{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P12643","uniProtkbId":"BMP2_HUMAN","entryAudit":{"firstPublicDate":"1989-10-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1989-10-01","entryVersion":252,"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":{"value":"Bone morphogenetic protein 2"},"shortNames":[{"value":"BMP-2"}]},"alternativeNames":[{"fullName":{"value":"Bone morphogenetic protein 2A"},"shortNames":[{"value":"BMP-2A"}]}],"flag":"Precursor"},"genes":[{"geneName":{"value":"BMP2"},"synonyms":[{"value":"BMP2A"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P21274"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15064755"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"17295905"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18436533"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20851880"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24362451"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31019025"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31800957"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"3201241"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"7791754"}],"value":"Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis (PubMed:18436533, PubMed:24362451, PubMed:31019025). Induces cartilage and bone formation (PubMed:3201241). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2 (PubMed:15064755, PubMed:17295905, PubMed:18436533). Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A (PubMed:7791754). In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes. Also acts to promote expression of HAMP, via the interaction with its receptor BMPR1A/ALK3 (PubMed:31800957). Can also signal through non-canonical pathways such as ERK/MAP kinase signaling cascade that regulates osteoblast differentiation (PubMed:16771708, PubMed:20851880). Also stimulates the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A phosphorylation which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation (PubMed:24362451). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P21274"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10074410"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15020244"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16771708"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18184661"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18339631"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31800957"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"33308444"}],"value":"Homodimer; disulfide-linked (PubMed:10074410). Interacts with SOSTDC1 (PubMed:15020244). Interacts with GREM2, RGMA, RGMB and RGMC. Interacts with ASPN (By similarity). Interacts with MAFP5 (By similarity). Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631). Interacts with type I receptor BMPR1A (PubMed:15064755). Interacts with type II receptor BMPR2 (PubMed:7791754). Interacts with SCUBE3 (PubMed:33308444). Interacts with TNFAIP6 (primarily via Link domain); this interaction is inhibited by hyaluronan. Interacts with ERFE (PubMed:31800957). Interacts with BMPR1A/ALK3; the interaction may induce HAMP expression (PubMed:31800957). Forms heterodimers with BMP6 in vitro; the heterodimer then binds to its receptor BMPR1A /ALK3 and may induce HAMP expression (PubMed:31800957). Interacts with TGFBR3 (PubMed:18184661)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"P36894","geneName":"BMPR1A","intActId":"EBI-1029237"},"numberOfExperiments":17,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"O00238","geneName":"BMPR1B","intActId":"EBI-7527193"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"Q12841","geneName":"FSTL1","intActId":"EBI-2349801"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"Q6ZVN8","geneName":"HJV","intActId":"EBI-10900704"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"Q6ZVN8-1","geneName":"HJV","intActId":"EBI-16155543"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"Q13253","geneName":"NOG","intActId":"EBI-1035205"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"Q96B86-1","geneName":"RGMA","intActId":"EBI-16155394"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"Q6NW40","geneName":"RGMB","intActId":"EBI-16155464"},"numberOfExperiments":7,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P12643","intActId":"EBI-1029262"},"interactantTwo":{"uniProtKBAccession":"P27038","geneName":"Acvr2a","intActId":"EBI-1036102"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"chainId":"PRO_0000033825","intActId":"EBI-9697918"},"interactantTwo":{"uniProtKBAccession":"P98066","geneName":"TNFAIP6","intActId":"EBI-11700693"},"numberOfExperiments":3,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"value":"Secreted","id":"SL-0243"}}]},{"texts":[{"value":"Particularly abundant in lung, spleen and colon and in low but significant levels in heart, brain, placenta, liver, skeletal muscle, kidney, pancreas, prostate, ovary and small intestine"}],"commentType":"TISSUE SPECIFICITY"},{"commentType":"DISEASE","disease":{"diseaseId":"Brachydactyly A2","diseaseAccession":"DI-00195","acronym":"BDA2","description":"A form of brachydactyly. 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Duplications of a cis-regulatory element located approximately 110 kb downstream of BMP2 have been found in BDA2 families. They likely cause altered BMP2 expression with pathological consequences"}]}},{"commentType":"DISEASE","disease":{"diseaseId":"Short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies 1","diseaseAccession":"DI-05196","acronym":"SSFSC1","description":"An autosomal dominant disorder characterized by short stature, facial dysmorphism, skeletal anomalies, and variable cardiac defects. Distinctive facial features include midface retrusion, short upturned nose, long philtrum, high-arched or cleft palate, and variable degrees of micrognathia and dental crowding. Skeletal anomalies include patterning defects of the axial skeleton, characterized by 11 pairs of ribs and brachydactyly of the fifth ray. 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