ID   BMP10_HUMAN             Reviewed;         424 AA.
AC   O95393; Q53R17; Q6NTE0;
DT   21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   13-FEB-2019, entry version 151.
DE   RecName: Full=Bone morphogenetic protein 10;
DE            Short=BMP-10;
DE   Flags: Precursor;
GN   Name=BMP10;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RA   Celeste A.J.;
RT   "Homo sapiens bone morphogenetic protein 10 (BMP-10) mRNA.";
RL   Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   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.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   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.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Cerebellum;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   FUNCTION.
RX   PubMed=16049014; DOI=10.1074/jbc.M504629200;
RA   Mazerbourg S., Sangkuhl K., Luo C.-W., Sudo S., Klein C.,
RA   Hsueh A.J.W.;
RT   "Identification of receptors and signaling pathways for orphan bone
RT   morphogenetic protein/growth differentiation factor ligands based on
RT   genomic analyses.";
RL   J. Biol. Chem. 280:32122-32132(2005).
RN   [5]
RP   FUNCTION.
RX   PubMed=17068149; DOI=10.1182/blood-2006-07-034124;
RA   David L., Mallet C., Mazerbourg S., Feige J.-J., Bailly S.;
RT   "Identification of BMP9 and BMP10 as functional activators of the
RT   orphan activin receptor-like kinase 1 (ALK1) in endothelial cells.";
RL   Blood 109:1953-1961(2007).
RN   [6]
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.,
RA   Keene D.R., 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   [7]
RP   INTERACTION WITH ENG.
RX   PubMed=21737454; DOI=10.1074/jbc.M111.260133;
RA   Castonguay R., Werner E.D., Matthews R.G., Presman E., Mulivor A.W.,
RA   Solban N., Sako D., Pearsall R.S., Underwood K.W., Seehra J.,
RA   Kumar R., Grinberg A.V.;
RT   "Soluble endoglin specifically binds bone morphogenetic proteins 9 and
RT   10 via its orphan domain, inhibits blood vessel formation, and
RT   suppresses tumor growth.";
RL   J. Biol. Chem. 286:30034-30046(2011).
RN   [8]
RP   FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX   PubMed=20608934; DOI=10.1111/j.1349-7006.2010.01648.x;
RA   Ye L., Bokobza S., Li J., Moazzam M., Chen J., Mansel R.E.,
RA   Jiang W.G.;
RT   "Bone morphogenetic protein-10 (BMP-10) inhibits aggressiveness of
RT   breast cancer cells and correlates with poor prognosis in breast
RT   cancer.";
RL   Cancer Sci. 101:2137-2144(2010).
CC   -!- FUNCTION: Required for maintaining the proliferative activity of
CC       embryonic cardiomyocytes by preventing premature activation of the
CC       negative cell cycle regulator CDKN1C/p57KIP and maintaining the
CC       required expression levels of cardiogenic factors such as MEF2C
CC       and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and
CC       BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8
CC       transcription factors. Inhibits endothelial cell migration and
CC       growth. May reduce cell migration and cell matrix adhesion in
CC       breast cancer cell lines. {ECO:0000269|PubMed:16049014,
CC       ECO:0000269|PubMed:17068149, ECO:0000269|PubMed:20608934}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts
CC       with FBN1 (via N-terminal domain) and FBN2 (PubMed:18339631).
CC       Interacts with ENG (PubMed:21737454).
CC       {ECO:0000250|UniProtKB:P12643, ECO:0000269|PubMed:18339631,
CC       ECO:0000269|PubMed:21737454}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Detected in mammary epithelia (at protein
CC       level). {ECO:0000269|PubMed:20608934}.
CC   -!- INDUCTION: Down-regulated in some breast cancer subtypes and
CC       breast cancer cell lines. {ECO:0000269|PubMed:20608934}.
CC   -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Wikipedia; Note=Bone morphogenetic protein 10
CC       entry;
CC       URL="https://en.wikipedia.org/wiki/Bone_morphogenetic_protein_10";
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; AF101441; AAC77462.1; -; mRNA.
DR   EMBL; AC097495; AAY15075.1; -; Genomic_DNA.
DR   EMBL; BC069080; AAH69080.1; -; mRNA.
DR   EMBL; BC101734; AAI01735.1; -; mRNA.
DR   EMBL; BC105063; AAI05064.1; -; mRNA.
DR   CCDS; CCDS1890.1; -.
DR   RefSeq; NP_055297.1; NM_014482.2.
DR   UniGene; Hs.158317; -.
DR   ProteinModelPortal; O95393; -.
DR   BioGrid; 118125; 4.
DR   IntAct; O95393; 48.
DR   STRING; 9606.ENSP00000295379; -.
DR   ChEMBL; CHEMBL3713453; -.
DR   iPTMnet; O95393; -.
DR   PhosphoSitePlus; O95393; -.
DR   BioMuta; BMP10; -.
DR   MaxQB; O95393; -.
DR   PaxDb; O95393; -.
DR   PeptideAtlas; O95393; -.
DR   PRIDE; O95393; -.
DR   ProteomicsDB; 50844; -.
DR   DNASU; 27302; -.
DR   Ensembl; ENST00000295379; ENSP00000295379; ENSG00000163217.
DR   GeneID; 27302; -.
DR   KEGG; hsa:27302; -.
DR   UCSC; uc002sez.1; human.
DR   CTD; 27302; -.
DR   DisGeNET; 27302; -.
DR   EuPathDB; HostDB:ENSG00000163217.1; -.
DR   GeneCards; BMP10; -.
DR   HGNC; HGNC:20869; BMP10.
DR   MIM; 608748; gene.
DR   neXtProt; NX_O95393; -.
DR   OpenTargets; ENSG00000163217; -.
DR   PharmGKB; PA134953092; -.
DR   eggNOG; KOG3900; Eukaryota.
DR   eggNOG; ENOG410XT8Z; LUCA.
DR   GeneTree; ENSGT00940000156279; -.
DR   HOGENOM; HOG000249477; -.
DR   HOVERGEN; HBG106648; -.
DR   InParanoid; O95393; -.
DR   KO; K22670; -.
DR   OMA; MSLEQSP; -.
DR   OrthoDB; 749511at2759; -.
DR   PhylomeDB; O95393; -.
DR   TreeFam; TF316134; -.
DR   Reactome; R-HSA-201451; Signaling by BMP.
DR   Reactome; R-HSA-2129379; Molecules associated with elastic fibres.
DR   SIGNOR; O95393; -.
DR   GeneWiki; Bone_morphogenetic_protein_10; -.
DR   GenomeRNAi; 27302; -.
DR   PRO; PR:O95393; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   Bgee; ENSG00000163217; Expressed in 46 organ(s), highest expression level in right atrium auricular region.
DR   Genevisible; O95393; HS.
DR   GO; GO:0009986; C:cell surface; IDA:BHF-UCL.
DR   GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0030018; C:Z disc; IDA:BHF-UCL.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0005179; F:hormone activity; IDA:BHF-UCL.
DR   GO; GO:0033612; F:receptor serine/threonine kinase binding; IDA:UniProtKB.
DR   GO; GO:0031433; F:telethonin binding; IPI:BHF-UCL.
DR   GO; GO:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central.
DR   GO; GO:0032924; P:activin receptor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0007512; P:adult heart development; ISS:BHF-UCL.
DR   GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0030509; P:BMP signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0060038; P:cardiac muscle cell proliferation; ISS:UniProtKB.
DR   GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR   GO; GO:0048468; P:cell development; IBA:GO_Central.
DR   GO; GO:0060347; P:heart trabecula formation; ISS:BHF-UCL.
DR   GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISS:BHF-UCL.
DR   GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR   GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB.
DR   GO; GO:0010596; P:negative regulation of endothelial cell migration; IDA:BHF-UCL.
DR   GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; ISS:BHF-UCL.
DR   GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IMP:BHF-UCL.
DR   GO; GO:0061036; P:positive regulation of cartilage development; IEA:Ensembl.
DR   GO; GO:2000138; P:positive regulation of cell proliferation involved in heart morphogenesis; ISS:BHF-UCL.
DR   GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
DR   GO; GO:0060298; P:positive regulation of sarcomere organization; IDA:BHF-UCL.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR   GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
DR   GO; GO:0055117; P:regulation of cardiac muscle contraction; IMP:BHF-UCL.
DR   GO; GO:1903242; P:regulation of cardiac muscle hypertrophy in response to stress; IDA:BHF-UCL.
DR   GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR   GO; GO:0045214; P:sarcomere organization; ISS:BHF-UCL.
DR   GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR   GO; GO:0055015; P:ventricular cardiac muscle cell development; ISS:BHF-UCL.
DR   GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; ISS:BHF-UCL.
DR   Gene3D; 2.10.90.10; -; 1.
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   Cell adhesion; Cleavage on pair of basic residues; Complete proteome;
KW   Cytokine; Developmental protein; Disulfide bond; Glycoprotein;
KW   Growth factor; Polymorphism; Reference proteome; Secreted; Signal.
FT   SIGNAL        1     21       {ECO:0000255}.
FT   PROPEP       22    316       {ECO:0000255}.
FT                                /FTId=PRO_0000033888.
FT   CHAIN       317    424       Bone morphogenetic protein 10.
FT                                /FTId=PRO_0000033889.
FT   CARBOHYD     67     67       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    131    131       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    323    389       {ECO:0000250}.
FT   DISULFID    352    421       {ECO:0000250}.
FT   DISULFID    356    423       {ECO:0000250}.
FT   DISULFID    388    388       Interchain. {ECO:0000250}.
FT   VARIANT     200    200       T -> S (in dbSNP:rs2231342).
FT                                /FTId=VAR_052572.
FT   VARIANT     250    250       N -> K (in dbSNP:rs2231345).
FT                                /FTId=VAR_052573.
FT   CONFLICT    143    143       A -> T (in Ref. 3; AAH69080).
FT                                {ECO:0000305}.
SQ   SEQUENCE   424 AA;  48047 MW;  3FDB3B7221BB2254 CRC64;
     MGSLVLTLCA LFCLAAYLVS GSPIMNLEQS PLEEDMSLFG DVFSEQDGVD FNTLLQSMKD
     EFLKTLNLSD IPTQDSAKVD PPEYMLELYN KFATDRTSMP SANIIRSFKN EDLFSQPVSF
     NGLRKYPLLF NVSIPHHEEV IMAELRLYTL VQRDRMIYDG VDRKITIFEV LESKGDNEGE
     RNMLVLVSGE IYGTNSEWET FDVTDAIRRW QKSGSSTHQL EVHIESKHDE AEDASSGRLE
     IDTSAQNKHN PLLIVFSDDQ SSDKERKEEL NEMISHEQLP ELDNLGLDSF SSGPGEEALL
     QMRSNIIYDS TARIRRNAKG NYCKRTPLYI DFKEIGWDSW IIAPPGYEAY ECRGVCNYPL
     AEHLTPTKHA IIQALVHLKN SQKASKACCV PTKLEPISIL YLDKGVVTYK FKYEGMAVSE
     CGCR
//