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Q02363

- ID2_HUMAN

UniProt

Q02363 - ID2_HUMAN

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Protein

DNA-binding protein inhibitor ID-2

Gene
ID2, BHLHB26
Organism
Homo sapiens (Human)
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.

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. embryonic digestive tract morphogenesis Source: UniProtKB
  7. endodermal digestive tract morphogenesis Source: UniProtKB
  8. entrainment of circadian clock Source: Ensembl
  9. enucleate erythrocyte differentiation Source: Ensembl
  10. epithelial cell differentiation involved in mammary gland alveolus development Source: UniProtKB
  11. mammary gland alveolus development Source: UniProtKB
  12. mammary gland epithelial cell proliferation Source: UniProtKB
  13. membranous septum morphogenesis Source: Ensembl
  14. metanephros development Source: Ensembl
  15. multicellular organismal development Source: ProtInc
  16. natural killer cell differentiation Source: Ensembl
  17. negative regulation of B cell differentiation Source: Ensembl
  18. negative regulation of DNA binding Source: Ensembl
  19. negative regulation of gene expression Source: UniProtKB
  20. negative regulation of neural precursor cell proliferation Source: UniProtKB
  21. negative regulation of neuron differentiation Source: UniProtKB
  22. negative regulation of oligodendrocyte differentiation Source: Ensembl
  23. negative regulation of osteoblast differentiation Source: Ensembl
  24. negative regulation of sequence-specific DNA binding transcription factor activity Source: GDB
  25. negative regulation of transcription, DNA-templated Source: GDB
  26. negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  27. neuron fate commitment Source: UniProtKB
  28. olfactory bulb development Source: Ensembl
  29. oligodendrocyte development Source: Ensembl
  30. Peyer's patch development Source: Ensembl
  31. positive regulation of astrocyte differentiation Source: Ensembl
  32. positive regulation of blood pressure Source: UniProtKB
  33. positive regulation of cell cycle Source: Ensembl
  34. positive regulation of cell cycle arrest Source: UniProtKB
  35. positive regulation of erythrocyte differentiation Source: Ensembl
  36. positive regulation of fat cell differentiation Source: Ensembl
  37. positive regulation of gene expression Source: UniProtKB
  38. positive regulation of macrophage differentiation Source: Ensembl
  39. positive regulation of smooth muscle cell proliferation Source: UniProtKB
  40. positive regulation of transcription, DNA-templated Source: UniProtKB
  41. positive regulation of transcription involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
  42. regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
  43. regulation of lipid metabolic process Source: Ensembl
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):
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

GO - Cellular componenti

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

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/BMAL1.1 Publication

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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini23 – 7553bHLHAdd
BLAST

Motif

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

Domaini

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

Sequence similaritiesi

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

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti68 – 681V → L in AAA58681. 1 Publication
Sequence conflicti98 – 981A → R in AAA58681. 1 Publication

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

« Hide 'large scale' publications
  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: September 3, 2014
This is version 131 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

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