SYMC_YEAST
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 03-AUG-2022, entry version 206.
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;
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 (2.20 ANGSTROMS) OF 2-160 IN COMPLEX WITH ARC1, AND
RP 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=ATP + L-methionine + tRNA(Met) = AMP + diphosphate + L-
CC methionyl-tRNA(Met); Xref=Rhea:RHEA:13481, Rhea:RHEA-COMP:9667,
CC Rhea:RHEA-COMP:9698, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57844, ChEBI:CHEBI:78442, ChEBI:CHEBI:78530,
CC ChEBI:CHEBI:456215; EC=6.1.1.10;
CC Evidence={ECO:0000269|PubMed:3312199, ECO:0000269|PubMed:8895587,
CC 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=7; 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}.
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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 PDBsum; 2HSN; -.
DR AlphaFoldDB; P00958; -.
DR SMR; P00958; -.
DR BioGRID; 33515; 420.
DR ComplexPortal; CPX-1947; Methionyl glutamyl tRNA synthetase complex.
DR DIP; DIP-2211N; -.
DR IntAct; P00958; 12.
DR MINT; P00958; -.
DR STRING; 4932.YGR264C; -.
DR iPTMnet; P00958; -.
DR MaxQB; P00958; -.
DR PaxDb; P00958; -.
DR PRIDE; P00958; -.
DR EnsemblFungi; YGR264C_mRNA; YGR264C; YGR264C.
DR GeneID; 853181; -.
DR KEGG; sce:YGR264C; -.
DR SGD; S000003496; MES1.
DR VEuPathDB; FungiDB:YGR264C; -.
DR eggNOG; KOG1247; Eukaryota.
DR GeneTree; ENSGT00550000075017; -.
DR HOGENOM; CLU_009710_4_1_1; -.
DR InParanoid; P00958; -.
DR OMA; YMRMAGH; -.
DR BioCyc; YEAST:G3O-30933-MON; -.
DR BRENDA; 6.1.1.10; 984.
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: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:UniProtKB-KW.
DR GO; GO:0004825; F:methionine-tRNA ligase activity; IDA:SGD.
DR GO; GO:0006424; P:glutamyl-tRNA aminoacylation; IC:ComplexPortal.
DR GO; GO:0006431; P:methionyl-tRNA aminoacylation; IDA:SGD.
DR CDD; cd07957; Anticodon_Ia_Met; 1.
DR CDD; cd00814; MetRS_core; 1.
DR Gene3D; 2.20.28.20; -; 1.
DR Gene3D; 3.40.50.620; -; 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 PANTHER; PTHR45765; PTHR45765; 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; SSF47323; 1.
DR SUPFAM; SSF57770; SSF57770; 1.
DR TIGRFAMs; TIGR00398; metG; 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..86
FT /evidence="ECO:0007829|PDB:2HSN"
FT TURN 87..89
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..111
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
