Glutathione S-transferase A1

Details

Name
Glutathione S-transferase A1
Synonyms
  • 2.5.1.18
  • GST class-alpha member 1
  • GST HA subunit 1
  • GST-epsilon
  • GSTA1-1
  • GTH1
Gene Name
GSTA1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0011643|Glutathione S-transferase A1
MAEKPKLHYFNARGRMESTRWLLAAAGVEFEEKFIKSAEDLDKLRNDGYLMFQQVPMVEI
DGMKLVQTRAILNYIASKYNLYGKDIKERALIDMYIEGIADLGEMILLLPVCPPEEKDAK
LALIKEKIKNRYFPAFEKVLKSHGQDYLVGNKLSRADIHLVELLYYVEELDSSLISSFPL
LKALKTRISNLPTVKKFLQPGSPRKPPMDEKSLEEARKIFRF
Number of residues
222
Molecular Weight
25630.785
Theoretical pI
9.34
GO Classification
Functions
glutathione transferase activity
Processes
epithelial cell differentiation / glutathione derivative biosynthetic process / glutathione metabolic process / metabolic process / small molecule metabolic process / xenobiotic metabolic process
Components
cytosol / extracellular exosome
General Function
Glutathione transferase activity
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0011644|Glutathione S-transferase A1 (GSTA1)
ATGGCAGAGAAGCCCAAGCTCCACTACTTCAATGCACGGGGCAGAATGGAGTCCACCCGG
TGGCTCCTGGCTGCAGCTGGAGTAGAGTTTGAAGAGAAATTTATAAAATCTGCAGAAGAT
TTGGACAAGTTAAGAAATGATGGATATTTGATGTTCCAGCAAGTGCCAATGGTTGAGATT
GATGGGATGAAGCTGGTGCAGACCAGAGCCATTCTCAACTACATTGCCAGCAAATACAAC
CTCTATGGGAAAGACATAAAGGAGAGAGCCCTGATTGATATGTATATAGAAGGTATAGCA
GATTTGGGTGAAATGATCCTCCTTCTGCCCGTATGTCCACCTGAGGAAAAAGATGCCAAG
CTTGCCTTGATCAAAGAGAAAATAAAAAATCGCTACTTCCCTGCCTTTGAAAAAGTCTTA
AAGAGCCATGGACAAGACTACCTTGTTGGCAACAAGCTGAGCCGGGCTGACATTCATCTG
GTGGAACTTCTCTACTACGTCGAGGAGCTTGACTCCAGTCTTATCTCCAGCTTCCCTCTG
CTGAAGGCCCTGAAAACCAGAATCAGCAACCTGCCCACAGTGAAGAAGTTTCTACAGCCT
GGCAGCCCAAGGAAGCCTCCCATGGATGAGAAATCTTTAGAAGAAGCAAGGAAGATTTTC
AGGTTTTAA
Chromosome Location
6
Locus
6p12.1
External Identifiers
ResourceLink
UniProtKB IDP08263
UniProtKB Entry NameGSTA1_HUMAN
GenBank Protein ID306809
GenBank Gene IDM15872
GenAtlas IDGSTA1
HGNC IDHGNC:4626
General References
  1. Tu CP, Qian B: Human liver glutathione S-transferases: complete primary sequence of an Ha subunit cDNA. Biochem Biophys Res Commun. 1986 Nov 26;141(1):229-37. [PubMed:3800996]
  2. Rhoads DM, Zarlengo RP, Tu CP: The basic glutathione S-transferases from human livers are products of separate genes. Biochem Biophys Res Commun. 1987 May 29;145(1):474-81. [PubMed:3036131]
  3. Tu CP, Qian B: Nucleotide sequence of the human liver glutathione S-transferase subunit 1 cDNA. Biochem Soc Trans. 1987 Aug;15(4):734-6. [PubMed:3678589]
  4. Board PG, Webb GC: Isolation of a cDNA clone and localization of human glutathione S-transferase 2 genes to chromosome band 6p12. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2377-81. [PubMed:3031680]
  5. Rozen F, Nguyen T, Pickett CB: Isolation and characterization of a human glutathione S-transferase Ha1 subunit gene. Arch Biochem Biophys. 1992 Feb 1;292(2):589-93. [PubMed:1731620]
  6. Stenberg G, Bjornestedt R, Mannervik B: Heterologous expression of recombinant human glutathione transferase A1-1 from a hepatoma cell line. Protein Expr Purif. 1992 Feb;3(1):80-4. [PubMed:1330133]
  7. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [PubMed:14574404]
  8. 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. [PubMed:15489334]
  9. Chow NW, Whang-Peng J, Kao-Shan CS, Tam MF, Lai HC, Tu CP: Human glutathione S-transferases. The Ha multigene family encodes products of different but overlapping substrate specificities. J Biol Chem. 1988 Sep 15;263(26):12797-800. [PubMed:3138230]
  10. Ahmad H, Singhal SS, Saxena M, Awasthi YC: Characterization of two novel subunits of the alpha-class glutathione S-transferases of human liver. Biochim Biophys Acta. 1993 Feb 13;1161(2-3):333-6. [PubMed:8431482]
  11. Hayes JD, Kerr LA, Cronshaw AD: Evidence that glutathione S-transferases B1B1 and B2B2 are the products of separate genes and that their expression in human liver is subject to inter-individual variation. Molecular relationships between the B1 and B2 subunits and other Alpha class glutathione S-transferases. Biochem J. 1989 Dec 1;264(2):437-45. [PubMed:2604726]
  12. Board PG, Mannervik B: The contribution of the C-terminal sequence to the catalytic activity of GST2, a human alpha-class glutathione transferase. Biochem J. 1991 Apr 1;275 ( Pt 1):171-4. [PubMed:2018473]
  13. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  14. Sinning I, Kleywegt GJ, Cowan SW, Reinemer P, Dirr HW, Huber R, Gilliland GL, Armstrong RN, Ji X, Board PG, et al.: Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes. J Mol Biol. 1993 Jul 5;232(1):192-212. [PubMed:8331657]
  15. Cameron AD, Sinning I, L'Hermite G, Olin B, Board PG, Mannervik B, Jones TA: Structural analysis of human alpha-class glutathione transferase A1-1 in the apo-form and in complexes with ethacrynic acid and its glutathione conjugate. Structure. 1995 Jul 15;3(7):717-27. [PubMed:8591048]
  16. Le Trong I, Stenkamp RE, Ibarra C, Atkins WM, Adman ET: 1.3-A resolution structure of human glutathione S-transferase with S-hexyl glutathione bound reveals possible extended ligandin binding site. Proteins. 2002 Sep 1;48(4):618-27. [PubMed:12211029]
  17. Hederos S, Broo KS, Jakobsson E, Kleywegt GJ, Mannervik B, Baltzer L: Incorporation of a single His residue by rational design enables thiol-ester hydrolysis by human glutathione transferase A1-1. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13163-7. Epub 2004 Aug 27. [PubMed:15333749]
  18. Kuhnert DC, Sayed Y, Mosebi S, Sayed M, Sewell T, Dirr HW: Tertiary interactions stabilise the C-terminal region of human glutathione transferase A1-1: a crystallographic and calorimetric study. J Mol Biol. 2005 Jun 17;349(4):825-38. [PubMed:15893769]
  19. Grahn E, Novotny M, Jakobsson E, Gustafsson A, Grehn L, Olin B, Madsen D, Wahlberg M, Mannervik B, Kleywegt GJ: New crystal structures of human glutathione transferase A1-1 shed light on glutathione binding and the conformation of the C-terminal helix. Acta Crystallogr D Biol Crystallogr. 2006 Feb;62(Pt 2):197-207. Epub 2006 Jan 18. [PubMed:16421451]
  20. Balogh LM, Le Trong I, Kripps KA, Tars K, Stenkamp RE, Mannervik B, Atkins WM: Structural analysis of a glutathione transferase A1-1 mutant tailored for high catalytic efficiency with toxic alkenals. Biochemistry. 2009 Aug 18;48(32):7698-704. doi: 10.1021/bi900895b. [PubMed:19618965]
  21. Achilonu I, Gildenhuys S, Fisher L, Burke J, Fanucchi S, Sewell BT, Fernandes M, Dirr HW: The role of a topologically conserved isoleucine in glutathione transferase structure, stability and function. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2010 Jul 1;66(Pt 7):776-80. doi: 10.1107/S1744309110019135. Epub 2010 Jun 23. [PubMed:20606271]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01915S-HydroxycysteineexperimentalunknownDetails
DB03003Glutathione Sulfonic AcidexperimentalunknownDetails
DB00143Glutathioneapproved, investigational, nutraceuticalunknownDetails
DB024862-Hydroxyethyl DisulfideexperimentalunknownDetails
DB02943N-(4-Aminobutanoyl)-S-(4-Methoxybenzyl)-L-CysteinylglycineexperimentalunknownDetails
DB03602S-Benzyl-GlutathioneexperimentalunknownDetails
DB04132S-HexylglutathioneexperimentalunknownDetails
DB00143Glutathioneapproved, investigational, nutraceuticalunknownsubstrateDetails
DB01008Busulfanapproved, investigationalunknownsubstrateDetails
DB024862-Hydroxyethyl DisulfideexperimentalunknownDetails
DB02943N-(4-Aminobutanoyl)-S-(4-Methoxybenzyl)-L-CysteinylglycineexperimentalunknownDetails
DB03602S-Benzyl-GlutathioneexperimentalunknownDetails
DB04132S-HexylglutathioneexperimentalunknownDetails
DB00993AzathioprineapprovedunknownsubstrateDetails
DB13014HypericininvestigationalunknownDetails
DB11672Curcuminapproved, experimental, investigationalunknowninhibitorDetails
DB14635Curcumin sulfateexperimentalunknownDetails