Bone morphogenetic protein 4

Details

Name

Bone morphogenetic protein 4

Synonyms

• BMP-2B
• BMP-4
• BMP2B
• Bone morphogenetic protein 2B
• DVR4

Gene Name

BMP4

Organism

Humans

Amino acid sequence

>lcl|BSEQ0049714|Bone morphogenetic protein 4
MIPGNRMLMVVLLCQVLLGGASHASLIPETGKKKVAEIQGHAGGRRSGQSHELLRDFEAT
LLQMFGLRRRPQPSKSAVIPDYMRDLYRLQSGEEEEEQIHSTGLEYPERPASRANTVRSF
HHEEHLENIPGTSENSAFRFLFNLSSIPENEVISSAELRLFREQVDQGPDWERGFHRINI
YEVMKPPAEVVPGHLITRLLDTRLVHHNVTRWETFDVSPAVLRWTREKQPNYGLAIEVTH
LHQTRTHQGQHVRISRSLPQGSGNWAQLRPLLVTFGHDGRGHALTRRRRAKRSPKHHSQR
ARKKNKNCRRHSLYVDFSDVGWNDWIVAPPGYQAFYCHGDCPFPLADHLNSTNHAIVQTL
VNSVNSSIPKACCVPTELSAISMLYLDEYDKVVLKNYQEMVVEGCGCR

Number of residues

408

Molecular Weight

46554.545

Theoretical pI

Not Available

GO Classification

Functions

BMP receptor binding / chemoattractant activity / co-receptor binding / cytokine activity / growth factor activity / heparin binding / transforming growth factor beta receptor binding

Processes

activation of MAPKK activity / anterior/posterior axis specification / aortic valve morphogenesis / blood vessel endothelial cell proliferation involved in sprouting angiogenesis / BMP signaling pathway / BMP signaling pathway involved in heart development / BMP signaling pathway involved in heart induction / BMP signaling pathway involved in nephric duct formation / BMP signaling pathway involved in renal system segmentation / BMP signaling pathway involved in ureter morphogenesis / branching involved in prostate gland morphogenesis / branching involved in ureteric bud morphogenesis / branching morphogenesis of an epithelial tube / bronchus development / bud dilation involved in lung branching / bud elongation involved in lung branching / cardiac muscle cell differentiation / cardiac septum development / cellular response to BMP stimulus / chondrocyte differentiation / cloacal septation / common-partner SMAD protein phosphorylation / coronary vasculature development / cranial suture morphogenesis / deltoid tuberosity development / dorsal/ventral neural tube patterning / embryonic cranial skeleton morphogenesis / embryonic digit morphogenesis / embryonic hindlimb morphogenesis / embryonic skeletal joint morphogenesis / endocardial cushion development / endochondral ossification / endoderm development / epithelial cell proliferation involved in lung morphogenesis / epithelial tube branching involved in lung morphogenesis / epithelial-mesenchymal cell signaling / erythrocyte differentiation / germ cell development / glomerular capillary formation / glomerular visceral epithelial cell development / hematopoietic progenitor cell differentiation / inner ear receptor cell differentiation / intermediate mesodermal cell differentiation / kidney development / lens induction in camera-type eye / lung alveolus development / lung morphogenesis / lymphoid progenitor cell differentiation / macrophage differentiation / mammary gland formation / membranous septum morphogenesis / mesenchymal cell differentiation involved in kidney development / mesenchymal cell proliferation involved in ureter development / mesenchymal cell proliferation involved in ureteric bud development / mesenchymal to epithelial transition involved in metanephros morphogenesis / mesodermal cell fate determination / mesonephros development / metanephric collecting duct development / monocyte differentiation / negative regulation of apoptotic process / negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway / negative regulation of branching involved in ureteric bud morphogenesis / negative regulation of cell cycle / negative regulation of cell death / negative regulation of cell proliferation / negative regulation of cell proliferation involved in heart morphogenesis / negative regulation of chondrocyte differentiation / negative regulation of epithelial cell proliferation / negative regulation of extrinsic apoptotic signaling pathway / negative regulation of glomerular mesangial cell proliferation / negative regulation of glomerulus development / negative regulation of immature T cell proliferation in thymus / negative regulation of MAP kinase activity / negative regulation of mesenchymal cell proliferation involved in ureter development / negative regulation of metanephric comma-shaped body morphogenesis / negative regulation of metanephric S-shaped body morphogenesis / negative regulation of mitotic nuclear division / negative regulation of myoblast differentiation / negative regulation of phosphorylation / negative regulation of prostatic bud formation / negative regulation of striated muscle tissue development / negative regulation of T cell differentiation in thymus / negative regulation of thymocyte apoptotic process / negative regulation of transcription from RNA polymerase II promoter / negative regulation of transcription, DNA-templated / neural tube closure / neuron fate commitment / odontogenesis / odontogenesis of dentin-containing tooth / osteoblast differentiation / outflow tract septum morphogenesis / pharyngeal arch artery morphogenesis / pituitary gland development / positive regulation of apoptotic process / positive regulation of BMP signaling pathway / positive regulation of bone mineralization / positive regulation of branching involved in lung morphogenesis / positive regulation of cardiac muscle fiber development / positive regulation of cartilage development / positive regulation of cell death / positive regulation of cell proliferation involved in outflow tract morphogenesis / positive regulation of collagen biosynthetic process / positive regulation of DNA-dependent DNA replication / positive regulation of endothelial cell differentiation / positive regulation of endothelial cell migration / positive regulation of endothelial cell proliferation / positive regulation of epidermal cell differentiation / positive regulation of epithelial cell proliferation / positive regulation of ERK1 and ERK2 cascade / positive regulation of kidney development / positive regulation of neuron differentiation / positive regulation of ossification / positive regulation of osteoblast differentiation / positive regulation of pathway-restricted SMAD protein phosphorylation / positive regulation of production of miRNAs involved in gene silencing by miRNA / positive regulation of protein binding / positive regulation of protein phosphorylation / positive regulation of SMAD protein import into nucleus / positive regulation of smooth muscle cell proliferation / positive regulation of transcription from RNA polymerase II promoter / positive regulation of transcription, DNA-templated / post-embryonic development / protein localization to nucleus / pulmonary artery endothelial tube morphogenesis / pulmonary valve morphogenesis / regulation of branching involved in prostate gland morphogenesis / regulation of cell fate commitment / regulation of odontogenesis of dentin-containing tooth / regulation of pathway-restricted SMAD protein phosphorylation / regulation of protein import into nucleus / regulation of smooth muscle cell differentiation / renal system development / renal system process / secondary heart field specification / SMAD protein signal transduction / smooth muscle tissue development / smoothened signaling pathway / specification of animal organ position / specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway / steroid hormone mediated signaling pathway / telencephalon development / telencephalon regionalization / tendon cell differentiation / trachea development / trachea formation / type B pancreatic cell development / ureter epithelial cell differentiation / ureter smooth muscle cell differentiation / ureteric bud 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

Pfam Domain Function

• TGF_beta (PF00019)
• TGFb_propeptide (PF00688)

Transmembrane Regions

Not Available

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

Chromosome Location

14

Locus

14q22.2

External Identifiers

Resource	Link
UniProtKB ID	P12644
UniProtKB Entry Name	BMP4_HUMAN
HGNC ID	HGNC:1071

General References

1. 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. [Article]
2. 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. [Article]
3. 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. [Article]
4. 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. [Article]
5. 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. [Article]
6. 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. [Article]
7. 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. [Article]
8. 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. [Article]
9. 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. [Article]
10. 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. [Article]
11. 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. [Article]

Drug Relations

Drug Relations

DrugBank ID	Name	Drug group	Pharmacological action?	Actions	Details
DB01373	Calcium	nutraceutical	unknown		Details