C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; 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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817117854  80 DWLLQGDPAVLALIAENDLGFKHHLNRYKYAERYPERPMEAYRADGEVFLQKLEALLADRAYLLADHPSLADMAVAPFVR 159
Cdd:cd03196    1 SLDPGALPEMLALIAENDGPFKPHLDRYKYADRYPEDDEEEYRAQAEEFLAELEARLSQHAYLFGDRPSLADYAIFPFVR 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 817117854 160 QFAHVDREWFARTSYRRVQAWLQWFLDSPLFIAVM 194
Cdd:cd03196   81 QFAHVDRDWFDASPYPNLRRWLNRFLQSPLFSKIM 115

C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; 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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817117854  80 DWLLQGDPAVLALIAENDLGFKHHLNRYKYAERYPERPMEAYRADGEVFLQKLEALLADRAYLLADHPSLADMAVAPFVR 159
Cdd:cd03196    1 SLDPGALPEMLALIAENDGPFKPHLDRYKYADRYPEDDEEEYRAQAEEFLAELEARLSQHAYLFGDRPSLADYAIFPFVR 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 817117854 160 QFAHVDREWFARTSYRRVQAWLQWFLDSPLFIAVM 194
Cdd:cd03196   81 QFAHVDRDWFDASPYPNLRRWLNRFLQSPLFSKIM 115

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega 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. 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 Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. Like Omega enzymes, proteins in this subfamily contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 817117854   4 ALRYSFRRCPYAMRARLALRYCGVPLRIVEVSLKAKPAEMLALSPKGTVPVL-SVDGRVIDESLDIMRWAL 73
Cdd:cd03060    1 PILYSFRRCPYAMRARMALLLAGITVELREVELKNKPAEMLAASPKGTVPVLvLGNGTVIEESLDIMRWAL 71

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 817117854  129 LQKLEALLADRAYLLADHPSLADMAVAPFVRQFAHVDREWFARTSYRRVQAWLQ 182
Cdd:pfam13410  13 LDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLDLREGYPRLRAWLE 66

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 817117854   7 YSFRRCPYAMRARLALRYCGVPLRIVEVSL-KAKPAEMLALSPKGTVPVLSVDGRVI 62
Cdd:COG0695    5 YTTPGCPYCARAKRLLDEKGIPYEEIDVDEdPEAREELRERSGRRTVPVIFIGGEHL 61

Glutaredoxin, GrxC family; Glutaredoxins are thioltransferases (disulfide reductases) which utilize glutathione and NADPH as cofactors. Oxidized glutathione is regenerated by glutathione reductase. Together these components compose the glutathione system. Glutaredoxins utilize the CXXC motif common to thioredoxins and are involved in multiple cellular processes including protection from redox stress, reduction of critical enzymes such as ribonucleotide reductase and the generation of reduced sulfur for iron sulfur cluster formation. Glutaredoxins are capable of reduction of mixed disulfides of glutathione as well as the formation of glutathione mixed disulfides. This family of glutaredoxins includes the E. coli protein GrxC (Grx3) which appears to have a secondary role in reducing ribonucleotide reductase (in the absence of GrxA) possibly indicating a role in the reduction of other protein disulfides. [Energy metabolism, Electron transport]

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 817117854    7 YSFRRCPYAMRARLALRYCGVPLRIVEVSL-KAKPAEMLALSPKGTVPVLSVDGRVIDESLDIMrwALAQNDPQDWLL 83
Cdd:TIGR02181   4 YTKPYCPYCTRAKALLSSKGVTFTEIRVDGdPALRDEMMQRSGRRTVPQIFIGDVHVGGCDDLY--ALDREGKLDPLL 79

C-terminal, alpha helical domain of an unknown subfamily 5 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 5; 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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817117854  80 DWLLQGDPAVLALIAENDLGFKHHLNRYKYAERYPERPMEAYRADGEVFLQKLEALLADRAYLLADHPSLADMAVAPFVR 159
Cdd:cd03196    1 SLDPGALPEMLALIAENDGPFKPHLDRYKYADRYPEDDEEEYRAQAEEFLAELEARLSQHAYLFGDRPSLADYAIFPFVR 80

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 817117854 160 QFAHVDREWFARTSYRRVQAWLQWFLDSPLFIAVM 194
Cdd:cd03196   81 QFAHVDRDWFDASPYPNLRRWLNRFLQSPLFSKIM 115

GST_N family, Omega-like subfamily; composed of uncharacterized proteins with similarity to class Omega 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. 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 Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. Like Omega enzymes, proteins in this subfamily contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 817117854   4 ALRYSFRRCPYAMRARLALRYCGVPLRIVEVSLKAKPAEMLALSPKGTVPVL-SVDGRVIDESLDIMRWAL 73
Cdd:cd03060    1 PILYSFRRCPYAMRARMALLLAGITVELREVELKNKPAEMLAASPKGTVPVLvLGNGTVIEESLDIMRWAL 71

Glutathione S-transferase, N-terminal domain; This family is closely related to pfam02798.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 817117854   12 CPYAMRARLALRYCGVPLRIVEVSLKA--KPAEMLALSPKGTVPVLSV-DGRVIDESLDIMRW 71
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDLDPkdKPPELLALNPLGTVPVLVLpDGTVLTDSLVILEY 64

GST_N family, Class Omega 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 Omega GSTs show little or no GSH-conjugating activity towards standard GST substrates. Instead, they catalyze the GSH dependent reduction of protein disulfides, dehydroascorbate and monomethylarsonate, activities which are more characteristic of glutaredoxins. They contain a conserved cysteine equivalent to the first cysteine in the CXXC motif of glutaredoxins, which is a redox active residue capable of reducing GSH mixed disulfides in a monothiol mechanism. Polymorphisms of the class Omega GST genes may be associated with the development of some types of cancer and the age-at-onset of both Alzheimer's and Parkinson's diseases.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 817117854   7 YSFRRCPYAMRARLALRYCGVPLRIVEVSLKAKPAEMLALSPKGTVPVLSVD-GRVIDESLDI 68
Cdd:cd03055   22 YSMRFCPYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQGKVPALEIDeGKVVYESLII 84

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 817117854  89 VLALIAENDLGFKHHLNRYKYAERYP----ERPMEAYRADGEVFLQKLEALLADRAYLLADHPSLADMAVAPFVRQFAHV 164
Cdd:cd00299    1 VRALEDWADATLAPPLVRLLYLEKVPlpkdEAAVEAAREELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEAL 80

                         90
                 ....*....|....*...
gi 817117854 165 DREWFARTSYRRVQAWLQ 182
Cdd:cd00299   81 GPYYDLLDEYPRLKAWYD 98

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        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817117854 107 YKYAERYPERPMEAYRADGEVFLQKLEALLADRAYLLADHPSLADMAVAPFVRQFAHVDREWFARtsYRRVQAWLQWFLD 186
Cdd:cd03178   27 LYFAPEKIPYAIERYTDEVKRLYGVLDKRLSDRPYLAGEEYSIADIALYPWTHYADLGGFADLSE--YPNVKRWLERIAA 104

                 ....*
gi 817117854 187 SPLFI 191
Cdd:cd03178  105 RPAVQ 109

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 817117854  129 LQKLEALLADRAYLLADHPSLADMAVAPFVRQFAHVDREWFARTSYRRVQAWLQ 182
Cdd:pfam13410  13 LDALEARLADGPGLLGDRPTLADIALAPVLARLDAAYPGLDLREGYPRLRAWLE 66

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 817117854   7 YSFRRCPYAMRARLALRYCGVPLRIVEVSLKA---KPAEMLALSPKGTVPVLSVDGRVIDESLDIMRWALAQ 75
Cdd:cd03053    5 YGAAMSTCVRRVLLCLEEKGVDYELVPVDLTKgehKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

GST_N family, Class Tau 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 plant-specific class Tau GST subfamily has undergone extensive gene duplication. The Arabidopsis and Oryza genomes contain 28 and 40 Tau GSTs, respectively. They are primarily responsible for herbicide detoxification together with class Phi GSTs, showing class specificity in substrate preference. Tau enzymes are highly efficient in detoxifying diphenylether and aryloxyphenoxypropionate herbicides. In addition, Tau GSTs play important roles in intracellular signalling, biosynthesis of anthocyanin, responses to soil stresses and responses to auxin and cytokinin hormones.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 817117854  13 PYAMRARLALRYCGVPLRIVEVSLKAKPAEMLALSP-KGTVPVLSVDGRVIDESLDI 68
Cdd:cd03058   10 PFVLRVRIALALKGVPYEYVEEDLGNKSELLLASNPvHKKIPVLLHNGKPICESLII 66

GST_N family, Saccharomyces cerevisiae GTT2-like subfamily; composed of predominantly uncharacterized proteins with similarity to the S. cerevisiae GST protein, GTT2. 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. GTT2, a homodimer, exhibits GST activity with standard substrates. Strains with deleted GTT2 genes are viable but exhibit increased sensitivity to heat shock.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 817117854   7 YSFRRCPYAMRARLALRYCGVPLRIVEVSLKA---KPAEMLALSPKGTVPVLSV-DGRVIDESLDIMRW 71
Cdd:cd03051    4 YDSPTAPNPRRVRIFLAEKGIDVPLVTVDLAAgeqRSPEFLAKNPAGTVPVLELdDGTVITESVAICRY 72

Glutaredoxin [Posttranslational modification, protein turnover, chaperones];

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 817117854   7 YSFRRCPYAMRARLALRYCGVPLRIVEVSL-KAKPAEMLALSPKGTVPVLSVDGRVI 62
Cdd:COG0695    5 YTTPGCPYCARAKRLLDEKGIPYEEIDVDEdPEAREELRERSGRRTVPVIFIGGEHL 61

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        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 817117854   7 YSFRRCPYAMRARLALRYCGVPLRIVEVSLKAKPAEMLALSPKGTVPVLsVD-------GRVIDESLD 67
Cdd:cd03059    4 YSGPDDVYSHRVRIVLAEKGVSVEIIDVDPDNPPEDLAELNPYGTVPTL-VDrdlvlyeSRIIMEYLD 70

Glutathione S-transferase C-terminal-like, alpha helical domain of the Gamma subunit of Elongation Factor 1B and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Gamma subunit of Elongation Factor 1B (EF1Bgamma) subfamily; EF1Bgamma is part of the eukaryotic translation elongation factor-1 (EF1) complex which plays a central role in the elongation cycle during protein biosynthesis. EF1 consists of two functionally distinct units, EF1A and EF1B. EF1A catalyzes the GTP-dependent binding of aminoacyl-tRNA to the ribosomal A site concomitant with the hydrolysis of GTP. The resulting inactive EF1A:GDP complex is recycled to the active GTP form by the guanine-nucleotide exchange factor EF1B, a complex composed of at least two subunits, alpha and gamma. Metazoan EFB1 contain a third subunit, beta. The EF1B gamma subunit contains a GST fold consisting of an N-terminal thioredoxin-fold domain and a C-terminal alpha helical domain. The GST-like domain of EF1Bgamma is believed to mediate the dimerization of the EF1 complex, which in yeast is a dimer of the heterotrimer EF1A:EF1Balpha:EF1Bgamma. In addition to its role in protein biosynthesis, EF1Bgamma may also display other functions. The recombinant rice protein has been shown to possess GSH conjugating activity. The yeast EF1Bgamma binds to membranes in a calcium dependent manner and is also part of a complex that binds to the msrA (methionine sulfoxide reductase) promoter suggesting a function in the regulation of its gene expression. Also included in this subfamily is the GST_C-like domain at the N-terminus of human valyl-tRNA synthetase (ValRS) and its homologs. Metazoan ValRS forms a stable complex with Elongation Factor-1H (EF-1H), and together, they catalyze consecutive steps in protein biosynthesis, tRNA aminoacylation and its transfer to EF.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 817117854 129 LQKLEALLADRAYLLADHPSLADMAVA-PFVRQFAHV-DREWfaRTSYRRVQAWLQWFLDSPLFIAVMAKPE 198
Cdd:cd03181   49 LGVLEEHLLTRTYLVGERITLADIFVAsALLRGFETVlDPEF--RKKYPNVTRWFNTVVNQPKFKAVFGEVK 118

GST_N family, Metaxin subfamily; composed of metaxins and related proteins. Metaxin 1 is a component of a preprotein import complex of the mitochondrial outer membrane. It extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. In humans, alterations in the metaxin gene may be associated with Gaucher disease. Metaxin 2 binds to metaxin 1 and may also play a role in protein translocation into the mitochondria. Genome sequencing shows that a third metaxin gene also exists in zebrafish, Xenopus, chicken and mammals. Sequence analysis suggests that all three metaxins share a common ancestry and that they possess similarity to GSTs. Also included in the subfamily are uncharacterized proteins with similarity to metaxins, including a novel GST from Rhodococcus with toluene o-monooxygenase and glutamylcysteine synthetase activities.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 817117854  12 CPYAMRARLALRYCGVPLRIVEVSLKAkpaemlaLSPKGTVPVLSVDGRVIDESLDIMRWALAQ 75
Cdd:cd03054   16 SPECLKVETYLRMAGIPYEVVFSSNPW-------RSPTGKLPFLELNGEKIADSEKIIEYLKKK 72

C-terminal, alpha helical domain of an unknown subfamily 2 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817117854 102 HHLNRYKYAERYPERpMEAYRADGEVFLQKLEALLADRAYLLADHPSLADMAVAPFVRQFAHVDrewFARTSYRRVQAWL 181
Cdd:cd03180   26 WGLVRTPPEQRDPAA-IAASLAACNKLMAILDAQLARQAYLAGDRFTLADIALGCSVYRWLELP---IERPALPHLERWY 101

                 .
gi 817117854 182 Q 182
Cdd:cd03180  102 A 102

GST_N family, Beta etherase LigE subfamily; composed of proteins similar to Sphingomonas paucimobilis beta etherase, LigE, a GST-like protein that catalyzes the cleavage of the beta-aryl ether linkages present in low-moleculer weight lignins using GSH as the hydrogen donor. This reaction is an essential step in the degradation of lignin, a complex phenolic polymer that is the most abundant aromatic material in the biosphere. The beta etherase activity of LigE is enantioselective and it complements the activity of the other GST family beta etherase, LigF.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 817117854  13 PYAMRARLALRYCGVPLRIVEVSLKAKPA--EMLALSPKGTVPVL-SVDGRVIDESLDI 68
Cdd:cd03038   17 PNVWKTRLALNHKGLEYKTVPVEFPDIPPilGELTSGGFYTVPVIvDGSGEVIGDSFAI 75

C-terminal, alpha helical domain of Class Delta and Epsilon Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Delta and Epsilon 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. 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. The class Delta and Epsilon subfamily is made up primarily of insect GSTs, which play major roles in insecticide resistance by facilitating reductive dehydrochlorination of insecticides or conjugating them with GSH to produce water-soluble metabolites that are easily excreted. They are also implicated in protection against cellular damage by oxidative stress.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....
gi 817117854 129 LQKLEALLADRAYLLADHPSLADMAVAPFVRQFAHVDrewFARTSYRRVQAWLQ 182
Cdd:cd03177   47 LEFLETFLEGSDYVAGDQLTIADLSLVATVSTLEVVG---FDLSKYPNVAAWYE 97

GST_N family, Metaxin subfamily, Metaxin-like proteins; a heterogenous group of proteins, predominantly uncharacterized, with similarity to metaxins and GSTs. Metaxin 1 is a component of a preprotein import complex of the mitochondrial outer membrane. It extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. In humans, alterations in the metaxin gene may be associated with Gaucher disease. One characterized member of this subgroup is a novel GST from Rhodococcus with toluene o-monooxygenase and gamma-glutamylcysteine synthetase activities. Also members are the cadmium-inducible lysosomal protein CDR-1 and its homologs from C. elegans, and the failed axon connections (fax) protein from Drosophila. CDR-1 is an integral membrane protein that functions to protect against cadmium toxicity and may also have a role in osmoregulation to maintain salt balance in C. elegans. The fax gene of Drosophila was identified as a genetic modifier of Abelson (Abl) tyrosine kinase. The fax protein is localized in cellular membranes and is expressed in embryonic mesoderm and axons of the central nervous system.

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gi 817117854   7 YSFRRC-------PYAMRARLALRYCGVPLRIVEVSLKAKpaemlalSPKGTVPVLSVDGRVIDESlDIMRWALAQ 75
Cdd:cd03080    5 YQFPRAfgvpslsPFCLKVETFLRMAGIPYENKFGGLAKR-------SPKGKLPFIELNGEKIADS-ELIIDHLEE 72