C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized 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 498118155  95 VQKFLTLAAGEIAFGPAAARLITVFDAPFDAQFCQIVAEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVAHAPEGNVS 174
Cdd:cd03206    1 VQRWLSFAAGEIAHGPAAARLIHLFGAPLDPERARAISHRLLRLLDQHLAGRDWLAGDRPTIADVACYPYIALAPEGGVS 80

                         90       100
                 ....*....|....*....|
gi 498118155 175 LDKYPNVLRLLSNIENLDGF 194
Cdd:cd03206   81 LEPYPAIRAWLARVEALPGF 100

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155   5 IRIYSfPLSGHAHRVELFVSIANIKHEIVYVDLPSGEHKKEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLARRY---A 81
Cdd:PLN02395   3 LKVYG-PAFASPKRALVTLIEKGVEFETVPVDLMKGEHKQPEYLALQPFGVVPVIVDGDYKIFESRAIMRYYAEKYrsqG 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155  82 PDFLPS--------DPMLEAEVQKF------LTLaagEIAFGPAAArlitvfdAPFDAQFCQIVAEKALTKLDTL---LA 144
Cdd:PLN02395  82 PDLLGKtieergqvEQWLDVEATSYhppllnLTL---HILFASKMG-------FPADEKVIKESEEKLAKVLDVYearLS 151

                        170
                 ....*....|....*.
gi 498118155 145 NKDFLVGGRPTIADIA 160
Cdd:PLN02395 152 KSKYLAGDFVSLADLA 167

C-terminal, alpha helical domain of an unknown subfamily 7 of Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, unknown subfamily 7; composed of uncharacterized 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 498118155  95 VQKFLTLAAGEIAFGPAAARLITVFDAPFDAQFCQIVAEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVAHAPEGNVS 174
Cdd:cd03206    1 VQRWLSFAAGEIAHGPAAARLIHLFGAPLDPERARAISHRLLRLLDQHLAGRDWLAGDRPTIADVACYPYIALAPEGGVS 80

                         90       100
                 ....*....|....*....|
gi 498118155 175 LDKYPNVLRLLSNIENLDGF 194
Cdd:cd03206   81 LEPYPAIRAWLARVEALPGF 100

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 498118155   5 IRIYSFPLSGHAHRVELFVSIANIKHEIVYVDLPSGEHKKepFLTLNPLGQVPVIEDNDIVISDSNAILVYLA 77
Cdd:cd00570    1 LKLYYFPGSPRSLRVRLALEEKGLPYELVPVDLGEGEQEE--FLALNPLGKVPVLEDGGLVLTESLAILEYLA 71

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 498118155   5 IRIYSFPLSgHAHRVELFVSIANIKHEIVYVDLPSGEHKKEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLARRYA 81
Cdd:cd03046    1 ITLYHLPRS-RSFRILWLLEELGLPYELVLYDRGPGEQAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 76

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 498118155    5 IRIYSFPLSGHAHRVELFVSIANIKHEIVYVDLPSGEHKKEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLAR 78
Cdd:pfam02798   3 LTLYGIRGSPRAHRIRWLLAEKGVEYEIVPLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAILEYIAR 76

GST_N 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 TRX-fold domain and a C-terminal alpha helical domain, with an active site located in a cleft between the two domains. 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        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 498118155   5 IRIYSFPLSGHAHRVELFVSIANIKHEIVYVDLPSGEHKKEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLA 77
Cdd:cd03045    1 IDLYYLPGSPPCRAVLLTAKALGLELNLKEVNLMKGEHLKPEFLKLNPQHTVPTLVDNGFVLWESHAILIYLV 73

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 498118155   5 IRIYSFPLSGHAHRVELFVSIANIKHEIVYVDLpsgEHKKEPFLTLNPLGQVPVIE-DNDIVISDSNAILVYL 76
Cdd:cd03055   19 IRLYSMRFCPYAQRARLVLAAKNIPHEVININL---KDKPDWFLEKNPQGKVPALEiDEGKVVYESLIICEYL 88

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

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 498118155   13 SGHAHRVELFVSIANIKHEIVYVDLPsGEHKKEPFLTLNPLGQVPVIED-NDIVISDSNAILVYLARR 79
Cdd:pfam13409   2 SPFSHRVRLALEEKGLPYEIELVDLD-PKDKPPELLALNPLGTVPVLVLpDGTVLTDSLVILEYLEEL 68

Glutathione S-transferase C-terminal-like, alpha helical domain of various Aminoacyl-tRNA synthetases and similar domains; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl-tRNA synthetase (AaRS)-like subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of some eukaryotic AaRSs, as well as similar domains found in proteins involved in protein synthesis including Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 2 (AIMP2), AIMP3, and eukaryotic translation Elongation Factor 1 beta (eEF1b). AaRSs comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. AaRSs in this subfamily include GluRS from lower eukaryotes, as well as GluProRS, MetRS, and CysRS from higher eukaryotes. AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex found in higher eukaryotes. The GST_C-like domain is involved in protein-protein interactions, mediating the formation of aaRS complexes such as the MetRS-Arc1p-GluRS ternary complex in lower eukaryotes and the multi-aaRS complex in higher eukaryotes, that act as molecular hubs for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 498118155 133 EKALTKLDTLLANKDFLVGGRPTIADIAVYSYVAHAPEGNVSLD--KYPNVLRLLSNIENL 191
Cdd:cd10289   22 EALLKSLNSYLASRTFLVGYSLTLADVAVFSALYPSGQKLSDKEkkKFPHVTRWFNHIQNL 82

GST_N family, Class Beta 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit limited GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they also bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH.

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 498118155  26 ANIKHEIVYVDLPSGEHKKEPFLTLNPLGQVPVIE-DNDIVISDSNAILVYLARRY 80
Cdd:cd03057   21 LGLPFELVRVDLRTKTQKGADYLAINPKGQVPALVlDDGEVLTESAAILQYLADLH 76

GSH-dependent disulfide bond oxidoreductase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155  10 FPLSGHAHRVELFVSIANIKHEIVYVDLPSGEHKKEPFLTLNPLGQVPVIEDND-------IVISDSNAILVYLARRYAP 82
Cdd:PRK13972   6 FAPTPNGHKITLFLEEAELDYRLIKVDLGKGGQFRPEFLRISPNNKIPAIVDHSpadggepLSLFESGAILLYLAEKTGL 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155  83 dFLPSDPMLEAEVQKFLTLAAGEIA--------FGPAAARLItvfdaPFDAQFCQIVAEKALTKLDTLLANKDFLVGGRP 154
Cdd:PRK13972  86 -FLSHETRERAATLQWLFWQVGGLGpmlgqnhhFNHAAPQTI-----PYAIERYQVETQRLYHVLNKRLENSPWLGGENY 159

                        170       180
                 ....*....|....*....|....*..
gi 498118155 155 TIADIAVYSYVAHAPEGNVSLDKYPNV 181
Cdd:PRK13972 160 SIADIACWPWVNAWTRQRIDLAMYPAV 186

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        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 498118155   8 YSFPLSGHAHRVELFVSIANIKHEIVYVDLpsgEHKKEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLARRY 80
Cdd:cd03059    4 YSGPDDVYSHRVRIVLAEKGVSVEIIDVDP---DNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73

Glutathione S-transferase C-terminal-like, alpha helical domain of bifunctional Glutamyl-Prolyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, bifunctional GluRS-Prolyl-tRNA synthetase (GluProRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of GluProRS from higher eukaryotes. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. The GST_C-like domain of GluProRS may be involved in protein-protein interactions, mediating the formation of the multi-aaRS complex in higher eukaryotes. The multi-aaRS complex acts as a molecular hub for protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 498118155 128 CQIVAEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVAHAPEGNVSLDKYPNVLRLLSNIENL 191
Cdd:cd10309   18 CDQDFSSALSYLDKALSLRTYLVGNSLTLADFAVWAALRGNGEWLASKEKYVNVTRWFKFISSQ 81

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.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155   5 IRIYSFP-------LSGHAHRVELFVSIANIKHEIVYVDLPSgehkkepfltLNPLGQVPVIEDNDIVISDSNAILVYLA 77
Cdd:cd03080    2 ITLYQFPrafgvpsLSPFCLKVETFLRMAGIPYENKFGGLAK----------RSPKGKLPFIELNGEKIADSELIIDHLE 71

                 ...
gi 498118155  78 RRY 80
Cdd:cd03080   72 EKY 74

putative S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155  47 FLTLNPLGQVPVIEDND----IVISDSNAILVYLARRYApDFLPSDPMLEAEVQKFL--------TLAAGeiaFGPAAAR 114
Cdd:PRK11752  92 FVEINPNSKIPALLDRSgnppIRVFESGAILLYLAEKFG-AFLPKDLAARTETLNWLfwqqgsapFLGGG---FGHFYAY 167

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 498118155 115 LITVFDAPFDaQFCqIVAEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVAHAPEGNV-------SLDKYPNVLR 183
Cdd:PRK11752 168 APEKIEYAIN-RFT-MEAKRQLDVLDKQLAEHEYIAGDEYTIADIAIWPWYGNLVLGNLydaaeflDVGSYKHVQR 241

glutathione transferase;

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155  31 EIVYVDLPSGEHKKEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLARRYAP----DFLPSDPMLEA---EVQKFL--TL 101
Cdd:PRK15113  34 ELKTVDLDAGEHLQPTYQGYSLTRRVPTLQHDDFELSESSAIAEYLEERFAPpaweRIYPADLQARArarQIQAWLrsDL 113

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 498118155 102 AA------GEIAFGPAAArlitvfdAPFDAQfCQIVAEKALTKLDTLLANKDFLVGGRPTIAD 158
Cdd:PRK15113 114 MPlreerpTDVVFAGAKK-------APLSEA-GKAAAEKLFAVAERLLAPGQPNLFGEWCIAD 168

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 498118155   5 IRIYSFPLSGHAHRVELFVSIANIKHEIVYVDlpSGEHKKEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLAR 78
Cdd:cd03039    1 YKLTYFNIRGRGEPIRLLLADAGVEYEDVRIT--YEEWPELDLKPTLPFGQLPVLEIDGKKLTQSNAILRYLAR 72

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155 132 AEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVAHAP---EGNVSLDKYPNVLRLLSNI 188
Cdd:cd00299   41 LPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLEalgPYYDLLDEYPRLKAWYDRL 100

Glutathione S-transferase C-terminal-like, alpha helical domain of Glutamyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Glutamyl-tRNA synthetase (GluRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of GluRS from lower eukaryotes. Aminoacyl-tRNA synthetases (aaRSs) comprise a family of enzymes that catalyze the coupling of amino acids with their matching tRNAs. This involves the formation of an aminoacyl adenylate using ATP, followed by the transfer of the activated amino acid to the 3'-adenosine moiety of the tRNA. AaRSs may also be involved in translational and transcriptional regulation, as well as in tRNA processing. The GST_C-like domain of GluRS is involved in protein-protein interactions. This domain mediates the formation of the MetRS-Arc1p-GluRS ternary complex found in lower eukaryotes, which is considered an evolutionary intermediate between prokaryotic aaRS and the multi-aaRS complex found in higher eukaryotes. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 498118155 133 EKALTKLDTLLANKDFLVGGRPTIADIAVYSY-----VAHAPEGNvslDKYPNVLRLLSNIENL 191
Cdd:cd10306   27 SQALEELDSHLTLRTFIVGYSLSLADIAVWGAlrgngVAGSLIKN---KVYVNLSRWFSFLESL 87

Glutathione S-transferase C-terminal-like, alpha helical domain of the Aminoacyl tRNA synthetase cofactor 1 and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase cofactor 1 (Arc1p)-like subfamily; Arc1p, also called GU4 nucleic binding protein 1 (G4p1) or p42, is a tRNA-aminoacylation and nuclear-export cofactor. It contains a domain in the N-terminal region with similarity to the C-terminal alpha helical domain of GSTs. This domain mediates the association of the aminoacyl tRNA synthetases (aaRSs), MetRS and GluRS, in yeast to form a stable stoichiometric ternany complex. The GST_C-like domain of Arc1p is a protein-protein interaction domain containing two binding sites which enable it to bind the two aaRSs simultaneously and independently. The MetRS-Arc1p-GluRS complex selectively recruits and aminoacylates its cognate tRNAs without additional cofactors. Arc1p also plays a role in the transport of tRNA from the nucleus to the cytoplasm. It may also control the subcellular distribution of GluRS in the cytoplasm, nucleoplasm, and the mitochondrial matrix.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155  92 EAEVQKFLTLAAGeiafGPAAARLitvfdapfdaqfcqivaEKALTKLDTLLANKDFLVG-GRPTIADIAVYSYVAHA-- 168
Cdd:cd10304    4 SAEVAQWLSVAKS----GPVSKDV-----------------QETLGQLNLHLRTRTFLLGtGKPSVADVAVFEAVLPVvk 62

                         90       100
                 ....*....|....*....|....*.
gi 498118155 169 ---PEGNVSLDKYPNVLRLLSNIENL 191
Cdd:cd10304   63 ewsDEVKTGYAKYRHILRWVDYVQNL 88

C-terminal, alpha helical domain of Metaxin and related proteins; Glutathione S-transferase (GST) C-terminal domain 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. Other 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 498118155 132 AEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVA-------HAPEGNVSLDKYPNVLRLLSNI 188
Cdd:cd03193   24 ALEDLEALSTLLGDKKFLFGDKPTSVDATVFAHLAsilyppeDSPLLRVLVASSPNLVEYCERI 87

C-terminal, alpha helical domain of Escherichia coli Yghu Glutathione S-transferases and related uncharacterized proteins; Glutathione S-transferase (GST) C-terminal domain family, YghU-like subfamily; composed of the Escherichia coli YghU and related 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. 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. YghU is one of nine GST homologs in the genome of Escherichia coli. It is similar to Escherichia coli YfcG in that it has poor GSH transferase activity towards typical substrates. It shows modest reductase activity towards some organic hydroperoxides. Like YfcG, YghU also shows good disulfide bond oxidoreductase activity comparable to the activities of glutaredoxins and thioredoxins. YghU does not contain a redox active cysteine residue, and may use a bound thiol disulfide couple such as 2GSH/GSSG for activity. The crystal structure of YghU reveals two GSH molecules bound in its active site.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 498118155 132 AEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVAHAPEGNV-------SLDKYPNVLRLLSNIEN 190
Cdd:cd10292   45 AKRQLDVLDRQLATHKYLAGDEYTIADMAIWPWYGGLALGSLydaaeflDVDEYKHVQRWAKDIAA 110

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

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 498118155  132 AEKALTKLDTLLANKDFLVGGRPTIADIAVYS---YVAHAPEGNVSLDKYPNVLRLL 185
Cdd:pfam13410   9 LRAALDALEARLADGPGLLGDRPTLADIALAPvlaRLDAAYPGLDLREGYPRLRAWL 65

Glutathione S-transferase, C-terminal domain; This domain is closely related to PF00043.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 498118155  132 AEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVA---HAPEGNVSL----DKYPNVLR 183
Cdd:pfam17171   1 AKKDLRALSERLGDKPFFFGDKPTSLDALVFGHLAlilYTPLPSPALrihlKEYPNLVA 59

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 498118155   7 IYSFPLSGHAHRVELFVSIANIKHE---IVYVDLPSGEHKKEPFltlnplGQVPVIEDNDIVISDSNAILVYLAR 78
Cdd:cd03076    4 LTYFPVRGRAEAIRLLLADQGISWEeerVTYEEWQESLKPKMLF------GQLPCFKDGDLTLVQSNAILRHLGR 72

C-terminal, alpha helical domain of Class Beta Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Class Beta 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. Unlike mammalian GSTs which detoxify a broad range of compounds, the bacterial class Beta GSTs exhibit GSH conjugating activity with a narrow range of substrates. In addition to GSH conjugation, they are involved in the protection against oxidative stress and are able to bind antibiotics and reduce the antimicrobial activity of beta-lactam drugs, contributing to antibiotic resistance. The structure of the Proteus mirabilis enzyme reveals that the cysteine in the active site forms a covalent bond with GSH. One member of this subfamily is a GST from Burkholderia xenovorans LB400 that is encoded by the bphK gene and is part of the biphenyl catabolic pathway.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155  90 MLEAEVQKFLTLAAGEI--AFGP--AAARLITVFDAPFDAQFCQIVAEKALTKLDTLLANKDFLVGGRPTIADIAVYSYV 165
Cdd:cd03188    1 LERARLLEWLNFIASELhkAFGPlfYPARWADDALAEEVKAAARERLERRLAYLDAQLAGGPYLLGDQFSVADAYLFVVL 80

                         90       100       110
                 ....*....|....*....|....*....|.
gi 498118155 166 AHAPEGNVSLDKYPNVLRLLSNIENLDGFKA 196
Cdd:cd03188   81 RWARAVGLDLSDWPHLAAYLARVAARPAVQA 111

glutathione dehydrogenase (ascorbate)

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 498118155  17 HRVELFVSIANIKHEIVYVDLpsgEHKKEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLARRYaPD 83
Cdd:PLN02817  77 QRVLLTLEEKHLPYDMKLVDL---TNKPEWFLKISPEGKVPVVKLDEKWVADSDVITQALEEKY-PD 139

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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 498118155 136 LTKLDTLLANKDFLVGGRPTIADIAVYSYVAH----APEgnvSLDKYPNVLRLLSNIENLDGFKA 196
Cdd:cd03209   44 LKLFSEFLGDRPWFAGDKITYVDFLLYEALDQhrifEPD---CLDAFPNLKDFLERFEALPKISA 105

C-terminal, alpha helical domain of Metaxin 1, Metaxin 3, and similar proteins; Glutathione S-transferase (GST) C-terminal domain family, Metaxin subfamily, Metaxin 1-like proteins; composed of metaxins 1 and 3, and similar proteins. Mammalian metaxin (or metaxin 1) is a component of the preprotein import complex of the mitochondrial outer membrane. Metaxin extends to the cytosol and is anchored to the mitochondrial membrane through its C-terminal domain. In mice, metaxin is required for embryonic development. Like the murine gene, the human metaxin gene is located downstream to the glucocerebrosidase (GBA) pseudogene and is convergently transcribed. Inherited deficiency of GBA results in Gaucher disease, which presents many diverse clinical phenotypes. Alterations in the metaxin gene, in addition to GBA mutations, may be associated with Gaucher disease. Genome sequencing shows that a third metaxin gene also exists in zebrafish, Xenopus, chicken, and mammals.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 498118155 132 AEKALTKLDTLLANKDFLVGGRPTIADIAVYSYVA---HAPEGNVSLdkyPNVLRLLSNIEN 190
Cdd:cd03212   69 AKECLNLLSERLGEKKFFFGDRPTSLDALVFGYLApllKAPLPNNKL---QNHLKGCPNLVQ 127

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 2; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 2 subfamily; AIMPs are non-enzymatic cofactors that play critical roles in the assembly and formation of a macromolecular multi-tRNA synthetase protein complex that functions as a molecular hub to coordinate protein synthesis. There are three AIMPs, named AIMP1-3, which play diverse regulatory roles. AIMP2, also called p38 or JTV-1, contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It plays an important role in the control of cell fate via antiproliferative (by enhancing the TGF-beta signal) and proapoptotic (activation of p53 and TNF-alpha) activities. Its roles in the control of cell proliferation and death suggest that it is a potent tumor suppressor. AIMP2 heterozygous mice with lower than normal expression of AIMP2 show high susceptibility to tumorigenesis. AIMP2 is also a substrate of Parkin, an E3 ubiquitin ligase that is involved in the ubiquitylation and proteasomal degradation of its substrates. Mutations in the Parkin gene is found in 50% of patients with autosomal-recessive early-onset parkinsonism. The accumulation of AIMP2, due to impaired Parkin function, may play a role in the pathogenesis of Parkinson's disease.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155  97 KFLTLAAGEIAFGPAAARLItvfDAPFDAQFCQIV----AEKA--LTKLDTLLANKDFLVGGRPTIADIAVYSYVAHApe 170
Cdd:cd03200    2 RFLFRLLGDESDDPVNATLI---DSWVDTAIFQLLegssKEKAavLRALNSALGRSPWLVGSEPTVADIALWSAVLQT-- 76

                         90       100
                 ....*....|....*....|.
gi 498118155 171 GNVSlDKYPNVLRLLSNIENL 191
Cdd:cd03200   77 GLAS-GAPANVQRWMKSCENL 96

stringent starvation protein A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 498118155   2 SHGIRIYSfplsghaHRVELFVSIANIKHEIVYVD---LPsgehkkEPFLTLNPLGQVPVIEDNDIVISDSNAILVYLAR 78
Cdd:PRK09481  15 SGPTDIYS-------HQVRIVLAEKGVSVEIEQVEkdnLP------QDLIDLNPYQSVPTLVDRELTLYESRIIMEYLDE 81

                         90
                 ....*....|..
gi 498118155  79 RYA-PDFLPSDP 89
Cdd:PRK09481  82 RFPhPPLMPVYP 93