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

Genomic context

Location:: 2p25.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
109.20190905	current	GRCh38.p13 (GCF_000001405.39)	2	NC_000002.12 (8682056..8684461)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (8822113..8824583)

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?

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.
Results show that self-assembly decreases the backbone flexibility of ID2 protein regions: helix-loop-helix (HLH) and the nuclear export signal (NES), that are important for interaction with basic-HLH transcription factors or for nucleocytoplasmic shuttling.
Title: The Recombinant Inhibitor of DNA Binding Id2 Forms Multimeric Structures via the Helix-Loop-Helix Domain and the Nuclear Export Signal.
the results of the present study suggest that lncRNA H19 regulates the expression of ID2 through competitive binding to hsamiR19a and hsamiR19b, which may serve a role in acute myelocytic leukemia cell proliferation.
Title: LncRNA H19 regulates ID2 expression through competitive binding to hsa-miR-19a/b in acute myelocytic leukemia.
ID2 is localized to peritoneal mesothelial and stromal cells of women with and without endometriosis. ID2 mRNA expression is lower in peritoneum adjacent to the endometriosis lesions compared to distal sites
Title: ID2 mediates the transforming growth factor-β1-induced Warburg-like effect seen in the peritoneum of women with endometriosis.
The ID2 gene expression was increased in the most advanced stage of endometriosis and in ovarian endometriomas. Considering that the genes studied participate either directly or indirectly in cellular processes that can lead to cell migration, angiogenesis, and inappropriate invasion, it is possible that the deregulation of these genes caused the development and maintenance of ectopic tissue.
Title: Increased expression of ID2, PRELP and SMOC2 genes in patients with endometriosis.
Data indicate that the expression level of ID2 in GBM cells can predict the sensitivity of GBM-derived tumor cells to decreased glucose levels.
Title: ID2 promotes survival of glioblastoma cells during metabolic stress by regulating mitochondrial function.

Submit: New GeneRIF Correction See all GeneRIFs (95)

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

NHGRI GWAS Catalog

Description
A genome-wide association meta-analysis of self-reported allergy identifies shared and allergy-specific susceptibility loci. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
A genome-wide association study of plasma total IgE concentrations in the Framingham Heart Study. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from BioSystems

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Circadian rythm related genes, organism-specific biosystem (from WikiPathways)
Circadian rythm related genes, organism-specific biosystemThis is currently not a pathway but a list of circadian rhythm related genes and proteins. The source for this information is the gene ontology. The genes and proteins were filtered for "circadian rh...
Development and heterogeneity of the ILC family, organism-specific biosystem (from WikiPathways)
Development and heterogeneity of the ILC family, organism-specific biosystemDevelopment and heterogeneity of the ILC family. ILCs develop from distinct progenitors in the fetal liver or bone marrow and then develop into mature ILCs in the periphery. Different transcription f...
Development of pulmonary dendritic cells and macrophage subsets, organism-specific biosystem (from WikiPathways)
Development of pulmonary dendritic cells and macrophage subsets, organism-specific biosystemDevelopment of pulmonary DC and macrophage subsets. This model of pulmonary DC and macrophage subset differentiation in mice summarizes recent findings suggesting early lineage commitment of cDCs in ...
HIF-1-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
HIF-1-alpha transcription factor network, organism-specific biosystem
HIF-1-alpha transcription factor network
Hippo signaling pathway, organism-specific biosystem (from KEGG)
Hippo signaling pathway, organism-specific biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
Hippo signaling pathway, conserved biosystem (from KEGG)
Hippo signaling pathway, conserved biosystemHippo signaling is an evolutionarily conserved signaling pathway that controls organ size from flies to humans. In humans and mice, the pathway consists of the MST1 and MST2 kinases, their cofactor S...
ID signaling pathway, organism-specific biosystem (from WikiPathways)
ID signaling pathway, organism-specific biosystemThe Inhibitor of DNA binding (ID) proteins belong to the class V HLH family of transcription factors. Four ID proteins (ID 1-4)are known in humans. Unlike the basic HLH (bHLH) transcription factors, ...
Regulation of Wnt-mediated beta catenin signaling and target gene transcription, organism-specific biosystem (from Pathway Interaction Database)
Regulation of Wnt-mediated beta catenin signaling and target gene transcription, organism-specific biosystem
Regulation of Wnt-mediated beta catenin signaling and target gene transcription
Signaling pathways regulating pluripotency of stem cells, organism-specific biosystem (from KEGG)
Signaling pathways regulating pluripotency of stem cells, organism-specific biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
Signaling pathways regulating pluripotency of stem cells, conserved biosystem (from KEGG)
Signaling pathways regulating pluripotency of stem cells, conserved biosystemPluripotent stem cells (PSCs) are basic cells with an indefinite self-renewal capacity and the potential to generate all the cell types of the three germinal layers. The types of PSCs known to date i...
TGF-beta signaling pathway, organism-specific biosystem (from KEGG)
TGF-beta signaling pathway, organism-specific biosystemThe transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species r...
TGF-beta signaling pathway, conserved biosystem (from KEGG)
TGF-beta signaling pathway, conserved biosystemThe transforming growth factor-beta (TGF-beta) family members, which include TGF-betas, activins and bone morphogenetic proteins (BMPs), are structurally related secreted cytokines found in species r...
Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
Transcriptional misregulation in cancer, organism-specific biosystem
Transcriptional misregulation in cancer
Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
Transcriptional misregulation in cancer, conserved biosystem
Transcriptional misregulation in cancer
Validated targets of C-MYC transcriptional activation, organism-specific biosystem (from Pathway Interaction Database)
Validated targets of C-MYC transcriptional activation, organism-specific biosystem
Validated targets of C-MYC transcriptional activation
Validated targets of C-MYC transcriptional repression, organism-specific biosystem (from Pathway Interaction Database)
Validated targets of C-MYC transcriptional repression, organism-specific biosystem
Validated targets of C-MYC transcriptional repression
miR-517 relationship with ARCN1 and USP1, organism-specific biosystem (from WikiPathways)
miR-517 relationship with ARCN1 and USP1, organism-specific biosystemSchematic summarizing predicted miR-517a relationships with ARCN1 and USP1. A genomewide miRNA mimic toxicity screen indicates common and selective vulnerabilities of epithelial ovarian cancer cells...
miRs in Muscle Cell Differentiation, organism-specific biosystem (from WikiPathways)
miRs in Muscle Cell Differentiation, organism-specific biosystem
miRs in Muscle Cell Differentiation

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: 279 organisms have orthologs with human gene ID2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
DNA-binding transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
RNA polymerase II transcription factor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
ion channel binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein dimerization activity	IEA Inferred from Electronic Annotation more info
transcription factor binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
Peyer's patch development	IEA Inferred from Electronic Annotation more info
adipose tissue development	IEA Inferred from Electronic Annotation more info
adult locomotory behavior	IEA Inferred from Electronic Annotation more info
bundle of His development	IEA Inferred from Electronic Annotation more info
cell maturation	IEA Inferred from Electronic Annotation more info
cell morphogenesis involved in neuron differentiation	IEA Inferred from Electronic Annotation more info
cellular response to lithium ion	IEA Inferred from Electronic Annotation more info
cellular senescence	ISS Inferred from Sequence or Structural Similarity more info
circadian regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
circadian rhythm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
embryonic digestive tract morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
endodermal digestive tract morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
entrainment of circadian clock by photoperiod	ISS Inferred from Sequence or Structural Similarity more info
enucleate erythrocyte differentiation	IEA Inferred from Electronic Annotation more info
epithelial cell differentiation involved in mammary gland alveolus development	ISS Inferred from Sequence or Structural Similarity more info
locomotor rhythm	ISS Inferred from Sequence or Structural Similarity more info
mammary gland alveolus development	ISS Inferred from Sequence or Structural Similarity more info
mammary gland epithelial cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
membranous septum morphogenesis	IEA Inferred from Electronic Annotation more info
metanephros development	IEA Inferred from Electronic Annotation more info
multicellular organism development	TAS Traceable Author Statement more info	PubMed
natural killer cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of B cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of neural precursor cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
negative regulation of oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of transcription by RNA polymerase II	IEA Inferred from Electronic Annotation more info
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neuron fate commitment	ISS Inferred from Sequence or Structural Similarity more info
olfactory bulb development	IEA Inferred from Electronic Annotation more info
oligodendrocyte development	IEA Inferred from Electronic Annotation more info
positive regulation of astrocyte differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of blood pressure	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cell cycle arrest	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of erythrocyte differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of fat cell differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of macrophage differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of smooth muscle cell proliferation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of transcription involved in G1/S transition of mitotic cell cycle	IC Inferred by Curator more info	PubMed
positive regulation of transcription, DNA-templated	ISS Inferred from Sequence or Structural Similarity more info
regulation of G1/S transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of cell cycle	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
regulation of lipid metabolic process	ISS Inferred from Sequence or Structural Similarity more info
thigmotaxis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
colocalizes_with cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
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

cd00083
Location:38 → 79

HLH; Helix-loop-helix domain, found in specific DNA- binding proteins that act as transcription factors; 60-100 amino acids long. A DNA-binding basic region is followed by two alpha-helices separated by a variable loop region; HLH forms homo- and heterodimers, ...