ID BMP4_MOUSE Reviewed; 408 AA.
AC P21275;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 2.
DT 27-MAR-2024, entry version 214.
DE RecName: Full=Bone morphogenetic protein 4 {ECO:0000312|MGI:MGI:88180};
DE Short=BMP-4 {ECO:0000312|MGI:MGI:88180};
DE AltName: Full=Bone morphogenetic protein 2B {ECO:0000312|MGI:MGI:88180};
DE Short=BMP-2B {ECO:0000312|MGI:MGI:88180};
DE Flags: Precursor;
GN Name=Bmp4 {ECO:0000312|MGI:MGI:88180};
GN Synonyms=Bmp-4 {ECO:0000312|MGI:MGI:88180}, Dvr-4;
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].
RA Dickinson M.E., van der Meer-De Jong R., Hogan B.L.M.;
RT "Nucleotide sequence of the mouse bone morphogenetic protein-4 (BMP-4)
RT cDNA.";
RL Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8507180; DOI=10.1006/bbrc.1993.1523;
RA Kurihara T., Kitamura K., Takaoka K., Nakazato H.;
RT "Murine bone morphogenetic protein-4 gene: existence of multiple promoters
RT and exons for the 5'-untranslated region.";
RL Biochem. Biophys. Res. Commun. 192:1049-1056(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8358941;
RA Takaoka K., Yoshikawa H., Hasimoto J., Masuhara K., Miyamoto S., Suzuki S.,
RA Ono K., Matsui M., Oikawa S., Tsuruoka N.;
RT "Gene cloning and expression of a bone morphogenetic protein derived from a
RT murine osteosarcoma.";
RL Clin. Orthop. Relat. Res. 294:344-352(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=129/Sv; TISSUE=Liver;
RX PubMed=7499338; DOI=10.1074/jbc.270.47.28364;
RA Feng J.Q., Chen D., Cooney A.J., Tsai M., Harris M.A., Tsai S.Y., Feng M.,
RA Mundy G.R., Harris S.E.;
RT "The mouse bone morphogenetic protein-4 gene. Analysis of promoter
RT utilization in fetal rat calvarial osteoblasts and regulation by COUP-TFI
RT orphan receptor.";
RL J. Biol. Chem. 270:28364-28373(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C3H/He, and FVB/N; TISSUE=Colon, Osteoblast, and Salivary gland;
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 [6]
RP NUCLEOTIDE SEQUENCE OF 241-408.
RX PubMed=1970330; DOI=10.1016/0888-7543(90)90480-i;
RA Dickinson M.E., Kobrin M.S., Silan C.M., Kingsley D.M., Justice M.J.,
RA Miller D.A., Ceci J.D., Lock L.F., Lee A., Buchberg A.M., Siracusa L.D.,
RA Lyons K.M., Derynck R., Hogan B.L.M., Copeland N.G., Jenkins N.A.;
RT "Chromosomal localization of seven members of the murine TGF-beta
RT superfamily suggests close linkage to several morphogenetic mutant loci.";
RL Genomics 6:505-520(1990).
RN [7]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=8898217; DOI=10.1242/dev.122.10.3035;
RA Chen Y., Bei M., Woo I., Satokata I., Maas R.;
RT "Msx1 controls inductive signaling in mammalian tooth morphogenesis.";
RL Development 122:3035-3044(1996).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=10049358; DOI=10.1101/gad.13.4.424;
RA Lawson K.A., Dunn N.R., Roelen B.A., Zeinstra L.M., Davis A.M.,
RA Wright C.V., Korving J.P., Hogan B.L.;
RT "Bmp4 is required for the generation of primordial germ cells in the mouse
RT embryo.";
RL Genes Dev. 13:424-436(1999).
RN [9]
RP INTERACTION WITH TWSG1 AND CHRD.
RX PubMed=11260715; DOI=10.1038/35068572;
RA Scott I.C., Blitz I.L., Pappano W.N., Maas S.A., Cho K.W.Y.,
RA Greenspan D.S.;
RT "Homologues of Twisted gastrulation are extracellular cofactors in
RT antagonism of BMP signalling.";
RL Nature 410:475-478(2001).
RN [10]
RP INTERACTION WITH SOSTDC1.
RX PubMed=14623234; DOI=10.1016/j.ydbio.2003.08.011;
RA Laurikkala J., Kassai Y., Pakkasjaervi L., Thesleff I., Itoh N.;
RT "Identification of a secreted BMP antagonist, ectodin, integrating BMP,
RT FGF, and SHH signals from the tooth enamel knot.";
RL Dev. Biol. 264:91-105(2003).
RN [11]
RP INTERACTION WITH HTRA3, AND FUNCTION.
RX PubMed=15206957; DOI=10.1111/j.1440-169x.2004.00743.x;
RA Tocharus J., Tsuchiya A., Kajikawa M., Ueta Y., Oka C., Kawaichi M.;
RT "Developmentally regulated expression of mouse HtrA3 and its role as an
RT inhibitor of TGF-beta signaling.";
RL Dev. Growth Differ. 46:257-274(2004).
RN [12]
RP INTERACTION WITH HTRA1, AND FUNCTION.
RX PubMed=14973287; DOI=10.1242/dev.00999;
RA Oka C., Tsujimoto R., Kajikawa M., Koshiba-Takeuchi K., Ina J., Yano M.,
RA Tsuchiya A., Ueta Y., Soma A., Kanda H., Matsumoto M., Kawaichi M.;
RT "HtrA1 serine protease inhibits signaling mediated by Tgfbeta family
RT proteins.";
RL Development 131:1041-1053(2004).
RN [13]
RP INTERACTION WITH GREM2.
RX PubMed=15039429; DOI=10.1074/jbc.m402376200;
RA Sudo S., Avsian-Kretchmer O., Wang L.S., Hsueh A.J.;
RT "Protein related to DAN and cerberus is a bone morphogenetic protein
RT antagonist that participates in ovarian paracrine regulation.";
RL J. Biol. Chem. 279:23134-23141(2004).
RN [14]
RP INTERACTION WITH RGMB.
RX PubMed=15671031; DOI=10.1074/jbc.m410034200;
RA Samad T.A., Rebbapragada A., Bell E., Zhang Y., Sidis Y., Jeong S.-J.,
RA Campagna J.A., Perusini S., Fabrizio D.A., Schneyer A.L., Lin H.Y.,
RA Brivanlou A.H., Attisano L., Woolf C.J.;
RT "DRAGON, a bone morphogenetic protein co-receptor.";
RL J. Biol. Chem. 280:14122-14129(2005).
RN [15]
RP INTERACTION WITH RGMA.
RX PubMed=15975920; DOI=10.1074/jbc.m503511200;
RA Babitt J.L., Zhang Y., Samad T.A., Xia Y., Tang J., Campagna J.A.,
RA Schneyer A.L., Woolf C.J., Lin H.Y.;
RT "Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone
RT morphogenetic protein co-receptor.";
RL J. Biol. Chem. 280:29820-29827(2005).
RN [16]
RP INTERACTION WITH RGMC.
RX PubMed=16604073; DOI=10.1038/ng1777;
RA Babitt J.L., Huang F.W., Wrighting D.M., Xia Y., Sidis Y., Samad T.A.,
RA Campagna J.A., Chung R.T., Schneyer A.L., Woolf C.J., Andrews N.C.,
RA Lin H.Y.;
RT "Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin
RT expression.";
RL Nat. Genet. 38:531-539(2006).
RN [17]
RP FUNCTION.
RX PubMed=17301089; DOI=10.1242/dev.000182;
RA Hens J.R., Dann P., Zhang J.P., Harris S., Robinson G.W., Wysolmerski J.;
RT "BMP4 and PTHrP interact to stimulate ductal outgrowth during embryonic
RT mammary development and to inhibit hair follicle induction.";
RL Development 134:1221-1230(2007).
RN [18]
RP INTERACTION WITH RGMA.
RX PubMed=17472960; DOI=10.1074/jbc.m701679200;
RA Xia Y., Yu P.B., Sidis Y., Beppu H., Bloch K.D., Schneyer A.L., Lin H.Y.;
RT "Repulsive guidance molecule RGMa alters utilization of bone morphogenetic
RT protein (BMP) type II receptors by BMP2 and BMP4.";
RL J. Biol. Chem. 282:18129-18140(2007).
RN [19]
RP DEVELOPMENTAL STAGE.
RX PubMed=24028588; DOI=10.1111/eos.12078;
RA Feng X.Y., Zhao Y.M., Wang W.J., Ge L.H.;
RT "Msx1 regulates proliferation and differentiation of mouse dental
RT mesenchymal cells in culture.";
RL Eur. J. Oral Sci. 121:412-420(2013).
RN [20]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27713059; DOI=10.1016/j.ydbio.2016.10.001;
RA Jia S., Kwon H.E., Lan Y., Zhou J., Liu H., Jiang R.;
RT "Bmp4-Msx1 signaling and Osr2 control tooth organogenesis through
RT antagonistic regulation of secreted Wnt antagonists.";
RL Dev. Biol. 420:110-119(2016).
RN [21]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=29148101; DOI=10.1111/eos.12390;
RA Feng X.Y., Wu X.S., Wang J.S., Zhang C.M., Wang S.L.;
RT "Homeobox protein MSX-1 inhibits expression of bone morphogenetic protein
RT 2, bone morphogenetic protein 4, and lymphoid enhancer-binding factor 1 via
RT Wnt/beta-catenin signaling to prevent differentiation of dental mesenchymal
RT cells during the late bell stage.";
RL Eur. J. Oral Sci. 126:1-12(2018).
RN [22]
RP TISSUE SPECIFICITY.
RX PubMed=32127020; DOI=10.1186/s13041-020-00570-z;
RA Miwa T., Ohta K., Ito N., Hattori S., Miyakawa T., Takeo T., Nakagata N.,
RA Song W.J., Minoda R.;
RT "Tsukushi is essential for the development of the inner ear.";
RL Mol. Brain 13:29-29(2020).
RN [23]
RP FUNCTION.
RX PubMed=34995814; DOI=10.1016/j.cdev.2021.203763;
RA She Y., Zhang Y., Xiao Z., Yuan G., Yang G.;
RT "The regulation of Msx1 by BMP4/pSmad1/5 signaling is mediated by importin7
RT in dental mesenchymal cells.";
RL Cells Dev. 169:203763-203763(2022).
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:14973287, PubMed:15206957, PubMed:10049358). Acts in concert
CC with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary
CC development and to inhibit hair follicle induction (PubMed:17301089).
CC Initiates the canonical BMP signaling cascade by associating with type
CC I receptor BMPR1A and type II receptor BMPR2. Once all three components
CC 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. Positively
CC regulates the expression of odontogenic development regulator MSX1 via
CC inducing the IPO7-mediated import of SMAD1 to the nucleus
CC (PubMed:34995814). Required for MSX1-mediated mesenchymal molar tooth
CC bud development beyond the bud stage, via promoting Wnt signaling
CC (PubMed:8898217, PubMed:27713059). Acts as a positive regulator of
CC odontoblast differentiation during mesenchymal tooth germ formation,
CC expression is repressed during the bell stage by MSX1-mediated
CC inhibition of CTNNB1 signaling (PubMed:29148101). Able to induce its
CC own expression in dental mesenchymal cells and also in the neighboring
CC dental epithelial cells via an MSX1-mediated pathway (PubMed:8898217).
CC Can also signal through non-canonical BMP pathways such as ERK/MAP
CC kinase, PI3K/Akt or SRC cascades. For example, induces SRC
CC phosphorylation which, in turn, activates VEGFR2, leading to an
CC angiogenic response (By similarity). {ECO:0000250|UniProtKB:P12644,
CC ECO:0000269|PubMed:10049358, ECO:0000269|PubMed:14973287,
CC ECO:0000269|PubMed:15206957, ECO:0000269|PubMed:17301089,
CC ECO:0000269|PubMed:27713059, ECO:0000269|PubMed:29148101,
CC ECO:0000269|PubMed:34995814, ECO:0000269|PubMed:8898217}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC SOSTDC1, GREM2, RGMA, RGMB and RGMC. Part of a complex consisting of
CC TWSG1 and CHRD. Interacts with the serine proteases, HTRA1 and HTRA3;
CC the interaction with either inhibits BMP4-mediated signaling. The HTRA
CC protease activity is required for this inhibition. Interacts with FBN1
CC (via N-terminal domain) and FBN2 (By similarity). Interacts with type I
CC receptor BMPR1A (By similarity). Interacts with type II receptor BMPR2
CC (By similarity). Interacts with FSTL1; this interaction inhibits the
CC activation of the BMP4/Smad1/5/8 signaling pathway (By similarity).
CC Interacts with SCUBE3 (By similarity). {ECO:0000250|UniProtKB:P12644,
CC ECO:0000269|PubMed:11260715, ECO:0000269|PubMed:14623234,
CC ECO:0000269|PubMed:14973287, ECO:0000269|PubMed:15039429,
CC ECO:0000269|PubMed:15206957, ECO:0000269|PubMed:15671031,
CC ECO:0000269|PubMed:15975920, ECO:0000269|PubMed:16604073,
CC ECO:0000269|PubMed:17472960}.
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC matrix.
CC -!- TISSUE SPECIFICITY: In the cochlea, detected in nonprosensory regions
CC and outer sulcus (at protein level) (PubMed:32127020). Prior to
CC gastrulation, expressed in the extraembryonic ectoderm. Later,
CC expressed in the extraembryonic mesoderm (PubMed:10049358).
CC {ECO:0000269|PubMed:10049358, ECO:0000269|PubMed:32127020}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the lower molar mesenchyme at 13.5
CC dpc and 14.5 dpc (PubMed:8898217). Expressed in early bell stage dental
CC mesenchymal cells at 15.5 dpc (at protein level) (PubMed:24028588).
CC Expressed in bell stage dental mesenchymal cells at 17.5 dpc (at
CC protein level) (PubMed:29148101). {ECO:0000269|PubMed:24028588,
CC ECO:0000269|PubMed:29148101, ECO:0000269|PubMed:8898217}.
CC -!- DISRUPTION PHENOTYPE: Homozygous null embryos contain no primordial
CC germ cells (PubMed:10049358). They also lack an allantois, an
CC extraembryonic mesodermal tissue derived from precursors in the
CC proximal epiblast (PubMed:10049358). Mandibular molar tooth germs
CC arrest in the bud stage (PubMed:27713059). Failure to form the primary
CC enamel knot in the mandibular molar tooth buds at 13.5 dpc.
CC Significantly reduces the expression of Lef1 and Axin2 in the maxillary
CC molar tooth germs and mandibular molar buds at 13.5 dpc
CC (PubMed:27713059). Expression of Dkk2 and Sfrp2 expanded into the
CC distal tooth mesenchyme in molar mandibular tooth buds at 13.5 dpc
CC (PubMed:27713059). {ECO:0000269|PubMed:10049358,
CC ECO:0000269|PubMed:27713059}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC37698.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; X56848; CAA40179.1; -; mRNA.
DR EMBL; D14814; BAA03555.1; -; Genomic_DNA.
DR EMBL; S65032; AAB28021.1; -; mRNA.
DR EMBL; L47480; AAC37698.1; ALT_INIT; Genomic_DNA.
DR EMBL; BC013459; AAH13459.1; -; mRNA.
DR EMBL; BC034053; AAH34053.1; -; mRNA.
DR EMBL; BC052846; AAH52846.1; -; mRNA.
DR CCDS; CCDS36897.1; -.
DR PIR; I49541; I49541.
DR PIR; JH0801; JH0801.
DR RefSeq; NP_001303289.1; NM_001316360.1.
DR RefSeq; NP_031580.2; NM_007554.3.
DR RefSeq; XP_006518530.1; XM_006518467.3.
DR RefSeq; XP_006518531.1; XM_006518468.3.
DR RefSeq; XP_011243236.1; XM_011244934.2.
DR RefSeq; XP_011243237.1; XM_011244935.2.
DR AlphaFoldDB; P21275; -.
DR SMR; P21275; -.
DR BioGRID; 198364; 3.
DR STRING; 10090.ENSMUSP00000073720; -.
DR BindingDB; P21275; -.
DR ChEMBL; CHEMBL2384894; -.
DR GlyCosmos; P21275; 4 sites, No reported glycans.
DR GlyGen; P21275; 4 sites.
DR iPTMnet; P21275; -.
DR PhosphoSitePlus; P21275; -.
DR PaxDb; 10090-ENSMUSP00000073720; -.
DR ProteomicsDB; 265221; -.
DR Antibodypedia; 3485; 939 antibodies from 45 providers.
DR DNASU; 12159; -.
DR Ensembl; ENSMUST00000074077.12; ENSMUSP00000073720.6; ENSMUSG00000021835.16.
DR Ensembl; ENSMUST00000100676.3; ENSMUSP00000098242.3; ENSMUSG00000021835.16.
DR GeneID; 12159; -.
DR KEGG; mmu:12159; -.
DR UCSC; uc007thd.2; mouse.
DR AGR; MGI:88180; -.
DR CTD; 652; -.
DR MGI; MGI:88180; Bmp4.
DR VEuPathDB; HostDB:ENSMUSG00000021835; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000159502; -.
DR HOGENOM; CLU_020515_4_2_1; -.
DR InParanoid; P21275; -.
DR OMA; HEEHMEQ; -.
DR OrthoDB; 2912454at2759; -.
DR PhylomeDB; P21275; -.
DR TreeFam; TF351789; -.
DR Reactome; R-MMU-2129379; Molecules associated with elastic fibres.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 12159; 1 hit in 78 CRISPR screens.
DR ChiTaRS; Bmp4; mouse.
DR PRO; PR:P21275; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P21275; Protein.
DR Bgee; ENSMUSG00000021835; Expressed in extraembryonic ectoderm and 415 other cell types or tissues.
DR ExpressionAtlas; P21275; baseline and differential.
DR Genevisible; P21275; MM.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0031982; C:vesicle; ISO:MGI.
DR GO; GO:0070700; F:BMP receptor binding; ISS:UniProtKB.
DR GO; GO:0042056; F:chemoattractant activity; ISS:UniProtKB.
DR GO; GO:0039706; F:co-receptor binding; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; ISO:MGI.
DR GO; GO:0008083; F:growth factor activity; ISO:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0036305; P:ameloblast differentiation; IDA:MGI.
DR GO; GO:0048856; P:anatomical structure development; IGI:MGI.
DR GO; GO:0048646; P:anatomical structure formation involved in morphogenesis; IGI:MGI.
DR GO; GO:0001525; P:angiogenesis; IMP:MGI.
DR GO; GO:0009948; P:anterior/posterior axis specification; IGI:MGI.
DR GO; GO:0003180; P:aortic valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0001568; P:blood vessel development; IDA:MGI.
DR GO; GO:0002043; P:blood vessel endothelial cell proliferation involved in sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
DR GO; GO:0060348; P:bone development; IDA:MGI.
DR GO; GO:0060442; P:branching involved in prostate gland morphogenesis; IMP:MGI.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IGI:MGI.
DR GO; GO:0060433; P:bronchus development; ISO:MGI.
DR GO; GO:0060503; P:bud dilation involved in lung branching; ISO:MGI.
DR GO; GO:0060449; P:bud elongation involved in lung branching; IDA:MGI.
DR GO; GO:0043010; P:camera-type eye development; IMP:MGI.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IMP:MGI.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IGI:BHF-UCL.
DR GO; GO:0014898; P:cardiac muscle hypertrophy in response to stress; ISO:MGI.
DR GO; GO:0045165; P:cell fate commitment; IDA:MGI.
DR GO; GO:0008283; P:cell population proliferation; IGI:MGI.
DR GO; GO:0071773; P:cellular response to BMP stimulus; ISO:MGI.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; ISO:MGI.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IDA:MGI.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISO:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IDA:MGI.
DR GO; GO:0060976; P:coronary vasculature development; IMP:BHF-UCL.
DR GO; GO:0060363; P:cranial suture morphogenesis; IDA:MGI.
DR GO; GO:0035993; P:deltoid tuberosity development; IMP:UniProtKB.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; IDA:MGI.
DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IGI:MGI.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IGI:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IMP:MGI.
DR GO; GO:0048598; P:embryonic morphogenesis; IMP:MGI.
DR GO; GO:0060272; P:embryonic skeletal joint morphogenesis; IMP:MGI.
DR GO; GO:0048706; P:embryonic skeletal system development; IMP:MGI.
DR GO; GO:0048704; P:embryonic skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0003197; P:endocardial cushion development; IMP:BHF-UCL.
DR GO; GO:0001958; P:endochondral ossification; IMP:UniProtKB.
DR GO; GO:0007492; P:endoderm development; IDA:MGI.
DR GO; GO:0050673; P:epithelial cell proliferation; IGI:MGI.
DR GO; GO:0060502; P:epithelial cell proliferation involved in lung morphogenesis; ISO:MGI.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; ISO:MGI.
DR GO; GO:0060684; P:epithelial-mesenchymal cell signaling; IDA:MGI.
DR GO; GO:0060429; P:epithelium development; IDA:MGI.
DR GO; GO:0030218; P:erythrocyte differentiation; IDA:MGI.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0010467; P:gene expression; IDA:MGI.
DR GO; GO:0007281; P:germ cell development; IMP:MGI.
DR GO; GO:0072104; P:glomerular capillary formation; IMP:UniProtKB.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0003129; P:heart induction; ISS:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; ISO:MGI.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IDA:MGI.
DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IGI:MGI.
DR GO; GO:0048392; P:intermediate mesodermal cell differentiation; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0060235; P:lens induction in camera-type eye; IMP:MGI.
DR GO; GO:0048286; P:lung alveolus development; ISO:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0060425; P:lung morphogenesis; ISO:MGI.
DR GO; GO:0060426; P:lung vasculature development; ISS:UniProtKB.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; ISS:UniProtKB.
DR GO; GO:0030225; P:macrophage differentiation; ISO:MGI.
DR GO; GO:0060592; P:mammary gland formation; IMP:MGI.
DR GO; GO:0003149; P:membranous septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0001707; P:mesoderm formation; IDA:MGI.
DR GO; GO:0048333; P:mesodermal cell differentiation; IDA:MGI.
DR GO; GO:0007500; P:mesodermal cell fate determination; IMP:MGI.
DR GO; GO:0001823; P:mesonephros development; ISS:UniProtKB.
DR GO; GO:0001656; P:metanephros development; IDA:MGI.
DR GO; GO:0030224; P:monocyte differentiation; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:MGI.
DR GO; GO:0072125; P:negative regulation of glomerular mesangial cell proliferation; ISS:UniProtKB.
DR GO; GO:0090194; P:negative regulation of glomerulus development; ISS:UniProtKB.
DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; ISS:UniProtKB.
DR GO; GO:0072200; P:negative regulation of mesenchymal cell proliferation involved in ureter development; ISS:UniProtKB.
DR GO; GO:2000007; P:negative regulation of metanephric comma-shaped body morphogenesis; ISS:UniProtKB.
DR GO; GO:2000005; P:negative regulation of metanephric S-shaped body morphogenesis; ISS:UniProtKB.
DR GO; GO:1902894; P:negative regulation of miRNA transcription; ISO:MGI.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; ISS:UniProtKB.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; ISO:MGI.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; ISO:MGI.
DR GO; GO:0060686; P:negative regulation of prostatic bud formation; IDA:MGI.
DR GO; GO:0045843; P:negative regulation of striated muscle tissue development; ISO:MGI.
DR GO; GO:0033085; P:negative regulation of T cell differentiation in thymus; ISO:MGI.
DR GO; GO:0070244; P:negative regulation of thymocyte apoptotic process; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0072179; P:nephric duct formation; ISS:UniProtKB.
DR GO; GO:0001843; P:neural tube closure; IDA:MGI.
DR GO; GO:0048663; P:neuron fate commitment; IDA:MGI.
DR GO; GO:0042476; P:odontogenesis; ISS:UniProtKB.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IDA:MGI.
DR GO; GO:0001759; P:organ induction; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IDA:MGI.
DR GO; GO:0003151; P:outflow tract morphogenesis; IGI:BHF-UCL.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0001541; P:ovarian follicle development; ISO:MGI.
DR GO; GO:1904238; P:pericyte cell differentiation; IDA:MGI.
DR GO; GO:0061626; P:pharyngeal arch artery morphogenesis; IMP:BHF-UCL.
DR GO; GO:0021983; P:pituitary gland development; IMP:MGI.
DR GO; GO:0050918; P:positive chemotaxis; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0061047; P:positive regulation of branching involved in lung morphogenesis; IMP:UniProtKB.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISO:MGI.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; ISO:MGI.
DR GO; GO:0055020; P:positive regulation of cardiac muscle fiber development; ISS:UniProtKB.
DR GO; GO:1905312; P:positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis; IGI:BHF-UCL.
DR GO; GO:0061036; P:positive regulation of cartilage development; ISO:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:CACAO.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISS:UniProtKB.
DR GO; GO:2000353; P:positive regulation of endothelial cell apoptotic process; ISO:MGI.
DR GO; GO:0045603; P:positive regulation of endothelial cell differentiation; IDA:DFLAT.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; TAS:DFLAT.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:DFLAT.
DR GO; GO:0045606; P:positive regulation of epidermal cell differentiation; ISS:CAFA.
DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IDA:MGI.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IGI:BHF-UCL.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:CACAO.
DR GO; GO:0070368; P:positive regulation of hepatocyte differentiation; ISO:MGI.
DR GO; GO:1902462; P:positive regulation of mesenchymal stem cell proliferation; ISO:MGI.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IGI:BHF-UCL.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IDA:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; ISO:MGI.
DR GO; GO:1901331; P:positive regulation of odontoblast differentiation; IMP:UniProtKB.
DR GO; GO:0045778; P:positive regulation of ossification; IDA:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISO:MGI.
DR GO; GO:2000636; P:positive regulation of primary miRNA processing; ISO:MGI.
DR GO; GO:0043068; P:positive regulation of programmed cell death; ISO:MGI.
DR GO; GO:1900182; P:positive regulation of protein localization to nucleus; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; TAS:DFLAT.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0012501; P:programmed cell death; ISO:MGI.
DR GO; GO:0060512; P:prostate gland morphogenesis; IMP:MGI.
DR GO; GO:0060513; P:prostatic bud formation; IMP:MGI.
DR GO; GO:0003184; P:pulmonary valve morphogenesis; IMP:BHF-UCL.
DR GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IMP:MGI.
DR GO; GO:0061035; P:regulation of cartilage development; IDA:MGI.
DR GO; GO:0045595; P:regulation of cell differentiation; IGI:MGI.
DR GO; GO:0010453; P:regulation of cell fate commitment; ISS:CAFA.
DR GO; GO:0001936; P:regulation of endothelial cell proliferation; TAS:DFLAT.
DR GO; GO:0070372; P:regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IDA:MGI.
DR GO; GO:1905770; P:regulation of mesodermal cell differentiation; IDA:MGI.
DR GO; GO:0060688; P:regulation of morphogenesis of a branching structure; IMP:MGI.
DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IGI:MGI.
DR GO; GO:0042306; P:regulation of protein import into nucleus; ISO:MGI.
DR GO; GO:0051150; P:regulation of smooth muscle cell differentiation; IDA:MGI.
DR GO; GO:0048660; P:regulation of smooth muscle cell proliferation; IDA:MGI.
DR GO; GO:0003014; P:renal system process; IMP:MGI.
DR GO; GO:0003139; P:secondary heart field specification; ISS:UniProtKB.
DR GO; GO:0001501; P:skeletal system development; IDA:MGI.
DR GO; GO:0051145; P:smooth muscle cell differentiation; IDA:MGI.
DR GO; GO:0048745; P:smooth muscle tissue development; IMP:UniProtKB.
DR GO; GO:0010159; P:specification of animal organ position; IMP:MGI.
DR GO; GO:0042305; P:specification of segmental identity, mandibular segment; IDA:MGI.
DR GO; GO:0021537; P:telencephalon development; ISO:MGI.
DR GO; GO:0021978; P:telencephalon regionalization; IDA:MGI.
DR GO; GO:0035990; P:tendon cell differentiation; IMP:UniProtKB.
DR GO; GO:0060438; P:trachea development; ISO:MGI.
DR GO; GO:0060440; P:trachea formation; IMP:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0003323; P:type B pancreatic cell development; ISS:UniProtKB.
DR GO; GO:0072197; P:ureter morphogenesis; IMP:UniProtKB.
DR GO; GO:0001657; P:ureteric bud development; IDA:MGI.
DR GO; GO:0001944; P:vasculature development; IMP:MGI.
DR CDD; cd19391; TGF_beta_BMP4_BMP2B; 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; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Growth factor; Osteogenesis;
KW Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..292
FT /id="PRO_0000033858"
FT CHAIN 293..408
FT /note="Bone morphogenetic protein 4"
FT /id="PRO_0000033859"
FT REGION 91..111
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 281..307
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 284..307
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 91
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12644"
FT CARBOHYD 144
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
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 CONFLICT 407
FT /note="C -> S (in Ref. 2; BAA03555)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 408 AA; 46497 MW; 35053D844624EF9D CRC64;
MIPGNRMLMV VLLCQVLLGG ASHASLIPET GKKKVAEIQG HAGGRRSGQS HELLRDFEAT
LLQMFGLRRR PQPSKSAVIP DYMRDLYRLQ SGEEEEEEQS QGTGLEYPER PASRANTVRS
FHHEEHLENI PGTSESSAFR FLFNLSSIPE NEVISSAELR LFREQVDQGP DWEQGFHRIN
IYEVMKPPAE MVPGHLITRL LDTRLVHHNV TRWETFDVSP AVLRWTREKQ PNYGLAIEVT
HLHQTRTHQG QHVRISRSLP QGSGDWAQLR PLLVTFGHDG RGHTLTRRRA KRSPKHHPQR
SRKKNKNCRR HSLYVDFSDV GWNDWIVAPP GYQAFYCHGD CPFPLADHLN STNHAIVQTL
VNSVNSSIPK ACCVPTELSA ISMLYLDEYD KVVLKNYQEM VVEGCGCR
//
