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Protein

Methionine--tRNA ligase, mitochondrial

Gene

MARS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

ATP + L-methionine + tRNA(Met) = AMP + diphosphate + L-methionyl-tRNA(Met).1 Publication

Kineticsi

  1. KM=18 µM for Met1 Publication
  2. KM=85 µM for ATP1 Publication
  3. KM=2.1 µM for tRNA-Met1 Publication

    pH dependencei

    Optimum pH is 7.8-8.2.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei350 – 3501ATPBy similarity

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • methionine-tRNA ligase activity Source: UniProtKB

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Aminoacyl-tRNA synthetase, Ligase

    Keywords - Biological processi

    Protein biosynthesis

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    ReactomeiR-HSA-379726. Mitochondrial tRNA aminoacylation.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Methionine--tRNA ligase, mitochondrial (EC:6.1.1.10)
    Alternative name(s):
    Methionyl-tRNA synthetase 2
    Mitochondrial methionyl-tRNA synthetase
    Short name:
    MtMetRS
    Gene namesi
    Name:MARS2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:25133. MARS2.

    Subcellular locationi

    GO - Cellular componenti

    • mitochondrial matrix Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Spastic ataxia 3, autosomal recessive (SPAX3)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA neurologic disorder characterized by cerebellar ataxia, ataxic gait, spasticity, and hyperreflexia. Other variable features include dysarthria, dysmetria, mild cognitive impairment, urinary urgency and dystonic positioning.
    See also OMIM:611390
    Combined oxidative phosphorylation deficiency 25 (COXPD25)1 Publication
    The disease is caused by mutations affecting the gene represented in this entry.
    Disease descriptionA mitochondrial disorder resulting in developmental delay, growth failure, and sensorineural hearing loss.
    See also OMIM:616430
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti142 – 1421R → W in COXPD25. 1 Publication
    VAR_073858

    Keywords - Diseasei

    Deafness, Disease mutation, Neurodegeneration

    Organism-specific databases

    MalaCardsiMARS2.
    MIMi611390. phenotype.
    616430. phenotype.
    Orphaneti314603. Autosomal recessive spastic ataxia with leukoencephalopathy.
    PharmGKBiPA134863396.

    Chemistry

    DrugBankiDB00134. L-Methionine.

    Polymorphism and mutation databases

    BioMutaiMARS2.
    DMDMi85541638.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 2929MitochondrionSequence analysisAdd
    BLAST
    Chaini30 – 593564Methionine--tRNA ligase, mitochondrialPRO_0000045493Add
    BLAST

    Proteomic databases

    EPDiQ96GW9.
    MaxQBiQ96GW9.
    PaxDbiQ96GW9.
    PRIDEiQ96GW9.

    Expressioni

    Gene expression databases

    BgeeiQ96GW9.
    CleanExiHS_MARS2.
    GenevisibleiQ96GW9. HS.

    Organism-specific databases

    HPAiHPA035589.
    HPA035590.

    Interactioni

    Protein-protein interaction databases

    BioGridi124988. 12 interactions.
    STRINGi9606.ENSP00000282276.

    Structurei

    3D structure databases

    ProteinModelPortaliQ96GW9.
    SMRiQ96GW9. Positions 46-579.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi52 – 6211"HIGH" regionAdd
    BLAST
    Motifi347 – 3515"KMSKS" region

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiKOG0436. Eukaryota.
    COG0143. LUCA.
    GeneTreeiENSGT00550000075136.
    HOGENOMiHOG000200401.
    HOVERGENiHBG080702.
    InParanoidiQ96GW9.
    KOiK01874.
    OMAiTYPAFCT.
    OrthoDBiEOG76MK87.
    PhylomeDBiQ96GW9.
    TreeFamiTF105709.

    Family and domain databases

    Gene3Di1.10.730.10. 1 hit.
    3.40.50.620. 1 hit.
    InterProiIPR014758. Met-tRNA_synth.
    IPR015413. Methionyl/Leucyl_tRNA_Synth.
    IPR014729. Rossmann-like_a/b/a_fold.
    IPR009080. tRNAsynth_1a_anticodon-bd.
    [Graphical view]
    PfamiPF09334. tRNA-synt_1g. 1 hit.
    [Graphical view]
    PRINTSiPR01041. TRNASYNTHMET.
    SUPFAMiSSF47323. SSF47323. 1 hit.
    TIGRFAMsiTIGR00398. metG. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    Q96GW9-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLRTSVLRLL GRTGASRLSL LEDFGPRYYS SGSLSAGDDA CDVRAYFTTP
    60 70 80 90 100
    IFYVNAAPHI GHLYSALLAD ALCRHRRLRG PSTAATRFST GTDEHGLKIQ
    110 120 130 140 150
    QAAATAGLAP TELCDRVSEQ FQQLFQEAGI SCTDFIRTTE ARHRVAVQHF
    160 170 180 190 200
    WGVLKSRGLL YKGVYEGWYC ASDECFLPEA KVTQQPGPSG DSFPVSLESG
    210 220 230 240 250
    HPVSWTKEEN YIFRLSQFRK PLQRWLRGNP QAITPEPFHH VVLQWLDEEL
    260 270 280 290 300
    PDLSVSRRSS HLHWGIPVPG DDSQTIYVWL DALVNYLTVI GYPNAEFKSW
    310 320 330 340 350
    WPATSHIIGK DILKFHAIYW PAFLLGAGMS PPQRICVHSH WTVCGQKMSK
    360 370 380 390 400
    SLGNVVDPRT CLNRYTVDGF RYFLLRQGVP NWDCDYYDEK VVKLLNSELA
    410 420 430 440 450
    DALGGLLNRC TAKRINPSET YPAFCTTCFP SEPGLVGPSV RAQAEDYALV
    460 470 480 490 500
    SAVATLPKQV ADHYDNFRIY KALEAVSSCV RQTNGFVQRH APWKLNWESP
    510 520 530 540 550
    VDAPWLGTVL HVALECLRVF GTLLQPVTPS LADKLLSRLG VSASERSLGE
    560 570 580 590
    LYFLPRFYGH PCPFEGRRLG PETGLLFPRL DQSRTWLVKA HRT
    Length:593
    Mass (Da):66,591
    Last modified:January 10, 2006 - v2
    Checksum:iA5076FD9F31F4B96
    GO

    Sequence cautioni

    The sequence AAH09115.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
    The sequence AAH40934.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti535 – 5362LL → MM in BAC92749 (Ref. 1) Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti142 – 1421R → W in COXPD25. 1 Publication
    VAR_073858

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB107013 mRNA. Translation: BAC92749.1.
    AK098121 mRNA. Translation: BAC05238.1.
    AC073058 Genomic DNA. Translation: AAX93244.1.
    BC009115 mRNA. Translation: AAH09115.1. Different initiation.
    BC040934 mRNA. Translation: AAH40934.1. Different initiation.
    BC126294 mRNA. Translation: AAI26295.1.
    CCDSiCCDS33358.1.
    RefSeqiNP_612404.1. NM_138395.3.
    UniGeneiHs.744330.

    Genome annotation databases

    EnsembliENST00000282276; ENSP00000282276; ENSG00000247626.
    GeneIDi92935.
    KEGGihsa:92935.
    UCSCiuc002uuq.4. human.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AB107013 mRNA. Translation: BAC92749.1.
    AK098121 mRNA. Translation: BAC05238.1.
    AC073058 Genomic DNA. Translation: AAX93244.1.
    BC009115 mRNA. Translation: AAH09115.1. Different initiation.
    BC040934 mRNA. Translation: AAH40934.1. Different initiation.
    BC126294 mRNA. Translation: AAI26295.1.
    CCDSiCCDS33358.1.
    RefSeqiNP_612404.1. NM_138395.3.
    UniGeneiHs.744330.

    3D structure databases

    ProteinModelPortaliQ96GW9.
    SMRiQ96GW9. Positions 46-579.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi124988. 12 interactions.
    STRINGi9606.ENSP00000282276.

    Chemistry

    DrugBankiDB00134. L-Methionine.

    Polymorphism and mutation databases

    BioMutaiMARS2.
    DMDMi85541638.

    Proteomic databases

    EPDiQ96GW9.
    MaxQBiQ96GW9.
    PaxDbiQ96GW9.
    PRIDEiQ96GW9.

    Protocols and materials databases

    DNASUi92935.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000282276; ENSP00000282276; ENSG00000247626.
    GeneIDi92935.
    KEGGihsa:92935.
    UCSCiuc002uuq.4. human.

    Organism-specific databases

    CTDi92935.
    GeneCardsiMARS2.
    HGNCiHGNC:25133. MARS2.
    HPAiHPA035589.
    HPA035590.
    MalaCardsiMARS2.
    MIMi609728. gene.
    611390. phenotype.
    616430. phenotype.
    neXtProtiNX_Q96GW9.
    Orphaneti314603. Autosomal recessive spastic ataxia with leukoencephalopathy.
    PharmGKBiPA134863396.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0436. Eukaryota.
    COG0143. LUCA.
    GeneTreeiENSGT00550000075136.
    HOGENOMiHOG000200401.
    HOVERGENiHBG080702.
    InParanoidiQ96GW9.
    KOiK01874.
    OMAiTYPAFCT.
    OrthoDBiEOG76MK87.
    PhylomeDBiQ96GW9.
    TreeFamiTF105709.

    Enzyme and pathway databases

    ReactomeiR-HSA-379726. Mitochondrial tRNA aminoacylation.

    Miscellaneous databases

    GenomeRNAii92935.
    NextBioi77920.
    PROiQ96GW9.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ96GW9.
    CleanExiHS_MARS2.
    GenevisibleiQ96GW9. HS.

    Family and domain databases

    Gene3Di1.10.730.10. 1 hit.
    3.40.50.620. 1 hit.
    InterProiIPR014758. Met-tRNA_synth.
    IPR015413. Methionyl/Leucyl_tRNA_Synth.
    IPR014729. Rossmann-like_a/b/a_fold.
    IPR009080. tRNAsynth_1a_anticodon-bd.
    [Graphical view]
    PfamiPF09334. tRNA-synt_1g. 1 hit.
    [Graphical view]
    PRINTSiPR01041. TRNASYNTHMET.
    SUPFAMiSSF47323. SSF47323. 1 hit.
    TIGRFAMsiTIGR00398. metG. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Downregulation of mitochondrial translation factors during the differentiation of HL-60 cells by TPA."
      Murata H., Takeuchi-Tomita N.
      Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Trachea.
    3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain and Colon.
    5. "Characterization of the human mitochondrial methionyl-tRNA synthetase."
      Spencer A.C., Heck A., Takeuchi N., Watanabe K., Spremulli L.L.
      Biochemistry 43:9743-9754(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
    6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    7. "Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans."
      Bayat V., Thiffault I., Jaiswal M., Tetreault M., Donti T., Sasarman F., Bernard G., Demers-Lamarche J., Dicaire M.J., Mathieu J., Vanasse M., Bouchard J.P., Rioux M.F., Lourenco C.M., Li Z., Haueter C., Shoubridge E.A., Graham B.H., Brais B., Bellen H.J.
      PLoS Biol. 10:E1001288-E1001288(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN SPAX3.
    8. "Novel, compound heterozygous, single-nucleotide variants in MARS2 associated with developmental delay, poor growth, and sensorineural hearing loss."
      Webb B.D., Wheeler P.G., Hagen J.J., Cohen N., Linderman M.D., Diaz G.A., Naidich T.P., Rodenburg R.J., Houten S.M., Schadt E.E.
      Hum. Mutat. 36:587-592(2015) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN COXPD25, VARIANT COXPD25 TRP-142.
    9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiSYMM_HUMAN
    AccessioniPrimary (citable) accession number: Q96GW9
    Secondary accession number(s): A0AVC3
    , Q76E79, Q8IW62, Q8N7N4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 10, 2006
    Last sequence update: January 10, 2006
    Last modified: March 16, 2016
    This is version 119 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Aminoacyl-tRNA synthetases
      List of aminoacyl-tRNA synthetase entries
    2. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.