Database: UniProt
Entry: P12643
LinkDB: P12643
Original site: P12643 
ID   BMP2_HUMAN              Reviewed;         396 AA.
AC   P12643;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1989, sequence version 1.
DT   26-NOV-2014, entry version 173.
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=BMP2A;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RX   PubMed=3201241; DOI=10.1126/science.3201241;
RA   Wozney J.M., Rosen V., Celeste A.J., Mitsock L.M., Whitters M.J.,
RA   Kriz R.W., Hewick R.M., Wang E.A.;
RT   "Novel regulators of bone formation: molecular clones and
RT   activities.";
RL   Science 242:1528-1534(1988).
RN   [2]
RA   Shore E.M., Xu M.-Q., Calvert G., Moriatis J., Kaplan F.S.;
RT   "Human bone morphogenetic protein 2 (BMP-2) genomic DNA sequence.";
RL   Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [4]
RX   PubMed=9265423; DOI=10.1021/ac9611172;
RA   Yeung B., Porter T.J., Vath J.E.;
RT   "Direct isoform analysis of high-mannose-containing glycoproteins by
RT   on-line capillary electrophoresis electrospray mass spectrometry.";
RL   Anal. Chem. 69:2510-2516(1997).
RN   [5]
RX   PubMed=15020244; DOI=10.1016/j.bbrc.2004.02.075;
RA   Yanagita M., Oka M., Watabe T., Iguchi H., Niida A., Takahashi S.,
RA   Akiyama T., Miyazono K., Yanagisawa M., Sakurai T.;
RT   "USAG-1: a bone morphogenetic protein antagonist abundantly expressed
RT   in the kidney.";
RL   Biochem. Biophys. Res. Commun. 316:490-500(2004).
RN   [6]
RX   PubMed=20555025; DOI=10.1210/en.2010-0326;
RA   Heng S., Paule S., Hardman B., Li Y., Singh H., Rainczuk A.,
RA   Stephens A.N., Nie G.;
RT   "Posttranslational activation of bone morphogenetic protein 2 is
RT   mediated by proprotein convertase 6 during decidualization for
RT   pregnancy establishment.";
RL   Endocrinology 151:3909-3917(2010).
RN   [7]
RX   PubMed=10074410; DOI=10.1006/jmbi.1999.2590;
RA   Scheufler C., Sebald W., Huelsmeyer M.;
RT   "Crystal structure of human bone morphogenetic protein-2 at 2.7 A
RT   resolution.";
RL   J. Mol. Biol. 287:103-115(1999).
CC   -!- FUNCTION: Induces cartilage and bone formation.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with SOSTDC1.
CC       Interacts with GREM2, RGMA, RGMB and RGMC. Interacts with ASPN (By
CC       similarity). {ECO:0000250}.
CC       P36894:BMPR1A; NbExp=11; IntAct=EBI-1029262, EBI-1029237;
CC       O00238:BMPR1B; NbExp=3; IntAct=EBI-1029262, EBI-7527193;
CC       Q12841:FSTL1; NbExp=2; IntAct=EBI-1029262, EBI-2349801;
CC       Q13253:NOG; NbExp=2; IntAct=EBI-1029262, EBI-1035205;
CC   -!- TISSUE SPECIFICITY: Particularly abundant in lung, spleen and
CC       colon and in low but significant levels in heart, brain, placenta,
CC       liver, skeletal muscle, kidney, pancreas, prostate, ovary and
CC       small intestine.
CC   -!- PHARMACEUTICAL: Available under the name Infuse (Medtronic Sofamor
CC       Danek). Used for treating open tibial shaft fractures.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Bone morphogenetic protein 2
CC       entry;
CC       URL="";
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DR   EMBL; M22489; AAA51834.1; -; mRNA.
DR   EMBL; AF040249; AAF21646.1; -; Genomic_DNA.
DR   EMBL; AL035668; CAB82007.1; -; Genomic_DNA.
DR   CCDS; CCDS13099.1; -.
DR   PIR; B37278; BMHU2.
DR   RefSeq; NP_001191.1; NM_001200.2.
DR   UniGene; Hs.73853; -.
DR   PDB; 1ES7; X-ray; 2.90 A; A/C=283-396.
DR   PDB; 1REU; X-ray; 2.65 A; A=294-396.
DR   PDB; 1REW; X-ray; 1.86 A; A/B=283-396.
DR   PDB; 2GOO; X-ray; 2.20 A; A/D=283-396.
DR   PDB; 2H62; X-ray; 1.85 A; A/B=283-396.
DR   PDB; 2H64; X-ray; 1.92 A; A=283-396.
DR   PDB; 2QJ9; X-ray; 2.44 A; A/B=283-396.
DR   PDB; 2QJA; X-ray; 2.60 A; A/B=283-396.
DR   PDB; 2QJB; X-ray; 2.50 A; A/B=283-396.
DR   PDB; 3BK3; X-ray; 2.70 A; A/B=283-396.
DR   PDB; 3BMP; X-ray; 2.70 A; A=283-396.
DR   PDB; 4MID; X-ray; 2.14 A; A=283-312.
DR   PDB; 4N1D; X-ray; 1.91 A; A=283-305, A=362-396.
DR   PDBsum; 1ES7; -.
DR   PDBsum; 1REU; -.
DR   PDBsum; 1REW; -.
DR   PDBsum; 2GOO; -.
DR   PDBsum; 2H62; -.
DR   PDBsum; 2H64; -.
DR   PDBsum; 2QJ9; -.
DR   PDBsum; 2QJA; -.
DR   PDBsum; 2QJB; -.
DR   PDBsum; 3BK3; -.
DR   PDBsum; 3BMP; -.
DR   PDBsum; 4MID; -.
DR   PDBsum; 4N1D; -.
DR   ProteinModelPortal; P12643; -.
DR   SMR; P12643; 293-396.
DR   BioGrid; 107118; 8.
DR   DIP; DIP-5792N; -.
DR   IntAct; P12643; 8.
DR   MINT; MINT-6772716; -.
DR   STRING; 9606.ENSP00000368104; -.
DR   ChEMBL; CHEMBL1926496; -.
DR   PhosphoSite; P12643; -.
DR   DMDM; 115068; -.
DR   PaxDb; P12643; -.
DR   PRIDE; P12643; -.
DR   DNASU; 650; -.
DR   Ensembl; ENST00000378827; ENSP00000368104; ENSG00000125845.
DR   GeneID; 650; -.
DR   KEGG; hsa:650; -.
DR   UCSC; uc002wmu.1; human.
DR   CTD; 650; -.
DR   GeneCards; GC20P006696; -.
DR   HGNC; HGNC:1069; BMP2.
DR   MIM; 112261; gene.
DR   neXtProt; NX_P12643; -.
DR   Orphanet; 261295; 20p12.3 microdeletion syndrome.
DR   Orphanet; 93396; Brachydactyly type A2.
DR   PharmGKB; PA25379; -.
DR   eggNOG; NOG243555; -.
DR   GeneTree; ENSGT00760000118883; -.
DR   HOGENOM; HOG000249478; -.
DR   HOVERGEN; HBG004860; -.
DR   InParanoid; P12643; -.
DR   KO; K04662; -.
DR   OrthoDB; EOG7WHH9D; -.
DR   PhylomeDB; P12643; -.
DR   TreeFam; TF351789; -.
DR   Reactome; REACT_12034; Signaling by BMP.
DR   Reactome; REACT_150331; Molecules associated with elastic fibres.
DR   SignaLink; P12643; -.
DR   ChiTaRS; BMP2; human.
DR   EvolutionaryTrace; P12643; -.
DR   GeneWiki; Bone_morphogenetic_protein_2; -.
DR   GenomeRNAi; 650; -.
DR   NextBio; 2640; -.
DR   PRO; PR:P12643; -.
DR   Bgee; P12643; -.
DR   CleanEx; HS_BMP2; -.
DR   ExpressionAtlas; P12643; baseline and differential.
DR   Genevestigator; P12643; -.
DR   GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0070700; F:BMP receptor binding; IDA:MGI.
DR   GO; GO:0019211; F:phosphatase activator activity; IDA:MGI.
DR   GO; GO:0046982; F:protein heterodimerization activity; IDA:MGI.
DR   GO; GO:0005102; F:receptor binding; TAS:ProtInc.
DR   GO; GO:0004745; F:retinol dehydrogenase activity; ISS:UniProtKB.
DR   GO; GO:0046332; F:SMAD binding; IDA:BHF-UCL.
DR   GO; GO:0000187; P:activation of MAPK activity; IDA:AgBase.
DR   GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:UniProtKB.
DR   GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0003130; P:BMP signaling pathway involved in heart induction; IDA:BHF-UCL.
DR   GO; GO:0030282; P:bone mineralization; ISS:UniProtKB.
DR   GO; GO:0035630; P:bone mineralization involved in bone maturation; IDA:BHF-UCL.
DR   GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR   GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IDA:BHF-UCL.
DR   GO; GO:0055007; P:cardiac muscle cell differentiation; IMP:BHF-UCL.
DR   GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISS:UniProtKB.
DR   GO; GO:0035051; P:cardiocyte differentiation; IMP:BHF-UCL.
DR   GO; GO:0045165; P:cell fate commitment; ISS:UniProtKB.
DR   GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR   GO; GO:0071773; P:cellular response to BMP stimulus; IDA:BHF-UCL.
DR   GO; GO:0071407; P:cellular response to organic cyclic compound; IEA:Ensembl.
DR   GO; GO:0002062; P:chondrocyte differentiation; IDA:AgBase.
DR   GO; GO:0060128; P:corticotropin hormone secreting cell differentiation; ISS:UniProtKB.
DR   GO; GO:0009790; P:embryo development; ISS:UniProtKB.
DR   GO; GO:0035054; P:embryonic heart tube anterior/posterior pattern specification; ISS:UniProtKB.
DR   GO; GO:0003203; P:endocardial cushion morphogenesis; ISS:UniProtKB.
DR   GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:BHF-UCL.
DR   GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
DR   GO; GO:0040007; P:growth; IEA:InterPro.
DR   GO; GO:0007507; P:heart development; ISS:UniProtKB.
DR   GO; GO:0001701; P:in utero embryonic development; ISS:UniProtKB.
DR   GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR   GO; GO:0048839; P:inner ear development; ISS:UniProtKB.
DR   GO; GO:0048762; P:mesenchymal cell differentiation; IDA:UniProtKB.
DR   GO; GO:0072138; P:mesenchymal cell proliferation involved in ureteric bud development; ISS:UniProtKB.
DR   GO; GO:0060485; P:mesenchyme development; IMP:BHF-UCL.
DR   GO; GO:0032348; P:negative regulation of aldosterone biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0051042; P:negative regulation of calcium-independent cell-cell adhesion; IDA:AgBase.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IEP:AgBase.
DR   GO; GO:2000726; P:negative regulation of cardiac muscle cell differentiation; IDA:BHF-UCL.
DR   GO; GO:0045786; P:negative regulation of cell cycle; IDA:HGNC.
DR   GO; GO:0008285; P:negative regulation of cell proliferation; IDA:BHF-UCL.
DR   GO; GO:2000065; P:negative regulation of cortisol biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0010894; P:negative regulation of steroid biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR   GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR   GO; GO:0003308; P:negative regulation of Wnt signaling pathway involved in heart development; IDA:BHF-UCL.
DR   GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB.
DR   GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISS:UniProtKB.
DR   GO; GO:0009887; P:organ morphogenesis; ISS:UniProtKB.
DR   GO; GO:0001649; P:osteoblast differentiation; IDA:MGI.
DR   GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0060039; P:pericardium development; ISS:UniProtKB.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; IDA:MGI.
DR   GO; GO:0048711; P:positive regulation of astrocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0030501; P:positive regulation of bone mineralization; IDA:BHF-UCL.
DR   GO; GO:0061036; P:positive regulation of cartilage development; IDA:MGI.
DR   GO; GO:0030335; P:positive regulation of cell migration; ISS:UniProtKB.
DR   GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB.
DR   GO; GO:0010718; P:positive regulation of epithelial to mesenchymal transition; IDA:BHF-UCL.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:DFLAT.
DR   GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR   GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:DFLAT.
DR   GO; GO:0045666; P:positive regulation of neuron differentiation; ISS:UniProtKB.
DR   GO; GO:0042482; P:positive regulation of odontogenesis; ISS:UniProtKB.
DR   GO; GO:0045778; P:positive regulation of ossification; IDA:MGI.
DR   GO; GO:0045669; P:positive regulation of osteoblast differentiation; IDA:BHF-UCL.
DR   GO; GO:0033690; P:positive regulation of osteoblast proliferation; ISS:UniProtKB.
DR   GO; GO:1900745; P:positive regulation of p38MAPK cascade; IDA:DFLAT.
DR   GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:UniProtKB.
DR   GO; GO:0010922; P:positive regulation of phosphatase activity; IDA:MGI.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:MGI.
DR   GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR   GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; IDA:BHF-UCL.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR   GO; GO:0060804; P:positive regulation of Wnt signaling pathway by BMP signaling pathway; ISS:UniProtKB.
DR   GO; GO:0031648; P:protein destabilization; IEA:Ensembl.
DR   GO; GO:0006468; P:protein phosphorylation; IDA:DFLAT.
DR   GO; GO:0006029; P:proteoglycan metabolic process; IEA:Ensembl.
DR   GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:HGNC.
DR   GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR   GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR   GO; GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
DR   GO; GO:0021537; P:telencephalon development; IDA:MGI.
DR   GO; GO:0021978; P:telencephalon regionalization; ISS:UniProtKB.
DR   GO; GO:0060129; P:thyroid-stimulating hormone-secreting cell differentiation; ISS:UniProtKB.
DR   Gene3D;; -; 1.
DR   InterPro; IPR029034; Cystine-knot_cytokine.
DR   InterPro; IPR002405; Inhibin_asu.
DR   InterPro; IPR001839; TGF-b_C.
DR   InterPro; IPR001111; TGF-b_N.
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   1: Evidence at protein level;
KW   3D-structure; Chondrogenesis; Cleavage on pair of basic residues;
KW   Complete proteome; Cytokine; Developmental protein; Differentiation;
KW   Disulfide bond; Glycoprotein; Growth factor; Osteogenesis;
KW   Pharmaceutical; Polymorphism; Reference proteome; Secreted; Signal.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   PROPEP       24    282       Cleaved by PCSK5.
FT                                /FTId=PRO_0000033824.
FT   CHAIN       283    396       Bone morphogenetic protein 2.
FT                                /FTId=PRO_0000033825.
FT   CARBOHYD    135    135       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    163    163       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    164    164       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    200    200       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    338    338       N-linked (GlcNAc...) (high mannose).
FT                                {ECO:0000269|PubMed:9265423}.
FT   DISULFID    296    361
FT   DISULFID    325    393
FT   DISULFID    329    395
FT   DISULFID    360    360       Interchain.
FT   VARIANT      37     37       S -> A (in dbSNP:rs2273073).
FT                                /FTId=VAR_020061.
FT   VARIANT      77     77       P -> S (in dbSNP:rs36105541).
FT                                /FTId=VAR_052568.
FT   VARIANT     106    106       A -> T (in dbSNP:rs2273074).
FT                                /FTId=VAR_020062.
FT   VARIANT     161    161       L -> S (in dbSNP:rs34183594).
FT                                /FTId=VAR_052569.
FT   VARIANT     190    190       R -> S (in dbSNP:rs235768).
FT                                /FTId=VAR_024232.
FT   VARIANT     387    387       D -> G (in dbSNP:rs11545591).
FT                                /FTId=VAR_052570.
FT   STRAND      295    299       {ECO:0000244|PDB:2H62}.
FT   STRAND      302    304       {ECO:0000244|PDB:2H62}.
FT   HELIX       305    308       {ECO:0000244|PDB:2H62}.
FT   TURN        311    313       {ECO:0000244|PDB:2H62}.
FT   STRAND      314    316       {ECO:0000244|PDB:2H62}.
FT   STRAND      318    321       {ECO:0000244|PDB:2H62}.
FT   STRAND      324    326       {ECO:0000244|PDB:2H62}.
FT   STRAND      337    339       {ECO:0000244|PDB:2H62}.
FT   HELIX       341    352       {ECO:0000244|PDB:2H62}.
FT   STRAND      354    356       {ECO:0000244|PDB:1REU}.
FT   STRAND      360    374       {ECO:0000244|PDB:2H62}.
FT   STRAND      380    396       {ECO:0000244|PDB:2H62}.
SQ   SEQUENCE   396 AA;  44702 MW;  20653A3987B25E60 CRC64;
DBGET integrated database retrieval system