C-terminal, alpha helical domain of Dehydroascorbate Reductase; Glutathione S-transferase (GST) C-terminal domain family, Dehydroascorbate Reductase (DHAR) subfamily; composed of plant-specific DHARs, which are monomeric enzymes catalyzing the reduction of DHA into ascorbic acid (AsA) using glutathione as the reductant. DHAR allows plants to recycle oxidized AsA before it is lost. AsA serves as a cofactor of violaxanthin de-epoxidase in the xanthophyll cycle and as an antioxidant in the detoxification of reactive oxygen species. Because AsA is the major reductant in plants, DHAR serves to regulate their redox state. It has been suggested that a significant portion of DHAR activity is plastidic, acting to reduce the large amounts of ascorbate oxidized during hydrogen peroxide scavenging by ascorbate peroxidase. DHAR contains a conserved cysteine in its active site and in addition to its reductase activity, shows thiol transferase activity similar to glutaredoxins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215  89 LIAPPEFASVGSKIFPTFVSFLKSKDSSDSTEQALLDELKALEEHLKAHGPCINGQNVCSVDMSLAPKLYHLKVALGHFK 168
Cdd:cd03201     1 LKTPPEFASVGSKIFSTFVTFLKSKDANDGSEQALLDELTALDEHLKTNGPFIAGEKITAVDLSLAPKLYHLRVALGHYK 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1807852215 169 KWSVPESLSLVRNYMKLLFERESFHKTKAEEKYVIAGWAPK 209
Cdd:cd03201    81 GWSVPESLTAVHKYMELLFSRESFKKTKAPDEMIIAGWAPK 121

intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A.12) Proteins of the O-ClC family are voltage-sensitive chloride channels found in intracellular membranes but not the plasma membranes of animal cells. They are found in human nuclear membranes, and the bovine protein targets to the microsomes, but not the plasma membrane, when expressed in Xenopus laevis oocytes. These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney. [Transport and binding proteins, Anions]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215   3 VEVCVKAAVGAPDVlGDCPFSQRVLLTLEEKKVTYKKHLINVSDKPKWFLEVNPEGKVPVINFGDKWIPDSDVIVGILEE 82
Cdd:TIGR00862   3 IELFVKAGSDGESI-GNCPFSQRLFMILWLKGVVFNVTTVDLKRKPEDLQNLAPGTHPPFLTYNTEVKTDVNKIEEFLEE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215  83 -----KYPNpslIAP--PEFASVGSKIFPTFVSFLKS--KDSSDSTEQALLDELKALEEHLKAHGP-------------- 139
Cdd:TIGR00862  82 tlcppRYPK---LSPkhPESNTAGLDIFAKFSAYIKNsnPEANDNLEKGLLKALKKLDDYLNSPLPeeidedsaedekvs 158

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1807852215 140 ---CINGQNVCSVDMSLAPKLYHLKVALGHFKKWSVPESLSLVRNYMKLLFERESFHKTKAEEKYV 202
Cdd:TIGR00862 159 rrkFLDGDELTLADCNLLPKLHIVKVVAKKYRNFDIPAEFTGVWRYLSNAYAREEFTNTCPDDKEI 224

glutathione S-transferase DHAR1

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215   1 MVVEVCVKAAVGAPDVLGDCPFSQRVLLTLEEKKVTYKKHLINVSDKPKWFLEVNPEGKVPVINFGDKWIPDSDVIVGIL 80
Cdd:PLN02378    1 MALEICVKAAVGAPDHLGDCPFSQRALLTLEEKSLTYKIHLINLSDKPQWFLDISPQGKVPVLKIDDKWVTDSDVIVGIL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215  81 EEKYPNPSLIAPPEFASVGSKIFPTFVSFLKSKDSSDSTEQALLDELKALEEHLKAH-GPCINGQNVCSVDMSLAPKLYH 159
Cdd:PLN02378   81 EEKYPDPPLKTPAEFASVGSNIFGTFGTFLKSKDSNDGSEHALLVELEALENHLKSHdGPFIAGERVSAVDLSLAPKLYH 160

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1807852215 160 LKVALGHFKKWSVPESLSLVRNYMKLLFERESFHKTKAEEKYVIAGWAPKV 210
Cdd:PLN02378  161 LQVALGHFKSWSVPESFPHVHNYMKTLFSLDSFEKTKTEEKYVISGWAPKV 211

C-terminal, alpha helical domain of Chloride Intracellular Channels; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) subfamily; composed of CLICs (CLIC1-6 in vertebrates), p64, parchorin, and similar proteins. They are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. Biochemical studies of the Caenorhabditis elegans homolog, EXC-4, show that the membrane localization domain is present in the N-terminal part of the protein. CLICs display structural plasticity, with CLIC1 adopting two soluble conformations. The structure of soluble human CLIC1 reveals that it is monomeric and adopts a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. Upon oxidation, the N-terminal domain of CLIC1 undergoes a structural change to form a non-covalent dimer stabilized by the formation of an intramolecular disulfide bond between two cysteines that are far apart in the reduced form. The CLIC1 dimer bears no similarity to GST dimers. The redox-controlled structural rearrangement exposes a large hydrophobic surface, which is masked by dimerization in vitro. In vivo, this surface may represent the docking interface of CLIC1 in its membrane-bound state. The two cysteines in CLIC1 that form the disulfide bond in oxidizing conditions are essential for dimerization and chloride channel activity, however, in other subfamily members, the second cysteine is not conserved.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215  93 PEFASVGSKIFPTFVSFLKSKDSS--DSTEQALLDELKALEEHLKAH-GPCINGQNVCSVDMSLAPKLYHLKVALGHFKK 169
Cdd:cd03198     2 PEANTAGEDLFAKFSAYIKNKDPAadEALRKALLKELSKLDAYLSSSsRKFLDGDTLTLADCNLLPKLHHIRVAGKAYKD 81

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1807852215 170 WSVPESLSLVRNYMKLLFERESFHKTKAEEKYVIAGWA 207
Cdd:cd03198    82 FDIPDDFTGLWRYLKNAYETDEFTKTCPADQEIILHYK 119

intracellular chloride channel protein; The Organellar Chloride Channel (O-ClC) Family (TC 1.A.12) Proteins of the O-ClC family are voltage-sensitive chloride channels found in intracellular membranes but not the plasma membranes of animal cells. They are found in human nuclear membranes, and the bovine protein targets to the microsomes, but not the plasma membrane, when expressed in Xenopus laevis oocytes. These proteins are thought to function in the regulation of the membrane potential and in transepithelial ion absorption and secretion in the kidney. [Transport and binding proteins, Anions]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215   3 VEVCVKAAVGAPDVlGDCPFSQRVLLTLEEKKVTYKKHLINVSDKPKWFLEVNPEGKVPVINFGDKWIPDSDVIVGILEE 82
Cdd:TIGR00862   3 IELFVKAGSDGESI-GNCPFSQRLFMILWLKGVVFNVTTVDLKRKPEDLQNLAPGTHPPFLTYNTEVKTDVNKIEEFLEE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215  83 -----KYPNpslIAP--PEFASVGSKIFPTFVSFLKS--KDSSDSTEQALLDELKALEEHLKAHGP-------------- 139
Cdd:TIGR00862  82 tlcppRYPK---LSPkhPESNTAGLDIFAKFSAYIKNsnPEANDNLEKGLLKALKKLDDYLNSPLPeeidedsaedekvs 158

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1807852215 140 ---CINGQNVCSVDMSLAPKLYHLKVALGHFKKWSVPESLSLVRNYMKLLFERESFHKTKAEEKYV 202
Cdd:TIGR00862 159 rrkFLDGDELTLADCNLLPKLHIVKVVAKKYRNFDIPAEFTGVWRYLSNAYAREEFTNTCPDDKEI 224

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1807852215  20 CPFSQRVLLTLEEKKVTYKKHLINVSDKP-KWFLEVNPEGKVPVINFGDKWIPDSDVIV 77
Cdd:cd00570     9 SPRSLRVRLALEEKGLPYELVPVDLGEGEqEEFLALNPLGKVPVLEDGGLVLTESLAIL 67

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
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1807852215  20 CPFSQRVLLTLEEKKVTYKKHLINVSDKPKWFLEVNPEGKVPVI-NFGDKWIPDSDVIV 77
Cdd:cd03055    27 CPYAQRARLVLAAKNIPHEVININLKDKPDWFLEKNPQGKVPALeIDEGKVVYESLIIC 85

C-terminal, alpha helical domain of Chloride Intracellular Channel 4; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 4 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. CLIC4, also known as p64H1, is expressed ubiquitously and its localization varies depending on the nature of the cells and tissues, from the plasma membrane to subcellular compartments including the nucleus, mitochondria, ER, and the trans-Golgi network, among others. In response to cellular stress such as DNA damage and senescence, cytoplasmic CLIC4 translocates to the nucleus, where it acts on the TGF-beta pathway. Studies on knockout mice suggest that CLIC4 also plays an important role in angiogenesis, specifically in network formation, capillary sprouting, and lumen formation. CLIC4 has been found to induce apoptosis in several cell types and to retard the growth of grafted tumors in vivo.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215  93 PEFASVGSKIFPTFVSFLKSK--DSSDSTEQALLDELKALEEHLKAHGP-----------------CINGQNVCSVDMSL 153
Cdd:cd10296     2 PESNTAGMDIFAKFSAYIKNSrpEANEALERGLLKTLQKLDEYLNSPLPdeidensmedikfstrkFLDGNEMTLADCNL 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1807852215 154 APKLYHLKVALGHFKKWSVPESLSLVRNYMKLLFERESFHKTKAEEKYVIAGWA 207
Cdd:cd10296    82 LPKLHIVKVVAKKYRNFEIPKEMTGIWRYLSNAYSRDEFTNTCPSDKEIEIAYS 135

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 1807852215  19 DCPFSQRVLLTLEEKKVTYKKHLINVSDKPKWFLEVNPEGKVPVINFGDKWIPDSDVIVGILEEKY 84
Cdd:cd03059     8 DDVYSHRVRIVLAEKGVSVEIIDVDPDNPPEDLAELNPYGTVPTLVDRDLVLYESRIIMEYLDERF 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1807852215  23 SQRVLLTLEEKKVTYKKHLINVSD---KPKWFLEVNPEGKVPVINFGDKWIPDSDVIVGILEEKYP 85
Cdd:cd03046    11 SFRILWLLEELGLPYELVLYDRGPgeqAPPEYLAINPLGKVPVLVDGDLVLTESAAIILYLAEKYG 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 1807852215  20 CPFSQRVLLTLEEKKVTYKkhLINVS-----DKPKWFLEVNPEGKVPVINFGDKWIPDSDVIVGILEEK 83
Cdd:cd03053    10 STCVRRVLLCLEEKGVDYE--LVPVDltkgeHKSPEHLARNPFGQIPALEDGDLKLFESRAITRYLAEK 76

C-terminal, alpha helical domain of Chloride Intracellular Channel 2; Glutathione S-transferase (GST) C-terminal domain family, Chloride Intracellular Channel (CLIC) 2 subfamily; CLICs are auto-inserting, self-assembling intracellular anion channels involved in a wide variety of functions including regulated secretion, cell division, and apoptosis. They can exist in both water-soluble and membrane-bound states and are found in various vesicles and membranes, and they may play roles in the maintenance of these intracellular membranes. The membrane localization domain is present in the N-terminal part of the protein. Structures of soluble CLICs reveal that they adopt a fold similar to GSTs, containing an N-terminal domain with a thioredoxin fold and a C-terminal alpha helical domain. CLIC2 contains an intramolecular disulfide bond and exists as a monomer regardless of redox conditions, in contrast to CLIC1 which forms a dimer under oxidizing conditions. It is expressed in most tissues except the brain, and is highly expressed in the lung, spleen, and in cardiac and skeletal muscles. CLIC2 interacts with ryanodine receptors (cardiac RyR2 and skeletal RyR1) and modulates their activity, suggesting that CLIC2 may function in the regulation of calcium release and signaling in cardiac and skeletal muscles.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1807852215  93 PEFASVGSKIFPTFVSFLK-SKDSSDSTEQALLDELKALEEHLKAHGP-----------------CINGQNVCSVDMSLA 154
Cdd:cd10298     2 KESFDVGSDIFAKFSAYIKnSPENNANQEKALLREFKRLDDYLNTPLPeeidhdsaenitvskrkFLDGDRLTLADCNLL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1807852215 155 PKLYHLKVALGHFKKWSVPESLSLVRNYMKLLFERESFHKT 195
Cdd:cd10298    82 PKLHVIKVAAKKYCDFDIPADFTGVWRYLNNAYEREEFSQT 122

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
                  ....*....|....*....|....*....|....
gi 1807852215  47 KPKWFLEVNPEGKVPVINFGDKWIPDSDVIVGIL 80
Cdd:cd03056    39 RTPEFLALNPNGEVPVLELDGRVLAESNAILVYL 72

GST_N family, unknown subfamily 3; 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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1807852215  21 PFSQRVLLTLEEK--KVTYKKHLINVSDKPKWFLEVNPEGKVPV-INFGDKWIPDSDVIVGILE 81
Cdd:cd03049    10 PYVRKVRVAAHETglGDDVELVLVNPWSDDESLLAVNPLGKIPAlVLDDGEALFDSRVICEYLD 73

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1807852215  19 DCPFSQRVLLTLEEKKVTYK---KHLINVSDKPKWFLEVNPEGKVPVINFGDKWIPDSDVIV 77
Cdd:pfam02798  10 GSPRAHRIRWLLAEKGVEYEivpLDFGAGPEKSPELLKLNPLGKVPALEDGGKKLTESRAIL 71

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        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1807852215   6 CVKAAVGAPDVlgdCPFSQRVLLTLEEKKVTYKKHLINvsdkpkwFLEVNPEGKVPVINFGDKWIPDSDVIVGILEEK 83
Cdd:cd03054     5 QWGRAFGLPSL---SPECLKVETYLRMAGIPYEVVFSS-------NPWRSPTGKLPFLELNGEKIADSEKIIEYLKKK 72

Glutaredoxin (GRX) family; composed of GRX, approximately 10 kDa in size, and proteins containing a GRX or GRX-like domain. GRX is a glutathione (GSH) dependent reductase, catalyzing the disulfide reduction of target proteins such as ribonucleotide reductase. It contains a redox active CXXC motif in a TRX fold and uses a similar dithiol mechanism employed by TRXs for intramolecular disulfide bond reduction of protein substrates. Unlike TRX, GRX has preference for mixed GSH disulfide substrates, in which it uses a monothiol mechanism where only the N-terminal cysteine is required. The flow of reducing equivalents in the GRX system goes from NADPH -> GSH reductase -> GSH -> GRX -> protein substrates. By altering the redox state of target proteins, GRX is involved in many cellular functions including DNA synthesis, signal transduction and the defense against oxidative stress. Different classes are known including human GRX1 and GRX2, as well as E. coli GRX1 and GRX3, which are members of this family. E. coli GRX2, however, is a 24-kDa protein that belongs to the GSH S-transferase (GST) family.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1807852215  18 GDCPFSQRVLLTLEEKKVTYkkHLINVSDKP---KWFLEVNPEGKVPVINFGDKWIPDSDVIV 77
Cdd:cd02066     8 STCPYCKRAKRLLESLGIEF--EEIDILEDGelrEELKELSGWPTVPQIFINGEFIGGYDDLK 68