ID SYMC_YEAST Reviewed; 751 AA. AC P00958; D6VV43; DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 04-NOV-2026, entry version 223. DE RecName: Full=Methionine--tRNA ligase, cytoplasmic; DE EC=6.1.1.10; DE AltName: Full=Methionyl-tRNA synthetase; DE Short=MetRS; GN Name=MES1; OrderedLocusNames=YGR264C; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=6341994; DOI=10.1073/pnas.80.9.2437; RA Walter P., Gangloff J., Bonnet J., Boulanger Y., Ebel J.-P., Fasiolo F.; RT "Primary structure of the Saccharomyces cerevisiae gene for methionyl-tRNA RT synthetase."; RL Proc. Natl. Acad. Sci. U.S.A. 80:2437-2441(1983). RN [2] RP SEQUENCE REVISION. RA Fasiolo F.; RL Submitted (SEP-1983) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PARTIAL PROTEIN SEQUENCE, CLEAVAGE OF RP INITIATOR METHIONINE, AND ACETYLATION AT SER-2. RX PubMed=3905796; DOI=10.1016/s0021-9258(17)36295-6; RA Fasiolo F., Gibson B.W., Walter P., Chatton B., Biemann K., Boulanger Y.; RT "Cytoplasmic methionyl-tRNA synthetase from Bakers' yeast. A monomer with a RT post-translationally modified N-terminus."; RL J. Biol. Chem. 260:15571-15576(1985). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 96604 / S288c / FY1679; RX PubMed=9090059; RX DOI=10.1002/(sici)1097-0061(19970315)13:3<287::aid-yea75>3.0.co;2-5; RA Clemente M.L., Sartori G., Cardazzo B., Carignani G.; RT "Analysis of an 11.6 kb region from the right arm of chromosome VII of RT Saccharomyces cerevisiae between the RAD2 and the MES1 genes reveals the RT presence of three new genes."; RL Yeast 13:287-290(1997). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169869; DOI=10.1038/387s081; RA Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J., RA Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M., RA Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L., RA Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H., RA Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P., RA Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M., RA Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A., RA Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K., RA Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P., RA Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E., RA Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K., RA Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A., RA Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S., RA Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M., RA Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C., RA Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M., RA Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M., RA Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y., RA Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L., RA Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D., RA Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F., RA Zaccaria P., Zimmermann M., Zollner A., Kleine K.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII."; RL Nature 387:81-84(1997). RN [6] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [7] RP PROTEIN SEQUENCE OF 10-90, CLEAVAGE OF INITIATOR METHIONINE, AND RP ACETYLATION AT SER-2. RX PubMed=6371805; DOI=10.1073/pnas.81.7.1956; RA Gibson B.W., Biemann K.; RT "Strategy for the mass spectrometric verification and correction of the RT primary structures of proteins deduced from their DNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 81:1956-1960(1984). RN [8] RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND MUTAGENESIS OF RP GLY-502. RX PubMed=3312199; DOI=10.1016/s0021-9258(18)48142-2; RA Chatton B., Winsor B., Boulanger Y., Fasiolo F.; RT "Cloning and characterization of the yeast methionyl-tRNA synthetase RT mutation mes1."; RL J. Biol. Chem. 262:15094-15097(1987). RN [9] RP MUTAGENESIS OF ASN-584 AND ARG-588. RX PubMed=1915850; DOI=10.1016/0014-5793(91)81073-h; RA Despons L., Walter P., Senger B., Ebel J.-P., Fasiolo F.; RT "Identification of potential amino acid residues supporting anticodon RT recognition in yeast methionyl-tRNA synthetase."; RL FEBS Lett. 289:217-220(1991). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP INTERACTION WITH ARC1. RX PubMed=8895587; DOI=10.1002/j.1460-2075.1996.tb00927.x; RA Simos G., Segref A., Fasiolo F., Hellmuth K., Shevshenko A., Mann M., RA Hurt E.C.; RT "The yeast protein Arc1p binds to tRNA and functions as a cofactor for the RT methionyl- and glutamyl-tRNA synthetases."; RL EMBO J. 15:5437-5448(1996). RN [11] RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND INTERACTION WITH RP ARC1. RX PubMed=9659920; DOI=10.1016/s1097-2765(00)80024-6; RA Simos G., Sauer A., Fasiolo F., Hurt E.C.; RT "A conserved domain within Arc1p delivers tRNA to aminoacyl-tRNA RT synthetases."; RL Mol. Cell 1:235-242(1998). RN [12] RP SUBUNIT, INTERACTION WITH ARC1, AND SUBCELLULAR LOCATION. RX PubMed=11726524; DOI=10.1093/emboj/20.23.6889; RA Galani K., Grosshans H., Deinert K., Hurt E.C., Simos G.; RT "The intracellular location of two aminoacyl-tRNA synthetases depends on RT complex formation with Arc1p."; RL EMBO J. 20:6889-6898(2001). RN [13] RP SUBUNIT. RX PubMed=11069915; DOI=10.1074/jbc.m008682200; RA Deinert K., Fasiolo F., Hurt E.C., Simos G.; RT "Arc1p organizes the yeast aminoacyl-tRNA synthetase complex and stabilizes RT its interaction with the cognate tRNAs."; RL J. Biol. Chem. 276:6000-6008(2001). RN [14] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [15] RP X-RAY CRYSTALLOGRAPHY IN COMPLEX WITH ARC1, AND MUTAGENESIS OF ALA-63. RX PubMed=16914447; DOI=10.1093/nar/gkl560; RA Simader H., Hothorn M., Koehler C., Basquin J., Simos G., Suck D.; RT "Structural basis of yeast aminoacyl-tRNA synthetase complex formation RT revealed by crystal structures of two binary sub-complexes."; RL Nucleic Acids Res. 34:3968-3979(2006). CC -!- FUNCTION: Catalyzes the attachment of methionine to tRNA(Met) in a two- CC step reaction: methionine is first activated by ATP to form Met-AMP and CC then transferred to the acceptor end of tRNA(Met). CC {ECO:0000269|PubMed:8895587}. CC -!- CATALYTIC ACTIVITY: CC Reaction=tRNA(Met) + L-methionine + ATP = L-methionyl-tRNA(Met) + AMP + CC diphosphate; Xref=Rhea:RHEA:13481, Rhea:RHEA-COMP:9667, Rhea:RHEA- CC COMP:9698, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57844, CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78530, ChEBI:CHEBI:456215; CC EC=6.1.1.10; Evidence={ECO:0000269|PubMed:3312199, CC ECO:0000269|PubMed:8895587, ECO:0000269|PubMed:9659920}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=6.6 uM for tRNA(Met) (in the absence of ARC1) CC {ECO:0000269|PubMed:3312199, ECO:0000269|PubMed:8895587, CC ECO:0000269|PubMed:9659920}; CC KM=10 uM for methionine {ECO:0000269|PubMed:3312199, CC ECO:0000269|PubMed:8895587, ECO:0000269|PubMed:9659920}; CC Note=The presence of ARC1 reduces the KM for tRNA(Met) to less than CC 0.1 uM and increases the catalytic efficiency more than 500-fold.; CC -!- SUBUNIT: Component of a yeast aminoacyl-tRNA synthase (aaRS) complex CC formed by methionyl-tRNA synthase MES1, glutamyl-tRNA synthase GUS1 and CC the tRNA aminoacylation cofactor ARC1 in a stoichiometric complex. CC Interacts (via N-ter) with ARC1 (via N-ter). Can also form a stable CC binary complex with ARC1 that is functional in terms of aminoacylation. CC ARC1 increases the affinity for cognate tRNAs due to the presence of a CC tRNA binding domain in the middle and C-terminal part of ARC1. CC {ECO:0000269|PubMed:11069915, ECO:0000269|PubMed:11726524, CC ECO:0000269|PubMed:16914447, ECO:0000269|PubMed:8895587, CC ECO:0000269|PubMed:9659920}. CC -!- INTERACTION: CC P00958; P46672: ARC1; NbExp=8; IntAct=EBI-18762, EBI-7224; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11726524}. CC Note=Largely excluded from the nucleus. CC -!- MISCELLANEOUS: Present with 85000 molecules/cell in log phase SD CC medium. {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; V01316; CAA24627.1; -; Genomic_DNA. DR EMBL; Y07777; CAA69086.1; -; Genomic_DNA. DR EMBL; Z73049; CAA97293.1; -; Genomic_DNA. DR EMBL; BK006941; DAA08354.1; -; Genomic_DNA. DR PIR; S64597; SYBYMT. DR RefSeq; NP_011780.3; NM_001181393.3. DR PDB; 2HSN; X-ray; 2.20 A; A=2-160. DR AlphaFoldDB; P00958; -. DR MDposit; P00958; -. DR SMR; P00958; -. DR BioGRID; 33515; 457. DR ComplexPortal; CPX-1947; Methionyl glutamyl tRNA synthetase complex. DR DIP; DIP-2211N; -. DR FunCoup; P00958; 1265. DR IntAct; P00958; 30. DR STRING; 4932.YGR264C; -. DR iPTMnet; P00958; -. DR PaxDb; 4932-YGR264C; -. DR PeptideAtlas; P00958; -. DR EnsemblFungi; YGR264C_mRNA; YGR264C; YGR264C. DR GeneID; 853181; -. DR KEGG; sce:YGR264C; -. DR AGR; SGD:S000003496; -. DR SGD; S000003496; MES1. DR VEuPathDB; FungiDB:YGR264C; -. DR eggNOG; KOG1247; Eukaryota. DR HOGENOM; CLU_009710_4_1_1; -. DR InParanoid; P00958; -. DR OMA; AAAEXII; -. DR OrthoDB; 5844513at2759; -. DR BioCyc; YEAST:G3O-30933-MONOMER; -. DR BRENDA; 6.1.1.10; 984. DR BioGRID-ORCS; 853181; 0 hits in 10 CRISPR screens. DR CD-CODE; E03F929F; Stress granule. DR EvolutionaryTrace; P00958; -. DR PRO; PR:P00958; -. DR Proteomes; UP000002311; Chromosome VII. DR RNAct; P00958; protein. DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:SGD. DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:SGD. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0017102; C:methionyl glutamyl tRNA synthetase complex; IDA:SGD. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0004825; F:methionine-tRNA ligase activity; IDA:SGD. DR GO; GO:1990825; F:sequence-specific mRNA binding; IDA:SGD. DR GO; GO:0006424; P:glutamyl-tRNA aminoacylation; NAS:ComplexPortal. DR GO; GO:0006431; P:methionyl-tRNA aminoacylation; IDA:SGD. DR CDD; cd07957; Anticodon_Ia_Met; 1. DR CDD; cd10290; GST_C_MetRS_N_fungi; 1. DR CDD; cd00814; MetRS_core; 1. DR FunFam; 2.20.28.20:FF:000001; Methionine--tRNA ligase; 1. DR FunFam; 1.20.1050.110:FF:000001; Methionine-tRNA ligase; 1. DR FunFam; 3.40.30.170:FF:000001; Methionine-tRNA ligase; 1. DR FunFam; 1.10.730.10:FF:000037; Methionyl-tRNA synthetase; 1. DR Gene3D; 1.20.1050.110; -; 1. DR Gene3D; 3.40.30.170; -; 1. DR Gene3D; 3.40.50.620; HUPs; 1. DR Gene3D; 1.10.730.10; Isoleucyl-tRNA Synthetase, Domain 1; 1. DR Gene3D; 2.20.28.20; Methionyl-tRNA synthetase, Zn-domain; 1. DR HAMAP; MF_00098; Met_tRNA_synth_type1; 1. DR InterPro; IPR001412; aa-tRNA-synth_I_CS. DR InterPro; IPR041872; Anticodon_Met. DR InterPro; IPR018285; Met-tRNA-synth_N. DR InterPro; IPR023458; Met-tRNA_ligase_1. DR InterPro; IPR014758; Met-tRNA_synth. DR InterPro; IPR015413; Methionyl/Leucyl_tRNA_Synth. DR InterPro; IPR033911; MetRS_core. DR InterPro; IPR029038; MetRS_Zn. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR InterPro; IPR009080; tRNAsynth_Ia_anticodon-bd. DR NCBIfam; NF001100; metG; 1. DR NCBIfam; TIGR00398; metG; 1. DR PANTHER; PTHR45765; METHIONINE--TRNA LIGASE; 1. DR PANTHER; PTHR45765:SF1; METHIONINE--TRNA LIGASE, CYTOPLASMIC; 1. DR Pfam; PF19303; Anticodon_3; 1. DR Pfam; PF09635; MetRS-N; 1. DR Pfam; PF09334; tRNA-synt_1g; 1. DR PRINTS; PR01041; TRNASYNTHMET. DR SUPFAM; SSF47323; Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases; 1. DR SUPFAM; SSF57770; Methionyl-tRNA synthetase (MetRS), Zn-domain; 1. DR SUPFAM; SSF52374; Nucleotidylyl transferase; 1. DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; KW Cytoplasm; Direct protein sequencing; Ligase; Nucleotide-binding; KW Protein biosynthesis; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:3905796, FT ECO:0000269|PubMed:6371805" FT CHAIN 2..751 FT /note="Methionine--tRNA ligase, cytoplasmic" FT /id="PRO_0000139269" FT REGION 36..92 FT /note="Interaction with ARC1" FT MOTIF 205..215 FT /note="'HIGH' region" FT MOTIF 525..529 FT /note="'KMSKS' region" FT BINDING 411 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|PubMed:3905796, FT ECO:0000269|PubMed:6371805" FT MUTAGEN 63 FT /note="A->H: Abolishes interaction with ARC1." FT /evidence="ECO:0000269|PubMed:16914447" FT MUTAGEN 502 FT /note="G->D: In mes1; renders the protein unstable in FT vitro, elevates the KM for methionine in vivo." FT /evidence="ECO:0000269|PubMed:3312199" FT MUTAGEN 584 FT /note="N->D,Q: Abolishes aminoacylation activity." FT /evidence="ECO:0000269|PubMed:1915850" FT MUTAGEN 588 FT /note="R->A,K,Q: Abolishes aminoacylation activity." FT /evidence="ECO:0000269|PubMed:1915850" FT CONFLICT 122 FT /note="T -> A (in Ref. 1; CAA24627 and 3)" FT /evidence="ECO:0000305" FT STRAND 3..5 FT /evidence="ECO:0007829|PDB:2HSN" FT STRAND 10..12 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 15..31 FT /evidence="ECO:0007829|PDB:2HSN" FT STRAND 49..51 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 61..68 FT /evidence="ECO:0007829|PDB:2HSN" FT TURN 73..76 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 78..82 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 83..87 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 90..92 FT /evidence="ECO:0007829|PDB:2HSN" FT STRAND 93..95 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 98..107 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 108..112 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 122..142 FT /evidence="ECO:0007829|PDB:2HSN" FT HELIX 148..157 FT /evidence="ECO:0007829|PDB:2HSN" SQ SEQUENCE 751 AA; 85678 MW; 11679C1AB8BB5E39 CRC64; MSFLISFDKS KKHPAHLQLA NNLKIALALE YASKNLKPEV DNDNAAMELR NTKEPFLLFD ANAILRYVMD DFEGQTSDKY QFALASLQNL LYHKELPQQH VEVLTNKAIE NYLVELKEPL TTTDLILFAN VYALNSSLVH SKFPELPSKV HNAVALAKKH VPRDSSSFKN IGAVKIQADL TVKPKDSEIL PKPNERNILI TSALPYVNNV PHLGNIIGSV LSADIFARYC KGRNYNALFI CGTDEYGTAT ETKALEEGVT PRQLCDKYHK IHSDVYKWFQ IGFDYFGRTT TDKQTEIAQH IFTKLNSNGY LEEQSMKQLY CPVHNSYLAD RYVEGECPKC HYDDARGDQC DKCGALLDPF ELINPRCKLD DASPEPKYSD HIFLSLDKLE SQISEWVEKA SEEGNWSKNS KTITQSWLKD GLKPRCITRD LVWGTPVPLE KYKDKVLYVW FDATIGYVSI TSNYTKEWKQ WWNNPEHVSL YQFMGKDNVP FHTVVFPGSQ LGTEENWTML HHLNTTEYLQ YENGKFSKSR GVGVFGNNAQ DSGISPSVWR YYLASVRPES SDSHFSWDDF VARNNSELLA NLGNFVNRLI KFVNAKYNGV VPKFDPKKVS NYDGLVKDIN EILSNYVKEM ELGHERRGLE IAMSLSARGN QFLQENKLDN TLFSQSPEKS DAVVAVGLNI IYAVSSIITP YMPEIGEKIN KMLNAPALKI DDRFHLAILE GHNINKAEYL FQRIDEKKID EWRAKYGGQQ V //