Glutaredoxin-2, mitochondrial

Details

Name
Glutaredoxin-2, mitochondrial
Synonyms
  • GRX2
Gene Name
GLRX2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004500|Glutaredoxin-2, mitochondrial
MIWRRAALAGTRLVWSRSGSAGWLDRAAGAAGAAAAAASGMESNTSSSLENLATAPVNQI
QETISDNCVVIFSKTSCSYCTMAKKLFHDMNVNYKVVELDLLEYGNQFQDALYKMTGERT
VPRIFVNGTFIGGATDTHRLHKEGKLLPLVHQCYLKKSKRKEFQ
Number of residues
164
Molecular Weight
18051.515
Theoretical pI
9.49
GO Classification
Functions
2 iron, 2 sulfur cluster binding / arsenate reductase (glutaredoxin) activity / electron carrier activity / glutathione disulfide oxidoreductase activity / metal ion binding / protein disulfide isomerase activity / protein disulfide oxidoreductase activity
Processes
aging / apoptotic process / cell differentiation / cell redox homeostasis / cellular response to superoxide / DNA protection / glutathione metabolic process / protein folding / regulation of signal transduction / regulation of transcription, DNA-templated / response to hydrogen peroxide / response to organic substance / response to redox state / response to temperature stimulus
Components
dendrite / intracellular membrane-bounded organelle / mitochondrial matrix / mitochondrion / neuronal cell body / nucleoplasm / nucleus
General Function
Protein disulfide oxidoreductase activity
Specific Function
Glutathione-dependent oxidoreductase that facilitates the maintenance of mitochondrial redox homeostasis upon induction of apoptosis by oxidative stress. Involved in response to hydrogen peroxide and regulation of apoptosis caused by oxidative stress. Acts as a very efficient catalyst of monothiol reactions because of its high affinity for protein glutathione-mixed disulfides. Can receive electrons not only from glutathione (GSH), but also from thioredoxin reductase supporting both monothiol and dithiol reactions. Efficiently catalyzes both glutathionylation and deglutathionylation of mitochondrial complex I, which in turn regulates the superoxide production by the complex. Overexpression decreases the susceptibility to apoptosis and prevents loss of cardiolipin and cytochrome c release.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion
Gene sequence
>lcl|BSEQ0011651|Glutaredoxin-2, mitochondrial (GLRX2)
ATGGAGAGCAATACATCATCATCTTTGGAGAATTTAGCGACGGCGCCTGTGAACCAGATC
CAAGAAACAATTTCTGATAATTGTGTGGTGATTTTCTCAAAAACATCCTGTTCTTACTGT
ACAATGGCAAAAAAGCTTTTCCATGACATGAATGTTAACTATAAAGTGGTGGAACTGGAC
CTGCTTGAATATGGAAACCAGTTCCAAGATGCTCTTTACAAAATGACTGGTGAAAGAACT
GTTCCAAGAATATTTGTCAATGGTACTTTTATTGGAGGTGCAACTGACACTCATAGGCTT
CACAAAGAAGGAAAATTGCTCCCACTAGTTCATCAGTGTTATTTAAAAAAAAGTAAGAGG
AAAGAATTTCAGTGA
Chromosome Location
1
Locus
1q31.2-q31.3
External Identifiers
ResourceLink
UniProtKB IDQ9NS18
UniProtKB Entry NameGLRX2_HUMAN
GenBank Protein ID9507250
GenBank Gene IDAF132495
GenAtlas IDGLRX2
HGNC IDHGNC:16065
General References
  1. Lundberg M, Johansson C, Chandra J, Enoksson M, Jacobsson G, Ljung J, Johansson M, Holmgren A: Cloning and expression of a novel human glutaredoxin (Grx2) with mitochondrial and nuclear isoforms. J Biol Chem. 2001 Jul 13;276(28):26269-75. Epub 2001 Apr 10. [Article]
  2. Gladyshev VN, Liu A, Novoselov SV, Krysan K, Sun QA, Kryukov VM, Kryukov GV, Lou MF: Identification and characterization of a new mammalian glutaredoxin (thioltransferase), Grx2. J Biol Chem. 2001 Aug 10;276(32):30374-80. Epub 2001 Jun 7. [Article]
  3. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [Article]
  4. Lai CH, Chou CY, Ch'ang LY, Liu CS, Lin W: Identification of novel human genes evolutionarily conserved in Caenorhabditis elegans by comparative proteomics. Genome Res. 2000 May;10(5):703-13. [Article]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  6. Lundberg M, Fernandes AP, Kumar S, Holmgren A: Cellular and plasma levels of human glutaredoxin 1 and 2 detected by sensitive ELISA systems. Biochem Biophys Res Commun. 2004 Jul 2;319(3):801-9. [Article]
  7. Peltoniemi M, Kaarteenaho-Wiik R, Saily M, Sormunen R, Paakko P, Holmgren A, Soini Y, Kinnula VL: Expression of glutaredoxin is highly cell specific in human lung and is decreased by transforming growth factor-beta in vitro and in interstitial lung diseases in vivo. Hum Pathol. 2004 Aug;35(8):1000-7. [Article]
  8. Johansson C, Lillig CH, Holmgren A: Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. J Biol Chem. 2004 Feb 27;279(9):7537-43. Epub 2003 Dec 4. [Article]
  9. Lillig CH, Lonn ME, Enoksson M, Fernandes AP, Holmgren A: Short interfering RNA-mediated silencing of glutaredoxin 2 increases the sensitivity of HeLa cells toward doxorubicin and phenylarsine oxide. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13227-32. Epub 2004 Aug 24. [Article]
  10. Enoksson M, Fernandes AP, Prast S, Lillig CH, Holmgren A, Orrenius S: Overexpression of glutaredoxin 2 attenuates apoptosis by preventing cytochrome c release. Biochem Biophys Res Commun. 2005 Feb 18;327(3):774-9. [Article]
  11. Lillig CH, Berndt C, Vergnolle O, Lonn ME, Hudemann C, Bill E, Holmgren A: Characterization of human glutaredoxin 2 as iron-sulfur protein: a possible role as redox sensor. Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8168-73. Epub 2005 May 25. [Article]
  12. Johansson C, Kavanagh KL, Gileadi O, Oppermann U: Reversible sequestration of active site cysteines in a 2Fe-2S-bridged dimer provides a mechanism for glutaredoxin 2 regulation in human mitochondria. J Biol Chem. 2007 Feb 2;282(5):3077-82. Epub 2006 Nov 22. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00143Glutathioneapproved, investigational, nutraceuticalunknownDetails