SYMM_DROME
ID SYMM_DROME Reviewed; 582 AA.
AC Q9VFL5; A0A0B4KH54; Q8T0Q6;
DT 10-JAN-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Methionine--tRNA ligase, mitochondrial {ECO:0000303|PubMed:22448145, ECO:0000312|FlyBase:FBgn0027083};
DE EC=6.1.1.10;
DE AltName: Full=Mitochondrial methionyl-tRNA synthetase;
DE Short=MtMetRS;
DE Flags: Precursor;
GN Name=MetRS-m {ECO:0000303|PubMed:22448145,
GN ECO:0000312|FlyBase:FBgn0027083};
GN Synonyms=Aats-met {ECO:0000312|FlyBase:FBgn0027083},
GN Aats-met-m {ECO:0000312|FlyBase:FBgn0027083};
GN ORFNames=CG31322 {ECO:0000312|FlyBase:FBgn0027083},
GN CG8684 {ECO:0000312|FlyBase:FBgn0027083};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP MUTAGENESIS OF VAL-42 AND SER-224.
RX PubMed=22448145; DOI=10.1371/journal.pbio.1001288;
RA Bayat V., Thiffault I., Jaiswal M., Tetreault M., Donti T., Sasarman F.,
RA Bernard G., Demers-Lamarche J., Dicaire M.J., Mathieu J., Vanasse M.,
RA Bouchard J.P., Rioux M.F., Lourenco C.M., Li Z., Haueter C.,
RA Shoubridge E.A., Graham B.H., Brais B., Bellen H.J.;
RT "Mutations in the mitochondrial methionyl-tRNA synthetase cause a
RT neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in
RT humans.";
RL PLoS Biol. 10:E1001288-E1001288(2012).
RN [5]
RP MUTAGENESIS OF VAL-42.
RX PubMed=25594180; DOI=10.1016/j.cell.2014.12.019;
RA Liu L., Zhang K., Sandoval H., Yamamoto S., Jaiswal M., Sanz E., Li Z.,
RA Hui J., Graham B.H., Quintana A., Bellen H.J.;
RT "Glial lipid droplets and ROS induced by mitochondrial defects promote
RT neurodegeneration.";
RL Cell 160:177-190(2015).
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 -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}.
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; AE014297; AAF55037.2; -; Genomic_DNA.
DR EMBL; AE014297; AGB95945.1; -; Genomic_DNA.
DR EMBL; AE014297; ALI30570.1; -; Genomic_DNA.
DR EMBL; AY069128; AAL39273.1; -; mRNA.
DR RefSeq; NP_001262564.1; NM_001275635.2.
DR RefSeq; NP_001303507.1; NM_001316578.1.
DR RefSeq; NP_650348.1; NM_142091.5.
DR AlphaFoldDB; Q9VFL5; -.
DR SMR; Q9VFL5; -.
DR BioGRID; 66809; 5.
DR IntAct; Q9VFL5; 1.
DR STRING; 7227.FBpp0082356; -.
DR PaxDb; Q9VFL5; -.
DR PRIDE; Q9VFL5; -.
DR DNASU; 41733; -.
DR EnsemblMetazoa; FBtr0082895; FBpp0082356; FBgn0027083.
DR EnsemblMetazoa; FBtr0337021; FBpp0307950; FBgn0027083.
DR EnsemblMetazoa; FBtr0347148; FBpp0312479; FBgn0027083.
DR GeneID; 41733; -.
DR KEGG; dme:Dmel_CG31322; -.
DR CTD; 41733; -.
DR FlyBase; FBgn0027083; MetRS-m.
DR VEuPathDB; VectorBase:FBgn0027083; -.
DR eggNOG; KOG0436; Eukaryota.
DR GeneTree; ENSGT00550000075136; -.
DR HOGENOM; CLU_009710_9_0_1; -.
DR InParanoid; Q9VFL5; -.
DR OMA; SDMHGTP; -.
DR OrthoDB; 788159at2759; -.
DR PhylomeDB; Q9VFL5; -.
DR SignaLink; Q9VFL5; -.
DR BioGRID-ORCS; 41733; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 41733; -.
DR PRO; PR:Q9VFL5; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0027083; Expressed in egg chamber and 19 other tissues.
DR Genevisible; Q9VFL5; DM.
DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; TAS:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004825; F:methionine-tRNA ligase activity; ISS:UniProtKB.
DR GO; GO:0006431; P:methionyl-tRNA aminoacylation; ISS:UniProtKB.
DR CDD; cd00814; MetRS_core; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR041872; Anticodon_Met.
DR InterPro; IPR014758; Met-tRNA_synth.
DR InterPro; IPR023457; Met-tRNA_synth_2.
DR InterPro; IPR015413; Methionyl/Leucyl_tRNA_Synth.
DR InterPro; IPR033911; MetRS_core.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR009080; tRNAsynth_Ia_anticodon-bd.
DR PANTHER; PTHR43326; PTHR43326; 1.
DR Pfam; PF19303; Anticodon_3; 1.
DR Pfam; PF09334; tRNA-synt_1g; 1.
DR PRINTS; PR01041; TRNASYNTHMET.
DR SUPFAM; SSF47323; SSF47323; 1.
DR TIGRFAMs; TIGR00398; metG; 1.
PE 1: Evidence at protein level;
KW Aminoacyl-tRNA synthetase; ATP-binding; Ligase; Mitochondrion;
KW Nucleotide-binding; Protein biosynthesis; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..95
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 96..582
FT /note="Methionine--tRNA ligase, mitochondrial"
FT /id="PRO_0000045497"
FT REGION 555..582
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 27..37
FT /note="'HIGH' region"
FT MOTIF 317..321
FT /note="'KMSKS' region"
FT BINDING 320
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MUTAGEN 42
FT /note="V->D: Semi-viable with reduced cell proliferation
FT and lifespan including progressive degeneration of
FT photoreceptors and glia. Shows aberrant mitochondrial
FT respiration probably leading to an increased oxidative
FT stress. Shows high levels of reactive oxygen species (ROS)
FT and accumulation of lipid droplets in pigment and
FT epithelial glia. Lipid droplet accumulation occurs early,
FT prior to the onset of neurodegeneration."
FT /evidence="ECO:0000269|PubMed:22448145,
FT ECO:0000269|PubMed:25594180"
FT MUTAGEN 224
FT /note="S->L: Results in progressive degeneration of
FT photoreceptors and glia that show accumulation of large
FT lipid droplets. Results in reduced cell proliferation, up-
FT regulation of the mitochondrial unfolded protein response
FT and cell aberrant mitochondrial respiration leading to an
FT increased oxidative stress."
FT /evidence="ECO:0000269|PubMed:22448145"
SQ SEQUENCE 582 AA; 65998 MW; 581A3D42A746F9AC CRC64;
MLIRRIKCLR YLGTRYNSSH YVTTPIFYVN AAPHIGHLYS AVIADAHCRY QRLRYPEQDV
RLCTGTDEHG TKIQQAASLH GVPVAKYCDD ISQRYREVFR SASIQQDDFI RTTEDRHKRA
VANFWRTLHT RGHIYSAAYS GWYCVSDETF LTDSQLRLDE ATGTRYSLES GHPVEWTEET
NYMFRLSQFQ DDVRHWVKTE ARVRPAKFEK ILLDTLSEPL PDVSVSRPSN RVHWAIPVPD
DDSQTVYVWL DALVNYLSSV GYPDEKFSAH WPPAQQVIGK DILKFHGIYW TAFLLAAGLE
PPGQLYVHSH WTVDGQKMSK SKHNVVDPLQ AAQQYTMEGL RYFLLREGVA HSDGNYSHVK
AQRILNSELA DTLGNLLSRA SAKSLNPGQI YPSPSAEHLA DLLRSLDVAK RLQDSLLQLS
ERCESHYECN HFHLVADTTM AALHAANNFF ESSKPWTLKA GAPDGNQARL ETIIAMTMDA
LRLSGIVLQP IIPQLANRLL DKLSVPTAQR GWNYLAESFA TSPNSSNSPA GLGESRQLDG
QTSALLFQRI LEETSAKEVK EQKPQPAKRS KSKKKERRET MS
