THOC5

THO complex subunit 5 homolog is a protein that in humans is encoded by the THOC5 gene. THOCs is a member of THO complex which is a subcomplex of the transcription/export complex (TREX).

THOC5
Identifiers
Aliases	THOC5, C22orf19, Fmip, PK1.3, fSAP79, THO complex 5
External IDs	OMIM: 612733 MGI: 1351333 HomoloGene: 37836 GeneCards: THOC5
Gene location (Human) Chr. Chromosome 22 (human)[1] Band 22q12.2 Start 29,505,879 bp[1] End 29,555,216 bp[1]
Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 A1 Start 4,895,320 bp[2] End 4,928,867 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • RNA binding • mRNA binding Cellular component • cytoplasm • THO complex • THO complex part of transcription export complex • transcription export complex • cell nucleus • nuclear chromosome, telomeric region • nucleoplasm • nuclear chromosome Biological process • positive regulation of DNA-templated transcription, elongation • primitive hemopoiesis • mRNA processing • cell differentiation • mRNA transport • viral mRNA export from host cell nucleus • negative regulation of DNA damage checkpoint • monocyte differentiation • RNA splicing • RNA export from nucleus • mRNA export from nucleus • mRNA 3'-end processing Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	8563	107829
Ensembl	ENSG00000100296	ENSMUSG00000034274
UniProt	Q13769	Q8BKT7
RefSeq (mRNA)	NM_001002877 NM_001002878 NM_001002879 NM_003678	NM_172438
RefSeq (protein)	NP_001002877 NP_001002878 NP_001002879 NP_003669	NP_766026
Location (UCSC)	Chr 22: 29.51 – 29.56 Mb	Chr 11: 4.9 – 4.93 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

THOC5 is evolutionarily conserved in higher eukaryotes, however the exact roles of THOC5 in transcription and mRNA export are still unclear. THOC5 is phosphorylated by several protein kinases at multiple residues upon extracellular stimuli. These include stimulation with growth factors/cytokines/chemokines, or DNA damage reagents. Furthermore, THOC5 is a substrate for several oncogenic tyrosine kinases, suggesting that THOC5 may be involved in cancer development.

Recent THOC5 knockout mouse data reveal that THOC5 is an essential element in the maintenance of stem cells and growth factor/cytokine-mediated differentiation/proliferation. Furthermore, depletion of THOC5 influences less than 1% of total mRNA export in the steady state, however it influences more than 90% of growth factor/cytokine induced genes. THOC5, thereby contributes to the 3′ processing and/or export of immediate-early genes induced by extracellular stimuli. These studies bring new insight into the link between the mRNA export complex and immediate-early gene response. T

he data from these studies also suggest that THOC5 may be a useful tool for studying stem cell biology, for modifying the differentiation processes and for cancer therapy.[5][6][7][8][9][10][11][12][13][14][15][16]

[17][18][19][20][21][22]

References

1. GRCh38: Ensembl release 89: ENSG00000100296 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000034274 - 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. Tran DDH, Koch A and Tamura T. THOC5, a member of the mRNA export complex: a novel link between mRNA export machinery and signal transduction pathways in cell proliferation and differentiation. Cell Communication and Signaling 2014, 12:3
6. Tran DD, Saran S, Dittrich-Breiholz O, Williamson AJ, Klebba-Farber S, Koch A, Kracht M, Whetton AD, Tamura T (2013) Transcriptional regulation of immediate-early gene response by THOC5, a member of mRNA export complex, contributes to the M-CSF-induced macrophage differentiation. Cell death & disease 4: e879
7. Saran S, Tran DD, Klebba-Farber S, Moran-Losada P, Wiehlmann L, Koch A, Chopra H, Pabst O, Hoffmann A, Klopfleisch R, Tamura T (2013) THOC5, a member of the mRNA export complex, contributes to processing of a subset of wingless/integrated (Wnt) target mRNAs and integrity of the gut epithelial barrier. BMC Cell Biol 14: 51
8. Griaud, F., Pierce, A., Gonzalez Sanchez, M.B., Scott, M., Abraham, S.A., Holyoake, T.L., Tran, D.D., Tamura, T., and Whetton, A.D. (2013). A pathway from leukemogenic oncogenes and stem cell chemokines to RNA processing via THOC5. Leukemia 27, 932-940.
9. Katahira J, Okuzaki D, Inoue H, Yoneda Y, Maehara K, Ohkawa Y (2013) Human TREX component Thoc5 affects alternative polyadenylation site choice by recruiting mammalian cleavage factor I. Nucleic Acids Research 41: 7060-7072
10. Katahira J, Inoue H, Hurt E, Yoneda Y (2009) Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. The EMBO Journal 28: 556-567
11. Ramachandran S., Tran DD., Klebba-Faerber S., Kardinal C., Whetton AD., Tamura T. An ataxia-teleaniectasia-mutated (ATM) kinase mediated response to DNA damage down-regulates the mRNA-binding potential of THOC5. RNA 17(11):1957-66, 2011
12. Guria A., Tran D.D.H,Ramachandran S.,Koch A.,Bounkari O.,Dutta P,Hauser H,Tamura T. Identification of mRNAs that are spliced but not exported to the cytoplasm in the absence of THOC5 in mouse embryo fibroblasts, RNA, 2011 17:00-00.
13. Mancini, A., Niemann-Seyde, S. C., Pankow, R., El Bounkari, O., Klebba-Färber, S., Koch, A., EJaworska, E., Spooncer, E., Gruber, A. D. , Whetton, A. D., Tamura, T. (2010) THOC5/FMIP, an mRNA export TREX complex protein, is essential for hematopoietic primitive cell survival in vivo. BMC Biology 8, 1.
14. Mancini, A., El Bounkari, O., Norrenbrock, A-F., Scherr, M., Schaefer, D., Eder M., Banham, A. H., Pulford, K., Lyne, L., Whetton A. D., and Tamura, T. (2007) FMIP controls the adipocyte lineage commitment of C2C12 cells by down-modulation of C/EBPalpha. Oncogene 26, 1020-1027.
15. Mancini A., Koch A., Whetton A.D., and Tamura T. (2004)The M-CSF receptor substrate and interacting protein FMIP is governed in its subcellular localization by protein kinase C-mediated phosphorylation and thereby potentiates M-CSF-mediated differentiation. Oncogene, 23, 6581-9.
16. Tamura, T., Mancini, A., Joos, H., Koch, A., Hakim, C., Dumanski, J., Weidner, K.M., and Niemann, H. (1999) FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage. Oncogene, 18, 6488-6495.
17. Strasser K, Masuda S, Mason P, Pfannstiel J, Oppizzi M, Rodriguez-Navarro S, Rondon AG, Aguilera A, Struhl K, Reed R, Hurt E (May 2002). "TREX is a conserved complex coupling transcription with messenger RNA export". Nature. 417 (6886): 304–8. doi:10.1038/nature746. PMID 11979277.
18. Xie YG, Han FY, Peyrard M, Ruttledge MH, Fransson I, DeJong P, Collins J, Dunham I, Nordenskjold M, Dumanski JP (Dec 1993). "Cloning of a novel, anonymous gene from a megabase-range YAC and cosmid contig in the neurofibromatosis type 2/meningioma region on human chromosome 22q12". Hum Mol Genet. 2 (9): 1361–8. doi:10.1093/hmg/2.9.1361. PMID 8242058.
19. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jul 1999). "Prediction of the coding sequences of unidentified human genes. XIII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID 10231032.
20. Carney L, Pierce A, Rijnen M, Gonzalez Sanchez MB, Hamzah HG, Zhang L, Tamura T, Whetton AD (Dec 2008). "THOC5 couples M-CSF receptor signaling to transcription factor expression". Cell Signal. 21 (2): 309–16. doi:10.1016/j.cellsig.2008.10.018. PMID 19015024.
21. Pierce A, Carney L, Hamza HG, Griffiths JR, Zhang L, Whetton BA, Gonzalez Sanchez MB, Tamura T, Sternberg D, Whetton AD (May 2008). "THOC5 spliceosome protein: a target for leukaemogenic tyrosine kinases that affects inositol lipid turnover". Br J Haematol. 141 (5): 641–50. doi:10.1111/j.1365-2141.2008.07090.x. PMID 18373705.
22. "Entrez Gene: THOC5 THO complex 5".

Further reading

• Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
• Tamura T, Mancini A, Joos H, et al. (2000). "FMIP, a novel Fms-interacting protein, affects granulocyte/macrophage differentiation". Oncogene. 18 (47): 6488–95. doi:10.1038/sj.onc.1203062. PMID 10597251.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Mancini A, Koch A, Whetton AD, Tamura T (2004). "The M-CSF receptor substrate and interacting protein FMIP is governed in its subcellular localization by protein kinase C-mediated phosphorylation, and thereby potentiates M-CSF-mediated differentiation". Oncogene. 23 (39): 6581–9. doi:10.1038/sj.onc.1207841. PMID 15221008.
• Collins JE, Wright CL, Edwards CA, et al. (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biol. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Carroll JS, Liu XS, Brodsky AS, et al. (2005). "Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1". Cell. 122 (1): 33–43. doi:10.1016/j.cell.2005.05.008. PMID 16009131.
• Olsen JV, Blagoev B, Gnad F, et al. (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.

External links

• THOC5 on biosignaling