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P41136

- ID2_MOUSE

UniProt

P41136 - ID2_MOUSE

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
  1. 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. protein binding Source: UniProtKB

    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

    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. chromatin Source: Ensembl
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: Ensembl
    4. nucleus Source: MGI
    5. protein complex Source: UniProtKB

    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

    ArrayExpressiP41136.
    BgeeiP41136.
    CleanExiMM_ID2.
    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

    Protein-protein interaction databases

    BioGridi200506. 8 interactions.
    DIPiDIP-167N.
    IntActiP41136. 7 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

    MKAFSPVRSV RKNSLSDHSL GISRSKTPVD DPMSLLYNMN DCYSKLKELV    50
    PSIPQNKKVT KMEILQHVID YILDLQIALD SHPTIVSLHH QRPGQNQASR 100
    TPLTTLNTDI SILSLQASEF PSELMSNDSK VLCG 134
    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.

    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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. 7 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

    ArrayExpressi P41136.
    Bgeei P41136.
    CleanExi MM_ID2.
    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

    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: October 1, 2014
    This is version 130 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