GSTP1

Glutathione S-transferase P is an enzyme that in humans is encoded by the GSTP1 gene.^[4][5]

GSTP1
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 10GS, 11GS, 12GS, 13GS, 14GS, 16GS, 17GS, 18GS, 19GS, 1AQV, 1AQW, 1AQX, 1EOG, 1EOH, 1GSS, 1KBN, 1LBK, 1MD3, 1MD4, 1PGT, 1PX6, 1PX7, 1ZGN, 20GS, 22GS, 2A2R, 2A2S, 2GSS, 2J9H, 2PGT, 3CSH, 3CSI, 3CSJ, 3DD3, 3DGQ, 3GSS, 3GUS, 3HJM, 3HJO, 3HKR, 3IE3, 3KM6, 3KMN, 3KMO, 3N9J, 3PGT, 4GSS, 4PGT, 5GSS, 6GSS, 7GSS, 8GSS, 9GSS
Identifiers
Aliases	GSTP1, DFN7, FAEES3, GST3, GSTP, HEL-S-22, PI, glutathione S-transferase pi 1
External IDs	OMIM: 134660 MGI: 3782108 HomoloGene: 660 GeneCards: GSTP1
Gene location (Human) Chr. Chromosome 11 (human)^[1] Band 11q13.2 Start 67,583,742 bp^[1] End 67,586,656 bp^[1]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube right lobe of thyroid gland left lobe of thyroid gland skin of abdomen right lung upper lobe of left lung anterior pituitary ascending aorta gallbladder canal of the cervix n/a More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity JUN kinase binding kinase regulator activity glutathione binding nitric oxide binding protein binding S-nitrosoglutathione binding dinitrosyl-iron complex binding glutathione transferase activity protein kinase binding glutathione peroxidase activity Cellular component vesicle TRAF2-GSTP1 complex plasma membrane intracellular anatomical structure mitochondrion extracellular exosome nucleus extracellular region extracellular space cytoplasm cytosol secretory granule lumen ficolin-1-rich granule lumen Biological process negative regulation of monocyte chemotactic protein-1 production cellular response to cell-matrix adhesion response to amino acid response to estradiol negative regulation of interleukin-1 beta production negative regulation of acute inflammatory response glutathione metabolic process negative regulation of tumor necrosis factor-mediated signaling pathway negative regulation of leukocyte proliferation common myeloid progenitor cell proliferation nitric oxide storage negative regulation of extrinsic apoptotic signaling pathway negative regulation of apoptotic process response to L-ascorbic acid negative regulation of I-kappaB kinase/NF-kappaB signaling cellular response to epidermal growth factor stimulus central nervous system development cellular response to glucocorticoid stimulus response to nutrient levels negative regulation of MAP kinase activity animal organ regeneration regulation of ERK1 and ERK2 cascade cellular response to insulin stimulus negative regulation of MAPK cascade negative regulation of ERK1 and ERK2 cascade negative regulation of stress-activated MAPK cascade oligodendrocyte development positive regulation of superoxide anion generation negative regulation of tumor necrosis factor production metabolism response to ethanol cellular response to lipopolysaccharide negative regulation of JUN kinase activity negative regulation of fibroblast proliferation negative regulation of nitric-oxide synthase biosynthetic process glutathione derivative biosynthetic process response to toxic substance regulation of stress-activated MAPK cascade negative regulation of biosynthetic process cellular oxidant detoxification negative regulation of protein kinase activity xenobiotic metabolic process negative regulation of smooth muscle cell chemotaxis linoleic acid metabolic process negative regulation of vascular associated smooth muscle cell proliferation neutrophil degranulation response to reactive oxygen species cellular response to oxidative stress xenobiotic catabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2950 100042625 Ensembl ENSG00000084207 n/a UniProt P09211 n/a RefSeq (mRNA) NM_000852 XM_036155425 RefSeq (protein) NP_000843 n/a Location (UCSC) Chr 11: 67.58 – 67.59 Mb n/a PubMed search ^[2] ^[3]
Wikidata
View/Edit Human View/Edit Mouse

Function

Glutathione S-transferases (GSTs) are a family of enzymes that play an important role in detoxification by catalyzing the conjugation of many hydrophobic and electrophilic compounds with reduced glutathione. Based on their biochemical, immunologic, and structural properties, the soluble GSTs are categorized into four main classes: alpha, mu, pi, and theta. The glutathione S-transferase pi gene (GSTP1) is a polymorphic gene encoding active, functionally different GSTP1 variant proteins that are thought to function in xenobiotic metabolism and play a role in susceptibility to cancer, and other diseases.^[6]

Interactions

GSTP1 has been shown to interact with Fanconi anemia, complementation group C^[7][8] and MAPK8.^[9]

GST-Pi is expressed in many human tissues, particularly in the biliary tree, renal distal convoluted tubules and lungs.^[10]

Possible drug target

Triple-negative breast cancer cells rely on glutathione-S-transferase Pi1, and inhibitors are being studied.^[11] Piperlongumine has been found to silence the gene.^[12]

References

1. GRCh38: Ensembl release 89: ENSG00000084207 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Bora PS, Bora NS, Wu XL, Lange LG (October 1991). "Molecular cloning, sequencing, and expression of human myocardial fatty acid ethyl ester synthase-III cDNA". J. Biol. Chem. 266 (25): 16774–7. doi:10.1016/S0021-9258(18)55367-9. PMID 1885604.
5. Smith CM, Bora PS, Bora NS, Jones C, Gerhard DS (November 1995). "Genetic and radiation-reduced somatic cell hybrid sublocalization of the human GSTP1 gene". Cytogenet. Cell Genet. 71 (3): 235–9. doi:10.1159/000134117. PMID 7587384.
6. "Entrez Gene: GSTP1 glutathione S-transferase pi".
7. Cumming RC, Lightfoot J, Beard K, Youssoufian H, O'Brien PJ, Buchwald M (July 2001). "Fanconi anemia group C protein prevents apoptosis in hematopoietic cells through redox regulation of GSTP1". Nat. Med. 7 (7): 814–20. doi:10.1038/89937. PMID 11433346. S2CID 35177844.
8. Reuter TY, Medhurst AL, Waisfisz Q, Zhi Y, Herterich S, Hoehn H, Gross HJ, Joenje H, Hoatlin ME, Mathew CG, Huber PA (October 2003). "Yeast two-hybrid screens imply involvement of Fanconi anemia proteins in transcription regulation, cell signaling, oxidative metabolism, and cellular transport". Exp. Cell Res. 289 (2): 211–21. doi:10.1016/S0014-4827(03)00261-1. PMID 14499622.
9. Wang T, Arifoglu P, Ronai Z, Tew KD (15 June 2001). "Glutathione S-transferase P1-1 (GSTP1-1) inhibits c-Jun N-terminal kinase (JNK1) signaling through interaction with the C terminus". J. Biol. Chem. 276 (24): 20999–1003. doi:10.1074/jbc.M101355200. PMID 11279197.
10. Terrier, P; Townsend, AJ; Coindre, JM; Triche, TJ; Cowan, KH (October 1990). "An immunohistochemical study of pi class glutathione S-transferase expression in normal human tissue". The American Journal of Pathology. 137 (4): 845–53. PMC 1877535. PMID 1977319.
11. Triple-negative breast cancer target is found. May 2016
12. "Researchers uncover mechanism for cancer-killing properties of pepper plant".

Further reading

• Strange RC, Fryer AA (1999). "The glutathione S-transferases: influence of polymorphism on cancer susceptibility". IARC Sci. Publ. (148): 231–49. PMID 10493261.
• Kellen E, Hemelt M, Broberg K, Golka K, Kristensen VN, Hung RJ, Matullo G, Mittal RD, Porru S, Povey A, Schulz WA, Shen J, Buntinx F, Zeegers MP, Taioli E (2007). "Pooled analysis and meta-analysis of the glutathione S-transferase P1 Ile 105Val polymorphism and bladder cancer: a HuGE-GSEC review". Am. J. Epidemiol. 165 (11): 1221–30. doi:10.1093/aje/kwm003. PMID 17404387.
• Sekine I, Minna JD, Nishio K, Tamura T, Saijo N (2006). "A literature review of molecular markers predictive of clinical response to cytotoxic chemotherapy in patients with lung cancer". J Thorac Oncol. 1 (1): 31–7. doi:10.1097/01243894-200601000-00008. PMID 17409824.