TBRG4
Beta regulator 4 transformirajućeg faktora rasta (TBRG4), poznat i kao protein za obnavljanje progresije ćelijskog ciklusa 2 (CPR2) i protein 4 koji sadrži domen FAST-kinaze (FASTKD4), je protein koji je kod ljudi kodiran genom TBRG4 na hromosomu 7.[5][6][7] Ovaj protein je dio porodice FASTKD, koja je poznata po regulaciji energetske ravnoteže mitohondrija pod stresom i progresije ćelijskog ciklusa.[8][9] TBRG4 je uključen u proliferaciju ćelija u hematopoezi i multipli mijelom.[10][11]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 631 aminokiselina, а molekulska težina 70.738 Da.[12]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MAAHLVKRCT | CLLREAARQA | PAMAPVGRLR | LAWVAHKTLT | SSATSPISHL | ||||
| PGSLMEPVEK | ERASTPYIEK | QVDHLIKKAT | RPEELLELLG | GSHDLDSNQA | ||||
| AMVLIRLSHL | LSEKPEDKGL | LIQDAHFHQL | LCLLNSQIAS | VWHGTLSKLL | ||||
| GSLYALGIPK | ASKELQSVEQ | EVRWRMRKLK | YKHLAFLAES | CATLSQEQHS | ||||
| QELLAELLTH | LERRWTEIED | SHTLVTVMMK | VGHLSEPLMN | RLEDKCLELV | ||||
| EHFGPNELRK | VLVMLAAQSR | RSVPLLRAIS | YHLVQKPFSL | TKDVLLDVAY | ||||
| AYGKLSFHQT | QVSQRLATDL | LSLMPSLTSG | EVAHCAKSFA | LLKWLSLPLF | ||||
| EAFAQHVLNR | AQDITLPHLC | SVLLAFARLN | FHPDQEDQFF | SLVHEKLGSE | ||||
| LPGLEPALQV | DLVWALCVLQ | QAREAELQAV | LHPEFHIQFL | GGKSQKDQNT | ||||
| FQKLLHINAT | ALLEYPEYSG | PLLPASAVAP | GPSALDRKVT | PLQKELQETL | ||||
| KGLLGSADKG | SLEVATQYGW | VLDAEVLLDS | DGEFLPVRDF | VAPHLAQPTG | ||||
| SQSPPPGSKR | LAFLRWEFPN | FNSRSKDLLG | RFVLARRHIV | AAGFLIVDVP | ||||
| FYEWLELKSE | WQKGAYLKDK | MRKAVAEELA | K |
Struktura
urediTBRG4 ima strukturne karakteristike porodice FASTKD, uključujući N-terminal mitohondrijski ciljani domen i tri C-terminalna domena: dva domena slična FAST-kinazi (FAST_1 i FAST_2) i RNK-vezujući domen (RAP).[8][9] Mitohondrijsko ciljno područje usmjerava TBRG4 na import u mitohondrije. Iako su funkcije C-terminalnih domena nepoznate, RAP vjerovatno veže RNK tokom trans-spajanja.[8] TBRG4 također sadrži više navodnih domena leucinskog zatvarača.[6]
Funkcija
urediKao član porodice FASTKD, TBRG4 nalazi se u mitohondrijama, kako bi modulirao njihovu energetsku ravnotežu, posebno u uslovima stresa. Iako je sveprisutno ieksprimiran u svim tkivima, TBRG4 se obilnije pojavljuje u skeletnim mišićima, srčanom mišiću i drugim tkivima obogaćenim mitohondrijama.[8] TBRG4 se također lokalizira u koštanoj srži (BM), gdje funkcionira u hematopoezi, inducirajući lučenje IL-6 i VEGF, koji zatim stimuliraju proliferaciju ćelija i angiogenezu. Međutim, inhibira izlučivanje imunoglobulina normalnim B-ćelijama.[10]
Klinički značaj
urediUčešće TBRG4 u hematopoezi povezuje ga s multiplim mijelomom (MM), što proizlazi iz maligne proliferacije plazmatskih ćelija u koštanoj srži.[10] Visoka ekspresija TBRG4 povezana je sa poboljšanom proliferacijom ćelija i lošijim ishodom; stoga snižena regulacija njegove ekspresije može doprinijeti smanjenju rasta tumora, zaustavljanjem progresije ćelijskog ciklusa.[11]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000136270 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000000384 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ UniProt: Q969Z0
- ^ a b Edwards MC, Liegeois N, Horecka J, DePinho RA, Sprague GF, Tyers M, Elledge SJ (Nov 1997). "Human CPR (cell cycle progression restoration) genes impart a Far- phenotype on yeast cells". Genetics. 147 (3): 1063–76. PMC 1208234. PMID 9383053.
- ^ "Entrez Gene: TBRG4 transforming growth factor beta regulator 4".
- ^ a b c d Simarro M, Gimenez-Cassina A, Kedersha N, Lazaro JB, Adelmant GO, Marto JA, Rhee K, Tisdale S, Danial N, Benarafa C, Orduña A, Anderson P (Oct 2010). "Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration". Biochemical and Biophysical Research Communications. 401 (3): 440–6. doi:10.1016/j.bbrc.2010.09.075. PMC 2963690. PMID 20869947.
- ^ a b Yeung KT, Das S, Zhang J, Lomniczi A, Ojeda SR, Xu CF, Neubert TA, Samuels HH (Jun 2011). "A novel transcription complex that selectively modulates apoptosis of breast cancer cells through regulation of FASTKD2". Molecular and Cellular Biology. 31 (11): 2287–98. doi:10.1128/MCB.01381-10. PMC 3133243. PMID 21444724.
- ^ a b c Sevcikova S, Paszekova H, Besse L, Sedlarikova L, Kubaczkova V, Almasi M, Pour L, Hajek R (Apr 2015). "Extramedullary relapse of multiple myeloma defined as the highest risk group based on deregulated gene expression data" (PDF). Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia. 159 (2): 288–93. doi:10.5507/bp.2015.014. PMID 25877407.
- ^ a b Sarasquete ME, Martínez-López J, Chillón MC, Alcoceba M, Corchete LA, Paiva B, Puig N, Sebastián E, Jiménez C, Mateos MV, Oriol A, Rosiñol L, Palomera L, Teruel AI, González Y, Lahuerta JJ, Bladé J, Gutiérrez NC, Fernández-Redondo E, González M, San Miguel JF, García-Sanz R (Oct 2013). "Evaluating gene expression profiling by quantitative polymerase chain reaction to develop a clinically feasible test for outcome prediction in multiple myeloma". British Journal of Haematology. 163 (2): 223–34. doi:10.1111/bjh.12519. PMID 23952215. S2CID 207081358.
- ^ "UniProt, Q969Z0" (jezik: engleski). Pristupljeno 29. 9. 2021.
Dopunska literatura
uredi- Maruyama K, Sugano S (Jan 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.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 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.
- Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Feb 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 Research. 6 (1): 63–70. doi:10.1093/dnares/6.1.63. PMID 10231032.
- Simpson JC, Wellenreuther R, Poustka A, Pepperkok R, Wiemann S (Sep 2000). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Reports. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
- Rival-Gervier S, Thépot D, Jolivet G, Houdebine LM (maj 2003). "Pig whey acidic protein gene is surrounded by two ubiquitously expressed genes". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1627 (1): 7–14. doi:10.1016/s0167-4781(03)00051-4. PMID 12759187.
- Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (Oct 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
- Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.