ID3_MOUSE
ID ID3_MOUSE Reviewed; 119 AA.
AC P41133;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=DNA-binding protein inhibitor ID-3;
DE AltName: Full=ID-like protein inhibitor HLH 462;
DE AltName: Full=Inhibitor of DNA binding 3;
DE AltName: Full=Inhibitor of differentiation 3;
GN Name=Id3; Synonyms=Hlh462, Id-3, Idb3;
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].
RX PubMed=2000388; DOI=10.1073/pnas.88.5.1815;
RA Christy B.A., Sanders L.K., Lau L.F., Copeland N.G., Jenkins N.A.,
RA Nathans D.;
RT "An Id-related helix-loop-helix protein encoded by a growth factor-
RT inducible gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:1815-1819(1991).
RN [2]
RP INTERACTION WITH IFI204.
RX PubMed=11940648; DOI=10.1128/mcb.22.9.2893-2905.2002;
RA Liu C.-J., Ding B., Wang H., Lengyel P.;
RT "The MyoD-inducible p204 protein overcomes the inhibition of myoblast
RT differentiation by Id proteins.";
RL Mol. Cell. Biol. 22:2893-2905(2002).
RN [3]
RP INTERACTION WITH COPS5 AND COPS7A.
RX PubMed=15451666; DOI=10.1016/j.jmb.2004.08.043;
RA Berse M., Bounpheng M., Huang X., Christy B., Pollmann C., Dubiel W.;
RT "Ubiquitin-dependent degradation of Id1 and Id3 is mediated by the COP9
RT signalosome.";
RL J. Mol. Biol. 343:361-370(2004).
RN [4]
RP INTERACTION WITH GATA4 AND NKX2-5, UBIQUITINATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=16556596; DOI=10.1074/jbc.m511748200;
RA Ding B., Liu C.-J., Huang Y., Yu J., Kong W., Lengyel P.;
RT "p204 protein overcomes the inhibition of the differentiation of P19 murine
RT embryonal carcinoma cells to beating cardiac myocytes by Id proteins.";
RL J. Biol. Chem. 281:14893-14906(2006).
RN [5]
RP FUNCTION, AND INDUCTION.
RX PubMed=19217292; DOI=10.1016/j.cub.2008.12.052;
RA Duffield G.E., Watson N.P., Mantani A., Peirson S.N., Robles-Murguia M.,
RA Loros J.J., Israel M.A., Dunlap J.C.;
RT "A role for Id2 in regulating photic entrainment of the mammalian circadian
RT system.";
RL Curr. Biol. 19:297-304(2009).
RN [6]
RP FUNCTION.
RX PubMed=22862948; DOI=10.1016/j.stem.2012.05.022;
RA Diao Y., Guo X., Li Y., Sun K., Lu L., Jiang L., Fu X., Zhu H., Sun H.,
RA Wang H., Wu Z.;
RT "Pax3/7BP is a Pax7- and Pax3-binding protein that regulates the
RT proliferation of muscle precursor cells by an epigenetic mechanism.";
RL Cell Stem Cell 11:231-241(2012).
RN [7]
RP FUNCTION IN MYOBLAST DIFFERENTIATION, INTERACTION WITH ANKRD2, AND TISSUE
RP SPECIFICITY.
RX PubMed=23824195; DOI=10.1074/jbc.m112.434423;
RA Mohamed J.S., Lopez M.A., Cox G.A., Boriek A.M.;
RT "Ankyrin repeat domain protein 2 and inhibitor of DNA binding 3
RT cooperatively inhibit myoblast differentiation by physical interaction.";
RL J. Biol. Chem. 288:24560-24568(2013).
CC -!- FUNCTION: Transcriptional regulator (lacking a basic DNA binding
CC domain) which negatively regulates the basic helix-loop-helix (bHLH)
CC transcription factors by forming heterodimers and inhibiting their DNA
CC binding and transcriptional activity. Implicated in regulating a
CC variety of cellular processes, including cellular growth, senescence,
CC differentiation, apoptosis, angiogenesis, and neoplastic
CC transformation. Involved in myogenesis by inhibiting skeletal muscle
CC and cardiac myocyte differentiation and promoting muscle precursor
CC cells proliferation. Inhibits the binding of E2A-containing protein
CC complexes to muscle creatine kinase E-box enhancer. Regulates the
CC circadian clock by repressing the transcriptional activator activity of
CC the CLOCK-ARNTL/BMAL1 heterodimer. {ECO:0000269|PubMed:19217292,
CC ECO:0000269|PubMed:22862948, ECO:0000269|PubMed:23824195}.
CC -!- SUBUNIT: Homodimer, and heterodimer with other HLH proteins. Interacts
CC with CLOCK and ARNTL/BMAL1 (By similarity). Interacts with COPS5 and
CC COPS7A. Interacts with IFI204. Interacts with GATA4 and NKX2-5.
CC Interacts with ANKRD2; both proteins cooperate in myoblast
CC differentiation. {ECO:0000250, ECO:0000269|PubMed:11940648,
CC ECO:0000269|PubMed:15451666, ECO:0000269|PubMed:16556596,
CC ECO:0000269|PubMed:23824195}.
CC -!- INTERACTION:
CC P41133; Q9WV06: Ankrd2; NbExp=4; IntAct=EBI-309448, EBI-8854438;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00981,
CC ECO:0000269|PubMed:16556596}. Cytoplasm {ECO:0000269|PubMed:16556596}.
CC Note=Nuclear in proliferating cells, translocates to cytosol during
CC cell differentiation.
CC -!- TISSUE SPECIFICITY: Expressed by myoblasts (at protein level).
CC {ECO:0000269|PubMed:23824195}.
CC -!- INDUCTION: By a variety of mitogenic agents in serum starved cells.
CC Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of
CC the brain and heart with peak levels between CT16 and CT20 in SCN and
CC between CT8 and CT12 in the heart. {ECO:0000269|PubMed:19217292}.
CC -!- PTM: Polyubiquitinated; which is favored by Ifi204 and leads to
CC proteasomal degradation. {ECO:0000269|PubMed:16556596}.
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; M60523; AAA37818.1; -; mRNA.
DR CCDS; CCDS18800.1; -.
DR PIR; A39114; A39114.
DR RefSeq; NP_032347.1; NM_008321.2.
DR AlphaFoldDB; P41133; -.
DR SMR; P41133; -.
DR BioGRID; 200507; 11.
DR IntAct; P41133; 6.
DR MINT; P41133; -.
DR STRING; 10090.ENSMUSP00000008016; -.
DR iPTMnet; P41133; -.
DR PhosphoSitePlus; P41133; -.
DR jPOST; P41133; -.
DR PaxDb; P41133; -.
DR PRIDE; P41133; -.
DR ProteomicsDB; 273089; -.
DR Antibodypedia; 4480; 626 antibodies from 38 providers.
DR DNASU; 15903; -.
DR Ensembl; ENSMUST00000008016; ENSMUSP00000008016; ENSMUSG00000007872.
DR GeneID; 15903; -.
DR KEGG; mmu:15903; -.
DR UCSC; uc012dnf.1; mouse.
DR CTD; 3399; -.
DR MGI; MGI:96398; Id3.
DR VEuPathDB; HostDB:ENSMUSG00000007872; -.
DR eggNOG; ENOG502S53I; Eukaryota.
DR GeneTree; ENSGT00940000160504; -.
DR HOGENOM; CLU_116790_1_0_1; -.
DR InParanoid; P41133; -.
DR OMA; PARGCYE; -.
DR OrthoDB; 1624054at2759; -.
DR PhylomeDB; P41133; -.
DR TreeFam; TF326217; -.
DR BioGRID-ORCS; 15903; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Id3; mouse.
DR PRO; PR:P41133; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P41133; protein.
DR Bgee; ENSMUSG00000007872; Expressed in endothelial cell of lymphatic vessel and 360 other tissues.
DR ExpressionAtlas; P41133; baseline and differential.
DR Genevisible; P41133; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IMP:MGI.
DR GO; GO:0043425; F:bHLH transcription factor binding; IPI:UniProtKB.
DR GO; GO:1901707; F:leptomycin B binding; IDA:MGI.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0019904; F:protein domain specific binding; IDA:MGI.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IDA:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0072750; P:cellular response to leptomycin B; IDA:MGI.
DR GO; GO:0007417; P:central nervous system development; IEP:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IBA:GO_Central.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0030855; P:epithelial cell differentiation; IDA:MGI.
DR GO; GO:0007507; P:heart development; IGI:MGI.
DR GO; GO:0001656; P:metanephros development; IEP:UniProtKB.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:MGI.
DR GO; GO:0045662; P:negative regulation of myoblast differentiation; IMP:UniProtKB.
DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IEA:Ensembl.
DR GO; GO:0030903; P:notochord development; IEP:UniProtKB.
DR GO; GO:0042476; P:odontogenesis; IEP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; ISO:MGI.
DR GO; GO:0006275; P:regulation of DNA replication; ISO:MGI.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR Gene3D; 4.10.280.10; -; 1.
DR InterPro; IPR011598; bHLH_dom.
DR InterPro; IPR026052; DNA-bd_prot-inh.
DR InterPro; IPR036638; HLH_DNA-bd_sf.
DR PANTHER; PTHR11723; PTHR11723; 1.
DR Pfam; PF00010; HLH; 1.
DR SMART; SM00353; HLH; 1.
DR SUPFAM; SSF47459; SSF47459; 1.
DR PROSITE; PS50888; BHLH; 1.
PE 1: Evidence at protein level;
KW Biological rhythms; Cytoplasm; Developmental protein; Myogenesis; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..119
FT /note="DNA-binding protein inhibitor ID-3"
FT /id="PRO_0000127248"
FT DOMAIN 28..80
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 35..87
FT /note="Interaction with IFI204"
FT /evidence="ECO:0000250"
SQ SEQUENCE 119 AA; 13089 MW; 49F3B841D2D2BF15 CRC64;
MKALSPVRGC YEAVCCLSER SLAIARGRGK SPSTEEPLSL LDDMNHCYSR LRELVPGVPR
GTQLSQVEIL QRVIDYILDL QVVLAEPAPG PPDGPHLPIQ TAELTPELVI SKDKRSFCH
