Bone morphogenetic protein 4

Details

Name
Bone morphogenetic protein 4
Kind
protein
Synonyms
  • BMP-2B
  • BMP-4
  • BMP2B
  • Bone morphogenetic protein 2B
  • DVR4
Gene Name
BMP4
UniProtKB Entry
P12644Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
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
Processes
ameloblast differentiation / heart induction / heart morphogenesis / inner ear auditory receptor cell differentiation / lung vasculature development / metanephros development / negative regulation of cell population proliferation / negative regulation of DNA-templated transcription / negative regulation of gene expression / negative regulation of miRNA transcription / negative regulation of transcription by RNA polymerase II / negative regulation of vascular associated smooth muscle cell migration / negative regulation of vascular associated smooth muscle cell proliferation / nephric duct formation / pericyte cell differentiation / positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis / positive regulation of cell population proliferation / positive regulation of DNA-templated transcription / positive regulation of epithelial to mesenchymal transition / positive regulation of gene expression / positive regulation of odontoblast differentiation / positive regulation of p38MAPK cascade / positive regulation of primary miRNA processing / positive regulation of programmed cell death / positive regulation of protein localization to nucleus / positive regulation of SMAD protein signal transduction / positive regulation of transcription by RNA polymerase II / prostatic bud formation / regulation of mesodermal cell differentiation / sinoatrial node development / smooth muscle cell differentiation / transcription by RNA polymerase II / ureter morphogenesis
Components
endoplasmic reticulum lumen
General Function
Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including neurogenesis, vascular development, angiogenesis and osteogenesis (PubMed:31363885). Acts in concert with PTHLH/PTHRP to stimulate ductal outgrowth during embryonic mammary development and to inhibit hair follicle induction (By similarity). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2 (PubMed:25868050, PubMed:8006002). Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A propagates signal by phosphorylating SMAD1/5/8 that travel to the nucleus and act as activators and repressors of transcription of target genes (PubMed:25868050, PubMed:29212066). Positively regulates the expression of odontogenic development regulator MSX1 via inducing the IPO7-mediated import of SMAD1 to the nucleus (By similarity). Required for MSX1-mediated mesenchymal molar tooth bud development beyond the bud stage, via promoting Wnt signaling (By similarity). Acts as a positive regulator of odontoblast differentiation during mesenchymal tooth germ formation, expression is repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 signaling (By similarity). Able to induce its own expression in dental mesenchymal cells and also in the neighboring dental epithelial cells via an MSX1-mediated pathway (By similarity). Can also signal through non-canonical BMP pathways such as ERK/MAP kinase, PI3K/Akt, or SRC cascades (PubMed:31363885). For example, induces SRC phosphorylation which, in turn, activates VEGFR2, leading to an angiogenic response (PubMed:31363885)
Specific Function
Bmp receptor binding
Pfam Domain Function
Signal Regions
1-19
Transmembrane Regions
Not Available
Cellular Location
Secreted, extracellular space, extracellular matrix
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
ResourceLink
UniProtKB IDP12644
UniProtKB Entry NameBMP4_HUMAN
GeneCard IDBMP4
HGNC IDHGNC:1071
KEGG IDhsa:652
NCBI Gene ID652
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]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
CalciumnutraceuticalunknowntargetDetails