ID IHH_MOUSE Reviewed; 411 AA. AC P97812; Q61724; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1999, sequence version 2. DT 04-NOV-2026, entry version 209. DE RecName: Full=Indian hedgehog protein {ECO:0000303|PubMed:9079674}; DE Short=IHH {ECO:0000303|PubMed:9079674}; DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226}; DE AltName: Full=HHG-2; DE Contains: DE RecName: Full=Indian hedgehog protein N-product; DE Flags: Precursor; GN Name=Ihh {ECO:0000303|PubMed:9079674, ECO:0000312|MGI:MGI:96533}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEOLYTIC PROCESSING, DEVELOPMENTAL STAGE, RP TISSUE SPECIFICITY, AND AUTOCATALYTIC CLEAVAGE. RC STRAIN=CD-1; TISSUE=Kidney; RX PubMed=9079674; DOI=10.1074/jbc.272.13.8466; RA Valentini R.P., Brookhiser W.T., Park J., Yang T., Briggs J., Dressler G., RA Holzman L.B.; RT "Post-translational processing and renal expression of mouse indian RT hedgehog."; RL J. Biol. Chem. 272:8466-8473(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 76-411. RC STRAIN=C57BL/6J; TISSUE=Embryo; RX PubMed=7916661; DOI=10.1016/0092-8674(93)90627-3; RA Echelard Y., Epstein D.J., St Jacques B., Shen L., Mohler J., McMahon J.A., RA McMahon A.P.; RT "Sonic hedgehog, a member of a family of putative signaling molecules, is RT implicated in the regulation of CNS polarity."; RL Cell 75:1417-1430(1993). RN [3] RP SEQUENCE REVISION. RA St Jacques B.; RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 124-172. RX PubMed=7720571; DOI=10.1242/dev.120.11.3339; RA Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K., Zhao R., RA Seldin M.F., Fallon J.F., Beachy P.A.; RT "Products, genetic linkage and limb patterning activity of a murine RT hedgehog gene."; RL Development 120:3339-3353(1994). RN [5] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=10465785; DOI=10.1101/gad.13.16.2072; RA St-Jacques B., Hammerschmidt M., McMahon A.P.; RT "Indian hedgehog signaling regulates proliferation and differentiation of RT chondrocytes and is essential for bone formation."; RL Genes Dev. 13:2072-2086(1999). RN [6] RP FUNCTION. RX PubMed=10631175; DOI=10.1242/dev.127.3.543; RA Karp S.J., Schipani E., St-Jacques B., Hunzelman J., Kronenberg H., RA McMahon A.P.; RT "Indian hedgehog coordinates endochondral bone growth and morphogenesis via RT parathyroid hormone related-protein-dependent and -independent pathways."; RL Development 127:543-548(2000). RN [7] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=18582859; DOI=10.1016/j.ydbio.2008.05.528; RA Dakubo G.D., Mazerolle C., Furimsky M., Yu C., St-Jacques B., McMahon A.P., RA Wallace V.A.; RT "Indian hedgehog signaling from endothelial cells is required for sclera RT and retinal pigment epithelium development in the mouse eye."; RL Dev. Biol. 320:242-255(2008). RN [8] RP FUNCTION, AND MUTAGENESIS OF GLU-95. RX PubMed=19252479; DOI=10.1038/nature07862; RA Gao B., Hu J., Stricker S., Cheung M., Ma G., Law K.F., Witte F., RA Briscoe J., Mundlos S., He L., Cheah K.S., Chan D.; RT "A mutation in Ihh that causes digit abnormalities alters its signalling RT capacity and range."; RL Nature 458:1196-1200(2009). RN [9] RP INTERACTION WITH GPC3. RX PubMed=23665349; DOI=10.1016/j.ajpath.2013.03.013; RA Bhave V.S., Mars W., Donthamsetty S., Zhang X., Tan L., Luo J., Bowen W.C., RA Michalopoulos G.K.; RT "Regulation of liver growth by glypican 3, CD81, hedgehog, and Hhex."; RL Am. J. Pathol. 183:153-159(2013). CC -!- FUNCTION: [Indian hedgehog protein]: Precursor of indian hedgehog, a CC morphogen that activates the smoothened signaling pathway, and which is CC essential for bone and cartilage development (PubMed:10465785, CC PubMed:10631175, PubMed:18582859, PubMed:19252479). The C-terminal part CC of the precursor displays an autoproteolysis and a cholesterol CC transferase activity, resulting (1) in the cleavage of the full-length CC protein into two parts, indian hedgehog protein N-product and C-product CC and (2) covalent attachment of a cholesterol moiety to the C-terminus CC of the newly generated N-product (By similarity). Both autoproteolysis CC and a cholesterol transferase activities occur in the endoplasmic CC reticulum (By similarity). Following additional lipidation, N-product CC acts as a morphogen, while C-product is degraded in the endoplasmic CC reticulum (By similarity). {ECO:0000250|UniProtKB:Q62226, CC ECO:0000269|PubMed:10465785, ECO:0000269|PubMed:10631175, CC ECO:0000269|PubMed:18582859, ECO:0000269|PubMed:19252479}. CC -!- FUNCTION: [Indian hedgehog protein N-product]: The dually lipidated CC indian hedgehog protein N-product is a morphogen that activates the CC smoothened signaling pathway, and which is essential for bone and CC cartilage development (PubMed:10465785, PubMed:10631175, CC PubMed:19252479). Acts by binding to the patched receptor (PTCH1 or CC PTCH2), relieving smoothened (SMO) inhibition by patched, activating CC the smoothened signaling pathway and transcription of target genes CC (PubMed:19252479). In the absence of IHH, patched represses the CC constitutive signaling activity of SMO (By similarity). Plays a role in CC morphogenesis of the skeleton by coordinating growth and CC differentiation of the endochondral skeleton (PubMed:10465785, CC PubMed:10631175, PubMed:19252479). Positively regulates PTHLH CC expression during endochondral bone formation preventing chondrocyte CC hypertrophy (PubMed:10465785, PubMed:10631175). In contrast, CC participates in normal chondrocyte proliferation in a PTHLH-independent CC pathway (PubMed:10631175). Involved in the development of retinal CC pigment epithelium (RPE), photoreceptors and periocular tissues CC (PubMed:18582859). Plays a role in hedgehog paracrine signaling (By CC similarity). Associated with the very-low-density lipoprotein (VLDL) CC particles to function as a circulating morphogen for endothelial cell CC integrity maintenance (By similarity). {ECO:0000250|UniProtKB:Q14623, CC ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:10465785, CC ECO:0000269|PubMed:10631175, ECO:0000269|PubMed:18582859, CC ECO:0000269|PubMed:19252479}. CC -!- CATALYTIC ACTIVITY: [Indian hedgehog protein]: CC Reaction=glycyl-L-cysteinyl-[protein] + cholesterol + H(+) = [protein]- CC C-terminal glycyl cholesterol ester + N-terminal L-cysteinyl- CC [protein]; Xref=Rhea:RHEA:59504, Rhea:RHEA-COMP:12707, Rhea:RHEA- CC COMP:15369, Rhea:RHEA-COMP:15374, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:16113, ChEBI:CHEBI:65250, ChEBI:CHEBI:143135, CC ChEBI:CHEBI:143140; Evidence={ECO:0000250|UniProtKB:Q62226}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59505; CC Evidence={ECO:0000250|UniProtKB:Q62226}; CC -!- SUBUNIT: [Indian hedgehog protein N-product]: Multimer. CC {ECO:0000250|UniProtKB:Q14623}. CC -!- SUBUNIT: Interacts with BOC and CDON. Interacts with PTCH1 (By CC similarity). Interacts with glypican GPC3 (PubMed:23665349). CC {ECO:0000250|UniProtKB:Q14623, ECO:0000269|PubMed:23665349}. CC -!- SUBCELLULAR LOCATION: [Indian hedgehog protein]: Endoplasmic reticulum CC membrane {ECO:0000250|UniProtKB:Q15465}. Golgi apparatus membrane CC {ECO:0000250|UniProtKB:Q15465}. Note=Co-localizes with HHAT in the ER CC and Golgi membrane. {ECO:0000250|UniProtKB:Q15465}. CC -!- SUBCELLULAR LOCATION: [Indian hedgehog protein N-product]: Secreted CC {ECO:0000250|UniProtKB:Q14623}. Cell membrane CC {ECO:0000250|UniProtKB:Q14623}; Lipid-anchor CC {ECO:0000250|UniProtKB:Q15465}. Note=The dual-lipidated N-product is CC tethered to the cell membrane where it forms multimers. Further CC solubilization from the cell surface is required to promote its release CC from producing cells and act as a morphogen for distant signaling. CC {ECO:0000250|UniProtKB:Q15465}. CC -!- TISSUE SPECIFICITY: In the adult kidney, found in proximal convoluted CC and proximal straight tubule (PubMed:9079674). Expressed in the CC developing eye (PubMed:18582859). {ECO:0000269|PubMed:18582859, CC ECO:0000269|PubMed:9079674}. CC -!- DEVELOPMENTAL STAGE: Detected at 10 dpc in developing gut, at 14.5 days CC dpc in the cartilage primordium and in the developing urogenital sinus. CC Expression increases with gestional age in kidney and duodenum, CC becoming maximal in adulthood. {ECO:0000269|PubMed:9079674}. CC -!- DOMAIN: [Indian hedgehog protein N-product]: Binds calcium and zinc CC ions; this stabilizes the protein fold and is essential for protein- CC protein interactions mediated by this domain. CC {ECO:0000250|UniProtKB:Q14623}. CC -!- PTM: [Indian hedgehog protein]: The C-terminal domain displays an CC autoproteolysis activity and a cholesterol transferase activity. Both CC activities result in the cleavage of the full-length protein and CC covalent attachment of a cholesterol moiety to the C-terminal of the CC newly generated N-terminal fragment (N-product). N-product is the CC active species in both local and long-range signaling, whereas the C- CC product is degraded in the endoplasmic reticulum. CC {ECO:0000250|UniProtKB:Q62226}. CC -!- PTM: [Indian hedgehog protein N-product]: Dually lipidated: a CC cholesterol moiety is attached to its C-terminus following cleavage. N- CC palmitoylated by HHAT following cholesterylation; palmitoylation is CC required for indian hedgehog protein N-product multimerization and full CC activity. {ECO:0000250|UniProtKB:Q14623}. CC -!- DISRUPTION PHENOTYPE: Almost half of homozygous embryos mice for IHH CC died between 10.5 and 12.5 dpc. Also some lethality occurred in late CC gestation, most of the remaining embryos developed to term but died at CC birth, due to respiratory failure. Mutants display markedly reduced CC chondrocyte proliferation, maturation of chondrocytes at inappropriate CC position, and a failure of osteoblast development in endochondral bones CC (PubMed:10465785). Ocular anomalies include hypopigmented and misshapen CC eyes, focal loss of the sclera in the posterior (optic nerve head) CC region of the eye, and a thin retinal pigment epithelium that is CC frequently detached from the neural retina (PubMed:18582859). CC {ECO:0000269|PubMed:10465785, ECO:0000269|PubMed:18582859}. CC -!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB49692.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U85610; AAB49692.1; ALT_INIT; mRNA. DR EMBL; X76291; CAA53923.1; -; mRNA. DR CCDS; CCDS15061.2; -. DR PIR; C49425; C49425. DR RefSeq; NP_034674.2; NM_010544.3. DR AlphaFoldDB; P97812; -. DR SMR; P97812; -. DR BioGRID; 200599; 2. DR DIP; DIP-59800N; -. DR FunCoup; P97812; 155. DR IntAct; P97812; 1. DR STRING; 10090.ENSMUSP00000128056; -. DR MEROPS; C46.003; -. DR GlyCosmos; P97812; 1 site, No reported glycans. DR GlyGen; P97812; 1 site. DR PaxDb; 10090-ENSMUSP00000128056; -. DR PeptideAtlas; P97812; -. DR ProteomicsDB; 267304; -. DR Antibodypedia; 3977; 575 antibodies from 42 providers. DR DNASU; 16147; -. DR Ensembl; ENSMPUT00000016699; ENSMPUP00000016454; ENSMPUG00000016557. DR Ensembl; ENSMUST00000164097.4; ENSMUSP00000128056.3; ENSMUSG00000006538.13. DR GeneID; 16147; -. DR KEGG; mmu:16147; -. DR AGR; MGI:96533; -. DR CTD; 3549; -. DR MGI; MGI:96533; Ihh. DR VEuPathDB; HostDB:ENSMUSG00000006538; -. DR eggNOG; KOG3638; Eukaryota. DR GeneTree; ENSGT00940000159207; -. DR InParanoid; P97812; -. DR OMA; AATDHLW; -. DR OrthoDB; 5212at2759; -. DR PhylomeDB; P97812; -. DR Reactome; R-MMU-5358346; Hedgehog ligand biogenesis. DR Reactome; R-MMU-5362798; Release of Hh-Np from the secreting cell. DR Reactome; R-MMU-5632681; Ligand-receptor interactions. DR Reactome; R-MMU-5635838; Activation of SMO. DR BioGRID-ORCS; 16147; 4 hits in 79 CRISPR screens. DR PRO; PR:P97812; -. DR Proteomes; UP000000589; Chromosome 1. DR RNAct; P97812; protein. DR Bgee; ENSMUSG00000006538; Expressed in forelimb zeugopod and 145 other cell types or tissues. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0031012; C:extracellular matrix; IDA:MGI. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; ISO:GO_Central. DR GO; GO:0140853; F:cholesterol-protein transferase activity; ISS:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB. DR GO; GO:0016015; F:morphogen activity; ISO:GO_Central. DR GO; GO:0005113; F:patched binding; IPI:BHF-UCL. DR GO; GO:0034189; F:very-low-density lipoprotein particle binding; ISS:UniProtKB. DR GO; GO:0045453; P:bone resorption; IDA:MGI. DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:MGI. DR GO; GO:0043010; P:camera-type eye development; IMP:MGI. DR GO; GO:0060220; P:camera-type eye photoreceptor cell fate commitment; IMP:MGI. DR GO; GO:0051216; P:cartilage development; IMP:MGI. DR GO; GO:0030154; P:cell differentiation; IDA:MGI. DR GO; GO:0001708; P:cell fate specification; IMP:MGI. DR GO; GO:0048469; P:cell maturation; IMP:MGI. DR GO; GO:0007267; P:cell-cell signaling; IEA:InterPro. DR GO; GO:0003413; P:chondrocyte differentiation involved in endochondral bone morphogenesis; IMP:MGI. DR GO; GO:0035988; P:chondrocyte proliferation; IMP:MGI. DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IMP:MGI. DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IMP:MGI. DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI. DR GO; GO:0009880; P:embryonic pattern specification; IMP:MGI. DR GO; GO:0072498; P:embryonic skeletal joint development; IMP:MGI. DR GO; GO:0003382; P:epithelial cell morphogenesis; IMP:MGI. DR GO; GO:0090136; P:epithelial cell-cell adhesion; IMP:MGI. DR GO; GO:0060323; P:head morphogenesis; IMP:MGI. DR GO; GO:0001947; P:heart looping; IMP:BHF-UCL. DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI. DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro. DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl. DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl. DR GO; GO:0001763; P:morphogenesis of a branching structure; IMP:MGI. DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI. DR GO; GO:0046639; P:negative regulation of alpha-beta T cell differentiation; IMP:BHF-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:GO_Central. DR GO; GO:0045596; P:negative regulation of cell differentiation; IMP:MGI. DR GO; GO:0048074; P:negative regulation of eye pigmentation; IMP:MGI. DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; IMP:BHF-UCL. DR GO; GO:0033085; P:negative regulation of T cell differentiation in thymus; IMP:BHF-UCL. DR GO; GO:0048666; P:neuron development; IMP:MGI. DR GO; GO:0001503; P:ossification; IMP:MGI. DR GO; GO:0001649; P:osteoblast differentiation; IDA:MGI. DR GO; GO:0031016; P:pancreas development; IMP:MGI. DR GO; GO:0007389; P:pattern specification process; IMP:MGI. DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; IMP:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI. DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:MGI. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:GO_Central. DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:MGI. DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISO:GO_Central. DR GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB. DR GO; GO:0006029; P:proteoglycan metabolic process; IGI:MGI. DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central. DR GO; GO:0040008; P:regulation of growth; IGI:MGI. DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0003406; P:retinal pigment epithelium development; IMP:MGI. DR GO; GO:0001501; P:skeletal system development; IMP:MGI. DR GO; GO:0048745; P:smooth muscle tissue development; IMP:MGI. DR GO; GO:0007224; P:smoothened signaling pathway; IDA:MGI. DR GO; GO:0061053; P:somite development; IMP:BHF-UCL. DR GO; GO:0001944; P:vasculature development; IMP:MGI. DR GO; GO:0030704; P:vitelline membrane formation; IMP:MGI. DR CDD; cd00081; Hint; 1. DR FunFam; 2.170.16.10:FF:000001; Indian hedgehog; 1. DR FunFam; 3.30.1380.10:FF:000001; Indian hedgehog; 1. DR Gene3D; 3.30.1380.10; -; 1. DR Gene3D; 2.170.16.10; Hedgehog/Intein (Hint) domain; 1. DR InterPro; IPR001657; Hedgehog. DR InterPro; IPR001767; Hedgehog_Hint. DR InterPro; IPR050387; Hedgehog_Signaling. DR InterPro; IPR000320; Hedgehog_signalling_dom. DR InterPro; IPR003587; Hint_dom_N. DR InterPro; IPR036844; Hint_dom_sf. DR InterPro; IPR006141; Intein_N. DR InterPro; IPR009045; Zn_M74/Hedgehog-like. DR PANTHER; PTHR11889; HEDGEHOG; 1. DR PANTHER; PTHR11889:SF39; INDIAN HEDGEHOG PROTEIN; 1. DR Pfam; PF01085; HH_signal; 1. DR Pfam; PF01079; Hint; 1. DR PIRSF; PIRSF009400; Peptidase_C46; 1. DR PRINTS; PR00632; SONICHHOG. DR SMART; SM00306; HintN; 1. DR SUPFAM; SSF55166; Hedgehog/DD-peptidase; 1. DR SUPFAM; SSF51294; Hedgehog/intein (Hint) domain; 1. DR PROSITE; PS50817; INTEIN_N_TER; 1. PE 1: Evidence at protein level; KW Autocatalytic cleavage; Calcium; Cell membrane; Developmental protein; KW Endoplasmic reticulum; Glycoprotein; Golgi apparatus; Hydrolase; KW Lipoprotein; Membrane; Metal-binding; Palmitate; Protease; KW Reference proteome; Secreted; Signal; Transferase; Zinc. FT SIGNAL 1..27 FT /evidence="ECO:0000255" FT CHAIN 28..411 FT /note="Indian hedgehog protein" FT /id="PRO_0000013232" FT CHAIN 28..202 FT /note="Indian hedgehog protein N-product" FT /id="PRO_0000013233" FT BINDING 94 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 95 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 95 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 100 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 130 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 131 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 131 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 134 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 136 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 145 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 152 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT BINDING 187 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT SITE 202..203 FT /note="Cleavage; by autolysis" FT SITE 248 FT /note="Involved in cholesterol transfer" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT SITE 272 FT /note="Involved in auto-cleavage" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT SITE 275 FT /note="Essential for auto-cleavage" FT /evidence="ECO:0000250|UniProtKB:Q02936" FT LIPID 28 FT /note="N-palmitoyl cysteine" FT /evidence="ECO:0000250|UniProtKB:Q14623" FT LIPID 202 FT /note="Cholesterol glycine ester" FT /evidence="ECO:0000250|UniProtKB:Q62226" FT CARBOHYD 282 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT MUTAGEN 95 FT /note="E->K: Knockin mice display brachydactyly type A1 FT phenotype, characterized by shortened or absent middle FT phalanges in digits. Defects are due to impaired FT interaction with PTCH1, leading to decreased smoothened FT signaling pathway." FT /evidence="ECO:0000269|PubMed:19252479" FT CONFLICT 383 FT /note="W -> S (in Ref. 2)" FT /evidence="ECO:0000305" SQ SEQUENCE 411 AA; 45485 MW; 08BE7AD8507C0D9B CRC64; MSPAWLRPRL RFCLFLLLLL LVPAARGCGP GRVVGSRRRP PRKLVPLAYK QFSPNVPEKT LGASGRYEGK IARSSERFKE LTPNYNPDII FKDEENTGAD RLMTQRCKDR LNSLAISVMN QWPGVKLRVT EGWDEDGHHS EESLHYEGRA VDITTSDRDR NKYGLLARLA VEAGFDWVYY ESKAHVHCSV KSEHSAAAKT GGCFPAGAQV RLENGERVAL SAVKPGDRVL AMGEDGTPTF SDVLIFLDRE PNRLRAFQVI ETQDPPRRLA LTPAHLLFIA DNHTEPAAHF RATFASHVQP GQYVLVSGVP GLQPARVAAV STHVALGSYA PLTRHGTLVV EDVVASCFAA VADHHLAQLA FWPLRLFPSL AWGSWTPSEG VHWYPQMLYR LGRLLLEEST FHPLGMSGAG S //