SYG_YEAST
ID SYG_YEAST Reviewed; 690 AA.
AC P38088; D6VQB9;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Glycine--tRNA ligase 1, mitochondrial;
DE EC=6.1.1.14 {ECO:0000269|PubMed:23816885};
DE AltName: Full=Diadenosine tetraphosphate synthetase;
DE Short=Ap4A synthetase;
DE EC=2.7.7.- {ECO:0000250|UniProtKB:P41250};
DE AltName: Full=Glycyl-tRNA synthetase 1;
DE Short=GlyRS 1;
DE Short=GlyRS1;
DE Flags: Precursor;
GN Name=GRS1; OrderedLocusNames=YBR121C; ORFNames=YBR0917;
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].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7900426; DOI=10.1002/yea.320101014;
RA Mannhaupt G., Stucka R., Ehnle S., Vetter I., Feldmann H.;
RT "Analysis of a 70 kb region on the right arm of yeast chromosome II.";
RL Yeast 10:1363-1381(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [3]
RP GENOME REANNOTATION, AND SEQUENCE REVISION TO 586-587.
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 [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10874035; DOI=10.1074/jbc.m003416200;
RA Turner R.J., Lovato M., Schimmel P.;
RT "One of two genes encoding glycyl-tRNA synthetase in Saccharomyces
RT cerevisiae provides mitochondrial and cytoplasmic functions.";
RL J. Biol. Chem. 275:27681-27688(2000).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=14690591; DOI=10.1016/s1097-2765(03)00476-3;
RA Hazbun T.R., Malmstroem L., Anderson S., Graczyk B.J., Fox B., Riffle M.,
RA Sundin B.A., Aranda J.D., McDonald W.H., Chiu C.-H., Snydsman B.E.,
RA Bradley P., Muller E.G.D., Fields S., Baker D., Yates J.R. III, Davis T.N.;
RT "Assigning function to yeast proteins by integration of technologies.";
RL Mol. Cell 12:1353-1365(2003).
RN [6]
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 [7]
RP ALTERNATIVE INITIATION.
RX PubMed=14734560; DOI=10.1074/jbc.m311269200;
RA Chang K.J., Wang C.C.;
RT "Translation initiation from a naturally occurring non-AUG codon in
RT Saccharomyces cerevisiae.";
RL J. Biol. Chem. 279:13778-13785(2004).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=YAL6B;
RX PubMed=15665377; DOI=10.1074/mcp.m400219-mcp200;
RA Gruhler A., Olsen J.V., Mohammed S., Mortensen P., Faergeman N.J., Mann M.,
RA Jensen O.N.;
RT "Quantitative phosphoproteomics applied to the yeast pheromone signaling
RT pathway.";
RL Mol. Cell. Proteomics 4:310-327(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226; SER-476 AND SER-528, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-226; SER-476 AND THR-689, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-25, CLEAVAGE OF TRANSIT PEPTIDE
RP [LARGE SCALE ANALYSIS] AFTER MET-24, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=23816885; DOI=10.1128/mcb.00122-13;
RA Wu Y.H., Chang C.P., Chien C.I., Tseng Y.K., Wang C.C.;
RT "An insertion peptide in yeast glycyl-tRNA synthetase facilitates both
RT productive docking and catalysis of cognate tRNAs.";
RL Mol. Cell. Biol. 33:3515-3523(2013).
CC -!- FUNCTION: Catalyzes the ATP-dependent ligation of glycine to the 3'-end
CC of its cognate tRNA, via the formation of an aminoacyl-adenylate
CC intermediate (Gly-AMP) (PubMed:23816885). Also produces diadenosine
CC tetraphosphate (Ap4A), a universal pleiotropic signaling molecule
CC needed for cell regulation pathways, by direct condensation of 2 ATPs.
CC Thereby, may play a special role in Ap4A homeostasis (By similarity).
CC {ECO:0000250|UniProtKB:P41250, ECO:0000269|PubMed:23816885}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + glycine + tRNA(Gly) = AMP + diphosphate + glycyl-
CC tRNA(Gly); Xref=Rhea:RHEA:16013, Rhea:RHEA-COMP:9664, Rhea:RHEA-
CC COMP:9683, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57305,
CC ChEBI:CHEBI:78442, ChEBI:CHEBI:78522, ChEBI:CHEBI:456215;
CC EC=6.1.1.14; Evidence={ECO:0000269|PubMed:23816885};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16014;
CC Evidence={ECO:0000305|PubMed:23816885};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 ATP + H(+) = diphosphate + P(1),P(4)-bis(5'-adenosyl)
CC tetraphosphate; Xref=Rhea:RHEA:34935, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58141;
CC Evidence={ECO:0000250|UniProtKB:P41250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=135 uM for glycine (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:23816885};
CC KM=0.33 uM for tRNA(Gly) (at 25 degrees Celsius)
CC {ECO:0000269|PubMed:23816885};
CC Note=kcat is 0.38 sec(-1) for the aminoacylation reaction (at 25
CC degrees Celsius). {ECO:0000269|PubMed:23816885};
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P41250}.
CC -!- SUBCELLULAR LOCATION: [Isoform Cytoplasmic]: Cytoplasm.
CC -!- SUBCELLULAR LOCATION: [Isoform Mitochondrial]: Mitochondrion matrix.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Mitochondrial;
CC IsoId=P38088-1; Sequence=Displayed;
CC Name=Cytoplasmic;
CC IsoId=P38088-2; Sequence=VSP_041147;
CC -!- MISCELLANEOUS: Present with 98400 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- MISCELLANEOUS: [Isoform Mitochondrial]: Produced by alternative
CC initiation at an upstream UUG codon in-frame of the first AUG used for
CC isoform Cytoplasmic.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC {ECO:0000305}.
CC -!- CAUTION: GRS1, which appears to be a duplication of GRS2, is necessary
CC and sufficient for both mitochondrial and cytoplasmic glycyl-tRNA
CC synthetase activities, suggesting that GRS2 may not be essential.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA55623.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=CAA85078.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=DAA07239.2; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X78993; CAA55623.1; ALT_INIT; Genomic_DNA.
DR EMBL; Z35990; CAA85078.1; ALT_INIT; Genomic_DNA.
DR EMBL; BK006936; DAA07239.2; ALT_INIT; Genomic_DNA.
DR PIR; S48285; S48285.
DR RefSeq; NP_009679.2; NM_001178469.2. [P38088-2]
DR AlphaFoldDB; P38088; -.
DR SMR; P38088; -.
DR BioGRID; 32823; 181.
DR DIP; DIP-6526N; -.
DR IntAct; P38088; 17.
DR MINT; P38088; -.
DR STRING; 4932.YBR121C; -.
DR iPTMnet; P38088; -.
DR MaxQB; P38088; -.
DR PaxDb; P38088; -.
DR PRIDE; P38088; -.
DR EnsemblFungi; YBR121C_mRNA; YBR121C; YBR121C. [P38088-2]
DR GeneID; 852418; -.
DR KEGG; sce:YBR121C; -.
DR SGD; S000000325; GRS1.
DR eggNOG; KOG2298; Eukaryota.
DR GeneTree; ENSGT00940000153759; -.
DR HOGENOM; CLU_015515_1_0_1; -.
DR InParanoid; P38088; -.
DR OMA; EPSYGID; -.
DR BioCyc; YEAST:G3O-29078-MON; -.
DR BRENDA; 6.1.1.14; 984.
DR PRO; PR:P38088; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38088; protein.
DR GO; GO:0005737; C:cytoplasm; IMP:SGD.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IMP:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004820; F:glycine-tRNA ligase activity; IDA:SGD.
DR GO; GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0015966; P:diadenosine tetraphosphate biosynthetic process; ISS:UniProtKB.
DR GO; GO:0006353; P:DNA-templated transcription, termination; IMP:SGD.
DR GO; GO:0006426; P:glycyl-tRNA aminoacylation; IMP:SGD.
DR GO; GO:0070150; P:mitochondrial glycyl-tRNA aminoacylation; IMP:SGD.
DR CDD; cd00774; GlyRS-like_core; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR Gene3D; 3.40.50.800; -; 1.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004154; Anticodon-bd.
DR InterPro; IPR036621; Anticodon-bd_dom_sf.
DR InterPro; IPR027031; Gly-tRNA_synthase/POLG2.
DR InterPro; IPR033731; GlyRS-like_core.
DR InterPro; IPR002315; tRNA-synt_gly.
DR PANTHER; PTHR10745; PTHR10745; 1.
DR Pfam; PF03129; HGTP_anticodon; 1.
DR PRINTS; PR01043; TRNASYNTHGLY.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00389; glyS_dimeric; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative initiation; Aminoacyl-tRNA synthetase;
KW ATP-binding; Cytoplasm; Ligase; Mitochondrion; Nucleotide-binding;
KW Phosphoprotein; Protein biosynthesis; Reference proteome; Transferase;
KW Transit peptide.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000255, ECO:0007744|PubMed:22814378"
FT CHAIN 25..690
FT /note="Glycine--tRNA ligase 1, mitochondrial"
FT /id="PRO_0000073005"
FT BINDING 251
FT /ligand="glycine"
FT /ligand_id="ChEBI:CHEBI:57305"
FT /evidence="ECO:0000250|UniProtKB:P41250"
FT BINDING 283..285
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P41250"
FT BINDING 294..295
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P41250"
FT BINDING 302
FT /ligand="glycine"
FT /ligand_id="ChEBI:CHEBI:57305"
FT /evidence="ECO:0000250|UniProtKB:P41250"
FT BINDING 410..411
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P41250"
FT BINDING 531..533
FT /ligand="glycine"
FT /ligand_id="ChEBI:CHEBI:57305"
FT /evidence="ECO:0000250|UniProtKB:P41250"
FT BINDING 538
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P41250"
FT MOD_RES 25
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 226
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:15665377,
FT ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 476
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956,
FT ECO:0007744|PubMed:19779198"
FT MOD_RES 528
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 689
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform Cytoplasmic)"
FT /id="VSP_041147"
FT CONFLICT 586..587
FT /note="TT -> HH (in Ref. 1; CAA55623 and 2; CAA85078)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 690 AA; 78184 MW; 4EBDE6F0A942F7F6 CRC64;
MSFFNISRRF YSQIVKKSVK IKRMSVEDIK KARAAVPFNR EQLESVLRGR FFYAPAFDLY
GGVSGLYDYG PPGCAFQNNI IDAWRKHFIL EEDMLEVDCT MLTPYEVLKT SGHVDKFSDW
MCRDLKTGEI FRADHLVEEV LEARLKGDQE ARGLVEDANA AAKDDAEKKK RKKKVKQIKA
VKLDDDVVKE YEEILAKIDG YSGPELGELM EKYDIGNPVT GETLESPRAF NLMFETAIGP
SGQLKGYLRP ETAQGQFLNF NKLLEFNNSK TPFASASIGK SFRNEISPRA GLLRVREFLM
AEIEHFVDPL DKSHPKFNEI KDIKLSFLPR DVQEAGSTEP IVKTVGEAVA SRMVDNETLG
YFIARIYQFL MKIGVDESKL RFRQHMANEM AHYAADCWDG ELKTSYGWIE CVGCADRSAY
DLTVHSKKTK EKLVVRQKLD NPIEVTKWEI DLTKKLFGPK FRKDAPKVES HLLNMSQDDL
ASKAELLKAN GKFTIKVDGV DGEVELDDKL VKIEQRTKVE HVREYVPSVI EPSFGIGRII
YSVFEHSFWN RPEDNARSVL SFPPLVAPTK VLLVPLSNHK DLVPVTTEVA KILRKSQIPF
KIDDSGVSIG KRYARNDELG TPFGVTIDFE SAKDHSVTLR ERDSTKQVRG SVENVIKAIR
DITYNGASWE EGTKDLTPFI AQAEAEAETD
