UniProtKB - Q02363 (ID2_HUMAN)
Protein
DNA-binding protein inhibitor ID-2
Gene
ID2
Organism
Homo sapiens (Human)
Status
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
- ion channel binding Source: BHF-UCL
- protein dimerization activity Source: InterPro
- RNA polymerase II activating transcription factor binding Source: ARUK-UCL
- transcription regulator inhibitor activity Source: ARUK-UCL
GO - Biological processi
- cell differentiation Source: GO_Central
- cellular senescence Source: UniProtKB
- circadian regulation of gene expression Source: UniProtKB
- embryonic digestive tract morphogenesis Source: UniProtKB
- endodermal digestive tract morphogenesis Source: UniProtKB
- entrainment of circadian clock by photoperiod Source: UniProtKB
- epithelial cell differentiation involved in mammary gland alveolus development Source: UniProtKB
- locomotor rhythm Source: UniProtKB
- mammary gland alveolus development Source: UniProtKB
- mammary gland epithelial cell proliferation Source: UniProtKB
- negative regulation of DNA-binding transcription factor activity Source: GDB
- negative regulation of gene expression Source: UniProtKB
- negative regulation of muscle cell differentiation Source: ARUK-UCL
- negative regulation of transcription, DNA-templated Source: GDB
- negative regulation of transcription by RNA polymerase II Source: ARUK-UCL
- neuron fate commitment Source: UniProtKB
- positive regulation of blood pressure Source: UniProtKB
- positive regulation of cell cycle arrest Source: UniProtKB
- positive regulation of gene expression Source: UniProtKB
- positive regulation of smooth muscle cell proliferation Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription involved in G1/S transition of mitotic cell cycle Source: BHF-UCL
- regulation of circadian rhythm Source: UniProtKB
- regulation of G1/S transition of mitotic cell cycle Source: BHF-UCL
- regulation of lipid metabolic process Source: UniProtKB
- regulation of neural precursor cell proliferation Source: UniProtKB
- regulation of neuron differentiation Source: UniProtKB
Keywordsi
Molecular function | Developmental protein, Repressor |
Biological process | Biological rhythms, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | Q02363 |
Reactomei | R-HSA-9031628, NGF-stimulated transcription |
SIGNORi | Q02363 |
Names & Taxonomyi
Protein namesi | Recommended name: DNA-binding protein inhibitor ID-2Alternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:5361, ID2 |
MIMi | 600386, gene |
neXtProti | NX_Q02363 |
VEuPathDBi | HostDB:ENSG00000115738.9 |
Subcellular locationi
Cytosol
- cytosol Source: BHF-UCL
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: BHF-UCL
Other locations
- cytoplasm Source: UniProtKB
- euchromatin Source: ARUK-UCL
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Organism-specific databases
DisGeNETi | 3398 |
OpenTargetsi | ENSG00000115738 |
PharmGKBi | PA29609 |
Miscellaneous databases
Pharosi | Q02363, Tbio |
Genetic variation databases
BioMutai | ID2 |
DMDMi | 729806 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000127240 | 1 – 134 | DNA-binding protein inhibitor ID-2Add BLAST | 134 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 14 | PhosphoserineCombined sources | 1 | |
Modified residuei | 25 | PhosphoserineBy similarity | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q02363 |
MassIVEi | Q02363 |
PaxDbi | Q02363 |
PeptideAtlasi | Q02363 |
PRIDEi | Q02363 |
ProteomicsDBi | 58083 |
PTM databases
iPTMneti | Q02363 |
PhosphoSitePlusi | Q02363 |
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
Bgeei | ENSG00000115738, Expressed in adrenal gland and 237 other tissues |
ExpressionAtlasi | Q02363, baseline and differential |
Genevisiblei | Q02363, HS |
Organism-specific databases
HPAi | ENSG00000115738, Tissue enhanced (parathyroid) |
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 PublicationsBinary interactionsi
Hide detailsQ02363
GO - Molecular functioni
- ion channel binding Source: BHF-UCL
- protein dimerization activity Source: InterPro
- RNA polymerase II activating transcription factor binding Source: ARUK-UCL
Protein-protein interaction databases
BioGRIDi | 109624, 90 interactors |
DIPi | DIP-46874N |
ELMi | Q02363 |
IntActi | Q02363, 61 interactors |
MINTi | Q02363 |
STRINGi | 9606.ENSP00000234091 |
Miscellaneous databases
RNActi | Q02363, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | Q02363 |
SMRi | Q02363 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 23 – 75 | bHLHPROSITE-ProRule annotationAdd BLAST | 53 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 106 – 115 | Nuclear export signalBy similarity | 10 |
Domaini
The bHLH domain is essential for its repressor activity towards the CLOCK-ARNTL/BMAL1 heterodimer.By similarity
Phylogenomic databases
eggNOGi | ENOG502RZP5, Eukaryota |
GeneTreei | ENSGT00940000156464 |
HOGENOMi | CLU_116790_2_1_1 |
InParanoidi | Q02363 |
OMAi | EHTLGIS |
OrthoDBi | 1624054at2759 |
PhylomeDBi | Q02363 |
TreeFami | TF326217 |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR026052, DNA-bd_prot-inh IPR036638, HLH_DNA-bd_sf |
PANTHERi | PTHR11723, PTHR11723, 1 hit |
Pfami | View protein in Pfam PF00010, HLH, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit |
i Sequence
Sequence statusi: Complete.
Q02363-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 68 | V → L in AAA58681 (PubMed:1741406).Curated | 1 | |
Sequence conflicti | 98 | A → R in AAA58681 (PubMed:1741406).Curated | 1 |
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 |
CCDSi | CCDS1659.1 |
PIRi | A40227 JC2007 |
RefSeqi | NP_002157.2, NM_002166.4 |
Genome annotation databases
Ensembli | ENST00000234091; ENSP00000234091; ENSG00000115738 ENST00000331129; ENSP00000385465; ENSG00000115738 ENST00000396290; ENSP00000379585; ENSG00000115738 |
GeneIDi | 3398 |
KEGGi | hsa:3398 |
Similar proteinsi
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 |
CCDSi | CCDS1659.1 |
PIRi | A40227 JC2007 |
RefSeqi | NP_002157.2, NM_002166.4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
4AYA | X-ray | 2.10 | A/B | 1-82 | [»] | |
BMRBi | Q02363 | |||||
SMRi | Q02363 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 109624, 90 interactors |
DIPi | DIP-46874N |
ELMi | Q02363 |
IntActi | Q02363, 61 interactors |
MINTi | Q02363 |
STRINGi | 9606.ENSP00000234091 |
PTM databases
iPTMneti | Q02363 |
PhosphoSitePlusi | Q02363 |
Genetic variation databases
BioMutai | ID2 |
DMDMi | 729806 |
Proteomic databases
jPOSTi | Q02363 |
MassIVEi | Q02363 |
PaxDbi | Q02363 |
PeptideAtlasi | Q02363 |
PRIDEi | Q02363 |
ProteomicsDBi | 58083 |
Protocols and materials databases
Antibodypediai | 12350, 448 antibodies |
DNASUi | 3398 |
Genome annotation databases
Ensembli | ENST00000234091; ENSP00000234091; ENSG00000115738 ENST00000331129; ENSP00000385465; ENSG00000115738 ENST00000396290; ENSP00000379585; ENSG00000115738 |
GeneIDi | 3398 |
KEGGi | hsa:3398 |
Organism-specific databases
CTDi | 3398 |
DisGeNETi | 3398 |
GeneCardsi | ID2 |
HGNCi | HGNC:5361, ID2 |
HPAi | ENSG00000115738, Tissue enhanced (parathyroid) |
MIMi | 600386, gene |
neXtProti | NX_Q02363 |
OpenTargetsi | ENSG00000115738 |
PharmGKBi | PA29609 |
VEuPathDBi | HostDB:ENSG00000115738.9 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | ENOG502RZP5, Eukaryota |
GeneTreei | ENSGT00940000156464 |
HOGENOMi | CLU_116790_2_1_1 |
InParanoidi | Q02363 |
OMAi | EHTLGIS |
OrthoDBi | 1624054at2759 |
PhylomeDBi | Q02363 |
TreeFami | TF326217 |
Enzyme and pathway databases
PathwayCommonsi | Q02363 |
Reactomei | R-HSA-9031628, NGF-stimulated transcription |
SIGNORi | Q02363 |
Miscellaneous databases
BioGRID-ORCSi | 3398, 20 hits in 985 CRISPR screens |
ChiTaRSi | ID2, human |
GeneWikii | ID2 |
GenomeRNAii | 3398 |
Pharosi | Q02363, Tbio |
PROi | PR:Q02363 |
RNActi | Q02363, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000115738, Expressed in adrenal gland and 237 other tissues |
ExpressionAtlasi | Q02363, baseline and differential |
Genevisiblei | Q02363, HS |
Family and domain databases
Gene3Di | 4.10.280.10, 1 hit |
InterProi | View protein in InterPro IPR011598, bHLH_dom IPR026052, DNA-bd_prot-inh IPR036638, HLH_DNA-bd_sf |
PANTHERi | PTHR11723, PTHR11723, 1 hit |
Pfami | View protein in Pfam PF00010, HLH, 1 hit |
SMARTi | View protein in SMART SM00353, HLH, 1 hit |
SUPFAMi | SSF47459, SSF47459, 1 hit |
PROSITEi | View protein in PROSITE PS50888, BHLH, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ID2_HUMAN | |
Accessioni | Q02363Primary (citable) accession number: Q02363 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 1, 1995 |
Last sequence update: | February 1, 1995 | |
Last modified: | April 7, 2021 | |
This is version 187 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 2
Human chromosome 2: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references