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 04-NOV-2026, entry version 253. 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 INTERACTION WITH TGFBR3. RX PubMed=18184661; DOI=10.1074/jbc.m704883200; RA Kirkbride K.C., Townsend T.A., Bruinsma M.W., Barnett J.V., Blobe G.C.; RT "Bone morphogenetic proteins signal through the transforming growth factor- RT beta type III receptor."; RL J. Biol. Chem. 283:7628-7637(2008). RN [10] 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 [11] 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 [12] 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 [13] RP FUNCTION, AND INTERACTION WITH MOUSE ERFE; MOUSE BMPR1A AND BMP6. RX PubMed=31800957; DOI=10.1182/blood.2019002620; RA Wang C.Y., Xu Y., Traeger L., Dogan D.Y., Xiao X., Steinbicker A.U., RA Babitt J.L.; RT "Erythroferrone lowers hepcidin by sequestering BMP2/6 heterodimer from RT binding to the BMP type I receptor ALK3."; RL Blood 135:453-456(2020). RN [14] 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 [15] 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 [16] RP X-RAY CRYSTALLOGRAPHY, 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 [17] {ECO:0007744|PDB:1REU, ECO:0007744|PDB:1REW} RP X-RAY CRYSTALLOGRAPHY, FUNCTION, INTERACTION WITH BMPR1A, AND MUTAGENESIS RP 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 [18] {ECO:0007744|PDB:2H62, ECO:0007744|PDB:2H64} RP X-RAY CRYSTALLOGRAPHY, AND INTERACTION WITH 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 [19] {ECO:0007744|PDB:6OMN} RP X-RAY CRYSTALLOGRAPHY, 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 [20] 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 [21] 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 [22] RP INVOLVEMENT IN SSFSC1, AND VARIANTS SSFSC1 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:24362451, PubMed:31019025). 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. Also acts to promote expression of HAMP, via the interaction CC with its receptor BMPR1A/ALK3 (PubMed:31800957). Can also signal CC through non-canonical pathways such as ERK/MAP kinase signaling cascade CC that regulates osteoblast differentiation (PubMed:16771708, CC PubMed:20851880). Also stimulates the differentiation of myoblasts into CC osteoblasts via the EIF2AK3-EIF2A-ATF4 pathway by stimulating EIF2A CC phosphorylation which leads to increased expression of ATF4 which plays CC a central role in osteoblast differentiation (PubMed:24362451). Acts as CC a positive regulator of odontoblast differentiation during mesenchymal CC tooth germ formation, expression is repressed during the bell stage by CC MSX1-mediated inhibition of CTNNB1 signaling (By similarity). CC {ECO:0000250|UniProtKB:P21274, 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:31800957, CC ECO:0000269|PubMed:3201241, 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. Interacts with ERFE (PubMed:31800957). Interacts with CC BMPR1A/ALK3; the interaction may induce HAMP expression CC (PubMed:31800957). Forms heterodimers with BMP6 in vitro; the CC heterodimer then binds to its receptor BMPR1A /ALK3 and may induce HAMP CC expression (PubMed:31800957). Interacts with TGFBR3 (PubMed:18184661). CC {ECO:0000250|UniProtKB:P21274, ECO:0000269|PubMed:10074410, CC ECO:0000269|PubMed:15020244, ECO:0000269|PubMed:16771708, CC ECO:0000269|PubMed:18184661, ECO:0000269|PubMed:18339631, CC ECO:0000269|PubMed:31800957, 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 1 (SSFSC1) [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"; 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; 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_001200.4. 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, A=331-364. 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 PDB; 8E3G; X-ray; 2.80 A; A/C=283-396. DR AlphaFoldDB; P12643; -. DR MDposit; P12643; -. DR SMR; P12643; -. DR BioGRID; 107118; 59. DR CORUM; P12643; -. DR DIP; DIP-5792N; -. DR FunCoup; P12643; 540. DR IntAct; P12643; 22. DR NDEx; IQUERY-CP-BMP2; 22 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000368104; -. DR BindingDB; P12643; -. DR ChEMBL; CHEMBL1926496; -. DR GlyCosmos; P12643; 7 sites, 2 glycans. DR GlyGen; P12643; 7 sites, 2 N-linked glycans (3 sites), 1 O-linked glycan (1 site). DR iPTMnet; P12643; -. DR PhosphoSitePlus; P12643; -. DR BioMuta; BMP2; -. DR DMDM; 115068; -. DR MassIVE; P12643; -. DR PaxDb; 9606-ENSP00000368104; -. DR PeptideAtlas; P12643; -. DR ProteomicsDB; 52860; -. DR Antibodypedia; 8441; 1106 antibodies from 47 providers. DR DNASU; 650; -. DR Ensembl; ENST00000378827.5; ENSP00000368104.3; ENSG00000125845.8. DR Ensembl; ENST00000936876.1; ENSP00000606935.1; ENSG00000125845.8. DR Ensembl; ENST00000953442.1; ENSP00000623501.1; ENSG00000125845.8. DR Ensembl; ENST00000953443.1; ENSP00000623502.1; ENSG00000125845.8. 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 AGR; HGNC:1069; -. DR ClinPGx; PA25379; -. 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 OpenTargets; ENSG00000125845; -. DR Orphanet; 261295; 20p12.3 microdeletion syndrome. DR Orphanet; 93396; Brachydactyly type A2. DR VEuPathDB; HostDB:ENSG00000125845; -. DR eggNOG; KOG3900; Eukaryota. DR GeneTree; ENSGT00940000155666; -. DR HOGENOM; CLU_020515_4_2_1; -. DR InParanoid; P12643; -. DR OMA; ACCVPSD; -. DR OrthoDB; 5987191at2759; -. DR PAN-GO; P12643; 5 GO annotations based on evolutionary models. DR PhylomeDB; P12643; -. 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 Agora; ENSG00000125845; -. DR BioGRID-ORCS; 650; 9 hits in 1151 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 166 other cell types or tissues. DR ExpressionAtlas; P12643; baseline and differential. 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; IDA:BHF-UCL. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProt. 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; IMP:BHF-UCL. DR GO; GO:0008083; F:growth factor activity; IDA:UniProt. DR GO; GO:0019211; F:phosphatase activator activity; IDA:MGI. DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc. DR GO; GO:0009887; P:animal organ morphogenesis; ISS:UniProtKB. DR GO; GO:0003176; P:aortic valve development; ISS:BHF-UCL. 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:0030282; P:bone mineralization; ISS:UniProtKB. 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; IMP:BHF-UCL. 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:0003133; P:endodermal-mesodermal cell signaling; IDA:BHF-UCL. DR GO; GO:0001837; P:epithelial to mesenchymal transition; IDA:MGI. DR GO; GO:0007507; P:heart development; IDA:BHF-UCL. DR GO; GO:0003129; P:heart induction; IDA:BHF-UCL. DR GO; GO:0003007; P:heart morphogenesis; IBA:GO_Central. 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:0006879; P:intracellular iron ion homeostasis; IDA:UniProt. DR GO; GO:0060426; P:lung vasculature development; IMP: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; 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-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:0045892; P:negative regulation of DNA-templated transcription; IDA:BHF-UCL. DR GO; GO:0045599; P:negative regulation of fat cell differentiation; 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: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:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; IGI:ARUK-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:0030316; P:osteoclast differentiation; IMP: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:1900159; P:positive regulation of bone mineralization involved in bone maturation; 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:0008284; P:positive regulation of cell population proliferation; IMP:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; 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: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:1901331; P:positive regulation of odontoblast 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; IEA:Ensembl. 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: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: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:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IDA:HGNC-UCL. DR GO; GO:0001666; P:response to hypoxia; ISS:UniProtKB. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. 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 CDD; cd19390; TGF_beta_BMP2; 1. DR FunFam; 2.10.90.10:FF:000103; Bone morphogenetic protein 16; 1. DR FunFam; 2.60.120.970:FF:000009; bone morphogenetic protein 2; 1. DR Gene3D; 2.60.120.970; -; 1. DR Gene3D; 2.10.90.10; Cystine-knot cytokines; 1. DR IDEAL; IID00354; -. 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-like. 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 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; Proteomics identification; Reference proteome; Secreted; KW 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 274..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 SSFSC1)" 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 SSFSC1)" 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 SSFSC1)" 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 HELIX 357..360 FT /evidence="ECO:0007829|PDB:2QJB" FT STRAND 361..374 FT /evidence="ECO:0007829|PDB:2H62" FT HELIX 376..378 FT /evidence="ECO:0007829|PDB:4UI1" FT STRAND 380..395 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 //