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HMDB Protein ID HMDBP14532
Secondary Accession Numbers None
Name Bone morphogenetic protein 4
  1. BMP-4
  2. Bone morphogenetic protein 2B
  3. BMP-2B
Gene Name BMP4
Protein Type Unknown
Biological Properties
General Function Not Available
Specific 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). 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).
  • Basal cell carcinoma
  • Cytokine-cytokine receptor interaction
  • Fluid shear stress and atherosclerosis
  • Hippo signaling pathway
  • Signaling pathways regulating pluripotency of stem cells
  • TGF-beta signaling pathway
  • Thyroid hormone signaling pathway
Reactions Not Available
GO Classification
Biological Process
mesenchymal to epithelial transition involved in metanephros morphogenesis
mesodermal cell fate determination
mesonephros development
metanephric collecting duct development
negative regulation of branch elongation involved in ureteric bud branching by BMP signaling pathway
negative regulation of striated muscle tissue development
negative regulation of branching involved in ureteric bud morphogenesis
negative regulation of cell proliferation involved in heart morphogenesis
negative regulation of glomerular mesangial cell proliferation
negative regulation of glomerulus development
negative regulation of immature T cell proliferation in thymus
negative regulation of mesenchymal cell proliferation involved in ureter development
negative regulation of cell cycle
negative regulation of metanephric comma-shaped body morphogenesis
negative regulation of metanephric S-shaped body morphogenesis
negative regulation of prostatic bud formation
positive regulation of bone mineralization
negative regulation of T cell differentiation in thymus
positive regulation of cardiac muscle fiber development
positive regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis
positive regulation of cell proliferation involved in outflow tract morphogenesis
positive regulation of epidermal cell differentiation
positive regulation of kidney development
positive regulation of production of miRNAs involved in gene silencing by miRNA
positive regulation of apoptotic process
pulmonary artery endothelial tube 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
negative regulation of MAP kinase activity
secondary heart field specification
sinoatrial node development
specification of animal organ position
specification of ureteric bud anterior/posterior symmetry by BMP signaling pathway
branching morphogenesis of a tube
tendon cell differentiation
trachea development
trachea formation
ureter epithelial cell differentiation
ureter smooth muscle cell differentiation
positive regulation of cell death
positive regulation of cell proliferation
negative regulation of apoptotic process
positive regulation of branching involved in lung morphogenesis
chondrocyte differentiation
negative regulation of epithelial cell proliferation
SMAD protein signal transduction
positive regulation of neuron differentiation
BMP signaling pathway
negative regulation of extrinsic apoptotic signaling pathway
negative regulation of pri-miRNA transcription by RNA polymerase II
negative regulation of chondrocyte differentiation
post-translational protein modification
positive regulation of pathway-restricted SMAD protein phosphorylation
positive regulation of collagen biosynthetic process
positive regulation of endothelial cell differentiation
positive regulation of epithelial to mesenchymal transition
cellular protein metabolic process
positive regulation of protein binding
positive regulation of endothelial cell migration
positive regulation of protein phosphorylation
coronary vasculature development
pharyngeal arch artery morphogenesis
aortic valve morphogenesis
positive regulation of ossification
pulmonary valve morphogenesis
activation of MAPKK activity
telencephalon regionalization
positive regulation of ERK1 and ERK2 cascade
osteoblast differentiation
hematopoietic progenitor cell differentiation
lung morphogenesis
embryonic hindlimb morphogenesis
negative regulation of mitosis
negative regulation of transcription, DNA-dependent
positive regulation of transcription, DNA-dependent
erythrocyte differentiation
steroid hormone mediated signaling pathway
germ cell development
negative regulation of transcription from RNA polymerase II promoter
endoderm development
positive regulation of transcription from RNA polymerase II promoter
branching involved in ureteric bud morphogenesis
neuron fate commitment
anterior/posterior axis specification
positive regulation of cartilage development
embryonic cranial skeleton morphogenesis
smooth muscle tissue development
negative regulation of phosphorylation
positive regulation of BMP signaling pathway
odontogenesis of dentin-containing tooth
cardiac septum development
positive regulation of osteoblast differentiation
type B pancreatic cell development
outflow tract septum morphogenesis
positive regulation of epithelial cell proliferation
positive regulation of SMAD protein signal transduction
monocyte differentiation
kidney development
lung alveolus development
negative regulation of cell proliferation
pituitary gland development
negative regulation of thymocyte apoptotic process
positive regulation of gene expression
negative regulation of cell death
neural tube closure
telencephalon development
positive regulation of endothelial cell proliferation
bud elongation involved in lung branching
positive regulation of smooth muscle cell proliferation
negative regulation of gene expression
common-partner SMAD protein phosphorylation
blood vessel endothelial cell proliferation involved in sprouting angiogenesis
BMP signaling pathway involved in heart development
negative regulation of myoblast differentiation
BMP signaling pathway involved in heart induction
BMP signaling pathway involved in nephric duct formation
embryonic digit morphogenesis
BMP signaling pathway involved in renal system segmentation
cardiac muscle cell differentiation
BMP signaling pathway involved in ureter morphogenesis
branching involved in prostate gland morphogenesis
bronchus development
bud dilation involved in lung branching
post-embryonic development
ureteric bud development
membranous septum morphogenesis
cloacal septation
cranial suture morphogenesis
deltoid tuberosity development
cellular response to BMP stimulus
dorsal/ventral neural tube patterning
embryonic skeletal joint morphogenesis
endocardial cushion development
epithelial cell proliferation involved in lung morphogenesis
epithelial tube branching involved in lung morphogenesis
epithelial-mesenchymal cell signaling
glomerular capillary formation
glomerular visceral epithelial cell development
inner ear receptor cell differentiation
intermediate mesodermal cell differentiation
lens induction in camera-type eye
lymphoid progenitor cell differentiation
macrophage differentiation
endochondral ossification
protein localization to nucleus
mammary gland formation
mesenchymal cell differentiation involved in kidney development
renal system process
mesenchymal cell proliferation involved in ureter development
mesenchymal cell proliferation involved in ureteric bud development
Cellular Component
endoplasmic reticulum lumen
extracellular region
extracellular space
Molecular Function
BMP receptor binding
growth factor activity
chemoattractant activity
heparin binding
cytokine activity
co-receptor binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 408
Molecular Weight 46554.545
Theoretical pI 8.725
Pfam Domain Function
  • 1-19;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID P12644
UniProtKB/Swiss-Prot Entry Name BMP4_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
General References
  1. 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. [PubMed:15489334 ]
  2. 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. [PubMed:3201241 ]
  3. 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. [PubMed:15020244 ]
  4. 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. [PubMed:26091039 ]
  5. 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. [PubMed:18339631 ]
  6. 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. doi: 10.1007/s002239900518. [PubMed:9701626 ]
  7. 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. doi: 10.3109/10425179509030980. [PubMed:7579580 ]
  8. ten Dijke P, Yamashita H, Sampath TK, Reddi AH, Estevez M, Riddle DL, Ichijo H, Heldin CH, Miyazono K: Identification of type I receptors for osteogenic protein-1 and bone morphogenetic protein-4. J Biol Chem. 1994 Jun 24;269(25):16985-8. [PubMed:8006002 ]
  9. Rege J, Nishimoto HK, Nishimoto K, Rodgers RJ, Auchus RJ, Rainey WE: Bone Morphogenetic Protein-4 (BMP4): A Paracrine Regulator of Human Adrenal C19 Steroid Synthesis. Endocrinology. 2015 Jul;156(7):2530-40. doi: 10.1210/en.2014-1942. Epub 2015 Apr 13. [PubMed:25868050 ]
  10. Jin X, Nie E, Zhou X, Zeng A, Yu T, Zhi T, Jiang K, Wang Y, Zhang J, You Y: Fstl1 Promotes Glioma Growth Through the BMP4/Smad1/5/8 Signaling Pathway. Cell Physiol Biochem. 2017;44(4):1616-1628. doi: 10.1159/000485759. Epub 2017 Dec 6. [PubMed:29212066 ]
  11. Rezzola S, Di Somma M, Corsini M, Leali D, Ravelli C, Polli VAB, Grillo E, Presta M, Mitola S: VEGFR2 activation mediates the pro-angiogenic activity of BMP4. Angiogenesis. 2019 Nov;22(4):521-533. doi: 10.1007/s10456-019-09676-y. Epub 2019 Jul 30. [PubMed:31363885 ]
  12. 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. doi: 10.1038/sj.ejhg.5200875. [PubMed:12404109 ]
  13. 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. [PubMed:18252212 ]
  14. 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. [PubMed:19249007 ]