BMP10_MOUSE
ID BMP10_MOUSE Reviewed; 421 AA.
AC Q9R229; A6H6S5; Q9Z1V8;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Bone morphogenetic protein 10;
DE Short=BMP-10;
DE Flags: Precursor;
GN Name=Bmp10;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=NIH Swiss; TISSUE=Heart;
RX PubMed=10072785; DOI=10.1016/s0925-4773(98)00221-4;
RA Neuhaus H., Rosen V., Thies R.S.;
RT "Heart specific expression of mouse BMP-10 a novel member of the TGF-beta
RT superfamily.";
RL Mech. Dev. 80:181-184(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Celeste A.J.;
RT "Mouse bone morphogenetic protein 10 (BMP-10) genomic sequence, full coding
RT region of exon 2.";
RL Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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, AND TISSUE SPECIFICITY.
RX PubMed=15109497; DOI=10.1016/s0092-8674(04)00405-2;
RA Pashmforoush M., Lu J.T., Chen H., Amand T.S., Kondo R., Pradervand S.,
RA Evans S.M., Clark B., Feramisco J.R., Giles W., Ho S.Y., Benson D.W.,
RA Silberbach M., Shou W., Chien K.R.;
RT "Nkx2-5 pathways and congenital heart disease: loss of ventricular myocyte
RT lineage specification leads to progressive cardiomyopathy and complete
RT heart block.";
RL Cell 117:373-386(2004).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=15073151; DOI=10.1242/dev.01094;
RA Chen H., Shi S., Acosta L., Li W., Lu J., Bao S., Chen Z., Yang Z.,
RA Schneider M.D., Chien K.R., Conway S.J., Yoder M.C., Haneline L.S.,
RA Franco D., Shou W.;
RT "BMP10 is essential for maintaining cardiac growth during murine
RT cardiogenesis.";
RL Development 131:2219-2231(2004).
RN [6]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=16798733; DOI=10.1074/jbc.m604818200;
RA Chen H., Yong W., Ren S., Shen W., He Y., Cox K.A., Zhu W., Li W.,
RA Soonpaa M., Payne R.M., Franco D., Field L.J., Rosen V., Wang Y., Shou W.;
RT "Overexpression of bone morphogenetic protein 10 in myocardium disrupts
RT cardiac postnatal hypertrophic growth.";
RL J. Biol. Chem. 281:27481-27491(2006).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
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., Kumar R.,
RA Grinberg A.V.;
RT "Soluble endoglin specifically binds bone morphogenetic proteins 9 and 10
RT via its orphan domain, inhibits blood vessel formation, and suppresses
RT tumor growth.";
RL J. Biol. Chem. 286:30034-30046(2011).
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 and
CC NKX2-5. Acts as a ligand for ACVRL1/ALK1, BMPR1A/ALK3 and BMPR1B/ALK6,
CC leading to activation of SMAD1, SMAD5 and SMAD8 transcription factors.
CC Inhibits endothelial cell migration and growth. May reduce cell
CC migration and cell matrix adhesion in breast cancer cell lines (By
CC similarity). {ECO:0000250|UniProtKB:O95393,
CC ECO:0000269|PubMed:15073151, ECO:0000269|PubMed:15109497,
CC ECO:0000269|PubMed:16798733}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Interacts with
CC FBN1 (via N-terminal domain) and FBN2 (By similarity). Interacts with
CC ENG (PubMed:21737454). {ECO:0000250|UniProtKB:O95393,
CC ECO:0000250|UniProtKB:P12643, ECO:0000269|PubMed:21737454}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: In the embryo, expressed exclusively in the
CC ventricular trabecular myocardium of the developing heart from 9.0 dpc-
CC 13.5 dpc. By 16.5 dpc-18.5 dpc, only detectable in atria. Highly
CC expressed in the adult heart where it is found in the right atrium but
CC not in the left atrium. Lower levels in adult liver and lung.
CC {ECO:0000269|PubMed:10072785, ECO:0000269|PubMed:15073151,
CC ECO:0000269|PubMed:15109497}.
CC -!- DEVELOPMENTAL STAGE: Down-regulation after 14.5 dpc is critical for
CC cardiomyocytes to undergo normal developmental hypertrophic growth in
CC early postnatal life. {ECO:0000269|PubMed:16798733}.
CC -!- DISRUPTION PHENOTYPE: Mice die in utero between 9.5 dpc and 10.5 dpc.
CC They appear normal at 8.5 dpc-8.75 dpc but display cardiac dysgenesis
CC at 9.0 dpc-9.5 dpc with profound hypoplastic ventricular walls and
CC absence of ventricular trabeculae and have a significantly lower heart
CC rate than wild type embryos. Mutants show up-regulation of
CC Cdkn1c/p57KIP throughout the ventricular wall while levels of Mef2c and
CC Nkx2-5 are normal at 8.5 dpc-8.75 dpc but are down-regulated at 9.25
CC dpc-9.5 dpc. {ECO:0000269|PubMed:15073151}.
CC -!- SIMILARITY: Belongs to the TGF-beta family. {ECO:0000305}.
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DR EMBL; AF101033; AAC95357.1; -; mRNA.
DR EMBL; AF101440; AAC77461.1; -; Genomic_DNA.
DR EMBL; AF101439; AAC77461.1; JOINED; Genomic_DNA.
DR EMBL; BC145983; AAI45984.1; -; mRNA.
DR CCDS; CCDS51838.1; -.
DR RefSeq; NP_033886.2; NM_009756.3.
DR AlphaFoldDB; Q9R229; -.
DR SMR; Q9R229; -.
DR STRING; 10090.ENSMUSP00000032125; -.
DR GlyGen; Q9R229; 2 sites.
DR PhosphoSitePlus; Q9R229; -.
DR MaxQB; Q9R229; -.
DR PaxDb; Q9R229; -.
DR PRIDE; Q9R229; -.
DR ProteomicsDB; 265217; -.
DR Antibodypedia; 16182; 402 antibodies from 37 providers.
DR DNASU; 12154; -.
DR Ensembl; ENSMUST00000032125; ENSMUSP00000032125; ENSMUSG00000030046.
DR GeneID; 12154; -.
DR KEGG; mmu:12154; -.
DR UCSC; uc012eol.1; mouse.
DR CTD; 27302; -.
DR MGI; MGI:1338820; Bmp10.
DR VEuPathDB; HostDB:ENSMUSG00000030046; -.
DR eggNOG; KOG3900; Eukaryota.
DR GeneTree; ENSGT00940000156279; -.
DR HOGENOM; CLU_020515_2_0_1; -.
DR InParanoid; Q9R229; -.
DR OMA; MIAHEQL; -.
DR OrthoDB; 749511at2759; -.
DR PhylomeDB; Q9R229; -.
DR TreeFam; TF316134; -.
DR Reactome; R-MMU-201451; Signaling by BMP.
DR Reactome; R-MMU-2129379; Molecules associated with elastic fibres.
DR BioGRID-ORCS; 12154; 4 hits in 71 CRISPR screens.
DR PRO; PR:Q9R229; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9R229; protein.
DR Bgee; ENSMUSG00000030046; Expressed in cardiac atrium and 24 other tissues.
DR Genevisible; Q9R229; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0030018; C:Z disc; ISO: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:0005179; F:hormone activity; ISO:MGI.
DR GO; GO:0033612; F:receptor serine/threonine kinase binding; ISS:UniProtKB.
DR GO; GO:0031433; F:telethonin binding; ISO:MGI.
DR GO; GO:0032924; P:activin receptor signaling pathway; ISO:MGI.
DR GO; GO:0007512; P:adult heart development; IMP:BHF-UCL.
DR GO; GO:0055009; P:atrial cardiac muscle tissue morphogenesis; IEP:BHF-UCL.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:MGI.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; IMP:UniProtKB.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; IMP:MGI.
DR GO; GO:0060347; P:heart trabecula formation; IMP:BHF-UCL.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IMP:BHF-UCL.
DR GO; GO:0030308; P:negative regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; ISO:MGI.
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; IMP:BHF-UCL.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; ISO:MGI.
DR GO; GO:0061036; P:positive regulation of cartilage development; IDA:UniProtKB.
DR GO; GO:2000138; P:positive regulation of cell proliferation involved in heart morphogenesis; IGI:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
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; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:MGI.
DR GO; GO:1903242; P:regulation of cardiac muscle hypertrophy in response to stress; ISO:MGI.
DR GO; GO:0045214; P:sarcomere organization; ISO:MGI.
DR GO; GO:0060395; P:SMAD protein signal transduction; IBA:GO_Central.
DR GO; GO:0055015; P:ventricular cardiac muscle cell development; IDA:BHF-UCL.
DR GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP: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; Cytokine;
KW Developmental protein; Disulfide bond; Glycoprotein; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT PROPEP 22..313
FT /evidence="ECO:0000255"
FT /id="PRO_0000033890"
FT CHAIN 314..421
FT /note="Bone morphogenetic protein 10"
FT /id="PRO_0000033891"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 131
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 320..386
FT /evidence="ECO:0000250"
FT DISULFID 349..418
FT /evidence="ECO:0000250"
FT DISULFID 353..420
FT /evidence="ECO:0000250"
FT DISULFID 385
FT /note="Interchain"
FT /evidence="ECO:0000250"
FT CONFLICT 83
FT /note="E -> K (in Ref. 1; AAC95357 and 2; AAC77461)"
FT /evidence="ECO:0000305"
FT CONFLICT 112
FT /note="Missing (in Ref. 1; AAC95357)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="A -> T (in Ref. 1; AAC95357 and 2; AAC77461)"
FT /evidence="ECO:0000305"
SQ 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
