Glutathione S-transferase P

Details

Name
Glutathione S-transferase P
Synonyms
  • 2.5.1.18
  • FAEES3
  • GST class-pi
  • GST3
  • GSTP1-1
Gene Name
GSTP1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0010574|Glutathione S-transferase P
MPPYTVVYFPVRGRCAALRMLLADQGQSWKEEVVTVETWQEGSLKASCLYGQLPKFQDGD
LTLYQSNTILRHLGRTLGLYGKDQQEAALVDMVNDGVEDLRCKYISLIYTNYEAGKDDYV
KALPGQLKPFETLLSQNQGGKTFIVGDQISFADYNLLDLLLIHEVLAPGCLDAFPLLSAY
VGRLSARPKLKAFLASPEYVNLPINGNGKQ
Number of residues
210
Molecular Weight
23355.625
Theoretical pI
5.3
GO Classification
Functions
dinitrosyl-iron complex binding / glutathione transferase activity / JUN kinase binding / kinase regulator activity / nitric oxide binding / S-nitrosoglutathione binding
Processes
cellular response to lipopolysaccharide / central nervous system development / common myeloid progenitor cell proliferation / glutathione derivative biosynthetic process / glutathione metabolic process / negative regulation of acute inflammatory response / negative regulation of apoptotic process / negative regulation of biosynthetic process / negative regulation of ERK1 and ERK2 cascade / negative regulation of extrinsic apoptotic signaling pathway / negative regulation of fibroblast proliferation / negative regulation of I-kappaB kinase/NF-kappaB signaling / negative regulation of interleukin-1 beta production / negative regulation of JUN kinase activity / negative regulation of leukocyte proliferation / negative regulation of MAP kinase activity / negative regulation of MAPK cascade / negative regulation of monocyte chemotactic protein-1 production / negative regulation of nitric-oxide synthase biosynthetic process / negative regulation of protein kinase activity / negative regulation of stress-activated MAPK cascade / negative regulation of tumor necrosis factor production / negative regulation of tumor necrosis factor-mediated signaling pathway / nitric oxide storage / positive regulation of superoxide anion generation / regulation of ERK1 and ERK2 cascade / regulation of stress-activated MAPK cascade / response to reactive oxygen species / small molecule metabolic process / xenobiotic metabolic process
Components
cytoplasm / cytosol / extracellular exosome / extracellular space / intracellular / mitochondrion / nucleus / TRAF2-GSTP1 complex / vesicle
General Function
S-nitrosoglutathione binding
Specific Function
Conjugation of reduced glutathione to a wide number of exogenous and endogenous hydrophobic electrophiles. Regulates negatively CDK5 activity via p25/p35 translocation to prevent neurodegeneration.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0010575|Glutathione S-transferase P (GSTP1)
ATGCCGCCCTACACCGTGGTCTATTTCCCAGTTCGAGGCCGCTGCGCGGCCCTGCGCATG
CTGCTGGCAGATCAGGGCCAGAGCTGGAAGGAGGAGGTGGTGACCGTGGAGACGTGGCAG
GAGGGCTCACTCAAAGCCTCCTGCCTATACGGGCAGCTCCCCAAGTTCCAGGACGGAGAC
CTCACCCTGTACCAGTCCAATACCATCCTGCGTCACCTGGGCCGCACCCTTGGGCTCTAT
GGGAAGGACCAGCAGGAGGCAGCCCTGGTGGACATGGTGAATGACGGCGTGGAGGACCTC
CGCTGCAAATACATCTCCCTCATCTACACCAACTATGAGGCGGGCAAGGATGACTATGTG
AAGGCACTGCCCGGGCAACTGAAGCCTTTTGAGACCCTGCTGTCCCAGAACCAGGGAGGC
AAGACCTTCATTGTGGGAGACCAGATCTCCTTCGCTGACTACAACCTGCTGGACTTGCTG
CTGATCCATGAGGTCCTAGCCCCTGGCTGCCTGGATGCGTTCCCCCTGCTCTCAGCATAT
GTGGGGCGCCTCAGTGCCCGGCCCAAGCTCAAGGCCTTCCTGGCCTCCCCTGAGTACGTG
AACCTCCCCATCAATGGCAACGGGAAACAGTGA
Chromosome Location
11
Locus
11q13
External Identifiers
ResourceLink
UniProtKB IDP09211
UniProtKB Entry NameGSTP1_HUMAN
GenBank Protein ID31946
GenBank Gene IDM24485
GenAtlas IDGSTP1
HGNC IDHGNC:4638
General References
  1. Kano T, Sakai M, Muramatsu M: Structure and expression of a human class pi glutathione S-transferase messenger RNA. Cancer Res. 1987 Nov 1;47(21):5626-30. [Article]
  2. Cowell IG, Dixon KH, Pemble SE, Ketterer B, Taylor JB: The structure of the human glutathione S-transferase pi gene. Biochem J. 1988 Oct 1;255(1):79-83. [Article]
  3. Morrow CS, Cowan KH, Goldsmith ME: Structure of the human genomic glutathione S-transferase-pi gene. Gene. 1989 Jan 30;75(1):3-11. [Article]
  4. Moscow JA, Fairchild CR, Madden MJ, Ransom DT, Wieand HS, O'Brien EE, Poplack DG, Cossman J, Myers CE, Cowan KH: Expression of anionic glutathione-S-transferase and P-glycoprotein genes in human tissues and tumors. Cancer Res. 1989 Mar 15;49(6):1422-8. [Article]
  5. Ali-Osman F, Akande O, Antoun G, Mao JX, Buolamwini J: Molecular cloning, characterization, and expression in Escherichia coli of full-length cDNAs of three human glutathione S-transferase Pi gene variants. Evidence for differential catalytic activity of the encoded proteins. J Biol Chem. 1997 Apr 11;272(15):10004-12. [Article]
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  7. Alin P, Mannervik B, Jornvall H: Structural evidence for three different types of glutathione transferase in human tissues. FEBS Lett. 1985 Mar 25;182(2):319-22. [Article]
  8. Mannervik B, Alin P, Guthenberg C, Jensson H, Tahir MK, Warholm M, Jornvall H: Identification of three classes of cytosolic glutathione transferase common to several mammalian species: correlation between structural data and enzymatic properties. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7202-6. [Article]
  9. Singh SV, Ahmad H, Kurosky A, Awasthi YC: Purification and characterization of unique glutathione S-transferases from human muscle. Arch Biochem Biophys. 1988 Jul;264(1):13-22. [Article]
  10. Gevaert K, Goethals M, Martens L, Van Damme J, Staes A, Thomas GR, Vandekerckhove J: Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9. Epub 2003 Mar 31. [Article]
  11. Ji H, Reid GE, Moritz RL, Eddes JS, Burgess AW, Simpson RJ: A two-dimensional gel database of human colon carcinoma proteins. Electrophoresis. 1997 Mar-Apr;18(3-4):605-13. [Article]
  12. Ahmad H, Wilson DE, Fritz RR, Singh SV, Medh RD, Nagle GT, Awasthi YC, Kurosky A: Primary and secondary structural analyses of glutathione S-transferase pi from human placenta. Arch Biochem Biophys. 1990 May 1;278(2):398-408. [Article]
  13. Kong KH, Takasu K, Inoue H, Takahashi K: Tyrosine-7 in human class Pi glutathione S-transferase is important for lowering the pKa of the thiol group of glutathione in the enzyme-glutathione complex. Biochem Biophys Res Commun. 1992 Apr 15;184(1):194-7. [Article]
  14. Kong KH, Nishida M, Inoue H, Takahashi K: Tyrosine-7 is an essential residue for the catalytic activity of human class PI glutathione S-transferase: chemical modification and site-directed mutagenesis studies. Biochem Biophys Res Commun. 1992 Feb 14;182(3):1122-9. [Article]
  15. Kong KH, Inoue H, Takahashi K: Site-directed mutagenesis study on the roles of evolutionally conserved aspartic acid residues in human glutathione S-transferase P1-1. Protein Eng. 1993 Jan;6(1):93-9. [Article]
  16. Goto S, Kawakatsu M, Izumi S, Urata Y, Kageyama K, Ihara Y, Koji T, Kondo T: Glutathione S-transferase pi localizes in mitochondria and protects against oxidative stress. Free Radic Biol Med. 2009 May 15;46(10):1392-403. doi: 10.1016/j.freeradbiomed.2009.02.025. Epub 2009 Mar 6. [Article]
  17. Okamura T, Singh S, Buolamwini J, Haystead T, Friedman H, Bigner D, Ali-Osman F: Tyrosine phosphorylation of the human glutathione S-transferase P1 by epidermal growth factor receptor. J Biol Chem. 2009 Jun 19;284(25):16979-89. doi: 10.1074/jbc.M808153200. Epub 2009 Mar 2. [Article]
  18. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [Article]
  19. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [Article]
  20. Sun KH, Chang KH, Clawson S, Ghosh S, Mirzaei H, Regnier F, Shah K: Glutathione-S-transferase P1 is a critical regulator of Cdk5 kinase activity. J Neurochem. 2011 Sep;118(5):902-14. doi: 10.1111/j.1471-4159.2011.07343.x. Epub 2011 Jul 8. [Article]
  21. Bienvenut WV, Sumpton D, Martinez A, Lilla S, Espagne C, Meinnel T, Giglione C: Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-alpha-acetylation features. Mol Cell Proteomics. 2012 Jun;11(6):M111.015131. doi: 10.1074/mcp.M111.015131. Epub 2012 Jan 5. [Article]
  22. Van Damme P, Lasa M, Polevoda B, Gazquez C, Elosegui-Artola A, Kim DS, De Juan-Pardo E, Demeyer K, Hole K, Larrea E, Timmerman E, Prieto J, Arnesen T, Sherman F, Gevaert K, Aldabe R: N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12449-54. doi: 10.1073/pnas.1210303109. Epub 2012 Jul 18. [Article]
  23. 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. [Article]
  24. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  25. Reinemer P, Dirr HW, Ladenstein R, Huber R, Lo Bello M, Federici G, Parker MW: Three-dimensional structure of class pi glutathione S-transferase from human placenta in complex with S-hexylglutathione at 2.8 A resolution. J Mol Biol. 1992 Sep 5;227(1):214-26. [Article]
  26. Oakley AJ, Rossjohn J, Lo Bello M, Caccuri AM, Federici G, Parker MW: The three-dimensional structure of the human Pi class glutathione transferase P1-1 in complex with the inhibitor ethacrynic acid and its glutathione conjugate. Biochemistry. 1997 Jan 21;36(3):576-85. [Article]
  27. Ji X, Tordova M, O'Donnell R, Parsons JF, Hayden JB, Gilliland GL, Zimniak P: Structure and function of the xenobiotic substrate-binding site and location of a potential non-substrate-binding site in a class pi glutathione S-transferase. Biochemistry. 1997 Aug 12;36(32):9690-702. [Article]
  28. Oakley AJ, Lo Bello M, Battistoni A, Ricci G, Rossjohn J, Villar HO, Parker MW: The structures of human glutathione transferase P1-1 in complex with glutathione and various inhibitors at high resolution. J Mol Biol. 1997 Nov 21;274(1):84-100. [Article]
  29. Prade L, Huber R, Manoharan TH, Fahl WE, Reuter W: Structures of class pi glutathione S-transferase from human placenta in complex with substrate, transition-state analogue and inhibitor. Structure. 1997 Oct 15;5(10):1287-95. [Article]
  30. Ji X, Blaszczyk J, Xiao B, O'Donnell R, Hu X, Herzog C, Singh SV, Zimniak P: Structure and function of residue 104 and water molecules in the xenobiotic substrate-binding site in human glutathione S-transferase P1-1. Biochemistry. 1999 Aug 10;38(32):10231-8. [Article]
  31. Nicotra M, Paci M, Sette M, Oakley AJ, Parker MW, Lo Bello M, Caccuri AM, Federici G, Ricci G: Solution structure of glutathione bound to human glutathione transferase P1-1: comparison of NMR measurements with the crystal structure. Biochemistry. 1998 Mar 3;37(9):3020-7. [Article]
  32. Ang WH, Parker LJ, De Luca A, Juillerat-Jeanneret L, Morton CJ, Lo Bello M, Parker MW, Dyson PJ: Rational design of an organometallic glutathione transferase inhibitor. Angew Chem Int Ed Engl. 2009;48(21):3854-7. doi: 10.1002/anie.200900185. [Article]
  33. Federici L, Lo Sterzo C, Pezzola S, Di Matteo A, Scaloni F, Federici G, Caccuri AM: Structural basis for the binding of the anticancer compound 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio)hexanol to human glutathione s-transferases. Cancer Res. 2009 Oct 15;69(20):8025-34. doi: 10.1158/0008-5472.CAN-09-1314. Epub 2009 Oct 6. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB01242Clomipramineapproved, investigational, vet_approvedunknowninhibitorDetails
DB00143Glutathioneapproved, investigational, nutraceuticalunknownDetails
DB01834(9R,10R)-9-(S-glutathionyl)-10-hydroxy-9,10-dihydrophenanthreneexperimentalunknownDetails
DB01915S-HydroxycysteineexperimentalunknownDetails
DB02633Cibacron BlueexperimentalunknownDetails
DB038142-(N-morpholino)ethanesulfonic acidexperimentalunknownDetails
DB04132S-HexylglutathioneexperimentalunknownDetails
DB03003Glutathione sulfonic acidexperimentalunknownDetails
DB03686S-(4-nitrobenzyl)glutathioneexperimentalunknownDetails
DB04972CanfosfamideinvestigationalunknownDetails
DB05460EzatiostatinvestigationalunknownDetails
DB07849S-NONYL-CYSTEINEexperimentalunknownDetails
DB08370S-(4-BROMOBENZYL)CYSTEINEexperimentalunknownDetails
DB00163Vitamin Eapproved, nutraceutical, vet_approvedunknowninhibitorDetails
DB00291ChlorambucilapprovedunknownsubstrateDetails
DB01008Busulfanapproved, investigationalunknownsubstrateDetails
DB00773EtoposideapprovedunknownsubstrateDetails
DB00515CisplatinapprovedunknownsubstrateDetails
DB00958CarboplatinapprovedunknownsubstrateDetails
DB00526Oxaliplatinapproved, investigationalnosubstrateDetails
DB03619Deoxycholic acidapprovedunknownDetails
DB06246ExisulindinvestigationalunknowninhibitorDetails
DB13014HypericininvestigationalunknowninhibitorDetails
DB00363ClozapineapprovedunknownDetails
DB00197Troglitazoneapproved, investigational, withdrawnunknownDetails
DB11831DinitrochlorobenzeneinvestigationalunknownDetails
DB11672Curcuminapproved, investigationalunknownDetails
DB00903Etacrynic acidapproved, investigationalunknowninhibitorDetails
DB14001alpha-Tocopherol succinateapproved, nutraceutical, vet_approvedunknowninhibitorDetails
DB14002D-alpha-Tocopherol acetateapproved, nutraceutical, vet_approvedunknowninhibitorDetails
DB11672Curcuminapproved, investigationalunknowninhibitorDetails
DB14635Curcumin sulfateexperimentalunknownDetails
DB00316AcetaminophenapprovedunknownsubstrateDetails
DB14924Ritlecitinibapproved, investigationalunknownsubstrateDetails
DB03310Glutathione disulfideapproved, experimental, investigationalunknownactivatorDetails
DB03619Deoxycholic acidapprovedunknowninhibitorDetails
DB00321AmitriptylineapprovedunknowninhibitorDetails
DB00291ChlorambucilapprovedunknownsubstrateDetails