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   24-JAN-2024, entry version 199.
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 differentiation 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";
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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; 5.
DR   MINT; P12645; -.
DR   STRING; 9606.ENSP00000282701; -.
DR   GlyCosmos; P12645; 5 sites, No reported glycans.
DR   GlyGen; P12645; 11 sites, 2 O-linked glycans (6 sites).
DR   iPTMnet; P12645; -.
DR   PhosphoSitePlus; P12645; -.
DR   BioMuta; BMP3; -.
DR   DMDM; 215273985; -.
DR   MassIVE; P12645; -.
DR   PaxDb; 9606-ENSP00000282701; -.
DR   PeptideAtlas; P12645; -.
DR   ProteomicsDB; 52862; -.
DR   Antibodypedia; 25010; 549 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   AGR; HGNC:1070; -.
DR   CTD; 651; -.
DR   DisGeNET; 651; -.
DR   GeneCards; BMP3; -.
DR   HGNC; HGNC:1070; BMP3.
DR   HPA; ENSG00000152785; Tissue enhanced (intestine, lung, ovary, 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; HWGTINN; -.
DR   OrthoDB; 2912454at2759; -.
DR   PhylomeDB; P12645; -.
DR   TreeFam; TF316134; -.
DR   PathwayCommons; P12645; -.
DR   SignaLink; P12645; -.
DR   BioGRID-ORCS; 651; 13 hits in 1144 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 81 other cell types or tissues.
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:0001501; P:skeletal system development; TAS:ProtInc.
DR   CDD; cd19393; TGF_beta_BMP3; 1.
DR   Gene3D; 2.10.90.10; Cystine-knot cytokines; 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:SF144; BONE MORPHOGENETIC PROTEIN 3; 1.
DR   PANTHER; PTHR11848; TGF-BETA FAMILY; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   PIRSF; PIRSF037403; BMP3/GDF10; 1.
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.
DR   Genevisible; P12645; HS.
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
//