Bone morphogenetic protein 4

Name	Bone morphogenetic protein 4
Synonyms	BMP-2B BMP-4 BMP2B Bone morphogenetic protein 2B DVR4
Gene Name	BMP4
Organism	Human
Amino acid sequence	>lcl\|BSEQ0049714\|Bone morphogenetic protein 4 MIPGNRMLMVVLLCQVLLGGASHASLIPETGKKKVAEIQGHAGGRRSGQSHELLRDFEAT LLQMFGLRRRPQPSKSAVIPDYMRDLYRLQSGEEEEEQIHSTGLEYPERPASRANTVRSF HHEEHLENIPGTSENSAFRFLFNLSSIPENEVISSAELRLFREQVDQGPDWERGFHRINI YEVMKPPAEVVPGHLITRLLDTRLVHHNVTRWETFDVSPAVLRWTREKQPNYGLAIEVTH LHQTRTHQGQHVRISRSLPQGSGNWAQLRPLLVTFGHDGRGHALTRRRRAKRSPKHHSQR ARKKNKNCRRHSLYVDFSDVGWNDWIVAPPGYQAFYCHGDCPFPLADHLNSTNHAIVQTL VNSVNSSIPKACCVPTELSAISMLYLDEYDKVVLKNYQEMVVEGCGCR
Number of residues	None
Molecular Weight	46554.545
Theoretical pI	None
GO Classification	Functions growth factor activity co-receptor binding cytokine activity chemoattractant activity transforming growth factor beta receptor binding BMP receptor binding heparin binding Processes mesenchymal to epithelial transition involved in metanephros morphogenesis epithelial cell proliferation involved in lung morphogenesis mammary gland formation positive regulation of endothelial cell migration lung alveolus development negative regulation of extrinsic apoptotic signaling pathway negative regulation of cell death glomerular visceral epithelial cell development type B pancreatic cell development negative regulation of metanephric S-shaped body morphogenesis BMP signaling pathway involved in nephric duct formation post-embryonic development specification of animal organ position macrophage differentiation regulation of smooth muscle cell differentiation dorsal/ventral neural tube patterning negative regulation of chondrocyte differentiation negative regulation of phosphorylation mesenchymal cell differentiation involved in kidney development odontogenesis of dentin-containing tooth negative regulation of MAP kinase activity positive regulation of bone mineralization positive regulation of protein binding renal system process regulation of pathway-restricted SMAD protein phosphorylation negative regulation of prostatic bud formation lymphoid progenitor cell differentiation BMP signaling pathway involved in renal system segmentation activation of MAPKK activity specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway negative regulation of transcription, DNA-templated ureteric bud development chondrocyte differentiation mesenchymal cell proliferation involved in ureter development positive regulation of epithelial cell proliferation negative regulation of T cell differentiation in thymus positive regulation of osteoblast differentiation branching involved in prostate gland morphogenesis epithelial-mesenchymal cell signaling neuron fate commitment BMP signaling pathway involved in ureter morphogenesis negative regulation of apoptotic process tendon cell differentiation pituitary gland development positive regulation of ossification mesodermal cell fate determination positive regulation of ERK1 and ERK2 cascade positive regulation of branching involved in lung morphogenesis positive regulation of pathway-restricted SMAD protein phosphorylation bud elongation involved in lung branching metanephric collecting duct development aortic valve morphogenesis renal system development bronchus development negative regulation of cell proliferation trachea development branching morphogenesis of an epithelial tube monocyte differentiation cardiac muscle cell differentiation negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway positive regulation of smooth muscle cell proliferation positive regulation of cardiac muscle fiber development mesonephros development embryonic cranial skeleton morphogenesis endoderm development telencephalon regionalization bud dilation involved in lung branching positive regulation of transcription from RNA polymerase II promoter ureter epithelial cell differentiation regulation of branching involved in prostate gland morphogenesis lung morphogenesis hematopoietic progenitor cell differentiation negative regulation of branching involved in ureteric bud morphogenesis smooth muscle tissue development positive regulation of apoptotic process positive regulation of cell proliferation involved in outflow tract morphogenesis positive regulation of endothelial cell proliferation membranous septum morphogenesis erythrocyte differentiation regulation of odontogenesis of dentin-containing tooth trachea formation coronary vasculature development cardiac septum development smoothened signaling pathway ureter smooth muscle cell differentiation blood vessel endothelial cell proliferation involved in sprouting angiogenesis pharyngeal arch artery morphogenesis negative regulation of cell proliferation involved in heart morphogenesis positive regulation of neuron differentiation embryonic skeletal joint morphogenesis positive regulation of protein phosphorylation positive regulation of DNA-dependent DNA replication neural tube closure negative regulation of epithelial cell proliferation negative regulation of thymocyte apoptotic process anterior/posterior axis specification mesenchymal cell proliferation involved in ureteric bud development cloacal septation positive regulation of collagen biosynthetic process positive regulation of BMP signaling pathway BMP signaling pathway involved in heart induction negative regulation of glomerular mesangial cell proliferation positive regulation of cell death positive regulation of epidermal cell differentiation endochondral ossification positive regulation of kidney development negative regulation of mitotic nuclear division negative regulation of striated muscle tissue development branching involved in ureteric bud morphogenesis steroid hormone mediated signaling pathway deltoid tuberosity development kidney development positive regulation of endothelial cell differentiation positive regulation of SMAD protein import into nucleus negative regulation of glomerulus development BMP signaling pathway inner ear receptor cell differentiation osteoblast differentiation positive regulation of production of miRNAs involved in gene silencing by miRNA cranial suture morphogenesis odontogenesis positive regulation of cartilage development embryonic digit morphogenesis secondary heart field specification glomerular capillary formation negative regulation of transcription from RNA polymerase II promoter negative regulation of immature T cell proliferation in thymus SMAD protein signal transduction negative regulation of mesenchymal cell proliferation involved in ureter development cellular response to BMP stimulus regulation of protein import into nucleus positive regulation of transcription, DNA-templated pulmonary artery endothelial tube morphogenesis embryonic hindlimb morphogenesis outflow tract septum morphogenesis lens induction in camera-type eye epithelial tube branching involved in lung morphogenesis negative regulation of myoblast differentiation intermediate mesodermal cell differentiation telencephalon development negative regulation of cell cycle common-partner SMAD protein phosphorylation negative regulation of metanephric comma-shaped body morphogenesis germ cell development BMP signaling pathway involved in heart development protein localization to nucleus pulmonary valve morphogenesis regulation of cell fate commitment endocardial cushion development Components extracellular region extracellular space proteinaceous extracellular matrix
General Function	Induces cartilage and bone formation. Also act in mesoderm induction, tooth development, limb formation and fracture repair. Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity).
Specific Function	Bmp receptor binding
Transmembrane Regions
GenBank Protein ID
UniProtKB ID	P12644
UniProtKB Entry Name
Cellular Location	Secreted
Gene sequence	>lcl\|BSEQ0049715\|Bone morphogenetic protein 4 (BMP4) ATGATTCCTGGTAACCGAATGCTGATGGTCGTTTTATTATGCCAAGTCCTGCTAGGAGGC GCGAGCCATGCTAGTTTGATACCTGAGACGGGGAAGAAAAAAGTCGCCGAGATTCAGGGC CACGCGGGAGGACGCCGCTCAGGGCAGAGCCATGAGCTCCTGCGGGACTTCGAGGCGACA CTTCTGCAGATGTTTGGGCTGCGCCGCCGCCCGCAGCCTAGCAAGAGTGCCGTCATTCCG GACTACATGCGGGATCTTTACCGGCTTCAGTCTGGGGAGGAGGAGGAAGAGCAGATCCAC AGCACTGGTCTTGAGTATCCTGAGCGCCCGGCCAGCCGGGCCAACACCGTGAGGAGCTTC CACCACGAAGAACATCTGGAGAACATCCCAGGGACCAGTGAAAACTCTGCTTTTCGTTTC CTCTTTAACCTCAGCAGCATCCCTGAGAACGAGGTGATCTCCTCTGCAGAGCTTCGGCTC TTCCGGGAGCAGGTGGACCAGGGCCCTGATTGGGAAAGGGGCTTCCACCGTATAAACATT TATGAGGTTATGAAGCCCCCAGCAGAAGTGGTGCCTGGGCACCTCATCACACGACTACTG GACACGAGACTGGTCCACCACAATGTGACACGGTGGGAAACTTTTGATGTGAGCCCTGCG GTCCTTCGCTGGACCCGGGAGAAGCAGCCAAACTATGGGCTAGCCATTGAGGTGACTCAC CTCCATCAGACTCGGACCCACCAGGGCCAGCATGTCAGGATTAGCCGATCGTTACCTCAA GGGAGTGGGAATTGGGCCCAGCTCCGGCCCCTCCTGGTCACCTTTGGCCATGATGGCCGG GGCCATGCCTTGACCCGACGCCGGAGGGCCAAGCGTAGCCCTAAGCATCACTCACAGCGG GCCAGGAAGAAGAATAAGAACTGCCGGCGCCACTCGCTCTATGTGGACTTCAGCGATGTG GGCTGGAATGACTGGATTGTGGCCCCACCAGGCTACCAGGCCTTCTACTGCCATGGGGAC TGCCCCTTTCCACTGGCTGACCACCTCAACTCAACCAACCATGCCATTGTGCAGACCCTG GTCAATTCTGTCAATTCCAGTATCCCCAAAGCCTGTTGTGTGCCCACTGAACTGAGTGCC ATCTCCATGCTGTACCTGGATGAGTATGATAAGGTGGTACTGAAAAATTATCAGGAGATG GTAGTAGAGGGATGTGGGTGCCGCTGA
GenBank Gene ID
GeneCard ID	None
GenAtlas ID
HGNC ID
Chromosome Location	14
Locus	14q22.2
References	Wozney JM, Rosen V, Celeste AJ, Mitsock LM, Whitters MJ, Kriz RW, Hewick RM, Wang EA: Novel regulators of bone formation: molecular clones and activities. Science. 1988 Dec 16;242(4885):1528-34. [3201241 ] Shore EM, Xu M, Shah PB, Janoff HB, Hahn GV, Deardorff MA, Sovinsky L, Spinner NB, Zasloff MA, Wozney JM, Kaplan FS: The human bone morphogenetic protein 4 (BMP-4) gene: molecular structure and transcriptional regulation. Calcif Tissue Int. 1998 Sep;63(3):221-9. [9701626 ] Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [15489334 ] Oida S, Iimura T, Maruoka Y, Takeda K, Sasaki S: Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library. DNA Seq. 1995;5(5):273-5. [7579580 ] Yanagita M, Oka M, Watabe T, Iguchi H, Niida A, Takahashi S, Akiyama T, Miyazono K, Yanagisawa M, Sakurai T: USAG-1: a bone morphogenetic protein antagonist abundantly expressed in the kidney. Biochem Biophys Res Commun. 2004 Apr 2;316(2):490-500. [15020244 ] Sengle G, Charbonneau NL, Ono RN, Sasaki T, Alvarez J, Keene DR, Bachinger HP, Sakai LY: Targeting of bone morphogenetic protein growth factor complexes to fibrillin. J Biol Chem. 2008 May 16;283(20):13874-88. doi: 10.1074/jbc.M707820200. Epub 2008 Mar 13. [18339631 ] Tagliabracci VS, Wiley SE, Guo X, Kinch LN, Durrant E, Wen J, Xiao J, Cui J, Nguyen KB, Engel JL, Coon JJ, Grishin N, Pinna LA, Pagliarini DJ, Dixon JE: A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell. 2015 Jun 18;161(7):1619-32. doi: 10.1016/j.cell.2015.05.028. [26091039 ] Felder B, Stegmann K, Schultealbert A, Geller F, Strehl E, Ermert A, Koch MC: Evaluation of BMP4 and its specific inhibitor NOG as candidates in human neural tube defects (NTDs). Eur J Hum Genet. 2002 Nov;10(11):753-6. [12404109 ] Bakrania P, Efthymiou M, Klein JC, Salt A, Bunyan DJ, Wyatt A, Ponting CP, Martin A, Williams S, Lindley V, Gilmore J, Restori M, Robson AG, Neveu MM, Holder GE, Collin JR, Robinson DO, Farndon P, Johansen-Berg H, Gerrelli D, Ragge NK: Mutations in BMP4 cause eye, brain, and digit developmental anomalies: overlap between the BMP4 and hedgehog signaling pathways. Am J Hum Genet. 2008 Feb;82(2):304-19. doi: 10.1016/j.ajhg.2007.09.023. Epub 2008 Jan 31. [18252212 ] Weber S, Taylor JC, Winyard P, Baker KF, Sullivan-Brown J, Schild R, Knuppel T, Zurowska AM, Caldas-Alfonso A, Litwin M, Emre S, Ghiggeri GM, Bakkaloglu A, Mehls O, Antignac C, Network E, Schaefer F, Burdine RD: SIX2 and BMP4 mutations associate with anomalous kidney development. J Am Soc Nephrol. 2008 May;19(5):891-903. doi: 10.1681/ASN.2006111282. Epub 2008 Feb 27. [18305125 ] Suzuki S, Marazita ML, Cooper ME, Miwa N, Hing A, Jugessur A, Natsume N, Shimozato K, Ohbayashi N, Suzuki Y, Niimi T, Minami K, Yamamoto M, Altannamar TJ, Erkhembaatar T, Furukawa H, Daack-Hirsch S, L'heureux J, Brandon CA, Weinberg SM, Neiswanger K, Deleyiannis FW, de Salamanca JE, Vieira AR, Lidral AC, Martin JF, Murray JC: Mutations in BMP4 are associated with subepithelial, microform, and overt cleft lip. Am J Hum Genet. 2009 Mar;84(3):406-11. doi: 10.1016/j.ajhg.2009.02.002. Epub 2009 Feb 26. [19249007 ]

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