BMP3_HUMAN
ID BMP3_HUMAN Reviewed; 472 AA.
AC P12645; Q4VAS5;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Bone morphogenetic protein 3;
DE Short=BMP-3;
DE AltName: Full=Bone morphogenetic protein 3A;
DE Short=BMP-3A;
DE AltName: Full=Osteogenin;
DE Flags: Precursor;
GN Name=BMP3; Synonyms=BMP3A;
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 VARIANT PHE-205.
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 [LARGE SCALE GENOMIC DNA], AND VARIANT PHE-205.
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-205.
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION.
RX PubMed=11138004; DOI=10.1038/83810;
RA Daluiski A., Engstrand T., Bahamonde M.E., Gamer L.W., Agius E.,
RA Stevenson S.L., Cox K., Rosen V., Lyons K.M.;
RT "Bone morphogenetic protein-3 is a negative regulator of bone density.";
RL Nat. Genet. 27:84-88(2001).
RN [5]
RP INDUCTION.
RX PubMed=13678778; DOI=10.1016/s8756-3282(03)00191-1;
RA Kloen P., Di Paola M., Borens O., Richmond J., Perino G., Helfet D.L.,
RA Goumans M.J.;
RT "BMP signaling components are expressed in human fracture callus.";
RL Bone 33:362-371(2003).
RN [6]
RP FUNCTION.
RX PubMed=15269709; DOI=10.1038/sj.gt.3302298;
RA Kang Q., Sun M.H., Cheng H., Peng Y., Montag A.G., Deyrup A.T., Jiang W.,
RA Luu H.H., Luo J., Szatkowski J.P., Vanichakarn P., Park J.Y., Li Y.,
RA Haydon R.C., He T.-C.;
RT "Characterization of the distinct orthotopic bone-forming activity of 14
RT BMPs using recombinant adenovirus-mediated gene delivery.";
RL Gene Ther. 11:1312-1320(2004).
RN [7]
RP TISSUE SPECIFICITY.
RX PubMed=15475196; DOI=10.1016/j.orthres.2004.02.013;
RA Chen A.L., Fang C., Liu C., Leslie M.P., Chang E., Di Cesare P.E.;
RT "Expression of bone morphogenetic proteins, receptors, and tissue
RT inhibitors in human fetal, adult, and osteoarthritic articular cartilage.";
RL J. Orthop. Res. 22:1188-1192(2004).
RN [8]
RP FUNCTION, AND INTERACTION WITH ACVR2B.
RX PubMed=31665064; DOI=10.1186/s13046-019-1435-1;
RA Wen J., Liu X., Qi Y., Niu F., Niu Z., Geng W., Zou Z., Huang R., Wang J.,
RA Zou H.;
RT "BMP3 suppresses colon tumorigenesis via ActRIIB/SMAD2-dependent and
RT TAK1/JNK signaling pathways.";
RL J. Exp. Clin. Cancer Res. 38:428-428(2019).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 363-472, AND DISULFIDE BONDS.
RX PubMed=17924656; DOI=10.1021/bi700907k;
RA Allendorph G.P., Isaacs M.J., Kawakami Y., Izpisua Belmonte J.C., Choe S.;
RT "BMP-3 and BMP-6 structures illuminate the nature of binding specificity
RT with receptors.";
RL Biochemistry 46:12238-12247(2007).
CC -!- FUNCTION: Growth factor of the TGF-beta superfamily that plays an
CC essential role in developmental process by inducing and patterning
CC early skeletal formation and by negatively regulating bone density.
CC Antagonizes the ability of certain osteogenic BMPs to induce
CC osteoprogenitor differentitation and ossification (PubMed:11138004,
CC PubMed:15269709). Initiates signaling cascades by associating with type
CC II receptor ACVR2B to activate SMAD2-dependent and SMAD-independent
CC signaling cascades including TAK1 and JNK pathways (PubMed:31665064).
CC {ECO:0000269|PubMed:11138004, ECO:0000269|PubMed:15269709,
CC ECO:0000269|PubMed:31665064}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Interacts with type II receptor
CC ACVR2B. {ECO:0000269|PubMed:31665064}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed in adult and fetal cartilage.
CC {ECO:0000269|PubMed:15475196}.
CC -!- INDUCTION: Highly expressed in fracture tissue, particularly in
CC osteoblasts, osteoclasts and chondroblasts.
CC {ECO:0000269|PubMed:13678778}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Bone morphogenetic protein 3 entry;
CC URL="https://en.wikipedia.org/wiki/Bone_morphogenetic_protein_3";
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; M22491; AAA51836.1; -; mRNA.
DR EMBL; AC093883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC096269; AAH96269.1; -; mRNA.
DR EMBL; BC096270; AAH96270.1; -; mRNA.
DR EMBL; BC096271; AAH96271.1; -; mRNA.
DR EMBL; BC117514; AAI17515.1; -; mRNA.
DR CCDS; CCDS3588.1; -.
DR PIR; D37278; BMHU3.
DR RefSeq; NP_001192.3; NM_001201.3.
DR PDB; 2QCQ; X-ray; 2.21 A; A/B=363-472.
DR PDBsum; 2QCQ; -.
DR AlphaFoldDB; P12645; -.
DR SMR; P12645; -.
DR BioGRID; 107119; 3.
DR IntAct; P12645; 4.
DR MINT; P12645; -.
DR STRING; 9606.ENSP00000282701; -.
DR GlyGen; P12645; 5 sites.
DR iPTMnet; P12645; -.
DR PhosphoSitePlus; P12645; -.
DR BioMuta; BMP3; -.
DR DMDM; 215273985; -.
DR MassIVE; P12645; -.
DR PaxDb; P12645; -.
DR PeptideAtlas; P12645; -.
DR PRIDE; P12645; -.
DR ProteomicsDB; 52862; -.
DR Antibodypedia; 25010; 501 antibodies from 35 providers.
DR DNASU; 651; -.
DR Ensembl; ENST00000282701.4; ENSP00000282701.2; ENSG00000152785.8.
DR GeneID; 651; -.
DR KEGG; hsa:651; -.
DR MANE-Select; ENST00000282701.4; ENSP00000282701.2; NM_001201.5; NP_001192.4.
DR UCSC; uc003hmg.4; human.
DR CTD; 651; -.
DR DisGeNET; 651; -.
DR GeneCards; BMP3; -.
DR HGNC; HGNC:1070; BMP3.
DR HPA; ENSG00000152785; Tissue enhanced (intestine, lung, urinary bladder).
DR MIM; 112263; gene.
DR neXtProt; NX_P12645; -.
DR OpenTargets; ENSG00000152785; -.
DR PharmGKB; PA25380; -.
DR VEuPathDB; HostDB:ENSG00000152785; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000159775; -.
DR HOGENOM; CLU_020515_10_0_1; -.
DR InParanoid; P12645; -.
DR OMA; KWDSHIR; -.
DR OrthoDB; 1002140at2759; -.
DR PhylomeDB; P12645; -.
DR TreeFam; TF316134; -.
DR PathwayCommons; P12645; -.
DR SignaLink; P12645; -.
DR BioGRID-ORCS; 651; 11 hits in 1066 CRISPR screens.
DR EvolutionaryTrace; P12645; -.
DR GeneWiki; Bone_morphogenetic_protein_3; -.
DR GenomeRNAi; 651; -.
DR Pharos; P12645; Tbio.
DR PRO; PR:P12645; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; P12645; protein.
DR Bgee; ENSG00000152785; Expressed in muscle layer of sigmoid colon and 80 other tissues.
DR Genevisible; P12645; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0070700; F:BMP receptor binding; IDA:MGI.
DR GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0051216; P:cartilage development; IEA:UniProtKB-KW.
DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:InterPro.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IBA:GO_Central.
DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR017197; BMP3/BMP3B.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR001839; TGF-b_C.
DR InterPro; IPR015615; TGF-beta-rel.
DR InterPro; IPR017948; TGFb_CS.
DR PANTHER; PTHR11848; PTHR11848; 1.
DR Pfam; PF00019; TGF_beta; 1.
DR PIRSF; PIRSF037403; BMP3/GDF10; 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; Disulfide bond; Glycoprotein;
KW Growth factor; Osteogenesis; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT PROPEP 23..362
FT /evidence="ECO:0000250"
FT /id="PRO_0000033836"
FT CHAIN 363..472
FT /note="Bone morphogenetic protein 3"
FT /id="PRO_0000033837"
FT REGION 27..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 320..350
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 117
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 141
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 175
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 220
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 463
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 370..437
FT /evidence="ECO:0000269|PubMed:17924656"
FT DISULFID 399..469
FT /evidence="ECO:0000269|PubMed:17924656"
FT DISULFID 403..471
FT /evidence="ECO:0000269|PubMed:17924656"
FT DISULFID 436
FT /note="Interchain"
FT /evidence="ECO:0000269|PubMed:17924656"
FT VARIANT 176
FT /note="Q -> K (in dbSNP:rs34213771)"
FT /id="VAR_047418"
FT VARIANT 176
FT /note="Q -> L (in dbSNP:rs34847147)"
FT /id="VAR_047419"
FT VARIANT 192
FT /note="R -> Q (in dbSNP:rs3733549)"
FT /id="VAR_020063"
FT VARIANT 205
FT /note="L -> F (in dbSNP:rs6831040)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15815621, ECO:0000269|PubMed:3201241"
FT /id="VAR_047420"
FT VARIANT 222
FT /note="T -> M (in dbSNP:rs34505126)"
FT /id="VAR_047421"
FT STRAND 368..373
FT /evidence="ECO:0007829|PDB:2QCQ"
FT STRAND 376..378
FT /evidence="ECO:0007829|PDB:2QCQ"
FT TURN 379..383
FT /evidence="ECO:0007829|PDB:2QCQ"
FT TURN 385..387
FT /evidence="ECO:0007829|PDB:2QCQ"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:2QCQ"
FT STRAND 392..395
FT /evidence="ECO:0007829|PDB:2QCQ"
FT STRAND 398..400
FT /evidence="ECO:0007829|PDB:2QCQ"
FT HELIX 409..411
FT /evidence="ECO:0007829|PDB:2QCQ"
FT HELIX 415..425
FT /evidence="ECO:0007829|PDB:2QCQ"
FT STRAND 437..439
FT /evidence="ECO:0007829|PDB:2QCQ"
FT STRAND 441..450
FT /evidence="ECO:0007829|PDB:2QCQ"
FT STRAND 456..466
FT /evidence="ECO:0007829|PDB:2QCQ"
FT STRAND 469..471
FT /evidence="ECO:0007829|PDB:2QCQ"
SQ SEQUENCE 472 AA; 53372 MW; 2809B7EF5E37596A CRC64;
MAGASRLLFL WLGCFCVSLA QGERPKPPFP ELRKAVPGDR TAGGGPDSEL QPQDKVSEHM
LRLYDRYSTV QAARTPGSLE GGSQPWRPRL LREGNTVRSF RAAAAETLER KGLYIFNLTS
LTKSENILSA TLYFCIGELG NISLSCPVSG GCSHHAQRKH IQIDLSAWTL KFSRNQSQLL
GHLSVDMAKS HRDIMSWLSK DITQLLRKAK ENEEFLIGFN ITSKGRQLPK RRLPFPEPYI
LVYANDAAIS EPESVVSSLQ GHRNFPTGTV PKWDSHIRAA LSIERRKKRS TGVLLPLQNN
ELPGAEYQYK KDEVWEERKP YKTLQAQAPE KSKNKKKQRK GPHRKSQTLQ FDEQTLKKAR
RKQWIEPRNC ARRYLKVDFA DIGWSEWIIS PKSFDAYYCS GACQFPMPKS LKPSNHATIQ
SIVRAVGVVP GIPEPCCVPE KMSSLSILFF DENKNVVLKV YPNMTVESCA CR
