THOC5

Last updated
THOC5
Identifiers
Aliases THOC5 , C22orf19, Fmip, PK1.3, fSAP79, THO complex 5
External IDs OMIM: 612733; MGI: 1351333; HomoloGene: 37836; GeneCards: THOC5; OMA:THOC5 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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: 4.85 – 4.88 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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).

Contents

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. The 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]

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References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000100296 Ensembl, May 2017
  2. 1 2 3 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
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  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.
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  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. S2CID   21122818.
  22. "Entrez Gene: THOC5 THO complex 5".

Further reading