TXN2

TXN2
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	1UVZ, 1W4V, 1W89
Identifikatori
Aliasi	TXN2
Vanjski ID-jevi	OMIM: 609063 MGI: 1929468 HomoloGene: 40849 GeneCards: TXN2
Lokacija gena (miš)
Hrom.	Hromosom 15 (miš)
Kraj	77,813,206 bp
Obrazac RNK ekspresije
	; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• peptide-methionine (S)-S-oxide reductase activity; • peptide-methionine (R)-S-oxide reductase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • protein-disulfide reductase activity; • GO:0032403 protein-containing complex binding;
Ćelijska komponenta	• Jedarce; • mitohondrija; • mitochondrial matrix; • soma; • dendrit;
Biološki proces	• response to hypoxia; • response to hormone; • cellular response to nutrient levels; • GO:1904578 response to organic cyclic compound; • GO:0001306 response to oxidative stress; • glycerol ether metabolic process; • response to axon injury; • response to glucose; • cell redox homeostasis; • sulfur amino acid catabolic process;
	Izvori:Amigo / QuickGO
Ortolozi
	25828
	56551
	n/a
	ENSMUSG00000005354
	Q99757
	P97493
	NM_012473
	NM_019913
	NP_036605
	NP_064297
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Mitohondrijski tioredoksin znan i kao tioredoksin-2 je protein koji je kod ljudi kodiran geno TXN2 sa hromosoma 22.^[4]^[5]^[6] Ovaj jedarni gen kodira mitohondrijskog člana porodice tioredoksin, grupe malih multifunkcionalnih redoks-aktivnih proteina. Kodirani protein može imati važnu ulogu u regulaciji mitohondrijskog membranskog potencijala i u zaštiti od oksidansom-indukovane apoptoze.^[4]

Aminokiselinska sekvenca

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

|content=

10	20	30	40	50
MAQRLLLRRF	LASVISRKPS	QGQWPPLTSR	ALQTPQCSPG	GLTVTPNPAR
TIYTTRISLT	TFNIQDGPDF	QDRVVNSETP	VVVDFHAQWC	GPCKILGPRL
EKMVAKQHGK	VVMAKVDIDD	HTDLAIEYEV	SAVPTVLAMK	NGDVVDKFVG
IKDEDQLEAF	LKKLIG

Struktura

Kao tioredoksin, TXN2 je protein od 12 kDa karakteriziran redoks aktivnim mjestom Trp-Cys-Gly-Pro-Cys. U svom oksidiranom (neaktivnom) obliku, dva cisteina formiraju disulfidnu vezu. Ova veza se zatim redukuje pomoću tioredoksin-reduktaze i NADPH do ditiola, koji služi kao disulfidnu reduktazu. Za razliku od TXN1, TXN2 sadrži pretpostavljenu N-terminalnu mitohondrijsku ciljajuću sekvencu, odgovornu za njegovu mitohondrijsku lokalizaciju, i nema strukturne cisteine.^[7]^[8] Dva iRNK transkripta gena TXN2 razlikuju se za ~330 bp u dužini 3′-neprevedene regije, i vjeruje se da oba postoje in vivo.^[8]

Funkcija

Ovaj jedarni gen kodira mitohondrijskog člana porodice tioredoksin, grupe malih multifunkcionalnih redoks-aktivnih proteina.^[4] Kodirani protein je sveprisutno eksprimiran u svim prokariotskim i eukariotskim organizmima, ali pokazuje posebno visoku ekspresiju u tkivima s teškom metaboličkom aktivnošću, uključujući želudac, testis, jajnik, jetru, srce, neurone i nadbubrežnu žlijezdu.^[7]^[8] Može imati važnu ulogu u regulaciji mitohondrijskog membranskog potencijala i u zaštiti od oksidans-inducirane apoptoze.^[4]^[7] Konkretno, sposobnost TXN2 da redukuje disulfidne veze omogućava proteinu da reguliše mitohondrijski redoks i, na taj način, proizvodnju reaktivnih vrsta kisika (ROS). Posljedično, smanjenje ekspresije TXN2 može dovesti do povećanog stvaranja ROS-a i ćelijske smrti.^[7] Antiaptozna funkcija TXN2 pripisuje se njegovom učešću u mehanizmima zavisnim od GSH za uklanjanje ROS-a ili njegovoj interakciji sa, i time regulaciji, tiola u komponenti mitohondrijske propusne tranzicijske pore translokatora adeninskih nukleotida (ANT).^[8]

Pokazalo se da prekomjerna ekspresija TXN2 smanjuje hipoksijski-induciranu akumulaciju HIF-1alfa, što je u direktnoj suprotnosti sa citosolnim TXN1, koji je povećao nivoe HIF-1alfa.^[6] Štaviše, iako su i TXN2 i TXN1 sposobni da redukuju insulin, TXN2 ne zavisi od oksidativnog statusa proteina za ovu aktivnost, što može doprinijeti njihovoj razlici u funkciji.^[7]

Klinički značaj

Dokazano je da genetički polimorfizmiu genu TXN2 mogu biti povezani sa rizikom od spina bifida.^[9]

Poznato je da TXN2 inhibira stvaranje ROS-a stimulirano transformirajućim faktorom rasta (TGF)-β, neovisno o signalizaciji Smad. TGF-β je pro-onkogeni citokin koji inducira epitelno-mezenhimsku tranziciju (EMT), što je ključni događaj u progresiji metastaza. Posebno, TXN2 inhibira TGF-β-posredovanu indukciju HMGA2, centralnog EMT medijatora, i fibronektina, EMT markera.^[10]

Interakcije

Pokazano je da TXN2 interraguje sa ANT.^[8]

Reference

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000005354 - 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.
^ ^a ^b ^c ^d "Entrez Gene: TXN2 thioredoxin 2".
^ Spyrou G, Enmark E, Miranda-Vizuete A, Gustafsson J (Jan 1997). "Cloning and expression of a novel mammalian thioredoxin". The Journal of Biological Chemistry. 272 (5): 2936–41. doi:10.1074/jbc.272.5.2936. PMID 9006939.
^ ^a ^b Zhou J, Damdimopoulos AE, Spyrou G, Brüne B (Mar 2007). "Thioredoxin 1 and thioredoxin 2 have opposed regulatory functions on hypoxia-inducible factor-1alpha". The Journal of Biological Chemistry. 282 (10): 7482–90. doi:10.1074/jbc.M608289200. PMID 17220299.
^ ^a ^b ^c ^d ^e Damdimopoulos AE, Miranda-Vizuete A, Pelto-Huikko M, Gustafsson JA, Spyrou G (Sep 2002). "Human mitochondrial thioredoxin. Involvement in mitochondrial membrane potential and cell death". The Journal of Biological Chemistry. 277 (36): 33249–57. doi:10.1074/jbc.M203036200. PMID 12080052.
^ ^a ^b ^c ^d ^e Chen Y, Cai J, Murphy TJ, Jones DP (Sep 2002). "Overexpressed human mitochondrial thioredoxin confers resistance to oxidant-induced apoptosis in human osteosarcoma cells". The Journal of Biological Chemistry. 277 (36): 33242–8. doi:10.1074/jbc.M202026200. PMID 12032145.
^ Wen S, Lu W, Zhu H, Yang W, Shaw GM, Lammer EJ, Islam A, Finnell RH (Feb 2009). "Genetic polymorphisms in the thioredoxin 2 (TXN2) gene and risk for spina bifida". American Journal of Medical Genetics Part A. 149A (2): 155–160. doi:10.1002/ajmg.a.32589. PMC 2970524. PMID 19165900.
^ Ishikawa F, Kaneko E, Sugimoto T, Ishijima T, Wakamatsu M, Yuasa A, Sampei R, Mori K, Nose K, Shibanuma M (Jan 2014). "A mitochondrial thioredoxin-sensitive mechanism regulates TGF-β-mediated gene expression associated with epithelial-mesenchymal transition". Biochemical and Biophysical Research Communications. 443 (3): 821–7. doi:10.1016/j.bbrc.2013.12.050. PMID 24342608.

Dodatni izvori

Wang Z, Zhang H, Li XF, Le XC (2007). "Study of interactions between arsenicals and thioredoxins (human and E. coli) using mass spectrometry". Rapid Communications in Mass Spectrometry. 21 (22): 3658–66. Bibcode:2007RCMS...21.3658W. doi:10.1002/rcm.3263. PMID 17939155.
Udler M, Maia AT, Cebrian A, Brown C, Greenberg D, Shah M, Caldas C, Dunning A, Easton D, Ponder B, Pharoah P (Jul 2007). "Common germline genetic variation in antioxidant defense genes and survival after diagnosis of breast cancer". Journal of Clinical Oncology. 25 (21): 3015–23. doi:10.1200/JCO.2006.10.0099. PMID 17634480.
Zhang H, Go YM, Jones DP (Sep 2007). "Mitochondrial thioredoxin-2/peroxiredoxin-3 system functions in parallel with mitochondrial GSH system in protection against oxidative stress". Archives of Biochemistry and Biophysics. 465 (1): 119–26. doi:10.1016/j.abb.2007.05.001. PMID 17548047.
Oestergaard MZ, Tyrer J, Cebrian A, Shah M, Dunning AM, Ponder BA, Easton DF, Pharoah PD (Aug 2006). "Interactions between genes involved in the antioxidant defence system and breast cancer risk". British Journal of Cancer. 95 (4): 525–31. doi:10.1038/sj.bjc.6603272. PMC 2360671. PMID 16868544.
Cebrian A, Pharoah PD, Ahmed S, Smith PL, Luccarini C, Luben R, Redman K, Munday H, Easton DF, Dunning AM, Ponder BA (Jan 2006). "Tagging single-nucleotide polymorphisms in antioxidant defense enzymes and susceptibility to breast cancer". Cancer Research. 66 (2): 1225–33. doi:10.1158/0008-5472.CAN-05-1857. PMID 16424062.
Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
Damdimopoulos AE, Miranda-Vizuete A, Pelto-Huikko M, Gustafsson JA, Spyrou G (Sep 2002). "Human mitochondrial thioredoxin. Involvement in mitochondrial membrane potential and cell death". The Journal of Biological Chemistry. 277 (36): 33249–57. doi:10.1074/jbc.M203036200. PMID 12080052.
Chen Y, Cai J, Murphy TJ, Jones DP (Sep 2002). "Overexpressed human mitochondrial thioredoxin confers resistance to oxidant-induced apoptosis in human osteosarcoma cells". The Journal of Biological Chemistry. 277 (36): 33242–8. doi:10.1074/jbc.M202026200. PMID 12032145.

[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000005354 - Ensembl, maj 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-4] "Entrez Gene: TXN2 thioredoxin 2".

[pmid9006939-5] Spyrou G, Enmark E, Miranda-Vizuete A, Gustafsson J (Jan 1997). "Cloning and expression of a novel mammalian thioredoxin". The Journal of Biological Chemistry. 272 (5): 2936–41. doi:10.1074/jbc.272.5.2936. PMID 9006939.

[pmid17220299-6] Zhou J, Damdimopoulos AE, Spyrou G, Brüne B (Mar 2007). "Thioredoxin 1 and thioredoxin 2 have opposed regulatory functions on hypoxia-inducible factor-1alpha". The Journal of Biological Chemistry. 282 (10): 7482–90. doi:10.1074/jbc.M608289200. PMID 17220299.

[pmid12080052-7] Damdimopoulos AE, Miranda-Vizuete A, Pelto-Huikko M, Gustafsson JA, Spyrou G (Sep 2002). "Human mitochondrial thioredoxin. Involvement in mitochondrial membrane potential and cell death". The Journal of Biological Chemistry. 277 (36): 33249–57. doi:10.1074/jbc.M203036200. PMID 12080052.

[pmid12032145-8] Chen Y, Cai J, Murphy TJ, Jones DP (Sep 2002). "Overexpressed human mitochondrial thioredoxin confers resistance to oxidant-induced apoptosis in human osteosarcoma cells". The Journal of Biological Chemistry. 277 (36): 33242–8. doi:10.1074/jbc.M202026200. PMID 12032145.

[9] Wen S, Lu W, Zhu H, Yang W, Shaw GM, Lammer EJ, Islam A, Finnell RH (Feb 2009). "Genetic polymorphisms in the thioredoxin 2 (TXN2) gene and risk for spina bifida". American Journal of Medical Genetics Part A. 149A (2): 155–160. doi:10.1002/ajmg.a.32589. PMC 2970524. PMID 19165900.

[pmid24342608-10] Ishikawa F, Kaneko E, Sugimoto T, Ishijima T, Wakamatsu M, Yuasa A, Sampei R, Mori K, Nose K, Shibanuma M (Jan 2014). "A mitochondrial thioredoxin-sensitive mechanism regulates TGF-β-mediated gene expression associated with epithelial-mesenchymal transition". Biochemical and Biophysical Research Communications. 443 (3): 821–7. doi:10.1016/j.bbrc.2013.12.050. PMID 24342608.

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