C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The class Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845  86 LKERTLIDMYVEGTLDLLELLIMHPFLKPDDQQKEVVNMAQKAIIRYFPVFEKILRGHGQSFLVGNQLSLADVILLQTIL 165
Cdd:cd03208    1 LKERALIDMYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAIL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 530381845 166 ALEEKIPNILSAFPFLQEYTVKLSNIPTIKRFLEPGSKKKPPPDEIYVRTVYNIF 220
Cdd:cd03208   81 MVEELDPSILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The class Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845  86 LKERTLIDMYVEGTLDLLELLIMHPFLKPDDQQKEVVNMAQKAIIRYFPVFEKILRGHGQSFLVGNQLSLADVILLQTIL 165
Cdd:cd03208    1 LKERALIDMYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAIL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 530381845 166 ALEEKIPNILSAFPFLQEYTVKLSNIPTIKRFLEPGSKKKPPPDEIYVRTVYNIF 220
Cdd:cd03208   81 MVEELDPSILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845   1 MAARPKLHYPNGRGRMESVRWVLAAAGVEF-DEEFLETKEQLYKLQD---GNHLLFQQVPMVEIDGMKLVQTRSILHYIA 76
Cdd:PTZ00057   1 MAEEIVLYYFDARGKAELIRLIFAYLGIEYtDKRFGENGDAFIEFKNfkkEKDTPFEQVPILEMDNIIFAQSQAIVRYLS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845  77 DKHNLFGKNLKERTLIDMYVEGTLDllellIMHPFLKPDDQQKEVVNMAQKAIIRYFPVFEKILRGHGQSFLVGNQLSLA 156
Cdd:PTZ00057  81 KKYKICGESELNEFYADMIFCGVQD-----IHYKFNNTNLFKQNETTFLNEELPKWSGYFENILKKNHCNYFVGDNLTYA 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 530381845 157 DVILLQTILALEEKIPNILSAFPFLQEYTVKLSNIPTIKRFL 198
Cdd:PTZ00057 156 DLAVFNLYDDIETKYPNSLKNFPLLKAHNEFISNLPNIKNYI 197

Glutathione S-transferase, C-terminal domain; This domain is closely related to pfam00043.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845  101 DLLELLIMHPFLKPDDQQKEVVNM-AQKAIIRYFPVFEKILRGHGQSFLVGNQLSLADVILLQTILALEEKI-PNILSAF 178
Cdd:pfam14497   2 DLHHPIASSLYYEDEKKKAKRRKEfREERLPKFLGYFEKVLNKNGGGYLVGDKLTYADLALFQVLDGLLYPKaPDALDKY 81

                          90       100
                  ....*....|....*....|.
gi 530381845  179 PFLQEYTVKLSNIPTIKRFLE 199
Cdd:pfam14497  82 PKLKALHERVAARPNIKAYLA 102

C-terminal, alpha helical domain of Class Alpha Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Alpha subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. The class Alpha subfamily is composed of vertebrate GSTs which can form homodimer and heterodimers. There are at least six types of class Alpha GST subunits in rats, four of which have human counterparts, resulting in many possible isoenzymes with different activities, tissue distribution and substrate specificities. Human GSTA1-1 and GSTA2-2 show high GSH peroxidase activity. GSTA3-3 catalyzes the isomerization of intermediates in steroid hormone biosynthesis. GSTA4-4 preferentially catalyzes the GSH conjugation of alkenals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845  86 LKERTLIDMYVEGTLDLLELLIMHPFLKPDDQQKEVVNMAQKAIIRYFPVFEKILRGHGQSFLVGNQLSLADVILLQTIL 165
Cdd:cd03208    1 LKERALIDMYVEGTADLMEMIMMLPFLPPEEKEAKLALIKEKAKNRYFPVFEKVLKDHGQDFLVGNKLSRADVQLLEAIL 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 530381845 166 ALEEKIPNILSAFPFLQEYTVKLSNIPTIKRFLEPGSKKKPPPDEIYVRTVYNIF 220
Cdd:cd03208   81 MVEELDPSILSDFPLLQAFKTRISNIPTIKKFLQPGSKRKPPPDEKYVETVRKVF 135

GST_N family, Class Sigma_like; composed of GSTs belonging to class Sigma and similar proteins, including GSTs from class Mu, Pi and Alpha. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. Vertebrate class Sigma GSTs are characterized as GSH-dependent hematopoietic prostaglandin (PG) D synthases and are responsible for the production of PGD2 by catalyzing the isomerization of PGH2. The functions of PGD2 include the maintenance of body temperature, inhibition of platelet aggregation, bronchoconstriction, vasodilation and mediation of allergy and inflammation. Other class Sigma members include the class II insect GSTs, S-crystallins from cephalopods and 28-kDa GSTs from parasitic flatworms. Drosophila GST2 is associated with indirect flight muscle and exhibits preference for catalyzing GSH conjugation to lipid peroxidation products, indicating an anti-oxidant role. S-crystallin constitutes the major lens protein in cephalopod eyes and is responsible for lens transparency and proper refractive index. The 28-kDa GST from Schistosoma is a multifunctional enzyme, exhibiting GSH transferase, GSH peroxidase and PGD2 synthase activities, and may play an important role in host-parasite interactions. Also members are novel GSTs from the fungus Cunninghamella elegans, designated as class Gamma, and from the protozoan Blepharisma japonicum, described as a light-inducible GST.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 530381845   5 PKLHYPNGRGRMESVRWVLAAAGVEFDEEFLETKEQLYKLQDGNhLLFQQVPMVEIDGMKLVQTRSILHYIAD 77
Cdd:cd03039    1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPELDLKPT-LPFGQLPVLEIDGKKLTQSNAILRYLAR 72

Glutathione S-transferase [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845   6 KLHY--PNGRGRmeSVRWVLAAAGVEFDEEfletkeqLYKLQDGNH----LL----FQQVPMVEIDGMKLVQTRSILHYI 75
Cdd:COG0625    3 KLYGspPSPNSR--RVRIALEEKGLPYELV-------PVDLAKGEQkspeFLalnpLGKVPVLVDDGLVLTESLAILEYL 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845  76 ADKH---NLFGKNLKERTLIDM---YVEGTLDLLELLIMHPFLKPDDQqkEVVNMAQKAIIRYFPVFEKILRGHGqsFLV 149
Cdd:COG0625   74 AERYpepPLLPADPAARARVRQwlaWADGDLHPALRNLLERLAPEKDP--AAIARARAELARLLAVLEARLAGGP--YLA 149

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 530381845 150 GNQLSLADVILLQTILALEE-KIPniLSAFPFLQEYTVKLSNIPTIKRFLEPG 201
Cdd:COG0625  150 GDRFSIADIALAPVLRRLDRlGLD--LADYPNLAAWLARLAARPAFQRALAAA 200

C-terminal, alpha helical domain of Class Pi Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Pi subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Class Pi GST is a homodimeric eukaryotic protein. The human GSTP1 is mainly found in erythrocytes, kidney, placenta and fetal liver. It is involved in stress responses and in cellular proliferation pathways as an inhibitor of JNK (c-Jun N-terminal kinase). Following oxidative stress, monomeric GSTP1 dissociates from JNK and dimerizes, losing its ability to bind JNK and causing an increase in JNK activity, thereby promoting apoptosis. GSTP1 is expressed in various tumors and is the predominant GST in a wide range of cancer cells. It has been implicated in the development of multidrug-resistant tumors.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845  87 KERTLIDMYVEGTLDLLELLIMHPFLKPDDQQKEVVnmaqKAIIRYFPVFEKILRGH-GQSFLVGNQLSLADVILLQTIL 165
Cdd:cd03210    2 KEAALIDMVNDGVEDLRLKYVRMIYQNYEAGKDDYI----KDLPEQLKPFEKLLAKNnGKGFIVGDKISFADYNLFDLLD 77

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 530381845 166 ALEEKIPNILSAFPFLQEYTVKLSNIPTIKRFLEPGSKKKPP 207
Cdd:cd03210   78 IHLVLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRP 119

Glutathione S-transferase, N-terminal domain; Function: conjugation of reduced glutathione to a variety of targets. Also included in the alignment, but not GSTs: S-crystallins from squid (similarity to GST previously noted); eukaryotic elongation factors 1-gamma (not known to have GST activity and similarity not previously recognized); HSP26 family of stress-related proteins including auxin-regulated proteins in plants and stringent starvation proteins in E. coli (not known to have GST activity and similarity not previously recognized). The glutathione molecule binds in a cleft between the N- and C-terminal domains - the catalytically important residues are proposed to reside in the N-terminal domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 530381845    5 PKLHYPNGRG--RMESVRWVLAAAGVEFDEEFLETK---EQLYKLQDGNHLlfQQVPMVEIDGMKLVQTRSILHYIAD 77
Cdd:pfam02798   1 MVLTLYGIRGspRAHRIRWLLAEKGVEYEIVPLDFGagpEKSPELLKLNPL--GKVPALEDGGKKLTESRAILEYIAR 76

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845  110 PFLKPDDQQKEVVNMAQKAIIRYFPVFEKILRGHGqsFLVGNQLSLADVILLQTILALEEKIPNILS-AFPFLQEYTVKL 188
Cdd:pfam00043  12 PYVPPEEKKEPEVDEALEKVARVLSALEEVLKGQT--YLVGDKLTLADIALAPALLWLYELDPACLReKFPNLKAWFERV 89

                  ....
gi 530381845  189 SNIP 192
Cdd:pfam00043  90 AARP 93

C-terminal, alpha helical domain of Class Zeta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Zeta subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins, and products of oxidative stress. The GST fold contains an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain. Class Zeta GSTs, also known as maleylacetoacetate (MAA) isomerases, catalyze the isomerization of MAA to fumarylacetoacetate, the penultimate step in tyrosine/phenylalanine catabolism, using GSH as a cofactor. They show little GSH-conjugating activity towards traditional GST substrates, but display modest GSH peroxidase activity. They are also implicated in the detoxification of the carcinogen dichloroacetic acid by catalyzing its dechlorination to glyoxylic acid.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845 113 KPDDQQKEVVNMAQKAIIRYFPVFEKILRGHGQSFLVGNQLSLADVILlqtilaleekIPNILSAfpflQEYTVKLSNIP 192
Cdd:cd03191   33 KLGVSEEEKLAWAQHWIERGFQALEKLLASTAGKYCVGDEPTLADICL----------VPQVYNA----RRFGVDLSPYP 98

                 ....
gi 530381845 193 TIKR 196
Cdd:cd03191   99 TIVR 102

GST_N family, Class Mu subfamily; GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Mu subfamily is composed of eukaryotic GSTs. In rats, at least six distinct class Mu subunits have been identified, with homologous genes in humans for five of these subunits. Class Mu GSTs can form homodimers and heterodimers, giving a large number of possible isoenzymes that can be formed, all with overlapping activities but different substrate specificities. They are the most abundant GSTs in human liver, skeletal muscle and brain, and are believed to provide protection against diseases including cancer and neurodegenerative disorders. Some isoenzymes have additional specific functions. Human GST M1-1 acts as an endogenous inhibitor of ASK1 (apoptosis signal-regulating kinase 1), thereby suppressing ASK1-mediated cell death. Human GSTM2-2 and 3-3 have been identified as prostaglandin E2 synthases in the brain and may play crucial roles in temperature and sleep-wake regulation.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845   5 PKLHYPNGRGRMESVRWVLAAAGVEFDEEFLET-------KEQLYKLQDGNHLLFQQVPMVEIDGMKLVQTRSILHYIAD 77
Cdd:cd03075    1 PTLGYWDIRGLAQPIRLLLEYTGEKYEEKRYELgdapdydRSQWLNEKFKLGLDFPNLPYYIDGDVKLTQSNAILRYIAR 80

                 ..
gi 530381845  78 KH 79
Cdd:cd03075   81 KH 82

GST_N family, Saccharomyces cerevisiae GTT1-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT1, and the Schizosaccharomyces pombe GST-III. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. GTT1, a homodimer, exhibits GST activity with standard substrates and associates with the endoplasmic reticulum. Its expression is induced after diauxic shift and remains high throughout the stationary phase. S. pombe GST-III is implicated in the detoxification of various metals.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 530381845   8 HYPNGRGRMesVRWVLAAAGVEFDEEfletkeqLYKLQDGNH----LL----FQQVPMVEIDGMKLVQTRSILHYIADKH 79
Cdd:cd03046    5 HLPRSRSFR--ILWLLEELGLPYELV-------LYDRGPGEQappeYLainpLGKVPVLVDGDLVLTESAAIILYLAEKY 75

GST_N family, Class Phi subfamily; composed of plant-specific class Phi GSTs and related fungal and bacterial proteins. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of glutathione (GSH) with a wide range of endogenous and xenobiotic alkylating agents, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress. The GST fold contains an N-terminal TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Phi GST subfamily has experience extensive gene duplication. The Arabidopsis and Oryza genomes contain 13 and 16 Phi GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Tau GSTs, showing class specificity in substrate preference. Phi enzymes are highly reactive toward chloroacetanilide and thiocarbamate herbicides. Some Phi GSTs have other functions including transport of flavonoid pigments to the vacuole, shoot regeneration and GSH peroxidase activity.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 530381845  19 VRWVLAAAGVEFDEEFLE------TKEQLYKLQDgnhllFQQVPMVEIDGMKLVQTRSILHYIADK 78
Cdd:cd03053   16 VLLCLEEKGVDYELVPVDltkgehKSPEHLARNP-----FGQIPALEDGDLKLFESRAITRYLAEK 76