ID2 explained

DNA-binding protein inhibitor ID-2 is a protein that in humans is encoded by the ID2 gene.^[1]

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.^[2] The ID2 protein may play a role in the development and resistance to therapies of glioblastoma, the most aggressive of brain cancers.^[3]

Interactions

ID2 has been shown to interact with MyoD^[4] and NEDD9.^[5]

See also

• Inhibitor of DNA-binding protein

Further reading

• Biggs J, Murphy EV, Israel MA . A human Id-like helix-loop-helix protein expressed during early development . Proceedings of the National Academy of Sciences of the United States of America . 89 . 4 . 1512–1516 . February 1992 . 1741406 . 48481 . 10.1073/pnas.89.4.1512 . free . 1992PNAS...89.1512B .
• Iavarone A, Garg P, Lasorella A, Hsu J, Israel MA . The helix-loop-helix protein Id-2 enhances cell proliferation and binds to the retinoblastoma protein . Genes & Development . 8 . 11 . 1270–1284 . June 1994 . 7926730 . 10.1101/gad.8.11.1270 . free .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1-2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Kurabayashi M, Jeyaseelan R, Kedes L . Two distinct cDNA sequences encoding the human helix-loop-helix protein Id2 . Gene . 133 . 2 . 305–306 . November 1993 . 8224921 . 10.1016/0378-1119(93)90658-P .
• Mathew S, Chen W, Murty VV, Benezra R, Chaganti RS . Chromosomal assignment of human ID1 and ID2 genes . Genomics . 30 . 2 . 385–387 . November 1995 . 8586447 . 10.1006/geno.1995.0037 .
• Lasorella A, Iavarone A, Israel MA . Id2 specifically alters regulation of the cell cycle by tumor suppressor proteins . Molecular and Cellular Biology . 16 . 6 . 2570–2578 . June 1996 . 8649364 . 231247 . 10.1128/MCB.16.6.2570 .
• Hara E, Hall M, Peters G . Cdk2-dependent phosphorylation of Id2 modulates activity of E2A-related transcription factors . The EMBO Journal . 16 . 2 . 332–342 . January 1997 . 9029153 . 1169639 . 10.1093/emboj/16.2.332 .
• Langlands K, Yin X, Anand G, Prochownik EV . Differential interactions of Id proteins with basic-helix-loop-helix transcription factors . The Journal of Biological Chemistry . 272 . 32 . 19785–19793 . August 1997 . 9242638 . 10.1074/jbc.272.32.19785 . free .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1-2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Yates PR, Atherton GT, Deed RW, Norton JD, Sharrocks AD . Id helix-loop-helix proteins inhibit nucleoprotein complex formation by the TCF ETS-domain transcription factors . The EMBO Journal . 18 . 4 . 968–976 . February 1999 . 10022839 . 1171189 . 10.1093/emboj/18.4.968 .
• Yokota Y, Mansouri A, Mori S, Sugawara S, Adachi S, Nishikawa S, Gruss P . Development of peripheral lymphoid organs and natural killer cells depends on the helix-loop-helix inhibitor Id2 . Nature . 397 . 6721 . 702–706 . February 1999 . 10067894 . 10.1038/17812 . 4428856 . 1999Natur.397..702Y .
• Law SF, Zhang YZ, Fashena SJ, Toby G, Estojak J, Golemis EA . Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain . Experimental Cell Research . 252 . 1 . 224–235 . October 1999 . 10502414 . 10.1006/excr.1999.4609 .
• Moldes M, Boizard M, Liepvre XL, Fève B, Dugail I, Pairault J . Functional antagonism between inhibitor of DNA binding (Id) and adipocyte determination and differentiation factor 1/sterol regulatory element-binding protein-1c (ADD1/SREBP-1c) trans-factors for the regulation of fatty acid synthase promoter in adipocytes . The Biochemical Journal . 344 . Pt 3 . 873–880 . December 1999 . 10585876 . 1220711 . 10.1042/0264-6021:3440873 .
• Liu J, Shi W, Warburton D . A cysteine residue in the helix-loop-helix domain of Id2 is critical for homodimerization and function . Biochemical and Biophysical Research Communications . 273 . 3 . 1042–1047 . July 2000 . 10891368 . 10.1006/bbrc.2000.3055 .
• Lasorella A, Noseda M, Beyna M, Yokota Y, Iavarone A . Id2 is a retinoblastoma protein target and mediates signalling by Myc oncoproteins . Nature . 407 . 6804 . 592–598 . October 2000 . 11034201 . 10.1038/35036504 . 4335368 . 2000Natur.407..592L .
• Roberts EC, Deed RW, Inoue T, Norton JD, Sharrocks AD . Id helix-loop-helix proteins antagonize pax transcription factor activity by inhibiting DNA binding . Molecular and Cellular Biology . 21 . 2 . 524–533 . January 2001 . 11134340 . 86614 . 10.1128/MCB.21.2.524-533.2001 .
• Wang S, Sdrulla A, Johnson JE, Yokota Y, Barres BA . A role for the helix-loop-helix protein Id2 in the control of oligodendrocyte development . Neuron . 29 . 3 . 603–614 . March 2001 . 11301021 . 10.1016/S0896-6273(01)00237-9 . 7978661 . free .
• Wong J, Funes-Duran M, Ahlberg J, Round J, O'Connell R, Miller R, Chen E, Richmond PA, Vierra CA . Characterization of a basic helix-loop-helix protein, ABF-1: nuclear localization, transcriptional properties, and interaction with Id-2 . DNA and Cell Biology . 20 . 8 . 465–471 . August 2001 . 11560778 . 10.1089/104454901316976091 .
• Suzuki H, Fukunishi Y, Kagawa I, Saito R, Oda H, Endo T, Kondo S, Bono H, Okazaki Y, Hayashizaki Y . Protein-protein interaction panel using mouse full-length cDNAs . Genome Research . 11 . 10 . 1758–1765 . October 2001 . 11591653 . 311163 . 10.1101/gr.180101 .

Notes and References

1. Hara E, Yamaguchi T, Nojima H, Ide T, Campisi J, Okayama H, Oda K . 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 . January 1994 . 8294468 . 10.1016/S0021-9258(17)42146-6 . free .
2. Web site: Entrez Gene: ID2 inhibitor of DNA binding 2, dominant negative helix-loop-helix protein.
3. Lee SB, Frattini V, Bansal M, Castano AM, Sherman D, Hutchinson K, Bruce JN, Califano A, Liu G, Cardozo T, Iavarone A, Lasorella A . An ID2-dependent mechanism for VHL inactivation in cancer . Nature . 529 . 7585 . 172–177 . January 2016 . 26735018 . 5384647 . 10.1038/nature16475 . 2016Natur.529..172L .
4. Langlands K, Yin X, Anand G, Prochownik EV . Differential interactions of Id proteins with basic-helix-loop-helix transcription factors . The Journal of Biological Chemistry . 272 . 32 . 19785–19793 . August 1997 . 9242638 . 10.1074/jbc.272.32.19785 . free .
5. Law SF, Zhang YZ, Fashena SJ, Toby G, Estojak J, Golemis EA . Dimerization of the docking/adaptor protein HEF1 via a carboxy-terminal helix-loop-helix domain . Experimental Cell Research . 252 . 1 . 224–235 . October 1999 . 10502414 . 10.1006/excr.1999.4609 .