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 2024458820 174 ARFLFSLFG-QKYNAITSTLIDSWVDTAIFQLKEGSSKEKGAVLRSMNAALGKTSWLVGNELTVADIVAWCALQQTGSAN 252
Cdd:cd03200     1 ARFLFRLLGdESDDPVNATLIDSWVDTAIFQLLEGSSKEKAAVLRALNSALGRSPWLVGSEPTVADIALWSAVLQTGLAS 80

                          90
                  ....*....|....*.
gi 2024458820 253 AAPSNVQKWMKSCENL 268
Cdd:cd03200    81 GAPANVQRWMKSCENL 96

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 2024458820 174 ARFLFSLFG-QKYNAITSTLIDSWVDTAIFQLKEGSSKEKGAVLRSMNAALGKTSWLVGNELTVADIVAWCALQQTGSAN 252
Cdd:cd03200     1 ARFLFRLLGdESDDPVNATLIDSWVDTAIFQLLEGSSKEKAAVLRALNSALGRSPWLVGSEPTVADIALWSAVLQTGLAS 80

                          90
                  ....*....|....*.
gi 2024458820 253 AAPSNVQKWMKSCENL 268
Cdd:cd03200    81 GAPANVQRWMKSCENL 96

glutamate-tRNA ligase

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024458820 179 SLFGQkyNAITSTLIDSWVDTAIfQLKEGSSKEKGAVlrSMNAALGKTSWLVGNELTVADIVAWCALQQTGsanaapsnv 258
Cdd:PLN02907   67 GFYGQ--DAFESSQVDEWLDYAP-TFSSGSEFENACE--YVDGYLASRTFLVGYSLTIADIAIWSGLAGSG--------- 132

                          90
                  ....*....|....*.
gi 2024458820 259 QKW-----MKSCENLA 269
Cdd:PLN02907  133 QRWeslrkSKKYQNLV 148

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 2024458820 203 QLKEGSSKEKGAVLRSMNAALGKTSWLVGNELTVADIVAWCALQQTGSANAAPS-----NVQKWMKSCENL 268
Cdd:pfam00043  22 PEVDEALEKVARVLSALEEVLKGQTYLVGDKLTLADIALAPALLWLYELDPACLrekfpNLKAWFERVAAR 92

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 2024458820 174 ARFLFSLFG-QKYNAITSTLIDSWVDTAIFQLKEGSSKEKGAVLRSMNAALGKTSWLVGNELTVADIVAWCALQQTGSAN 252
Cdd:cd03200     1 ARFLFRLLGdESDDPVNATLIDSWVDTAIFQLLEGSSKEKAAVLRALNSALGRSPWLVGSEPTVADIALWSAVLQTGLAS 80

                          90
                  ....*....|....*.
gi 2024458820 253 AAPSNVQKWMKSCENL 268
Cdd:cd03200    81 GAPANVQRWMKSCENL 96

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        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024458820 189 TSTLIDSWVDTAIFQLKEgssKEKGAVLRSMNAALGKTSWLVGNELTVADIVAWCALQQTGSANAA-----PSNVQKWMK 263
Cdd:cd10289     1 EAAQVDQWLDLAGSLLKG---KELEALLKSLNSYLASRTFLVGYSLTLADVAVFSALYPSGQKLSDkekkkFPHVTRWFN 77

                  ....*
gi 2024458820 264 SCENL 268
Cdd:cd10289    78 HIQNL 82

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
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 2024458820 215 VLRSMNAALGKTSWLVGNELTVADIVAW----CALQQTGSANAAPsNVQKWMKSCEN 267
Cdd:cd03189    66 HLDFLEDHLAKHPYFAGDELTAADIMMSfpleAALARGPLLEQYP-NIAAYLERIEA 121

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024458820 177 LFSLFGQKYNAITSTLIDSWVDTAIFQLKegsskekgAVLRSMNAALGKTSWLVGNELTVADIVAWCAL---QQTGSANA 253
Cdd:COG0625   104 LHPALRNLLERLAPEKDPAAIARARAELA--------RLLAVLEARLAGGPYLAGDRFSIADIALAPVLrrlDRLGLDLA 175

                          90       100
                  ....*....|....*....|..
gi 2024458820 254 APSNVQKWMKSCENLAPFSSVM 275
Cdd:COG0625   176 DYPNLAAWLARLAARPAFQRAL 197

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        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024458820 219 MNAALGKTSWLVGNELTVADIvawCALQQTGSANAAP------SNVQKWMKSCENLAPFS 272
Cdd:cd03177    50 LETFLEGSDYVAGDQLTIADL---SLVATVSTLEVVGfdlskyPNVAAWYERLKALPPGE 106

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 2024458820 193 IDSWVDTAIFQLKEGSSKEKGAVLRSMNAALGKTSWLVGNELTVADIVAWCALQQTGSA-----NAAPSNVQKWMKSCEN 267
Cdd:cd10306     7 VAEWIDFATTLLVLKDFKALSQALEELDSHLTLRTFIVGYSLSLADIAVWGALRGNGVAgslikNKVYVNLSRWFSFLES 86

                  .
gi 2024458820 268 L 268
Cdd:cd10306    87 L 87

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 2024458820 214 AVLRSMNAALGKTSWLVGNELTVADIVAWCAL---QQTGSA---NAAPSNVQKWMKSC 265
Cdd:cd00299    43 ALLAALEQLLAGRPYLAGDQFSLADVALAPVLarlEALGPYydlLDEYPRLKAWYDRL 100

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2024458820 168 EGEGNIARFLFSLFG-QKYNAITstlidswVDTAIFQLKegsskekgAVLRSMNAALGKTSWLVGNELTVADIVAWCALQ 246
Cdd:cd03181    15 ELLPAAATWVLPLLGiAPYNKKA-------VDKAKEDLK--------RALGVLEEHLLTRTYLVGERITLADIFVASALL 79

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 2024458820 247 QTGSANAAPS------NVQKWMKSCENLAPFSSVMK 276
Cdd:cd03181    80 RGFETVLDPEfrkkypNVTRWFNTVVNQPKFKAVFG 115