{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P28360","secondaryAccessions":["A0SZU5","A8K3M1","Q96NY4"],"uniProtkbId":"MSX1_HUMAN","entryAudit":{"firstPublicDate":"1992-12-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2013-11-13","entryVersion":240,"sequenceVersion":3},"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:0000305"}],"value":"Homeobox protein MSX-1"}},"alternativeNames":[{"fullName":{"value":"Homeobox protein Hox-7"}},{"fullName":{"value":"Msh homeobox 1-like protein"}}]},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000312","source":"HGNC","id":"HGNC:7391"}],"value":"MSX1"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1685479"}],"value":"HOX7"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13297"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12807959"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"8696335"}],"value":"Acts as a transcriptional repressor (By similarity). Capable of transcription autoinactivation (By similarity). Binds to the consensus sequence 5'-C/GTAAT-3' in downstream activin regulatory elements (DARE) in the gene promoter, thereby repressing the transcription of CGA/alpha-GSU and GNRHR (By similarity). Represses transcription of myoblast differentiation factors (By similarity). Binds to core enhancer regions in target gene promoters of myoblast differentiation factors with binding specificity facilitated by interaction with PIAS1 (By similarity). Regulates, in a stage-specific manner, a developmental program of gene expression in the fetal tooth bud that controls odontoblast differentiation and proliferation of dental mesenchymal cells (By similarity). At the bud stage, required for mesenchymal molar tooth bud development via facilitating reciprocal signaling between dental epithelial and mesenchymal cells (By similarity). May also regulate expression of Wnt antagonists such as DKK2 and SFPR2 in the developing tooth mesenchyme (By similarity). Required for BMP4 expression in dental mesenchyme cells (By similarity). Also, in response to BMP4, required for BMP4 expression in neighboring dental epithelial cells (By similarity). Required for maximal FGF4-induced expression of SDC1 in dental mesenchyme cells (By similarity). Also in response to SDC1, required for SDC1 expression in neighboring dental epithelial cells (By similarity). At the early bell stage, acts to drive proliferation of dental mesenchyme cells, however during the late bell stage acts as an homeostatic regulator of the cell cycle (By similarity). Regulates proliferation and inhibits premature mesenchymal odontogenesis during the bell stage via inhibition of the Wnt signaling component CTNNB1 and subsequent repression of the odontoblast differentiation factors BMP2, BMP4, LEF1, ALPL and BGLAP/OCN (By similarity). Additionally, required for correct development and fusion of the palatal shelves and embryonic mandibular formation (By similarity). Plays a role in embryonic bone formation of the middle ear, skull and nasal bones (By similarity). Required for correct formation and thickness of the nail plate (By similarity). May play a role in limb-pattern formation (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13297"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16600910"}],"value":"Interacts with CREBBP/CBP, TBP and SP1; interaction with these transcription activators may inhibit autoinactivation (By similarity). Interacts (via C-terminus) with PIAS1 (via N-terminus); the interaction is required for the localization of both proteins to the nuclear periphery and specific binding of MSX1 to the core enhancer region in target gene promoters (PubMed:16600910). Interacts with H1-5 (By similarity)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P28360","intActId":"EBI-3919342"},"interactantTwo":{"uniProtKBAccession":"Q93062-3","geneName":"RBPMS","intActId":"EBI-740343"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13297"}],"value":"Interaction with PIAS1 is required for localization to the nuclear periphery (By similarity)"}]},"subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13297"}],"value":"Nucleus","id":"SL-0191"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13297"}],"value":"Sumoylated by PIAS1, desumoylated by SENP1 (By similarity). Sumoylation of Lys-15 and Lys-133 not required for interaction with H1-5, transcriptional repression, inhibition of myoblast differentiation, or binding to gene promoters (By similarity)"}],"commentType":"PTM"},{"commentType":"DISEASE","disease":{"diseaseId":"Tooth agenesis, selective, 1","diseaseAccession":"DI-01211","acronym":"STHAG1","description":"A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG1 can be associated with orofacial cleft in some patients.","diseaseCrossReference":{"database":"MIM","id":"106600"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12097313"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8696335"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"1969845"}],"value":"MSX1 is deleted in some patients with Wolf-Hirschhorn syndrome (WHS). WHS results from sub-telomeric deletions in the short arm of chromosome 4"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Ectodermal dysplasia 3, Witkop type","diseaseAccession":"DI-01148","acronym":"ECTD3","description":"A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures such as hair, teeth, nails and sweat glands, with or without any additional clinical sign. Each combination of clinical features represents a different type of ectodermal dysplasia. ECTD3 is characterized by abnormalities largely limited largely to teeth (some of which are missing) and nails (which are poorly formed early in life, especially toenails). This condition is distinguished from anhidrotic ectodermal dysplasia by autosomal dominant inheritance and little involvement of hair and sweat glands. The teeth are not as severely affected.","diseaseCrossReference":{"database":"MIM","id":"189500"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11369996"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Non-syndromic orofacial cleft 5","diseaseAccession":"DI-00826","acronym":"OFC5","description":"A birth defect consisting of cleft lips with or without cleft palate. Cleft lips are associated with cleft palate in two-third of cases. A cleft lip can occur on one or both sides and range in severity from a simple notch in the upper lip to a complete opening in the lip extending into the floor of the nostril and involving the upper gum.","diseaseCrossReference":{"database":"MIM","id":"608874"},"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12807959"}]},"note":{"texts":[{"value":"The disease is caused by variants affecting the gene represented in this entry"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the Msh homeobox family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"It is uncertain whether Met-1 or Met-7 is the initiator"}],"commentType":"CAUTION"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"AAA52683.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"AAA58665.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"AAH67353.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"AAL17870.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"ABK81117.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Erroneous initiation","sequence":"BAF83325.1","note":"Truncated N-terminus.","evidences":[{"evidenceCode":"ECO:0000305"}]}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":303,"modifier":"EXACT"}},"description":"Homeobox protein MSX-1","featureId":"PRO_0000049086"},{"type":"DNA binding","location":{"start":{"value":172,"modifier":"EXACT"},"end":{"value":231,"modifier":"EXACT"}},"description":"Homeobox","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00108"}]},{"type":"Region","location":{"start":{"value":18,"modifier":"EXACT"},"end":{"value":55,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":69,"modifier":"EXACT"},"end":{"value":117,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Region","location":{"start":{"value":133,"modifier":"EXACT"},"end":{"value":174,"modifier":"EXACT"}},"description":"Disordered","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":31,"modifier":"EXACT"},"end":{"value":44,"modifier":"EXACT"}},"description":"Low complexity","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Compositional bias","location":{"start":{"value":133,"modifier":"EXACT"},"end":{"value":142,"modifier":"EXACT"}},"description":"Basic and acidic residues","evidences":[{"evidenceCode":"ECO:0000256","source":"SAM","id":"MobiDB-lite"}]},{"type":"Cross-link","location":{"start":{"value":15,"modifier":"EXACT"},"end":{"value":15,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13297"}]},{"type":"Cross-link","location":{"start":{"value":133,"modifier":"EXACT"},"end":{"value":133,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P13297"}]},{"type":"Natural variant","location":{"start":{"value":67,"modifier":"EXACT"},"end":{"value":67,"modifier":"EXACT"}},"description":"in STHAG1; 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