ID2_HUMAN
ID ID2_HUMAN Reviewed; 134 AA.
AC Q02363;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1995, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=DNA-binding protein inhibitor ID-2;
DE AltName: Full=Class B basic helix-loop-helix protein 26;
DE Short=bHLHb26;
DE AltName: Full=Inhibitor of DNA binding 2;
DE AltName: Full=Inhibitor of differentiation 2;
GN Name=ID2; Synonyms=BHLHB26;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung;
RX PubMed=8294468; DOI=10.1016/s0021-9258(17)42146-6;
RA Hara E., Yamaguchi T., Nojima H., Ide T., Campisi J., Okayama H., Oda K.;
RT "Id-related genes encoding helix-loop-helix proteins are required for G1
RT progression and are repressed in senescent human fibroblasts.";
RL J. Biol. Chem. 269:2139-2145(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1741406; DOI=10.1073/pnas.89.4.1512;
RA Biggs J., Murphy E.V., Israel M.A.;
RT "A human Id-like helix-loop-helix protein expressed during early
RT development.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1512-1516(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Hippocampus;
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 NR0B2.
RX PubMed=14752053; DOI=10.1210/me.2003-0311;
RA Kim J.Y., Chu K., Kim H.J., Seong H.A., Park K.C., Sanyal S., Takeda J.,
RA Ha H., Shong M., Tsai M.J., Choi H.S.;
RT "Orphan nuclear receptor small heterodimer partner, a novel corepressor for
RT a basic helix-loop-helix transcription factor BETA2/neuroD.";
RL Mol. Endocrinol. 18:776-790(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CLOCK AND ARNTL.
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).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
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:20861012}.
CC -!- SUBUNIT: Heterodimer with other HLH proteins. Interacts with GATA4,
CC IFI204 and NKX2-5 (By similarity). Interacts with NR0B2. Interacts with
CC CLOCK and ARNTL/BMAL1. {ECO:0000250, ECO:0000269|PubMed:14752053,
CC ECO:0000269|PubMed:20861012}.
CC -!- INTERACTION:
CC Q02363; Q6XD76: ASCL4; NbExp=3; IntAct=EBI-713450, EBI-10254793;
CC Q02363; Q6P5X5: C22orf39; NbExp=3; IntAct=EBI-713450, EBI-7317823;
CC Q02363; O95273: CCNDBP1; NbExp=4; IntAct=EBI-713450, EBI-748961;
CC Q02363; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-713450, EBI-744099;
CC Q02363; Q9NW38: FANCL; NbExp=3; IntAct=EBI-713450, EBI-2339898;
CC Q02363; P11362-2: FGFR1; NbExp=3; IntAct=EBI-713450, EBI-25852941;
CC Q02363; Q9BVV2: FNDC11; NbExp=3; IntAct=EBI-713450, EBI-744935;
CC Q02363; O43559: FRS3; NbExp=3; IntAct=EBI-713450, EBI-725515;
CC Q02363; Q5SUL5: HLA-A; NbExp=3; IntAct=EBI-713450, EBI-8561769;
CC Q02363; O43464: HTRA2; NbExp=3; IntAct=EBI-713450, EBI-517086;
CC Q02363; P42858: HTT; NbExp=6; IntAct=EBI-713450, EBI-466029;
CC Q02363; Q92993: KAT5; NbExp=3; IntAct=EBI-713450, EBI-399080;
CC Q02363; Q8TAP4-4: LMO3; NbExp=3; IntAct=EBI-713450, EBI-11742507;
CC Q02363; A6NI15: MSGN1; NbExp=3; IntAct=EBI-713450, EBI-11991020;
CC Q02363; Q96HC4: PDLIM5; NbExp=5; IntAct=EBI-713450, EBI-751267;
CC Q02363; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-713450, EBI-79165;
CC Q02363; Q13563: PKD2; NbExp=7; IntAct=EBI-713450, EBI-7813714;
CC Q02363; D3DTS7: PMP22; NbExp=3; IntAct=EBI-713450, EBI-25882629;
CC Q02363; P62937-2: PPIA; NbExp=3; IntAct=EBI-713450, EBI-25884072;
CC Q02363; P23284: PPIB; NbExp=3; IntAct=EBI-713450, EBI-359252;
CC Q02363; P17252: PRKCA; NbExp=3; IntAct=EBI-713450, EBI-1383528;
CC Q02363; Q15047-2: SETDB1; NbExp=3; IntAct=EBI-713450, EBI-9090795;
CC Q02363; Q13148: TARDBP; NbExp=6; IntAct=EBI-713450, EBI-372899;
CC Q02363; Q99081: TCF12; NbExp=2; IntAct=EBI-713450, EBI-722877;
CC Q02363; P15923-1: TCF3; NbExp=3; IntAct=EBI-713450, EBI-769645;
CC Q02363; P15884: TCF4; NbExp=3; IntAct=EBI-713450, EBI-533224;
CC Q02363; Q9BT92: TCHP; NbExp=3; IntAct=EBI-713450, EBI-740781;
CC Q02363; P61981: YWHAG; NbExp=3; IntAct=EBI-713450, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P41136}. Nucleus
CC {ECO:0000250|UniProtKB:P41136}.
CC -!- TISSUE SPECIFICITY: Highly expressed in early fetal tissues, including
CC those of the central nervous system.
CC -!- DEVELOPMENTAL STAGE: Found in most early fetal tissues but not in the
CC corresponding mature tissues.
CC -!- DOMAIN: The bHLH domain is essential for its repressor activity towards
CC the CLOCK-ARNTL/BMAL1 heterodimer. {ECO:0000250}.
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; D13891; BAA02990.1; -; mRNA.
DR EMBL; M97796; AAA58681.1; -; mRNA.
DR EMBL; BC030639; AAH30639.1; -; mRNA.
DR CCDS; CCDS1659.1; -.
DR PIR; A40227; A40227.
DR PIR; JC2007; JC2007.
DR RefSeq; NP_002157.2; NM_002166.4.
DR PDB; 4AYA; X-ray; 2.10 A; A/B=1-82.
DR PDBsum; 4AYA; -.
DR AlphaFoldDB; Q02363; -.
DR BMRB; Q02363; -.
DR SMR; Q02363; -.
DR BioGRID; 109624; 89.
DR DIP; DIP-46874N; -.
DR ELM; Q02363; -.
DR IntAct; Q02363; 61.
DR MINT; Q02363; -.
DR STRING; 9606.ENSP00000234091; -.
DR iPTMnet; Q02363; -.
DR PhosphoSitePlus; Q02363; -.
DR BioMuta; ID2; -.
DR DMDM; 729806; -.
DR jPOST; Q02363; -.
DR MassIVE; Q02363; -.
DR PaxDb; Q02363; -.
DR PeptideAtlas; Q02363; -.
DR PRIDE; Q02363; -.
DR ProteomicsDB; 58083; -.
DR Antibodypedia; 12350; 468 antibodies from 38 providers.
DR DNASU; 3398; -.
DR Ensembl; ENST00000234091.8; ENSP00000234091.4; ENSG00000115738.10.
DR Ensembl; ENST00000331129.3; ENSP00000385465.2; ENSG00000115738.10.
DR Ensembl; ENST00000396290.2; ENSP00000379585.1; ENSG00000115738.10.
DR GeneID; 3398; -.
DR KEGG; hsa:3398; -.
DR MANE-Select; ENST00000396290.2; ENSP00000379585.1; NM_002166.5; NP_002157.2.
DR CTD; 3398; -.
DR DisGeNET; 3398; -.
DR GeneCards; ID2; -.
DR HGNC; HGNC:5361; ID2.
DR HPA; ENSG00000115738; Tissue enhanced (parathyroid).
DR MIM; 600386; gene.
DR neXtProt; NX_Q02363; -.
DR OpenTargets; ENSG00000115738; -.
DR PharmGKB; PA29609; -.
DR VEuPathDB; HostDB:ENSG00000115738; -.
DR eggNOG; ENOG502RZP5; Eukaryota.
DR GeneTree; ENSGT00940000156464; -.
DR HOGENOM; CLU_116790_2_1_1; -.
DR InParanoid; Q02363; -.
DR OMA; SFRKNGA; -.
DR OrthoDB; 1624054at2759; -.
DR PhylomeDB; Q02363; -.
DR TreeFam; TF326217; -.
DR PathwayCommons; Q02363; -.
DR Reactome; R-HSA-9031628; NGF-stimulated transcription.
DR SignaLink; Q02363; -.
DR SIGNOR; Q02363; -.
DR BioGRID-ORCS; 3398; 24 hits in 1071 CRISPR screens.
DR ChiTaRS; ID2; human.
DR GeneWiki; ID2; -.
DR GenomeRNAi; 3398; -.
DR Pharos; Q02363; Tbio.
DR PRO; PR:Q02363; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q02363; protein.
DR Bgee; ENSG00000115738; Expressed in popliteal artery and 205 other tissues.
DR ExpressionAtlas; Q02363; baseline and differential.
DR Genevisible; Q02363; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0000791; C:euchromatin; ISS:ARUK-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0032991; C:protein-containing complex; ISS: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; ISS:ARUK-UCL.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISS:ARUK-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0003166; P:bundle of His development; ISS:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0090398; P:cellular senescence; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007623; P:circadian rhythm; ISS:ARUK-UCL.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; ISS:UniProtKB.
DR GO; GO:0061031; P:endodermal digestive tract morphogenesis; ISS:UniProtKB.
DR GO; GO:0043153; P:entrainment of circadian clock by photoperiod; ISS:UniProtKB.
DR GO; GO:0043353; P:enucleate erythrocyte differentiation; ISS:ARUK-UCL.
DR GO; GO:0061030; P:epithelial cell differentiation involved in mammary gland alveolus development; ISS:UniProtKB.
DR GO; GO:0007507; P:heart development; ISS:BHF-UCL.
DR GO; GO:0045475; P:locomotor rhythm; ISS:UniProtKB.
DR GO; GO:0060749; P:mammary gland alveolus development; ISS:UniProtKB.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045578; P:negative regulation of B cell differentiation; ISS:ARUK-UCL.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; IDA:GDB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0051148; P:negative regulation of muscle cell differentiation; ISS:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:ARUK-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:GDB.
DR GO; GO:0048663; P:neuron fate commitment; ISS:UniProtKB.
DR GO; GO:0021772; P:olfactory bulb development; ISS:ARUK-UCL.
DR GO; GO:0048711; P:positive regulation of astrocyte differentiation; ISS:ARUK-UCL.
DR GO; GO:0045777; P:positive regulation of blood pressure; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:ARUK-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; ISS:ARUK-UCL.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISS:UniProtKB.
DR GO; GO:0071931; P:positive regulation of transcription involved in G1/S transition of mitotic cell cycle; IC:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0019216; P:regulation of lipid metabolic process; ISS:UniProtKB.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; ISS:UniProtKB.
DR GO; GO:0045664; P:regulation of neuron differentiation; ISS:UniProtKB.
DR DisProt; DP02697; -.
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 3D-structure; Biological rhythms; Cytoplasm; Developmental protein;
KW Nucleus; Phosphoprotein; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..134
FT /note="DNA-binding protein inhibitor ID-2"
FT /id="PRO_0000127240"
FT DOMAIN 23..75
FT /note="bHLH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00981"
FT MOTIF 106..115
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 25
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P41136"
FT CONFLICT 68
FT /note="V -> L (in Ref. 2; AAA58681)"
FT /evidence="ECO:0000305"
FT CONFLICT 98
FT /note="A -> R (in Ref. 2; AAA58681)"
FT /evidence="ECO:0000305"
FT HELIX 32..49
FT /evidence="ECO:0007829|PDB:4AYA"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:4AYA"
FT HELIX 61..80
FT /evidence="ECO:0007829|PDB:4AYA"
SQ SEQUENCE 134 AA; 14917 MW; A0D98B96396EB11E CRC64;
MKAFSPVRSV RKNSLSDHSL GISRSKTPVD DPMSLLYNMN DCYSKLKELV PSIPQNKKVS
KMEILQHVID YILDLQIALD SHPTIVSLHH QRPGQNQASR TPLTTLNTDI SILSLQASEF
PSELMSNDSK ALCG
