BMP2_HUMAN
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 03-AUG-2022, entry version 233.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
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 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., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., 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., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP FUNCTION, AND INTERACTION WITH BMPR2.
RX PubMed=7791754; DOI=10.1128/mcb.15.7.3479;
RA Liu F., Ventura F., Doody J., Massague J.;
RT "Human type II receptor for bone morphogenic proteins (BMPs): extension of
RT the two-kinase receptor model to the BMPs.";
RL Mol. Cell. Biol. 15:3479-3486(1995).
RN [5]
RP GLYCOSYLATION AT ASN-338.
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 on-
RT line capillary electrophoresis electrospray mass spectrometry.";
RL Anal. Chem. 69:2510-2516(1997).
RN [6]
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 in
RT the kidney.";
RL Biochem. Biophys. Res. Commun. 316:490-500(2004).
RN [7]
RP FUNCTION, AND INTERACTION WITH TNFAIP6.
RX PubMed=16771708; DOI=10.1042/bj20060027;
RA Tsukahara S., Ikeda R., Goto S., Yoshida K., Mitsumori R., Sakamoto Y.,
RA Tajima A., Yokoyama T., Toh S., Furukawa K., Inoue I.;
RT "Tumour necrosis factor alpha-stimulated gene-6 inhibits osteoblastic
RT differentiation of human mesenchymal stem cells induced by osteogenic
RT differentiation medium and BMP-2.";
RL Biochem. J. 398:595-603(2006).
RN [8]
RP INTERACTION WITH FBN1 AND FBN2.
RX PubMed=18339631; DOI=10.1074/jbc.m707820200;
RA Sengle G., Charbonneau N.L., Ono R.N., Sasaki T., Alvarez J., Keene D.R.,
RA Baechinger H.P., Sakai L.Y.;
RT "Targeting of bone morphogenetic protein growth factor complexes to
RT fibrillin.";
RL J. Biol. Chem. 283:13874-13888(2008).
RN [9]
RP FUNCTION.
RX PubMed=18436533; DOI=10.1074/jbc.m800850200;
RA Lavery K., Swain P., Falb D., Alaoui-Ismaili M.H.;
RT "BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to
RT induce osteoblastic differentiation of human bone marrow-derived
RT mesenchymal stem cells.";
RL J. Biol. Chem. 283:20948-20958(2008).
RN [10]
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., Stephens A.N.,
RA Nie G.;
RT "Posttranslational activation of bone morphogenetic protein 2 is mediated
RT by proprotein convertase 6 during decidualization for pregnancy
RT establishment.";
RL Endocrinology 151:3909-3917(2010).
RN [11]
RP FUNCTION.
RX PubMed=20851880; DOI=10.1074/jbc.m110.142307;
RA Jun J.H., Yoon W.J., Seo S.B., Woo K.M., Kim G.S., Ryoo H.M., Baek J.H.;
RT "BMP2-activated Erk/MAP kinase stabilizes Runx2 by increasing p300 levels
RT and histone acetyltransferase activity.";
RL J. Biol. Chem. 285:36410-36419(2010).
RN [12]
RP FUNCTION.
RX PubMed=24362451; DOI=10.1007/s00223-013-9828-1;
RA Tanaka K., Kaji H., Yamaguchi T., Kanazawa I., Canaff L., Hendy G.N.,
RA Sugimoto T.;
RT "Involvement of the osteoinductive factors, Tmem119 and BMP-2, and the ER
RT stress response PERK-eIF2alpha-ATF4 pathway in the commitment of myoblastic
RT into osteoblastic cells.";
RL Calcif. Tissue Int. 94:454-464(2014).
RN [13]
RP INTERACTION WITH SCUBE3.
RX PubMed=33308444; DOI=10.1016/j.ajhg.2020.11.015;
RG Genomics England Research Consortium;
RA Lin Y.C., Niceta M., Muto V., Vona B., Pagnamenta A.T., Maroofian R.,
RA Beetz C., van Duyvenvoorde H., Dentici M.L., Lauffer P., Vallian S.,
RA Ciolfi A., Pizzi S., Bauer P., Gruening N.M., Bellacchio E.,
RA Del Fattore A., Petrini S., Shaheen R., Tiosano D., Halloun R.,
RA Pode-Shakked B., Albayrak H.M., Isik E., Wit J.M., Dittrich M.,
RA Freire B.L., Bertola D.R., Jorge A.A.L., Barel O., Sabir A.H.,
RA Al Tenaiji A.M.J., Taji S.M., Al-Sannaa N., Al-Abdulwahed H., Digilio M.C.,
RA Irving M., Anikster Y., Bhavani G.S.L., Girisha K.M., Haaf T., Taylor J.C.,
RA Dallapiccola B., Alkuraya F.S., Yang R.B., Tartaglia M.;
RT "SCUBE3 loss-of-function causes a recognizable recessive developmental
RT disorder due to defective bone morphogenetic protein signaling.";
RL Am. J. Hum. Genet. 108:115-133(2021).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 292-396, AND SUBUNIT.
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).
RN [15] {ECO:0007744|PDB:1REU, ECO:0007744|PDB:1REW}
RP X-RAY CRYSTALLOGRAPHY (1.86 ANGSTROMS) OF 283-396, FUNCTION, INTERACTION
RP WITH BMPR1A, AND MUTAGENESIS OF LEU-333.
RX PubMed=15064755; DOI=10.1038/nsmb756;
RA Keller S., Nickel J., Zhang J.L., Sebald W., Mueller T.D.;
RT "Molecular recognition of BMP-2 and BMP receptor IA.";
RL Nat. Struct. Mol. Biol. 11:481-488(2004).
RN [16] {ECO:0007744|PDB:2H62, ECO:0007744|PDB:2H64}
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 283-396, AND INTERACTION WITH
RP BMPR1A AND ACVR2B.
RX PubMed=17295905; DOI=10.1186/1472-6807-7-6;
RA Weber D., Kotzsch A., Nickel J., Harth S., Seher A., Mueller U., Sebald W.,
RA Mueller T.D.;
RT "A silent H-bond can be mutationally activated for high-affinity
RT interaction of BMP-2 and activin type IIB receptor.";
RL BMC Struct. Biol. 7:6-6(2007).
RN [17] {ECO:0007744|PDB:6OMN}
RP X-RAY CRYSTALLOGRAPHY (2.68 ANGSTROMS) OF 289-396, AND FUNCTION.
RX PubMed=31019025; DOI=10.1126/scitranslmed.aar4953;
RA Seeherman H.J., Berasi S.P., Brown C.T., Martinez R.X., Juo Z.S.,
RA Jelinsky S., Cain M.J., Grode J., Tumelty K.E., Bohner M., Grinberg O.,
RA Orr N., Shoseyov O., Eyckmans J., Chen C., Morales P.R., Wilson C.G.,
RA Vanderploeg E.J., Wozney J.M.;
RT "A BMP/activin A chimera is superior to native BMPs and induces bone repair
RT in nonhuman primates when delivered in a composite matrix.";
RL Sci. Transl. Med. 11:0-0(2019).
RN [18]
RP INVOLVEMENT IN BDA2.
RX PubMed=19327734; DOI=10.1016/j.ajhg.2009.03.001;
RA Dathe K., Kjaer K.W., Brehm A., Meinecke P., Nuernberg P., Neto J.C.,
RA Brunoni D., Tommerup N., Ott C.E., Klopocki E., Seemann P., Mundlos S.;
RT "Duplications involving a conserved regulatory element downstream of BMP2
RT are associated with brachydactyly type A2.";
RL Am. J. Hum. Genet. 84:483-492(2009).
RN [19]
RP INVOLVEMENT IN BDA2.
RX PubMed=21357617; DOI=10.1136/jmg.2010.084814;
RA Su P., Ding H., Huang D., Zhou Y., Huang W., Zhong L., Vyse T.J., Wang Y.;
RT "A 4.6 kb genomic duplication on 20p12.2-12.3 is associated with
RT brachydactyly type A2 in a Chinese family.";
RL J. Med. Genet. 48:312-316(2011).
RN [20]
RP INVOLVEMENT IN SSFSC, AND VARIANTS SSFSC 27-GLU--ARG-396 DEL;
RP 154-ARG--ARG-396 DEL AND 329-CYS--ARG-396 DEL.
RX PubMed=29198724; DOI=10.1016/j.ajhg.2017.10.006;
RA Tan T.Y., Gonzaga-Jauregui C., Bhoj E.J., Strauss K.A., Brigatti K.,
RA Puffenberger E., Li D., Xie L., Das N., Skubas I., Deckelbaum R.A.,
RA Hughes V., Brydges S., Hatsell S., Siao C.J., Dominguez M.G.,
RA Economides A., Overton J.D., Mayne V., Simm P.J., Jones B.O., Eggers S.,
RA Le Guyader G., Pelluard F., Haack T.B., Sturm M., Riess A., Waldmueller S.,
RA Hofbeck M., Steindl K., Joset P., Rauch A., Hakonarson H., Baker N.L.,
RA Farlie P.G.;
RT "Monoallelic BMP2 variants predicted to result in haploinsufficiency cause
RT craniofacial, skeletal, and cardiac features overlapping those of 20p12
RT deletions.";
RL Am. J. Hum. Genet. 101:985-994(2017).
CC -!- FUNCTION: Growth factor of the TGF-beta superfamily that plays
CC essential roles in many developmental processes, including
CC cardiogenesis, neurogenesis, and osteogenesis (PubMed:18436533,
CC PubMed:31019025, PubMed:24362451). Induces cartilage and bone formation
CC (PubMed:3201241). Initiates the canonical BMP signaling cascade by
CC associating with type I receptor BMPR1A and type II receptor BMPR2
CC (PubMed:15064755, PubMed:17295905, PubMed:18436533). Once all three
CC components are bound together in a complex at the cell surface, BMPR2
CC phosphorylates and activates BMPR1A (PubMed:7791754). 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 (PubMed:20851880, PubMed:16771708). Stimulates also the differentiation
CC of myoblasts into osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by
CC stimulating EIF2A phosphorylation which leads to increased expression
CC of ATF4 which plays a central role in osteoblast differentiation
CC (PubMed:24362451). {ECO:0000269|PubMed:15064755,
CC ECO:0000269|PubMed:17295905, ECO:0000269|PubMed:18436533,
CC ECO:0000269|PubMed:20851880, ECO:0000269|PubMed:24362451,
CC ECO:0000269|PubMed:31019025, ECO:0000269|PubMed:3201241,
CC ECO:0000269|PubMed:7791754}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (PubMed:10074410). Interacts with
CC SOSTDC1 (PubMed:15020244). Interacts with GREM2, RGMA, RGMB and RGMC.
CC Interacts with ASPN (By similarity). Interacts with MAFP5 (By
CC similarity). Interacts with FBN1 (via N-terminal domain) and FBN2
CC (PubMed:18339631). Interacts with type I receptor BMPR1A
CC (PubMed:15064755). Interacts with type II receptor BMPR2
CC (PubMed:7791754). Interacts with SCUBE3 (PubMed:33308444). Interacts
CC with TNFAIP6 (primarily via Link domain); this interaction is inhibited
CC by hyaluronan. {ECO:0000250|UniProtKB:P21274,
CC ECO:0000269|PubMed:10074410, ECO:0000269|PubMed:15020244,
CC ECO:0000269|PubMed:16771708, ECO:0000269|PubMed:18339631,
CC ECO:0000269|PubMed:33308444}.
CC -!- INTERACTION:
CC P12643; P36894: BMPR1A; NbExp=17; IntAct=EBI-1029262, EBI-1029237;
CC P12643; O00238: BMPR1B; NbExp=3; IntAct=EBI-1029262, EBI-7527193;
CC P12643; Q12841: FSTL1; NbExp=2; IntAct=EBI-1029262, EBI-2349801;
CC P12643; Q6ZVN8: HJV; NbExp=2; IntAct=EBI-1029262, EBI-10900704;
CC P12643; Q6ZVN8-1: HJV; NbExp=2; IntAct=EBI-1029262, EBI-16155543;
CC P12643; Q13253: NOG; NbExp=2; IntAct=EBI-1029262, EBI-1035205;
CC P12643; Q96B86-1: RGMA; NbExp=2; IntAct=EBI-1029262, EBI-16155394;
CC P12643; Q6NW40: RGMB; NbExp=7; IntAct=EBI-1029262, EBI-16155464;
CC P12643; P27038: Acvr2a; Xeno; NbExp=2; IntAct=EBI-1029262, EBI-1036102;
CC PRO_0000033825; P98066: TNFAIP6; NbExp=3; IntAct=EBI-9697918, EBI-11700693;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Particularly abundant in lung, spleen and colon and
CC in low but significant levels in heart, brain, placenta, liver,
CC skeletal muscle, kidney, pancreas, prostate, ovary and small intestine.
CC -!- DISEASE: Brachydactyly A2 (BDA2) [MIM:112600]: A form of brachydactyly.
CC Brachydactyly defines a group of inherited malformations characterized
CC by shortening of the digits due to abnormal development of the
CC phalanges and/or the metacarpals. In brachydactyly type A2 shortening
CC of the middle phalanges is confined to the index finger and the second
CC toe, all other digits being more or less normal. Because of a rhomboid
CC or triangular shape of the affected middle phalanx, the end of the
CC second finger usually deviates radially. {ECO:0000269|PubMed:19327734,
CC ECO:0000269|PubMed:21357617}. Note=The gene represented in this entry
CC is involved in disease pathogenesis. Duplications of a cis-regulatory
CC element located approximately 110 kb downstream of BMP2 have been found
CC in BDA2 families. They likely cause altered BMP2 expression with
CC pathological consequences. {ECO:0000269|PubMed:19327734,
CC ECO:0000269|PubMed:21357617}.
CC -!- DISEASE: Short stature, facial dysmorphism, and skeletal anomalies with
CC or without cardiac anomalies (SSFSC) [MIM:617877]: An autosomal
CC dominant disorder characterized by short stature, facial dysmorphism,
CC skeletal anomalies, and variable cardiac defects. Distinctive facial
CC features include midface retrusion, short upturned nose, long philtrum,
CC high-arched or cleft palate, and variable degrees of micrognathia and
CC dental crowding. Skeletal anomalies include patterning defects of the
CC axial skeleton, characterized by 11 pairs of ribs and brachydactyly of
CC the fifth ray. Congenital heart defects are variably observed and
CC appear to involve primarily the cardiac outflow tract.
CC {ECO:0000269|PubMed:29198724}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
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 entry;
CC URL="https://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; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS13099.1; -.
DR PIR; B37278; BMHU2.
DR RefSeq; NP_001191.1; NM_001200.3.
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=283-314.
DR PDB; 4N1D; X-ray; 1.91 A; A=283-305, A=362-396.
DR PDB; 4UHY; X-ray; 3.20 A; A/B=283-396.
DR PDB; 4UHZ; X-ray; 2.85 A; A=283-396.
DR PDB; 4UI0; X-ray; 2.80 A; A/B=283-396.
DR PDB; 4UI1; X-ray; 2.35 A; A/B=283-396.
DR PDB; 4UI2; X-ray; 3.15 A; B=283-396.
DR PDB; 6OMN; X-ray; 2.68 A; E/F/G/H=289-396.
DR PDB; 7AG0; X-ray; 3.10 A; B=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 PDBsum; 4MID; -.
DR PDBsum; 4N1D; -.
DR PDBsum; 4UHY; -.
DR PDBsum; 4UHZ; -.
DR PDBsum; 4UI0; -.
DR PDBsum; 4UI1; -.
DR PDBsum; 4UI2; -.
DR PDBsum; 6OMN; -.
DR PDBsum; 7AG0; -.
DR AlphaFoldDB; P12643; -.
DR SMR; P12643; -.
DR BioGRID; 107118; 58.
DR CORUM; P12643; -.
DR DIP; DIP-5792N; -.
DR IntAct; P12643; 18.
DR MINT; P12643; -.
DR STRING; 9606.ENSP00000368104; -.
DR BindingDB; P12643; -.
DR ChEMBL; CHEMBL1926496; -.
DR GlyGen; P12643; 5 sites.
DR iPTMnet; P12643; -.
DR PhosphoSitePlus; P12643; -.
DR BioMuta; BMP2; -.
DR DMDM; 115068; -.
DR EPD; P12643; -.
DR MassIVE; P12643; -.
DR PaxDb; P12643; -.
DR PeptideAtlas; P12643; -.
DR PRIDE; P12643; -.
DR ProteomicsDB; 52860; -.
DR Antibodypedia; 8441; 995 antibodies from 42 providers.
DR DNASU; 650; -.
DR Ensembl; ENST00000378827.5; ENSP00000368104.3; ENSG00000125845.7.
DR GeneID; 650; -.
DR KEGG; hsa:650; -.
DR MANE-Select; ENST00000378827.5; ENSP00000368104.3; NM_001200.4; NP_001191.1.
DR UCSC; uc002wmu.2; human.
DR CTD; 650; -.
DR DisGeNET; 650; -.
DR GeneCards; BMP2; -.
DR HGNC; HGNC:1069; BMP2.
DR HPA; ENSG00000125845; Low tissue specificity.
DR MalaCards; BMP2; -.
DR MIM; 112261; gene.
DR MIM; 112600; phenotype.
DR MIM; 617877; phenotype.
DR neXtProt; NX_P12643; -.
DR OpenTargets; ENSG00000125845; -.
DR Orphanet; 261295; 20p12.3 microdeletion syndrome.
DR Orphanet; 93396; Brachydactyly type A2.
DR PharmGKB; PA25379; -.
DR VEuPathDB; HostDB:ENSG00000125845; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000155666; -.
DR HOGENOM; CLU_020515_4_2_1; -.
DR InParanoid; P12643; -.
DR OMA; KFPMTRL; -.
DR OrthoDB; 962484at2759; -.
DR PhylomeDB; P12643; -.
DR TreeFam; TF351789; -.
DR PathwayCommons; P12643; -.
DR Reactome; R-HSA-201451; Signaling by BMP.
DR Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR Reactome; R-HSA-8878166; Transcriptional regulation by RUNX2.
DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity.
DR SignaLink; P12643; -.
DR SIGNOR; P12643; -.
DR BioGRID-ORCS; 650; 8 hits in 1073 CRISPR screens.
DR ChiTaRS; BMP2; human.
DR EvolutionaryTrace; P12643; -.
DR GeneWiki; Bone_morphogenetic_protein_2; -.
DR GenomeRNAi; 650; -.
DR Pharos; P12643; Tbio.
DR PRO; PR:P12643; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P12643; protein.
DR Bgee; ENSG00000125845; Expressed in cartilage tissue and 164 other tissues.
DR ExpressionAtlas; P12643; baseline and differential.
DR Genevisible; P12643; HS.
DR GO; GO:0070724; C:BMP receptor complex; IDA:BHF-UCL.
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; IDA:BHF-UCL.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0070700; F:BMP receptor binding; IDA:MGI.
DR GO; GO:0039706; F:co-receptor binding; IPI:BHF-UCL.
DR GO; GO:0005125; F:cytokine activity; ISS:BHF-UCL.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0019211; F:phosphatase activator activity; IDA:MGI.
DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; IEA:Ensembl.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0046332; F:SMAD binding; IDA:BHF-UCL.
DR GO; GO:0036305; P:ameloblast differentiation; IEA:Ensembl.
DR GO; GO:0009887; P:animal organ morphogenesis; ISS:UniProtKB.
DR GO; GO:0003176; P:aortic valve development; ISS:BHF-UCL.
DR GO; GO:0048708; P:astrocyte differentiation; IEA:Ensembl.
DR GO; GO:1905222; P:atrioventricular canal morphogenesis; ISS:BHF-UCL.
DR GO; GO:0003181; P:atrioventricular valve morphogenesis; ISS:UniProtKB.
DR GO; GO:0030509; P:BMP signaling pathway; IDA:UniProtKB.
DR GO; GO:0061312; P:BMP signaling pathway involved in heart development; ISS: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:0003210; P:cardiac atrium formation; ISS:BHF-UCL.
DR GO; GO:0060317; P:cardiac epithelial to mesenchymal transition; IDA:BHF-UCL.
DR GO; GO:1905072; P:cardiac jelly development; ISS: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; IDA:MGI.
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:0035054; P:embryonic heart tube anterior/posterior pattern specification; ISS:UniProtKB.
DR GO; GO:0003272; P:endocardial cushion formation; ISS:BHF-UCL.
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: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-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:BHF-UCL.
DR GO; GO:2000065; P:negative regulation of cortisol biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:BHF-UCL.
DR GO; GO:0043569; P:negative regulation of insulin-like growth factor receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IDA:BHF-UCL.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; 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 by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IGI:ARUK-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: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:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0030858; P:positive regulation of epithelial cell differentiation; IEA:Ensembl.
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:0003331; P:positive regulation of extracellular matrix constituent secretion; ISS:BHF-UCL.
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:1902895; P:positive regulation of miRNA transcription; IEA:Ensembl.
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:0035360; P:positive regulation of peroxisome proliferator activated receptor signaling pathway; IGI:ARUK-UCL.
DR GO; GO:0010922; P:positive regulation of phosphatase activity; IDA:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; 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-UCL.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
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 GO; GO:0006366; P:transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:Ensembl.
DR Gene3D; 2.10.90.10; -; 1.
DR IDEAL; IID00354; -.
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 1: Evidence at protein level;
KW 3D-structure; Chondrogenesis; Cleavage on pair of basic residues; Cytokine;
KW Developmental protein; Differentiation; Disease variant; Disulfide bond;
KW Dwarfism; Glycoprotein; Growth factor; Osteogenesis; Pharmaceutical;
KW Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT PROPEP 24..282
FT /note="Cleaved by PCSK5"
FT /id="PRO_0000033824"
FT CHAIN 283..396
FT /note="Bone morphogenetic protein 2"
FT /id="PRO_0000033825"
FT REGION 84..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 271..293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..121
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..293
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 87
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12644"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000269|PubMed:9265423"
FT DISULFID 296..361
FT DISULFID 325..393
FT DISULFID 329..395
FT DISULFID 360
FT /note="Interchain"
FT VARIANT 27..396
FT /note="Missing (in SSFSC)"
FT /evidence="ECO:0000269|PubMed:29198724"
FT /id="VAR_080742"
FT VARIANT 37
FT /note="S -> A (in dbSNP:rs2273073)"
FT /id="VAR_020061"
FT VARIANT 77
FT /note="P -> S (in dbSNP:rs36105541)"
FT /id="VAR_052568"
FT VARIANT 106
FT /note="A -> T (in dbSNP:rs2273074)"
FT /id="VAR_020062"
FT VARIANT 154..396
FT /note="Missing (in SSFSC)"
FT /evidence="ECO:0000269|PubMed:29198724"
FT /id="VAR_080743"
FT VARIANT 161
FT /note="L -> S (in dbSNP:rs34183594)"
FT /id="VAR_052569"
FT VARIANT 190
FT /note="R -> S (in dbSNP:rs235768)"
FT /id="VAR_024232"
FT VARIANT 329..396
FT /note="Missing (in SSFSC)"
FT /evidence="ECO:0000269|PubMed:29198724"
FT /id="VAR_080744"
FT VARIANT 387
FT /note="D -> G (in dbSNP:rs11545591)"
FT /id="VAR_052570"
FT MUTAGEN 333
FT /note="L->P: Complete loss of type I receptor binding."
FT /evidence="ECO:0000269|PubMed:15064755"
FT STRAND 295..299
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 302..304
FT /evidence="ECO:0007829|PDB:2H62"
FT HELIX 305..308
FT /evidence="ECO:0007829|PDB:2H62"
FT TURN 311..313
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 314..316
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 318..321
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 324..326
FT /evidence="ECO:0007829|PDB:2H62"
FT HELIX 333..336
FT /evidence="ECO:0007829|PDB:4UI2"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:2H62"
FT HELIX 341..352
FT /evidence="ECO:0007829|PDB:2H62"
FT STRAND 354..356
FT /evidence="ECO:0007829|PDB:1REU"
FT STRAND 360..374
FT /evidence="ECO:0007829|PDB:2H62"
FT HELIX 376..378
FT /evidence="ECO:0007829|PDB:4UI1"
FT STRAND 380..396
FT /evidence="ECO:0007829|PDB:2H62"
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
