Transformation/transcription domain-associated protein

Transformation/transcription domain-associated protein, also known as TRRAP, is a protein that in humans is encoded by the TRRAP gene.[5][6] TRRAP belongs to the phosphatidylinositol 3-kinase-related kinase protein family.

TRRAP
Identifiers
AliasesTRRAP, PAF350/400, PAF400, STAF40, TR-AP, Tra1, transformation/transcription domain associated protein, DEDDFA, DFNA75
External IDsOMIM: 603015 MGI: 2153272 HomoloGene: 39246 GeneCards: TRRAP
Gene location (Human)
Chr.Chromosome 7 (human)[1]
Band7q22.1Start98,877,933 bp[1]
End99,050,831 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

8295

100683

Ensembl

ENSG00000196367

ENSMUSG00000045482

UniProt

Q9Y4A5

Q80YV3

RefSeq (mRNA)

NM_003496
NM_001244580
NM_001375524

NM_001081362

RefSeq (protein)

NP_001231509
NP_003487
NP_001362453

n/a

Location (UCSC)Chr 7: 98.88 – 99.05 MbChr 5: 144.77 – 144.86 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

TRRAP is an adaptor protein, which is found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT), which in turn is responsible for epigenetic transcription activation. TRRAP has a central role in MYC (c-Myc) transcription activation, and also participates in cell transformation by MYC. It is required for p53/TP53-, E2F1-, and E2F4-mediated transcription activation. It is also involved in transcription activation mediated by the adenovirus E1A, a viral oncoprotein that deregulates transcription of key genes.[7]

TRRAP is also required for the mitotic checkpoint and normal cell cycle progression. The MRN complex (composed of MRE11, RAD50, and NBS1) is involved in the detection and repair of DNA double-strand breaks (DSBs). TRRAP associates with the MRN complex and when TRRAP is removed, the complex shows reduced cDNA end-joining activity. Hence, TRRAP may function as a link between DSB repair and chromatin remodeling.[8][9]

Model organisms

Model organisms have been used in the study of TRRAP function. A conditional knockout mouse line, called Trraptm1a(EUCOMM)Wtsi[15][16] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[17][18][19]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[13][20] Twenty four tests were carried out on mutant mice and two significant abnormalities were observed.[13] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.[13]

Interactions

Transformation/transcription domain-associated protein has been shown to interact with:

References
  1. GRCh38: Ensembl release 89: ENSG00000196367 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000045482 - 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. McMahon SB, Van Buskirk HA, Dugan KA, Copeland TD, Cole MD (August 1998). "The novel ATM-related protein TRRAP is an essential cofactor for the c-Myc and E2F oncoproteins". Cell. 94 (3): 363–74. doi:10.1016/S0092-8674(00)81479-8. PMID 9708738. S2CID 17693834.
  6. Vassilev A, Yamauchi J, Kotani T, Prives C, Avantaggiati ML, Qin J, Nakatani Y (December 1998). "The 400 kDa subunit of the PCAF histone acetylase complex belongs to the ATM superfamily". Mol. Cell. 2 (6): 869–75. doi:10.1016/S1097-2765(00)80301-9. PMID 9885574.
  7. Murr R, Vaissière T, Sawan C, Shukla V, Herceg Z (August 2007). "Orchestration of chromatin-based processes: mind the TRRAP". Oncogene. 26 (37): 5358–72. doi:10.1038/sj.onc.1210605. PMID 17694078.
  8. Robert F, Hardy S, Nagy Z, Baldeyron C, Murr R, Déry U, Masson JY, Papadopoulo D, Herceg Z, Tora L (January 2006). "The Transcriptional Histone Acetyltransferase Cofactor TRRAP Associates with the MRN Repair Complex and Plays a Role in DNA Double-Strand Break Repair". Mol. Cell. Biol. 26 (2): 402–12. doi:10.1128/MCB.26.2.402-412.2006. PMC 1346889. PMID 16382133.
  9. Herceg Z, Wang ZQ (March 2005). "Rendez-vous at mitosis: TRRAPed in the chromatin". Cell Cycle. 4 (3): 383–7. doi:10.4161/cc.4.3.1546. PMID 15711126.
  10. "Haematology data for Trrap". Wellcome Trust Sanger Institute.
  11. "Salmonella infection data for Trrap". Wellcome Trust Sanger Institute.
  12. "Citrobacter infection data for Trrap". Wellcome Trust Sanger Institute.
  13. 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. S2CID 85911512.
  14. Mouse Resources Portal, Wellcome Trust Sanger Institute.
  15. "International Knockout Mouse Consortium".
  16. "Mouse Genome Informatics".
  17. 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 (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  18. Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  19. Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
  20. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
  21. Park J, Wood MA, Cole MD (March 2002). "BAF53 forms distinct nuclear complexes and functions as a critical c-Myc-interacting nuclear cofactor for oncogenic transformation". Mol. Cell. Biol. 22 (5): 1307–16. doi:10.1128/mcb.22.5.1307-1316.2002. PMC 134713. PMID 11839798.
  22. Fuchs M, Gerber J, Drapkin R, Sif S, Ikura T, Ogryzko V, Lane WS, Nakatani Y, Livingston DM (August 2001). "The p400 complex is an essential E1A transformation target". Cell. 106 (3): 297–307. doi:10.1016/s0092-8674(01)00450-0. PMID 11509179. S2CID 15634637.
  23. McMahon SB, Wood MA, Cole MD (January 2000). "The essential cofactor TRRAP recruits the histone acetyltransferase hGCN5 to c-Myc". Mol. Cell. Biol. 20 (2): 556–62. doi:10.1128/mcb.20.2.556-562.2000. PMC 85131. PMID 10611234.
  24. Liu X, Tesfai J, Evrard YA, Dent SY, Martinez E (May 2003). "c-Myc transformation domain recruits the human STAGA complex and requires TRRAP and GCN5 acetylase activity for transcription activation". J. Biol. Chem. 278 (22): 20405–12. doi:10.1074/jbc.M211795200. PMC 4031917. PMID 12660246.
  25. Martinez E, Palhan VB, Tjernberg A, Lymar ES, Gamper AM, Kundu TK, Chait BT, Roeder RG (October 2001). "Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo". Mol. Cell. Biol. 21 (20): 6782–95. doi:10.1128/MCB.21.20.6782-6795.2001. PMC 99856. PMID 11564863.

Further reading
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