Glutathione S-transferase C-terminal-like, alpha helical domain of Methionyl-tRNA synthetase from higher eukaryotes; Glutathione S-transferase (GST) C-terminal domain family, Methionyl-tRNA synthetase (MetRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of MetRS 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. MetRS is a class I aaRS, containing a Rossman fold catalytic core. It recognizes the initiator tRNA as well as the Met-tRNA for protein chain elongation. The GST_C-like domain of MetRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       77 QDDLTNQWLEWEATELQPALSAALYYLVVQGKKGEDVLGSVRRALTHIDHSLSRQNCPFLaGETESLADIVLWGALYPLL 156
Cdd:cd10307   1 DDDLSNQWLEWEAWLLQPALSLALALTHVQGKKSEADLNTVLNALVHLDQSLLKKSTPLL-GDKLSSADVVVWSALYPLG 79

                        90       100
                ....*....|....*....|...
4BL7_A      157 QDPAYLPEELSALHSWFQTLSTQ 179
Cdd:cd10307  80 TDKSALPENLDNLRRWFQNVSTL 102

Glutathione S-transferase C-terminal-like, alpha helical domain of Methionyl-tRNA synthetase from higher eukaryotes; Glutathione S-transferase (GST) C-terminal domain family, Methionyl-tRNA synthetase (MetRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of MetRS 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. MetRS is a class I aaRS, containing a Rossman fold catalytic core. It recognizes the initiator tRNA as well as the Met-tRNA for protein chain elongation. The GST_C-like domain of MetRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       77 QDDLTNQWLEWEATELQPALSAALYYLVVQGKKGEDVLGSVRRALTHIDHSLSRQNCPFLaGETESLADIVLWGALYPLL 156
Cdd:cd10307   1 DDDLSNQWLEWEAWLLQPALSLALALTHVQGKKSEADLNTVLNALVHLDQSLLKKSTPLL-GDKLSSADVVVWSALYPLG 79

                        90       100
                ....*....|....*....|...
4BL7_A      157 QDPAYLPEELSALHSWFQTLSTQ 179
Cdd:cd10307  80 TDKSALPENLDNLRRWFQNVSTL 102

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       47 KVPVLQlDSGNYLFSTSAICRYF--------FLLSGWEQDDLTNQWLEWEATELQPALSAALYYLVVQG--KKGEDVLGS 116
Cdd:COG0625  52 KVPVLV-DDGLVLTESLAILEYLaerypeppLLPADPAARARVRQWLAWADGDLHPALRNLLERLAPEKdpAAIARARAE 130

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4BL7_A      117 VRRALTHIDHSLSRQncPFLAGETESLADIVLWGALYPLLQDPAYLpEELSALHSWFQTLSTQEPCQRAAE 187
Cdd:COG0625 131 LARLLAVLEARLAGG--PYLAGDRFSIADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLAARPAFQRALA 198

glutathione S-transferase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A        47 KVPVLQldSGNY-LFSTSAICRYF----------FLLSGWEQDDLTNQWLEWEATELQPALSAALYYLVVQGKKG----E 111
Cdd:PLN02395  52 VVPVIV--DGDYkIFESRAIMRYYaekyrsqgpdLLGKTIEERGQVEQWLDVEATSYHPPLLNLTLHILFASKMGfpadE 129

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
4BL7_A       112 DVLGSVRRALTHI----DHSLSRQNcpFLAGETESLADIV-------LWGALypllqDPAYLPEELSALHSWFQTLSTQ 179
Cdd:PLN02395 130 KVIKESEEKLAKVldvyEARLSKSK--YLAGDFVSLADLAhlpfteyLVGPI-----GKAYLIKDRKHVSAWWDDISSR 201

Glutathione S-transferase C-terminal-like, alpha helical domain of Methionyl-tRNA synthetase from higher eukaryotes; Glutathione S-transferase (GST) C-terminal domain family, Methionyl-tRNA synthetase (MetRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of MetRS 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. MetRS is a class I aaRS, containing a Rossman fold catalytic core. It recognizes the initiator tRNA as well as the Met-tRNA for protein chain elongation. The GST_C-like domain of MetRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. AaRSs from prokaryotes, which are active as dimers, do not contain this GST_C-like domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       77 QDDLTNQWLEWEATELQPALSAALYYLVVQGKKGEDVLGSVRRALTHIDHSLSRQNCPFLaGETESLADIVLWGALYPLL 156
Cdd:cd10307   1 DDDLSNQWLEWEAWLLQPALSLALALTHVQGKKSEADLNTVLNALVHLDQSLLKKSTPLL-GDKLSSADVVVWSALYPLG 79

                        90       100
                ....*....|....*....|...
4BL7_A      157 QDPAYLPEELSALHSWFQTLSTQ 179
Cdd:cd10307  80 TDKSALPENLDNLRRWFQNVSTL 102

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       47 KVPVLQlDSGNYLFSTSAICRYF--------FLLSGWEQDDLTNQWLEWEATELQPALSAALYYLVVQG--KKGEDVLGS 116
Cdd:COG0625  52 KVPVLV-DDGLVLTESLAILEYLaerypeppLLPADPAARARVRQWLAWADGDLHPALRNLLERLAPEKdpAAIARARAE 130

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4BL7_A      117 VRRALTHIDHSLSRQncPFLAGETESLADIVLWGALYPLLQDPAYLpEELSALHSWFQTLSTQEPCQRAAE 187
Cdd:COG0625 131 LARLLAVLEARLAGG--PYLAGDRFSIADIALAPVLRRLDRLGLDL-ADYPNLAAWLARLAARPAFQRALA 198

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       83 QWLEWEATELQPALSAALYYLVVQGKKGED---VLGSVRRALTHI---DHSLSRQncPFLAGETESLADIVLWGALYPLL 156
Cdd:cd03180   8 RWMDWQTSTLNPAFRYAFWGLVRTPPEQRDpaaIAASLAACNKLMailDAQLARQ--AYLAGDRFTLADIALGCSVYRWL 85

                        90       100       110
                ....*....|....*....|....*....|
4BL7_A      157 QDPAYLPeELSALHSWFQTLStqepcQRAA 186
Cdd:cd03180  86 ELPIERP-ALPHLERWYARLS-----QRPA 109

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       81 TNQWLEWEATELQPALSAALYY----LVVQGKKGEDVLGSVRRALTHIDHSLSRQncPFLAGETESLADIVLWGALY--P 154
Cdd:cd00299   1 VRALEDWADATLAPPLVRLLYLekvpLPKDEAAVEAAREELPALLAALEQLLAGR--PYLAGDQFSLADVALAPVLArlE 78

                        90       100
                ....*....|....*....|..
4BL7_A      155 LLQDPAYLPEELSALHSWFQTL 176
Cdd:cd00299  79 ALGPYYDLLDEYPRLKAWYDRL 100

Glutathione S-transferase, C-terminal domain; GST conjugates reduced glutathione to a variety of targets including S-crystallin from squid, the eukaryotic elongation factor 1-gamma, the HSP26 family of stress-related proteins and auxin-regulated proteins in plants. Stringent starvation proteins in E. coli are also included in the alignment but are not known to have GST activity. The glutathione molecule binds in a cleft between N and C-terminal domains. The catalytically important residues are proposed to reside in the N-terminal domain. In plants, GSTs are encoded by a large gene family (48 GST genes in Arabidopsis) and can be divided into the phi, tau, theta, zeta, and lambda classes.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
4BL7_A        111 EDVLGSVRRALTHIDHSLSrqNCPFLAGETESLADIVLWGAL-YPLLQDPAYLPEELSALHSWFQTLSTQE 180
Cdd:pfam00043  25 DEALEKVARVLSALEEVLK--GQTYLVGDKLTLADIALAPALlWLYELDPACLREKFPNLKAWFERVAARP 93

Glutathione S-transferase C-terminal-like, alpha helical domain of vertebrate Valyl-tRNA synthetase; Glutathione S-transferase (GST) C-terminal domain family, Valyl-tRNA synthetase (ValRS) subfamily; This model characterizes the GST_C-like domain found in the N-terminal region of human ValRS and its homologs from other vertebrates such as frog and zebrafish. 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. They typically form large stable complexes with other proteins. 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. The GST_C-like domain of ValRS from higher eukaryotes is likely involved in protein-protein interactions, to mediate the formation of the multi-aaRS complex that acts as a molecular hub to coordinate protein synthesis. ValRSs from prokaryotes and lower eukaryotes, such as fungi and plants, do not appear to contain this GST_C-like domain.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       77 QDDLTNQWLEWEATELQPALSAALYYLV----VQGKKGEDVLGSVRRALTHIDHSLSRQNcpFLAGETESLADIVLWGAL 152
Cdd:cd10294   1 ACALVWQWVSFADNELTPAACAAAFPLLglsgSDKQNQQRSLAELQRVLKVLDCYLKLRT--YLVGEAITLADIAVACAL 78

                        90       100       110
                ....*....|....*....|....*....|
4BL7_A      153 ---YPLLQDPAyLPEELSALHSWFQTLSTQ 179
Cdd:cd10294  79 llpFKYVLDPA-RRESLLNVTRWFLTCVNQ 107

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
                ....*....|....*....|....*....|....*....|..
4BL7_A       27 EVLISTVGPEDCVVPFLTRPKVPVLQLDSGNYLFSTSAICRY 68
Cdd:cd03049  30 LVLVNPWSDDESLLAVNPLGKIPALVLDDGEALFDSRVICEY 71

C-terminal, alpha helical domain of Class Omega-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain family, Saccharomyces cerevisiae Omega-like subfamily; composed of three Saccharomyces cerevisiae GST omega-like (Gto) proteins, Gto1p, Gto2p (also known as Extracellular mutant protein 4 or ECM4p), and Gto3p, as well as similar uncharacterized proteins from fungi and bacteria. The three Saccharomyces cerevisiae Gto proteins are omega-class GSTs with low or no GST activity against standard substrates, but have glutaredoxin/thiol oxidoreductase and dehydroascorbate reductase activity through a single cysteine residue in the active site. Gto1p is located in the peroxisomes while Gto2p and Gto3p are cytosolic. The gene encoding Gto2p, called ECM4, is involved in cell surface biosynthesis and architecture. S. cerevisiae ECM4 mutants show increased amounts of the cell wall hexose, N-acetylglucosamine. More recently, global gene expression analysis shows that ECM4 is upregulated during genotoxic conditions and together with the expression profiles of 18 other genes could potentially differentiate between genotoxic and cytotoxic insults in yeast.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A      111 EDVLGSVRRALTHIDHSLSRQncPFLAGETESLADIVLWGALYPLlqDPAYLP---------EELSALHSWFQTLSTQEP 181
Cdd:cd03190  36 DKAVKELFEALDKLEKRLSKQ--PYLLGDRLTEADIRLFTTLIRF--DPVYHQhfkcnlktiRDYPNLWRYLRRLYQNPG 111

                ....*...
4BL7_A      182 cqrAAETV 189
Cdd:cd03190 112 ---VFETT 116

Glutathione S-transferase C-terminal-like, alpha helical domain of Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein 3; Glutathione S-transferase (GST) C-terminal domain family, Aminoacyl tRNA synthetase complex-Interacting Multifunctional Protein (AIMP) 3 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. AIMP3, also called p18 or eukaryotic translation elongation factor 1 epsilon-1 (EEF1E1), contains a C-terminal domain with similarity to the C-terminal alpha helical domain of GSTs. It specifically interacts with methionyl-tRNA synthetase (MetRS) and is translocated to the nucleus during DNA synthesis or in response to DNA damage and oncogenic stress. In the nucleus, it interacts with ATM and ATR, which are upstream kinase regulators of p53. It appears to work against DNA damage in cooperation with AIMP2, and similar to AIMP2, AIMP3 is also a haploinsufficient tumor suppressor. AIMP3 transgenic mice have shorter lifespans than wild-type mice and they show characteristics of progeria, suggesting that AIMP3 may also be involved in cellular and organismal aging.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
4BL7_A       80 LTNQWLEWEATELQPALSAALyylvvqgkkgedvlgsVRRALTHIDHSLsrQNCPFLAGETESLADIVLWGALYPLLQDP 159
Cdd:cd10305   6 QVDQWLEYRVTQVAPASDKAD----------------AKSLLKELNSYL--QDRTYLVGHKLTLADVVLYYGLHPIMKDL 67

                        90
                ....*....|....*...
4BL7_A      160 AYLPEE-LSALHSWFQTL 176
Cdd:cd10305  68 SPQEKEqYLNVSRWFDHV 85