PubMed:10753901, PubMed:29995851, PubMed:31548691, PubMed:31555730). In the absence of SHH, patched represses the constitutive signaling activity of SMO (PubMed:10753901). ShhN is widely expressed and plays a key role in the patterning of the central nervous system and limb development (By similarity). Induces ventral cell fate in the neural tube and somites (By similarity). Involved in the patterning of the anterior-posterior axis of the developing limb bud (By similarity). Essential for axon guidance (By similarity)"}],"commentType":"FUNCTION","molecule":"Sonic hedgehog protein N-product"},{"commentType":"CATALYTIC ACTIVITY","molecule":"Sonic hedgehog protein","reaction":{"name":"glycyl-L-cysteinyl-[protein] + cholesterol + H(+) = [protein]-C-terminal glycyl cholesterol ester + N-terminal L-cysteinyl-[protein]","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:59504"},{"database":"Rhea","id":"RHEA-COMP:12707"},{"database":"Rhea","id":"RHEA-COMP:15369"},{"database":"Rhea","id":"RHEA-COMP:15374"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:16113"},{"database":"ChEBI","id":"CHEBI:65250"},{"database":"ChEBI","id":"CHEBI:143135"},{"database":"ChEBI","id":"CHEBI:143140"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"}]},"physiologicalReactions":[{"directionType":"left-to-right","reactionCrossReference":{"database":"Rhea","id":"RHEA:59505"},"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"}]}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19561609"}],"value":"Interacts with HHATL/GUP1 which negatively regulates HHAT-mediated palmitoylation of the SHH N-terminus (By similarity). Interacts with HHIP (PubMed:19561609). Interacts with glypican GPC3 (By similarity)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19561609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22677548"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22902404"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24522195"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"}],"value":"Multimer (PubMed:19561609, PubMed:24522195). Interacts with SCUBE2; SCUBE2 acts as a carrier to promote release of the dual-lipidated sonic hedgehog protein N-product (ShhN) from the cell surface (PubMed:22677548, PubMed:22902404, PubMed:24522195, PubMed:35231446). Interacts with DISP1 via its cholesterol anchor (PubMed:22902404). Interacts with BOC and CDON; BOC and CDON form a heterodimer that acts as a coreceptor for ShhN (By similarity). Interacts with GAS1; GAS1 acts as a coreceptor for ShhN (PubMed:35231446)"}],"commentType":"SUBUNIT","molecule":"Sonic hedgehog protein N-product"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q15465","intActId":"EBI-11666886"},"interactantTwo":{"uniProtKBAccession":"Q96QV1","geneName":"HHIP","intActId":"EBI-6598521"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15465","intActId":"EBI-11666886"},"interactantTwo":{"uniProtKBAccession":"Q13635","geneName":"PTCH1","intActId":"EBI-8775406"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15465","intActId":"EBI-11666886"},"interactantTwo":{"uniProtKBAccession":"Q13635-1","geneName":"PTCH1","intActId":"EBI-13635488"},"numberOfExperiments":11,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Sonic hedgehog protein","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18534984"}],"value":"Co-localizes with HHAT in the ER and Golgi membrane"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"18534984"}],"value":"Endoplasmic reticulum membrane","id":"SL-0097"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"18534984"}],"value":"Golgi apparatus membrane","id":"SL-0134"}}]},{"commentType":"SUBCELLULAR LOCATION","molecule":"Sonic hedgehog protein N-product","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24522195"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"}],"value":"The dual-lipidated sonic hedgehog protein N-product (ShhN) is firmly tethered to the cell membrane where it forms multimers (PubMed:24522195, PubMed:35231446). Further solubilization from the cell surface is achieved by SCUBE2 carrier, which promotes its release from producing cells, allowing it to act as a morphogen for distant signaling (PubMed:24522195, PubMed:35231446). ShhN is then transferred to the CDON-BOC heterodimer and GAS1 coreceptors to reach the patched receptor (PTCH1 or PTCH2) (PubMed:35231446)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24342078"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24522195"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"}],"value":"Secreted","id":"SL-0243"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24522195"}],"value":"Cell membrane","id":"SL-0039"},"topology":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24522195"}],"value":"Lipid-anchor","id":"SL-9901"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10753901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19561609"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"}],"value":"Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain"}],"commentType":"DOMAIN","molecule":"Sonic hedgehog protein N-product"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23118222"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24522195"}],"value":"The Cardin-Weintraub (CW) motif is required for heparan sulfate binding of the solubilized ShhN (PubMed:23118222). The N-terminal palmitoylated peptide is cleaved at the heparan sulfate-binding Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduced the interactions with heparan sulfate and is enhanced by SCUBE2 (PubMed:24522195)"}],"commentType":"DOMAIN","molecule":"Sonic hedgehog protein N-product"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24522195"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26875496"}],"value":"The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (ShhN) (By similarity). Cholesterylation is required for the sonic hedgehog protein N-product targeting to lipid rafts and multimerization (PubMed:24522195, PubMed:26875496). ShhN is the active species in both local and long-range signaling, whereas the C-product (ShhC) is degraded in the endoplasmic reticulum (By similarity)"}],"commentType":"PTM","molecule":"Sonic hedgehog protein"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23118222"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24522195"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34112694"}],"value":"Dually lipidated: a cholesterol moiety is attached to its C-terminus following cleavage (By similarity). N-palmitoylated by HHAT following cholesterylation; palmitoylation is required for sonic hedgehog protein N-product multimerization and full activity (PubMed:34112694). It is a prerequisite for the membrane-proximal positioning (PubMed:24522195). The lipidated N- and C-terminal peptides of ShhN can be cleaved (shedding) (PubMed:24522195). The N-terminal palmitoylated peptide is cleaved at the Cardin-Weintraub (CW) motif site (PubMed:24522195). The cleavage reduces the interactions with heparan sulfate and is enhanced by SCUBE2 (PubMed:23118222, PubMed:24522195)"}],"commentType":"PTM","molecule":"Sonic hedgehog protein N-product"},{"commentType":"MASS SPECTROMETRY","molecule":"Sonic hedgehog protein N-product","method":"Electrospray","molWeight":19.56,"molWeightError":0.0,"note":"Sonic hedgehog protein N-product: soluble product, purified from insect cells.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9593755"}]},{"commentType":"MASS SPECTROMETRY","molecule":"Sonic hedgehog protein N-product","method":"Electrospray","molWeight":20.167,"molWeightError":0.0,"note":"Sonic hedgehog protein N-product: Membrane-bound product, purified from insect cells.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9593755"}]},{"commentType":"DISEASE","disease":{"diseaseId":"Microphthalmia/Coloboma 5","diseaseAccession":"DI-00760","acronym":"MCOPCB5","description":"A disorder of eye formation, ranging from small size of a single eye to complete bilateral absence of ocular tissues. Ocular abnormalities like opacities of the cornea and lens, scaring of the retina and choroid, and other abnormalities may also be present. Ocular colobomas are a set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure).","diseaseCrossReference":{"database":"MIM","id":"611638"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12503095"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Holoprosencephaly 3","diseaseAccession":"DI-00567","acronym":"HPE3","description":"A form of holoprosencephaly, a structural anomaly of the brain in which the developing forebrain fails to correctly separate into right and left hemispheres. It is a genetically and clinically heterogeneous disorder with a wide spectrum of severity, ranging from alobar holoprosencephaly with severe facial abnormalities, such as cyclopia and proboscis, to mild forms that include lobar or microform holoprosencephaly, without cerebral malformations and with mild craniofacial defects. The majority of HPE3 cases are apparently sporadic, although clear examples of autosomal dominant inheritance have been described.","diseaseCrossReference":{"database":"MIM","id":"142945"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10441331"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10556296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11479728"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15107988"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15942952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15942953"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17001669"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8896572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9302262"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Solitary median maxillary central incisor","diseaseAccession":"DI-02316","acronym":"SMMCI","description":"Rare dental anomaly characterized by the congenital absence of one maxillary central incisor.","diseaseCrossReference":{"database":"MIM","id":"147250"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11471164"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15103725"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Triphalangeal thumb with polysyndactyly","diseaseAccession":"DI-02391","acronym":"TPTPS","description":"Autosomal dominant syndrome. It is characterized by a wide spectrum of pre- and post-axial abnormalities due to altered SHH expression pattern during limb development.","diseaseCrossReference":{"database":"MIM","id":"190605"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12837695"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18417549"}]},"note":{"texts":[{"value":"The gene represented in this entry is involved in disease pathogenesis. SHH expression is altered due to disease-causing variants located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Preaxial polydactyly 2","diseaseAccession":"DI-03095","acronym":"PPD2","description":"Polydactyly consists of duplication of the distal phalanx. The thumb in PPD2 is usually opposable and possesses a normal metacarpal.","diseaseCrossReference":{"database":"MIM","id":"174500"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12837695"}]},"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12837695"}],"value":"The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH and result in abnormal, ectopic SHH expression with pathological consequences (PubMed:12837695)"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Hypoplasia or aplasia of tibia with polydactyly","diseaseAccession":"DI-04241","acronym":"THYP","description":"An autosomal dominant disease characterized by hypoplastic or absent tibia, and polydactyly.","diseaseCrossReference":{"database":"MIM","id":"188740"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19847792"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24965254"}]},"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"19847792"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"24965254"}],"value":"The gene represented in this entry is involved in disease pathogenesis. Mutations located in intron 5 of LMBR1 disrupt a long-range, cis-regulatory element of SHH and result in abnormal, ectopic SHH expression with pathological consequences"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Laurin-Sandrow syndrome","diseaseAccession":"DI-04275","acronym":"LSS","description":"A rare autosomal dominant disorder characterized by polysyndactyly of hands and/or feet, mirror image duplication of the feet, nasal defects, and loss of identity between fibula and tibia. Some patients do not have nasal abnormalities (segmental Laurin-Sandrow syndrome).","diseaseCrossReference":{"database":"MIM","id":"135750"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24456159"}]},"note":{"texts":[{"value":"The gene represented in this entry is involved in disease pathogenesis. Abnormal SHH limb expression with pathological consequences is caused by duplications (16-75 kb) involving the ZPA regulatory sequence (ZRS), a SHH long-range cis-regulatory element, located in LMBR1 intron 5 (PubMed:24456159)"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the hedgehog family"}],"commentType":"SIMILARITY"},{"commentType":"WEB RESOURCE","resourceName":"Atlas of Genetics and Cytogenetics in Oncology and Haematology","resourceUrl":"https://atlasgeneticsoncology.org/gene/378/SHH","ftp":false}],"features":[{"type":"Signal","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":23,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9593755"}]},{"type":"Chain","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":462,"modifier":"EXACT"}},"description":"Sonic hedgehog protein","featureId":"PRO_0000013208"},{"type":"Chain","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":197,"modifier":"EXACT"}},"description":"Sonic hedgehog protein N-product","featureId":"PRO_0000013209"},{"type":"Region","location":{"start":{"value":279,"modifier":"EXACT"},"end":{"value":302,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":395,"modifier":"EXACT"},"end":{"value":414,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Motif","location":{"start":{"value":32,"modifier":"EXACT"},"end":{"value":38,"modifier":"EXACT"}},"description":"Cardin-Weintraub","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23118222"}]},{"type":"Compositional bias","location":{"start":{"value":283,"modifier":"EXACT"},"end":{"value":292,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":400,"modifier":"EXACT"},"end":{"value":412,"modifier":"EXACT"}},"description":"Gly residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Binding site","location":{"start":{"value":89,"modifier":"EXACT"},"end":{"value":89,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6DMY"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7G"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7K"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"1"}},{"type":"Binding site","location":{"start":{"value":90,"modifier":"EXACT"},"end":{"value":90,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"1"}},{"type":"Binding site","location":{"start":{"value":90,"modifier":"EXACT"},"end":{"value":90,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6DMY"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7G"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7K"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"2"}},{"type":"Binding site","location":{"start":{"value":95,"modifier":"EXACT"},"end":{"value":95,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6DMY"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7G"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7K"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"1"}},{"type":"Binding site","location":{"start":{"value":125,"modifier":"EXACT"},"end":{"value":125,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6DMY"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7G"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7K"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"1"}},{"type":"Binding site","location":{"start":{"value":126,"modifier":"EXACT"},"end":{"value":126,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"1"}},{"type":"Binding site","location":{"start":{"value":126,"modifier":"EXACT"},"end":{"value":126,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"2"}},{"type":"Binding site","location":{"start":{"value":129,"modifier":"EXACT"},"end":{"value":129,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"2"}},{"type":"Binding site","location":{"start":{"value":131,"modifier":"EXACT"},"end":{"value":131,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29108"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"}],"ligand":{"name":"Ca(2+)","id":"ChEBI:CHEBI:29108","label":"2"}},{"type":"Binding site","location":{"start":{"value":140,"modifier":"EXACT"},"end":{"value":140,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29105"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10753901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31555730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3M1N"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6DMY"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7G"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7K"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RMG"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Zn(2+)","id":"ChEBI:CHEBI:29105"}},{"type":"Binding site","location":{"start":{"value":147,"modifier":"EXACT"},"end":{"value":147,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29105"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10753901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31555730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3M1N"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6DMY"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7G"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7K"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RMG"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Zn(2+)","id":"ChEBI:CHEBI:29105"}},{"type":"Binding site","location":{"start":{"value":182,"modifier":"EXACT"},"end":{"value":182,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:29105"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10753901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20504762"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31548691"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31555730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3M1N"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"3MXW"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6DMY"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7G"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7K"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RMG"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}],"ligand":{"name":"Zn(2+)","id":"ChEBI:CHEBI:29105"}},{"type":"Site","location":{"start":{"value":197,"modifier":"EXACT"},"end":{"value":198,"modifier":"EXACT"}},"description":"Cleavage; by autolysis","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q02936"}]},{"type":"Site","location":{"start":{"value":243,"modifier":"EXACT"},"end":{"value":243,"modifier":"EXACT"}},"description":"Involved in cholesterol transfer","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q02936"}]},{"type":"Site","location":{"start":{"value":267,"modifier":"EXACT"},"end":{"value":267,"modifier":"EXACT"}},"description":"Involved in auto-cleavage","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q02936"}]},{"type":"Site","location":{"start":{"value":270,"modifier":"EXACT"},"end":{"value":270,"modifier":"EXACT"}},"description":"Essential for auto-cleavage","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q02936"}]},{"type":"Lipidation","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":"N-palmitoyl cysteine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18534984"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29995851"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31127104"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31875564"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"34112694"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9593755"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"7MHZ"}]},{"type":"Lipidation","location":{"start":{"value":197,"modifier":"EXACT"},"end":{"value":197,"modifier":"EXACT"}},"description":"Cholesterol glycine ester","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q62226"}]},{"type":"Glycosylation","location":{"start":{"value":278,"modifier":"EXACT"},"end":{"value":278,"modifier":"EXACT"}},"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16335952"}],"featureId":""},{"type":"Natural variant","location":{"start":{"value":6,"modifier":"EXACT"},"end":{"value":6,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023804","alternativeSequence":{"originalSequence":"R","alternativeSequences":["T"]}},{"type":"Natural variant","location":{"start":{"value":17,"modifier":"EXACT"},"end":{"value":17,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062592","alternativeSequence":{"originalSequence":"L","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":26,"modifier":"EXACT"},"end":{"value":26,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062593","alternativeSequence":{"originalSequence":"P","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":27,"modifier":"EXACT"},"end":{"value":27,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15107988"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_039888","alternativeSequence":{"originalSequence":"G","alternativeSequences":["A"]}},{"type":"Natural variant","location":{"start":{"value":31,"modifier":"EXACT"},"end":{"value":31,"modifier":"EXACT"}},"description":"in HPE3; the same mutation in the mouse sequence introduces a cleavage site for a furin-like protease resulting in abnormal protein processing; cleavage at this site removes 11 amino acids from the N-terminal domain and reduces affinity of Shh for Ptch1 and signaling potency in assays using chicken embryo neural plate explants and mouse C3H10T1/2 stem cells; dbSNP:rs28936675","featureCrossReferences":[{"database":"dbSNP","id":"rs28936675"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8896572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9302262"}],"featureId":"VAR_003619","alternativeSequence":{"originalSequence":"G","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":39,"modifier":"EXACT"},"end":{"value":39,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs1428916820","featureCrossReferences":[{"database":"dbSNP","id":"rs1428916820"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062594","alternativeSequence":{"originalSequence":"L","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":53,"modifier":"EXACT"},"end":{"value":53,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062595","alternativeSequence":{"originalSequence":"E","alternativeSequences":["K"]}},{"type":"Natural variant","location":{"start":{"value":83,"modifier":"EXACT"},"end":{"value":83,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062596","alternativeSequence":{"originalSequence":"D","alternativeSequences":["V"]}},{"type":"Natural variant","location":{"start":{"value":84,"modifier":"EXACT"},"end":{"value":84,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062597","alternativeSequence":{"originalSequence":"I","alternativeSequences":["F"]}},{"type":"Natural variant","location":{"start":{"value":88,"modifier":"EXACT"},"end":{"value":88,"modifier":"EXACT"}},"description":"in HPE3; familial; the same mutation in the mouse sequence moderately reduces Ptch1 binding in vitro and signaling potency in chicken embryo neural plate explant assays compared with wild-type sequence; dbSNP:rs104894050","featureCrossReferences":[{"database":"dbSNP","id":"rs104894050"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10556296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009163","alternativeSequence":{"originalSequence":"D","alternativeSequences":["V"]}},{"type":"Natural variant","location":{"start":{"value":100,"modifier":"EXACT"},"end":{"value":100,"modifier":"EXACT"}},"description":"in HPE3; sporadic; in the mouse sequence does not affect signaling activity in any of Shh signaling assays and causes no apparent defects in cholesterol-mediated autoprocessing reactions; dbSNP:rs587778792","featureCrossReferences":[{"database":"dbSNP","id":"rs587778792"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10441331"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009164","alternativeSequence":{"originalSequence":"Q","alternativeSequences":["H"]}},{"type":"Natural variant","location":{"start":{"value":102,"modifier":"EXACT"},"end":{"value":102,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062598","alternativeSequence":{"originalSequence":"C","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":102,"modifier":"EXACT"},"end":{"value":102,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062599","alternativeSequence":{"originalSequence":"C","alternativeSequences":["Y"]}},{"type":"Natural variant","location":{"start":{"value":106,"modifier":"EXACT"},"end":{"value":107,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023805","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":109,"modifier":"EXACT"},"end":{"value":109,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062600","alternativeSequence":{"originalSequence":"L","alternativeSequences":["F"]}},{"type":"Natural variant","location":{"start":{"value":110,"modifier":"EXACT"},"end":{"value":110,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023806","alternativeSequence":{"originalSequence":"A","alternativeSequences":["D"]}},{"type":"Natural variant","location":{"start":{"value":110,"modifier":"EXACT"},"end":{"value":110,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062601","alternativeSequence":{"originalSequence":"A","alternativeSequences":["T"]}},{"type":"Natural variant","location":{"start":{"value":111,"modifier":"EXACT"},"end":{"value":111,"modifier":"EXACT"}},"description":"in SMMCI; dbSNP:rs104894049","featureCrossReferences":[{"database":"dbSNP","id":"rs104894049"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11471164"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_017883","alternativeSequence":{"originalSequence":"I","alternativeSequences":["F"]}},{"type":"Natural variant","location":{"start":{"value":111,"modifier":"EXACT"},"end":{"value":111,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15942952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_039889","alternativeSequence":{"originalSequence":"I","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":115,"modifier":"EXACT"},"end":{"value":115,"modifier":"EXACT"}},"description":"in HPE3; familial; in the mouse sequence shows no change in activities at different temperatures; dbSNP:rs267607047","featureCrossReferences":[{"database":"dbSNP","id":"rs267607047"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10556296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009165","alternativeSequence":{"originalSequence":"N","alternativeSequences":["K"]}},{"type":"Natural variant","location":{"start":{"value":117,"modifier":"EXACT"},"end":{"value":117,"modifier":"EXACT"}},"description":"in HPE3; the same mutation in the mouse sequence causes a failure of Shh processing leading to retention of the immature glycosylated protein within the endoplasmic reticulum of transfected cells; causes a temperature-dependent conformational change that allows Shh to bind Ptch1 at 4 or 32 degrees Celsius but not at 37 degrees Celsius; the mutation drastically reduces signaling potency in chicken embryo neural plate explant assays; dbSNP:rs104894040","featureCrossReferences":[{"database":"dbSNP","id":"rs104894040"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8896572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9302262"}],"featureId":"VAR_003620","alternativeSequence":{"originalSequence":"W","alternativeSequences":["G"]}},{"type":"Natural variant","location":{"start":{"value":117,"modifier":"EXACT"},"end":{"value":117,"modifier":"EXACT"}},"description":"in HPE3; the same mutation in the mouse sequence causes a failure of Shh processing leading to retention of the immature glycosylated protein within the endoplasmic reticulum of transfected cells; causes a temperature-dependent conformational change that allows Shh to bind Ptch1 at 4 or 32 degrees Celsius but not at 37 degrees Celsius; drastically reduces signaling potency in chicken embryo neural plate explant assays; dbSNP:rs104894040","featureCrossReferences":[{"database":"dbSNP","id":"rs104894040"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8896572"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9302262"}],"featureId":"VAR_003621","alternativeSequence":{"originalSequence":"W","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":124,"modifier":"EXACT"},"end":{"value":124,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs1803365850","featureCrossReferences":[{"database":"dbSNP","id":"rs1803365850"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062602","alternativeSequence":{"originalSequence":"V","alternativeSequences":["M"]}},{"type":"Natural variant","location":{"start":{"value":136,"modifier":"EXACT"},"end":{"value":136,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062603","alternativeSequence":{"originalSequence":"E","alternativeSequences":["K"]}},{"type":"Natural variant","location":{"start":{"value":140,"modifier":"EXACT"},"end":{"value":140,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11479728"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_039890","alternativeSequence":{"originalSequence":"H","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":140,"modifier":"EXACT"},"end":{"value":140,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs2117137771","featureCrossReferences":[{"database":"dbSNP","id":"rs2117137771"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15942953"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17001669"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_039891","alternativeSequence":{"originalSequence":"H","alternativeSequences":["Q"]}},{"type":"Natural variant","location":{"start":{"value":143,"modifier":"EXACT"},"end":{"value":143,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062604","alternativeSequence":{"originalSequence":"G","alternativeSequences":["D"]}},{"type":"Natural variant","location":{"start":{"value":144,"modifier":"EXACT"},"end":{"value":144,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062605","alternativeSequence":{"originalSequence":"R","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":147,"modifier":"EXACT"},"end":{"value":147,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062606","alternativeSequence":{"originalSequence":"D","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":150,"modifier":"EXACT"},"end":{"value":150,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062607","alternativeSequence":{"originalSequence":"T","alternativeSequences":["K"]}},{"type":"Natural variant","location":{"start":{"value":150,"modifier":"EXACT"},"end":{"value":150,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023807","alternativeSequence":{"originalSequence":"T","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":156,"modifier":"EXACT"},"end":{"value":156,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs1554494372","featureCrossReferences":[{"database":"dbSNP","id":"rs1554494372"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062608","alternativeSequence":{"originalSequence":"S","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":170,"modifier":"EXACT"},"end":{"value":170,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062609","alternativeSequence":{"originalSequence":"F","alternativeSequences":["C"]}},{"type":"Natural variant","location":{"start":{"value":171,"modifier":"EXACT"},"end":{"value":171,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062610","alternativeSequence":{"originalSequence":"D","alternativeSequences":["H"]}},{"type":"Natural variant","location":{"start":{"value":176,"modifier":"EXACT"},"end":{"value":178,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023808","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":183,"modifier":"EXACT"},"end":{"value":183,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11479728"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_039892","alternativeSequence":{"originalSequence":"C","alternativeSequences":["F"]}},{"type":"Natural variant","location":{"start":{"value":183,"modifier":"EXACT"},"end":{"value":183,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062611","alternativeSequence":{"originalSequence":"C","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":183,"modifier":"EXACT"},"end":{"value":183,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062612","alternativeSequence":{"originalSequence":"C","alternativeSequences":["Y"]}},{"type":"Natural variant","location":{"start":{"value":184,"modifier":"EXACT"},"end":{"value":184,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062613","alternativeSequence":{"originalSequence":"S","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":188,"modifier":"EXACT"},"end":{"value":188,"modifier":"EXACT"}},"description":"in HPE3; familial; dbSNP:rs587778799","featureCrossReferences":[{"database":"dbSNP","id":"rs587778799"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10441331"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16282375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009166","alternativeSequence":{"originalSequence":"E","alternativeSequences":["Q"]}},{"type":"Natural variant","location":{"start":{"value":196,"modifier":"EXACT"},"end":{"value":200,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062614","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":196,"modifier":"EXACT"},"end":{"value":196,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs752650571","featureCrossReferences":[{"database":"dbSNP","id":"rs752650571"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062615","alternativeSequence":{"originalSequence":"G","alternativeSequences":["E"]}},{"type":"Natural variant","location":{"start":{"value":197,"modifier":"EXACT"},"end":{"value":197,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062616","alternativeSequence":{"originalSequence":"G","alternativeSequences":["V"]}},{"type":"Natural variant","location":{"start":{"value":198,"modifier":"EXACT"},"end":{"value":198,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062617","alternativeSequence":{"originalSequence":"C","alternativeSequences":["F"]}},{"type":"Natural variant","location":{"start":{"value":198,"modifier":"EXACT"},"end":{"value":198,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062618","alternativeSequence":{"originalSequence":"C","alternativeSequences":["S"]}},{"type":"Natural variant","location":{"start":{"value":218,"modifier":"EXACT"},"end":{"value":218,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17001669"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062619","alternativeSequence":{"originalSequence":"L","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":222,"modifier":"EXACT"},"end":{"value":222,"modifier":"EXACT"}},"description":"in HPE3; familial; dbSNP:rs587778805","featureCrossReferences":[{"database":"dbSNP","id":"rs587778805"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10441331"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009167","alternativeSequence":{"originalSequence":"D","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":224,"modifier":"EXACT"},"end":{"value":224,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs104894042","featureCrossReferences":[{"database":"dbSNP","id":"rs104894042"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9302262"}],"featureId":"VAR_009168","alternativeSequence":{"originalSequence":"V","alternativeSequences":["E"]}},{"type":"Natural variant","location":{"start":{"value":226,"modifier":"EXACT"},"end":{"value":226,"modifier":"EXACT"}},"description":"in HPE3; familial; dbSNP:rs104894043","featureCrossReferences":[{"database":"dbSNP","id":"rs104894043"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9302262"}],"featureId":"VAR_009169","alternativeSequence":{"originalSequence":"A","alternativeSequences":["T"]}},{"type":"Natural variant","location":{"start":{"value":231,"modifier":"EXACT"},"end":{"value":231,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062620","alternativeSequence":{"originalSequence":"G","alternativeSequences":["V"]}},{"type":"Natural variant","location":{"start":{"value":232,"modifier":"EXACT"},"end":{"value":232,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs1347054935","featureCrossReferences":[{"database":"dbSNP","id":"rs1347054935"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062621","alternativeSequence":{"originalSequence":"R","alternativeSequences":["G"]}},{"type":"Natural variant","location":{"start":{"value":234,"modifier":"EXACT"},"end":{"value":234,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062622","alternativeSequence":{"originalSequence":"L","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":236,"modifier":"EXACT"},"end":{"value":236,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062623","alternativeSequence":{"originalSequence":"S","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":236,"modifier":"EXACT"},"end":{"value":236,"modifier":"EXACT"}},"description":"in HPE3; familial; dbSNP:rs587778806","featureCrossReferences":[{"database":"dbSNP","id":"rs587778806"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10556296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009170","alternativeSequence":{"originalSequence":"S","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":241,"modifier":"EXACT"},"end":{"value":241,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062624","alternativeSequence":{"originalSequence":"F","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":241,"modifier":"EXACT"},"end":{"value":241,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062625","alternativeSequence":{"originalSequence":"F","alternativeSequences":["V"]}},{"type":"Natural variant","location":{"start":{"value":255,"modifier":"EXACT"},"end":{"value":255,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062626","alternativeSequence":{"originalSequence":"I","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":263,"modifier":"EXACT"},"end":{"value":269,"modifier":"EXACT"}},"description":"in HPE3; sporadic","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10556296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009171","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":267,"modifier":"EXACT"},"end":{"value":267,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15107988"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_039893","alternativeSequence":{"originalSequence":"T","alternativeSequences":["I"]}},{"type":"Natural variant","location":{"start":{"value":271,"modifier":"EXACT"},"end":{"value":271,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023809","alternativeSequence":{"originalSequence":"L","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":275,"modifier":"EXACT"},"end":{"value":275,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs556192490","featureCrossReferences":[{"database":"dbSNP","id":"rs556192490"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062627","alternativeSequence":{"originalSequence":"A","alternativeSequences":["E"]}},{"type":"Natural variant","location":{"start":{"value":280,"modifier":"EXACT"},"end":{"value":280,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062628","alternativeSequence":{"originalSequence":"S","alternativeSequences":["W"]}},{"type":"Natural variant","location":{"start":{"value":290,"modifier":"EXACT"},"end":{"value":290,"modifier":"EXACT"}},"description":"in HPE3; sporadic; dbSNP:rs104894047","featureCrossReferences":[{"database":"dbSNP","id":"rs104894047"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10556296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009172","alternativeSequence":{"originalSequence":"G","alternativeSequences":["D"]}},{"type":"Natural variant","location":{"start":{"value":296,"modifier":"EXACT"},"end":{"value":296,"modifier":"EXACT"}},"description":"in HPE3; uncertain significance; dbSNP:rs955894039","featureCrossReferences":[{"database":"dbSNP","id":"rs955894039"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062629","alternativeSequence":{"originalSequence":"G","alternativeSequences":["A"]}},{"type":"Natural variant","location":{"start":{"value":310,"modifier":"EXACT"},"end":{"value":310,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062630","alternativeSequence":{"originalSequence":"R","alternativeSequences":["C"]}},{"type":"Natural variant","location":{"start":{"value":321,"modifier":"EXACT"},"end":{"value":321,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs1803249091","featureCrossReferences":[{"database":"dbSNP","id":"rs1803249091"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062631","alternativeSequence":{"originalSequence":"R","alternativeSequences":["S"]}},{"type":"Natural variant","location":{"start":{"value":332,"modifier":"EXACT"},"end":{"value":332,"modifier":"EXACT"}},"description":"in HPE3 and SMMCI; dbSNP:rs104894052","featureCrossReferences":[{"database":"dbSNP","id":"rs104894052"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15103725"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023810","alternativeSequence":{"originalSequence":"V","alternativeSequences":["A"]}},{"type":"Natural variant","location":{"start":{"value":346,"modifier":"EXACT"},"end":{"value":346,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs2117126655","featureCrossReferences":[{"database":"dbSNP","id":"rs2117126655"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062632","alternativeSequence":{"originalSequence":"A","alternativeSequences":["V"]}},{"type":"Natural variant","location":{"start":{"value":347,"modifier":"EXACT"},"end":{"value":347,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs886042458","featureCrossReferences":[{"database":"dbSNP","id":"rs886042458"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062633","alternativeSequence":{"originalSequence":"P","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":347,"modifier":"EXACT"},"end":{"value":347,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023811","alternativeSequence":{"originalSequence":"P","alternativeSequences":["Q"]}},{"type":"Natural variant","location":{"start":{"value":347,"modifier":"EXACT"},"end":{"value":347,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs886042458","featureCrossReferences":[{"database":"dbSNP","id":"rs886042458"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062634","alternativeSequence":{"originalSequence":"P","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":354,"modifier":"EXACT"},"end":{"value":354,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs2117126521","featureCrossReferences":[{"database":"dbSNP","id":"rs2117126521"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023812","alternativeSequence":{"originalSequence":"I","alternativeSequences":["T"]}},{"type":"Natural variant","location":{"start":{"value":362,"modifier":"EXACT"},"end":{"value":362,"modifier":"EXACT"}},"description":"in HPE3; dbSNP:rs866005910","featureCrossReferences":[{"database":"dbSNP","id":"rs866005910"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062635","alternativeSequence":{"originalSequence":"S","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":363,"modifier":"EXACT"},"end":{"value":363,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17001669"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062636","alternativeSequence":{"originalSequence":"C","alternativeSequences":["Y"]}},{"type":"Natural variant","location":{"start":{"value":364,"modifier":"EXACT"},"end":{"value":364,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062637","alternativeSequence":{"originalSequence":"Y","alternativeSequences":["C"]}},{"type":"Natural variant","location":{"start":{"value":373,"modifier":"EXACT"},"end":{"value":373,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15107988"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_039894","alternativeSequence":{"originalSequence":"A","alternativeSequences":["T"]}},{"type":"Natural variant","location":{"start":{"value":374,"modifier":"EXACT"},"end":{"value":374,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062638","alternativeSequence":{"originalSequence":"H","alternativeSequences":["R"]}},{"type":"Natural variant","location":{"start":{"value":376,"modifier":"EXACT"},"end":{"value":376,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062639","alternativeSequence":{"originalSequence":"A","alternativeSequences":["D"]}},{"type":"Natural variant","location":{"start":{"value":377,"modifier":"EXACT"},"end":{"value":377,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062640","alternativeSequence":{"originalSequence":"F","alternativeSequences":["S"]}},{"type":"Natural variant","location":{"start":{"value":378,"modifier":"EXACT"},"end":{"value":380,"modifier":"EXACT"}},"description":"in HPE3; familial","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009173","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":381,"modifier":"EXACT"},"end":{"value":381,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15221788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_023813","alternativeSequence":{"originalSequence":"R","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":382,"modifier":"EXACT"},"end":{"value":382,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062641","alternativeSequence":{"originalSequence":"L","alternativeSequences":["P"]}},{"type":"Natural variant","location":{"start":{"value":383,"modifier":"EXACT"},"end":{"value":383,"modifier":"EXACT"}},"description":"in HPE3; sporadic; dbSNP:rs137853341","featureCrossReferences":[{"database":"dbSNP","id":"rs137853341"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9302262"}],"featureId":"VAR_009174","alternativeSequence":{"originalSequence":"A","alternativeSequences":["T"]}},{"type":"Natural variant","location":{"start":{"value":391,"modifier":"EXACT"},"end":{"value":391,"modifier":"EXACT"}},"description":"in HPE3; uncertain significance; dbSNP:rs1131692264","featureCrossReferences":[{"database":"dbSNP","id":"rs1131692264"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062642","alternativeSequence":{"originalSequence":"A","alternativeSequences":["T"]}},{"type":"Natural variant","location":{"start":{"value":401,"modifier":"EXACT"},"end":{"value":408,"modifier":"EXACT"}},"description":"in ocular coloboma","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12503095"}],"featureId":"VAR_017884","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":402,"modifier":"EXACT"},"end":{"value":409,"modifier":"EXACT"}},"description":"in HPE3; uncertain significance","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062643","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":404,"modifier":"EXACT"},"end":{"value":408,"modifier":"EXACT"}},"description":"in HPE3; familial","featureId":"VAR_009175","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":405,"modifier":"EXACT"},"end":{"value":409,"modifier":"EXACT"}},"description":"in HPE3; uncertain significance","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062644","alternativeSequence":{}},{"type":"Natural variant","location":{"start":{"value":411,"modifier":"EXACT"},"end":{"value":411,"modifier":"EXACT"}},"description":"in HPE3; uncertain significance","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062645","alternativeSequence":{"originalSequence":"G","alternativeSequences":["GG"]}},{"type":"Natural variant","location":{"start":{"value":416,"modifier":"EXACT"},"end":{"value":416,"modifier":"EXACT"}},"description":"in HPE3; uncertain significance; dbSNP:rs1412744230","featureCrossReferences":[{"database":"dbSNP","id":"rs1412744230"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062646","alternativeSequence":{"originalSequence":"T","alternativeSequences":["A"]}},{"type":"Natural variant","location":{"start":{"value":424,"modifier":"EXACT"},"end":{"value":424,"modifier":"EXACT"}},"description":"in HPE3; familial; dbSNP:rs104894048","featureCrossReferences":[{"database":"dbSNP","id":"rs104894048"}],"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10556296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009176","alternativeSequence":{"originalSequence":"P","alternativeSequences":["A"]}},{"type":"Natural variant","location":{"start":{"value":435,"modifier":"EXACT"},"end":{"value":435,"modifier":"EXACT"}},"description":"in HPE3","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062647","alternativeSequence":{"originalSequence":"Y","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":436,"modifier":"EXACT"},"end":{"value":436,"modifier":"EXACT"}},"description":"in HPE3; sporadic","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10556296"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_009177","alternativeSequence":{"originalSequence":"S","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":456,"modifier":"EXACT"},"end":{"value":456,"modifier":"EXACT"}},"description":"in HPE3; uncertain significance","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19603532"}],"featureId":"VAR_062648","alternativeSequence":{"originalSequence":"G","alternativeSequences":["R"]}},{"type":"Mutagenesis","location":{"start":{"value":24,"modifier":"EXACT"},"end":{"value":24,"modifier":"EXACT"}},"description":"Abolishes palmitoylation, leading to impaired smoothened signaling pathway.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18534984"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29995851"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30139912"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31875564"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9593755"}],"alternativeSequence":{"originalSequence":"C","alternativeSequences":["S","A"]}},{"type":"Mutagenesis","location":{"start":{"value":44,"modifier":"EXACT"},"end":{"value":45,"modifier":"EXACT"}},"description":"Impaired binding to PTCH1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"}],"alternativeSequence":{"originalSequence":"YK","alternativeSequences":["AA"]}},{"type":"Mutagenesis","location":{"start":{"value":77,"modifier":"EXACT"},"end":{"value":77,"modifier":"EXACT"}},"description":"Does not affect binding to PTCH1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"}],"alternativeSequence":{"originalSequence":"T","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":80,"modifier":"EXACT"},"end":{"value":80,"modifier":"EXACT"}},"description":"Reduced interaction with GAS1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"}],"alternativeSequence":{"originalSequence":"Y","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":89,"modifier":"EXACT"},"end":{"value":89,"modifier":"EXACT"}},"description":"Reduced interaction with GAS1 and CDON.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"35231446"}],"alternativeSequence":{"originalSequence":"E","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":111,"modifier":"EXACT"},"end":{"value":115,"modifier":"EXACT"}},"description":"Abolished binding to PTCH1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29995851"}],"alternativeSequence":{"originalSequence":"ISVMN","alternativeSequences":["ESVMK"]}},{"type":"Mutagenesis","location":{"start":{"value":153,"modifier":"EXACT"},"end":{"value":153,"modifier":"EXACT"}},"description":"Impaired binding to PTCH1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":155,"modifier":"EXACT"},"end":{"value":155,"modifier":"EXACT"}},"description":"Impaired binding to PTCH1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"}],"alternativeSequence":{"originalSequence":"R","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":177,"modifier":"EXACT"},"end":{"value":178,"modifier":"EXACT"}},"description":"Impaired binding to PTCH1.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29954986"}],"alternativeSequence":{"originalSequence":"SK","alternativeSequences":["AA"]}},{"type":"Beta strand","location":{"start":{"value":30,"modifier":"EXACT"},"end":{"value":32,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"3M1N"}]},{"type":"Helix","location":{"start":{"value":33,"modifier":"EXACT"},"end":{"value":37,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6E1H"}]},{"type":"Helix","location":{"start":{"value":40,"modifier":"EXACT"},"end":{"value":43,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Beta strand","location":{"start":{"value":47,"modifier":"EXACT"},"end":{"value":51,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Turn","location":{"start":{"value":56,"modifier":"EXACT"},"end":{"value":59,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Helix","location":{"start":{"value":65,"modifier":"EXACT"},"end":{"value":67,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"8Z3A"}]},{"type":"Beta strand","location":{"start":{"value":68,"modifier":"EXACT"},"end":{"value":70,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"8Z2V"}]},{"type":"Helix","location":{"start":{"value":71,"modifier":"EXACT"},"end":{"value":74,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Beta strand","location":{"start":{"value":84,"modifier":"EXACT"},"end":{"value":86,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Beta strand","location":{"start":{"value":91,"modifier":"EXACT"},"end":{"value":93,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"8Z3A"}]},{"type":"Helix","location":{"start":{"value":94,"modifier":"EXACT"},"end":{"value":96,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Helix","location":{"start":{"value":100,"modifier":"EXACT"},"end":{"value":116,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Beta strand","location":{"start":{"value":122,"modifier":"EXACT"},"end":{"value":126,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Beta strand","location":{"start":{"value":135,"modifier":"EXACT"},"end":{"value":137,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"3M1N"}]},{"type":"Helix","location":{"start":{"value":139,"modifier":"EXACT"},"end":{"value":141,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Beta strand","location":{"start":{"value":145,"modifier":"EXACT"},"end":{"value":150,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Helix","location":{"start":{"value":155,"modifier":"EXACT"},"end":{"value":157,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Helix","location":{"start":{"value":158,"modifier":"EXACT"},"end":{"value":167,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Beta strand","location":{"start":{"value":171,"modifier":"EXACT"},"end":{"value":177,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Beta strand","location":{"start":{"value":180,"modifier":"EXACT"},"end":{"value":184,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"6PJV"}]},{"type":"Helix","location":{"start":{"value":188,"modifier":"EXACT"},"end":{"value":190,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0007829","source":"PDB","id":"3MXW"}]}],"keywords":[{"id":"KW-0002","category":"Technical term","name":"3D-structure"},{"id":"KW-0068","category":"PTM","name":"Autocatalytic cleavage"},{"id":"KW-0106","category":"Ligand","name":"Calcium"},{"id":"KW-1003","category":"Cellular component","name":"Cell membrane"},{"id":"KW-0217","category":"Molecular function","name":"Developmental protein"},{"id":"KW-0903","category":"Technical term","name":"Direct protein sequencing"},{"id":"KW-0225","category":"Disease","name":"Disease variant"},{"id":"KW-0256","category":"Cellular component","name":"Endoplasmic reticulum"},{"id":"KW-0325","category":"PTM","name":"Glycoprotein"},{"id":"KW-0333","category":"Cellular component","name":"Golgi apparatus"},{"id":"KW-0370","category":"Disease","name":"Holoprosencephaly"},{"id":"KW-0378","category":"Molecular function","name":"Hydrolase"},{"id":"KW-0449","category":"PTM","name":"Lipoprotein"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"id":"KW-1013","category":"Disease","name":"Microphthalmia"},{"id":"KW-0564","category":"PTM","name":"Palmitate"},{"id":"KW-0645","category":"Molecular function","name":"Protease"},{"id":"KW-1267","category":"Technical term","name":"Proteomics identification"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0964","category":"Cellular component","name":"Secreted"},{"id":"KW-0732","category":"Domain","name":"Signal"},{"id":"KW-0808","category":"Molecular function","name":"Transferase"},{"id":"KW-0862","category":"Ligand","name":"Zinc"}],"references":[{"referenceNumber":1,"citation":{"id":"7590746","citationType":"journal article","authors":["Marigo V.","Roberts D.J.","Lee S.M.K.","Tsukurov O.","Levi T.","Gastier J.M.","Epstein D.J.","Gilbert D.J.","Copeland N.G.","Seidman C.E.","Jenkins N.A.","Seidman J.G.","McMahon A.P.","Tabin C."],"citationCrossReferences":[{"database":"PubMed","id":"7590746"},{"database":"DOI","id":"10.1006/geno.1995.1104"}],"title":"Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog.","publicationDate":"1995","journal":"Genomics","firstPage":"44","lastPage":"51","volume":"28"},"referencePositions":["NUCLEOTIDE SEQUENCE [MRNA]"],"referenceComments":[{"value":"Fetal lung","type":"TISSUE"}]},{"referenceNumber":2,"citation":{"id":"CI-6LTTKT1QIS46G","citationType":"journal article","authors":["Tate G.","Kishimoto K.","Mitsuya T."],"title":"Expression of Sonic hedgehog and its receptor Patched/Smoothened in human cancer cell lines and embryonic organs.","publicationDate":"2000","journal":"J. Biochem. Mol. Biol. Biophys.","firstPage":"27","lastPage":"34","volume":"4"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]"]},{"referenceNumber":3,"citation":{"id":"CI-9GALHV3PQVTVS","citationType":"submission","authoringGroup":["NIEHS SNPs program"],"publicationDate":"SEP-2003","submissionDatabase":"EMBL/GenBank/DDBJ databases"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]"]},{"referenceNumber":4,"citation":{"id":"12853948","citationType":"journal article","authors":["Hillier L.W.","Fulton R.S.","Fulton L.A.","Graves T.A.","Pepin K.H.","Wagner-McPherson C.","Layman D.","Maas J.","Jaeger S.","Walker R.","Wylie K.","Sekhon M.","Becker M.C.","O'Laughlin M.D.","Schaller M.E.","Fewell G.A.","Delehaunty K.D.","Miner T.L.","Nash W.E.","Cordes M.","Du H.","Sun H.","Edwards J.","Bradshaw-Cordum H.","Ali J.","Andrews S.","Isak A.","Vanbrunt A.","Nguyen C.","Du F.","Lamar B.","Courtney L.","Kalicki J.","Ozersky P.","Bielicki L.","Scott K.","Holmes A.","Harkins R.","Harris A.","Strong C.M.","Hou S.","Tomlinson C.","Dauphin-Kohlberg S.","Kozlowicz-Reilly A.","Leonard S.","Rohlfing T.","Rock S.M.","Tin-Wollam A.-M.","Abbott A.","Minx P.","Maupin R.","Strowmatt C.","Latreille P.","Miller N.","Johnson D.","Murray J.","Woessner J.P.","Wendl M.C.","Yang S.-P.","Schultz B.R.","Wallis J.W.","Spieth J.","Bieri T.A.","Nelson J.O.","Berkowicz N.","Wohldmann P.E.","Cook L.L.","Hickenbotham M.T.","Eldred J.","Williams D.","Bedell J.A.","Mardis E.R.","Clifton S.W.","Chissoe S.L.","Marra M.A.","Raymond C.","Haugen E.","Gillett W.","Zhou Y.","James R.","Phelps K.","Iadanoto S.","Bubb K.","Simms E.","Levy R.","Clendenning J.","Kaul R.","Kent W.J.","Furey T.S.","Baertsch R.A.","Brent M.R.","Keibler E.","Flicek P.","Bork P.","Suyama M.","Bailey J.A.","Portnoy M.E.","Torrents D.","Chinwalla A.T.","Gish W.R.","Eddy S.R.","McPherson J.D.","Olson M.V.","Eichler E.E.","Green E.D.","Waterston R.H.","Wilson R.K."],"citationCrossReferences":[{"database":"PubMed","id":"12853948"},{"database":"DOI","id":"10.1038/nature01782"}],"title":"The DNA sequence of human chromosome 7.","publicationDate":"2003","journal":"Nature","firstPage":"157","lastPage":"164","volume":"424"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"]},{"referenceNumber":5,"citation":{"id":"12690205","citationType":"journal article","authors":["Scherer S.W.","Cheung J.","MacDonald J.R.","Osborne L.R.","Nakabayashi K.","Herbrick J.-A.","Carson A.R.","Parker-Katiraee L.","Skaug J.","Khaja R.","Zhang J.","Hudek A.K.","Li M.","Haddad M.","Duggan G.E.","Fernandez B.A.","Kanematsu E.","Gentles S.","Christopoulos C.C.","Choufani S.","Kwasnicka D.","Zheng X.H.","Lai Z.","Nusskern D.R.","Zhang Q.","Gu Z.","Lu F.","Zeesman S.","Nowaczyk M.J.","Teshima I.","Chitayat D.","Shuman C.","Weksberg R.","Zackai E.H.","Grebe T.A.","Cox S.R.","Kirkpatrick S.J.","Rahman N.","Friedman J.M.","Heng H.H.Q.","Pelicci P.G.","Lo-Coco F.","Belloni E.","Shaffer L.G.","Pober B.","Morton C.C.","Gusella J.F.","Bruns G.A.P.","Korf B.R.","Quade B.J.","Ligon A.H.","Ferguson H.","Higgins A.W.","Leach N.T.","Herrick S.R.","Lemyre E.","Farra C.G.","Kim H.-G.","Summers A.M.","Gripp K.W.","Roberts W.","Szatmari P.","Winsor E.J.T.","Grzeschik K.-H.","Teebi A.","Minassian B.A.","Kere J.","Armengol L.","Pujana M.A.","Estivill X.","Wilson M.D.","Koop B.F.","Tosi S.","Moore G.E.","Boright A.P.","Zlotorynski E.","Kerem B.","Kroisel P.M.","Petek E.","Oscier D.G.","Mould S.J.","Doehner H.","Doehner K.","Rommens J.M.","Vincent J.B.","Venter J.C.","Li P.W.","Mural R.J.","Adams M.D.","Tsui L.-C."],"citationCrossReferences":[{"database":"PubMed","id":"12690205"},{"database":"DOI","id":"10.1126/science.1083423"}],"title":"Human chromosome 7: DNA sequence and biology.","publicationDate":"2003","journal":"Science","firstPage":"767","lastPage":"772","volume":"300"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"]},{"referenceNumber":6,"citation":{"id":"9593755","citationType":"journal article","authors":["Pepinsky R.B.","Zeng C.","Wen D.","Rayhorn P.","Baker D.P.","Williams K.P.","Bixler S.A.","Ambrose C.M.","Garber E.A.","Miatkowski K.","Taylor F.R.","Wang E.A.","Galdes A."],"citationCrossReferences":[{"database":"PubMed","id":"9593755"},{"database":"DOI","id":"10.1074/jbc.273.22.14037"}],"title":"Identification of a palmitic acid-modified form of human Sonic hedgehog.","publicationDate":"1998","journal":"J. Biol. Chem.","firstPage":"14037","lastPage":"14045","volume":"273"},"referencePositions":["PROTEIN SEQUENCE OF 24-32","PALMITOYLATION AT CYS-24","CHOLESTERYLATION","MUTAGENESIS OF CYS-24","MASS SPECTROMETRY"]},{"referenceNumber":7,"citation":{"id":"7720571","citationType":"journal article","authors":["Chang D.T.","Lopez A.","von Kessler D.P.","Chiang C.","Simandl B.K.","Zhao R.","Seldin M.F.","Fallon J.F.","Beachy P.A."],"citationCrossReferences":[{"database":"PubMed","id":"7720571"},{"database":"DOI","id":"10.1242/dev.120.11.3339"}],"title":"Products, genetic linkage and limb patterning activity of a murine hedgehog gene.","publicationDate":"1994","journal":"Development","firstPage":"3339","lastPage":"3353","volume":"120"},"referencePositions":["NUCLEOTIDE SEQUENCE [MRNA] OF 119-167"]},{"referenceNumber":8,"citation":{"id":"12837695","citationType":"journal article","authors":["Lettice L.A.","Heaney S.J.H.","Purdie L.A.","Li L.","de Beer P.","Oostra B.A.","Goode D.","Elgar G.","Hill R.E.","de Graaff E."],"citationCrossReferences":[{"database":"PubMed","id":"12837695"},{"database":"DOI","id":"10.1093/hmg/ddg180"}],"title":"A long-range Shh enhancer regulates expression in the developing limb and fin and is associated with preaxial polydactyly.","publicationDate":"2003","journal":"Hum. Mol. Genet.","firstPage":"1725","lastPage":"1735","volume":"12"},"referencePositions":["INVOLVEMENT IN TPTPS","INVOLVEMENT IN PPD2"]},{"referenceNumber":9,"citation":{"id":"16335952","citationType":"journal article","authors":["Liu T.","Qian W.-J.","Gritsenko M.A.","Camp D.G. II","Monroe M.E.","Moore R.J.","Smith R.D."],"citationCrossReferences":[{"database":"PubMed","id":"16335952"},{"database":"DOI","id":"10.1021/pr0502065"}],"title":"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry.","publicationDate":"2005","journal":"J. Proteome Res.","firstPage":"2070","lastPage":"2080","volume":"4"},"referencePositions":["GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278"],"referenceComments":[{"value":"Plasma","type":"TISSUE"}]},{"referenceNumber":10,"citation":{"id":"18534984","citationType":"journal article","authors":["Buglino J.A.","Resh M.D."],"citationCrossReferences":[{"database":"PubMed","id":"18534984"},{"database":"DOI","id":"10.1074/jbc.m803901200"}],"title":"Hhat is a palmitoylacyltransferase with specificity for N-palmitoylation of Sonic Hedgehog.","publicationDate":"2008","journal":"J. Biol. Chem.","firstPage":"22076","lastPage":"22088","volume":"283"},"referencePositions":["PALMITOYLATION AT CYS-24","MUTAGENESIS OF CYS-24","SUBCELLULAR LOCATION"]},{"referenceNumber":11,"citation":{"id":"18417549","citationType":"journal article","authors":["Sun M.","Ma F.","Zeng X.","Liu Q.","Zhao X.-L.","Wu F.-X.","Wu G.-P.","Zhang Z.-F.","Gu B.","Zhao Y.-F.","Tian S.-H.","Lin B.","Kong X.-Y.","Zhang X.-L.","Yang W.","Lo W.H.-Y.","Zhang X."],"citationCrossReferences":[{"database":"PubMed","id":"18417549"},{"database":"DOI","id":"10.1136/jmg.2008.057646"}],"title":"Triphalangeal thumb-polysyndactyly syndrome and syndactyly type IV are caused by genomic duplications involving the long range, limb-specific SHH enhancer.","publicationDate":"2008","journal":"J. Med. Genet.","firstPage":"589","lastPage":"595","volume":"45"},"referencePositions":["INVOLVEMENT IN TPTPS"]},{"referenceNumber":12,"citation":{"id":"19847792","citationType":"journal article","authors":["Wieczorek D.","Pawlik B.","Li Y.","Akarsu N.A.","Caliebe A.","May K.J.","Schweiger B.","Vargas F.R.","Balci S.","Gillessen-Kaesbach G.","Wollnik B."],"citationCrossReferences":[{"database":"PubMed","id":"19847792"},{"database":"DOI","id":"10.1002/humu.21142"}],"title":"A specific mutation in the distant sonic hedgehog (SHH) cis-regulator (ZRS) causes Werner mesomelic syndrome (WMS) while complete ZRS duplications underlie Haas type polysyndactyly and preaxial polydactyly (PPD) with or without triphalangeal thumb.","publicationDate":"2010","journal":"Hum. Mutat.","firstPage":"81","lastPage":"89","volume":"31"},"referencePositions":["INVOLVEMENT IN THYP"]},{"referenceNumber":13,"citation":{"id":"22902404","citationType":"journal article","authors":["Tukachinsky H.","Kuzmickas R.P.","Jao C.Y.","Liu J.","Salic A."],"citationCrossReferences":[{"database":"PubMed","id":"22902404"},{"database":"DOI","id":"10.1016/j.celrep.2012.07.010"}],"title":"Dispatched and scube mediate the efficient secretion of the cholesterol-modified hedgehog ligand.","publicationDate":"2012","journal":"Cell Rep.","firstPage":"308","lastPage":"320","volume":"2"},"referencePositions":["INTERACTION WITH DISP1 AND SCUBE2","SUBUNIT","CAUTION"]},{"referenceNumber":14,"citation":{"id":"31875564","citationType":"journal article","authors":["Asciolla J.J.","Resh M.D."],"citationCrossReferences":[{"database":"PubMed","id":"31875564"},{"database":"DOI","id":"10.1016/j.celrep.2019.11.110"}],"title":"Hedgehog Acyltransferase Promotes Uptake of Palmitoyl-CoA across the Endoplasmic Reticulum Membrane.","publicationDate":"2019","journal":"Cell Rep.","firstPage":"4608","lastPage":"4619","volume":"29"},"referencePositions":["PALMITOYLATION AT CYS-24","MUTAGENESIS OF CYS-24"]},{"referenceNumber":15,"citation":{"id":"22677548","citationType":"journal article","authors":["Creanga A.","Glenn T.D.","Mann R.K.","Saunders A.M.","Talbot W.S.","Beachy P.A."],"citationCrossReferences":[{"database":"PubMed","id":"22677548"},{"database":"DOI","id":"10.1101/gad.191866.112"}],"title":"Scube/You activity mediates release of dually lipid-modified Hedgehog signal in soluble form.","publicationDate":"2012","journal":"Genes Dev.","firstPage":"1312","lastPage":"1325","volume":"26"},"referencePositions":["INTERACTION WITH SCUBE2","SUBUNIT"]},{"referenceNumber":16,"citation":{"id":"23118222","citationType":"journal article","authors":["Ohlig S.","Pickhinke U.","Sirko S.","Bandari S.","Hoffmann D.","Dreier R.","Farshi P.","Goetz M.","Grobe K."],"citationCrossReferences":[{"database":"PubMed","id":"23118222"},{"database":"DOI","id":"10.1074/jbc.m112.356667"}],"title":"An emerging role of Sonic hedgehog shedding as a modulator of heparan sulfate interactions.","publicationDate":"2012","journal":"J. Biol. Chem.","firstPage":"43708","lastPage":"43719","volume":"287"},"referencePositions":["PTM","DOMAIN"]},{"referenceNumber":17,"citation":{"id":"23154980","citationType":"journal article","authors":["Ingham P.W."],"citationCrossReferences":[{"database":"PubMed","id":"23154980"},{"database":"DOI","id":"10.1101/gad.207126.112"}],"title":"Zebrafish genetics gets the Scube on Hedgehog secretion.","publicationDate":"2012","journal":"Genes Dev.","firstPage":"2468","lastPage":"2470","volume":"26"},"referencePositions":["REVIEW"]},{"referenceNumber":18,"citation":{"id":"24522195","citationType":"journal article","authors":["Jakobs P.","Exner S.","Schuermann S.","Pickhinke U.","Bandari S.","Ortmann C.","Kupich S.","Schulz P.","Hansen U.","Seidler D.G.","Grobe K."],"citationCrossReferences":[{"database":"PubMed","id":"24522195"},{"database":"DOI","id":"10.1242/jcs.137695"}],"title":"Scube2 enhances proteolytic Shh processing from the surface of Shh-producing cells.","publicationDate":"2014","journal":"J. Cell Sci.","firstPage":"1726","lastPage":"1737","volume":"127"},"referencePositions":["PTM","INTERACTION WITH SCUBE2","SUBUNIT","SUBCELLULAR LOCATION","FUNCTION"]},{"referenceNumber":19,"citation":{"id":"24342078","citationType":"journal article","authors":["Pettigrew C.A.","Asp E.","Emerson C.P. Jr."],"citationCrossReferences":[{"database":"PubMed","id":"24342078"},{"database":"DOI","id":"10.1016/j.mod.2013.12.002"}],"title":"A new role for Hedgehogs in juxtacrine signaling.","publicationDate":"2014","journal":"Mech. Dev.","firstPage":"137","lastPage":"149","volume":"131"},"referencePositions":["SUBCELLULAR LOCATION"]},{"referenceNumber":20,"citation":{"id":"24456159","citationType":"journal article","authors":["Lohan S.","Spielmann M.","Doelken S.C.","Floettmann R.","Muhammad F.","Baig S.M.","Wajid M.","Huelsemann W.","Habenicht R.","Kjaer K.W.","Patil S.J.","Girisha K.M.","Abarca-Barriga H.H.","Mundlos S.","Klopocki E."],"citationCrossReferences":[{"database":"PubMed","id":"24456159"},{"database":"DOI","id":"10.1111/cge.12352"}],"title":"Microduplications encompassing the Sonic hedgehog limb enhancer ZRS are associated with Haas-type polysyndactyly and Laurin-Sandrow syndrome.","publicationDate":"2014","journal":"Clin. Genet.","firstPage":"318","lastPage":"325","volume":"86"},"referencePositions":["INVOLVEMENT IN LSS"]},{"referenceNumber":21,"citation":{"id":"24965254","citationType":"journal article","authors":["Norbnop P.","Srichomthong C.","Suphapeetiporn K.","Shotelersuk V."],"citationCrossReferences":[{"database":"PubMed","id":"24965254"},{"database":"DOI","id":"10.1038/jhg.2014.50"}],"title":"ZRS 406A>G mutation in patients with tibial hypoplasia, polydactyly and triphalangeal first fingers.","publicationDate":"2014","journal":"J. Hum. Genet.","firstPage":"467","lastPage":"470","volume":"59"},"referencePositions":["INVOLVEMENT IN THYP"]},{"referenceNumber":22,"citation":{"id":"24863049","citationType":"journal article","authors":["Pal K.","Mukhopadhyay S."],"citationCrossReferences":[{"database":"PubMed","id":"24863049"},{"database":"DOI","id":"10.1002/dneu.22193"}],"title":"Primary cilium and sonic hedgehog signaling during neural tube patterning: role of GPCRs and second messengers.","publicationDate":"2015","journal":"Dev. Neurobiol.","firstPage":"337","lastPage":"348","volume":"75"},"referencePositions":["REVIEW","FUNCTION"]},{"referenceNumber":23,"citation":{"id":"26875496","citationType":"journal article","authors":["Xavier G.M.","Seppala M.","Barrell W.","Birjandi A.A.","Geoghegan F.","Cobourne M.T."],"citationCrossReferences":[{"database":"PubMed","id":"26875496"},{"database":"DOI","id":"10.1016/j.ydbio.2016.02.009"}],"title":"Hedgehog receptor function during craniofacial development.","publicationDate":"2016","journal":"Dev. Biol.","firstPage":"198","lastPage":"215","volume":"415"},"referencePositions":["REVIEW","SUBCELLULAR LOCATION","PTM"]},{"referenceNumber":24,"citation":{"id":"10753901","citationType":"journal article","authors":["Pepinsky R.B.","Rayhorn P.","Day E.S.","Dergay A.","Williams K.P.","Galdes A.","Taylor F.R.","Boriack-Sjodin P.A.","Garber E.A."],"citationCrossReferences":[{"database":"PubMed","id":"10753901"},{"database":"DOI","id":"10.1074/jbc.275.15.10995"}],"title":"Mapping sonic hedgehog-receptor interactions by steric interference.","publicationDate":"2000","journal":"J. Biol. Chem.","firstPage":"10995","lastPage":"11001","volume":"275"},"referencePositions":["X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 25-197 IN COMPLEX WITH ZINC IONS","FUNCTION","DOMAIN","SUBUNIT"]},{"referenceNumber":25,"citation":{"id":"19561609","citationType":"journal article","authors":["Bosanac I.","Maun H.R.","Scales S.J.","Wen X.","Lingel A.","Bazan J.F.","de Sauvage F.J.","Hymowitz S.G.","Lazarus R.A."],"citationCrossReferences":[{"database":"PubMed","id":"19561609"},{"database":"DOI","id":"10.1038/nsmb.1632"}],"title":"The structure of SHH in complex with HHIP reveals a recognition role for the Shh pseudo active site in signaling.","publicationDate":"2009","journal":"Nat. Struct. Mol. Biol.","firstPage":"691","lastPage":"697","volume":"16"},"referencePositions":["X-RAY CRYSTALLOGRAPHY (3.01 ANGSTROMS) OF 29-197 IN COMPLEX WITH HHIP; ZINC AND CALCIUM IONS","DOMAIN","INTERACTION WITH HHIP","SUBUNIT"]},{"referenceNumber":26,"citation":{"id":"20504762","citationType":"journal article","authors":["Maun H.R.","Wen X.","Lingel A.","de Sauvage F.J.","Lazarus R.A.","Scales S.J.","Hymowitz S.G."],"citationCrossReferences":[{"database":"PubMed","id":"20504762"},{"database":"DOI","id":"10.1074/jbc.m110.112284"}],"title":"Hedgehog pathway antagonist 5E1 binds hedgehog at the pseudo-active site.","publicationDate":"2010","journal":"J. Biol. Chem.","firstPage":"26570","lastPage":"26580","volume":"285"},"referencePositions":["X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 29-197 IN COMPLEX WITH MONOCLONAL ANTIBODY; ZINC AND CALCIUM IONS","DOMAIN"]},{"referenceNumber":27,"citation":{"id":"29995851","citationType":"journal article","authors":["Qi X.","Schmiege P.","Coutavas E.","Wang J.","Li X."],"citationCrossReferences":[{"database":"PubMed","id":"29995851"},{"database":"DOI","id":"10.1038/s41586-018-0308-7"}],"title":"Structures of human Patched and its complex with native palmitoylated sonic hedgehog.","publicationDate":"2018","journal":"Nature","firstPage":"128","lastPage":"132","volume":"560"},"referencePositions":["STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) OF 24-197 IN COMPLEX WITH PTCH1","FUNCTION","PALMITOYLATION AT CYS-24","MUTAGENESIS OF CYS-24 AND 111-ILE--ASN-115"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"6OEV"}]},{"referenceNumber":28,"citation":{"id":"29954986","citationType":"journal article","authors":["Gong X.","Qian H.","Cao P.","Zhao X.","Zhou Q.","Lei J.","Yan N."],"citationCrossReferences":[{"database":"PubMed","id":"29954986"},{"database":"DOI","id":"10.1126/science.aas8935"}],"title":"Structural basis for the recognition of Sonic Hedgehog by human Patched1.","publicationDate":"2018","journal":"Science","firstPage":"eaas8935","lastPage":"eaas8935","volume":"361"},"referencePositions":["STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 24-197 IN COMPLEX WITH PTCH1; CALCIUM AND ZINC IONS","FUNCTION","MUTAGENESIS OF 44-TYR-LYS-45; THR-77; ARG-153; ARG-155 AND 177-SER-LYS-178"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"6DMY"}]},{"referenceNumber":29,"citation":{"id":"30139912","citationType":"journal article","authors":["Qi X.","Schmiege P.","Coutavas E.","Li X."],"citationCrossReferences":[{"database":"PubMed","id":"30139912"},{"database":"DOI","id":"10.1126/science.aas8843"}],"title":"Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex.","publicationDate":"2018","journal":"Science","firstPage":"eaas8843","lastPage":"eaas8843","volume":"362"},"referencePositions":["STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS) OF 24-197 IN COMPLEX WITH PTCH1; CALCIUM AND ZINC IONS","FUNCTION","PALMITOYLATION AT CYS-24","MUTAGENESIS OF CYS-24"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"6E1H"}]},{"referenceNumber":30,"citation":{"id":"31548691","citationType":"journal article","authors":["Rudolf A.F.","Kinnebrew M.","Kowatsch C.","Ansell T.B.","El Omari K.","Bishop B.","Pardon E.","Schwab R.A.","Malinauskas T.","Qian M.","Duman R.","Covey D.F.","Steyaert J.","Wagner A.","Sansom M.S.P.","Rohatgi R.","Siebold C."],"citationCrossReferences":[{"database":"PubMed","id":"31548691"},{"database":"DOI","id":"10.1038/s41589-019-0370-y"}],"title":"The morphogen Sonic hedgehog inhibits its receptor Patched by a pincer grasp mechanism.","publicationDate":"2019","journal":"Nat. Chem. Biol.","firstPage":"975","lastPage":"982","volume":"15"},"referencePositions":["X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 24-197 IN COMPLEX WITH PTCH1; CALCIUM AND ZINC IONS","FUNCTION"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RVD"}]},{"referenceNumber":31,"citation":{"id":"31127104","citationType":"journal article","authors":["Qian H.","Cao P.","Hu M.","Gao S.","Yan N.","Gong X."],"citationCrossReferences":[{"database":"PubMed","id":"31127104"},{"database":"DOI","id":"10.1038/s41467-019-10234-9"}],"title":"Inhibition of tetrameric Patched1 by Sonic Hedgehog through an asymmetric paradigm.","publicationDate":"2019","journal":"Nat. Commun.","firstPage":"2320","lastPage":"2320","volume":"10"},"referencePositions":["STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 24-197 IN COMPLEX WITH PTCH1; CALCIUM AND ZINC IONS","FUNCTION","PALMITOYLATION AT CYS-24"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7G"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7H"},{"evidenceCode":"ECO:0007744","source":"PDB","id":"6N7K"}]},{"referenceNumber":32,"citation":{"id":"31555730","citationType":"journal article","authors":["Qi C.","Di Minin G.","Vercellino I.","Wutz A.","Korkhov V.M."],"citationCrossReferences":[{"database":"PubMed","id":"31555730"},{"database":"DOI","id":"10.1126/sciadv.aaw6490"}],"title":"Structural basis of sterol recognition by human hedgehog receptor PTCH1.","publicationDate":"2019","journal":"Sci. Adv.","firstPage":"eaaw6490","lastPage":"eaaw6490","volume":"5"},"referencePositions":["STRUCTURE BY ELECTRON MICROSCOPY (3.40 ANGSTROMS) OF 24-197 IN COMPLEX WITH PTCH1 AND ZINC","FUNCTION"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"6RMG"}]},{"referenceNumber":33,"citation":{"id":"34112694","citationType":"journal article","authors":["Jiang Y.","Benz T.L.","Long S.B."],"citationCrossReferences":[{"database":"PubMed","id":"34112694"},{"database":"DOI","id":"10.1126/science.abg4998"}],"title":"Substrate and product complexes reveal mechanisms of Hedgehog acylation by HHAT.","publicationDate":"2021","journal":"Science","firstPage":"1215","lastPage":"1219","volume":"372"},"referencePositions":["STRUCTURE BY ELECTRON MICROSCOPY (2.7 ANGSTROMS) OF 24-31 IN COMPLEX WITH HHAT","PALMITOYLATION AT CYS-24"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"7MHZ"}]},{"referenceNumber":34,"citation":{"id":"35231446","citationType":"journal article","authors":["Huang P.","Wierbowski B.M.","Lian T.","Chan C.","Garcia-Linares S.","Jiang J.","Salic A."],"citationCrossReferences":[{"database":"PubMed","id":"35231446"},{"database":"DOI","id":"10.1016/j.devcel.2022.02.008"}],"title":"Structural basis for catalyzed assembly of the Sonic hedgehog-Patched1 signaling complex.","publicationDate":"2022","journal":"Dev. Cell","firstPage":"670","lastPage":"685","volume":"57"},"referencePositions":["STRUCTURE BY ELECTRON MICROSCOPY (3.00 ANGSTROMS) OF 24-197 IN COMPLEX WITH XENOPUS PTCH1","SUBCELLULAR LOCATION","INTERACTION WITH GAS1 AND SCUBE2","MUTAGENESIS OF TYR-80 AND GLU-89"],"evidences":[{"evidenceCode":"ECO:0007744","source":"PDB","id":"7RHQ"}]},{"referenceNumber":35,"citation":{"id":"8896572","citationType":"journal article","authors":["Roessler E.","Belloni E.","Gaudenz K.","Jay P.","Berta P.","Scherer S.W.","Tsui L.-C.","Muenke M."],"citationCrossReferences":[{"database":"PubMed","id":"8896572"},{"database":"DOI","id":"10.1038/ng1196-357"}],"title":"Mutations in the human Sonic hedgehog gene cause holoprosencephaly.","publicationDate":"1996","journal":"Nat. Genet.","firstPage":"357","lastPage":"360","volume":"14"},"referencePositions":["VARIANTS HPE3 ARG-31; GLY-117 AND ARG-117"]},{"referenceNumber":36,"citation":{"id":"9302262","citationType":"journal article","authors":["Roessler E.","Belloni E.","Gaudenz K.","Vargas F.","Scherer S.W.","Tsui L.-C.","Muenke M."],"citationCrossReferences":[{"database":"PubMed","id":"9302262"},{"database":"DOI","id":"10.1093/hmg/6.11.1847"}],"title":"Mutations in the C-terminal domain of Sonic hedgehog cause holoprosencephaly.","publicationDate":"1997","journal":"Hum. Mol. Genet.","firstPage":"1847","lastPage":"1853","volume":"6"},"referencePositions":["VARIANTS HPE3 ARG-31; GLY-117; ARG-117; GLU-224; THR-226 AND THR-383"]},{"referenceNumber":37,"citation":{"id":"10441331","citationType":"journal article","authors":["Odent S.","Atti-Bitach T.","Blayau M.","Mathieu M.","Aug J.","Delezo de A.L.","Gall J.Y.","Le Marec B.","Munnich A.","David V.","Vekemans M."],"citationCrossReferences":[{"database":"PubMed","id":"10441331"},{"database":"DOI","id":"10.1093/hmg/8.9.1683"}],"title":"Expression of the Sonic hedgehog (SHH) gene during early human development and phenotypic expression of new mutations causing holoprosencephaly.","publicationDate":"1999","journal":"Hum. Mol. Genet.","firstPage":"1683","lastPage":"1689","volume":"8"},"referencePositions":["VARIANTS HPE3 HIS-100; GLN-188 AND ASN-222"]},{"referenceNumber":38,"citation":{"id":"10556296","citationType":"journal article","authors":["Nanni L.","Ming J.E.","Bocian M.","Steinhaus K.","Bianchi D.W.","Die-Smulders C.","Giannotti A.","Imaizumi K.","Jones K.L.","Campo M.D.","Martin R.A.","Meinecke P.","Pierpont M.E.M.","Robin N.H.","Young I.D.","Roessler E.","Muenke M."],"citationCrossReferences":[{"database":"PubMed","id":"10556296"},{"database":"DOI","id":"10.1093/hmg/8.13.2479"}],"title":"The mutational spectrum of the sonic hedgehog gene in holoprosencephaly: SHH mutations cause a significant proportion of autosomal dominant holoprosencephaly.","publicationDate":"1999","journal":"Hum. Mol. Genet.","firstPage":"2479","lastPage":"2488","volume":"8"},"referencePositions":["VARIANTS HPE3 VAL-88; LYS-115; ARG-236; 263-ARG--ALA-269 DEL; ASP-290; ALA-424 AND LEU-436"]},{"referenceNumber":39,"citation":{"id":"11471164","citationType":"journal article","authors":["Nanni L.","Ming J.E.","Du Y.","Hall R.K.","Aldred M.","Bankier A.","Muenke M."],"citationCrossReferences":[{"database":"PubMed","id":"11471164"},{"database":"DOI","id":"10.1002/1096-8628(20010722)102:1<1::aid-ajmg1336>3.0.co;2-u"}],"title":"SHH mutation is associated with solitary median maxillary central incisor: a study of 13 patients and review of the literature.","publicationDate":"2001","journal":"Am. J. Med. Genet.","firstPage":"1","lastPage":"10","volume":"102"},"referencePositions":["VARIANT SMMCI PHE-111"]},{"referenceNumber":40,"citation":{"id":"11479728","citationType":"journal article","authors":["Orioli I.M.","Castilla E.E.","Ming J.E.","Nazer J.","Burle de Aguiar M.J.","Llerena J.C.","Muenke M."],"citationCrossReferences":[{"database":"PubMed","id":"11479728"},{"database":"DOI","id":"10.1007/s004390100537"}],"title":"Identification of novel mutations in SHH and ZIC2 in a South American (ECLAMC) population with holoprosencephaly.","publicationDate":"2001","journal":"Hum. Genet.","firstPage":"1","lastPage":"6","volume":"109"},"referencePositions":["VARIANTS HPE3 PRO-140 AND PHE-183"]},{"referenceNumber":41,"citation":{"id":"12503095","citationType":"journal article","authors":["Schimmenti L.A.","de la Cruz J.","Lewis R.A.","Karkera J.D.","Manligas G.S.","Roessler E.","Muenke M."],"citationCrossReferences":[{"database":"PubMed","id":"12503095"},{"database":"DOI","id":"10.1002/ajmg.a.10884"}],"title":"Novel mutation in sonic hedgehog in non-syndromic colobomatous microphthalmia.","publicationDate":"2003","journal":"Am. J. Med. Genet. A","firstPage":"215","lastPage":"221","volume":"116"},"referencePositions":["VARIANT MCOPCB5 401-SER--GLY-408 DEL"]},{"referenceNumber":42,"citation":{"id":"15103725","citationType":"journal article","authors":["Garavelli L.","Zanacca C.","Caselli G.","Banchini G.","Dubourg C.","David V.","Odent S.","Gurrieri F.","Neri G."],"citationCrossReferences":[{"database":"PubMed","id":"15103725"},{"database":"DOI","id":"10.1002/ajmg.a.20685"}],"title":"Solitary median maxillary central incisor syndrome: clinical case with a novel mutation of sonic hedgehog.","publicationDate":"2004","journal":"Am. J. Med. Genet. A","firstPage":"93","lastPage":"95","volume":"127"},"referencePositions":["VARIANT SMMCI ALA-332"]},{"referenceNumber":43,"citation":{"id":"15107988","citationType":"journal article","authors":["Hehr U.","Gross C.","Diebold U.","Wahl D.","Beudt U.","Heidemann P.","Hehr A.","Mueller D."],"citationCrossReferences":[{"database":"PubMed","id":"15107988"},{"database":"DOI","id":"10.1007/s00431-004-1459-0"}],"title":"Wide phenotypic variability in families with holoprosencephaly and a sonic hedgehog mutation.","publicationDate":"2004","journal":"Eur. J. Pediatr.","firstPage":"347","lastPage":"352","volume":"163"},"referencePositions":["VARIANTS HPE3 ALA-27; ILE-267 AND THR-373"]},{"referenceNumber":44,"citation":{"id":"15221788","citationType":"journal article","authors":["Dubourg C.","Lazaro L.","Pasquier L.","Bendavid C.","Blayau M.","Le Duff F.","Durou M.-R.","Odent S.","David V."],"citationCrossReferences":[{"database":"PubMed","id":"15221788"},{"database":"DOI","id":"10.1002/humu.20056"}],"title":"Molecular screening of SHH, ZIC2, SIX3, and TGIF genes in patients with features of holoprosencephaly spectrum: mutation review and genotype-phenotype correlations.","publicationDate":"2004","journal":"Hum. Mutat.","firstPage":"43","lastPage":"51","volume":"24"},"referencePositions":["VARIANTS HPE3 THR-6; HIS-100; 106-LEU-ASN-107 DEL; ASP-110; ARG-150; 176-GLU--LYS-178 DEL; GLN-188; ASN-222; PRO-271; ALA-332; GLN-347; THR-354 AND PRO-381"]},{"referenceNumber":45,"citation":{"id":"15942952","citationType":"journal article","authors":["El-Jaick K.B.","Brunoni D.","Castilla E.E.","Moreira M.A.","Orioli I.M."],"citationCrossReferences":[{"database":"PubMed","id":"15942952"},{"database":"DOI","id":"10.1002/ajmg.a.30624"}],"title":"SHH Ile111Asp in alobar holoprosencephaly in a proposita, whose mother had only a solitary median maxillary incisor.","publicationDate":"2005","journal":"Am. J. Med. Genet. A","firstPage":"345","lastPage":"345","volume":"136"},"referencePositions":["VARIANT HPE3 ASN-111"]},{"referenceNumber":46,"citation":{"id":"15942953","citationType":"journal article","authors":["Ribeiro L.A.","Richieri-Costa A."],"citationCrossReferences":[{"database":"PubMed","id":"15942953"},{"database":"DOI","id":"10.1002/ajmg.a.30625"}],"title":"Single median maxillary central incisor, hypophyseal tumor, and SHH mutation.","publicationDate":"2005","journal":"Am. J. Med. Genet. A","firstPage":"346","lastPage":"347","volume":"136"},"referencePositions":["VARIANT HPE3 GLN-140"]},{"referenceNumber":47,"citation":{"id":"16282375","citationType":"journal article","authors":["Maity T.","Fuse N.","Beachy P.A."],"citationCrossReferences":[{"database":"PubMed","id":"16282375"},{"database":"DOI","id":"10.1073/pnas.0507848102"}],"title":"Molecular mechanisms of Sonic hedgehog mutant effects in holoprosencephaly.","publicationDate":"2005","journal":"Proc. Natl. Acad. Sci. U.S.A.","firstPage":"17026","lastPage":"17031","volume":"102"},"referencePositions":["CHARACTERIZATION OF VARIANTS HPE3 ARG-31; VAL-88; HIS-100; LYS-115; ARG-117; GLY-117 AND GLN-188"]},{"referenceNumber":48,"citation":{"id":"17001669","citationType":"journal article","authors":["Richieri-Costa A.","Ribeiro L.A."],"citationCrossReferences":[{"database":"PubMed","id":"17001669"},{"database":"DOI","id":"10.1002/ajmg.a.31378"}],"title":"Holoprosencephaly-like phenotype: clinical and genetic perspectives.","publicationDate":"2006","journal":"Am. J. Med. Genet. A","firstPage":"2587","lastPage":"2593","volume":"140"},"referencePositions":["VARIANTS HPE3 GLN-140; PRO-218 AND TYR-363"]},{"referenceNumber":49,"citation":{"id":"19603532","citationType":"journal article","authors":["Roessler E.","El-Jaick K.B.","Dubourg C.","Velez J.I.","Solomon B.D.","Pineda-Alvarez D.E.","Lacbawan F.","Zhou N.","Ouspenskaia M.","Paulussen A.","Smeets H.J.","Hehr U.","Bendavid C.","Bale S.","Odent S.","David V.","Muenke M."],"citationCrossReferences":[{"database":"PubMed","id":"19603532"},{"database":"DOI","id":"10.1002/humu.21090"}],"title":"The mutational spectrum of holoprosencephaly-associated changes within the SHH gene in humans predicts loss-of-function through either key structural alterations of the ligand or its altered synthesis.","publicationDate":"2009","journal":"Hum. Mutat.","firstPage":"E921","lastPage":"E935","volume":"30"},"referencePositions":["VARIANTS HPE3 THR-6; PRO-17; LEU-26; ALA-27; ARG-31; PRO-39; LYS-53; VAL-83; PHE-84; VAL-88; HIS-100; ARG-102; TYR-102; 106-LEU-ASN-107 DEL; PHE-109; THR-110; ASP-110; PHE-111; ASN-111; LYS-115; GLY-117; ARG-117; MET-124; LYS-136; PRO-140; GLN-140; ASP-143; PRO-144; ASN-147; ARG-150; LYS-150; ARG-156; CYS-170; HIS-171; 176-GLU--LYS-178 DEL; ARG-183; PHE-183; TYR-183; LEU-184; GLN-188; GLU-196; 196-GLY--PRO-200 DEL; VAL-197; SER-198; PHE-198; PRO-218; ASN-222; GLU-224; THR-226; VAL-231; GLY-232; PRO-234; ARG-236; ASN-236; VAL-241; LEU-241; ASN-255; 263-ARG--ALA-269 DEL; ILE-267; PRO-271; GLU-275; TRP-280; ASP-290; ALA-296; CYS-310; SER-321; ALA-332; VAL-346; ARG-347; GLN-347; LEU-347; THR-354; LEU-362; TYR-363; CYS-364; THR-373; ARG-374; ASP-376; SER-377; 378-ALA--PHE-380 DEL; PRO-381; PRO-382; THR-383; THR-391; 402-GLY--GLY-409 DEL; 405-ASP--GLY-409 DEL; GLY-411 INS; ALA-416; ALA-424; ASN-435; LEU-436 AND ARG-456"]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"L38518","properties":[{"key":"ProteinId","value":"AAA62179.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"mRNA"}]},{"database":"EMBL","id":"AY422195","properties":[{"key":"ProteinId","value":"AAQ87879.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"AC002484","properties":[{"key":"ProteinId","value":"AAB67604.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"AC078834","properties":[{"key":"ProteinId","value":"AAS01990.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"CH236954","properties":[{"key":"ProteinId","value":"EAL23913.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"CCDS","id":"CCDS5942.1","properties":[{"key":"Description","value":"-"}]},{"database":"RefSeq","id":"NP_000184.1","properties":[{"key":"NucleotideSequenceId","value":"NM_000193.4"}]},{"database":"PDB","id":"3HO5","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"3.01 A"},{"key":"Chains","value":"H=29-197"}]},{"database":"PDB","id":"3M1N","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"1.85 A"},{"key":"Chains","value":"A/B=23-197"}]},{"database":"PDB","id":"3MXW","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"1.83 A"},{"key":"Chains","value":"A=29-197"}]},{"database":"PDB","id":"6DMY","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"3.60 A"},{"key":"Chains","value":"B=24-197"}]},{"database":"PDB","id":"6E1H","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"3.50 A"},{"key":"Chains","value":"C=24-197"}]},{"database":"PDB","id":"6N7G","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"6.80 A"},{"key":"Chains","value":"C/F=24-197"}]},{"database":"PDB","id":"6N7H","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"3.60 A"},{"key":"Chains","value":"C=24-197"}]},{"database":"PDB","id":"6N7K","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"6.50 A"},{"key":"Chains","value":"C/F=24-197"}]},{"database":"PDB","id":"6OEV","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"3.80 A"},{"key":"Chains","value":"C=23-197"}]},{"database":"PDB","id":"6PJV","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"1.43 A"},{"key":"Chains","value":"A=29-197"}]},{"database":"PDB","id":"6RMG","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"3.40 A"},{"key":"Chains","value":"B=21-197"}]},{"database":"PDB","id":"6RVD","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"3.50 A"},{"key":"Chains","value":"C=24-197"}]},{"database":"PDB","id":"7E2I","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"4.07 A"},{"key":"Chains","value":"G=1-462"}]},{"database":"PDB","id":"7MHZ","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"3.20 A"},{"key":"Chains","value":"B=24-31"}]},{"database":"PDB","id":"7RHQ","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"3.53 A"},{"key":"Chains","value":"C=24-197"}]},{"database":"PDB","id":"7URF","properties":[{"key":"Method","value":"EM"},{"key":"Resolution","value":"2.80 A"},{"key":"Chains","value":"B=24-30"}]},{"database":"PDB","id":"8YYZ","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"1.90 A"},{"key":"Chains","value":"A=29-197"}]},{"database":"PDB","id":"8Z2V","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"1.89 A"},{"key":"Chains","value":"A=29-197"}]},{"database":"PDB","id":"8Z39","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"1.80 A"},{"key":"Chains","value":"A=29-197"}]},{"database":"PDB","id":"8Z3A","properties":[{"key":"Method","value":"X-ray"},{"key":"Resolution","value":"1.75 A"},{"key":"Chains","value":"A=29-197"}]},{"database":"PDBsum","id":"3HO5","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"3M1N","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"3MXW","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6DMY","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6E1H","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6N7G","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6N7H","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6N7K","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6OEV","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6PJV","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6RMG","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"6RVD","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"7E2I","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"7MHZ","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"7RHQ","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"7URF","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"8YYZ","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"8Z2V","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"8Z39","properties":[{"key":"Description","value":"-"}]},{"database":"PDBsum","id":"8Z3A","properties":[{"key":"Description","value":"-"}]},{"database":"AlphaFoldDB","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-0355","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-0356","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-0358","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-23837","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-24466","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-30958","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-4936","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-4939","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-7796","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-7968","properties":[{"key":"Description","value":"-"}]},{"database":"EMDB","id":"EMD-8955","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"BioGRID","id":"112365","properties":[{"key":"Interactions","value":"18"}]},{"database":"DIP","id":"DIP-61763N","properties":[{"key":"Description","value":"-"}]},{"database":"FunCoup","id":"Q15465","properties":[{"key":"Number of interactors","value":"306"}]},{"database":"IntAct","id":"Q15465","properties":[{"key":"Interactions","value":"5"}]},{"database":"NDEx","id":"IQUERY-CP-SHH","properties":[{"key":"Evidences","value":"28 NDEx IQuery Curated Pathways"}]},{"database":"STRING","id":"9606.ENSP00000297261","properties":[{"key":"Description","value":"-"}]},{"database":"BindingDB","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"ChEMBL","id":"CHEMBL5602","properties":[{"key":"Description","value":"-"}]},{"database":"DrugCentral","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"MEROPS","id":"C46.002","properties":[{"key":"Description","value":"-"}]},{"database":"GlyCosmos","id":"Q15465","properties":[{"key":"glycosylation","value":"1 site, No reported glycans"}]},{"database":"GlyGen","id":"Q15465","properties":[{"key":"glycosylation","value":"1 site"}]},{"database":"iPTMnet","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"PhosphoSitePlus","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"SwissPalm","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"BioMuta","id":"SHH","properties":[{"key":"Description","value":"-"}]},{"database":"DMDM","id":"6094283","properties":[{"key":"Description","value":"-"}]},{"database":"jPOST","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"MassIVE","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"PaxDb","id":"9606-ENSP00000297261","properties":[{"key":"Description","value":"-"}]},{"database":"PeptideAtlas","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"ABCD","id":"Q15465","properties":[{"key":"antibodies","value":"17 sequenced antibodies"}]},{"database":"Antibodypedia","id":"4514","properties":[{"key":"antibodies","value":"657 antibodies from 45 providers"}]},{"database":"DNASU","id":"6469","properties":[{"key":"Description","value":"-"}]},{"database":"Ensembl","id":"ENST00000297261.7","properties":[{"key":"ProteinId","value":"ENSP00000297261.2"},{"key":"GeneId","value":"ENSG00000164690.8"}]},{"database":"GeneID","id":"6469","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"hsa:6469","properties":[{"key":"Description","value":"-"}]},{"database":"MANE-Select","id":"ENST00000297261.7","properties":[{"key":"ProteinId","value":"ENSP00000297261.2"},{"key":"RefSeqNucleotideId","value":"NM_000193.4"},{"key":"RefSeqProteinId","value":"NP_000184.1"}]},{"database":"UCSC","id":"uc003wmk.2","properties":[{"key":"OrganismName","value":"human"}]},{"database":"AGR","id":"HGNC:10848","properties":[{"key":"Description","value":"-"}]},{"database":"ClinPGx","id":"PA35752","properties":[{"key":"Description","value":"-"}]},{"database":"CTD","id":"6469","properties":[{"key":"Description","value":"-"}]},{"database":"DisGeNET","id":"6469","properties":[{"key":"Description","value":"-"}]},{"database":"GeneCards","id":"SHH","properties":[{"key":"Description","value":"-"}]},{"database":"GeneReviews","id":"SHH","properties":[{"key":"Description","value":"-"}]},{"database":"HGNC","id":"HGNC:10848","properties":[{"key":"GeneName","value":"SHH"}]},{"database":"HPA","id":"ENSG00000164690","properties":[{"key":"ExpressionPatterns","value":"Tissue enhanced (adrenal gland, liver, stomach, urinary bladder)"}]},{"database":"MalaCards","id":"SHH","properties":[{"key":"Description","value":"-"}]},{"database":"MIM","id":"135750","properties":[{"key":"Type","value":"phenotype"}]},{"database":"MIM","id":"142945","properties":[{"key":"Type","value":"phenotype"}]},{"database":"MIM","id":"147250","properties":[{"key":"Type","value":"phenotype"}]},{"database":"MIM","id":"174500","properties":[{"key":"Type","value":"phenotype"}]},{"database":"MIM","id":"188740","properties":[{"key":"Type","value":"phenotype"}]},{"database":"MIM","id":"190605","properties":[{"key":"Type","value":"phenotype"}]},{"database":"MIM","id":"600725","properties":[{"key":"Type","value":"gene"}]},{"database":"MIM","id":"611638","properties":[{"key":"Type","value":"phenotype"}]},{"database":"OpenTargets","id":"ENSG00000164690","properties":[{"key":"Description","value":"-"}]},{"database":"Orphanet","id":"485275","properties":[{"key":"Disease","value":"Acquired schizencephaly"}]},{"database":"Orphanet","id":"93925","properties":[{"key":"Disease","value":"Alobar holoprosencephaly"}]},{"database":"Orphanet","id":"476119","properties":[{"key":"Disease","value":"Autosomal dominant preaxial polydactyly-upperback hypertrichosis syndrome"}]},{"database":"Orphanet","id":"98938","properties":[{"key":"Disease","value":"Colobomatous microphthalmia"}]},{"database":"Orphanet","id":"93321","properties":[{"key":"Disease","value":"Isolated radial hemimelia"}]},{"database":"Orphanet","id":"93924","properties":[{"key":"Disease","value":"Lobar holoprosencephaly"}]},{"database":"Orphanet","id":"280200","properties":[{"key":"Disease","value":"Microform holoprosencephaly"}]},{"database":"Orphanet","id":"93926","properties":[{"key":"Disease","value":"Midline interhemispheric variant of holoprosencephaly"}]},{"database":"Orphanet","id":"93336","properties":[{"key":"Disease","value":"Polydactyly of a triphalangeal thumb"}]},{"database":"Orphanet","id":"220386","properties":[{"key":"Disease","value":"Semilobar holoprosencephaly"}]},{"database":"Orphanet","id":"280195","properties":[{"key":"Disease","value":"Septopreoptic holoprosencephaly"}]},{"database":"Orphanet","id":"93405","properties":[{"key":"Disease","value":"Syndactyly type 4"}]},{"database":"Orphanet","id":"988","properties":[{"key":"Disease","value":"Tibial hemimelia-polysyndactyly-triphalangeal thumb syndrome"}]},{"database":"VEuPathDB","id":"HostDB:ENSG00000164690","properties":[{"key":"Description","value":"-"}]},{"database":"eggNOG","id":"KOG3638","properties":[{"key":"ToxonomicScope","value":"Eukaryota"}]},{"database":"GeneTree","id":"ENSGT00940000159119","properties":[{"key":"Description","value":"-"}]},{"database":"HOGENOM","id":"CLU_034686_0_0_1","properties":[{"key":"Description","value":"-"}]},{"database":"InParanoid","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"OMA","id":"HWVSSLL","properties":[{"key":"Fingerprint","value":"-"}]},{"database":"OrthoDB","id":"5212at2759","properties":[{"key":"Description","value":"-"}]},{"database":"PAN-GO","id":"Q15465","properties":[{"key":"Number of GO annotations","value":"7 GO annotations based on evolutionary models"}]},{"database":"PhylomeDB","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"PathwayCommons","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"Reactome","id":"R-HSA-373080","properties":[{"key":"PathwayName","value":"Class B/2 (Secretin family receptors)"}]},{"database":"Reactome","id":"R-HSA-5358346","properties":[{"key":"PathwayName","value":"Hedgehog ligand biogenesis"}]},{"database":"Reactome","id":"R-HSA-5362768","properties":[{"key":"PathwayName","value":"Hh mutants are degraded by ERAD"}]},{"database":"Reactome","id":"R-HSA-5362798","properties":[{"key":"PathwayName","value":"Release of Hh-Np from the secreting cell"}]},{"database":"Reactome","id":"R-HSA-5632681","properties":[{"key":"PathwayName","value":"Ligand-receptor interactions"}]},{"database":"Reactome","id":"R-HSA-5632684","properties":[{"key":"PathwayName","value":"Hedgehog 'on' state"}]},{"database":"Reactome","id":"R-HSA-5635838","properties":[{"key":"PathwayName","value":"Activation of SMO"}]},{"database":"Reactome","id":"R-HSA-5658034","properties":[{"key":"PathwayName","value":"HHAT G278V doesn't palmitoylate Hh-Np"}]},{"database":"Reactome","id":"R-HSA-9758920","properties":[{"key":"PathwayName","value":"Formation of lateral plate mesoderm"}]},{"database":"Reactome","id":"R-HSA-9796292","properties":[{"key":"PathwayName","value":"Formation of axial mesoderm"}]},{"database":"Reactome","id":"R-HSA-9937080","properties":[{"key":"PathwayName","value":"Developmental Lineage of Multipotent Pancreatic Progenitor Cells"}]},{"database":"SignaLink","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"SIGNOR","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"Agora","id":"ENSG00000164690","properties":[{"key":"NominatedTarget","value":"-"}]},{"database":"BioGRID-ORCS","id":"6469","properties":[{"key":"hits","value":"12 hits in 1151 CRISPR screens"}]},{"database":"ChiTaRS","id":"SHH","properties":[{"key":"OrganismName","value":"human"}]},{"database":"EvolutionaryTrace","id":"Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"GeneWiki","id":"Sonic_hedgehog","properties":[{"key":"Description","value":"-"}]},{"database":"GenomeRNAi","id":"6469","properties":[{"key":"Description","value":"-"}]},{"database":"Pharos","id":"Q15465","properties":[{"key":"DevelopmentLevel","value":"Tchem"}]},{"database":"PRO","id":"PR:Q15465","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP000005640","properties":[{"key":"Component","value":"Chromosome 7"}]},{"database":"RNAct","id":"Q15465","properties":[{"key":"moleculeType","value":"protein"}]},{"database":"Bgee","id":"ENSG00000164690","properties":[{"key":"ExpressionPatterns","value":"Expressed in right lobe of liver and 98 other cell types or tissues"}]},{"database":"ExpressionAtlas","id":"Q15465","properties":[{"key":"ExpressionPatterns","value":"baseline and differential"}]},{"database":"GO","id":"GO:0009986","properties":[{"key":"GoTerm","value":"C:cell surface"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0005829","properties":[{"key":"GoTerm","value":"C:cytosol"},{"key":"GoEvidenceType","value":"TAS:Reactome"}]},{"database":"GO","id":"GO:0005783","properties":[{"key":"GoTerm","value":"C:endoplasmic reticulum"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"18534984"}]},{"database":"GO","id":"GO:0005788","properties":[{"key":"GoTerm","value":"C:endoplasmic reticulum lumen"},{"key":"GoEvidenceType","value":"TAS:Reactome"}]},{"database":"GO","id":"GO:0005789","properties":[{"key":"GoTerm","value":"C:endoplasmic reticulum membrane"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"GO","id":"GO:0031012","properties":[{"key":"GoTerm","value":"C:extracellular matrix"},{"key":"GoEvidenceType","value":"HDA:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0007005","source":"PubMed","id":"28344315"}]},{"database":"GO","id":"GO:0005576","properties":[{"key":"GoTerm","value":"C:extracellular region"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"19561609"}]},{"database":"GO","id":"GO:0005794","properties":[{"key":"GoTerm","value":"C:Golgi apparatus"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"18534984"}]},{"database":"GO","id":"GO:0000139","properties":[{"key":"GoTerm","value":"C:Golgi membrane"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"GO","id":"GO:0045121","properties":[{"key":"GoTerm","value":"C:membrane raft"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0005886","properties":[{"key":"GoTerm","value":"C:plasma membrane"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0005509","properties":[{"key":"GoTerm","value":"F:calcium ion binding"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"19561609"}]},{"database":"GO","id":"GO:0140853","properties":[{"key":"GoTerm","value":"F:cholesterol-protein transferase activity"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0004175","properties":[{"key":"GoTerm","value":"F:endopeptidase activity"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0005539","properties":[{"key":"GoTerm","value":"F:glycosaminoglycan binding"},{"key":"GoEvidenceType","value":"IEA:Ensembl"}]},{"database":"GO","id":"GO:0043237","properties":[{"key":"GoTerm","value":"F:laminin-1 binding"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0016015","properties":[{"key":"GoTerm","value":"F:morphogen activity"},{"key":"GoEvidenceType","value":"TAS:ParkinsonsUK-UCL"}],"evidences":[{"evidenceCode":"ECO:0000304","source":"PubMed","id":"24431302"}]},{"database":"GO","id":"GO:0005113","properties":[{"key":"GoTerm","value":"F:patched binding"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"11472839"}]},{"database":"GO","id":"GO:0008270","properties":[{"key":"GoTerm","value":"F:zinc ion binding"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"19561609"}]},{"database":"GO","id":"GO:0008209","properties":[{"key":"GoTerm","value":"P:androgen metabolic process"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0097190","properties":[{"key":"GoTerm","value":"P:apoptotic signaling pathway"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0007411","properties":[{"key":"GoTerm","value":"P:axon guidance"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0001569","properties":[{"key":"GoTerm","value":"P:branching involved in blood vessel morphogenesis"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0001658","properties":[{"key":"GoTerm","value":"P:branching involved in ureteric bud morphogenesis"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0048754","properties":[{"key":"GoTerm","value":"P:branching morphogenesis of an epithelial tube"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0043369","properties":[{"key":"GoTerm","value":"P:CD4-positive or CD8-positive, alpha-beta T cell lineage commitment"},{"key":"GoEvidenceType","value":"IDA:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"17227833"}]},{"database":"GO","id":"GO:0048468","properties":[{"key":"GoTerm","value":"P:cell development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0001708","properties":[{"key":"GoTerm","value":"P:cell fate specification"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0007267","properties":[{"key":"GoTerm","value":"P:cell-cell signaling"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0007417","properties":[{"key":"GoTerm","value":"P:central nervous system development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0021930","properties":[{"key":"GoTerm","value":"P:cerebellar granule cell precursor proliferation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0003140","properties":[{"key":"GoTerm","value":"P:determination of left/right asymmetry in lateral mesoderm"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:0071542","properties":[{"key":"GoTerm","value":"P:dopaminergic neuron differentiation"},{"key":"GoEvidenceType","value":"TAS:ParkinsonsUK-UCL"}],"evidences":[{"evidenceCode":"ECO:0000304","source":"PubMed","id":"24431302"}]},{"database":"GO","id":"GO:0009953","properties":[{"key":"GoTerm","value":"P:dorsal/ventral pattern formation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0042733","properties":[{"key":"GoTerm","value":"P:embryonic digit morphogenesis"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0030326","properties":[{"key":"GoTerm","value":"P:embryonic limb morphogenesis"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0009880","properties":[{"key":"GoTerm","value":"P:embryonic pattern specification"},{"key":"GoEvidenceType","value":"TAS:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000304","source":"PubMed","id":"11001584"}]},{"database":"GO","id":"GO:0060684","properties":[{"key":"GoTerm","value":"P:epithelial-mesenchymal cell signaling"},{"key":"GoEvidenceType","value":"IDA:MGI"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"12221011"}]},{"database":"GO","id":"GO:0030900","properties":[{"key":"GoTerm","value":"P:forebrain development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0007507","properties":[{"key":"GoTerm","value":"P:heart development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0001947","properties":[{"key":"GoTerm","value":"P:heart looping"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:0030902","properties":[{"key":"GoTerm","value":"P:hindbrain development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0016539","properties":[{"key":"GoTerm","value":"P:intein-mediated protein splicing"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:0030324","properties":[{"key":"GoTerm","value":"P:lung development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0002320","properties":[{"key":"GoTerm","value":"P:lymphoid progenitor cell differentiation"},{"key":"GoEvidenceType","value":"IMP:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"14764698"}]},{"database":"GO","id":"GO:0030539","properties":[{"key":"GoTerm","value":"P:male genitalia development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0072205","properties":[{"key":"GoTerm","value":"P:metanephric collecting duct development"},{"key":"GoEvidenceType","value":"IEP:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000270","source":"PubMed","id":"17850284"}]},{"database":"GO","id":"GO:0072136","properties":[{"key":"GoTerm","value":"P:metanephric mesenchymal cell proliferation involved in metanephros development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0001656","properties":[{"key":"GoTerm","value":"P:metanephros development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0030901","properties":[{"key":"GoTerm","value":"P:midbrain development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0043066","properties":[{"key":"GoTerm","value":"P:negative regulation of apoptotic process"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0045596","properties":[{"key":"GoTerm","value":"P:negative regulation of cell differentiation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0030336","properties":[{"key":"GoTerm","value":"P:negative regulation of cell migration"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0090370","properties":[{"key":"GoTerm","value":"P:negative regulation of cholesterol efflux"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:1904339","properties":[{"key":"GoTerm","value":"P:negative regulation of dopaminergic neuron differentiation"},{"key":"GoEvidenceType","value":"IEA:Ensembl"}]},{"database":"GO","id":"GO:0010629","properties":[{"key":"GoTerm","value":"P:negative regulation of gene expression"},{"key":"GoEvidenceType","value":"IEA:Ensembl"}]},{"database":"GO","id":"GO:2000357","properties":[{"key":"GoTerm","value":"P:negative regulation of kidney smooth muscle cell differentiation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0000122","properties":[{"key":"GoTerm","value":"P:negative regulation of transcription by RNA polymerase II"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:2000062","properties":[{"key":"GoTerm","value":"P:negative regulation of ureter smooth muscle cell differentiation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0045060","properties":[{"key":"GoTerm","value":"P:negative thymic T cell selection"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0001755","properties":[{"key":"GoTerm","value":"P:neural crest cell migration"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0007405","properties":[{"key":"GoTerm","value":"P:neuroblast proliferation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0048663","properties":[{"key":"GoTerm","value":"P:neuron fate commitment"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0048709","properties":[{"key":"GoTerm","value":"P:oligodendrocyte differentiation"},{"key":"GoEvidenceType","value":"IBA:GO_Central"}]},{"database":"GO","id":"GO:0007389","properties":[{"key":"GoTerm","value":"P:pattern specification process"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0009949","properties":[{"key":"GoTerm","value":"P:polarity specification of anterior/posterior axis"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0046638","properties":[{"key":"GoTerm","value":"P:positive regulation of alpha-beta T cell differentiation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0051781","properties":[{"key":"GoTerm","value":"P:positive regulation of cell division"},{"key":"GoEvidenceType","value":"IDA:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"11331587"}]},{"database":"GO","id":"GO:0008284","properties":[{"key":"GoTerm","value":"P:positive regulation of cell population proliferation"},{"key":"GoEvidenceType","value":"IDA:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"11331587"}]},{"database":"GO","id":"GO:0045893","properties":[{"key":"GoTerm","value":"P:positive regulation of DNA-templated transcription"},{"key":"GoEvidenceType","value":"IDA:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"10654605"}]},{"database":"GO","id":"GO:0033092","properties":[{"key":"GoTerm","value":"P:positive regulation of immature T cell proliferation in thymus"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:2000358","properties":[{"key":"GoTerm","value":"P:positive regulation of kidney smooth muscle cell differentiation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:2000729","properties":[{"key":"GoTerm","value":"P:positive regulation of mesenchymal cell proliferation involved in ureter development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0061189","properties":[{"key":"GoTerm","value":"P:positive regulation of sclerotome development"},{"key":"GoEvidenceType","value":"IDA:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"10654605"}]},{"database":"GO","id":"GO:0045880","properties":[{"key":"GoTerm","value":"P:positive regulation of smoothened signaling pathway"},{"key":"GoEvidenceType","value":"IDA:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"19561609"},{"evidenceCode":"ECO:0000314","source":"PubMed","id":"24342078"}]},{"database":"GO","id":"GO:0033089","properties":[{"key":"GoTerm","value":"P:positive regulation of T cell differentiation in thymus"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0045944","properties":[{"key":"GoTerm","value":"P:positive regulation of transcription by RNA polymerase II"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:2000063","properties":[{"key":"GoTerm","value":"P:positive regulation of ureter smooth muscle cell differentiation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0045059","properties":[{"key":"GoTerm","value":"P:positive thymic T cell selection"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0030850","properties":[{"key":"GoTerm","value":"P:prostate gland development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0016540","properties":[{"key":"GoTerm","value":"P:protein autoprocessing"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0042127","properties":[{"key":"GoTerm","value":"P:regulation of cell population proliferation"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0010468","properties":[{"key":"GoTerm","value":"P:regulation of gene expression"},{"key":"GoEvidenceType","value":"IBA:GO_Central"}]},{"database":"GO","id":"GO:1900107","properties":[{"key":"GoTerm","value":"P:regulation of nodal signaling pathway"},{"key":"GoEvidenceType","value":"NAS:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"17507406"}]},{"database":"GO","id":"GO:0042481","properties":[{"key":"GoTerm","value":"P:regulation of odontogenesis"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:1900180","properties":[{"key":"GoTerm","value":"P:regulation of protein localization to nucleus"},{"key":"GoEvidenceType","value":"IDA:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"11331587"}]},{"database":"GO","id":"GO:0030162","properties":[{"key":"GoTerm","value":"P:regulation of proteolysis"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0048745","properties":[{"key":"GoTerm","value":"P:smooth muscle tissue development"},{"key":"GoEvidenceType","value":"IEP:UniProtKB"}],"evidences":[{"evidenceCode":"ECO:0000270","source":"PubMed","id":"17850284"}]},{"database":"GO","id":"GO:0007224","properties":[{"key":"GoTerm","value":"P:smoothened signaling pathway"},{"key":"GoEvidenceType","value":"IDA:FlyBase"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"31279575"}]},{"database":"GO","id":"GO:0061053","properties":[{"key":"GoTerm","value":"P:somite development"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:0048864","properties":[{"key":"GoTerm","value":"P:stem cell development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0033077","properties":[{"key":"GoTerm","value":"P:T cell differentiation in thymus"},{"key":"GoEvidenceType","value":"ISS:BHF-UCL"}]},{"database":"GO","id":"GO:0048538","properties":[{"key":"GoTerm","value":"P:thymus development"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0001570","properties":[{"key":"GoTerm","value":"P:vasculogenesis"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0007418","properties":[{"key":"GoTerm","value":"P:ventral midline development"},{"key":"GoEvidenceType","value":"TAS:BHF-UCL"}],"evidences":[{"evidenceCode":"ECO:0000304","source":"PubMed","id":"11001584"}]},{"database":"CDD","id":"cd00081","properties":[{"key":"EntryName","value":"Hint"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"2.170.16.10:FF:000001","properties":[{"key":"EntryName","value":"Indian hedgehog"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"3.30.1380.10:FF:000001","properties":[{"key":"EntryName","value":"Indian hedgehog"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.30.1380.10","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"2.170.16.10","properties":[{"key":"EntryName","value":"Hedgehog/Intein (Hint) domain"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR001657","properties":[{"key":"EntryName","value":"Hedgehog"}]},{"database":"InterPro","id":"IPR001767","properties":[{"key":"EntryName","value":"Hedgehog_Hint"}]},{"database":"InterPro","id":"IPR050387","properties":[{"key":"EntryName","value":"Hedgehog_Signaling"}]},{"database":"InterPro","id":"IPR000320","properties":[{"key":"EntryName","value":"Hedgehog_signalling_dom"}]},{"database":"InterPro","id":"IPR003586","properties":[{"key":"EntryName","value":"Hint_dom_C"}]},{"database":"InterPro","id":"IPR003587","properties":[{"key":"EntryName","value":"Hint_dom_N"}]},{"database":"InterPro","id":"IPR036844","properties":[{"key":"EntryName","value":"Hint_dom_sf"}]},{"database":"InterPro","id":"IPR006141","properties":[{"key":"EntryName","value":"Intein_N"}]},{"database":"InterPro","id":"IPR009045","properties":[{"key":"EntryName","value":"Zn_M74/Hedgehog-like"}]},{"database":"PANTHER","id":"PTHR11889","properties":[{"key":"EntryName","value":"HEDGEHOG"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR11889:SF36","properties":[{"key":"EntryName","value":"SONIC HEDGEHOG PROTEIN"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF01085","properties":[{"key":"EntryName","value":"HH_signal"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF01079","properties":[{"key":"EntryName","value":"Hint"},{"key":"MatchStatus","value":"1"}]},{"database":"PIRSF","id":"PIRSF009400","properties":[{"key":"EntryName","value":"Peptidase_C46"},{"key":"MatchStatus","value":"1"}]},{"database":"PRINTS","id":"PR00632","properties":[{"key":"EntryName","value":"SONICHHOG"}]},{"database":"SMART","id":"SM00305","properties":[{"key":"EntryName","value":"HintC"},{"key":"MatchStatus","value":"1"}]},{"database":"SMART","id":"SM00306","properties":[{"key":"EntryName","value":"HintN"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF55166","properties":[{"key":"EntryName","value":"Hedgehog/DD-peptidase"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF51294","properties":[{"key":"EntryName","value":"Hedgehog/intein (Hint) domain"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS50817","properties":[{"key":"EntryName","value":"INTEIN_N_TER"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MLLLARCLLLVLVSSLLVCSGLACGPGRGFGKRRHPKKLTPLAYKQFIPNVAEKTLGASGRYEGKISRNSERFKELTPNYNPDIIFKDEENTGADRLMTQRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAENSVAAKSGGCFPGSATVHLEQGGTKLVKDLSPGDRVLAADDQGRLLYSDFLTFLDRDDGAKKVFYVIETREPRERLLLTAAHLLFVAPHNDSATGEPEASSGSGPPSGGALGPRALFASRVRPGQRVYVVAERDGDRRLLPAAVHSVTLSEEAAGAYAPLTAQGTILINRVLASCYAVIEEHSWAHRAFAPFRLAHALLAALAPARTDRGGDSGGGDRGGGGGRVALTAPGAADAPGAGATAGIHWYSQLLYQIGTWLLDSEALHPLGMAVKSS","length":462,"molWeight":49607,"crc64":"DD687AFA582A4749","md5":"DE7C46413CAFD35F32F55196538802D6"},"extraAttributes":{"countByCommentType":{"FUNCTION":2,"CATALYTIC ACTIVITY":1,"SUBUNIT":2,"INTERACTION":3,"SUBCELLULAR LOCATION":2,"DOMAIN":2,"PTM":2,"MASS SPECTROMETRY":2,"DISEASE":7,"SIMILARITY":1,"WEB RESOURCE":1},"countByFeatureType":{"Signal":1,"Chain":2,"Region":2,"Motif":1,"Compositional bias":2,"Binding site":12,"Site":4,"Lipidation":2,"Glycosylation":1,"Natural variant":94,"Mutagenesis":9,"Beta strand":10,"Helix":10,"Turn":1},"uniParcId":"UPI0000135942"}},{"entryType":"UniProtKB unreviewed (TrEMBL)","primaryAccession":"F8WEH4","uniProtkbId":"F8WEH4_HUMAN","entryAudit":{"firstPublicDate":"2011-09-21","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2011-09-21","entryVersion":83,"sequenceVersion":1},"annotationScore":2.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000413871.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}],"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"submissionNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000413871.1"}],"value":"Sonic hedgehog signaling molecule"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000413871.1"}],"value":"SHH"}}],"comments":[{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00004236"}],"value":"Cell membrane","id":"SL-0039"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00010649"}],"value":"Belongs to the hedgehog family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Domain","location":{"start":{"value":12,"modifier":"EXACT"},"end":{"value":97,"modifier":"EXACT"}},"description":"Hedgehog N-terminal signalling","evidences":[{"evidenceCode":"ECO:0000259","source":"Pfam","id":"PF01085"}]}],"keywords":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022813"}],"id":"KW-0068","category":"PTM","name":"Autocatalytic cleavage"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022837"}],"id":"KW-0106","category":"Ligand","name":"Calcium"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022475"}],"id":"KW-1003","category":"Cellular component","name":"Cell membrane"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022473"}],"id":"KW-0217","category":"Molecular function","name":"Developmental protein"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022801"}],"id":"KW-0378","category":"Molecular function","name":"Hydrolase"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00023136"}],"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022723"}],"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022670"}],"id":"KW-0645","category":"Molecular function","name":"Protease"},{"evidences":[{"evidenceCode":"ECO:0007829","source":"PeptideAtlas","id":"F8WEH4"}],"id":"KW-1267","category":"Technical term","name":"Proteomics identification"},{"evidences":[{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}],"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022833"}],"id":"KW-0862","category":"Ligand","name":"Zinc"}],"references":[{"referenceNumber":1,"citation":{"id":"11237011","citationType":"journal article","authoringGroup":["International Human Genome Sequencing Consortium"],"authors":["Lander E.S.","Linton L.M.","Birren B.","Nusbaum C.","Zody M.C.","Baldwin J.","Devon K.","Dewar K.","Doyle M.","FitzHugh W.","Funke R.","Gage D.","Harris K.","Heaford A.","Howland J.","Kann L.","Lehoczky J.","LeVine R.","McEwan P.","McKernan K.","Meldrim J.","Mesirov J.P.","Miranda C.","Morris W.","Naylor J.","Raymond C.","Rosetti M.","Santos R.","Sheridan A.","Sougnez C.","Stange-Thomann N.","Stojanovic N.","Subramanian A.","Wyman D.","Rogers J.","Sulston J.","Ainscough R.","Beck S.","Bentley D.","Burton J.","Clee C.","Carter N.","Coulson A.","Deadman R.","Deloukas P.","Dunham A.","Dunham I.","Durbin R.","French L.","Grafham D.","Gregory S.","Hubbard T.","Humphray S.","Hunt A.","Jones M.","Lloyd C.","McMurray A.","Matthews L.","Mercer S.","Milne S.","Mullikin J.C.","Mungall A.","Plumb R.","Ross M.","Shownkeen R.","Sims S.","Waterston R.H.","Wilson R.K.","Hillier L.W.","McPherson J.D.","Marra M.A.","Mardis E.R.","Fulton L.A.","Chinwalla A.T.","Pepin K.H.","Gish W.R.","Chissoe S.L.","Wendl M.C.","Delehaunty K.D.","Miner T.L.","Delehaunty A.","Kramer J.B.","Cook L.L.","Fulton R.S.","Johnson D.L.","Minx P.J.","Clifton S.W.","Hawkins T.","Branscomb E.","Predki P.","Richardson P.","Wenning S.","Slezak T.","Doggett N.","Cheng J.F.","Olsen A.","Lucas S.","Elkin C.","Uberbacher E.","Frazier M.","Gibbs R.A.","Muzny D.M.","Scherer S.E.","Bouck J.B.","Sodergren E.J.","Worley K.C.","Rives C.M.","Gorrell J.H.","Metzker M.L.","Naylor S.L.","Kucherlapati R.S.","Nelson D.L.","Weinstock G.M.","Sakaki Y.","Fujiyama A.","Hattori M.","Yada T.","Toyoda A.","Itoh T.","Kawagoe C.","Watanabe H.","Totoki Y.","Taylor T.","Weissenbach J.","Heilig R.","Saurin W.","Artiguenave F.","Brottier P.","Bruls T.","Pelletier E.","Robert C.","Wincker P.","Smith D.R.","Doucette-Stamm L.","Rubenfield M.","Weinstock K.","Lee H.M.","Dubois J.","Rosenthal A.","Platzer M.","Nyakatura G.","Taudien S.","Rump A.","Yang H.","Yu J.","Wang J.","Huang G.","Gu J.","Hood L.","Rowen L.","Madan A.","Qin S.","Davis R.W.","Federspiel N.A.","Abola A.P.","Proctor M.J.","Myers R.M.","Schmutz J.","Dickson M.","Grimwood J.","Cox D.R.","Olson M.V.","Kaul R.","Raymond C.","Shimizu N.","Kawasaki K.","Minoshima S.","Evans G.A.","Athanasiou M.","Schultz R.","Roe B.A.","Chen F.","Pan H.","Ramser J.","Lehrach H.","Reinhardt R.","McCombie W.R.","de la Bastide M.","Dedhia N.","Blocker H.","Hornischer K.","Nordsiek G.","Agarwala R.","Aravind L.","Bailey J.A.","Bateman A.","Batzoglou S.","Birney E.","Bork P.","Brown D.G.","Burge C.B.","Cerutti L.","Chen H.C.","Church D.","Clamp M.","Copley R.R.","Doerks T.","Eddy S.R.","Eichler E.E.","Furey T.S.","Galagan J.","Gilbert J.G.","Harmon C.","Hayashizaki Y.","Haussler D.","Hermjakob H.","Hokamp K.","Jang W.","Johnson L.S.","Jones T.A.","Kasif S.","Kaspryzk A.","Kennedy S.","Kent W.J.","Kitts P.","Koonin E.V.","Korf I.","Kulp D.","Lancet D.","Lowe T.M.","McLysaght A.","Mikkelsen T.","Moran J.V.","Mulder N.","Pollara V.J.","Ponting C.P.","Schuler G.","Schultz J.","Slater G.","Smit A.F.","Stupka E.","Szustakowski J.","Thierry-Mieg D.","Thierry-Mieg J.","Wagner L.","Wallis J.","Wheeler R.","Williams A.","Wolf Y.I.","Wolfe K.H.","Yang S.P.","Yeh R.F.","Collins F.","Guyer M.S.","Peterson J.","Felsenfeld A.","Wetterstrand K.A.","Patrinos A.","Morgan M.J.","de Jong P.","Catanese J.J.","Osoegawa K.","Shizuya H.","Choi S.","Chen Y.J."],"citationCrossReferences":[{"database":"PubMed","id":"11237011"},{"database":"DOI","id":"10.1038/35057062"}],"title":"Initial sequencing and analysis of the human genome.","publicationDate":"2001","journal":"Nature","firstPage":"860","lastPage":"921","volume":"409"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000413871.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":2,"citation":{"id":"12853948","citationType":"journal article","authors":["Hillier L.W.","Fulton R.S.","Fulton L.A.","Graves T.A.","Pepin K.H.","Wagner-McPherson C.","Layman D.","Maas J.","Jaeger S.","Walker R.","Wylie K.","Sekhon M.","Becker M.C.","O'Laughlin M.D.","Schaller M.E.","Fewell G.A.","Delehaunty K.D.","Miner T.L.","Nash W.E.","Cordes M.","Du H.","Sun H.","Edwards J.","Bradshaw-Cordum H.","Ali J.","Andrews S.","Isak A.","Vanbrunt A.","Nguyen C.","Du F.","Lamar B.","Courtney L.","Kalicki J.","Ozersky P.","Bielicki L.","Scott K.","Holmes A.","Harkins R.","Harris A.","Strong C.M.","Hou S.","Tomlinson C.","Dauphin-Kohlberg S.","Kozlowicz-Reilly A.","Leonard S.","Rohlfing T.","Rock S.M.","Tin-Wollam A.M.","Abbott A.","Minx P.","Maupin R.","Strowmatt C.","Latreille P.","Miller N.","Johnson D.","Murray J.","Woessner J.P.","Wendl M.C.","Yang S.P.","Schultz B.R.","Wallis J.W.","Spieth J.","Bieri T.A.","Nelson J.O.","Berkowicz N.","Wohldmann P.E.","Cook L.L.","Hickenbotham M.T.","Eldred J.","Williams D.","Bedell J.A.","Mardis E.R.","Clifton S.W.","Chissoe S.L.","Marra M.A.","Raymond C.","Haugen E.","Gillett W.","Zhou Y.","James R.","Phelps K.","Iadanoto S.","Bubb K.","Simms E.","Levy R.","Clendenning J.","Kaul R.","Kent W.J.","Furey T.S.","Baertsch R.A.","Brent M.R.","Keibler E.","Flicek P.","Bork P.","Suyama M.","Bailey J.A.","Portnoy M.E.","Torrents D.","Chinwalla A.T.","Gish W.R.","Eddy S.R.","McPherson J.D.","Olson M.V.","Eichler E.E.","Green E.D.","Waterston R.H.","Wilson R.K."],"citationCrossReferences":[{"database":"PubMed","id":"12853948"},{"database":"DOI","id":"10.1038/nature01782"}],"title":"The DNA sequence of human chromosome 7.","publicationDate":"2003","journal":"Nature","firstPage":"157","lastPage":"164","volume":"424"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000413871.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":3,"citation":{"id":"15496913","citationType":"journal article","authoringGroup":["International Human Genome Sequencing Consortium"],"citationCrossReferences":[{"database":"PubMed","id":"15496913"},{"database":"DOI","id":"10.1038/nature03001"}],"title":"Finishing the euchromatic sequence of the human genome.","publicationDate":"2004","journal":"Nature","firstPage":"931","lastPage":"945","volume":"431"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000413871.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":4,"citation":{"id":"CI-20IM145UGQVF7","citationType":"submission","authoringGroup":["Ensembl"],"publicationDate":"JAN-2026","submissionDatabase":"UniProtKB"},"referencePositions":["IDENTIFICATION"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000413871.1"}]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"AC078834","properties":[{"key":"ProteinId","value":"-"},{"key":"Status","value":"NOT_ANNOTATED_CDS"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"AlphaFoldDB","id":"F8WEH4","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"F8WEH4","properties":[{"key":"Description","value":"-"}]},{"database":"MassIVE","id":"F8WEH4","properties":[{"key":"Description","value":"-"}]},{"database":"Ensembl","id":"ENST00000435425.1","properties":[{"key":"ProteinId","value":"ENSP00000413871.1"},{"key":"GeneId","value":"ENSG00000164690.8"}]},{"database":"UCSC","id":"uc064jpl.1","properties":[{"key":"OrganismName","value":"human"}]},{"database":"HGNC","id":"HGNC:10848","properties":[{"key":"GeneName","value":"SHH"}]},{"database":"OpenTargets","id":"ENSG00000164690","properties":[{"key":"Description","value":"-"}]},{"database":"VEuPathDB","id":"HostDB:ENSG00000164690","properties":[{"key":"Description","value":"-"}]},{"database":"GeneTree","id":"ENSGT00940000159119","properties":[{"key":"Description","value":"-"}]},{"database":"OrthoDB","id":"5212at2759","properties":[{"key":"Description","value":"-"}]},{"database":"ChiTaRS","id":"SHH","properties":[{"key":"OrganismName","value":"human"}]},{"database":"Proteomes","id":"UP000005640","properties":[{"key":"Component","value":"Chromosome 7"}]},{"database":"Bgee","id":"ENSG00000164690","properties":[{"key":"ExpressionPatterns","value":"Expressed in right lobe of liver and 98 other cell types or tissues"}]},{"database":"ExpressionAtlas","id":"F8WEH4","properties":[{"key":"ExpressionPatterns","value":"baseline and differential"}]},{"database":"GO","id":"GO:0005886","properties":[{"key":"GoTerm","value":"C:plasma membrane"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"GO","id":"GO:0048513","properties":[{"key":"GoTerm","value":"P:animal organ development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0048468","properties":[{"key":"GoTerm","value":"P:cell development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0045165","properties":[{"key":"GoTerm","value":"P:cell fate commitment"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0007267","properties":[{"key":"GoTerm","value":"P:cell-cell signaling"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:0007417","properties":[{"key":"GoTerm","value":"P:central nervous system development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0030182","properties":[{"key":"GoTerm","value":"P:neuron differentiation"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0009888","properties":[{"key":"GoTerm","value":"P:tissue development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"FunFam","id":"3.30.1380.10:FF:000005","properties":[{"key":"EntryName","value":"Sonic hedgehog signaling molecule"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.30.1380.10","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR001657","properties":[{"key":"EntryName","value":"Hedgehog"}]},{"database":"InterPro","id":"IPR050387","properties":[{"key":"EntryName","value":"Hedgehog_Signaling"}]},{"database":"InterPro","id":"IPR000320","properties":[{"key":"EntryName","value":"Hedgehog_signalling_dom"}]},{"database":"InterPro","id":"IPR009045","properties":[{"key":"EntryName","value":"Zn_M74/Hedgehog-like"}]},{"database":"PANTHER","id":"PTHR11889","properties":[{"key":"EntryName","value":"HEDGEHOG"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR11889:SF36","properties":[{"key":"EntryName","value":"SONIC HEDGEHOG PROTEIN"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF01085","properties":[{"key":"EntryName","value":"HH_signal"},{"key":"MatchStatus","value":"1"}]},{"database":"PRINTS","id":"PR00632","properties":[{"key":"EntryName","value":"SONICHHOG"}]},{"database":"SUPFAM","id":"SSF55166","properties":[{"key":"EntryName","value":"Hedgehog/DD-peptidase"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MLSLFPSPGPGSSRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAVQSDFKSVESEPEAPGTAAPLAV","length":123,"molWeight":13506,"crc64":"76D6E1E1B287F84E","md5":"F090459901F57A82609B4C002039A45C"},"extraAttributes":{"countByCommentType":{"SUBCELLULAR LOCATION":1,"SIMILARITY":1},"countByFeatureType":{"Domain":1},"uniParcId":"UPI0000579D86"}},{"entryType":"UniProtKB unreviewed (TrEMBL)","primaryAccession":"F8WB84","uniProtkbId":"F8WB84_HUMAN","entryAudit":{"firstPublicDate":"2011-09-21","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2011-09-21","entryVersion":83,"sequenceVersion":1},"annotationScore":2.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000410546.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}],"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"submissionNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000410546.1"}],"value":"Sonic hedgehog signaling molecule"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000410546.1"}],"value":"SHH"}}],"comments":[{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00004236"}],"value":"Cell membrane","id":"SL-0039"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00010649"}],"value":"Belongs to the hedgehog family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Domain","location":{"start":{"value":12,"modifier":"EXACT"},"end":{"value":97,"modifier":"EXACT"}},"description":"Hedgehog N-terminal signalling","evidences":[{"evidenceCode":"ECO:0000259","source":"Pfam","id":"PF01085"}]}],"keywords":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022813"}],"id":"KW-0068","category":"PTM","name":"Autocatalytic cleavage"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022837"}],"id":"KW-0106","category":"Ligand","name":"Calcium"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022475"}],"id":"KW-1003","category":"Cellular component","name":"Cell membrane"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022473"}],"id":"KW-0217","category":"Molecular function","name":"Developmental protein"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022801"}],"id":"KW-0378","category":"Molecular function","name":"Hydrolase"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00023136"}],"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022723"}],"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022670"}],"id":"KW-0645","category":"Molecular function","name":"Protease"},{"evidences":[{"evidenceCode":"ECO:0007829","source":"PeptideAtlas","id":"F8WB84"}],"id":"KW-1267","category":"Technical term","name":"Proteomics identification"},{"evidences":[{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}],"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022833"}],"id":"KW-0862","category":"Ligand","name":"Zinc"}],"references":[{"referenceNumber":1,"citation":{"id":"11237011","citationType":"journal article","authoringGroup":["International Human Genome Sequencing Consortium"],"authors":["Lander E.S.","Linton L.M.","Birren B.","Nusbaum C.","Zody M.C.","Baldwin J.","Devon K.","Dewar K.","Doyle M.","FitzHugh W.","Funke R.","Gage D.","Harris K.","Heaford A.","Howland J.","Kann L.","Lehoczky J.","LeVine R.","McEwan P.","McKernan K.","Meldrim J.","Mesirov J.P.","Miranda C.","Morris W.","Naylor J.","Raymond C.","Rosetti M.","Santos R.","Sheridan A.","Sougnez C.","Stange-Thomann N.","Stojanovic N.","Subramanian A.","Wyman D.","Rogers J.","Sulston J.","Ainscough R.","Beck S.","Bentley D.","Burton J.","Clee C.","Carter N.","Coulson A.","Deadman R.","Deloukas P.","Dunham A.","Dunham I.","Durbin R.","French L.","Grafham D.","Gregory S.","Hubbard T.","Humphray S.","Hunt A.","Jones M.","Lloyd C.","McMurray A.","Matthews L.","Mercer S.","Milne S.","Mullikin J.C.","Mungall A.","Plumb R.","Ross M.","Shownkeen R.","Sims S.","Waterston R.H.","Wilson R.K.","Hillier L.W.","McPherson J.D.","Marra M.A.","Mardis E.R.","Fulton L.A.","Chinwalla A.T.","Pepin K.H.","Gish W.R.","Chissoe S.L.","Wendl M.C.","Delehaunty K.D.","Miner T.L.","Delehaunty A.","Kramer J.B.","Cook L.L.","Fulton R.S.","Johnson D.L.","Minx P.J.","Clifton S.W.","Hawkins T.","Branscomb E.","Predki P.","Richardson P.","Wenning S.","Slezak T.","Doggett N.","Cheng J.F.","Olsen A.","Lucas S.","Elkin C.","Uberbacher E.","Frazier M.","Gibbs R.A.","Muzny D.M.","Scherer S.E.","Bouck J.B.","Sodergren E.J.","Worley K.C.","Rives C.M.","Gorrell J.H.","Metzker M.L.","Naylor S.L.","Kucherlapati R.S.","Nelson D.L.","Weinstock G.M.","Sakaki Y.","Fujiyama A.","Hattori M.","Yada T.","Toyoda A.","Itoh T.","Kawagoe C.","Watanabe H.","Totoki Y.","Taylor T.","Weissenbach J.","Heilig R.","Saurin W.","Artiguenave F.","Brottier P.","Bruls T.","Pelletier E.","Robert C.","Wincker P.","Smith D.R.","Doucette-Stamm L.","Rubenfield M.","Weinstock K.","Lee H.M.","Dubois J.","Rosenthal A.","Platzer M.","Nyakatura G.","Taudien S.","Rump A.","Yang H.","Yu J.","Wang J.","Huang G.","Gu J.","Hood L.","Rowen L.","Madan A.","Qin S.","Davis R.W.","Federspiel N.A.","Abola A.P.","Proctor M.J.","Myers R.M.","Schmutz J.","Dickson M.","Grimwood J.","Cox D.R.","Olson M.V.","Kaul R.","Raymond C.","Shimizu N.","Kawasaki K.","Minoshima S.","Evans G.A.","Athanasiou M.","Schultz R.","Roe B.A.","Chen F.","Pan H.","Ramser J.","Lehrach H.","Reinhardt R.","McCombie W.R.","de la Bastide M.","Dedhia N.","Blocker H.","Hornischer K.","Nordsiek G.","Agarwala R.","Aravind L.","Bailey J.A.","Bateman A.","Batzoglou S.","Birney E.","Bork P.","Brown D.G.","Burge C.B.","Cerutti L.","Chen H.C.","Church D.","Clamp M.","Copley R.R.","Doerks T.","Eddy S.R.","Eichler E.E.","Furey T.S.","Galagan J.","Gilbert J.G.","Harmon C.","Hayashizaki Y.","Haussler D.","Hermjakob H.","Hokamp K.","Jang W.","Johnson L.S.","Jones T.A.","Kasif S.","Kaspryzk A.","Kennedy S.","Kent W.J.","Kitts P.","Koonin E.V.","Korf I.","Kulp D.","Lancet D.","Lowe T.M.","McLysaght A.","Mikkelsen T.","Moran J.V.","Mulder N.","Pollara V.J.","Ponting C.P.","Schuler G.","Schultz J.","Slater G.","Smit A.F.","Stupka E.","Szustakowski J.","Thierry-Mieg D.","Thierry-Mieg J.","Wagner L.","Wallis J.","Wheeler R.","Williams A.","Wolf Y.I.","Wolfe K.H.","Yang S.P.","Yeh R.F.","Collins F.","Guyer M.S.","Peterson J.","Felsenfeld A.","Wetterstrand K.A.","Patrinos A.","Morgan M.J.","de Jong P.","Catanese J.J.","Osoegawa K.","Shizuya H.","Choi S.","Chen Y.J."],"citationCrossReferences":[{"database":"PubMed","id":"11237011"},{"database":"DOI","id":"10.1038/35057062"}],"title":"Initial sequencing and analysis of the human genome.","publicationDate":"2001","journal":"Nature","firstPage":"860","lastPage":"921","volume":"409"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000410546.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":2,"citation":{"id":"12853948","citationType":"journal article","authors":["Hillier L.W.","Fulton R.S.","Fulton L.A.","Graves T.A.","Pepin K.H.","Wagner-McPherson C.","Layman D.","Maas J.","Jaeger S.","Walker R.","Wylie K.","Sekhon M.","Becker M.C.","O'Laughlin M.D.","Schaller M.E.","Fewell G.A.","Delehaunty K.D.","Miner T.L.","Nash W.E.","Cordes M.","Du H.","Sun H.","Edwards J.","Bradshaw-Cordum H.","Ali J.","Andrews S.","Isak A.","Vanbrunt A.","Nguyen C.","Du F.","Lamar B.","Courtney L.","Kalicki J.","Ozersky P.","Bielicki L.","Scott K.","Holmes A.","Harkins R.","Harris A.","Strong C.M.","Hou S.","Tomlinson C.","Dauphin-Kohlberg S.","Kozlowicz-Reilly A.","Leonard S.","Rohlfing T.","Rock S.M.","Tin-Wollam A.M.","Abbott A.","Minx P.","Maupin R.","Strowmatt C.","Latreille P.","Miller N.","Johnson D.","Murray J.","Woessner J.P.","Wendl M.C.","Yang S.P.","Schultz B.R.","Wallis J.W.","Spieth J.","Bieri T.A.","Nelson J.O.","Berkowicz N.","Wohldmann P.E.","Cook L.L.","Hickenbotham M.T.","Eldred J.","Williams D.","Bedell J.A.","Mardis E.R.","Clifton S.W.","Chissoe S.L.","Marra M.A.","Raymond C.","Haugen E.","Gillett W.","Zhou Y.","James R.","Phelps K.","Iadanoto S.","Bubb K.","Simms E.","Levy R.","Clendenning J.","Kaul R.","Kent W.J.","Furey T.S.","Baertsch R.A.","Brent M.R.","Keibler E.","Flicek P.","Bork P.","Suyama M.","Bailey J.A.","Portnoy M.E.","Torrents D.","Chinwalla A.T.","Gish W.R.","Eddy S.R.","McPherson J.D.","Olson M.V.","Eichler E.E.","Green E.D.","Waterston R.H.","Wilson R.K."],"citationCrossReferences":[{"database":"PubMed","id":"12853948"},{"database":"DOI","id":"10.1038/nature01782"}],"title":"The DNA sequence of human chromosome 7.","publicationDate":"2003","journal":"Nature","firstPage":"157","lastPage":"164","volume":"424"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000410546.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":3,"citation":{"id":"15496913","citationType":"journal article","authoringGroup":["International Human Genome Sequencing Consortium"],"citationCrossReferences":[{"database":"PubMed","id":"15496913"},{"database":"DOI","id":"10.1038/nature03001"}],"title":"Finishing the euchromatic sequence of the human genome.","publicationDate":"2004","journal":"Nature","firstPage":"931","lastPage":"945","volume":"431"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000410546.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":4,"citation":{"id":"CI-20IM145UGQVF7","citationType":"submission","authoringGroup":["Ensembl"],"publicationDate":"JAN-2026","submissionDatabase":"UniProtKB"},"referencePositions":["IDENTIFICATION"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000410546.1"}]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"AC078834","properties":[{"key":"ProteinId","value":"-"},{"key":"Status","value":"NOT_ANNOTATED_CDS"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"AlphaFoldDB","id":"F8WB84","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"F8WB84","properties":[{"key":"Description","value":"-"}]},{"database":"MassIVE","id":"F8WB84","properties":[{"key":"Description","value":"-"}]},{"database":"Ensembl","id":"ENST00000441114.5","properties":[{"key":"ProteinId","value":"ENSP00000410546.1"},{"key":"GeneId","value":"ENSG00000164690.8"}]},{"database":"UCSC","id":"uc064jpk.1","properties":[{"key":"OrganismName","value":"human"}]},{"database":"HGNC","id":"HGNC:10848","properties":[{"key":"GeneName","value":"SHH"}]},{"database":"OpenTargets","id":"ENSG00000164690","properties":[{"key":"Description","value":"-"}]},{"database":"VEuPathDB","id":"HostDB:ENSG00000164690","properties":[{"key":"Description","value":"-"}]},{"database":"GeneTree","id":"ENSGT00940000159119","properties":[{"key":"Description","value":"-"}]},{"database":"HOGENOM","id":"CLU_162113_0_0_1","properties":[{"key":"Description","value":"-"}]},{"database":"OrthoDB","id":"5212at2759","properties":[{"key":"Description","value":"-"}]},{"database":"ChiTaRS","id":"SHH","properties":[{"key":"OrganismName","value":"human"}]},{"database":"Proteomes","id":"UP000005640","properties":[{"key":"Component","value":"Chromosome 7"}]},{"database":"Bgee","id":"ENSG00000164690","properties":[{"key":"ExpressionPatterns","value":"Expressed in right lobe of liver and 98 other cell types or tissues"}]},{"database":"ExpressionAtlas","id":"F8WB84","properties":[{"key":"ExpressionPatterns","value":"baseline and differential"}]},{"database":"GO","id":"GO:0005886","properties":[{"key":"GoTerm","value":"C:plasma membrane"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"GO","id":"GO:0048513","properties":[{"key":"GoTerm","value":"P:animal organ development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0048468","properties":[{"key":"GoTerm","value":"P:cell development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0045165","properties":[{"key":"GoTerm","value":"P:cell fate commitment"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0007267","properties":[{"key":"GoTerm","value":"P:cell-cell signaling"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:0007417","properties":[{"key":"GoTerm","value":"P:central nervous system development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0030182","properties":[{"key":"GoTerm","value":"P:neuron differentiation"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0009888","properties":[{"key":"GoTerm","value":"P:tissue development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"FunFam","id":"3.30.1380.10:FF:000005","properties":[{"key":"EntryName","value":"Sonic hedgehog signaling molecule"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.30.1380.10","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR001657","properties":[{"key":"EntryName","value":"Hedgehog"}]},{"database":"InterPro","id":"IPR050387","properties":[{"key":"EntryName","value":"Hedgehog_Signaling"}]},{"database":"InterPro","id":"IPR000320","properties":[{"key":"EntryName","value":"Hedgehog_signalling_dom"}]},{"database":"InterPro","id":"IPR009045","properties":[{"key":"EntryName","value":"Zn_M74/Hedgehog-like"}]},{"database":"PANTHER","id":"PTHR11889","properties":[{"key":"EntryName","value":"HEDGEHOG"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR11889:SF36","properties":[{"key":"EntryName","value":"SONIC HEDGEHOG PROTEIN"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF01085","properties":[{"key":"EntryName","value":"HH_signal"},{"key":"MatchStatus","value":"1"}]},{"database":"PRINTS","id":"PR00632","properties":[{"key":"EntryName","value":"SONICHHOG"}]},{"database":"SUPFAM","id":"SSF55166","properties":[{"key":"EntryName","value":"Hedgehog/DD-peptidase"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MLSLFPSPGPGSSRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAGGQQVPGWCLQSRRKCDGFCSFDSSV","length":126,"molWeight":14025,"crc64":"DC207977A9B25CBA","md5":"786B760D7B2FBF9805002ECA7454629F"},"extraAttributes":{"countByCommentType":{"SUBCELLULAR LOCATION":1,"SIMILARITY":1},"countByFeatureType":{"Domain":1},"uniParcId":"UPI0000579D85"}},{"entryType":"UniProtKB unreviewed (TrEMBL)","primaryAccession":"C9JC48","uniProtkbId":"C9JC48_HUMAN","entryAudit":{"firstPublicDate":"2009-11-03","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2009-11-03","entryVersion":101,"sequenceVersion":1},"annotationScore":2.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000396621.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}],"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"submissionNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000396621.1"}],"value":"Sonic hedgehog signaling molecule"}}],"flag":"Fragment"},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000396621.1"}],"value":"SHH"}}],"comments":[{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00004236"}],"value":"Cell membrane","id":"SL-0039"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00010649"}],"value":"Belongs to the hedgehog family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Domain","location":{"start":{"value":12,"modifier":"EXACT"},"end":{"value":97,"modifier":"EXACT"}},"description":"Hedgehog N-terminal signalling","evidences":[{"evidenceCode":"ECO:0000259","source":"Pfam","id":"PF01085"}]},{"type":"Non-terminal residue","location":{"start":{"value":169,"modifier":"EXACT"},"end":{"value":169,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000396621.1"}]}],"keywords":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022813"}],"id":"KW-0068","category":"PTM","name":"Autocatalytic cleavage"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022837"}],"id":"KW-0106","category":"Ligand","name":"Calcium"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022475"}],"id":"KW-1003","category":"Cellular component","name":"Cell membrane"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022473"}],"id":"KW-0217","category":"Molecular function","name":"Developmental protein"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022801"}],"id":"KW-0378","category":"Molecular function","name":"Hydrolase"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00023136"}],"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022723"}],"id":"KW-0479","category":"Ligand","name":"Metal-binding"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022670"}],"id":"KW-0645","category":"Molecular function","name":"Protease"},{"evidences":[{"evidenceCode":"ECO:0007829","source":"PeptideAtlas","id":"C9JC48"}],"id":"KW-1267","category":"Technical term","name":"Proteomics identification"},{"evidences":[{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}],"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00022833"}],"id":"KW-0862","category":"Ligand","name":"Zinc"}],"references":[{"referenceNumber":1,"citation":{"id":"11237011","citationType":"journal article","authoringGroup":["International Human Genome Sequencing Consortium"],"authors":["Lander E.S.","Linton L.M.","Birren B.","Nusbaum C.","Zody M.C.","Baldwin J.","Devon K.","Dewar K.","Doyle M.","FitzHugh W.","Funke R.","Gage D.","Harris K.","Heaford A.","Howland J.","Kann L.","Lehoczky J.","LeVine R.","McEwan P.","McKernan K.","Meldrim J.","Mesirov J.P.","Miranda C.","Morris W.","Naylor J.","Raymond C.","Rosetti M.","Santos R.","Sheridan A.","Sougnez C.","Stange-Thomann N.","Stojanovic N.","Subramanian A.","Wyman D.","Rogers J.","Sulston J.","Ainscough R.","Beck S.","Bentley D.","Burton J.","Clee C.","Carter N.","Coulson A.","Deadman R.","Deloukas P.","Dunham A.","Dunham I.","Durbin R.","French L.","Grafham D.","Gregory S.","Hubbard T.","Humphray S.","Hunt A.","Jones M.","Lloyd C.","McMurray A.","Matthews L.","Mercer S.","Milne S.","Mullikin J.C.","Mungall A.","Plumb R.","Ross M.","Shownkeen R.","Sims S.","Waterston R.H.","Wilson R.K.","Hillier L.W.","McPherson J.D.","Marra M.A.","Mardis E.R.","Fulton L.A.","Chinwalla A.T.","Pepin K.H.","Gish W.R.","Chissoe S.L.","Wendl M.C.","Delehaunty K.D.","Miner T.L.","Delehaunty A.","Kramer J.B.","Cook L.L.","Fulton R.S.","Johnson D.L.","Minx P.J.","Clifton S.W.","Hawkins T.","Branscomb E.","Predki P.","Richardson P.","Wenning S.","Slezak T.","Doggett N.","Cheng J.F.","Olsen A.","Lucas S.","Elkin C.","Uberbacher E.","Frazier M.","Gibbs R.A.","Muzny D.M.","Scherer S.E.","Bouck J.B.","Sodergren E.J.","Worley K.C.","Rives C.M.","Gorrell J.H.","Metzker M.L.","Naylor S.L.","Kucherlapati R.S.","Nelson D.L.","Weinstock G.M.","Sakaki Y.","Fujiyama A.","Hattori M.","Yada T.","Toyoda A.","Itoh T.","Kawagoe C.","Watanabe H.","Totoki Y.","Taylor T.","Weissenbach J.","Heilig R.","Saurin W.","Artiguenave F.","Brottier P.","Bruls T.","Pelletier E.","Robert C.","Wincker P.","Smith D.R.","Doucette-Stamm L.","Rubenfield M.","Weinstock K.","Lee H.M.","Dubois J.","Rosenthal A.","Platzer M.","Nyakatura G.","Taudien S.","Rump A.","Yang H.","Yu J.","Wang J.","Huang G.","Gu J.","Hood L.","Rowen L.","Madan A.","Qin S.","Davis R.W.","Federspiel N.A.","Abola A.P.","Proctor M.J.","Myers R.M.","Schmutz J.","Dickson M.","Grimwood J.","Cox D.R.","Olson M.V.","Kaul R.","Raymond C.","Shimizu N.","Kawasaki K.","Minoshima S.","Evans G.A.","Athanasiou M.","Schultz R.","Roe B.A.","Chen F.","Pan H.","Ramser J.","Lehrach H.","Reinhardt R.","McCombie W.R.","de la Bastide M.","Dedhia N.","Blocker H.","Hornischer K.","Nordsiek G.","Agarwala R.","Aravind L.","Bailey J.A.","Bateman A.","Batzoglou S.","Birney E.","Bork P.","Brown D.G.","Burge C.B.","Cerutti L.","Chen H.C.","Church D.","Clamp M.","Copley R.R.","Doerks T.","Eddy S.R.","Eichler E.E.","Furey T.S.","Galagan J.","Gilbert J.G.","Harmon C.","Hayashizaki Y.","Haussler D.","Hermjakob H.","Hokamp K.","Jang W.","Johnson L.S.","Jones T.A.","Kasif S.","Kaspryzk A.","Kennedy S.","Kent W.J.","Kitts P.","Koonin E.V.","Korf I.","Kulp D.","Lancet D.","Lowe T.M.","McLysaght A.","Mikkelsen T.","Moran J.V.","Mulder N.","Pollara V.J.","Ponting C.P.","Schuler G.","Schultz J.","Slater G.","Smit A.F.","Stupka E.","Szustakowski J.","Thierry-Mieg D.","Thierry-Mieg J.","Wagner L.","Wallis J.","Wheeler R.","Williams A.","Wolf Y.I.","Wolfe K.H.","Yang S.P.","Yeh R.F.","Collins F.","Guyer M.S.","Peterson J.","Felsenfeld A.","Wetterstrand K.A.","Patrinos A.","Morgan M.J.","de Jong P.","Catanese J.J.","Osoegawa K.","Shizuya H.","Choi S.","Chen Y.J."],"citationCrossReferences":[{"database":"PubMed","id":"11237011"},{"database":"DOI","id":"10.1038/35057062"}],"title":"Initial sequencing and analysis of the human genome.","publicationDate":"2001","journal":"Nature","firstPage":"860","lastPage":"921","volume":"409"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000396621.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":2,"citation":{"id":"12853948","citationType":"journal article","authors":["Hillier L.W.","Fulton R.S.","Fulton L.A.","Graves T.A.","Pepin K.H.","Wagner-McPherson C.","Layman D.","Maas J.","Jaeger S.","Walker R.","Wylie K.","Sekhon M.","Becker M.C.","O'Laughlin M.D.","Schaller M.E.","Fewell G.A.","Delehaunty K.D.","Miner T.L.","Nash W.E.","Cordes M.","Du H.","Sun H.","Edwards J.","Bradshaw-Cordum H.","Ali J.","Andrews S.","Isak A.","Vanbrunt A.","Nguyen C.","Du F.","Lamar B.","Courtney L.","Kalicki J.","Ozersky P.","Bielicki L.","Scott K.","Holmes A.","Harkins R.","Harris A.","Strong C.M.","Hou S.","Tomlinson C.","Dauphin-Kohlberg S.","Kozlowicz-Reilly A.","Leonard S.","Rohlfing T.","Rock S.M.","Tin-Wollam A.M.","Abbott A.","Minx P.","Maupin R.","Strowmatt C.","Latreille P.","Miller N.","Johnson D.","Murray J.","Woessner J.P.","Wendl M.C.","Yang S.P.","Schultz B.R.","Wallis J.W.","Spieth J.","Bieri T.A.","Nelson J.O.","Berkowicz N.","Wohldmann P.E.","Cook L.L.","Hickenbotham M.T.","Eldred J.","Williams D.","Bedell J.A.","Mardis E.R.","Clifton S.W.","Chissoe S.L.","Marra M.A.","Raymond C.","Haugen E.","Gillett W.","Zhou Y.","James R.","Phelps K.","Iadanoto S.","Bubb K.","Simms E.","Levy R.","Clendenning J.","Kaul R.","Kent W.J.","Furey T.S.","Baertsch R.A.","Brent M.R.","Keibler E.","Flicek P.","Bork P.","Suyama M.","Bailey J.A.","Portnoy M.E.","Torrents D.","Chinwalla A.T.","Gish W.R.","Eddy S.R.","McPherson J.D.","Olson M.V.","Eichler E.E.","Green E.D.","Waterston R.H.","Wilson R.K."],"citationCrossReferences":[{"database":"PubMed","id":"12853948"},{"database":"DOI","id":"10.1038/nature01782"}],"title":"The DNA sequence of human chromosome 7.","publicationDate":"2003","journal":"Nature","firstPage":"157","lastPage":"164","volume":"424"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000396621.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":3,"citation":{"id":"15496913","citationType":"journal article","authoringGroup":["International Human Genome Sequencing Consortium"],"citationCrossReferences":[{"database":"PubMed","id":"15496913"},{"database":"DOI","id":"10.1038/nature03001"}],"title":"Finishing the euchromatic sequence of the human genome.","publicationDate":"2004","journal":"Nature","firstPage":"931","lastPage":"945","volume":"431"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000396621.1"},{"evidenceCode":"ECO:0000313","source":"Proteomes","id":"UP000005640"}]},{"referenceNumber":4,"citation":{"id":"CI-20IM145UGQVF7","citationType":"submission","authoringGroup":["Ensembl"],"publicationDate":"JAN-2026","submissionDatabase":"UniProtKB"},"referencePositions":["IDENTIFICATION"],"evidences":[{"evidenceCode":"ECO:0000313","source":"Ensembl","id":"ENSP00000396621.1"}]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"AC078834","properties":[{"key":"ProteinId","value":"-"},{"key":"Status","value":"NOT_ANNOTATED_CDS"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"AlphaFoldDB","id":"C9JC48","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"C9JC48","properties":[{"key":"Description","value":"-"}]},{"database":"MassIVE","id":"C9JC48","properties":[{"key":"Description","value":"-"}]},{"database":"Antibodypedia","id":"4514","properties":[{"key":"antibodies","value":"657 antibodies from 45 providers"}]},{"database":"Ensembl","id":"ENST00000430104.5","properties":[{"key":"ProteinId","value":"ENSP00000396621.1"},{"key":"GeneId","value":"ENSG00000164690.8"}]},{"database":"UCSC","id":"uc003wmi.2","properties":[{"key":"OrganismName","value":"human"}]},{"database":"HGNC","id":"HGNC:10848","properties":[{"key":"GeneName","value":"SHH"}]},{"database":"OpenTargets","id":"ENSG00000164690","properties":[{"key":"Description","value":"-"}]},{"database":"VEuPathDB","id":"HostDB:ENSG00000164690","properties":[{"key":"Description","value":"-"}]},{"database":"GeneTree","id":"ENSGT00940000159119","properties":[{"key":"Description","value":"-"}]},{"database":"HOGENOM","id":"CLU_1582191_0_0_1","properties":[{"key":"Description","value":"-"}]},{"database":"OrthoDB","id":"5212at2759","properties":[{"key":"Description","value":"-"}]},{"database":"ChiTaRS","id":"SHH","properties":[{"key":"OrganismName","value":"human"}]},{"database":"Proteomes","id":"UP000005640","properties":[{"key":"Component","value":"Chromosome 7"}]},{"database":"Bgee","id":"ENSG00000164690","properties":[{"key":"ExpressionPatterns","value":"Expressed in right lobe of liver and 98 other cell types or tissues"}]},{"database":"ExpressionAtlas","id":"C9JC48","properties":[{"key":"ExpressionPatterns","value":"baseline and differential"}]},{"database":"GO","id":"GO:0005886","properties":[{"key":"GoTerm","value":"C:plasma membrane"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-SubCell"}]},{"database":"GO","id":"GO:0048513","properties":[{"key":"GoTerm","value":"P:animal organ development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0048468","properties":[{"key":"GoTerm","value":"P:cell development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0045165","properties":[{"key":"GoTerm","value":"P:cell fate commitment"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0007267","properties":[{"key":"GoTerm","value":"P:cell-cell signaling"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:0007417","properties":[{"key":"GoTerm","value":"P:central nervous system development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0030182","properties":[{"key":"GoTerm","value":"P:neuron differentiation"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"GO","id":"GO:0009888","properties":[{"key":"GoTerm","value":"P:tissue development"},{"key":"GoEvidenceType","value":"IEA:UniProtKB-ARBA"}]},{"database":"FunFam","id":"3.30.1380.10:FF:000005","properties":[{"key":"EntryName","value":"Sonic hedgehog signaling molecule"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.30.1380.10","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR001657","properties":[{"key":"EntryName","value":"Hedgehog"}]},{"database":"InterPro","id":"IPR050387","properties":[{"key":"EntryName","value":"Hedgehog_Signaling"}]},{"database":"InterPro","id":"IPR000320","properties":[{"key":"EntryName","value":"Hedgehog_signalling_dom"}]},{"database":"InterPro","id":"IPR009045","properties":[{"key":"EntryName","value":"Zn_M74/Hedgehog-like"}]},{"database":"PANTHER","id":"PTHR11889","properties":[{"key":"EntryName","value":"HEDGEHOG"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR11889:SF36","properties":[{"key":"EntryName","value":"SONIC HEDGEHOG PROTEIN"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF01085","properties":[{"key":"EntryName","value":"HH_signal"},{"key":"MatchStatus","value":"1"}]},{"database":"PRINTS","id":"PR00632","properties":[{"key":"EntryName","value":"SONICHHOG"}]},{"database":"SUPFAM","id":"SSF55166","properties":[{"key":"EntryName","value":"Hedgehog/DD-peptidase"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MLSLFPSPGPGSSRCKDKLNALAISVMNQWPGVKLRVTEGWDEDGHHSEESLHYEGRAVDITTSDRDRSKYGMLARLAVEAGFDWVYYESKAHIHCSVKAGKERKPLLRDTRYRASRGCSPAPPGRGADFSFRVDGAKSLCKMYAWWLLPASLMTKCISIPVKTCITMY","length":169,"molWeight":18932,"crc64":"2C25F09F132CD92D","md5":"3EBC71F9C27F8E86FCCCECDF5D1DC2C3"},"extraAttributes":{"countByCommentType":{"SUBCELLULAR LOCATION":1,"SIMILARITY":1},"countByFeatureType":{"Domain":1,"Non-terminal residue":1},"uniParcId":"UPI000173A292"}}]}