BMP4_HUMAN
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 03-AUG-2022, entry version 226.
DE RecName: Full=Bone morphogenetic protein 4;
DE Short=BMP-4;
DE AltName: Full=Bone morphogenetic protein 2B;
DE Short=BMP-2B;
DE Flags: Precursor;
GN Name=BMP4; Synonyms=BMP2B, 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 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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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). Can also signal through non-
CC canonical BMP pathways such as ERK/MAP kinase, PI3K/Akt, or SRC
CC cascades (PubMed:31363885). For example, induces SRC phosphorylation
CC which, in turn, activates VEGFR2, leading to an angiogenic response
CC (PubMed:31363885). {ECO:0000250|UniProtKB:P21275,
CC ECO:0000269|PubMed:25868050, ECO:0000269|PubMed:29212066,
CC ECO:0000269|PubMed:31363885, 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 {ECO:0000250|UniProtKB:P21275, ECO:0000269|PubMed:15020244,
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="http://atlasgeneticsoncology.org/Genes/BMP4ID811ch14q22.html";
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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; 177.
DR CORUM; P12644; -.
DR DIP; DIP-5795N; -.
DR ELM; P12644; -.
DR IntAct; P12644; 19.
DR MINT; P12644; -.
DR STRING; 9606.ENSP00000245451; -.
DR BindingDB; P12644; -.
DR ChEMBL; CHEMBL5350; -.
DR DrugBank; DB01373; Calcium.
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; P12644; -.
DR PeptideAtlas; P12644; -.
DR PRIDE; P12644; -.
DR ProteomicsDB; 52861; -.
DR Antibodypedia; 3485; 862 antibodies from 45 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 CTD; 652; -.
DR DisGeNET; 652; -.
DR GeneCards; BMP4; -.
DR HGNC; HGNC:1071; BMP4.
DR HPA; ENSG00000125378; Low tissue specificity.
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 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; 962484at2759; -.
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 SignaLink; P12644; -.
DR SIGNOR; P12644; -.
DR BioGRID-ORCS; 652; 13 hits in 1072 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 122 other tissues.
DR ExpressionAtlas; P12644; baseline and differential.
DR Genevisible; P12644; HS.
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:BHF-UCL.
DR GO; GO:0061312; P:BMP signaling pathway involved in heart development; ISS:BHF-UCL.
DR GO; GO:0003130; P:BMP signaling pathway involved in heart induction; IMP:BHF-UCL.
DR GO; GO:0071893; P:BMP signaling pathway involved in nephric duct formation; IDA:UniProtKB.
DR GO; GO:0061151; P:BMP signaling pathway involved in renal system segmentation; ISS:UniProtKB.
DR GO; GO:0061149; P:BMP signaling pathway involved in ureter morphogenesis; ISS: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:0048754; P:branching morphogenesis of an epithelial tube; 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:0060197; P:cloacal septation; IEA:Ensembl.
DR GO; GO:0007182; P:common-partner SMAD protein phosphorylation; IDA: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: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: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:0072161; P:mesenchymal cell differentiation involved in kidney development; IEA:Ensembl.
DR GO; GO:0072198; P:mesenchymal cell proliferation involved in ureter development; IEA:Ensembl.
DR GO; GO:0072138; P:mesenchymal cell proliferation involved in ureteric bud development; IEA:Ensembl.
DR GO; GO:0003337; P:mesenchymal to epithelial transition involved in metanephros morphogenesis; IDA:UniProtKB.
DR GO; GO:0007500; P:mesodermal cell fate determination; IEA:Ensembl.
DR GO; GO:0001823; P:mesonephros development; IEP:UniProtKB.
DR GO; GO:0072205; P:metanephric collecting duct development; ISS:UniProtKB.
DR GO; GO:0030224; P:monocyte differentiation; IDA:DFLAT.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0072097; P:negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway; IDA:UniProtKB.
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:0060548; P:negative regulation of cell death; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:MGI.
DR GO; GO:2000137; P:negative regulation of cell proliferation involved in heart morphogenesis; IMP:BHF-UCL.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IEA:Ensembl.
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:0043407; P:negative regulation of MAP kinase activity; IDA:UniProtKB.
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:0042326; P:negative regulation of phosphorylation; IDA:UniProtKB.
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:0045892; P:negative regulation of transcription, DNA-templated; 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:0072015; P:podocyte development; IEA:Ensembl.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
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:0010942; P:positive regulation of cell death; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:1901964; P:positive regulation of cell proliferation involved in outflow tract morphogenesis; ISS:BHF-UCL.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IEA:Ensembl.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB.
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:0090184; P:positive regulation of kidney development; IDA:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:1903800; P:positive regulation of miRNA maturation; IDA:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0045778; P:positive regulation of ossification; IDA:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:BHF-UCL.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:MGI.
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:BHF-UCL.
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:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IDA:MGI.
DR GO; GO:0060513; P:prostatic bud formation; IEA:Ensembl.
DR GO; GO:0034504; P:protein localization to nucleus; IDA:UniProtKB.
DR GO; GO:0061155; P:pulmonary artery endothelial tube morphogenesis; IDA:UniProtKB.
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:0060393; P:regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
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:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
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:0072101; P:specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0043401; P:steroid hormone mediated signaling pathway; IMP:UniProtKB.
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:0072192; P:ureter epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0072193; P:ureter smooth muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0001657; P:ureteric bud development; IDA:MGI.
DR Gene3D; 2.10.90.10; -; 1.
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; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 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; 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
