Homolog podjedinice 5 THO kompleksa jest protein koji je kod ljudi kodiran genom THOC5 sa hromosoma 22. THOCs je član THO kompleksa koji je potkompleks kompleksa za transkripciju/eksport (TREX).
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Zatvori
THOC5 je evolucijski konzerviran kod viših eukariota, ali tačne uloge THOC5 u transkripciji i ieksportu iRNK još uvijek nisu jasne. THOC5 je fosforiliziran pomoću nekoliko protein-kinaza na više ostataka nakon vanćelijskog stimulusa. To uključuje stimulaciju faktorima rasta/citokinima/hemokinima ili reagensima za oštećenje DNK. Nadalje, THOC5 je supstrat za nekoliko onkogenih tirozin-kinaza, što sugerira da THOC5 može biti uključen u razvoj raka.
Dužina polipeptidnog lanca je 683 aminokiseline, a molekulska težina 78.508 Da.
| 10 | | 20 | | 30 | | 40 | | 50 |
|---|
| MSSESSKKRK | | PKVIRSDGAP | | AEGKRNRSDT | | EQEGKYYSEE | | AEVDLRDPGR |
| DYELYKYTCQ | | ELQRLMAEIQ | | DLKSRGGKDV | | AIEIEERRIQ | | SCVHFMTLKK |
| LNRLAHIRLK | | KGRDQTHEAK | | QKVDAYHLQL | | QNLLYEVMHL | | QKEITKCLEF |
| KSKHEEIDLV | | SLEEFYKEAP | | PDISKAEVTM | | GDPHQQTLAR | | LDWELEQRKR |
| LAEKYRECLS | | NKEKILKEIE | | VKKEYLSSLQ | | PRLNSIMQAS | | LPVQEYLFMP |
| FDQAHKQYET | | ARHLPPPLYV | | LFVQATAYGQ | | ACDKTLSVAI | | EGSVDEAKAL |
| FKPPEDSQDD | | ESDSDAEEEQ | | TTKRRRPTLG | | VQLDDKRKEM | | LKRHPLSVML |
| DLKCKDDSVL | | HLTFYYLMNL | | NIMTVKAKVT | | TAMELITPIS | | AGDLLSPDSV |
| LSCLYPGDHG | | KKTPNPANQY | | QFDKVGILTL | | SDYVLELGHP | | YLWVQKLGGL |
| HFPKEQPQQT | | VIADHSLSAS | | HMETTMKLLK | | TRVQSRLALH | | KQFASLEHGI |
| VPVTSDCQYL | | FPAKVVSRLV | | KWVTVAHEDY | | MELHFTKDIV | | DAGLAGDTNL |
| YYMALIERGT | | AKLQAAVVLN | | PGYSSIPPVF | | QLCLNWKGEK | | TNSNDDNIRA |
| MEGEVNVCYK | | ELCGPWPSHQ | | LLTNQLQRLC | | VLLDVYLETE | | SHDDSVEGPK |
| EFPQEKMCLR | | LFRGPSRMKP | | FKYNHPQGFF | | SHR |
Nedavni podaci o THOC5 nokaut-miševima otkrivaju da je THOC5 bitan element u održavanju matičnih ćelija i faktor rasta/citokinom posredovane diferencijacije/ proliferacije. Nadalje, iscrpljivanje THOC5 utiče na manje od 1% ukupnog eksporta iRNK u stabilnom stanju, ali utiče na više od 90% gena indukovanih faktorom rasta/citokinom. THOC5, na taj način doprinosi 3′ obradi i/ili eksportu neposredno ranih gena induciranih vanćelijskim stimulansima. Ove studije donose novi uvid u vezu između kompleksa za eksport iRNK i neposrednog ranog genskog odgovora.
Podaci iz ovih studija takođe sugerišu da THOC5 može biti koristan alat za proučavanje biologije matičnih ćelija, za modifikaciju procesa diferencijacije i za terapiju raka.[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]
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
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
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
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.
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
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
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
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.
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.
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.
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.
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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