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 01-MAY-2013, entry version 157.
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]
RP NUCLEOTIDE SEQUENCE [MRNA].
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]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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]
RP INTERACTION WITH SOSTDC1.
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 [5]
RP PROTEOLYTIC PROCESSING, AND PROPEPTIDE.
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 [6]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 292-396.
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).
CC -!- INTERACTION:
CC P36894:BMPR1A; NbExp=2; IntAct=EBI-1029262, EBI-1029237;
CC -!- SUBCELLULAR LOCATION: Secreted.
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.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Bone morphogenetic protein 2
CC entry;
CC URL="http://en.wikipedia.org/wiki/Bone_morphogenetic_protein_2";
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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 IPI; IPI00025069; -.
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 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 ProteinModelPortal; P12643; -.
DR DIP; DIP-5792N; -.
DR IntAct; P12643; 1.
DR MINT; MINT-6772716; -.
DR STRING; 9606.ENSP00000368104; -.
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 Orphanet; 907; Wolff-Parkinson-White syndrome.
DR PharmGKB; PA25379; -.
DR eggNOG; NOG243555; -.
DR HOGENOM; HOG000249478; -.
DR HOVERGEN; HBG004860; -.
DR InParanoid; P12643; -.
DR KO; K04662; -.
DR OMA; DEHSWSQ; -.
DR OrthoDB; EOG4C2H9R; -.
DR PhylomeDB; P12643; -.
DR Pathway_Interaction_DB; bmppathway; BMP receptor signaling.
DR Reactome; REACT_111102; Signal Transduction.
DR Reactome; REACT_118779; Extracellular matrix organization.
DR ChEMBL; CHEMBL1926496; -.
DR DrugBank; DB00641; Simvastatin.
DR EvolutionaryTrace; P12643; -.
DR GenomeRNAi; 650; -.
DR NextBio; 2640; -.
DR ArrayExpress; P12643; -.
DR Bgee; P12643; -.
DR CleanEx; HS_BMP2; -.
DR Genevestigator; P12643; -.
DR GermOnline; ENSG00000125845; Homo sapiens.
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:0004745; F:retinol dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IDA:BHF-UCL.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:UniProtKB.
DR GO; GO:0003130; P:BMP signaling pathway involved in heart induction; IDA:BHF-UCL.
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:0051216; P:cartilage development; IEA:UniProtKB-KW.
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:Compara.
DR GO; GO:0060128; P:corticotropin hormone secreting cell differentiation; 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:0040007; P:growth; IEA:InterPro.
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:0072138; P:mesenchymal cell proliferation involved in ureteric bud development; ISS:UniProtKB.
DR GO; GO:0032348; P:negative regulation of aldosterone biosynthetic process; IDA:BHF-UCL.
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:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
DR GO; GO:0003308; P:negative regulation of Wnt receptor 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: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; IMP:BHF-UCL.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
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: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: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:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; IDA:BHF-UCL.
DR GO; GO:0060804; P:positive regulation of Wnt receptor signaling pathway by BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0031648; P:protein destabilization; IEA:Compara.
DR GO; GO:0006029; P:proteoglycan metabolic process; IEA:Compara.
DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Compara.
DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB.
DR GO; GO:0060395; P:SMAD protein signal transduction; IDA:UniProtKB.
DR GO; GO:0021978; P:telencephalon regionalization; ISS:UniProtKB.
DR GO; GO:0060129; P:thyroid-stimulating hormone-secreting cell differentiation; ISS:UniProtKB.
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 PRINTS; PR00669; INHIBINA.
DR SMART; SM00204; TGFB; 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 Potential.
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...) (Potential).
FT CARBOHYD 163 163 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 164 164 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 200 200 N-linked (GlcNAc...) (Potential).
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
FT STRAND 302 304
FT HELIX 305 308
FT TURN 311 313
FT STRAND 314 316
FT STRAND 318 321
FT STRAND 324 326
FT STRAND 337 339
FT HELIX 341 352
FT STRAND 354 356
FT STRAND 360 374
FT STRAND 380 396
SQ SEQUENCE 396 AA; 44702 MW; 20653A3987B25E60 CRC64;
MVAGTRCLLA LLLPQVLLGG AAGLVPELGR RKFAAASSGR PSSQPSDEVL SEFELRLLSM
FGLKQRPTPS RDAVVPPYML DLYRRHSGQP GSPAPDHRLE RAASRANTVR SFHHEESLEE
LPETSGKTTR RFFFNLSSIP TEEFITSAEL QVFREQMQDA LGNNSSFHHR INIYEIIKPA
TANSKFPVTR LLDTRLVNQN ASRWESFDVT PAVMRWTAQG HANHGFVVEV AHLEEKQGVS
KRHVRISRSL HQDEHSWSQI RPLLVTFGHD GKGHPLHKRE KRQAKHKQRK RLKSSCKRHP
LYVDFSDVGW NDWIVAPPGY HAFYCHGECP FPLADHLNST NHAIVQTLVN SVNSKIPKAC
CVPTELSAIS MLYLDENEKV VLKNYQDMVV EGCGCR
//
