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Bone morphogenetic protein 10 (BMP-10)

 BMP10_MOUSE             Reviewed;         421 AA.
Q9R229; A6H6S5; Q9Z1V8;
21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
13-NOV-2007, sequence version 2.
18-JUL-2018, entry version 141.
RecName: Full=Bone morphogenetic protein 10;
Short=BMP-10;
Flags: Precursor;
Name=Bmp10;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
STRAIN=NIH Swiss; TISSUE=Heart;
PubMed=10072785; DOI=10.1016/S0925-4773(98)00221-4;
Neuhaus H., Rosen V., Thies R.S.;
"Heart specific expression of mouse BMP-10 a novel member of the TGF-
beta superfamily.";
Mech. Dev. 80:181-184(1999).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Celeste A.J.;
"Mouse bone morphogenetic protein 10 (BMP-10) genomic sequence, full
coding region of exon 2.";
Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[4]
FUNCTION, AND TISSUE SPECIFICITY.
PubMed=15109497; DOI=10.1016/S0092-8674(04)00405-2;
Pashmforoush M., Lu J.T., Chen H., Amand T.S., Kondo R.,
Pradervand S., Evans S.M., Clark B., Feramisco J.R., Giles W.,
Ho S.Y., Benson D.W., Silberbach M., Shou W., Chien K.R.;
"Nkx2-5 pathways and congenital heart disease: loss of ventricular
myocyte lineage specification leads to progressive cardiomyopathy and
complete heart block.";
Cell 117:373-386(2004).
[5]
FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
PubMed=15073151; DOI=10.1242/dev.01094;
Chen H., Shi S., Acosta L., Li W., Lu J., Bao S., Chen Z., Yang Z.,
Schneider M.D., Chien K.R., Conway S.J., Yoder M.C., Haneline L.S.,
Franco D., Shou W.;
"BMP10 is essential for maintaining cardiac growth during murine
cardiogenesis.";
Development 131:2219-2231(2004).
[6]
FUNCTION, AND DEVELOPMENTAL STAGE.
PubMed=16798733; DOI=10.1074/jbc.M604818200;
Chen H., Yong W., Ren S., Shen W., He Y., Cox K.A., Zhu W., Li W.,
Soonpaa M., Payne R.M., Franco D., Field L.J., Rosen V., Wang Y.,
Shou W.;
"Overexpression of bone morphogenetic protein 10 in myocardium
disrupts cardiac postnatal hypertrophic growth.";
J. Biol. Chem. 281:27481-27491(2006).
[7]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Heart;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
[8]
INTERACTION WITH ENG.
PubMed=21737454; DOI=10.1074/jbc.M111.260133;
Castonguay R., Werner E.D., Matthews R.G., Presman E., Mulivor A.W.,
Solban N., Sako D., Pearsall R.S., Underwood K.W., Seehra J.,
Kumar R., Grinberg A.V.;
"Soluble endoglin specifically binds bone morphogenetic proteins 9 and
10 via its orphan domain, inhibits blood vessel formation, and
suppresses tumor growth.";
J. Biol. Chem. 286:30034-30046(2011).
-!- FUNCTION: Required for maintaining the proliferative activity of
embryonic cardiomyocytes by preventing premature activation of the
negative cell cycle regulator CDKN1C/p57KIP and maintaining the
required expression levels of cardiogenic factors such as MEF2C
and NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and
BMPR1B/ALK6, leading to activation of SMAD1, SMAD5 and SMAD8
transcription factors. Inhibits endothelial cell migration and
growth. May reduce cell migration and cell matrix adhesion in
breast cancer cell lines (By similarity).
{ECO:0000250|UniProtKB:O95393, ECO:0000269|PubMed:15073151,
ECO:0000269|PubMed:15109497, ECO:0000269|PubMed:16798733}.
-!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts
with FBN1 (via N-terminal domain) and FBN2 (By similarity).
Interacts with ENG (PubMed:21737454).
{ECO:0000250|UniProtKB:O95393, ECO:0000250|UniProtKB:P12643,
ECO:0000269|PubMed:21737454}.
-!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
-!- TISSUE SPECIFICITY: In the embryo, expressed exclusively in the
ventricular trabecular myocardium of the developing heart from
E9.0-E13.5. By E16.5-E18.5, only detectable in atria. Highly
expressed in the adult heart where it is found in the right atrium
but not in the left atrium. Lower levels in adult liver and lung.
{ECO:0000269|PubMed:10072785, ECO:0000269|PubMed:15073151,
ECO:0000269|PubMed:15109497}.
-!- DEVELOPMENTAL STAGE: Down-regulation after E14.5 is critical for
cardiomyocytes to undergo normal developmental hypertrophic growth
in early postnatal life. {ECO:0000269|PubMed:16798733}.
-!- DISRUPTION PHENOTYPE: Mice die in utero between E9.5 and E10.5.
They appear normal at E8.5-E8.75 but display cardiac dysgenesis at
E9.0-E9.5 with profound hypoplastic ventricular walls and absence
of ventricular trabeculae and have a significantly lower heart
rate than wild type embryos. Mutants show up-regulation of
Cdkn1c/p57KIP throughout the ventricular wall while levels of
Mef2c and Nkx2-5 are normal at E8.5-E8.75 but are down-regulated
at E9.25-E9.5. {ECO:0000269|PubMed:15073151}.
-!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
-----------------------------------------------------------------------
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-----------------------------------------------------------------------
EMBL; AF101033; AAC95357.1; -; mRNA.
EMBL; AF101440; AAC77461.1; -; Genomic_DNA.
EMBL; AF101439; AAC77461.1; JOINED; Genomic_DNA.
EMBL; BC145983; AAI45984.1; -; mRNA.
CCDS; CCDS51838.1; -.
RefSeq; NP_033886.2; NM_009756.3.
UniGene; Mm.483321; -.
ProteinModelPortal; Q9R229; -.
IntAct; Q9R229; 1.
MINT; Q9R229; -.
STRING; 10090.ENSMUSP00000032125; -.
PhosphoSitePlus; Q9R229; -.
MaxQB; Q9R229; -.
PaxDb; Q9R229; -.
PRIDE; Q9R229; -.
Ensembl; ENSMUST00000032125; ENSMUSP00000032125; ENSMUSG00000030046.
GeneID; 12154; -.
KEGG; mmu:12154; -.
UCSC; uc012eol.1; mouse.
CTD; 27302; -.
MGI; MGI:1338820; Bmp10.
eggNOG; KOG3900; Eukaryota.
eggNOG; ENOG410XT8Z; LUCA.
GeneTree; ENSGT00760000118883; -.
HOGENOM; HOG000249477; -.
HOVERGEN; HBG106648; -.
InParanoid; Q9R229; -.
KO; K22670; -.
OMA; NVSIPHH; -.
OrthoDB; EOG091G075U; -.
PhylomeDB; Q9R229; -.
TreeFam; TF316134; -.
Reactome; R-MMU-201451; Signaling by BMP.
Reactome; R-MMU-2129379; Molecules associated with elastic fibres.
PRO; PR:Q9R229; -.
Proteomes; UP000000589; Chromosome 6.
Bgee; ENSMUSG00000030046; -.
CleanEx; MM_BMP10; -.
Genevisible; Q9R229; MM.
GO; GO:0009986; C:cell surface; ISO:MGI.
GO; GO:0005737; C:cytoplasm; ISO:MGI.
GO; GO:0005615; C:extracellular space; ISO:MGI.
GO; GO:0030018; C:Z disc; ISO:MGI.
GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
GO; GO:0005179; F:hormone activity; ISO:MGI.
GO; GO:0033612; F:receptor serine/threonine kinase binding; ISS:UniProtKB.
GO; GO:0031433; F:telethonin binding; ISO:MGI.
GO; GO:0005160; F:transforming growth factor beta receptor binding; IBA:GO_Central.
GO; GO:0032924; P:activin receptor signaling pathway; ISO:MGI.
GO; GO:0007512; P:adult heart development; IMP:BHF-UCL.
GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; IEP:BHF-UCL.
GO; GO:0030509; P:BMP signaling pathway; ISO:MGI.
GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:UniProtKB.
GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
GO; GO:0007507; P:heart development; IMP:MGI.
GO; GO:0060347; P:heart trabecula formation; IMP:BHF-UCL.
GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IMP:BHF-UCL.
GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
GO; GO:0010596; P:negative regulation of endothelial cell migration; ISO:MGI.
GO; GO:0060389; P:pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
GO; GO:0060045; P:positive regulation of cardiac muscle cell proliferation; IMP:BHF-UCL.
GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:MGI.
GO; GO:0061036; P:positive regulation of cartilage development; IDA:UniProtKB.
GO; GO:2000138; P:positive regulation of cell proliferation involved in heart morphogenesis; IGI:BHF-UCL.
GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; IDA:BHF-UCL.
GO; GO:0060298; P:positive regulation of sarcomere organization; ISO:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
GO; GO:0042981; P:regulation of apoptotic process; IBA:GO_Central.
GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:MGI.
GO; GO:1903242; P:regulation of cardiac muscle hypertrophy in response to stress; ISO:MGI.
GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
GO; GO:0045214; P:sarcomere organization; ISO:MGI.
GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
GO; GO:0055015; P:ventricular cardiac muscle cell development; IDA:BHF-UCL.
GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
Gene3D; 2.10.90.10; -; 1.
InterPro; IPR029034; Cystine-knot_cytokine.
InterPro; IPR001839; TGF-b_C.
InterPro; IPR001111; TGF-b_propeptide.
InterPro; IPR015615; TGF-beta-rel.
InterPro; IPR017948; TGFb_CS.
PANTHER; PTHR11848; PTHR11848; 1.
Pfam; PF00019; TGF_beta; 1.
Pfam; PF00688; TGFb_propeptide; 1.
SMART; SM00204; TGFB; 1.
SUPFAM; SSF57501; SSF57501; 1.
PROSITE; PS00250; TGF_BETA_1; 1.
PROSITE; PS51362; TGF_BETA_2; 1.
1: Evidence at protein level;
Cell adhesion; Cleavage on pair of basic residues; Complete proteome;
Cytokine; Developmental protein; Disulfide bond; Glycoprotein;
Growth factor; Reference proteome; Secreted; Signal.
SIGNAL 1 21 {ECO:0000255}.
PROPEP 22 313 {ECO:0000255}.
/FTId=PRO_0000033890.
CHAIN 314 421 Bone morphogenetic protein 10.
/FTId=PRO_0000033891.
CARBOHYD 67 67 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
CARBOHYD 131 131 N-linked (GlcNAc...) asparagine.
{ECO:0000255}.
DISULFID 320 386 {ECO:0000250}.
DISULFID 349 418 {ECO:0000250}.
DISULFID 353 420 {ECO:0000250}.
DISULFID 385 385 Interchain. {ECO:0000250}.
CONFLICT 83 83 E -> K (in Ref. 1; AAC95357 and 2;
AAC77461). {ECO:0000305}.
CONFLICT 112 112 Missing (in Ref. 1; AAC95357).
{ECO:0000305}.
CONFLICT 309 309 A -> T (in Ref. 1; AAC95357 and 2;
AAC77461). {ECO:0000305}.
SEQUENCE 421 AA; 47888 MW; 770AF401A64C3F49 CRC64;
MGSLVLPLSA VFCLVAHSAS GSPIMGLEQS PLEEDMPFFD DIFTEQDGID FNTLLQSMKN
EFLKTLNLSD IPVQDTGRVD PPEYMLELYN KFATDRTSMP SANIIRSFKN EDLFSQPVTF
NGLRKYPLLF NVSIPHHEEV VMAELRLYTL VQRDRMMYDG VDRKITIFEV LESADGSEEE
RSMLVLVSTE IYGTNSEWET FDVTDATRRW QKSGPSTHQL EIHIESRQNQ AEDTGRGQLE
IDMSAQNKHD PLLVVFSDDQ SNDKEQKEEL NELITHEQDL DLDSDAFFSG PDEEALLQMR
SNMIDDSSAR IRRNAKGNYC KKTPLYIDFK EIGWDSWIIA PPGYEAYECR GVCNYPLAEH
LTPTKHAIIQ ALVHLKNSQK ASKACCVPTK LDPISILYLD KGVVTYKFKY EGMAVSECGC
R


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