ID2 inhibitor of DNA binding 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ID2provided by HGNC
Official Full Name: inhibitor of DNA binding 2provided by HGNC
Primary source: HGNC:HGNC:5361
See related: Ensembl:ENSG00000115738 MIM:600386
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GIG8; ID2A; ID2H; bHLHb26
Summary: The protein encoded by this gene belongs to the inhibitor of DNA binding family, members of which are transcriptional regulators that contain a helix-loop-helix (HLH) domain but not a basic domain. Members of the inhibitor of DNA binding family inhibit the functions of basic helix-loop-helix transcription factors in a dominant-negative manner by suppressing their heterodimerization partners through the HLH domains. This protein may play a role in negatively regulating cell differentiation. A pseudogene of this gene is located on chromosome 3. [provided by RefSeq, Aug 2011]
Expression: Ubiquitous expression in liver (RPKM 128.2), bone marrow (RPKM 111.2) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p25.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109.20211119	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (8682056..8684461)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (8822186..8824591)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Inhibitor of DNA Binding 2 (ID2): A Novel Marker for Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.
Title: Inhibitor of DNA Binding 2 (ID2): A Novel Marker for Lymph Node Metastasis in Head and Neck Squamous Cell Carcinoma.
MITF is a driver oncogene and potential therapeutic target in kidney angiomyolipoma tumors through transcriptional regulation of CYR61.
Title: MITF is a driver oncogene and potential therapeutic target in kidney angiomyolipoma tumors through transcriptional regulation of CYR61.
The study observed higher expression levels of HDGFRP3 and ID2 in bipolar disorder (BD) patients who favourably respond to lithium. Both of these genes are involved in neurogenesis.
Title: RNA sequencing of bipolar disorder lymphoblastoid cell lines implicates the neurotrophic factor HRP-3 in lithium's clinical efficacy.
Long noncoding RNA ANCR inhibits the differentiation of mesenchymal stem cells toward definitive endoderm by facilitating the association of PTBP1 with ID2.
Title: Long noncoding RNA ANCR inhibits the differentiation of mesenchymal stem cells toward definitive endoderm by facilitating the association of PTBP1 with ID2.
ID2-AS1 significantly suppressed the migration, invasion and metastasis of hepatocellular carcinoma (HCC) cells in vitro and in vivo. Mechanistically, ID2-AS1 regulated the transcription of its adjacent gene inhibitor of DNA binding 2 (ID2) by blocking the binding of histone deacetylase 8 (HDAC8) on the ID2 enhancer
Title: LncRNA ID2-AS1 suppresses tumor metastasis by activating the HDAC8/ID2 pathway in hepatocellular carcinoma.
We have identified ID2 as a key factor of DCIS initiation and GJB2 and INHBA as aggressive factors during progression of ID2-mediated DCIS to IDC. ID2 is capable of promoting the cancer stem cell population in pre-malignant cells and leads to DCIS formation
Title: ID2 and GJB2 promote early-stage breast cancer progression by regulating cancer stemness.
Study identifies ID2 as a key regulator of breast cancer metastasis to the brain. Data support a model in which breast cancer cells that have disseminated to the brain upregulate ID2 expression in response to astrocyte-secreted BMP7 and this serves to support metastatic expansion. Moreover, elevated ID2 expression identifies breast cancer patients at increased risk of developing metastatic relapse in the brain.
Title: Using an in-vivo syngeneic spontaneous metastasis model identifies ID2 as a promoter of breast cancer colonisation in the brain.
Oxidative stress increased ID2 expression in retinal pigment epithelium (RPE) cells. Knockdown of ID2 promoted cell apoptosis and increased reactive oxygen species level in RPE cells that were subjected to oxidative damage. In addition, over-expression of ID2 attenuated the oxidative damage response in RPE cells.
Title: ID2 protects retinal pigment epithelium cells from oxidative damage through p-ERK1/2/ID2/NRF2.
The author's study identified a novel association with PR near ID2 and generalised 10 previously identified loci to our Hispanic/Latino population.
Title: Genome-wide association study of PR interval in Hispanics/Latinos identifies novel locus at <i>ID2</i>.
CaMKII can directly phosphorylate Beclin 1 at Ser90 to promote K63-linked ubiquitination of Beclin 1 and activation of autophagy; it also promotes K63-linked ubiquitination of inhibitor of differentiation 1/2 (Id-1/2) by catalyzing phosphorylation of Id proteins and recruiting TRAF-6
Title: CaMKII-mediated Beclin 1 phosphorylation regulates autophagy that promotes degradation of Id and neuroblastoma cell differentiation.

Submit: New GeneRIF Correction See all GeneRIFs (100)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. GeneReviews: Not available
A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. GeneReviews: Not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH25021 (e-PCR)
- UniSTS:92939

D2S208E (e-PCR)
- UniSTS:147792

D3S4003 (e-PCR)
- UniSTS:67215

RH67912 (e-PCR)
- UniSTS:39848

RH11441 (e-PCR)
- UniSTS:87477

ID2_2310 (e-PCR)
- UniSTS:280771

Homology

Homologs of the ID2 gene: The ID2 gene is conserved in chimpanzee, Rhesus monkey, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 287 organisms have orthologs with human gene ID2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein dimerization activity	IEA Inferred from Electronic Annotation more info
enables transcription regulator activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
enables transcription regulator inhibitor activity	ISS Inferred from Sequence or Structural Similarity more info
enables transcription regulator inhibitor activity	TAS Traceable Author Statement more info	PubMed
enables transmembrane transporter binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
acts_upstream_of_or_within bundle of His development	ISS Inferred from Sequence or Structural Similarity more info
involved_in bundle of His development	NAS Non-traceable Author Statement more info	PubMed
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in cellular senescence	ISS Inferred from Sequence or Structural Similarity more info
involved_in circadian regulation of gene expression	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in embryonic digestive tract morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in endodermal digestive tract morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in entrainment of circadian clock by photoperiod	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within enucleate erythrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in epithelial cell differentiation involved in mammary gland alveolus development	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within heart development	ISS Inferred from Sequence or Structural Similarity more info
involved_in locomotor rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in mammary gland alveolus development	ISS Inferred from Sequence or Structural Similarity more info
involved_in mammary gland epithelial cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within negative regulation of B cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of muscle cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of neuron fate commitment	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within olfactory bulb development	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of astrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of blood pressure	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of fat cell differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_or_within positive regulation of macrophage differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of smooth muscle cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of transcription involved in G1/S transition of mitotic cell cycle	IC Inferred by Curator more info	PubMed
involved_in positive regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of G1/S transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of lipid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_negative_effect regulation of neural precursor cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
acts_upstream_of_negative_effect regulation of neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
colocalizes_with cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in euchromatin	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: DNA-binding protein inhibitor ID-2

Names: DNA-binding protein inhibitor ID2; cell growth-inhibiting gene 8; class B basic helix-loop-helix protein 26; helix-loop-helix protein ID2; inhibitor of DNA binding 2, HLH protein; inhibitor of DNA binding 2, dominant negative helix-loop-helix protein; inhibitor of differentiation 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_002166.5 → NP_002157.2 DNA-binding protein inhibitor ID-2

See identical proteins and their annotated locations for NP_002157.2

Status: REVIEWED

Source sequence(s)

AC011747

Consensus CDS

CCDS1659.1

UniProtKB/Swiss-Prot

Q02363

UniProtKB/TrEMBL

Q53T66

Related

ENSP00000379585.1, ENST00000396290.2

Conserved Domains (1) summary

cd19692
Location:18 → 83

bHLH_dnHLH_ID2; basic helix-loop-helix (bHLH) domain found in DNA-binding protein inhibitor ID2 and similar proteins