BMP2_RABIT
ID BMP2_RABIT Reviewed; 395 AA.
AC O46564;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 25-MAY-2022, entry version 116.
DE RecName: Full=Bone morphogenetic protein 2;
DE Short=BMP-2;
DE Flags: Precursor;
GN Name=BMP2; Synonyms=BMP-2;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Ocular ciliary epithelium;
RA Wan X.L., Sears J., Chen S., Sears M.;
RT "Cloning and expression of BMP-2/-4 from rabbit ocular ciliary
RT epithelium.";
RL Submitted (JAN-1998) 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|UniProtKB:P12643}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; AF041421; AAB96785.1; -; mRNA.
DR RefSeq; NP_001076119.1; NM_001082650.1.
DR AlphaFoldDB; O46564; -.
DR SMR; O46564; -.
DR STRING; 9986.ENSOCUP00000010036; -.
DR PRIDE; O46564; -.
DR GeneID; 100009349; -.
DR KEGG; ocu:100009349; -.
DR CTD; 650; -.
DR eggNOG; KOG3900; Eukaryota.
DR InParanoid; O46564; -.
DR OrthoDB; 962484at2759; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR GO; GO:0070700; F:BMP receptor binding; ISS:UniProtKB.
DR GO; GO:0005125; F:cytokine activity; IEA:UniProtKB-KW.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0019211; F:phosphatase activator activity; ISS:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; ISS:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0003130; P:BMP signaling pathway involved in heart induction; ISS:UniProtKB.
DR GO; GO:0035630; P:bone mineralization involved in bone maturation; ISS:UniProtKB.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0035051; P:cardiocyte differentiation; ISS:UniProtKB.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0048762; P:mesenchymal cell differentiation; ISS:UniProtKB.
DR GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; ISS:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0003308; P:negative regulation of Wnt signaling pathway involved in heart development; ISS:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB.
DR GO; GO:0061036; P:positive regulation of cartilage development; ISS:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045778; P:positive regulation of ossification; ISS:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0010922; P:positive regulation of phosphatase activity; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; ISS:UniProtKB.
DR GO; GO:0021537; P:telencephalon development; ISS:UniProtKB.
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..23
FT /evidence="ECO:0000255"
FT PROPEP 24..281
FT /note="Cleaved by PCSK5"
FT /evidence="ECO:0000250"
FT /id="PRO_0000033828"
FT CHAIN 282..395
FT /note="Bone morphogenetic protein 2"
FT /id="PRO_0000033829"
FT REGION 270..292
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..292
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 86
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12644"
FT CARBOHYD 134
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 337
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 295..360
FT /evidence="ECO:0000250"
FT DISULFID 324..392
FT /evidence="ECO:0000250"
FT DISULFID 328..394
FT /evidence="ECO:0000250"
FT DISULFID 359
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 395 AA; 44664 MW; 8D1DDCFBAC582496 CRC64;
MVAGTRCLLA LLLPQVLLGG AAGLIPELGR RKFAASSGRP SPQPSDDILS EFELRLLSMF
GLKQRPTPSR DAVVPPYMLD LYRRHSGQPG APAPDHRLER AASRANTVRS FHHEESLEEL
PETSGKTTRR FFFNLTSIPP EEFITSAELQ VFREQMQEAL GDDSGFHHRI NIYEIIKPAT
ANSKFPATRL LDTRLVNQNT SRWESFDVTP AVMRWTAQGH ANHGFVVEVT HLEEKQGVSK
RHVRISRSLH PDEHSWSQIR PLLVTFGHDG KGHPLHRREK RQAKHKQRKR LKSSCKRHPL
YVDFSDVGWN DWIVAPPGYH AFYCHGECPF PLADHLNSTN HAIVQTLVNS VNSKIPKACC
VPTELSAISM LYLDENEKVV LKNYQDMVVE GCGCR
