C-terminal, alpha helical domain of the Glutathione S-transferase family; Glutathione S-transferase (GST) family, C-terminal alpha helical domain; a large, diverse group of 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. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. 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. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxins, stringent starvation protein A, and aminoacyl-tRNA synthetases.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 197384917  84 QQEAALVDMVNDGLEDV----FRRIAWHY---------------------LHIC----------ISFADYRLLDLLLNLE 128
Cdd:cd03210    1 EKEAALIDMVNDGVEDLrlkyVRMIYQNYeagkddyikdlpeqlkpfeklLAKNngkgfivgdkISFADYNLFDLLDIHL 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 197384917 129 LLFPGYLKDFPLLSAYVARLKARPKLKAFLESPEHVNR 166
Cdd:cd03210   81 VLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNR 118

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 197384917  84 QQEAALVDMVNDGLEDV----FRRIAWHY---------------------LHIC----------ISFADYRLLDLLLNLE 128
Cdd:cd03210    1 EKEAALIDMVNDGVEDLrlkyVRMIYQNYeagkddyikdlpeqlkpfeklLAKNngkgfivgdkISFADYNLFDLLDIHL 80

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 197384917 129 LLFPGYLKDFPLLSAYVARLKARPKLKAFLESPEHVNR 166
Cdd:cd03210   81 VLAPGCLDAFPLLKAFVERLSARPKLKAYLESDAFKNR 118

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 197384917   6 IIYFPSRGHCEVMRMLLADQGQSWKEEV--VTLDVW-EQGTFKAS--CLFGQIPKFQDGKLTLYQSNAILRHLGHSFGLY 80
Cdd:PTZ00057   7 LYYFDARGKAELIRLIFAYLGIEYTDKRfgENGDAFiEFKNFKKEkdTPFEQVPILEMDNIIFAQSQAIVRYLSKKYKIC 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 197384917  81 GKDQQEAALVDMVNDGLEDVFRRI-------------------AW--------------HYLHICISFADYRLLDLLLNL 127
Cdd:PTZ00057  87 GESELNEFYADMIFCGVQDIHYKFnntnlfkqnettflneelpKWsgyfenilkknhcnYFVGDNLTYADLAVFNLYDDI 166

                        170       180       190
                 ....*....|....*....|....*....|.
gi 197384917 128 ELLFPGYLKDFPLLSAYVARLKARPKLKAFL 158
Cdd:PTZ00057 167 ETKYPNSLKNFPLLKAHNEFISNLPNIKNYI 197

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 197384917    5 TIIYFPSRGHC--EVMRMLLADQGQSWkeEVVTLDVWEQGT----FKASCLFGQIPKFQDGKLTLYQSNAILRHL 73
Cdd:pfam02798   2 VLTLYGIRGSPraHRIRWLLAEKGVEY--EIVPLDFGAGPEkspeLLKLNPLGKVPALEDGGKKLTESRAILEYI 74

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 197384917   4 YTIIYFPSRGHCEVMRMLLADQGQSWKEEVVTLDVWEQGTFKASCLFGQIPKFQDGKLTLYQSNAILRHLG 74
Cdd:cd03039    1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYLA 71

Glutathione S-transferase (GST) family, N-terminal domain; a large, diverse group of 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. In addition, GSTs also show GSH peroxidase activity and are involved in the synthesis of prostaglandins and leukotrienes. This family, also referred to as soluble GSTs, is the largest family of GSH transferases and is only distantly related to the mitochondrial GSTs (GSTK subfamily, a member of the DsbA family). Soluble GSTs bear no structural similarity to microsomal GSTs (MAPEG family) and display additional activities unique to their group, such as catalyzing thiolysis, reduction and isomerization of certain compounds. 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. Based on sequence similarity, different classes of GSTs have been identified, which display varying tissue distribution, substrate specificities and additional specific activities. In humans, GSTs display polymorphisms which may influence individual susceptibility to diseases such as cancer, arthritis, allergy and sclerosis. Some GST family members with non-GST functions include glutaredoxin 2, the CLIC subfamily of anion channels, prion protein Ure2p, crystallins, metaxin 2 and stringent starvation protein A.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 197384917   4 YTIIYFPSRGHCEVMRMLLADQGQSWKEEVVTLDVWEQGTFKASCLFGQIPKFQDGKLTLYQSNAILRHL 73
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYL 70

GST_N family, unknown subfamily 4; composed of uncharacterized bacterial proteins with similarity to GSTs. 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.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 197384917   4 YTIIYFPSRGHCEVMRMLLADQGQSWkeEVVTLDVWEQGT----FKASCLFGQIPKFQDGKLTLYQSNAILRHL 73
Cdd:cd03056    1 MKLYGFPLSGNCYKVRLLLALLGIPY--EWVEVDILKGETrtpeFLALNPNGEVPVLELDGRVLAESNAILVYL 72

glutathione s-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 197384917   6 IIYFPSRGHCEVMRMLLADQGQSWKEEV--VTLDVW-EQGTFKAS--CLFGQIPKFQDGKLTLYQSNAILRHLGHSFGLY 80
Cdd:PTZ00057   7 LYYFDARGKAELIRLIFAYLGIEYTDKRfgENGDAFiEFKNFKKEkdTPFEQVPILEMDNIIFAQSQAIVRYLSKKYKIC 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 197384917  81 GKDQQEAALVDMVNDGLEDVFRRI-------------------AW--------------HYLHICISFADYRLLDLLLNL 127
Cdd:PTZ00057  87 GESELNEFYADMIFCGVQDIHYKFnntnlfkqnettflneelpKWsgyfenilkknhcnYFVGDNLTYADLAVFNLYDDI 166

                        170       180       190
                 ....*....|....*....|....*....|.
gi 197384917 128 ELLFPGYLKDFPLLSAYVARLKARPKLKAFL 158
Cdd:PTZ00057 167 ETKYPNSLKNFPLLKAHNEFISNLPNIKNYI 197

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 197384917    5 TIIYFPSRGHC--EVMRMLLADQGQSWkeEVVTLDVWEQGT----FKASCLFGQIPKFQDGKLTLYQSNAILRHL 73
Cdd:pfam02798   2 VLTLYGIRGSPraHRIRWLLAEKGVEY--EIVPLDFGAGPEkspeLLKLNPLGKVPALEDGGKKLTESRAILEYI 74

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 197384917   5 TIIYFPSRGHCEVMRMLLADQGQSWKEEVVTLD--------VWEQGTFKASCLFGQIPKFQDGKLTLYQSNAILRHLG 74
Cdd:cd03075    2 TLGYWDIRGLAQPIRLLLEYTGEKYEEKRYELGdapdydrsQWLNEKFKLGLDFPNLPYYIDGDVKLTQSNAILRYIA 79

GST_N family, unknown subfamily 2; composed of uncharacterized bacterial proteins with similarity to GSTs. 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. The sequence from Burkholderia cepacia was identified as part of a gene cluster involved in the degradation of 2,4,5-trichlorophenoxyacetic acid. Some GSTs (e.g. Class Zeta and Delta) are known to catalyze dechlorination reactions.

                         10        20
                 ....*....|....*....|....*
gi 197384917  50 FGQIPKFQDGKLTLYQSNAILRHLG 74
Cdd:cd03047   49 NGRVPVLEDGDFVLWESNAILRYLA 73

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
                 ....*....|....*....|....*....
gi 197384917 131 FPGYLKDFPLLSAYVARLKARPKLKAFLE 159
Cdd:cd03208   86 DPSILSDFPLLQAFKTRISNIPTIKKFLQ 114

glutathione S-transferase

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 197384917  50 FGQIPKFQDGKLTLYQSNAILRHLGHSF-----GLYGKDQQEAALVD 91
Cdd:PLN02395  50 FGVVPVIVDGDYKIFESRAIMRYYAEKYrsqgpDLLGKTIEERGQVE 96