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. [PubMed:3664469]
  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. [PubMed:3196325]
  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. [PubMed:2542132]
  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. [PubMed:2466554]
  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. [PubMed:9092542]
  6. 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]
  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. [PubMed:3979555]
  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. [PubMed:3864155]
  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. [PubMed:3395118]
  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. [PubMed:12665801]
  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. [PubMed:9150948]
  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. [PubMed:2327795]
  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. [PubMed:1567427]
  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. [PubMed:1540159]
  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. [PubMed:8433974]
  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. [PubMed:19269317]
  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. [PubMed:19254954]
  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. [PubMed:19608861]
  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. [PubMed:21269460]
  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. [PubMed:21668448]
  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. [PubMed:22223895]
  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. [PubMed:22814378]
  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. [PubMed:24275569]
  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. [PubMed:25944712]
  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. [PubMed:1522586]
  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. [PubMed:9012673]
  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. [PubMed:9245401]
  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. [PubMed:9398518]
  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. [PubMed:9351803]
  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. [PubMed:10441116]
  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. [PubMed:9485454]
  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. [PubMed:19396894]
  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. [PubMed:19808963]

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
DB09462Glycerinapproved, investigationalunknownDetails
DB04132S-HexylglutathioneexperimentalunknownDetails
DB03003Glutathione Sulfonic AcidexperimentalunknownDetails
DB03686S-(P-Nitrobenzyl)GlutathioneexperimentalunknownDetails
DB04339Carbocisteineapproved, investigationalunknownDetails
DB04972CanfosfamideinvestigationalunknownDetails
DB05460EzatiostatinvestigationalunknownDetails
DB07849S-NONYL-CYSTEINEexperimentalunknownDetails
DB08370S-(4-BROMOBENZYL)CYSTEINEexperimentalunknownDetails
DB00163Vitamin Eapproved, nutraceutical, vet_approvedunknowninhibitorDetails
DB00291ChlorambucilapprovedunknownsubstrateDetails
DB01008Busulfanapproved, investigationalunknownsubstrateDetails
DB00773EtoposideapprovedunknownsubstrateDetails
DB00515CisplatinapprovedunknownsubstrateDetails
DB00958CarboplatinapprovedunknownsubstrateDetails
DB00526Oxaliplatinapproved, investigationalunknownsubstrateDetails
DB03619Deoxycholic AcidapprovedunknownDetails
DB06246ExisulindinvestigationalunknowninhibitorDetails
DB13014HypericininvestigationalunknownDetails
DB01015SulfamethoxazoleapprovedunknownDetails
DB00316AcetaminophenapprovedunknownDetails
DB00363ClozapineapprovedunknownDetails
DB00197Troglitazoneinvestigational, withdrawnunknownDetails
DB11831DinitrochlorobenzeneinvestigationalunknownDetails
DB11672Curcuminapproved, experimental, investigationalunknownDetails
DB00903Etacrynic acidapproved, investigationalunknowninhibitorDetails
DB14001alpha-Tocopherol succinateapproved, nutraceutical, vet_approvedunknowninhibitorDetails
DB14002D-alpha-Tocopherol acetateapproved, nutraceutical, vet_approvedunknowninhibitorDetails
DB11672Curcuminapproved, experimental, investigationalunknowninhibitorDetails
DB14635Curcumin sulfateexperimentalunknownDetails
DB14635Curcumin sulfateexperimentalunknownDetails