Bone morphogenetic protein 2

Details

Name
Bone morphogenetic protein 2
Synonyms
  • BMP-2
  • BMP-2A
  • BMP2A
  • Bone morphogenetic protein 2A
Gene Name
BMP2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052626|Bone morphogenetic protein 2
MVAGTRCLLALLLPQVLLGGAAGLVPELGRRKFAAASSGRPSSQPSDEVLSEFELRLLSM
FGLKQRPTPSRDAVVPPYMLDLYRRHSGQPGSPAPDHRLERAASRANTVRSFHHEESLEE
LPETSGKTTRRFFFNLSSIPTEEFITSAELQVFREQMQDALGNNSSFHHRINIYEIIKPA
TANSKFPVTRLLDTRLVNQNASRWESFDVTPAVMRWTAQGHANHGFVVEVAHLEEKQGVS
KRHVRISRSLHQDEHSWSQIRPLLVTFGHDGKGHPLHKREKRQAKHKQRKRLKSSCKRHP
LYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKAC
CVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR
Number of residues
396
Molecular Weight
44701.535
Theoretical pI
Not Available
GO Classification
Functions
BMP receptor binding / co-receptor binding / cytokine activity / growth factor activity / phosphatase activator activity / signaling receptor binding / SMAD binding
Processes
activation of MAPK activity / animal organ morphogenesis / aortic valve development / atrioventricular canal morphogenesis / atrioventricular valve morphogenesis / BMP signaling pathway / BMP signaling pathway involved in heart development / BMP signaling pathway involved in heart induction / bone mineralization / bone mineralization involved in bone maturation / branching involved in ureteric bud morphogenesis / cardiac atrium formation / cardiac epithelial to mesenchymal transition / cardiac jelly development / cardiac muscle cell differentiation / cardiac muscle tissue morphogenesis / cardiocyte differentiation / cell fate commitment / cell-cell signaling / cellular response to BMP stimulus / cellular response to organic cyclic compound / chondrocyte differentiation / corticotropin hormone secreting cell differentiation / embryonic heart tube anterior/posterior pattern specification / endocardial cushion formation / endocardial cushion morphogenesis / epithelial to mesenchymal transition / heart development / in utero embryonic development / inflammatory response / inner ear development / mesenchymal cell differentiation / mesenchymal cell proliferation involved in ureteric bud development / mesenchyme development / negative regulation of aldosterone biosynthetic process / negative regulation of BMP signaling pathway / negative regulation of calcium-independent cell-cell adhesion / negative regulation of canonical Wnt signaling pathway / negative regulation of cardiac muscle cell differentiation / negative regulation of cell cycle / negative regulation of cell population proliferation / negative regulation of cortisol biosynthetic process / negative regulation of gene expression / negative regulation of insulin-like growth factor receptor signaling pathway / negative regulation of steroid biosynthetic process / negative regulation of transcription by RNA polymerase II / negative regulation of transcription, DNA-templated / negative regulation of Wnt signaling pathway involved in heart development / Notch signaling pathway / odontogenesis of dentin-containing tooth / osteoblast differentiation / pathway-restricted SMAD protein phosphorylation / pericardium development / positive regulation of apoptotic process / positive regulation of astrocyte differentiation / positive regulation of bone mineralization / positive regulation of cartilage development / positive regulation of cell migration / positive regulation of endothelial cell proliferation / positive regulation of epithelial to mesenchymal transition / positive regulation of ERK1 and ERK2 cascade / positive regulation of extracellular matrix constituent secretion / positive regulation of fat cell differentiation / positive regulation of gene expression / positive regulation of MAPK cascade / positive regulation of neuron differentiation / positive regulation of odontogenesis / positive regulation of ossification / positive regulation of osteoblast differentiation / positive regulation of osteoblast proliferation / positive regulation of p38MAPK cascade / positive regulation of pathway-restricted SMAD protein phosphorylation / positive regulation of phosphatase activity / positive regulation of pri-miRNA transcription by RNA polymerase II / positive regulation of protein binding / positive regulation of protein phosphorylation / positive regulation of transcription by RNA polymerase II / positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus / positive regulation of transcription, DNA-templated / positive regulation of Wnt signaling pathway / positive regulation of Wnt signaling pathway by BMP signaling pathway / protein destabilization / protein phosphorylation / proteoglycan metabolic process / regulation of odontogenesis of dentin-containing tooth / regulation of transcription, DNA-templated / response to bacterium / response to hypoxia / sequestering of BMP from receptor via BMP binding / skeletal system development / SMAD protein signal transduction / telencephalon development / telencephalon regionalization / thyroid-stimulating hormone-secreting cell differentiation
Components
BMP receptor complex / cell surface / extracellular region / extracellular space / intracellular membrane-bounded organelle
General Function
Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis (PubMed:18436533, PubMed:31019025, PubMed:24362451). Induces cartilage and bone formation (PubMed:3201241). Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2 (PubMed:15064755, PubMed:17295905, PubMed:18436533). Once all three components are bound together in a complex at the cell surface, BMPR2 phosphorylates and activates BMPR1A (PubMed:7791754). 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. Can also signal through non-canonical pathways such as ERK/MAP kinase signaling cascade that regulates osteoblast differentiation (PubMed:20851880). Stimulates also the differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A phosphorylation which leads to increased expression of ATF4 which plays a central role in osteoblast differentiation (PubMed:24362451).
Specific Function
Bmp receptor binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Secreted
Gene sequence
>lcl|BSEQ0052627|Bone morphogenetic protein 2 (BMP2)
ATGGTGGCCGGGACCCGCTGTCTTCTAGCGTTGCTGCTTCCCCAGGTCCTCCTGGGCGGC
GCGGCTGGCCTCGTTCCGGAGCTGGGCCGCAGGAAGTTCGCGGCGGCGTCGTCGGGCCGC
CCCTCATCCCAGCCCTCTGACGAGGTCCTGAGCGAGTTCGAGTTGCGGCTGCTCAGCATG
TTCGGCCTGAAACAGAGACCCACCCCCAGCAGGGACGCCGTGGTGCCCCCCTACATGCTA
GACCTGTATCGCAGGCACTCAGGTCAGCCGGGCTCACCCGCCCCAGACCACCGGTTGGAG
AGGGCAGCCAGCCGAGCCAACACTGTGCGCAGCTTCCACCATGAAGAATCTTTGGAAGAA
CTACCAGAAACGAGTGGGAAAACAACCCGGAGATTCTTCTTTAATTTAAGTTCTATCCCC
ACGGAGGAGTTTATCACCTCAGCAGAGCTTCAGGTTTTCCGAGAACAGATGCAAGATGCT
TTAGGAAACAATAGCAGTTTCCATCACCGAATTAATATTTATGAAATCATAAAACCTGCA
ACAGCCAACTCGAAATTCCCCGTGACCAGACTTTTGGACACCAGGTTGGTGAATCAGAAT
GCAAGCAGGTGGGAAAGTTTTGATGTCACCCCCGCTGTGATGCGGTGGACTGCACAGGGA
CACGCCAACCATGGATTCGTGGTGGAAGTGGCCCACTTGGAGGAGAAACAAGGTGTCTCC
AAGAGACATGTTAGGATAAGCAGGTCTTTGCACCAAGATGAACACAGCTGGTCACAGATA
AGGCCATTGCTAGTAACTTTTGGCCATGATGGAAAAGGGCATCCTCTCCACAAAAGAGAA
AAACGTCAAGCCAAACACAAACAGCGGAAACGCCTTAAGTCCAGCTGTAAGAGACACCCT
TTGTACGTGGACTTCAGTGACGTGGGGTGGAATGACTGGATTGTGGCTCCCCCGGGGTAT
CACGCCTTTTACTGCCACGGAGAATGCCCTTTTCCTCTGGCTGATCATCTGAACTCCACT
AATCATGCCATTGTTCAGACGTTGGTCAACTCTGTTAACTCTAAGATTCCTAAGGCATGC
TGTGTCCCGACAGAACTCAGTGCTATCTCGATGCTGTACCTTGACGAGAATGAAAAGGTT
GTATTAAAGAACTATCAGGACATGGTTGTGGAGGGTTGTGGGTGTCGCTAG
Chromosome Location
20
Locus
20p12.3
External Identifiers
ResourceLink
UniProtKB IDP12643
UniProtKB Entry NameBMP2_HUMAN
HGNC IDHGNC:1069
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]
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  4. Yeung B, Porter TJ, Vath JE: Direct isoform analysis of high-mannose-containing glycoproteins by on-line capillary electrophoresis electrospray mass spectrometry. Anal Chem. 1997 Jul 1;69(13):2510-6. [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. Lavery K, Swain P, Falb D, Alaoui-Ismaili MH: BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J Biol Chem. 2008 Jul 25;283(30):20948-58. doi: 10.1074/jbc.M800850200. Epub 2008 Apr 24. [Article]
  8. Heng S, Paule S, Hardman B, Li Y, Singh H, Rainczuk A, Stephens AN, Nie G: Posttranslational activation of bone morphogenetic protein 2 is mediated by proprotein convertase 6 during decidualization for pregnancy establishment. Endocrinology. 2010 Aug;151(8):3909-17. doi: 10.1210/en.2010-0326. Epub 2010 Jun 16. [Article]
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  10. Tanaka K, Kaji H, Yamaguchi T, Kanazawa I, Canaff L, Hendy GN, Sugimoto T: Involvement of the osteoinductive factors, Tmem119 and BMP-2, and the ER stress response PERK-eIF2alpha-ATF4 pathway in the commitment of myoblastic into osteoblastic cells. Calcif Tissue Int. 2014 Apr;94(4):454-64. doi: 10.1007/s00223-013-9828-1. Epub 2013 Dec 22. [Article]
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  13. Weber D, Kotzsch A, Nickel J, Harth S, Seher A, Mueller U, Sebald W, Mueller TD: A silent H-bond can be mutationally activated for high-affinity interaction of BMP-2 and activin type IIB receptor. BMC Struct Biol. 2007 Feb 12;7:6. doi: 10.1186/1472-6807-7-6. [Article]
  14. Seeherman HJ, Berasi SP, Brown CT, Martinez RX, Juo ZS, Jelinsky S, Cain MJ, Grode J, Tumelty KE, Bohner M, Grinberg O, Orr N, Shoseyov O, Eyckmans J, Chen C, Morales PR, Wilson CG, Vanderploeg EJ, Wozney JM: A BMP/activin A chimera is superior to native BMPs and induces bone repair in nonhuman primates when delivered in a composite matrix. Sci Transl Med. 2019 Apr 24;11(489). pii: 11/489/eaar4953. doi: 10.1126/scitranslmed.aar4953. [Article]
  15. Dathe K, Kjaer KW, Brehm A, Meinecke P, Nurnberg P, Neto JC, Brunoni D, Tommerup N, Ott CE, Klopocki E, Seemann P, Mundlos S: Duplications involving a conserved regulatory element downstream of BMP2 are associated with brachydactyly type A2. Am J Hum Genet. 2009 Apr;84(4):483-92. doi: 10.1016/j.ajhg.2009.03.001. Epub 2009 Mar 26. [Article]
  16. Su P, Ding H, Huang D, Zhou Y, Huang W, Zhong L, Vyse TJ, Wang Y: A 4.6 kb genomic duplication on 20p12.2-12.3 is associated with brachydactyly type A2 in a Chinese family. J Med Genet. 2011 May;48(5):312-6. doi: 10.1136/jmg.2010.084814. Epub 2011 Feb 26. [Article]
  17. Tan TY, Gonzaga-Jauregui C, Bhoj EJ, Strauss KA, Brigatti K, Puffenberger E, Li D, Xie L, Das N, Skubas I, Deckelbaum RA, Hughes V, Brydges S, Hatsell S, Siao CJ, Dominguez MG, Economides A, Overton JD, Mayne V, Simm PJ, Jones BO, Eggers S, Le Guyader G, Pelluard F, Haack TB, Sturm M, Riess A, Waldmueller S, Hofbeck M, Steindl K, Joset P, Rauch A, Hakonarson H, Baker NL, Farlie PG: Monoallelic BMP2 Variants Predicted to Result in Haploinsufficiency Cause Craniofacial, Skeletal, and Cardiac Features Overlapping Those of 20p12 Deletions. Am J Hum Genet. 2017 Dec 7;101(6):985-994. doi: 10.1016/j.ajhg.2017.10.006. Epub 2017 Nov 30. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails