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 27-MAR-2024, entry version 152. 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. Also acts to promote expression of HAMP, via the interaction CC with its receptor BMPR1A/ALK3 (By similarity). Can also signal through CC non-canonical pathways such as ERK/MAP kinase signaling cascade that CC regulates osteoblast differentiation. Also stimulates the CC differentiation of myoblasts into osteoblasts via the EIF2AK3-EIF2A- CC ATF4 pathway by stimulating EIF2A phosphorylation which leads to CC increased expression of ATF4 which plays a central role in osteoblast CC differentiation. Acts as a positive regulator of odontoblast CC differentiation during mesenchymal tooth germ formation, expression is CC repressed during the bell stage by MSX1-mediated inhibition of CTNNB1 CC signaling (By similarity). {ECO:0000250|UniProtKB:P12643, CC ECO:0000250|UniProtKB:P21274}. 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. Interacts with ERFE (By similarity). Interacts with CC BMPR1A/ALK3; the interaction may induce HAMP expression (By CC similarity). Forms heterodimers with BMP6 in vitro; the heterodimer CC then binds to its receptor BMPR1A /ALK3 and may induce HAMP expression CC (By similarity). {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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 GlyCosmos; P49001; 4 sites, No reported glycans. DR GlyGen; P49001; 4 sites. DR PhosphoSitePlus; P49001; -. DR jPOST; P49001; -. DR PaxDb; 10116-ENSRNOP00000028904; -. DR GeneID; 29373; -. DR KEGG; rno:29373; -. DR UCSC; RGD:2211; rat. DR AGR; RGD:2211; -. DR CTD; 650; -. DR RGD; 2211; Bmp2. DR eggNOG; KOG3900; Eukaryota. DR InParanoid; P49001; -. DR OrthoDB; 2912454at2759; -. 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: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:0036305; P:ameloblast differentiation; 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:0048708; P:astrocyte differentiation; 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:0060348; P:bone development; ISO:RGD. DR GO; GO:0030282; P:bone mineralization; 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:0014898; P:cardiac muscle hypertrophy in response to stress; IMP: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:0003133; P:endodermal-mesodermal cell signaling; 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:0003129; P:heart induction; 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:0060426; P:lung vasculature 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:0045892; P:negative regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; 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: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:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; 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:0030316; P:osteoclast differentiation; ISO:RGD. DR GO; GO:0042698; P:ovulation cycle; IEP: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:1900159; P:positive regulation of bone mineralization involved in bone maturation; ISO:RGD. DR GO; GO:0061036; P:positive regulation of cartilage development; ISO:RGD. DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD. DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; 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:1901331; P:positive regulation of odontoblast differentiation; ISS:UniProtKB. 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:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; 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:0030177; P:positive regulation of Wnt signaling pathway; ISO:RGD. DR GO; GO:0031648; P:protein destabilization; ISO:RGD. DR GO; GO:0006029; P:proteoglycan metabolic process; ISO:RGD. DR GO; GO:0006355; P:regulation of DNA-templated transcription; ISO:RGD. DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; 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: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 GO; GO:0006366; P:transcription by RNA polymerase II; ISO:RGD. DR CDD; cd19390; TGF_beta_BMP2; 1. DR Gene3D; 2.60.120.970; -; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR InterPro; IPR047953; BMP2_TGF_beta-like. 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:SF143; BONE MORPHOGENETIC PROTEIN 2; 1. DR PANTHER; PTHR11848; TGF-BETA FAMILY; 1. DR Pfam; PF00019; TGF_beta; 1. DR Pfam; PF00688; TGFb_propeptide; 1. DR PRINTS; PR00669; INHIBINA. DR SMART; SM00204; TGFB; 1. DR SUPFAM; SSF57501; Cystine-knot cytokines; 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 //