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 2082271135   4 PVIHYFPIRGRAEVLRLAIVAGGDDFDVVDVNYQEQKSDREK--YPFGQCPRLVDGDLNIVQSNTIARYLAR 73
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPELDLKptLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

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 2082271135   4 PVIHYFPIRGRAEVLRLAIVAGGDDFDVVDVNYQEQKSDREK--YPFGQCPRLVDGDLNIVQSNTIARYLAR 73
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPELDLKptLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

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 2082271135  82 ETEMVAVDEIMEGVESLRVKYVNLIYNDklEEAAKDLYWKTYfdkttsegrngGAHMVYLANFLAKNGGKH-TVGAGLTI 160
Cdd:cd03210     1 EKEAALIDMVNDGVEDLRLKYVRMIYQN--YEAGKDDYIKDL-----------PEQLKPFEKLLAKNNGKGfIVGDKISF 67

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2082271135 161 ADLCLWEILDLHLRIFEDAIKKeYPELVVFHDHIASQPGIKEYLASPKRLAAP-NAN 216
Cdd:cd03210    68 ADYNLFDLLDIHLVLAPGCLDA-FPLLKAFVERLSARPKLKAYLESDAFKNRPiNGN 123

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2082271135   6 IHYFPIRGRAEVLRLAIVAGGDDFDVVDVNY--QEQKSD--REKYPFGQCPRLVDGDLNIVQSNTIARYLARKY---KLQ 78
Cdd:COG0625     4 LYGSPPSPNSRRVRIALEEKGLPYELVPVDLakGEQKSPefLALNPLGKVPVLVDDGLVLTESLAILEYLAERYpepPLL 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2082271135  79 GKDETEMVAVDEIM----EGVESLrVKYVNLIYNDKLEEAAKDLYWKtyfdkttsegrNGGAHMVYLANFLAknGGKHTV 154
Cdd:COG0625    84 PADPAARARVRQWLawadGDLHPA-LRNLLERLAPEKDPAAIARARA-----------ELARLLAVLEARLA--GGPYLA 149

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2082271135 155 GAGLTIADLCLWEILDLHLRIFEDAikKEYPELVVFHDHIASQPGIKEYLASPKRLAA 212
Cdd:COG0625   150 GDRFSIADIALAPVLRRLDRLGLDL--ADYPNLAAWLARLAARPAFQRALAAAEPDLA 205

glutathione S-transferase

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2082271135  20 LAIVAGGDDFDV--VDVNYQEQKSDRE--KYPFGQCPRLVDGDLNIVQSNTIARYLARKYKLQGKD 81
Cdd:PLN02473   19 LCFLEKGIEFEVihVDLDKLEQKKPEHllRQPFGQVPAIEDGDLKLFESRAIARYYATKYADQGTD 84

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 2082271135   4 PVIHYFPIRGRAEVLRLAIVAGGDDFDVVDVNYQEQKSDREK--YPFGQCPRLVDGDLNIVQSNTIARYLAR 73
Cdd:cd03039     1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRITYEEWPELDLKptLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

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 2082271135   4 PVIHYFPIRGRAEVLRLAIVAGGDDFDVVDVNYQE-QKSDREKYPFGQCPRLVDGDLNIVQSNTIARYLARK 74
Cdd:cd03076     2 YTLTYFPVRGRAEAIRLLLADQGISWEEERVTYEEwQESLKPKMLFGQLPCFKDGDLTLVQSNAILRHLGRK 73

glutathione s-transferase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2082271135   5 VIHYFPIRGRAEVLRLAIV------------AGGDDFdvvdVNYQEQKSDREKyPFGQCPRLVDGDLNIVQSNTIARYLA 72
Cdd:PTZ00057    6 VLYYFDARGKAELIRLIFAylgieytdkrfgENGDAF----IEFKNFKKEKDT-PFEQVPILEMDNIIFAQSQAIVRYLS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2082271135  73 RKYKLQGKDETEMVAVDEIMEGVESLRVKY--VNLIYNDKLEEAAKDL-YWKTYFDkttsegrnggahmvylaNFLAKNG 149
Cdd:PTZ00057   81 KKYKICGESELNEFYADMIFCGVQDIHYKFnnTNLFKQNETTFLNEELpKWSGYFE-----------------NILKKNH 143

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 2082271135 150 GKHTVGAGLTIADLCLWEILDLHLRIFEDAIKKeYPELVVFHDHIASQPGIKEYLASPK 208
Cdd:PTZ00057  144 CNYFVGDNLTYADLAVFNLYDDIETKYPNSLKN-FPLLKAHNEFISNLPNIKNYISNRK 201

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 2082271135   4 PVIHYFPIRGRAEVLRLAIVAGGDDFDVVDVNY--QEQKSDREKYPFGQCPRLVDGDLNIVQSNTIARYLA 72
Cdd:cd00570     1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLgeGEQEEFLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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 2082271135   4 PVIHYFPIRG--RAEVLRLAIVAGGDDFDVVDVNYQEQKSDREKY----PFGQCPRLVDGDLNIVQSNTIARYLAR 73
Cdd:pfam02798   1 MVLTLYGIRGspRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELlklnPLGKVPALEDGGKKLTESRAILEYIAR 76

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 2082271135  19 RLAIVAGGDDFDVVDVNYQ--EQKSDR--EKYPFGQCPRLVDGDLNIVQSNTIARYLARK 74
Cdd:cd03053    17 LLCLEEKGVDYELVPVDLTkgEHKSPEhlARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2082271135   3 RPVIHYFPIRGRAEVLRLAIVAGGDDFDVVdvnYQEQKSDREKYP------FGQCPRL-VDGdLNIVQSNTIARYLARKY 75
Cdd:cd03077     1 KPVLHYFNGRGRMESIRWLLAAAGVEFEEK---FIESAEDLEKLKkdgslmFQQVPMVeIDG-MKLVQTRAILNYIAGKY 76

                  ..
gi 2082271135  76 KL 77
Cdd:cd03077    77 NL 78

glutathione S-transferase

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2082271135   8 YFPIRGRAEVLRLAIVAGGDDFDVVDVNYQEQKSDREKY----PFGQCPRLVDGDLNIVQSNTIARYLARKYKLQGKD 81
Cdd:PLN02395    6 YGPAFASPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYlalqPFGVVPVIVDGDYKIFESRAIMRYYAEKYRSQGPD 83

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 2082271135   6 IHYFPIRGRAEVLRLAIVAGGDDFDVVDVNY--QEQKSD--REKYPFGQCPRLVDGDLNIVQSNTIARYLA 72
Cdd:cd03056     3 LYGFPLSGNCYKVRLLLALLGIPYEWVEVDIlkGETRTPefLALNPNGEVPVLELDGRVLAESNAILVYLA 73

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        30
                  ....*....|....*....|....*....|
gi 2082271135  43 REKYPFGQCPRLVDGDLNIVQSNTIARYLA 72
Cdd:cd03047    44 LAMNPNGRVPVLEDGDFVLWESNAILRYLA 73

GST_N family, Stringent starvation protein A (SspA) subfamily; SspA is a RNA polymerase (RNAP)-associated protein required for the lytic development of phage P1 and for stationary phase-induced acid tolerance of E. coli. It is implicated in survival during nutrient starvation. SspA adopts the GST fold with an N-terminal TRX-fold domain and a C-terminal alpha helical domain, but it does not bind glutathione (GSH) and lacks GST activity. SspA is highly conserved among gram-negative bacteria. Related proteins found in Neisseria (called RegF), Francisella and Vibrio regulate the expression of virulence factors necessary for pathogenesis.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 2082271135  19 RLAIVAGGDDFDVVDVNYQEQKSD-REKYPFGQCPRLVDGDLNIVQSNTIARYLARKY 75
Cdd:cd03059    16 RIVLAEKGVSVEIIDVDPDNPPEDlAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73