GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Alpha subfamily is composed of eukaryotic 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1728978028 149 KPKLHYSNGRGRMESIRWLLATAGVEFEEQFIEKKEDLEKLRNDGYLLFQQVPMVEIDGMKMVQTRAIGSYIAAKYNLY 227
Cdd:cd03077     1 KPVLHYFNGRGRMESIRWLLAAAGVEFEEKFIESAEDLEKLKKDGSLMFQQVPMVEIDGMKLVQTRAILNYIAGKYNLY 79

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Alpha subfamily is composed of eukaryotic 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1728978028 149 KPKLHYSNGRGRMESIRWLLATAGVEFEEQFIEKKEDLEKLRNDGYLLFQQVPMVEIDGMKMVQTRAIGSYIAAKYNLY 227
Cdd:cd03077     1 KPVLHYFNGRGRMESIRWLLAAAGVEFEEKFIESAEDLEKLKKDGSLMFQQVPMVEIDGMKLVQTRAILNYIAGKYNLY 79

glutathione s-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978028 146 MAGKPKLHYSNGRGRMESIRWLLATAGVEF-EEQFIEKKEDLEKLRN---DGYLLFQQVPMVEIDGMKMVQTRAIGSYIA 221
Cdd:PTZ00057    1 MAEEIVLYYFDARGKAELIRLIFAYLGIEYtDKRFGENGDAFIEFKNfkkEKDTPFEQVPILEMDNIIFAQSQAIVRYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978028 222 AKYNLYGKDLKERAWIDMYVEGTTDLmgmimYLPFQAADTKEKNLALIIERATTRYFPVYEKALKDHGQDYLVGNKLSWA 301
Cdd:PTZ00057   81 KKYKICGESELNEFYADMIFCGVQDI-----HYKFNNTNLFKQNETTFLNEELPKWSGYFENILKKNHCNYFVGDNLTYA 155

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1728978028 302 DIHLLEAILMAEECKPDILSAFPLLQAFKGRTSNIPTIKKFLqpgSQRK 350
Cdd:PTZ00057  156 DLAVFNLYDDIETKYPNSLKNFPLLKAHNEFISNLPNIKNYI---SNRK 201

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978028 150 PKLHYSNGRG--RMESIRWLLATAGVEFEEQFI------EKKEDLEKLRNdgyllFQQVPMVEIDGMKMVQTRAIGSYIA 221
Cdd:pfam02798   1 MVLTLYGIRGspRAHRIRWLLAEKGVEYEIVPLdfgagpEKSPELLKLNP-----LGKVPALEDGGKKLTESRAILEYIA 75

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. The class Alpha subfamily is composed of eukaryotic 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1728978028 149 KPKLHYSNGRGRMESIRWLLATAGVEFEEQFIEKKEDLEKLRNDGYLLFQQVPMVEIDGMKMVQTRAIGSYIAAKYNLY 227
Cdd:cd03077     1 KPVLHYFNGRGRMESIRWLLAAAGVEFEEKFIESAEDLEKLKKDGSLMFQQVPMVEIDGMKLVQTRAILNYIAGKYNLY 79

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978028 246 DLMGMIMYLPFQAADTKEKNL-ALIIERATTRYFPVYEKALKDHGQDYLVGNKLSWADIHLLEAILMAEE-CKPDILSAF 323
Cdd:pfam14497   2 DLHHPIASSLYYEDEKKKAKRrKEFREERLPKFLGYFEKVLNKNGGGYLVGDKLTYADLALFQVLDGLLYpKAPDALDKY 81

                          90       100
                  ....*....|....*....|.
gi 1728978028 324 PLLQAFKGRTSNIPTIKKFLQ 344
Cdd:pfam14497  82 PKLKALHERVAARPNIKAYLA 102

C-terminal, alpha helical domain of Class Sigma-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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-like members include the class II insect GSTs, S-crystallins from cephalopods, nematode-specific GSTs, 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. Members also include 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978028 233 ERAWIDMYVEGTTDLMGMIMYLPF--QAADTKEKNLALIIERATtRYFPVYEKALKDHGQDYLVGNKLSWADIHLLEAIL 310
Cdd:cd03192     2 EEARVDAIVDTIADLRAEFAPYFYepDGEEKKEKKKEFLEEALP-KFLGKFEKILKKSGGGYFVGDKLTWADLALFDVLD 80

                          90       100
                  ....*....|....*....|...
gi 1728978028 311 MAEECKP-DILSAFPLLQAFKGR 332
Cdd:cd03192    81 YLLYLLPkDLLEKYPKLKALRER 103

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 1728978028 232 KERAWIDMYVEGTTDLMGMIMYLPFQAADT-KEKNLALIIERattryFPVYEKALKDH-GQDYLVGNKLSWADIHLLEAI 309
Cdd:cd03210     2 KEAALIDMVNDGVEDLRLKYVRMIYQNYEAgKDDYIKDLPEQ-----LKPFEKLLAKNnGKGFIVGDKISFADYNLFDLL 76

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1728978028 310 LMAEECKPDILSAFPLLQAFKGRTSNIPTIKKFLQPGSQRKPP 352
Cdd:cd03210    77 DIHLVLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNRP 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978028 150 PKLHYSNGRG--RMESIRWLLATAGVEFEEQFI------EKKEDLEKLRNdgyllFQQVPMVEIDGMKMVQTRAIGSYIA 221
Cdd:pfam02798   1 MVLTLYGIRGspRAHRIRWLLAEKGVEYEIVPLdfgagpEKSPELLKLNP-----LGKVPALEDGGKKLTESRAILEYIA 75

C-terminal, alpha helical domain of Class Mu Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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 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 1728978028 232 KERAWIDMYVEGTTDLM---GMIMYLP-FQAAdtKEKNLALIIERattryFPVYEKALKDHgqDYLVGNKLSWADIHLLE 307
Cdd:cd03209     1 KERIRVDMLEQQAMDLRmglIRICYSPdFEKL--KPDYLEKLPDK-----LKLFSEFLGDR--PWFAGDKITYVDFLLYE 71

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1728978028 308 AILMAEECKPDILSAFPLLQAFKGRTSNIPTIKKFLQpgSQR 349
Cdd:cd03209    72 ALDQHRIFEPDCLDAFPNLKDFLERFEALPKISAYMK--SDR 111

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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 tumours.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1728978028 149 KPKLHYSNGRGRMESIRWLLATAGVEFEEQFIEKKEDLEKLRNDgyLLFQQVPMVEIDGMKMVQTRAIGSYIAAK 223
Cdd:cd03076     1 PYTLTYFPVRGRAEAIRLLLADQGISWEEERVTYEEWQESLKPK--MLFGQLPCFKDGDLTLVQSNAILRHLGRK 73

glutathione S-transferase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978028 168 LATAGVEFEEQFIekkeDLEK--LRNDGYLLFQ---QVPMVEIDGMKMVQTRAIGSYIAAKY-----NLYGKDLKERA-- 235
Cdd:PLN02395   20 LIEKGVEFETVPV----DLMKgeHKQPEYLALQpfgVVPVIVDGDYKIFESRAIMRYYAEKYrsqgpDLLGKTIEERGqv 95

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1728978028 236 --WIDmyVEGTT---DLMGMIMYLPFQA-----ADTK-----EKNLALIIErattryfpVYEKALKDhgQDYLVGNKLSW 300
Cdd:PLN02395   96 eqWLD--VEATSyhpPLLNLTLHILFASkmgfpADEKvikesEEKLAKVLD--------VYEARLSK--SKYLAGDFVSL 163

                  ....*.
gi 1728978028 301 ADI-HL 305
Cdd:PLN02395  164 ADLaHL 169

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1728978028 150 PKLHYSNgRGRMESIRWLLATAGVEFEeqFIEKKEDLEKLRNDGYLLFQ---QVPMVEIDGMKMVQTRAIGSYIAAKY 224
Cdd:cd03046     1 ITLYHLP-RSRSFRILWLLEELGLPYE--LVLYDRGPGEQAPPEYLAINplgKVPVLVDGDLVLTESAAIILYLAEKY 75

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1728978028 275 TRYFPVYEKALKDHGqdYLVGNKLSWADIHLLEAILMAEECKPDiLSAFPLLQAFKGRTSNIP 337
Cdd:cd03189    64 KRHLDFLEDHLAKHP--YFAGDELTAADIMMSFPLEAALARGPL-LEQYPNIAAYLERIEARP 123

C-terminal, alpha helical domain of Ure2p and related Glutathione S-transferase-like proteins; Glutathione S-transferase (GST) C-terminal domain family, Ure2p-like subfamily; composed of the Saccharomyces cerevisiae Ure2p, YfcG and YghU from Escherichia coli, and related GST-like proteins. Ure2p is a regulator for nitrogen catabolism in yeast. It represses the expression of several gene products involved in the use of poor nitrogen sources when rich sources are available. A transmissible conformational change of Ure2p results in a prion called [Ure3], an inactive, self-propagating and infectious amyloid. Ure2p displays a GST fold containing an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The N-terminal thioredoxin-fold domain is sufficient to induce the [Ure3] phenotype and is also called the prion domain of Ure2p. In addition to its role in nitrogen regulation, Ure2p confers protection to cells against heavy metal ion and oxidant toxicity, and shows glutathione (GSH) peroxidase activity. YfcG and YghU are two of the nine GST homologs in the genome of Escherichia coli. They display very low or no GSH transferase, but show very good disulfide bond oxidoreductase activity. YghU also shows modest organic hydroperoxide reductase activity. GSTs are cytosolic dimeric proteins involved in cellular detoxification by catalyzing the conjugation of 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 active site is located in a cleft between the N- and C-terminal domains. GSH binds to the N-terminal domain while the hydrophobic substrate occupies a pocket in the C-terminal domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1728978028 270 IERATT---RYFPVYEKALKDHgqDYLVGNKLSWADIHLLEAILMAEECKPDILSAFPLLQAFKGRTSNIPTIKK 341
Cdd:cd03178    38 IERYTDevkRLYGVLDKRLSDR--PYLAGEEYSIADIALYPWTHYADLGGFADLSEYPNVKRWLERIAARPAVQK 110