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Protein

DNA-binding protein inhibitor ID-2

Gene

Id2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional regulator (lacking a basic DNA binding domain) which negatively regulates the basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibiting their DNA binding and transcriptional activity. Implicated in regulating a variety of cellular processes, including cellular growth, senescence, differentiation, apoptosis, angiogenesis, and neoplastic transformation. Inhibits skeletal muscle and cardiac myocyte differentiation. Regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer. Restricts the CLOCK and ARNTL/BMAL1 localization to the cytoplasm. Plays a role in both the input and output pathways of the circadian clock: in the input component, is involved in modulating the magnitude of photic entrainment and in the output component, contributes to the regulation of a variety of liver clock-controlled genes involved in lipid metabolism.4 Publications

GO - Molecular functioni

  1. ion channel binding Source: MGI

GO - Biological processi

  1. adipose tissue development Source: MGI
  2. bundle of His development Source: MGI
  3. cell development Source: MGI
  4. cell maturation Source: MGI
  5. cellular response to lithium ion Source: MGI
  6. cellular senescence Source: UniProtKB
  7. circadian regulation of gene expression Source: UniProtKB
  8. circadian rhythm Source: UniProtKB
  9. embryonic digestive tract morphogenesis Source: UniProtKB
  10. endodermal digestive tract morphogenesis Source: UniProtKB
  11. entrainment of circadian clock Source: MGI
  12. entrainment of circadian clock by photoperiod Source: UniProtKB
  13. enucleate erythrocyte differentiation Source: MGI
  14. epithelial cell differentiation involved in mammary gland alveolus development Source: UniProtKB
  15. heart development Source: MGI
  16. leukocyte differentiation Source: MGI
  17. locomotor rhythm Source: UniProtKB
  18. lymph node development Source: MGI
  19. mammary gland alveolus development Source: UniProtKB
  20. mammary gland epithelial cell proliferation Source: UniProtKB
  21. membranous septum morphogenesis Source: BHF-UCL
  22. metanephros development Source: MGI
  23. natural killer cell differentiation Source: MGI
  24. negative regulation of B cell differentiation Source: MGI
  25. negative regulation of DNA binding Source: MGI
  26. negative regulation of gene expression Source: UniProtKB
  27. negative regulation of neural precursor cell proliferation Source: UniProtKB
  28. negative regulation of neuron differentiation Source: UniProtKB
  29. negative regulation of oligodendrocyte differentiation Source: MGI
  30. negative regulation of osteoblast differentiation Source: MGI
  31. negative regulation of sequence-specific DNA binding transcription factor activity Source: MGI
  32. negative regulation of transcription, DNA-templated Source: UniProtKB
  33. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  34. neuron fate commitment Source: UniProtKB
  35. olfactory bulb development Source: MGI
  36. oligodendrocyte development Source: MGI
  37. Peyer's patch development Source: MGI
  38. positive regulation of astrocyte differentiation Source: MGI
  39. positive regulation of blood pressure Source: UniProtKB
  40. positive regulation of cell cycle arrest Source: UniProtKB
  41. positive regulation of erythrocyte differentiation Source: MGI
  42. positive regulation of fat cell differentiation Source: MGI
  43. positive regulation of gene expression Source: UniProtKB
  44. positive regulation of macrophage differentiation Source: MGI
  45. positive regulation of smooth muscle cell proliferation Source: UniProtKB
  46. positive regulation of transcription, DNA-templated Source: UniProtKB
  47. regulation of circadian rhythm Source: UniProtKB
  48. regulation of G1/S transition of mitotic cell cycle Source: MGI
  49. regulation of lipid metabolic process Source: UniProtKB
  50. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Repressor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
DNA-binding protein inhibitor ID-2
Alternative name(s):
Inhibitor of DNA binding 2
Inhibitor of differentiation 2
Gene namesi
Name:Id2
Synonyms:Id-2, Idb2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 12

Organism-specific databases

MGIiMGI:96397. Id2.

Subcellular locationi

GO - Cellular componenti

  1. centrosome Source: MGI
  2. chromatin Source: Ensembl
  3. cytoplasm Source: UniProtKB
  4. cytosol Source: MGI
  5. microtubule cytoskeleton Source: MGI
  6. nucleoplasm Source: MGI
  7. nucleus Source: MGI
  8. protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice exhibit disrupted locomotor rhythms, reduced locomotor activity, enhanced phase shifts and an increased rate of entrainment when subjected to a large delay of the photoschedule. Show a reduction in lipid storage in the liver and white adipose tissue.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 134134DNA-binding protein inhibitor ID-2PRO_0000127242Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141PhosphoserineBy similarity

Post-translational modificationi

Polyubiquitinated; which is favored by Ifi204 and leads to proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PRIDEiP41136.

PTM databases

PhosphoSiteiP41136.

Expressioni

Inductioni

Expressed in a circadian manner in the liver with peak levels seen at CT12 (at protein level). Expressed in a circadian manner in the suprachiasmatic nucleus (SCN) of the brain and heart with peak levels seen between CT16 and CT20 in the SCN and between CT8 and CT12 in the heart.2 Publications

Gene expression databases

BgeeiP41136.
CleanExiMM_ID2.
ExpressionAtlasiP41136. baseline and differential.
GenevestigatoriP41136.

Interactioni

Subunit structurei

Heterodimer with other HLH proteins. Interacts with NR0B2. Interacts with CLOCK and ARNTL/BMAL1 (By similarity). Interacts with GATA4, IFI204 and NKX2-5.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Olig1Q9JKN55EBI-309167,EBI-1213712
Olig2Q9EQW64EBI-309167,EBI-1213740
Ppp1caP621372EBI-309167,EBI-357187
Tcf3P15806-26EBI-309167,EBI-413585

Protein-protein interaction databases

BioGridi200506. 8 interactions.
DIPiDIP-167N.
IntActiP41136. 9 interactions.
MINTiMINT-217665.

Structurei

3D structure databases

ProteinModelPortaliP41136.
SMRiP41136. Positions 30-77.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini23 – 7553bHLHPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni30 – 8354Interaction with IFI204Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi106 – 11510Nuclear export signal

Domaini

The bHLH domain is essential for its repressor activity towards the CLOCK-ARNTL/BMAL1 heterodimer.

Sequence similaritiesi

Contains 1 bHLH (basic helix-loop-helix) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiNOG76382.
HOGENOMiHOG000234788.
HOVERGENiHBG009009.
InParanoidiP41136.
KOiK17693.
OMAiKNVSKME.
OrthoDBiEOG7X9G8G.
PhylomeDBiP41136.
TreeFamiTF326217.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR026052. DNA-bd_prot-inh.
[Graphical view]
PANTHERiPTHR11723. PTHR11723. 1 hit.
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P41136-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKAFSPVRSV RKNSLSDHSL GISRSKTPVD DPMSLLYNMN DCYSKLKELV
60 70 80 90 100
PSIPQNKKVT KMEILQHVID YILDLQIALD SHPTIVSLHH QRPGQNQASR
110 120 130
TPLTTLNTDI SILSLQASEF PSELMSNDSK VLCG
Length:134
Mass (Da):14,959
Last modified:May 29, 2000 - v3
Checksum:iA0D98D54F2686CC5
GO

Sequence cautioni

The sequence AAA79771.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti5 – 84SPVR → RSGE in AAA79771 (PubMed:1922066).Curated
Sequence conflicti102 – 1021P → R in AAA79771 (PubMed:1922066).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M69293 mRNA. Translation: AAA79771.1. Different initiation.
AF077860 Genomic DNA. Translation: AAD05214.1.
BC006921 mRNA. Translation: AAH06921.1.
BC053699 mRNA. Translation: AAH53699.1.
CCDSiCCDS25846.1.
RefSeqiNP_034626.1. NM_010496.3.
UniGeneiMm.34871.

Genome annotation databases

EnsembliENSMUST00000020974; ENSMUSP00000020974; ENSMUSG00000020644.
GeneIDi15902.
KEGGimmu:15902.
UCSCiuc007nfe.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M69293 mRNA. Translation: AAA79771.1. Different initiation.
AF077860 Genomic DNA. Translation: AAD05214.1.
BC006921 mRNA. Translation: AAH06921.1.
BC053699 mRNA. Translation: AAH53699.1.
CCDSiCCDS25846.1.
RefSeqiNP_034626.1. NM_010496.3.
UniGeneiMm.34871.

3D structure databases

ProteinModelPortaliP41136.
SMRiP41136. Positions 30-77.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi200506. 8 interactions.
DIPiDIP-167N.
IntActiP41136. 9 interactions.
MINTiMINT-217665.

PTM databases

PhosphoSiteiP41136.

Proteomic databases

PRIDEiP41136.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000020974; ENSMUSP00000020974; ENSMUSG00000020644.
GeneIDi15902.
KEGGimmu:15902.
UCSCiuc007nfe.2. mouse.

Organism-specific databases

CTDi3398.
MGIiMGI:96397. Id2.

Phylogenomic databases

eggNOGiNOG76382.
HOGENOMiHOG000234788.
HOVERGENiHBG009009.
InParanoidiP41136.
KOiK17693.
OMAiKNVSKME.
OrthoDBiEOG7X9G8G.
PhylomeDBiP41136.
TreeFamiTF326217.

Miscellaneous databases

NextBioi288624.
PROiP41136.
SOURCEiSearch...

Gene expression databases

BgeeiP41136.
CleanExiMM_ID2.
ExpressionAtlasiP41136. baseline and differential.
GenevestigatoriP41136.

Family and domain databases

Gene3Di4.10.280.10. 1 hit.
InterProiIPR011598. bHLH_dom.
IPR026052. DNA-bd_prot-inh.
[Graphical view]
PANTHERiPTHR11723. PTHR11723. 1 hit.
PfamiPF00010. HLH. 1 hit.
[Graphical view]
SMARTiSM00353. HLH. 1 hit.
[Graphical view]
SUPFAMiSSF47459. SSF47459. 1 hit.
PROSITEiPS50888. BHLH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Id proteins Id1 and Id2 selectively inhibit DNA binding by one class of helix-loop-helix proteins."
    Sun X.H., Copeland N.G., Jenkins N.A., Baltimore D.
    Mol. Cell. Biol. 11:5603-5611(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "The mouse Id2 and Id4 genes: structural organization and chromosomal localization."
    Mantani A., Hernandez M.-C., Kuo W.-L., Israel M.A.
    Gene 222:229-235(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N-3.
    Tissue: Mammary gland.
  4. "The MyoD-inducible p204 protein overcomes the inhibition of myoblast differentiation by Id proteins."
    Liu C.-J., Ding B., Wang H., Lengyel P.
    Mol. Cell. Biol. 22:2893-2905(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH IFI204.
  5. "Nucleo-cytoplasmic shuttling of Id2, a negative regulator of basic helix-loop-helix transcription factors."
    Kurooka H., Yokota Y.
    J. Biol. Chem. 280:4313-4320(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, NUCLEAR EXPORT SIGNAL.
  6. "p204 protein overcomes the inhibition of the differentiation of P19 murine embryonal carcinoma cells to beating cardiac myocytes by Id proteins."
    Ding B., Liu C.-J., Huang Y., Yu J., Kong W., Lengyel P.
    J. Biol. Chem. 281:14893-14906(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GATA4 AND NKX2-5.
  7. "A role for Id2 in regulating photic entrainment of the mammalian circadian system."
    Duffield G.E., Watson N.P., Mantani A., Peirson S.N., Robles-Murguia M., Loros J.J., Israel M.A., Dunlap J.C.
    Curr. Biol. 19:297-304(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION, DISRUPTION PHENOTYPE.
  8. "ID2 (inhibitor of DNA binding 2) is a rhythmically expressed transcriptional repressor required for circadian clock output in mouse liver."
    Hou T.Y., Ward S.M., Murad J.M., Watson N.P., Israel M.A., Duffield G.E.
    J. Biol. Chem. 284:31735-31745(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION, DISRUPTION PHENOTYPE.
  9. "The transcriptional repressor ID2 can interact with the canonical clock components CLOCK and BMAL1 and mediate inhibitory effects on mPer1 expression."
    Ward S.M., Fernando S.J., Hou T.Y., Duffield G.E.
    J. Biol. Chem. 285:38987-39000(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, BHLH DOMAIN.

Entry informationi

Entry nameiID2_MOUSE
AccessioniPrimary (citable) accession number: P41136
Secondary accession number(s): O88604
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 1995
Last sequence update: May 29, 2000
Last modified: March 3, 2015
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.