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Identification
HMDB Protein ID HMDBP00827
Secondary Accession Numbers
  • 6108
Name Glutathione S-transferase A4
Synonyms
  1. GST class-alpha member 4
  2. Glutathione S-transferase A4-4
Gene Name GSTA4
Protein Type Enzyme
Biological Properties
General Function Involved in glutathione transferase activity
Specific Function Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. This isozyme has a high catalytic efficiency with 4-hydroxyalkenals such as 4-hydroxynonenal (4-HNE).
Pathways
  • Chemical carcinogenesis
  • Drug metabolism - cytochrome P450
  • Glutathione metabolism
  • Metabolism of xenobiotics by cytochrome P450
Reactions
RX + Glutathione → HX + R-S-glutathione details
RX + Glutathione → Halide + R-S-Glutathione details
Naphthalene epoxide + Glutathione → (1R)-Hydroxy-(2R)-glutathionyl-1,2-dihydronaphthalene details
(1S,2R)-Naphthalene 1,2-oxide + Glutathione → (1R)-Glutathionyl-(2R)-hydroxy-1,2-dihydronaphthalene details
(1S,2R)-Naphthalene 1,2-oxide + Glutathione → (1S)-Hydroxy-(2S)-glutathionyl-1,2-dihydronaphthalene details
1-Nitronaphthalene-7,8-oxide + Glutathione → 1-Nitro-7-hydroxy-8-glutathionyl-7,8-dihydronaphthalene details
1-Nitronaphthalene-7,8-oxide + Glutathione → 1-Nitro-7-glutathionyl-8-hydroxy-7,8-dihydronaphthalene details
1-Nitronaphthalene-5,6-oxide + Glutathione → 1-Nitro-5-hydroxy-6-glutathionyl-5,6-dihydronaphthalene details
1-Nitronaphthalene-5,6-oxide + Glutathione → 1-Nitro-5-glutathionyl-6-hydroxy-5,6-dihydronaphthalene details
Bromobenzene-3,4-oxide + Glutathione → 3,4-Dihydro-3-hydroxy-4-S-glutathionyl bromobenzene details
Bromobenzene-2,3-oxide + Glutathione → 2,3-Dihydro-2-S-glutathionyl-3-hydroxy bromobenzene details
Benzo[a]pyrene-4,5-oxide + Glutathione → 4,5-Dihydro-4-hydroxy-5-S-glutathionyl-benzo[a]pyrene details
Benzo[a]pyrene-7,8-diol + Glutathione → 7,8-Dihydro-7-hydroxy-8-S-glutathionyl-benzo[a]pyrene + Water details
2,2-Dichloroacetaldehyde + Glutathione → S-(2,2-Dichloro-1-hydroxy)ethyl glutathione details
1,1-Dichloroethylene epoxide + Glutathione → 2-(S-Glutathionyl)acetyl chloride + Hydrochloric acid details
Chloroacetyl chloride + Glutathione → S-(2-Chloroacetyl)glutathione + Hydrochloric acid details
2-(S-Glutathionyl)acetyl chloride + Glutathione → 2-(S-Glutathionyl)acetyl glutathione + Hydrochloric acid details
Trichloroethylene + Glutathione → S-(1,2-Dichlorovinyl)glutathione + Hydrochloric acid details
1,2-Dibromoethane + Glutathione + Hydrogen Ion → Glutathione episulfonium ion + Bromide details
2-Bromoacetaldehyde + Glutathione → S-(Formylmethyl)glutathione + Bromide details
Aldophosphamide + Glutathione → 4-Glutathionyl cyclophosphamide + Water details
2,3-Epoxyaflatoxin B1 + Glutathione → Aflatoxin B1exo-8,9-epoxide-GSH details
GO Classification
Biological Process
glutathione metabolic process
xenobiotic metabolic process
Cellular Component
cytosol
Function
catalytic activity
transferase activity
transferase activity, transferring alkyl or aryl (other than methyl) groups
glutathione transferase activity
Molecular Function
glutathione transferase activity
Process
metabolic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 6
Locus 6p12.1
SNPs GSTA4
Gene Sequence
>669 bp
ATGGCAGCAAGGCCCAAGCTCCACTATCCCAACGGAAGAGGCCGGATGGAGTCCGTGAGA
TGGGTTTTAGCTGCCGCCGGAGTCGAGTTTGATGAAGAATTTCTGGAAACAAAAGAACAG
TTGTACAAGTTGCAGGATGGTAACCACCTGCTGTTCCAACAAGTGCCCATGGTTGAAATT
GACGGGATGAAGTTGGTACAGACCCGAAGCATTCTCCACTACATAGCAGACAAGCACAAT
CTCTTTGGCAAGAACCTCAAGGAGAGAACCCTGATTGACATGTACGTGGAGGGGACACTG
GATCTGCTGGAACTGCTTATCATGCATCCTTTCTTAAAACCAGATGATCAGCAAAAGGAA
GTGGTTAACATGGCCCAGAAGGCTATAATTAGATACTTTCCTGTGTTTGAAAAGATTTTA
AGGGGTCACGGACAAAGCTTTCTTGTTGGTAATCAGCTGAGCCTTGCAGATGTGATTTTA
CTCCAAACCATTTTAGCTCTAGAAGAGAAAATTCCTAATATCCTGTCTGCATTTCCTTTC
CTCCAGGAATACACAGTGAAACTAAGTAATATCCCTACAATTAAGAGATTCCTTGAACCT
GGCAGCAAGAAGAAGCCTCCCCCTGATGAAATTTATGTGAGAACCGTCTACAACATCTTT
AGGCCATAA
Protein Properties
Number of Residues 222
Molecular Weight 25703.905
Theoretical pI 8.267
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Glutathione S-transferase A4
MAARPKLHYPNGRGRMESVRWVLAAAGVEFDEEFLETKEQLYKLQDGNHLLFQQVPMVEI
DGMKLVQTRSILHYIADKHNLFGKNLKERTLIDMYVEGTLDLLELLIMHPFLKPDDQQKE
VVNMAQKAIIRYFPVFEKILRGHGQSFLVGNQLSLADVILLQTILALEEKIPNILSAFPF
LQEYTVKLSNIPTIKRFLEPGSKKKPPPDEIYVRTVYNIFRP
GenBank ID Protein 2597924
UniProtKB/Swiss-Prot ID O15217
UniProtKB/Swiss-Prot Entry Name GSTA4_HUMAN
PDB IDs
GenBank Gene ID Y13047
GeneCard ID GSTA4
GenAtlas ID GSTA4
HGNC ID HGNC:4629
References
General References
  1. 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 ]
  2. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  3. 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 ]
  4. Board PG: Identification of cDNAs encoding two human alpha class glutathione transferases (GSTA3 and GSTA4) and the heterologous expression of GSTA4-4. Biochem J. 1998 Mar 1;330 ( Pt 2):827-31. [PubMed:9480897 ]
  5. Hubatsch I, Ridderstrom M, Mannervik B: Human glutathione transferase A4-4: an alpha class enzyme with high catalytic efficiency in the conjugation of 4-hydroxynonenal and other genotoxic products of lipid peroxidation. Biochem J. 1998 Feb 15;330 ( Pt 1):175-9. [PubMed:9461507 ]
  6. Liu S, Stoesz SP, Pickett CB: Identification of a novel human glutathione S-transferase using bioinformatics. Arch Biochem Biophys. 1998 Apr 15;352(2):306-13. [PubMed:9587421 ]
  7. Desmots F, Rauch C, Henry C, Guillouzo A, Morel F: Genomic organization, 5'-flanking region and chromosomal localization of the human glutathione transferase A4 gene. Biochem J. 1998 Dec 1;336 ( Pt 2):437-42. [PubMed:9820822 ]
  8. Bruns CM, Hubatsch I, Ridderstrom M, Mannervik B, Tainer JA: Human glutathione transferase A4-4 crystal structures and mutagenesis reveal the basis of high catalytic efficiency with toxic lipid peroxidation products. J Mol Biol. 1999 May 7;288(3):427-39. [PubMed:10329152 ]