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P41136

- ID2_MOUSE

UniProt

P41136 - ID2_MOUSE

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Protein

DNA-binding protein inhibitor ID-2

Gene

Id2

Organism
Mus musculus (Mouse)
Status
Reviewed - 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 - 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: Ensembl
  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 Source: Ensembl
  41. positive regulation of cell cycle arrest Source: UniProtKB
  42. positive regulation of erythrocyte differentiation Source: MGI
  43. positive regulation of fat cell differentiation Source: MGI
  44. positive regulation of gene expression Source: UniProtKB
  45. positive regulation of macrophage differentiation Source: MGI
  46. positive regulation of smooth muscle cell proliferation Source: UniProtKB
  47. positive regulation of transcription, DNA-templated Source: UniProtKB
  48. regulation of circadian rhythm Source: UniProtKB
  49. regulation of G1/S transition of mitotic cell cycle Source: Ensembl
  50. regulation of lipid metabolic process Source: UniProtKB
  51. 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: Chromosome 12

Organism-specific databases

MGIiMGI:96397. Id2.

Subcellular locationi

GO - Cellular componenti

  1. centrosome Source: Ensembl
  2. chromatin Source: Ensembl
  3. cytoplasm Source: UniProtKB
  4. cytosol Source: Ensembl
  5. nucleus Source: MGI
  6. 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

Post-translational modificationi

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

Keywords - PTMi

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 30-82.
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.
OMAiFPSEFMS.
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 30, 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 .
CCDSi CCDS25846.1.
RefSeqi NP_034626.1. NM_010496.3.
UniGenei Mm.34871.

3D structure databases

ProteinModelPortali P41136.
SMRi P41136. Positions 30-82.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 200506. 8 interactions.
DIPi DIP-167N.
IntActi P41136. 9 interactions.
MINTi MINT-217665.

PTM databases

PhosphoSitei P41136.

Proteomic databases

PRIDEi P41136.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000020974 ; ENSMUSP00000020974 ; ENSMUSG00000020644 .
GeneIDi 15902.
KEGGi mmu:15902.
UCSCi uc007nfe.2. mouse.

Organism-specific databases

CTDi 3398.
MGIi MGI:96397. Id2.

Phylogenomic databases

eggNOGi NOG76382.
HOGENOMi HOG000234788.
HOVERGENi HBG009009.
InParanoidi P41136.
KOi K17693.
OMAi FPSEFMS.
OrthoDBi EOG7X9G8G.
PhylomeDBi P41136.
TreeFami TF326217.

Miscellaneous databases

NextBioi 288624.
PROi P41136.
SOURCEi Search...

Gene expression databases

Bgeei P41136.
CleanExi MM_ID2.
ExpressionAtlasi P41136. baseline and differential.
Genevestigatori P41136.

Family and domain databases

Gene3Di 4.10.280.10. 1 hit.
InterProi IPR011598. bHLH_dom.
IPR026052. DNA-bd_prot-inh.
[Graphical view ]
PANTHERi PTHR11723. PTHR11723. 1 hit.
Pfami PF00010. HLH. 1 hit.
[Graphical view ]
SMARTi SM00353. HLH. 1 hit.
[Graphical view ]
SUPFAMi SSF47459. SSF47459. 1 hit.
PROSITEi PS50888. BHLH. 1 hit.
[Graphical view ]
ProtoNeti Search...

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(1991) [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(1998) [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(2004) [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(2002) [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(2005) [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(2006) [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(2009) [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(2009) [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(2010) [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: February 1, 1995
Last sequence update: May 30, 2000
Last modified: November 26, 2014
This is version 132 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