ID2_MOUSE
ID ID2_MOUSE Reviewed; 134 AA.
AC P41136; O88604;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=DNA-binding protein inhibitor ID-2;
DE AltName: Full=Inhibitor of DNA binding 2;
DE AltName: Full=Inhibitor of differentiation 2;
GN Name=Id2; Synonyms=Id-2, Idb2;
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=1922066; DOI=10.1128/mcb.11.11.5603-5611.1991;
RA Sun X.H., Copeland N.G., Jenkins N.A., Baltimore D.;
RT "Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of
RT helix-loop-helix proteins.";
RL Mol. Cell. Biol. 11:5603-5611(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9831657; DOI=10.1016/s0378-1119(98)00488-0;
RA Mantani A., Hernandez M.-C., Kuo W.-L., Israel M.A.;
RT "The mouse Id2 and Id4 genes: structural organization and chromosomal
RT localization.";
RL Gene 222:229-235(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary gland;
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 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 [5]
RP SUBCELLULAR LOCATION, AND NUCLEAR EXPORT SIGNAL.
RX PubMed=15563451; DOI=10.1074/jbc.m412614200;
RA Kurooka H., Yokota Y.;
RT "Nucleo-cytoplasmic shuttling of Id2, a negative regulator of basic helix-
RT loop-helix transcription factors.";
RL J. Biol. Chem. 280:4313-4320(2005).
RN [6]
RP FUNCTION, AND INTERACTION WITH GATA4 AND NKX2-5.
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 [7]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
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 [8]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19740747; DOI=10.1074/jbc.m109.013961;
RA Hou T.Y., Ward S.M., Murad J.M., Watson N.P., Israel M.A., Duffield G.E.;
RT "ID2 (inhibitor of DNA binding 2) is a rhythmically expressed
RT transcriptional repressor required for circadian clock output in mouse
RT liver.";
RL J. Biol. Chem. 284:31735-31745(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-25, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Lung, and Spleen;
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 [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND BHLH DOMAIN.
RX PubMed=20861012; DOI=10.1074/jbc.m110.175182;
RA Ward S.M., Fernando S.J., Hou T.Y., Duffield G.E.;
RT "The transcriptional repressor ID2 can interact with the canonical clock
RT components CLOCK and BMAL1 and mediate inhibitory effects on mPer1
RT expression.";
RL J. Biol. Chem. 285:38987-39000(2010).
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. Inhibits skeletal muscle and cardiac myocyte
CC differentiation. Regulates the circadian clock by repressing the
CC transcriptional activator activity of the CLOCK-ARNTL/BMAL1
CC heterodimer. Restricts the CLOCK and ARNTL/BMAL1 localization to the
CC cytoplasm. Plays a role in both the input and output pathways of the
CC circadian clock: in the input component, is involved in modulating the
CC magnitude of photic entrainment and in the output component,
CC contributes to the regulation of a variety of liver clock-controlled
CC genes involved in lipid metabolism. {ECO:0000269|PubMed:16556596,
CC ECO:0000269|PubMed:19217292, ECO:0000269|PubMed:19740747,
CC ECO:0000269|PubMed:20861012}.
CC -!- SUBUNIT: Heterodimer with other HLH proteins. Interacts with NR0B2.
CC Interacts with CLOCK and ARNTL/BMAL1 (By similarity). Interacts with
CC GATA4, IFI204 and NKX2-5. {ECO:0000250, ECO:0000269|PubMed:11940648,
CC ECO:0000269|PubMed:16556596}.
CC -!- INTERACTION:
CC P41136; Q9JKN5: Olig1; NbExp=5; IntAct=EBI-309167, EBI-1213712;
CC P41136; Q9EQW6: Olig2; NbExp=4; IntAct=EBI-309167, EBI-1213740;
CC P41136; P62137: Ppp1ca; NbExp=2; IntAct=EBI-309167, EBI-357187;
CC P41136; P15806: Tcf3; NbExp=2; IntAct=EBI-309167, EBI-81370;
CC P41136; P15806-2: Tcf3; NbExp=6; IntAct=EBI-309167, EBI-413585;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15563451,
CC ECO:0000269|PubMed:20861012}. Nucleus {ECO:0000269|PubMed:15563451}.
CC -!- INDUCTION: Expressed in a circadian manner in the liver with peak
CC levels seen at CT12 (at protein level). Expressed in a circadian manner
CC in the suprachiasmatic nucleus (SCN) of the brain and heart with peak
CC levels seen between CT16 and CT20 in the SCN and between CT8 and CT12
CC in the heart. {ECO:0000269|PubMed:19217292,
CC ECO:0000269|PubMed:19740747}.
CC -!- DOMAIN: The bHLH domain is essential for its repressor activity towards
CC the CLOCK-ARNTL/BMAL1 heterodimer.
CC -!- PTM: Polyubiquitinated; which is favored by Ifi204 and leads to
CC proteasomal degradation. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit disrupted locomotor rhythms, reduced
CC locomotor activity, enhanced phase shifts and an increased rate of
CC entrainment when subjected to a large delay of the photoschedule. Show
CC a reduction in lipid storage in the liver and white adipose tissue.
CC {ECO:0000269|PubMed:19217292, ECO:0000269|PubMed:19740747}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA79771.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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; M69293; AAA79771.1; ALT_INIT; mRNA.
DR EMBL; AF077860; AAD05214.1; -; Genomic_DNA.
DR EMBL; BC006921; AAH06921.1; -; mRNA.
DR EMBL; BC053699; AAH53699.1; -; mRNA.
DR CCDS; CCDS25846.1; -.
DR RefSeq; NP_034626.1; NM_010496.3.
DR AlphaFoldDB; P41136; -.
DR SMR; P41136; -.
DR BioGRID; 200506; 16.
DR DIP; DIP-167N; -.
DR IntAct; P41136; 18.
DR MINT; P41136; -.
DR STRING; 10090.ENSMUSP00000020974; -.
DR iPTMnet; P41136; -.
DR PhosphoSitePlus; P41136; -.
DR PaxDb; P41136; -.
DR PeptideAtlas; P41136; -.
DR PRIDE; P41136; -.
DR ProteomicsDB; 269526; -.
DR Antibodypedia; 12350; 468 antibodies from 38 providers.
DR DNASU; 15902; -.
DR Ensembl; ENSMUST00000020974; ENSMUSP00000020974; ENSMUSG00000020644.
DR Ensembl; ENSMUST00000221761; ENSMUSP00000152052; ENSMUSG00000020644.
DR GeneID; 15902; -.
DR KEGG; mmu:15902; -.
DR UCSC; uc007nfe.2; mouse.
DR CTD; 3398; -.
DR MGI; MGI:96397; Id2.
DR VEuPathDB; HostDB:ENSMUSG00000020644; -.
DR eggNOG; ENOG502RZP5; Eukaryota.
DR GeneTree; ENSGT00940000156464; -.
DR HOGENOM; CLU_116790_2_1_1; -.
DR InParanoid; P41136; -.
DR OMA; SFRKNGA; -.
DR OrthoDB; 1624054at2759; -.
DR PhylomeDB; P41136; -.
DR TreeFam; TF326217; -.
DR BioGRID-ORCS; 15902; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Id2; mouse.
DR PRO; PR:P41136; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P41136; protein.
DR Bgee; ENSMUSG00000020644; Expressed in vas deferens and 378 other tissues.
DR ExpressionAtlas; P41136; baseline and differential.
DR Genevisible; P41136; MM.
DR GO; GO:0000785; C:chromatin; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0000791; C:euchromatin; IDA:ARUK-UCL.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0046983; F:protein dimerization activity; IEA:InterPro.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:ARUK-UCL.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IDA:UniProtKB.
DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI.
DR GO; GO:0060612; P:adipose tissue development; IMP:MGI.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:MGI.
DR GO; GO:0048708; P:astrocyte differentiation; IMP:MGI.
DR GO; GO:0030183; P:B cell differentiation; IMP:MGI.
DR GO; GO:0003166; P:bundle of His development; IMP:MGI.
DR GO; GO:0048468; P:cell development; IGI:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0048469; P:cell maturation; IMP:MGI.
DR GO; GO:0048667; P:cell morphogenesis involved in neuron differentiation; IMP:MGI.
DR GO; GO:0071285; P:cellular response to lithium ion; IDA:MGI.
DR GO; GO:0090398; P:cellular senescence; IMP:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IMP:MGI.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IDA:UniProtKB.
DR GO; GO:0061031; P:endodermal digestive tract morphogenesis; IEP:UniProtKB.
DR GO; GO:0009649; P:entrainment of circadian clock; IMP:MGI.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; IMP:UniProtKB.
DR GO; GO:0043353; P:enucleate erythrocyte differentiation; IGI:MGI.
DR GO; GO:0061030; P:epithelial cell differentiation involved in mammary gland alveolus development; IMP:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:MGI.
DR GO; GO:0007507; P:heart development; IGI:MGI.
DR GO; GO:0002521; P:leukocyte differentiation; IMP:MGI.
DR GO; GO:0045475; P:locomotor rhythm; IMP:UniProtKB.
DR GO; GO:0048535; P:lymph node development; TAS:MGI.
DR GO; GO:0060749; P:mammary gland alveolus development; IMP:UniProtKB.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0003149; P:membranous septum morphogenesis; IMP:BHF-UCL.
DR GO; GO:0001656; P:metanephros development; IMP:MGI.
DR GO; GO:0001779; P:natural killer cell differentiation; IMP:MGI.
DR GO; GO:0045578; P:negative regulation of B cell differentiation; IMP:MGI.
DR GO; GO:1904797; P:negative regulation of core promoter binding; IDA:UniProtKB.
DR GO; GO:0043392; P:negative regulation of DNA binding; IDA:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; IDA:ARUK-UCL.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IMP:MGI.
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:ARUK-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0048663; P:neuron fate commitment; IMP:UniProtKB.
DR GO; GO:0021772; P:olfactory bulb development; IMP:MGI.
DR GO; GO:0014003; P:oligodendrocyte development; IMP:MGI.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:MGI.
DR GO; GO:0048541; P:Peyer's patch development; IGI:MGI.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; IMP:MGI.
DR GO; GO:0045777; P:positive regulation of blood pressure; IMP:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISO:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045648; P:positive regulation of erythrocyte differentiation; IMP:MGI.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IGI:MGI.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0010468; P:regulation of gene expression; IEP:UniProtKB.
DR GO; GO:0019216; P:regulation of lipid metabolic process; IMP:UniProtKB.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; IMP:UniProtKB.
DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:UniProtKB.
DR GO; GO:0001966; P:thigmotaxis; IMP:MGI.
DR GO; GO:0050872; P:white fat cell differentiation; IMP:MGI.
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; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..134
FT /note="DNA-binding protein inhibitor ID-2"
FT /id="PRO_0000127242"
FT DOMAIN 23..75
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT REGION 30..83
FT /note="Interaction with IFI204"
FT /evidence="ECO:0000269|PubMed:11940648"
FT MOTIF 106..115
FT /note="Nuclear export signal"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02363"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 5..8
FT /note="SPVR -> RSGE (in Ref. 1; AAA79771)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="P -> R (in Ref. 1; AAA79771)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 134 AA; 14959 MW; A0D98D54F2686CC5 CRC64;
MKAFSPVRSV RKNSLSDHSL GISRSKTPVD DPMSLLYNMN DCYSKLKELV PSIPQNKKVT
KMEILQHVID YILDLQIALD SHPTIVSLHH QRPGQNQASR TPLTTLNTDI SILSLQASEF
PSELMSNDSK VLCG
