ID BMP4_HUMAN Reviewed; 408 AA. AC P12644; Q9UM80; DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 1. DT 27-NOV-2024, entry version 239. DE RecName: Full=Bone morphogenetic protein 4 {ECO:0000312|HGNC:HGNC:1071}; DE Short=BMP-4 {ECO:0000250|UniProtKB:P21275}; DE AltName: Full=Bone morphogenetic protein 2B {ECO:0000250|UniProtKB:P21275}; DE Short=BMP-2B {ECO:0000312|HGNC:HGNC:1071}; DE Flags: Precursor; GN Name=BMP4 {ECO:0000312|HGNC:HGNC:1071}; GN Synonyms=BMP2B {ECO:0000312|HGNC:HGNC:1071}, DVR4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3201241; DOI=10.1126/science.3201241; RA Wozney J.M., Rosen V., Celeste A.J., Mitsock L.M., Whitters M.J., RA Kriz R.W., Hewick R.M., Wang E.A.; RT "Novel regulators of bone formation: molecular clones and activities."; RL Science 242:1528-1534(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-152. RX PubMed=9701626; DOI=10.1007/s002239900518; RA Shore E.M., Xu M., Shah P.B., Janoff H.B., Hahn G.V., Deardorff M.A., RA Sovinsky L., Spinner N.B., Zasloff M.A., Wozney J.M., Kaplan F.S.; RT "The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure RT and transcriptional regulation."; RL Calcif. Tissue Int. 63:221-229(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-152. RC TISSUE=Duodenum; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-408. RC TISSUE=Placenta; RX PubMed=7579580; DOI=10.3109/10425179509030980; RA Oida S., Iimura T., Maruoka Y., Takeda K., Sasaki S.; RT "Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human RT placental cDNA library."; RL DNA Seq. 5:273-275(1995). RN [5] RP INTERACTION WITH BMPR1A, AND FUNCTION. RX PubMed=8006002; DOI=10.1016/s0021-9258(17)32506-1; RA ten Dijke P., Yamashita H., Sampath T.K., Reddi A.H., Estevez M., RA Riddle D.L., Ichijo H., Heldin C.H., Miyazono K.; RT "Identification of type I receptors for osteogenic protein-1 and bone RT morphogenetic protein-4."; RL J. Biol. Chem. 269:16985-16988(1994). RN [6] RP INTERACTION WITH SOSTDC1. RX PubMed=15020244; DOI=10.1016/j.bbrc.2004.02.075; RA Yanagita M., Oka M., Watabe T., Iguchi H., Niida A., Takahashi S., RA Akiyama T., Miyazono K., Yanagisawa M., Sakurai T.; RT "USAG-1: a bone morphogenetic protein antagonist abundantly expressed in RT the kidney."; RL Biochem. Biophys. Res. Commun. 316:490-500(2004). RN [7] RP INTERACTION WITH FBN1 AND FBN2. RX PubMed=18339631; DOI=10.1074/jbc.m707820200; RA Sengle G., Charbonneau N.L., Ono R.N., Sasaki T., Alvarez J., Keene D.R., RA Baechinger H.P., Sakai L.Y.; RT "Targeting of bone morphogenetic protein growth factor complexes to RT fibrillin."; RL J. Biol. Chem. 283:13874-13888(2008). RN [8] RP INTERACTION WITH TGFBR3. RX PubMed=18184661; DOI=10.1074/jbc.m704883200; RA Kirkbride K.C., Townsend T.A., Bruinsma M.W., Barnett J.V., Blobe G.C.; RT "Bone morphogenetic proteins signal through the transforming growth factor- RT beta type III receptor."; RL J. Biol. Chem. 283:7628-7637(2008). RN [9] RP PHOSPHORYLATION AT SER-91. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted phosphoproteome."; RL Cell 161:1619-1632(2015). RN [10] RP FUNCTION. RX PubMed=25868050; DOI=10.1210/en.2014-1942; RA Rege J., Nishimoto H.K., Nishimoto K., Rodgers R.J., Auchus R.J., RA Rainey W.E.; RT "Bone Morphogenetic Protein-4 (BMP4): A Paracrine Regulator of Human RT Adrenal C19 Steroid Synthesis."; RL Endocrinology 156:2530-2540(2015). RN [11] RP FUNCTION, AND INTERACTION WITH BMPR2 AND FTLS1. RX PubMed=29212066; DOI=10.1159/000485759; RA Jin X., Nie E., Zhou X., Zeng A., Yu T., Zhi T., Jiang K., Wang Y., RA Zhang J., You Y.; RT "Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling RT Pathway."; RL Cell. Physiol. Biochem. 44:1616-1628(2017). RN [12] RP FUNCTION IN ANGIOGENESIS. RX PubMed=31363885; DOI=10.1007/s10456-019-09676-y; RA Rezzola S., Di Somma M., Corsini M., Leali D., Ravelli C., Polli V.A.B., RA Grillo E., Presta M., Mitola S.; RT "VEGFR2 activation mediates the pro-angiogenic activity of BMP4."; RL Angiogenesis 22:521-533(2019). RN [13] RP INTERACTION WITH SCUBE3. RX PubMed=33308444; DOI=10.1016/j.ajhg.2020.11.015; RG Genomics England Research Consortium; RA Lin Y.C., Niceta M., Muto V., Vona B., Pagnamenta A.T., Maroofian R., RA Beetz C., van Duyvenvoorde H., Dentici M.L., Lauffer P., Vallian S., RA Ciolfi A., Pizzi S., Bauer P., Gruening N.M., Bellacchio E., RA Del Fattore A., Petrini S., Shaheen R., Tiosano D., Halloun R., RA Pode-Shakked B., Albayrak H.M., Isik E., Wit J.M., Dittrich M., RA Freire B.L., Bertola D.R., Jorge A.A.L., Barel O., Sabir A.H., RA Al Tenaiji A.M.J., Taji S.M., Al-Sannaa N., Al-Abdulwahed H., Digilio M.C., RA Irving M., Anikster Y., Bhavani G.S.L., Girisha K.M., Haaf T., Taylor J.C., RA Dallapiccola B., Alkuraya F.S., Yang R.B., Tartaglia M.; RT "SCUBE3 loss-of-function causes a recognizable recessive developmental RT disorder due to defective bone morphogenetic protein signaling."; RL Am. J. Hum. Genet. 108:115-133(2021). RN [14] RP VARIANTS CYS-91; ALA-152; ALA-225; TRP-226 AND THR-367. RX PubMed=12404109; DOI=10.1038/sj.ejhg.5200875; RA Felder B., Stegmann K., Schultealbert A., Geller F., Strehl E., Ermert A., RA Koch M.C.; RT "Evaluation of BMP4 and its specific inhibitor NOG as candidates in human RT neural tube defects (NTDs)."; RL Eur. J. Hum. Genet. 10:753-756(2002). RN [15] RP VARIANT MCOPS6 GLY-93. RX PubMed=18252212; DOI=10.1016/j.ajhg.2007.09.023; RA Bakrania P., Efthymiou M., Klein J.C., Salt A., Bunyan D.J., Wyatt A., RA Ponting C.P., Martin A., Williams S., Lindley V., Gilmore J., Restori M., RA Robson A.G., Neveu M.M., Holder G.E., Collin J.R.O., Robinson D.O., RA Farndon P., Johansen-Berg H., Gerrelli D., Ragge N.K.; RT "Mutations in BMP4 cause eye, brain, and digit developmental anomalies: RT overlap between the BMP4 and hedgehog signaling pathways."; RL Am. J. Hum. Genet. 82d:304-319(2008). RN [16] RP VARIANTS CYS-91; SER-116 AND LYS-150. RX PubMed=18305125; DOI=10.1681/asn.2006111282; RA Weber S., Taylor J.C., Winyard P., Baker K.F., Sullivan-Brown J., RA Schild R., Knueppel T., Zurowska A.M., Caldas-Alfonso A., Litwin M., RA Emre S., Ghiggeri G.M., Bakkaloglu A., Mehls O., Antignac C., Schaefer F., RA Burdine R.D.; RT "SIX2 and BMP4 mutations associate with anomalous kidney development."; RL J. Am. Soc. Nephrol. 19:891-903(2008). RN [17] RP VARIANTS OFC11 CYS-91; GLN-162; HIS-287 AND VAL-346, AND VARIANTS ALA-102; RP ALA-152 AND ALA-168. RX PubMed=19249007; DOI=10.1016/j.ajhg.2009.02.002; RA Suzuki S., Marazita M.L., Cooper M.E., Miwa N., Hing A., Jugessur A., RA Natsume N., Shimozato K., Ohbayashi N., Suzuki Y., Niimi T., Minami K., RA Yamamoto M., Altannamar T.J., Erkhembaatar T., Furukawa H., RA Daack-Hirsch S., L'heureux J., Brandon C.A., Weinberg S.M., Neiswanger K., RA Deleyiannis F.W., de Salamanca J.E., Vieira A.R., Lidral A.C., Martin J.F., RA Murray J.C.; RT "Mutations in BMP4 are associated with subepithelial, microform, and overt RT cleft lip."; RL Am. J. Hum. Genet. 84:406-411(2009). CC -!- FUNCTION: Growth factor of the TGF-beta superfamily that plays CC essential roles in many developmental processes, including CC neurogenesis, vascular development, angiogenesis and osteogenesis CC (PubMed:31363885). Acts in concert with PTHLH/PTHRP to stimulate ductal CC outgrowth during embryonic mammary development and to inhibit hair CC follicle induction (By similarity). Initiates the canonical BMP CC signaling cascade by associating with type I receptor BMPR1A and type CC II receptor BMPR2 (PubMed:25868050, PubMed:8006002). Once all three CC components are bound together in a complex at the cell surface, BMPR2 CC phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal CC by phosphorylating SMAD1/5/8 that travel to the nucleus and act as CC activators and repressors of transcription of target genes CC (PubMed:25868050, PubMed:29212066). Positively regulates the expression CC of odontogenic development regulator MSX1 via inducing the IPO7- CC mediated import of SMAD1 to the nucleus (By similarity). Required for CC MSX1-mediated mesenchymal molar tooth bud development beyond the bud CC stage, via promoting Wnt signaling (By similarity). Acts as a positive CC regulator of odontoblast differentiation during mesenchymal tooth germ CC formation, expression is repressed during the bell stage by MSX1- CC mediated inhibition of CTNNB1 signaling (By similarity). Able to induce CC its own expression in dental mesenchymal cells and also in the CC neighboring dental epithelial cells via an MSX1-mediated pathway (By CC similarity). Can also signal through non-canonical BMP pathways such as CC ERK/MAP kinase, PI3K/Akt, or SRC cascades (PubMed:31363885). For CC example, induces SRC phosphorylation which, in turn, activates VEGFR2, CC leading to an angiogenic response (PubMed:31363885). CC {ECO:0000250|UniProtKB:P21275, ECO:0000269|PubMed:25868050, CC ECO:0000269|PubMed:29212066, ECO:0000269|PubMed:31363885, CC ECO:0000269|PubMed:8006002}. CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with CC GREM2. Part of a complex consisting of TWSG1 and CHRD. Interacts with CC the serine proteases, HTRA1 and HTRA3; the interaction with either CC inhibits BMP4-mediated signaling. The HTRA protease activity is CC required for this inhibition (By similarity). Interacts with SOSTDC1. CC Interacts with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631). CC Interacts with type I receptor BMPR1A (PubMed:8006002). Interacts with CC type II receptor BMPR2 (PubMed:29212066). Interacts with FSTL1; this CC interaction inhibits the activation of the BMP4/Smad1/5/8 signaling CC pathway (PubMed:29212066). Interacts with SCUBE3 (PubMed:33308444). CC Interacts with TGFBR3 (PubMed:18184661). {ECO:0000250|UniProtKB:P21275, CC ECO:0000269|PubMed:15020244, ECO:0000269|PubMed:18184661, CC ECO:0000269|PubMed:18339631, ECO:0000269|PubMed:29212066, CC ECO:0000269|PubMed:33308444, ECO:0000269|PubMed:8006002}. CC -!- INTERACTION: CC P12644; P36894: BMPR1A; NbExp=2; IntAct=EBI-1998134, EBI-1029237; CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular CC matrix. CC -!- TISSUE SPECIFICITY: Expressed in the lung and lower levels seen in the CC kidney. Present also in normal and neoplastic prostate tissues, and CC prostate cancer cell lines. CC -!- DISEASE: Microphthalmia, syndromic, 6 (MCOPS6) [MIM:607932]: A disease CC characterized by microphthalmia/anophthalmia associated with facial, CC genital, skeletal, neurologic and endocrine anomalies. Microphthalmia CC is a disorder of eye formation, ranging from small size of a single eye CC to complete bilateral absence of ocular tissues (anophthalmia). In many CC cases, microphthalmia/anophthalmia occurs in association with syndromes CC that include non-ocular abnormalities. {ECO:0000269|PubMed:18252212}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Non-syndromic orofacial cleft 11 (OFC11) [MIM:600625]: A birth CC defect consisting of cleft lips with or without cleft palate. Cleft CC lips are associated with cleft palate in two-third of cases. A cleft CC lip can occur on one or both sides and range in severity from a simple CC notch in the upper lip to a complete opening in the lip extending into CC the floor of the nostril and involving the upper gum. CC {ECO:0000269|PubMed:19249007}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Bone morphogenetic protein 4 entry; CC URL="https://en.wikipedia.org/wiki/Bone_morphogenetic_protein_4"; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/811/BMP4"; 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; M22490; AAA51835.1; -; mRNA. DR EMBL; U43842; AAC72278.1; -; Genomic_DNA. DR EMBL; BC020546; AAH20546.1; -; mRNA. DR EMBL; D30751; BAA06410.1; -; mRNA. DR CCDS; CCDS9715.1; -. DR PIR; C37278; BMHU4. DR RefSeq; NP_001193.2; NM_001202.5. DR RefSeq; NP_001334843.1; NM_001347914.1. DR RefSeq; NP_001334845.1; NM_001347916.1. DR RefSeq; NP_570911.2; NM_130850.4. DR RefSeq; NP_570912.2; NM_130851.3. DR AlphaFoldDB; P12644; -. DR SMR; P12644; -. DR BioGRID; 107120; 178. DR CORUM; P12644; -. DR DIP; DIP-5795N; -. DR ELM; P12644; -. DR IntAct; P12644; 50. DR MINT; P12644; -. DR STRING; 9606.ENSP00000245451; -. DR BindingDB; P12644; -. DR ChEMBL; CHEMBL5350; -. DR DrugBank; DB01373; Calcium. DR GlyCosmos; P12644; 4 sites, No reported glycans. DR GlyGen; P12644; 4 sites. DR iPTMnet; P12644; -. DR PhosphoSitePlus; P12644; -. DR BioMuta; BMP4; -. DR DMDM; 115073; -. DR jPOST; P12644; -. DR MassIVE; P12644; -. DR PaxDb; 9606-ENSP00000245451; -. DR PeptideAtlas; P12644; -. DR ProteomicsDB; 52861; -. DR Antibodypedia; 3485; 875 antibodies from 46 providers. DR DNASU; 652; -. DR Ensembl; ENST00000245451.9; ENSP00000245451.4; ENSG00000125378.16. DR Ensembl; ENST00000417573.5; ENSP00000394165.1; ENSG00000125378.16. DR Ensembl; ENST00000558984.1; ENSP00000454134.1; ENSG00000125378.16. DR Ensembl; ENST00000559087.5; ENSP00000453485.1; ENSG00000125378.16. DR GeneID; 652; -. DR KEGG; hsa:652; -. DR MANE-Select; ENST00000245451.9; ENSP00000245451.4; NM_001202.6; NP_001193.2. DR AGR; HGNC:1071; -. DR CTD; 652; -. DR DisGeNET; 652; -. DR GeneCards; BMP4; -. DR HGNC; HGNC:1071; BMP4. DR HPA; ENSG00000125378; Tissue enhanced (choroid). DR MalaCards; BMP4; -. DR MIM; 112262; gene. DR MIM; 600625; phenotype. DR MIM; 607932; phenotype. DR neXtProt; NX_P12644; -. DR OpenTargets; ENSG00000125378; -. DR Orphanet; 199306; Cleft lip/palate. DR Orphanet; 139471; Microphthalmia with brain and digit anomalies. DR Orphanet; 93100; Renal agenesis, unilateral. DR Orphanet; 828; Stickler syndrome. DR PharmGKB; PA25381; -. DR VEuPathDB; HostDB:ENSG00000125378; -. DR eggNOG; KOG3900; Eukaryota. DR GeneTree; ENSGT00940000159502; -. DR HOGENOM; CLU_020515_4_2_1; -. DR InParanoid; P12644; -. DR OMA; HEEHMEQ; -. DR OrthoDB; 2912454at2759; -. DR PhylomeDB; P12644; -. DR TreeFam; TF351789; -. DR PathwayCommons; P12644; -. DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres. DR Reactome; R-HSA-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR Reactome; R-HSA-9754189; Germ layer formation at gastrulation. DR Reactome; R-HSA-9758920; Formation of lateral plate mesoderm. DR Reactome; R-HSA-9761174; Formation of intermediate mesoderm. DR Reactome; R-HSA-9793380; Formation of paraxial mesoderm. DR Reactome; R-HSA-9827857; Specification of primordial germ cells. DR Reactome; R-HSA-9830364; Formation of the nephric duct. DR Reactome; R-HSA-9830674; Formation of the ureteric bud. DR Reactome; R-HSA-9834899; Specification of the neural plate border. DR SignaLink; P12644; -. DR SIGNOR; P12644; -. DR BioGRID-ORCS; 652; 13 hits in 1150 CRISPR screens. DR ChiTaRS; BMP4; human. DR GeneWiki; Bone_morphogenetic_protein_4; -. DR GenomeRNAi; 652; -. DR Pharos; P12644; Tchem. DR PRO; PR:P12644; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P12644; protein. DR Bgee; ENSG00000125378; Expressed in pigmented layer of retina and 124 other cell types or tissues. DR ExpressionAtlas; P12644; baseline and differential. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0070700; F:BMP receptor binding; IDA:MGI. DR GO; GO:0042056; F:chemoattractant activity; IDA:UniProtKB. DR GO; GO:0039706; F:co-receptor binding; IPI:BHF-UCL. DR GO; GO:0005125; F:cytokine activity; IDA:MGI. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0008201; F:heparin binding; IEA:Ensembl. DR GO; GO:0036305; P:ameloblast differentiation; IEA:Ensembl. DR GO; GO:0009948; P:anterior/posterior axis specification; IEA:Ensembl. DR GO; GO:0003180; P:aortic valve morphogenesis; ISS:BHF-UCL. DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; IDA:BHF-UCL. DR GO; GO:0030509; P:BMP signaling pathway; IDA:UniProtKB. DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IEA:Ensembl. DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IDA:UniProtKB. DR GO; GO:0060433; P:bronchus development; IDA:MGI. DR GO; GO:0060503; P:bud dilation involved in lung branching; IDA:MGI. DR GO; GO:0060449; P:bud elongation involved in lung branching; IEA:Ensembl. DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEA:Ensembl. DR GO; GO:0003279; P:cardiac septum development; TAS:BHF-UCL. DR GO; GO:0071773; P:cellular response to BMP stimulus; IMP:BHF-UCL. DR GO; GO:0002062; P:chondrocyte differentiation; ISS:UniProtKB. DR GO; GO:0060976; P:coronary vasculature development; ISS:BHF-UCL. DR GO; GO:0060363; P:cranial suture morphogenesis; IEA:Ensembl. DR GO; GO:0035993; P:deltoid tuberosity development; ISS:UniProtKB. DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IEA:Ensembl. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl. DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl. DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl. DR GO; GO:0060272; P:embryonic skeletal joint morphogenesis; IEA:Ensembl. DR GO; GO:0003197; P:endocardial cushion development; ISS:BHF-UCL. DR GO; GO:0001958; P:endochondral ossification; ISS:UniProtKB. DR GO; GO:0007492; P:endoderm development; IEA:Ensembl. DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; IDA:MGI. DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IDA:MGI. DR GO; GO:0060684; P:epithelial-mesenchymal cell signaling; IEA:Ensembl. DR GO; GO:0030218; P:erythrocyte differentiation; IEA:Ensembl. DR GO; GO:0007281; P:germ cell development; IEA:Ensembl. DR GO; GO:0072104; P:glomerular capillary formation; ISS:UniProtKB. DR GO; GO:0003129; P:heart induction; IMP:BHF-UCL. DR GO; GO:0003007; P:heart morphogenesis; IMP:BHF-UCL. DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IDA:UniProtKB. DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl. DR GO; GO:0048392; P:intermediate mesodermal cell differentiation; IDA:UniProtKB. DR GO; GO:0001822; P:kidney development; IMP:UniProtKB. DR GO; GO:0060235; P:lens induction in camera-type eye; IEA:Ensembl. DR GO; GO:0048286; P:lung alveolus development; IDA:MGI. DR GO; GO:0060425; P:lung morphogenesis; IDA:MGI. DR GO; GO:0060426; P:lung vasculature development; IMP:UniProtKB. DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IMP:BHF-UCL. DR GO; GO:0030225; P:macrophage differentiation; IDA:DFLAT. DR GO; GO:0060592; P:mammary gland formation; IEA:Ensembl. DR GO; GO:0003149; P:membranous septum morphogenesis; ISS:BHF-UCL. DR GO; GO:0007500; P:mesodermal cell fate determination; IEA:Ensembl. DR GO; GO:0001823; P:mesonephros development; IEP:UniProtKB. DR GO; GO:0001656; P:metanephros development; IEA:Ensembl. DR GO; GO:0030224; P:monocyte differentiation; IDA:DFLAT. DR GO; GO:0090191; P:negative regulation of branching involved in ureteric bud morphogenesis; IDA:UniProtKB. DR GO; GO:0045786; P:negative regulation of cell cycle; IDA:HGNC-UCL. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI. DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; ISS:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0072125; P:negative regulation of glomerular mesangial cell proliferation; IDA:UniProtKB. DR GO; GO:0090194; P:negative regulation of glomerulus development; IDA:UniProtKB. DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; IMP:BHF-UCL. DR GO; GO:0072200; P:negative regulation of mesenchymal cell proliferation involved in ureter development; IDA:UniProtKB. DR GO; GO:2000007; P:negative regulation of metanephric comma-shaped body morphogenesis; IDA:UniProtKB. DR GO; GO:2000005; P:negative regulation of metanephric S-shaped body morphogenesis; IDA:UniProtKB. DR GO; GO:1902894; P:negative regulation of miRNA transcription; IDA:BHF-UCL. DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; IDA:UniProtKB. DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IDA:MGI. DR GO; GO:0060686; P:negative regulation of prostatic bud formation; IEA:Ensembl. DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; IDA:MGI. DR GO; GO:0033085; P:negative regulation of T cell differentiation in thymus; IMP:BHF-UCL. DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; IMP:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI. DR GO; GO:1904753; P:negative regulation of vascular associated smooth muscle cell migration; TAS:BHF-UCL. DR GO; GO:1904706; P:negative regulation of vascular associated smooth muscle cell proliferation; TAS:BHF-UCL. DR GO; GO:0072179; P:nephric duct formation; IDA:UniProtKB. DR GO; GO:0001843; P:neural tube closure; IEA:Ensembl. DR GO; GO:0048663; P:neuron fate commitment; IEA:Ensembl. DR GO; GO:0042476; P:odontogenesis; IGI:UniProtKB. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0001649; P:osteoblast differentiation; IDA:BHF-UCL. DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISS:BHF-UCL. DR GO; GO:1904238; P:pericyte cell differentiation; IEA:Ensembl. DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; ISS:BHF-UCL. DR GO; GO:0021983; P:pituitary gland development; IEA:Ensembl. DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:MGI. DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISS:UniProtKB. DR GO; GO:0030501; P:positive regulation of bone mineralization; IDA:UniProtKB. DR GO; GO:0061047; P:positive regulation of branching involved in lung morphogenesis; ISS:UniProtKB. DR GO; GO:0055020; P:positive regulation of cardiac muscle fiber development; IMP:BHF-UCL. DR GO; GO:1905312; P:positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis; IEA:Ensembl. DR GO; GO:0061036; P:positive regulation of cartilage development; IDA:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL. DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IEA:Ensembl. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Ensembl. DR GO; GO:0045606; P:positive regulation of epidermal cell differentiation; IDA:UniProtKB. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IDA:BHF-UCL. DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; IDA:BHF-UCL. DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl. DR GO; GO:1901331; P:positive regulation of odontoblast differentiation; ISS:UniProtKB. DR GO; GO:0045778; P:positive regulation of ossification; IDA:MGI. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:MGI. DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:UniProtKB. DR GO; GO:2000636; P:positive regulation of primary miRNA processing; IDA:BHF-UCL. DR GO; GO:0043068; P:positive regulation of programmed cell death; IDA:MGI. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:MGI. DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; ISS:UniProtKB. DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:UniProtKB. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IDA:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0009791; P:post-embryonic development; IDA:MGI. DR GO; GO:0060513; P:prostatic bud formation; IEA:Ensembl. DR GO; GO:0003184; P:pulmonary valve morphogenesis; ISS:BHF-UCL. DR GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IEA:Ensembl. DR GO; GO:0010453; P:regulation of cell fate commitment; IDA:UniProtKB. DR GO; GO:1905770; P:regulation of mesodermal cell differentiation; IEA:Ensembl. DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0042306; P:regulation of protein import into nucleus; IDA:MGI. DR GO; GO:0051150; P:regulation of smooth muscle cell differentiation; IEA:Ensembl. DR GO; GO:0003014; P:renal system process; IEA:Ensembl. DR GO; GO:0003139; P:secondary heart field specification; IMP:BHF-UCL. DR GO; GO:0003163; P:sinoatrial node development; NAS:BHF-UCL. DR GO; GO:0051145; P:smooth muscle cell differentiation; IEA:Ensembl. DR GO; GO:0048745; P:smooth muscle tissue development; IEP:UniProtKB. DR GO; GO:0010159; P:specification of animal organ position; IEA:Ensembl. DR GO; GO:0042305; P:specification of segmental identity, mandibular segment; IEA:Ensembl. DR GO; GO:0021537; P:telencephalon development; IDA:MGI. DR GO; GO:0021978; P:telencephalon regionalization; IEA:Ensembl. DR GO; GO:0035990; P:tendon cell differentiation; ISS:UniProtKB. DR GO; GO:0060438; P:trachea development; IDA:MGI. DR GO; GO:0060440; P:trachea formation; IEA:Ensembl. DR GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl. DR GO; GO:0003323; P:type B pancreatic cell development; IDA:BHF-UCL. DR GO; GO:0072197; P:ureter morphogenesis; IEA:Ensembl. DR GO; GO:0001657; P:ureteric bud development; IDA:MGI. DR CDD; cd19391; TGF_beta_BMP4_BMP2B; 1. DR FunFam; 2.10.90.10:FF:000103; Bone morphogenetic protein 16; 1. DR FunFam; 2.60.120.970:FF:000005; Bone morphogenetic protein 4; 1. DR Gene3D; 2.60.120.970; -; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR InterPro; IPR047833; BMP4_TGF_beta-like. DR InterPro; IPR029034; Cystine-knot_cytokine. DR InterPro; IPR001839; TGF-b_C. DR InterPro; IPR001111; TGF-b_propeptide. DR InterPro; IPR015615; TGF-beta-rel. DR InterPro; IPR017948; TGFb_CS. DR PANTHER; PTHR11848:SF165; BONE MORPHOGENETIC PROTEIN 4; 1. DR PANTHER; PTHR11848; TGF-BETA FAMILY; 1. DR Pfam; PF00019; TGF_beta; 1. DR Pfam; PF00688; TGFb_propeptide; 1. DR SMART; SM00204; TGFB; 1. DR SUPFAM; SSF57501; Cystine-knot cytokines; 1. DR PROSITE; PS00250; TGF_BETA_1; 1. DR PROSITE; PS51362; TGF_BETA_2; 1. PE 1: Evidence at protein level; KW Chondrogenesis; Cleavage on pair of basic residues; Cytokine; KW Developmental protein; Differentiation; Disease variant; Disulfide bond; KW Extracellular matrix; Glycoprotein; Growth factor; Microphthalmia; KW Osteogenesis; Phosphoprotein; Proteomics identification; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT PROPEP 20..292 FT /id="PRO_0000033856" FT CHAIN 293..408 FT /note="Bone morphogenetic protein 4" FT /id="PRO_0000033857" FT REGION 283..307 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 91 FT /note="Phosphoserine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039" FT CARBOHYD 143 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 208 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 350 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 365 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 308..373 FT /evidence="ECO:0000250" FT DISULFID 337..405 FT /evidence="ECO:0000250" FT DISULFID 341..407 FT /evidence="ECO:0000250" FT DISULFID 372 FT /note="Interchain" FT /evidence="ECO:0000250" FT VARIANT 91 FT /note="S -> C (in OFC11; also found in renal hypodysplasia FT patients; dbSNP:rs121912767)" FT /evidence="ECO:0000269|PubMed:12404109, FT ECO:0000269|PubMed:18305125, ECO:0000269|PubMed:19249007" FT /id="VAR_043531" FT VARIANT 93 FT /note="E -> G (in MCOPS6; dbSNP:rs121912765)" FT /evidence="ECO:0000269|PubMed:18252212" FT /id="VAR_043532" FT VARIANT 102 FT /note="T -> A (in dbSNP:rs202159001)" FT /evidence="ECO:0000269|PubMed:19249007" FT /id="VAR_058314" FT VARIANT 116 FT /note="T -> S (in a renal hypodysplasia patient; FT dbSNP:rs750427266)" FT /evidence="ECO:0000269|PubMed:18305125" FT /id="VAR_043533" FT VARIANT 150 FT /note="N -> K (in a renal hypodysplasia patient; FT dbSNP:rs767216159)" FT /evidence="ECO:0000269|PubMed:18305125" FT /id="VAR_043534" FT VARIANT 152 FT /note="V -> A (in dbSNP:rs17563)" FT /evidence="ECO:0000269|PubMed:12404109, FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:19249007, FT ECO:0000269|PubMed:9701626" FT /id="VAR_016174" FT VARIANT 162 FT /note="R -> Q (in OFC11; dbSNP:rs770493925)" FT /evidence="ECO:0000269|PubMed:19249007" FT /id="VAR_058315" FT VARIANT 168 FT /note="G -> A" FT /evidence="ECO:0000269|PubMed:19249007" FT /id="VAR_058316" FT VARIANT 225 FT /note="T -> A (in dbSNP:rs144556455)" FT /evidence="ECO:0000269|PubMed:12404109" FT /id="VAR_043535" FT VARIANT 226 FT /note="R -> W (in dbSNP:rs140590144)" FT /evidence="ECO:0000269|PubMed:12404109" FT /id="VAR_043536" FT VARIANT 287 FT /note="R -> H (in OFC11; dbSNP:rs121912768)" FT /evidence="ECO:0000269|PubMed:19249007" FT /id="VAR_058317" FT VARIANT 346 FT /note="A -> V (in OFC11; dbSNP:rs121912766)" FT /evidence="ECO:0000269|PubMed:19249007" FT /id="VAR_058318" FT VARIANT 367 FT /note="S -> T (in dbSNP:rs1320581580)" FT /evidence="ECO:0000269|PubMed:12404109" FT /id="VAR_043537" SQ SEQUENCE 408 AA; 46555 MW; 79B01179DBB98204 CRC64; MIPGNRMLMV VLLCQVLLGG ASHASLIPET GKKKVAEIQG HAGGRRSGQS HELLRDFEAT LLQMFGLRRR PQPSKSAVIP DYMRDLYRLQ SGEEEEEQIH STGLEYPERP ASRANTVRSF HHEEHLENIP GTSENSAFRF LFNLSSIPEN EVISSAELRL FREQVDQGPD WERGFHRINI YEVMKPPAEV VPGHLITRLL DTRLVHHNVT RWETFDVSPA VLRWTREKQP NYGLAIEVTH LHQTRTHQGQ HVRISRSLPQ GSGNWAQLRP LLVTFGHDGR GHALTRRRRA KRSPKHHSQR ARKKNKNCRR HSLYVDFSDV GWNDWIVAPP GYQAFYCHGD CPFPLADHLN STNHAIVQTL VNSVNSSIPK ACCVPTELSA ISMLYLDEYD KVVLKNYQEM VVEGCGCR //