C19orf2
Unconventional prefoldin RPB5 interactor, also called URI1, is a protein that in humans is encoded by the C19orf2 gene.[1][2][3]
Function
The protein encoded by this gene binds to RNA polymerase II subunit 5 (RPB5) and negatively modulates transcription through its binding to RPB5. The encoded protein seems to have inhibitory effects on various types of activated transcription, but it requires the RPB5-binding region. This protein acts as a corepressor. It is suggested that it may require signaling processes for its function or that it negatively modulates genes in the chromatin structure. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.[3]
Interactions
C19orf2 has been shown to interact with DMAP1[4] and STAP1.[5]
Model organisms
Model organisms have been used in the study of URI1 function. A conditional knockout mouse line called Uri1tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12]
| Characteristic | Phenotype |
|---|---|
| All data available at.[7][12] | |
| Peripheral blood leukocytes 6 Weeks | Abnormal |
| Haematology 6 Weeks | Normal |
| Insulin | Normal |
| Homozygous viability at P14 | Normal |
| Homozygous Fertility | Normal |
| Body weight | Normal |
| Neurological assessment | Normal |
| Grip strength | Normal |
| Dysmorphology | Normal |
| Indirect calorimetry | Normal |
| Glucose tolerance test | Normal |
| Auditory brainstem response | Normal |
| DEXA | Normal |
| Radiography | Normal |
| Eye morphology | Normal |
| Clinical chemistry | Normal |
| Haematology 16 Weeks | Normal |
| Peripheral blood leukocytes 16 Weeks | Normal |
| Heart weight | Normal |
| Salmonella infection | Normal |
References
- ↑ Van Leuven F, Torrekens S, Moechars D, Hilliker C, Buellens M, Bollen M, Delabie J (Feb 1999). "Molecular cloning of a gene on chromosome 19q12 coding for a novel intracellular protein: analysis of expression in human and mouse tissues and in human tumor cells, particularly Reed-Sternberg cells in Hodgkin disease". Genomics 54 (3): 511–20. doi:10.1006/geno.1998.5609. PMID 9878255.
- ↑ Dorjsuren D, Lin Y, Wei W, Yamashita T, Nomura T, Hayashi N, Murakami S (Dec 1998). "RMP, a Novel RNA Polymerase II Subunit 5-Interacting Protein, Counteracts Transactivation by Hepatitis B Virus X Protein". Mol Cell Biol 18 (12): 7546–55. PMC 109335. PMID 9819440.
- 1 2 "Entrez Gene: C19orf2 chromosome 19 open reading frame 2".
- ↑ Delgermaa L, Hayashi N, Dorjsuren D, Nomura T, Thuy le TT, Murakami S (Oct 2004). "Subcellular Localization of RPB5-Mediating Protein and Its Putative Functional Partner". Mol. Cell. Biol. 24 (19): 8556–66. doi:10.1128/MCB.24.19.8556-8566.2004. PMC 516735. PMID 15367675.
- ↑ Gstaiger M, Luke B, Hess D, Oakeley EJ, Wirbelauer C, Blondel M, Vigneron M, Peter M, Krek W (Nov 2003). "Control of nutrient-sensitive transcription programs by the unconventional prefoldin URI". Science 302 (5648): 1208–12. doi:10.1126/science.1088401. PMID 14615539.
- ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
- 1 2 "International Mouse Phenotyping Consortium".
- ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
- 1 2 "Infection and Immunity Immunophenotyping (3i) Consortium".
Further reading
- Liu L, McKeehan WL (2002). "Sequence analysis of LRPPRC and its SEC1 domain interaction partners suggests roles in cytoskeletal organization, vesicular trafficking, nucleocytosolic shuttling, and chromosome activity". Genomics 79 (1): 124–36. doi:10.1006/geno.2001.6679. PMC 3241999. PMID 11827465.
- Wei W, Gu JX, Zhu CQ, Sun FY, Dorjsuren D, Lin Y, Murakami S (2003). "Interaction with general transcription factor IIF (TFIIF) is required for the suppression of activated transcription by RPB5-mediating protein (RMP)". Cell Res. 13 (2): 111–20. doi:10.1038/sj.cr.7290155. PMID 12737519.
- Gstaiger M, Luke B, Hess D, Oakeley EJ, Wirbelauer C, Blondel M, Vigneron M, Peter M, Krek W (2003). "Control of nutrient-sensitive transcription programs by the unconventional prefoldin URI". Science 302 (5648): 1208–12. doi:10.1126/science.1088401. PMID 14615539.
- Bouwmeester T, Bauch A, Ruffner H, Angrand PO, Bergamini G, Croughton K, Cruciat C, Eberhard D, Gagneur J, Ghidelli S, Hopf C, Huhse B, Mangano R, Michon AM, Schirle M, Schlegl J, Schwab M, Stein MA, Bauer A, Casari G, Drewes G, Gavin AC, Jackson DB, Joberty G, Neubauer G, Rick J, Kuster B, Superti-Furga G (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
- Delgermaa L, Hayashi N, Dorjsuren D, Nomura T, Thuy le TT, Murakami S (2004). "Subcellular Localization of RPB5-Mediating Protein and Its Putative Functional Partner". Mol. Cell. Biol. 24 (19): 8556–66. doi:10.1128/MCB.24.19.8556-8566.2004. PMC 516735. PMID 15367675.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
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