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   27-MAR-2024, entry version 171.
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   GlyCosmos; Q9R229; 2 sites, No reported glycans.
DR   GlyGen; Q9R229; 2 sites.
DR   PhosphoSitePlus; Q9R229; -.
DR   MaxQB; Q9R229; -.
DR   PaxDb; 10090-ENSMUSP00000032125; -.
DR   ProteomicsDB; 265217; -.
DR   Antibodypedia; 16182; 439 antibodies from 37 providers.
DR   DNASU; 12154; -.
DR   Ensembl; ENSMUST00000032125.7; ENSMUSP00000032125.6; ENSMUSG00000030046.7.
DR   GeneID; 12154; -.
DR   KEGG; mmu:12154; -.
DR   UCSC; uc012eol.1; mouse.
DR   AGR; MGI:1338820; -.
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; SAQNKHD; -.
DR   OrthoDB; 2912454at2759; -.
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 76 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 cell types or tissues.
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; ISO:MGI.
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; IDA:BHF-UCL.
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: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:0045893; P:positive regulation of DNA-templated transcription; ISO:MGI.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:MGI.
DR   GO; GO:0060298; P:positive regulation of sarcomere organization; ISO:MGI.
DR   GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; IDA:BHF-UCL.
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:0055015; P:ventricular cardiac muscle cell development; IDA:BHF-UCL.
DR   GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
DR   CDD; cd19401; TGF_beta_BMP10; 1.
DR   Gene3D; 2.60.120.970; -; 1.
DR   Gene3D; 2.10.90.10; Cystine-knot cytokines; 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:SF39; BONE MORPHOGENETIC PROTEIN 10; 1.
DR   PANTHER; PTHR11848; TGF-BETA FAMILY; 1.
DR   Pfam; PF00019; TGF_beta; 1.
DR   Pfam; PF00688; TGFb_propeptide; 1.
DR   PRINTS; PR00669; INHIBINA.
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; Q9R229; MM.
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
//