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Protein

DNA-binding protein inhibitor ID-2

Gene

ID2

Organism
Homo sapiens (Human)
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.1 Publication

GO - Molecular functioni

  1. ion channel binding Source: BHF-UCL

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 arrest Source: UniProtKB
  36. positive regulation of erythrocyte differentiation Source: Ensembl
  37. positive regulation of fat cell differentiation Source: Ensembl
  38. positive regulation of gene expression Source: UniProtKB
  39. positive regulation of macrophage differentiation Source: Ensembl
  40. positive regulation of smooth muscle cell proliferation Source: UniProtKB
  41. positive regulation of transcription, DNA-templated Source: UniProtKB
  42. positive regulation of transcription involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
  43. regulation of circadian rhythm Source: UniProtKB
  44. regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
  45. regulation of lipid metabolic process Source: UniProtKB
  46. 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):
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 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:5361. ID2.

Subcellular locationi

Cytoplasm 1 Publication. Nucleus PROSITE-ProRule annotation1 Publication

GO - Cellular componenti

  1. centrosome Source: HPA
  2. chromatin Source: Ensembl
  3. cytoplasm Source: UniProtKB
  4. cytosol Source: BHF-UCL
  5. microtubule cytoskeleton Source: HPA
  6. nucleoplasm Source: HPA
  7. nucleus Source: BHF-UCL
  8. 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

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei14 – 141Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

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

BgeeiQ02363.
CleanExiHS_ID2.
ExpressionAtlasiQ02363. baseline and differential.
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
PKD2Q135637EBI-713450,EBI-7813714
TCF3P15923-13EBI-713450,EBI-769645

Protein-protein interaction databases

BioGridi109624. 35 interactions.
DIPiDIP-46874N.
IntActiQ02363. 15 interactions.
MINTiMINT-1372728.
STRINGi9606.ENSP00000234091.

Structurei

Secondary structure

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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.
OMAiKNVSKME.
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

        10         20         30         40         50
MKAFSPVRSV RKNSLSDHSL GISRSKTPVD DPMSLLYNMN DCYSKLKELV
60 70 80 90 100
PSIPQNKKVS KMEILQHVID YILDLQIALD SHPTIVSLHH QRPGQNQASR
110 120 130
TPLTTLNTDI SILSLQASEF PSELMSNDSK ALCG
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi109624. 35 interactions.
DIPiDIP-46874N.
IntActiQ02363. 15 interactions.
MINTiMINT-1372728.
STRINGi9606.ENSP00000234091.

PTM databases

PhosphoSiteiQ02363.

Polymorphism databases

DMDMi729806.

Proteomic databases

MaxQBiQ02363.
PaxDbiQ02363.
PRIDEiQ02363.

Protocols and materials databases

DNASUi3398.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi3398.
GeneCardsiGC02P008818.
H-InvDBHIX0204445.
HGNCiHGNC:5361. ID2.
HPAiHPA027612.
HPA028681.
MIMi600386. gene.
neXtProtiNX_Q02363.
PharmGKBiPA29609.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG76382.
HOGENOMiHOG000234788.
HOVERGENiHBG009009.
InParanoidiQ02363.
KOiK17693.
OMAiKNVSKME.
OrthoDBiEOG7X9G8G.
PhylomeDBiQ02363.
TreeFamiTF326217.

Miscellaneous databases

GeneWikiiID2.
GenomeRNAii3398.
NextBioi13428.
PROiQ02363.
SOURCEiSearch...

Gene expression databases

BgeeiQ02363.
CleanExiHS_ID2.
ExpressionAtlasiQ02363. baseline and differential.
GenevestigatoriQ02363.

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-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(1993) [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(1991) [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(2003) [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(2003) [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(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CLOCK AND ARNTL.
  6. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

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: March 4, 2015
This is version 137 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

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.