TBRG4

TBRG4
Identifikatori
Aliasi	TBRG4
Vanjski ID-jevi	OMIM: 611325 MGI: 1100868 HomoloGene: 31259 GeneCards: TBRG4
Lokacija gena (čovjek)
Hrom.	Hromosom 7 (čovjek)
Kraj	45,112,047 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	6,576,067 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• protein kinase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje sa RNK;
Ćelijska komponenta	• mitohondrija; • mitochondrial matrix;
Biološki proces	• Ćelijsko disanje; • protein phosphorylation; • positive regulation of cell population proliferation; • mRNA metabolic process; • regulation of mitochondrial mRNA stability; • mitochondrial mRNA processing;
	Izvori:Amigo / QuickGO
Ortolozi
	9238
	21379
	ENSG00000136270
	ENSMUSG00000000384
	Q969Z0
	Q91YM4
	NM_199122; NM_001261834; NM_004749; NM_030900
NM_001130457; NM_134011; NM_001362713; NM_001362714; NM_001362715;
	NM_001362716
	NP_001248763; NP_004740; NP_112162; NP_954573
NP_001123929; NP_598772; NP_001349642; NP_001349643; NP_001349644;
	NP_001349645
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

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

Dužina polipeptidnog lanca je 631 aminokiselina, а molekulska težina 70.738 Da.^[12]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

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

TBRG4 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

Kao 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

Učešće 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

^ ^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

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000136270 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000000384 - Ensembl, maj 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.

[uniprot-5] UniProt: Q969Z0

[pmid9383053-6] 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-7] "Entrez Gene: TBRG4 transforming growth factor beta regulator 4".

[pmid20869947-8] 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.

[pmid21444724-9] 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.

[pmid25877407-10] 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.

[pmid23952215-11] 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-12] "UniProt, Q969Z0" (jezik: engleski). Pristupljeno 29. 9. 2021.

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