Protein: Bone morphogenetic protein 2 (BMP-2) (Bone morphogenetic protein 2A) (BMP-2A) (P12643)
Organism: Homo sapiens (Human)
Function: Growth factor of the TGF-beta superfamily that plays essential roles in many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Induces cartilage and bone formation. Initiates the canonical BMP signaling cascade by associating with type I receptor BMPR1A and type II receptor BMPR2. 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. Can also signal through non-canonical pathways such as ERK/MAP kinase signaling cascade that regulates osteoblast differentiation. 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.
Subcellular location: Secreted.
Sequence: MVAGTRCLLALLLPQVLLGGAAGLVPELGRRKFAAASSGRPSSQPSDEVLSEFELRLLSMFGLKQRPTPSRDAVVPPYMLDLYRRHSGQPGSPAPDHRLERAASRANTVRSFHHEESLEELPETSGKTTRRFFFNLSSIPTEEFITSAELQVFREQMQDALGNNSSFHHRINIYEIIKPATANSKFPVTRLLDTRLVNQNASRWESFDVTPAVMRWTAQGHANHGFVVEVAHLEEKQGVSKRHVRISRSLHQDEHSWSQIRPLLVTFGHDGKGHPLHKREKRQAKHKQRKRLKSSCKRHPLYVDFSDVGWNDWIVAPPGYHAFYCHGECPFPLADHLNSTNHAIVQTLVNSVNSKIPKACCVPTELSAISMLYLDENEKVVLKNYQDMVVEGCGCR
InterPro domains: - IPR015615: Transforming growth factor-beta-related (family) [8-396]
- IPR001839: Transforming growth factor-beta, C-terminal (domain) [279-396]
- IPR001111: TGF-beta, propeptide (domain) [49-267]
- IPR047953: Bone morphogenetic protein 2, TGF-beta-like domain (domain) [294-396]
- IPR017948: Transforming growth factor beta, conserved site (conserved_site) [314-329]
- IPR029034: Cystine-knot cytokine (homologous_superfamily) [288-396]
Interaction partners: - Bone morphogenetic protein receptor type-2
- Activin receptor type-2B
- Chordin
- Bone morphogenetic protein receptor type-1B
- Activin receptor type-2A
- Noggin
- Bone morphogenetic protein receptor type-1A
- Hemojuvelin
- Gremlin-1
- Repulsive guidance molecule B
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0098772 (molecular function regulator activity), GO:0005488 (binding), GO:0140677 (molecular function activator activity), GO:0030545 (signaling receptor regulator activity), GO:0005515 (protein binding), GO:0005102 (signaling receptor binding), GO:0030546 (signaling receptor activator activity), GO:0033612 (receptor serine/threonine kinase binding), GO:0048018 (receptor ligand activity), GO:0042056 (chemoattractant activity), GO:0070696 (transmembrane receptor protein serine/threonine kinase binding), GO:0005125 (cytokine activity)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0023052 (signaling), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0009653 (anatomical structure morphogenesis), GO:0042221 (response to chemical), GO:0051240 (positive regulation of multicellular organismal process), GO:0071840 (cellular component organization or biogenesis), GO:0051239 (regulation of multicellular organismal process), GO:0048646 (anatomical structure formation involved in morphogenesis), GO:0050793 (regulation of developmental process), GO:0009719 (response to endogenous stimulus), GO:0050794 (regulation of cellular process), GO:0048583 (regulation of response to stimulus), GO:0051716 (cellular response to stimulus), GO:0023051 (regulation of signaling), GO:0051093 (negative regulation of developmental process), GO:0048523 (negative regulation of cellular process), GO:0007165 (signal transduction), GO:0048869 (cellular developmental process), GO:0023056 (positive regulation of signaling), GO:0007275 (multicellular organism development), GO:0048584 (positive regulation of response to stimulus), GO:0019222 (regulation of metabolic process), GO:0007155 (cell adhesion), GO:0033036 (macromolecule localization), GO:0009893 (positive regulation of metabolic process), GO:0030029 (actin filament-based process), GO:0051094 (positive regulation of developmental process), GO:0007154 (cell communication), GO:0048522 (positive regulation of cellular process), GO:0048729 (tissue morphogenesis), GO:0060548 (negative regulation of cell death), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0070848 (response to growth factor), GO:0009966 (regulation of signal transduction), GO:0071495 (cellular response to endogenous stimulus), GO:0060255 (regulation of macromolecule metabolic process), GO:0010948 (negative regulation of cell cycle process), GO:0010712 (regulation of collagen metabolic process), GO:0030036 (actin cytoskeleton organization), GO:0035295 (tube development), GO:0051726 (regulation of cell cycle), GO:0001704 (formation of primary germ layer), GO:1904018 (positive regulation of vasculature development), GO:0048598 (embryonic morphogenesis), GO:0009888 (tissue development), GO:0009755 (hormone-mediated signaling pathway), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0022603 (regulation of anatomical structure morphogenesis), GO:0045595 (regulation of cell differentiation), GO:0045786 (negative regulation of cell cycle), GO:0016043 (cellular component organization), GO:0007166 (cell surface receptor signaling pathway), GO:0009790 (embryo development), GO:0048634 (regulation of muscle organ development), GO:0030036 (actin cytoskeleton organization), GO:1901861 (regulation of muscle tissue development), GO:0008284 (positive regulation of cell population proliferation), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0035239 (tube morphogenesis), GO:0009967 (positive regulation of signal transduction), GO:0045597 (positive regulation of cell differentiation), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0098609 (cell-cell adhesion), GO:0061138 (morphogenesis of a branching epithelium), GO:0030036 (actin cytoskeleton organization), GO:0009891 (positive regulation of biosynthetic process), GO:0045165 (cell fate commitment), GO:0001704 (formation of primary germ layer), GO:2000026 (regulation of multicellular organismal development), GO:0042127 (regulation of cell population proliferation), GO:0010941 (regulation of cell death), GO:0009888 (tissue development), GO:0031325 (positive regulation of cellular metabolic process), GO:0010646 (regulation of cell communication), GO:0045596 (negative regulation of cell differentiation), GO:0009889 (regulation of biosynthetic process), GO:0070727 (cellular macromolecule localization), GO:0031323 (regulation of cellular metabolic process), GO:0010647 (positive regulation of cell communication), GO:0080090 (regulation of primary metabolic process), GO:0061036 (positive regulation of cartilage development), GO:0048333 (mesodermal cell differentiation), GO:0060562 (epithelial tube morphogenesis), GO:0072009 (nephron epithelium development), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0051246 (regulation of protein metabolic process), GO:0001944 (vasculature development), GO:0001707 (mesoderm formation), GO:0007369 (gastrulation), GO:0090092 (regulation of transmembrane receptor protein serine/threonine kinase signaling pathway), GO:0002009 (morphogenesis of an epithelium), GO:0045669 (positive regulation of osteoblast differentiation), GO:0010468 (regulation of gene expression), GO:0045604 (regulation of epidermal cell differentiation), GO:0030501 (positive regulation of bone mineralization), GO:0048568 (embryonic organ development), GO:0003007 (heart morphogenesis), GO:0007399 (nervous system development), GO:0071772 (response to BMP), GO:0001501 (skeletal system development), GO:0002064 (epithelial cell development), GO:0072359 (circulatory system development), GO:0045930 (negative regulation of mitotic cell cycle), GO:0060395 (SMAD protein signal transduction), GO:1902533 (positive regulation of intracellular signal transduction), GO:0051252 (regulation of RNA metabolic process), GO:0048762 (mesenchymal cell differentiation), GO:2000027 (regulation of animal organ morphogenesis), GO:0007507 (heart development), GO:0071559 (response to transforming growth factor beta), GO:0007167 (enzyme-linked receptor protein signaling pathway), GO:0010562 (positive regulation of phosphorus metabolic process), GO:0001707 (mesoderm formation), GO:1901342 (regulation of vasculature development), GO:0045766 (positive regulation of angiogenesis), GO:0060485 (mesenchyme development), GO:0060795 (cell fate commitment involved in formation of primary germ layer), GO:0035987 (endodermal cell differentiation), GO:0050679 (positive regulation of epithelial cell proliferation), GO:0070167 (regulation of biomineral tissue development), GO:0010557 (positive regulation of macromolecule biosynthetic process), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0051254 (positive regulation of RNA metabolic process), GO:0090100 (positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway), GO:0031326 (regulation of cellular biosynthetic process), GO:0051247 (positive regulation of protein metabolic process), GO:0048332 (mesoderm morphogenesis), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0045765 (regulation of angiogenesis), GO:0008104 (protein localization), GO:0007498 (mesoderm development), GO:0060429 (epithelium development), GO:0006996 (organelle organization), GO:0031328 (positive regulation of cellular biosynthetic process), GO:0071363 (cellular response to growth factor stimulus), GO:1902531 (regulation of intracellular signal transduction), GO:0051174 (regulation of phosphorus metabolic process), GO:0071363 (cellular response to growth factor stimulus), GO:0097435 (supramolecular fiber organization), GO:0009792 (embryo development ending in birth or egg hatching), GO:0030856 (regulation of epithelial cell differentiation), GO:1901988 (negative regulation of cell cycle phase transition), GO:0042981 (regulation of apoptotic process), GO:0001837 (epithelial to mesenchymal transition), GO:0045937 (positive regulation of phosphate metabolic process), GO:2001141 (regulation of RNA biosynthetic process), GO:0045601 (regulation of endothelial cell differentiation), GO:0007010 (cytoskeleton organization), GO:0007178 (transmembrane receptor protein serine/threonine kinase signaling pathway), GO:0110020 (regulation of actomyosin structure organization), GO:0007178 (transmembrane receptor protein serine/threonine kinase signaling pathway), GO:0051896 (regulation of protein kinase B signaling), GO:1902680 (positive regulation of RNA biosynthetic process), GO:0010862 (positive regulation of pathway-restricted SMAD protein phosphorylation), GO:0031401 (positive regulation of protein modification process), GO:0061041 (regulation of wound healing), GO:0043408 (regulation of MAPK cascade), GO:0043009 (chordate embryonic development), GO:0001938 (positive regulation of endothelial cell proliferation), GO:0048738 (cardiac muscle tissue development), GO:0031399 (regulation of protein modification process), GO:0043066 (negative regulation of apoptotic process), GO:0006355 (regulation of DNA-templated transcription), GO:0019220 (regulation of phosphate metabolic process), GO:0048706 (embryonic skeletal system development), GO:2001237 (negative regulation of extrinsic apoptotic signaling pathway), GO:2001236 (regulation of extrinsic apoptotic signaling pathway), GO:0071773 (cellular response to BMP stimulus), GO:0001932 (regulation of protein phosphorylation), GO:0070374 (positive regulation of ERK1 and ERK2 cascade), GO:1903508 (positive regulation of nucleic acid-templated transcription), GO:0042327 (positive regulation of phosphorylation), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0001934 (positive regulation of protein phosphorylation), GO:0006357 (regulation of transcription by RNA polymerase II), GO:0042325 (regulation of phosphorylation), GO:0045893 (positive regulation of DNA-templated transcription), GO:0030509 (BMP signaling pathway), GO:0045944 (positive regulation of transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)