BMP2_RAT
ID BMP2_RAT Reviewed; 393 AA.
AC P49001;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 25-MAY-2022, entry version 143.
DE RecName: Full=Bone morphogenetic protein 2;
DE Short=BMP-2;
DE AltName: Full=Bone morphogenetic protein 2A;
DE Short=BMP-2A;
DE Flags: Precursor;
GN Name=Bmp2; Synonyms=Bmp-2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Bone;
RA Feng J.Q., Chen D., Feng M., Harris M.A., Mundy G.R., Harris S.E.;
RL Submitted (SEP-1993) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Growth factor of the TGF-beta superfamily that plays
CC essential roles in many developmental processes, including
CC cardiogenesis, neurogenesis, and osteogenesis. Induces cartilage and
CC bone formation. Initiates the canonical BMP signaling cascade by
CC associating with type I receptor BMPR1A and type II receptor BMPR2.
CC Once all three components are bound together in a complex at the cell
CC surface, BMPR2 phosphorylates and activates BMPR1A. In turn, BMPR1A
CC propagates signal by phosphorylating SMAD1/5/8 that travel to the
CC nucleus and act as activators and repressors of transcription of target
CC genes. Can also signal through non-canonical pathways such as ERK/MAP
CC kinase signaling cascade that regulates osteoblast differentiation.
CC Stimulates also the differentiation of myoblasts into osteoblasts via
CC the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A phosphorylation
CC which leads to increased expression of ATF4 which plays a central role
CC in osteoblast differentiation. {ECO:0000250|UniProtKB:P12643}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with SOSTDC1 (By
CC similarity). Interacts with GREM2, RGMA, RGMB and RGMC. Interacts with
CC ASPN (By similarity). Interacts with MAFP5 (By similarity). Interacts
CC with FBN1 (via N-terminal domain) and FBN2. Interacts with type I
CC receptor BMPR1A. Interacts with type II receptor BMPR2 (By similarity).
CC Interacts with SCUBE3 (By similarity). Interacts with TNFAIP6
CC (primarily via Link domain); this interaction is inhibited by
CC hyaluronan. {ECO:0000250|UniProtKB:P12643,
CC ECO:0000250|UniProtKB:P21274}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in femur, calvaria, trachea, lung and
CC ovary.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; Z25868; CAA81088.1; -; mRNA.
DR PIR; S37073; S37073.
DR RefSeq; NP_058874.1; NM_017178.1.
DR AlphaFoldDB; P49001; -.
DR SMR; P49001; -.
DR STRING; 10116.ENSRNOP00000028904; -.
DR GlyGen; P49001; 4 sites.
DR PhosphoSitePlus; P49001; -.
DR jPOST; P49001; -.
DR PaxDb; P49001; -.
DR GeneID; 29373; -.
DR KEGG; rno:29373; -.
DR UCSC; RGD:2211; rat.
DR CTD; 650; -.
DR RGD; 2211; Bmp2.
DR eggNOG; KOG3900; Eukaryota.
DR InParanoid; P49001; -.
DR OrthoDB; 962484at2759; -.
DR PhylomeDB; P49001; -.
DR Reactome; R-RNO-201451; Signaling by BMP.
DR Reactome; R-RNO-2129379; Molecules associated with elastic fibres.
DR PRO; PR:P49001; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070724; C:BMP receptor complex; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0031982; C:vesicle; IDA:RGD.
DR GO; GO:0070700; F:BMP receptor binding; ISO:RGD.
DR GO; GO:0039706; F:co-receptor binding; ISO:RGD.
DR GO; GO:0005125; F:cytokine activity; ISO:RGD.
DR GO; GO:0008083; F:growth factor activity; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0019211; F:phosphatase activator activity; ISO:RGD.
DR GO; GO:0019904; F:protein domain specific binding; IPI:RGD.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:RGD.
DR GO; GO:0048018; F:receptor ligand activity; ISO:RGD.
DR GO; GO:0046332; F:SMAD binding; ISO:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0003176; P:aortic valve development; ISO:RGD.
DR GO; GO:1905222; P:atrioventricular canal morphogenesis; ISO:RGD.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:RGD.
DR GO; GO:0061312; P:BMP signaling pathway involved in heart development; ISO:RGD.
DR GO; GO:0003130; P:BMP signaling pathway involved in heart induction; ISO:RGD.
DR GO; GO:0060348; P:bone development; ISO:RGD.
DR GO; GO:0030282; P:bone mineralization; ISO:RGD.
DR GO; GO:0035630; P:bone mineralization involved in bone maturation; ISO:RGD.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISO:RGD.
DR GO; GO:0003210; P:cardiac atrium formation; ISO:RGD.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:1905072; P:cardiac jelly development; ISO:RGD.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; ISO:RGD.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0035051; P:cardiocyte differentiation; ISO:RGD.
DR GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IEP:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; ISO:RGD.
DR GO; GO:0002062; P:chondrocyte differentiation; ISO:RGD.
DR GO; GO:0060128; P:corticotropin hormone secreting cell differentiation; ISO:RGD.
DR GO; GO:0035054; P:embryonic heart tube anterior/posterior pattern specification; ISO:RGD.
DR GO; GO:0003272; P:endocardial cushion formation; ISO:RGD.
DR GO; GO:0003203; P:endocardial cushion morphogenesis; ISO:RGD.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0006954; P:inflammatory response; ISO:RGD.
DR GO; GO:0048839; P:inner ear development; ISO:RGD.
DR GO; GO:0048762; P:mesenchymal cell differentiation; ISS:UniProtKB.
DR GO; GO:0072138; P:mesenchymal cell proliferation involved in ureteric bud development; ISO:RGD.
DR GO; GO:0060485; P:mesenchyme development; ISO:RGD.
DR GO; GO:0032348; P:negative regulation of aldosterone biosynthetic process; ISO:RGD.
DR GO; GO:0051042; P:negative regulation of calcium-independent cell-cell adhesion; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; ISO:RGD.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:2000065; P:negative regulation of cortisol biosynthetic process; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; ISO:RGD.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; ISO:RGD.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISO:RGD.
DR GO; GO:0010894; P:negative regulation of steroid biosynthetic process; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISO:RGD.
DR GO; GO:0003308; P:negative regulation of Wnt signaling pathway involved in heart development; ISO:RGD.
DR GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; ISO:RGD.
DR GO; GO:0042698; P:ovulation cycle; IEP:RGD.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0060039; P:pericardium development; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; ISO:RGD.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISO:RGD.
DR GO; GO:0061036; P:positive regulation of cartilage development; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:RGD.
DR GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0003331; P:positive regulation of extracellular matrix constituent secretion; ISO:RGD.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; ISO:RGD.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IDA:MGI.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0042482; P:positive regulation of odontogenesis; ISO:RGD.
DR GO; GO:0045778; P:positive regulation of ossification; ISO:RGD.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISO:RGD.
DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; ISO:RGD.
DR GO; GO:1900745; P:positive regulation of p38MAPK cascade; ISO:RGD.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; ISO:RGD.
DR GO; GO:0010922; P:positive regulation of phosphatase activity; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0060804; P:positive regulation of Wnt signaling pathway by BMP signaling pathway; ISO:RGD.
DR GO; GO:0031648; P:protein destabilization; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0006029; P:proteoglycan metabolic process; ISO:RGD.
DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; ISO:RGD.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; ISO:RGD.
DR GO; GO:0009612; P:response to mechanical stimulus; IEP:RGD.
DR GO; GO:0032526; P:response to retinoic acid; IEP:RGD.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0021537; P:telencephalon development; ISO:RGD.
DR GO; GO:0021978; P:telencephalon regionalization; ISO:RGD.
DR GO; GO:0060129; P:thyroid-stimulating hormone-secreting cell differentiation; ISO:RGD.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR001111; TGF-b_propeptide.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR Pfam; PF00688; TGFb_propeptide; 1.
DR SMART; SM00204; TGFB; 1.
DR SUPFAM; SSF57501; SSF57501; 1.
DR PROSITE; PS00250; TGF_BETA_1; 1.
DR PROSITE; PS51362; TGF_BETA_2; 1.
PE 2: Evidence at transcript level;
KW Chondrogenesis; Cleavage on pair of basic residues; Cytokine;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW Growth factor; Osteogenesis; Phosphoprotein; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..279
FT /note="Cleaved by PCSK5"
FT /evidence="ECO:0000305"
FT /id="PRO_0000033830"
FT CHAIN 280..393
FT /note="Bone morphogenetic protein 2"
FT /id="PRO_0000033831"
FT REGION 268..290
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..290
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12644"
FT CARBOHYD 133
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 161
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 293..358
FT /evidence="ECO:0000250"
FT DISULFID 322..390
FT /evidence="ECO:0000250"
FT DISULFID 326..392
FT /evidence="ECO:0000250"
FT DISULFID 357
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 393 AA; 44383 MW; 7D20865852E0F213 CRC64;
MVAGTRCLLV LLLPQVLLGG AAGLIPELGR KKFAGASRPL SRPSEDVLSE FELRLLSMFG
LKQRPTPSKD VVVPPYMLDL YRRHSGQPGA LAPDHRLERA ASRANTVLSF HHEEAIEELS
EMSGKTSRRF FFNLSSVPTD EFLTSAELQI FREQMQEALG NSSFQHRINI YEIIKPATAS
SKFPVTRLLD TRLVTQNTSQ WESFDVTPAV MRWTAQGHTN HGFVVEVAHL EEKPGVSKRH
VRISRSLHQD EHSWSQVRPL LVTFGHDGKG HPLHKREKRQ AKHKQRKRLK SSCKRHPLYV
DFSDVGWNDW IVAPPGYHAF YCHGECPFPL ADHLNSTNHA IVQTLVNSVN SKIPKACCVP
TELSAISMLY LDENEKVVLK NYQDMVVEGC GCR
