ID2

Last updated

ID2
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ID2 , GIG8, ID2A, ID2H, bHLHb26, inhibitor of DNA binding 2, HLH protein, inhibitor of DNA binding 2
External IDs OMIM: 600386; MGI: 96397; HomoloGene: 1632; GeneCards: ID2; OMA:ID2 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002166

NM_010496

RefSeq (protein)

NP_002157

NP_034626

Location (UCSC) Chr 2: 8.68 – 8.68 Mb Chr 12: 25.14 – 25.15 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

DNA-binding protein inhibitor ID-2 is a protein that in humans is encoded by the ID2 gene. [5]

Contents

Function

The protein encoded by this gene belongs to the inhibitor of DNA binding (ID) family, members of which are transcriptional regulators that contain a helix-loop-helix (HLH) domain but not a basic domain. Members of the ID 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 has been identified for this gene. [6] The ID2 protein may play a role in the development and resistance to therapies of glioblastoma, the most aggressive of brain cancers. [7]

Interactions

ID2 has been shown to interact with MyoD [8] and NEDD9. [9]

See also

Related Research Articles

<span class="mw-page-title-main">MyoD</span> Mammalian protein found in Homo sapiens

MyoD, also known as myoblast determination protein 1, is a protein in animals that plays a major role in regulating muscle differentiation. MyoD, which was discovered in the laboratory of Harold M. Weintraub, belongs to a family of proteins known as myogenic regulatory factors (MRFs). These bHLH transcription factors act sequentially in myogenic differentiation. Vertebrate MRF family members include MyoD1, Myf5, myogenin, and MRF4 (Myf6). In non-vertebrate animals, a single MyoD protein is typically found.

Inhibitor of DNA-binding/differentiation proteins, also known as ID proteins comprise a family of proteins that heterodimerize with basic helix-loop-helix (bHLH) transcription factors to inhibit DNA binding of bHLH proteins. ID proteins also contain the HLH-dimerization domain but lack the basic DNA-binding domain and thus regulate bHLH transcription factors when they heterodimerize with bHLH proteins. The first helix-loop-helix proteins identified were named E-proteins because they bind to Ephrussi-box (E-box) sequences. In normal development, E proteins form dimers with other bHLH transcription factors, allowing transcription to occur. However, in cancerous phenotypes, ID proteins can regulate transcription by binding E proteins, so no dimers can be formed and transcription is inactive. E proteins are members of the class I bHLH family and form dimers with bHLH proteins from class II to regulate transcription. Four ID proteins exist in humans: ID1, ID2, ID3, and ID4. The ID homologue gene in Drosophila is called extramacrochaetae (EMC) and encodes a transcription factor of the helix-loop-helix family that lacks a DNA binding domain. EMC regulates cell proliferation, formation of organs like the midgut, and wing development. ID proteins could be potential targets for systemic cancer therapies without inhibiting the functioning of most normal cells because they are highly expressed in embryonic stem cells, but not in differentiated adult cells. Evidence suggests that ID proteins are overexpressed in many types of cancer. For example, ID1 is overexpressed in pancreatic, breast, and prostate cancers. ID2 is upregulated in neuroblastoma, Ewing’s sarcoma, and squamous cell carcinoma of the head and neck.

<span class="mw-page-title-main">Myogenin</span> Mammalian protein found in Homo sapiens

Myogenin, is a transcriptional activator encoded by the MYOG gene. Myogenin is a muscle-specific basic-helix-loop-helix (bHLH) transcription factor involved in the coordination of skeletal muscle development or myogenesis and repair. Myogenin is a member of the MyoD family of transcription factors, which also includes MyoD, Myf5, and MRF4.

The scleraxis protein is a member of the basic helix-loop-helix (bHLH) superfamily of transcription factors. Currently two genes have been identified to code for identical scleraxis proteins.

<span class="mw-page-title-main">TCF3</span> Protein-coding gene in the species Homo sapiens

Transcription factor 3, also known as TCF3, is a protein that in humans is encoded by the TCF3 gene. TCF3 has been shown to directly enhance Hes1 expression.

<span class="mw-page-title-main">Sterol regulatory element-binding protein 1</span> Protein-coding gene in the species Homo sapiens

Sterol regulatory element-binding transcription factor 1 (SREBF1) also known as sterol regulatory element-binding protein 1 (SREBP-1) is a protein that in humans is encoded by the SREBF1 gene.

<span class="mw-page-title-main">Sterol regulatory element-binding protein 2</span> Protein-coding gene in the species Homo sapiens

Sterol regulatory element-binding protein 2 (SREBP-2) also known as sterol regulatory element binding transcription factor 2 (SREBF2) is a protein that in humans is encoded by the SREBF2 gene.

<span class="mw-page-title-main">ID1</span> Protein-coding gene in the species Homo sapiens

DNA-binding protein inhibitor ID-1 is a protein that in humans is encoded by the ID1 gene.

<span class="mw-page-title-main">Myocyte-specific enhancer factor 2A</span> Protein-coding gene in the species Homo sapiens

Myocyte-specific enhancer factor 2A is a protein that in humans is encoded by the MEF2A gene. MEF2A is a transcription factor in the Mef2 family. In humans it is located on chromosome 15q26. Certain mutations in MEF2A cause an autosomal dominant form of coronary artery disease and myocardial infarction.

<span class="mw-page-title-main">ID3 (gene)</span> Protein-coding gene in the species Homo sapiens

DNA-binding protein inhibitor ID-3 is a protein that in humans is encoded by the ID3 gene.

<span class="mw-page-title-main">TCF12</span> Protein-coding gene in the species Homo sapiens

Transcription factor 12 is a protein that in humans is encoded by the TCF12 gene.

<span class="mw-page-title-main">ELK4</span> Protein-coding gene in the species Homo sapiens

ETS domain-containing protein Elk-4 is a protein that in humans is encoded by the ELK4 gene.

<span class="mw-page-title-main">ID4</span> Protein-coding gene in humans

ID4 is a protein coding gene. In humans, it encodes the protein known as DNA-binding protein inhibitor ID-4. This protein is known to be involved in the regulation of many cellular processes during both prenatal development and tumorigenesis. This is inclusive of embryonic cellular growth, senescence, cellular differentiation, apoptosis, and as an oncogene in angiogenesis.

<span class="mw-page-title-main">ELK3</span> Protein-coding gene in humans

ETS domain-containing protein Elk-3 is a protein that in humans is encoded by the ELK3 gene.

<span class="mw-page-title-main">LYL1</span> Protein-coding gene in the species Homo sapiens

Protein lyl-1 is a protein that in humans is encoded by the LYL1 gene.

<span class="mw-page-title-main">TFAP4</span> Protein-coding gene in the species Homo sapiens

Transcription factor AP-4 , also known as TFAP4, is a protein which in humans is encoded by the TFAP4 gene.

<span class="mw-page-title-main">MSC (gene)</span> Protein-coding gene in the species Homo sapiens

Musculin is a protein that in humans is encoded by the MSC gene.

<span class="mw-page-title-main">BHLHE41</span> Protein-coding gene in humans

"Basic helix-loop-helix family, member e41", or BHLHE41, is a gene that encodes a basic helix-loop-helix transcription factor repressor protein in various tissues of both humans and mice. It is also known as DEC2, hDEC2, and SHARP1, and was previously known as "basic helix-loop-helix domain containing, class B, 3", or BHLHB3. BHLHE41 is known for its role in the circadian molecular mechanisms that influence sleep quantity as well as its role in immune function and the maturation of T helper type 2 cell lineages associated with humoral immunity.

<span class="mw-page-title-main">MYF6</span> Protein-coding gene in the species Homo sapiens

Myogenic factor 6 is a protein that in humans is encoded by the MYF6 gene. This gene is also known in the biomedical literature as MRF4 and herculin. MYF6 is a myogenic regulatory factor (MRF) involved in the process known as myogenesis.

<span class="mw-page-title-main">PKNOX2</span> Protein-coding gene in the species Homo sapiens

PBX/Knotted 1 Homeobox 2 (PKNOX2) protein belongs to the three amino acid loop extension (TALE) class of homeodomain proteins, and is encoded by PKNOX2 gene in humans. The protein regulates the transcription of other genes and affects anatomical development.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000115738 Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020644 Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Hara E, Yamaguchi T, Nojima H, Ide T, Campisi J, Okayama H, et al. (January 1994). "Id-related genes encoding helix-loop-helix proteins are required for G1 progression and are repressed in senescent human fibroblasts". The Journal of Biological Chemistry. 269 (3): 2139–2145. doi: 10.1016/S0021-9258(17)42146-6 . PMID   8294468.
  6. "Entrez Gene: ID2 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein".
  7. Lee SB, Frattini V, Bansal M, Castano AM, Sherman D, Hutchinson K, et al. (January 2016). "An ID2-dependent mechanism for VHL inactivation in cancer". Nature. 529 (7585): 172–177. Bibcode:2016Natur.529..172L. doi:10.1038/nature16475. PMC   5384647 . PMID   26735018.
  8. Langlands K, Yin X, Anand G, Prochownik EV (August 1997). "Differential interactions of Id proteins with basic-helix-loop-helix transcription factors". The Journal of Biological Chemistry. 272 (32): 19785–19793. doi: 10.1074/jbc.272.32.19785 . PMID   9242638.
  9. Law SF, Zhang YZ, Fashena SJ, Toby G, Estojak J, Golemis EA (October 1999). "Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain". Experimental Cell Research. 252 (1): 224–235. doi:10.1006/excr.1999.4609. PMID   10502414.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.