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Q02363

- ID2_HUMAN

UniProt

Q02363 - ID2_HUMAN

Protein

DNA-binding protein inhibitor ID-2

Gene

ID2

Organism
Homo sapiens (Human)
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.1 Publication

    GO - Molecular functioni

    1. ion channel binding Source: BHF-UCL
    2. protein binding Source: UniProtKB

    GO - Biological processi

    1. adipose tissue development Source: Ensembl
    2. bundle of His development Source: Ensembl
    3. cell maturation Source: Ensembl
    4. cellular response to lithium ion Source: Ensembl
    5. cellular senescence Source: UniProtKB
    6. circadian regulation of gene expression Source: UniProtKB
    7. embryonic digestive tract morphogenesis Source: UniProtKB
    8. endodermal digestive tract morphogenesis Source: UniProtKB
    9. entrainment of circadian clock by photoperiod Source: UniProtKB
    10. enucleate erythrocyte differentiation Source: Ensembl
    11. epithelial cell differentiation involved in mammary gland alveolus development Source: UniProtKB
    12. locomotor rhythm Source: UniProtKB
    13. mammary gland alveolus development Source: UniProtKB
    14. mammary gland epithelial cell proliferation Source: UniProtKB
    15. membranous septum morphogenesis Source: Ensembl
    16. metanephros development Source: Ensembl
    17. multicellular organismal development Source: ProtInc
    18. natural killer cell differentiation Source: Ensembl
    19. negative regulation of B cell differentiation Source: Ensembl
    20. negative regulation of DNA binding Source: Ensembl
    21. negative regulation of gene expression Source: UniProtKB
    22. negative regulation of neural precursor cell proliferation Source: UniProtKB
    23. negative regulation of neuron differentiation Source: UniProtKB
    24. negative regulation of oligodendrocyte differentiation Source: Ensembl
    25. negative regulation of osteoblast differentiation Source: Ensembl
    26. negative regulation of sequence-specific DNA binding transcription factor activity Source: GDB
    27. negative regulation of transcription, DNA-templated Source: GDB
    28. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
    29. neuron fate commitment Source: UniProtKB
    30. olfactory bulb development Source: Ensembl
    31. oligodendrocyte development Source: Ensembl
    32. Peyer's patch development Source: Ensembl
    33. positive regulation of astrocyte differentiation Source: Ensembl
    34. positive regulation of blood pressure Source: UniProtKB
    35. positive regulation of cell cycle Source: Ensembl
    36. positive regulation of cell cycle arrest Source: UniProtKB
    37. positive regulation of erythrocyte differentiation Source: Ensembl
    38. positive regulation of fat cell differentiation Source: Ensembl
    39. positive regulation of gene expression Source: UniProtKB
    40. positive regulation of macrophage differentiation Source: Ensembl
    41. positive regulation of smooth muscle cell proliferation Source: UniProtKB
    42. positive regulation of transcription, DNA-templated Source: UniProtKB
    43. positive regulation of transcription involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
    44. regulation of circadian rhythm Source: UniProtKB
    45. regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
    46. 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):
    Class B basic helix-loop-helix protein 26
    Short name:
    bHLHb26
    Inhibitor of DNA binding 2
    Inhibitor of differentiation 2
    Gene namesi
    Name:ID2
    Synonyms:BHLHB26
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:5361. ID2.

    Subcellular locationi

    Cytoplasm 1 Publication. Nucleus 1 PublicationPROSITE-ProRule annotation

    GO - Cellular componenti

    1. centrosome Source: HPA
    2. chromatin Source: Ensembl
    3. cytoplasm Source: UniProtKB
    4. cytosol Source: BHF-UCL
    5. nucleus Source: BHF-UCL
    6. protein complex Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29609.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 134134DNA-binding protein inhibitor ID-2PRO_0000127240Add
    BLAST

    Proteomic databases

    MaxQBiQ02363.
    PaxDbiQ02363.
    PRIDEiQ02363.

    PTM databases

    PhosphoSiteiQ02363.

    Expressioni

    Tissue specificityi

    Highly expressed in early fetal tissues, including those of the central nervous system.

    Developmental stagei

    Found in most early fetal tissues but not in the corresponding mature tissues.

    Gene expression databases

    ArrayExpressiQ02363.
    BgeeiQ02363.
    CleanExiHS_ID2.
    GenevestigatoriQ02363.

    Organism-specific databases

    HPAiHPA027612.
    HPA028681.

    Interactioni

    Subunit structurei

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

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CCNDBP1O952734EBI-713450,EBI-748961
    TCF3P15923-13EBI-713450,EBI-769645

    Protein-protein interaction databases

    BioGridi109624. 35 interactions.
    DIPiDIP-46874N.
    IntActiQ02363. 14 interactions.
    MINTiMINT-1372728.
    STRINGi9606.ENSP00000234091.

    Structurei

    Secondary structure

    1
    134
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi32 – 4918
    Beta strandi55 – 573
    Helixi61 – 8020

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4AYAX-ray2.10A/B1-82[»]
    ProteinModelPortaliQ02363.
    SMRiQ02363. Positions 30-82.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

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

    Motif

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

    Domaini

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

    Sequence similaritiesi

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

    Phylogenomic databases

    eggNOGiNOG76382.
    HOGENOMiHOG000234788.
    HOVERGENiHBG009009.
    InParanoidiQ02363.
    KOiK17693.
    OMAiFPSEFMS.
    OrthoDBiEOG7X9G8G.
    PhylomeDBiQ02363.
    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.

    Q02363-1 [UniParc]FASTAAdd to Basket

    « Hide

    MKAFSPVRSV RKNSLSDHSL GISRSKTPVD DPMSLLYNMN DCYSKLKELV    50
    PSIPQNKKVS KMEILQHVID YILDLQIALD SHPTIVSLHH QRPGQNQASR 100
    TPLTTLNTDI SILSLQASEF PSELMSNDSK ALCG 134
    Length:134
    Mass (Da):14,917
    Last modified:February 1, 1995 - v1
    Checksum:iA0D98B96396EB11E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti68 – 681V → L in AAA58681. (PubMed:1741406)Curated
    Sequence conflicti98 – 981A → R in AAA58681. (PubMed:1741406)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D13891 mRNA. Translation: BAA02990.1.
    M97796 mRNA. Translation: AAA58681.1.
    BC030639 mRNA. Translation: AAH30639.1.
    CCDSiCCDS1659.1.
    PIRiA40227.
    JC2007.
    RefSeqiNP_002157.2. NM_002166.4.
    UniGeneiHs.180919.
    Hs.726053.

    Genome annotation databases

    EnsembliENST00000234091; ENSP00000234091; ENSG00000115738.
    ENST00000331129; ENSP00000385465; ENSG00000115738.
    ENST00000396290; ENSP00000379585; ENSG00000115738.
    GeneIDi3398.
    KEGGihsa:3398.
    UCSCiuc002qza.3. human.

    Polymorphism databases

    DMDMi729806.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    D13891 mRNA. Translation: BAA02990.1 .
    M97796 mRNA. Translation: AAA58681.1 .
    BC030639 mRNA. Translation: AAH30639.1 .
    CCDSi CCDS1659.1.
    PIRi A40227.
    JC2007.
    RefSeqi NP_002157.2. NM_002166.4.
    UniGenei Hs.180919.
    Hs.726053.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4AYA X-ray 2.10 A/B 1-82 [» ]
    ProteinModelPortali Q02363.
    SMRi Q02363. Positions 30-82.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 109624. 35 interactions.
    DIPi DIP-46874N.
    IntActi Q02363. 14 interactions.
    MINTi MINT-1372728.
    STRINGi 9606.ENSP00000234091.

    PTM databases

    PhosphoSitei Q02363.

    Polymorphism databases

    DMDMi 729806.

    Proteomic databases

    MaxQBi Q02363.
    PaxDbi Q02363.
    PRIDEi Q02363.

    Protocols and materials databases

    DNASUi 3398.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000234091 ; ENSP00000234091 ; ENSG00000115738 .
    ENST00000331129 ; ENSP00000385465 ; ENSG00000115738 .
    ENST00000396290 ; ENSP00000379585 ; ENSG00000115738 .
    GeneIDi 3398.
    KEGGi hsa:3398.
    UCSCi uc002qza.3. human.

    Organism-specific databases

    CTDi 3398.
    GeneCardsi GC02P008818.
    H-InvDB HIX0204445.
    HGNCi HGNC:5361. ID2.
    HPAi HPA027612.
    HPA028681.
    MIMi 600386. gene.
    neXtProti NX_Q02363.
    PharmGKBi PA29609.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG76382.
    HOGENOMi HOG000234788.
    HOVERGENi HBG009009.
    InParanoidi Q02363.
    KOi K17693.
    OMAi FPSEFMS.
    OrthoDBi EOG7X9G8G.
    PhylomeDBi Q02363.
    TreeFami TF326217.

    Miscellaneous databases

    GeneWikii ID2.
    GenomeRNAii 3398.
    NextBioi 13428.
    PROi Q02363.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q02363.
    Bgeei Q02363.
    CleanExi HS_ID2.
    Genevestigatori Q02363.

    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-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts."
      Hara E., Yamaguchi T., Nojima H., Ide T., Campisi J., Okayama H., Oda K.
      J. Biol. Chem. 269:2139-2145(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Lung.
    2. "A human Id-like helix-loop-helix protein expressed during early development."
      Biggs J., Murphy E.V., Israel M.A.
      Proc. Natl. Acad. Sci. U.S.A. 89:1512-1516(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    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].
      Tissue: Hippocampus.
    4. "Orphan nuclear receptor small heterodimer partner, a novel corepressor for a basic helix-loop-helix transcription factor BETA2/neuroD."
      Kim J.Y., Chu K., Kim H.J., Seong H.A., Park K.C., Sanyal S., Takeda J., Ha H., Shong M., Tsai M.J., Choi H.S.
      Mol. Endocrinol. 18:776-790(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NR0B2.
    5. "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, INTERACTION WITH CLOCK AND ARNTL.

    Entry informationi

    Entry nameiID2_HUMAN
    AccessioniPrimary (citable) accession number: Q02363
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 132 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3