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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   65 AEEKAIVQQWLEYRVTQVDGHSSKNDIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLHRFIVDLTVQEKEKYLNVSR 144
Cdd:cd10305   1 AEERAQVDQWLEYRVTQVAPASDKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVSR 80

                        90       100
                ....*....|....*....|.
gi 4758862  145 WFCHIQHYPGIRQHLSSVVFI 165
Cdd:cd10305  81 WFDHVQHLPGIRQHLPLINFT 101

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   65 AEEKAIVQQWLEYRVTQVDGHSSKNDIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLHRFIVDLTVQEKEKYLNVSR 144
Cdd:cd10305   1 AEERAQVDQWLEYRVTQVAPASDKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVSR 80

                        90       100
                ....*....|....*....|.
gi 4758862  145 WFCHIQHYPGIRQHLSSVVFI 165
Cdd:cd10305  81 WFDHVQHLPGIRQHLPLINFT 101

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   28 RQIPVLQtNNGPSLTGLTTIAAHLVKQANKEYLLGSTAEEKAIVQQWLEY-----------RVTQVDGHSS-------KN 89
Cdd:COG0625  51 GKVPVLV-DDGLVLTESLAILEYLAERYPEPPLLPADPAARARVRQWLAWadgdlhpalrnLLERLAPEKDpaaiaraRA 129

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   90 DIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLH---RFIVDLtvqekEKYLNVSRWF 146
Cdd:COG0625 130 ELARLLAVLEARLAGGPYLAGDRFSIADIALAPVLRrldRLGLDL-----ADYPNLAAWL 184

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   65 AEEKAIVQQWLEYRVTQVDGHSSKNDIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLHRFIVDLTVQEKEKYLNVSR 144
Cdd:cd10305   1 AEERAQVDQWLEYRVTQVAPASDKADAKSLLKELNSYLQDRTYLVGHKLTLADVVLYYGLHPIMKDLSPQEKEQYLNVSR 80

                        90       100
                ....*....|....*....|.
gi 4758862  145 WFCHIQHYPGIRQHLSSVVFI 165
Cdd:cd10305  81 WFDHVQHLPGIRQHLPLINFT 101

glutamate-tRNA ligase

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862    30 IPVLQTNNGPSLTGLTTIAAHLVKQANKEYLLGSTAEEKAIVQQWLEYRVTQVDGHSSKNDIHTllkdLNSYLEDKVYLT 109
Cdd:PLN02907  38 APTLLFSSGEKLTGTNVLLRYIARSASLPGFYGQDAFESSQVDEWLDYAPTFSSGSEFENACEY----VDGYLASRTFLV 113

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 4758862   110 GYNFTLADILLYYGLH----RFIVdltVQEKEKYLNVSRWF 146
Cdd:PLN02907 114 GYSLTIADIAIWSGLAgsgqRWES---LRKSKKYQNLVRWF 151

Glutathione S-transferase C-terminal-like, alpha helical domain of eukaryotic translation Elongation Factor 1 beta; Glutathione S-transferase (GST) C-terminal domain family, eukaryotic translation Elongation Factor 1 beta (eEF1b) subfamily; eEF1b is a component 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. eEF1b contains a GST_C-like alpha helical domain at the N-terminal region and a C-terminal guanine nucleotide exchange domain. The GST_C-like domain likely functions as a protein-protein interaction domain, similar to the function of the GST_C-like domains of EF1Bgamma and various aminoacyl-tRNA synthetases (aaRSs) from higher eukaryotes.

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4758862   95 LKDLNSYLEDKVYLTGYNFTLADILLYYGLHRfivdltVQEKEKYLNVSRWFCHIQHY 152
Cdd:cd10308  31 LEALNEYLADRSYISGYSPSQADVEVFDKLKK------APDATKFPHLARWYRHIASF 82

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   28 RQIPVLQtNNGPSLTGLTTIAAHLVKQANKEYLLGSTAEEKAIVQQWLEY-----------RVTQVDGHSS-------KN 89
Cdd:COG0625  51 GKVPVLV-DDGLVLTESLAILEYLAERYPEPPLLPADPAARARVRQWLAWadgdlhpalrnLLERLAPEKDpaaiaraRA 129

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   90 DIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLH---RFIVDLtvqekEKYLNVSRWF 146
Cdd:COG0625 130 ELARLLAVLEARLAGGPYLAGDRFSIADIALAPVLRrldRLGLDL-----ADYPNLAAWL 184

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        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   65 AEEKAIVQQWLEYRVTQVDGHSSKnDIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLHRFIVDLTVQEKEKYLNVSR 144
Cdd:cd10306   1 NGDKEQVAEWIDFATTLLVLKDFK-ALSQALEELDSHLTLRTFIVGYSLSLADIAVWGALRGNGVAGSLIKNKVYVNLSR 79

                ....*
gi 4758862  145 WFCHI 149
Cdd:cd10306  80 WFSFL 84

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862   69 AIVQQWLEY--------------------RVTQVDGHSSKNDIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGL---H 125
Cdd:cd10294   3 ALVWQWVSFadneltpaacaaafpllglsGSDKQNQQRSLAELQRVLKVLDCYLKLRTYLVGEAITLADIAVACALllpF 82

                        90       100       110       120
                ....*....|....*....|....*....|....*....|.
gi 4758862  126 RFIVDLTvqEKEKYLNVSRWFCHIQHYPGIRQHLSSVVFIK 166
Cdd:cd10294  83 KYVLDPA--RRESLLNVTRWFLTCVNQPEFLAVLGEVSLCE 121

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 4758862   95 LKDLNSYLEDKVYLTGYNFTLADILLYY---GLHRFIVDLtvqekEKYLNVSRWF 146
Cdd:cd03177  47 LEFLETFLEGSDYVAGDQLTIADLSLVAtvsTLEVVGFDL-----SKYPNVAAWY 96

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
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4758862   90 DIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLHRF-IVDLTVQEKEKYLNVSRWF 146
Cdd:cd00299  40 ELPALLAALEQLLAGRPYLAGDQFSLADVALAPVLARLeALGPYYDLLDEYPRLKAWY 97

glutathionine S-transferase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4758862    29 QIPVLQTNNGPSLTGLTTIAAHLVKQANKEYLL---GSTAEEKAIvqQWLEYRVTQV-DGHS--------------SKND 90
Cdd:PRK10542  51 QVPALLLDDGTLLTEGVAIMQYLADSVPDRQLLapvGSLSRYHTI--EWLNYIATELhKGFTplfrpdtpeeykptVRAQ 128

                         90       100       110
                 ....*....|....*....|....*....|.
gi 4758862    91 IHTLLKDLNSYLEDKVYLTGYNFTLADILLY 121
Cdd:PRK10542 129 LEKKFQYVDEALADEQWICGQRFTIADAYLF 159

C-terminal, alpha helical domain of GTT1-like Glutathione S-transferases; Glutathione S-transferase (GST) C-terminal domain 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 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. 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 4758862   89 NDIHTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLhrFIVDLTVQEKEKYLNVSRWFCHIQHYP 153
Cdd:cd03189  61 PELKRHLDFLEDHLAKHPYFAGDELTAADIMMSFPL--EAALARGPLLEQYPNIAAYLERIEARP 123

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
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4758862   92 HTLLKDLNSYLEDKVYLTGYNFTLADILLYYGLHRFIvdLTVQEKEKYLNVSRWFCHIQHYPG 154
Cdd:cd03180  49 NKLMAILDAQLARQAYLAGDRFTLADIALGCSVYRWL--ELPIERPALPHLERWYARLSQRPA 109