Glutathione S-transferase A1

GSTA1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1GSD, 1GSE, 1GSF, 1GUH, 1K3L, 1K3O, 1K3Y, 1PKW, 1PKZ, 1PL1, 1PL2, 1USB, 1XWG, 1YDK, 2R3X, 2R6K, 3I69, 3I6A, 3IK9, 3KTL, 3L0H, 3Q74, 3U6V, 3ZFB, 3ZFL, 4HJ2
Identifiers
Aliases	GSTA1 , GST2, GSTA1-1, GTH1, GST-epsilon, glutathione S-transferase alpha 1
External IDs	OMIM: 138359 HomoloGene: 130684 GeneCards: GSTA1
Gene location (Human) Chr. Chromosome 6 (human) [1] Band 6p12.2 Start 52,791,371 bp [1] End 52,803,860 bp [1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bronchial epithelial cell jejunal mucosa Right adrenal gland duodenum glomerulus gallbladder right lobe of liver metanephric glomerulus islet of Langerhans kidney n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity glutathione peroxidase activity glutathione transferase activity steroid delta-isomerase activity peroxidase activity oxidoreductase activity isomerase activity Cellular component cytoplasm extracellular exosome cytosol Biological process metabolism epithelial cell differentiation glutathione derivative biosynthetic process glutathione metabolic process cellular oxidant detoxification linoleic acid metabolic process prostaglandin metabolic process xenobiotic metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2938 n/a Ensembl ENSG00000243955 n/a UniProt P08263 n/a RefSeq (mRNA) NM_145740 NM_001319059 n/a RefSeq (protein) NP_001305988 NP_665683 n/a Location (UCSC) Chr 6: 52.79 – 52.8 Mb n/a PubMed search [2] n/a
Wikidata
View/Edit Human

Glutathione S-transferase A1 is an enzyme that in humans is encoded by the GSTA1 gene. ^[3]

Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes function in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding these enzymes are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of some drugs. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-transferase belonging to the alpha class. The alpha class genes, located in a cluster mapped to chromosome 6, are the most abundantly expressed glutathione S-transferases in liver (hepatocytes) and kidney (proximal tubules). In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity, thereby protecting the cells from reactive oxygen species and the products of peroxidation. ^[4]

Release of GST-A1 as an indication of cellular necrosis

Increases in serum and urinary GST-A1 have been found in association with hepatocyte and renal proximal tubular necrosis respectively, and have potential for monitoring injury to these tissues. ^{[5] [6]}

References

1. GRCh38: Ensembl release 89: ENSG00000243955 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Mucher G, Becker J, Knapp M, Buttner R, Moser M, Rudnik-Schoneborn S, Somlo S, Germino G, Onuchic L, Avner E, Guay-Woodford L, Zerres K (Apr 1998). "Fine mapping of the autosomal recessive polycystic kidney disease locus (PKHD1) and the genes MUT, RDS, CSNK2 beta, and GSTA1 at 6p21.1-p12". Genomics. 48 (1): 40–5. doi: 10.1006/geno.1997.5145 . PMID   9503014.
4. "Entrez Gene: GSTA1 glutathione S-transferase A1".
5. Knapen, MF; Mulder, TP; Bisseling, JG; Penders, RH; Peters, WH; Steegers, EA (January 1998). "Plasma glutathione S-transferase alpha 1-1: a more sensitive marker for hepatocellular damage than serum alanine aminotransferase in hypertensive disorders of pregnancy". American Journal of Obstetrics and Gynecology. 178 (1 Pt 1): 161–5. doi:10.1016/S0002-9378(98)70645-3. PMID   9465822.
6. Heemskerk, S; Pickkers, P; Bouw, MP; Draisma, A; van der Hoeven, JG; Peters, WH; Smits, P; Russel, FG; Masereeuw, R (July 2006). "Upregulation of renal inducible nitric oxide synthase during human endotoxemia and sepsis is associated with proximal tubule injury". Clinical Journal of the American Society of Nephrology. 1 (4): 853–62. doi: 10.2215/cjn.00490206 . PMID   17699297.

Further reading

• Morel F, Schulz WA, Sies H (1995). "Gene structure and regulation of expression of human glutathione S-transferases alpha". Biol. Chem. Hoppe-Seyler. 375 (10): 641–9. PMID   7888077.
• Stenberg G, Björnestedt R, Mannervik B (1992). "Heterologous expression of recombinant human glutathione transferase A1-1 from a hepatoma cell line". Protein Expr. Purif. 3 (1): 80–4. doi:10.1016/1046-5928(92)90060-A. PMID   1330133.
• Bogaards JJ, van Ommen B, van Bladeren PJ (1992). "Purification and characterization of eight glutathione S-transferase isoenzymes of hamster. Comparison of subunit composition of enzymes from liver, kidney, testis, pancreas and trachea". Biochem. J. 286 (2): 383–8. doi:10.1042/bj2860383. PMC   1132909 . PMID   1530570.
• Rozen F, Nguyen T, Pickett CB (1992). "Isolation and characterization of a human glutathione S-transferase Ha1 subunit gene". Arch. Biochem. Biophys. 292 (2): 589–93. doi:10.1016/0003-9861(92)90035-U. PMID   1731620.
• Board PG, Mannervik B (1991). "The contribution of the C-terminal sequence to the catalytic activity of GST2, a human alpha-class glutathione transferase". Biochem. J. 275 (1): 171–4. doi:10.1042/bj2750171. PMC   1150028 . PMID   2018473.
• Hayes JD, Kerr LA, Cronshaw AD (1990). "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. 264 (2): 437–45. doi:10.1042/bj2640437. PMC   1133600 . PMID   2604726.
• Board PG, Webb GC (1987). "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. 84 (8): 2377–81. Bibcode:1987PNAS...84.2377B. doi: 10.1073/pnas.84.8.2377 . PMC   304654 . PMID   3031680.
• Rhoads DM, Zarlengo RP, Tu CP (1987). "The basic glutathione S-transferases from human livers are products of separate genes". Biochem. Biophys. Res. Commun. 145 (1): 474–81. doi:10.1016/0006-291X(87)91345-3. PMID   3036131.
• Chow NW, Whang-Peng J, Kao-Shan CS, et al. (1988). "Human glutathione S-transferases. The Ha multigene family encodes products of different but overlapping substrate specificities". J. Biol. Chem. 263 (26): 12797–800. doi: 10.1016/S0021-9258(18)37626-9 . PMID   3138230.
• Tu CP, Qian B (1988). "Nucleotide sequence of the human liver glutathione S-transferase subunit 1 cDNA". Biochem. Soc. Trans. 15 (4): 734–6. doi:10.1042/bst0150734. PMID   3678589.
• Tu CP, Qian B (1987). "Human liver glutathione S-transferases: complete primary sequence of an Ha subunit cDNA". Biochem. Biophys. Res. Commun. 141 (1): 229–37. doi:10.1016/S0006-291X(86)80358-8. PMID   3800996.
• Suzuki T, Smith S, Board PG (1994). "Structure and function of the 5' flanking sequences of the human alpha class glutathione S-transferase genes". Biochem. Biophys. Res. Commun. 200 (3): 1665–71. doi:10.1006/bbrc.1994.1643. PMID   8185623.
• Anttila S, Hirvonen A, Vainio H, et al. (1994). "Immunohistochemical localization of glutathione S-transferases in human lung". Cancer Res. 53 (23): 5643–8. PMID   8242618.
• Suzuki T, Johnston PN, Board PG (1994). "Structure and organization of the human alpha class glutathione S-transferase genes and related pseudogenes". Genomics. 18 (3): 680–6. doi:10.1016/S0888-7543(05)80373-8. PMID   8307579.
• Sinning I, Kleywegt GJ, Cowan SW, et al. (1993). "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. 232 (1): 192–212. doi:10.1006/jmbi.1993.1376. PMID   8331657.
• Ahmad H, Singhal SS, Saxena M, Awasthi YC (1993). "Characterization of two novel subunits of the alpha-class glutathione S-transferases of human liver". Biochim. Biophys. Acta. 1161 (2–3): 333–6. doi:10.1016/0167-4838(93)90234-i. PMID   8431482.
• Cameron AD, Sinning I, L'Hermite G, et al. (1996). "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. 3 (7): 717–27. doi: 10.1016/S0969-2126(01)00206-4 . PMID   8591048.
• Mulder TP, Peters WH, Court DA, Jansen JB (1996). "Sandwich ELISA for glutathione S-transferase Alpha 1-1: plasma concentrations in controls and in patients with gastrointestinal disorders". Clin. Chem. 42 (3): 416–9. doi: 10.1093/clinchem/42.3.416 . PMID   8598105.