LOCUS       NM_001083614            5196 bp    mRNA    linear   PRI 12-OCT-2024
DEFINITION  Homo sapiens glutamyl-tRNA synthetase 2, mitochondrial (EARS2),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_001083614
VERSION     NM_001083614.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 5196)
  AUTHORS   Pelayo,G., Paiva Coelho,M., Correia,J., Bandeira,A., Nogueira,C.,
            Vilarinho,L. and Martins,E.
  TITLE     Phenotyping mitochondrial glutamyl-tRNA synthetase deficiency
            (EARS2): A case series and systematic literature review
  JOURNAL   Neurobiol Dis 200, 106644 (2024)
   PUBMED   39173847
  REMARK    GeneRIF: Phenotyping mitochondrial glutamyl-tRNA synthetase
            deficiency (EARS2): A case series and systematic literature review.
REFERENCE   2  (bases 1 to 5196)
  AUTHORS   Lehrer,S. and Rheinstein,P.H.
  TITLE     EARS2 significantly coexpresses with PALB2 in breast and pancreatic
            cancer
  JOURNAL   Cancer Treat Res Commun 32, 100595 (2022)
   PUBMED   35779338
  REMARK    GeneRIF: EARS2 significantly coexpresses with PALB2 in breast and
            pancreatic cancer.
REFERENCE   3  (bases 1 to 5196)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   4  (bases 1 to 5196)
  AUTHORS   Talim,B., Pyle,A., Griffin,H., Topaloglu,H., Tokatli,A.,
            Keogh,M.J., Santibanez-Koref,M., Chinnery,P.F. and Horvath,R.
  TITLE     Multisystem fatal infantile disease caused by a novel homozygous
            EARS2 mutation
  JOURNAL   Brain 136 (Pt 2), e228 (2013)
   PUBMED   23008233
REFERENCE   5  (bases 1 to 5196)
  AUTHORS   Steenweg,M.E., Ghezzi,D., Haack,T., Abbink,T.E., Martinelli,D., van
            Berkel,C.G., Bley,A., Diogo,L., Grillo,E., Te Water Naude,J.,
            Strom,T.M., Bertini,E., Prokisch,H., van der Knaap,M.S. and
            Zeviani,M.
  TITLE     Leukoencephalopathy with thalamus and brainstem involvement and
            high lactate 'LTBL' caused by EARS2 mutations
  JOURNAL   Brain 135 (Pt 5), 1387-1394 (2012)
   PUBMED   22492562
  REMARK    GeneRIF: This study presented that a new neurological disease,
            early-onset leukoencephalopathy with thalamus and brainstem
            involvement and high lactate, defined by a peculiar biphasic
            clinical course and caused by mutations in a single gene, EARS2.
REFERENCE   6  (bases 1 to 5196)
  AUTHORS   Calvo,S.E., Compton,A.G., Hershman,S.G., Lim,S.C., Lieber,D.S.,
            Tucker,E.J., Laskowski,A., Garone,C., Liu,S., Jaffe,D.B.,
            Christodoulou,J., Fletcher,J.M., Bruno,D.L., Goldblatt,J.,
            Dimauro,S., Thorburn,D.R. and Mootha,V.K.
  TITLE     Molecular diagnosis of infantile mitochondrial disease with
            targeted next-generation sequencing
  JOURNAL   Sci Transl Med 4 (118), 118ra10 (2012)
   PUBMED   22277967
  REMARK    GeneRIF: Strong candidate gene for mitochondrial disease, based on
            recessive mutations detected in infantile patients
REFERENCE   7  (bases 1 to 5196)
  AUTHORS   Nagao,A., Suzuki,T., Katoh,T., Sakaguchi,Y. and Suzuki,T.
  TITLE     Biogenesis of glutaminyl-mt tRNAGln in human mitochondria
  JOURNAL   Proc Natl Acad Sci U S A 106 (38), 16209-16214 (2009)
   PUBMED   19805282
  REMARK    GeneRIF: Studies showed in vitro Gln-tRNA(Gln) formation catalyzed
            by the recombinant mtGluRS and hGatCAB.
REFERENCE   8  (bases 1 to 5196)
  AUTHORS   Bonnefond,L., Fender,A., Rudinger-Thirion,J., Giege,R., Florentz,C.
            and Sissler,M.
  TITLE     Toward the full set of human mitochondrial aminoacyl-tRNA
            synthetases: characterization of AspRS and TyrRS
  JOURNAL   Biochemistry 44 (12), 4805-4816 (2005)
   PUBMED   15779907
REFERENCE   9  (bases 1 to 5196)
  AUTHORS   Loftus,B.J., Kim,U.J., Sneddon,V.P., Kalush,F., Brandon,R.,
            Fuhrmann,J., Mason,T., Crosby,M.L., Barnstead,M., Cronin,L.,
            Deslattes Mays,A., Cao,Y., Xu,R.X., Kang,H.L., Mitchell,S.,
            Eichler,E.E., Harris,P.C., Venter,J.C. and Adams,M.D.
  TITLE     Genome duplications and other features in 12 Mb of DNA sequence
            from human chromosome 16p and 16q
  JOURNAL   Genomics 60 (3), 295-308 (1999)
   PUBMED   10493829
REFERENCE   10 (bases 1 to 5196)
  AUTHORS   Vanderver,A., Tonduti,D., Schiffmann,R., Schmidt,J. and van der
            Knaap,M.S.
  TITLE     Leukodystrophy Overview - RETIRED CHAPTER, FOR HISTORICAL REFERENCE
            ONLY
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   24501781
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AC002400.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jul 1, 2019 this sequence version replaced NM_001083614.1.
            
            Summary: This gene encodes a member of the class I family of
            aminoacyl-tRNA synthetases. These enzymes play a critical role in
            protein biosynthesis by charging tRNAs with their cognate amino
            acids. This protein is encoded by the nuclear genome but is likely
            to be imported to the mitochondrion where it is thought to catalyze
            the ligation of glutamate to tRNA molecules. Mutations in this gene
            have been associated with combined oxidative phosphorylation
            deficiency 12 (COXPD12). Alternative splicing results in multiple
            transcript variants. [provided by RefSeq, Mar 2015].
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (1).
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on alignments.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR18074969.2631253.1,
                                           SRR14038196.1053056.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000449606.7/
                                                  ENSP00000395196.2
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-146               AC002400.1         47939-48084
            147-302             AC002400.1         52985-53140
            303-492             AC002400.1         60586-60775
            493-965             AC002400.1         69929-70401
            966-1074            AC002400.1         72524-72632
            1075-1228           AC002400.1         75392-75545
            1229-1359           AC002400.1         75657-75787
            1360-1495           AC002400.1         79910-80045
            1496-5196           AC002400.1         80835-84535
FEATURES             Location/Qualifiers
     source          1..5196
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16p12.2"
     gene            1..5196
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /note="glutamyl-tRNA synthetase 2, mitochondrial"
                     /db_xref="GeneID:124454"
                     /db_xref="HGNC:HGNC:29419"
                     /db_xref="MIM:612799"
     exon            1..146
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     CDS             8..1579
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /EC_number="6.1.1.17"
                     /EC_number="6.1.1.24"
                     /note="isoform 1 is encoded by transcript variant 1;
                     probable glutamyl-tRNA synthetase, mitochondrial;
                     glutamate--tRNA ligase; glutamate tRNA ligase 2,
                     mitochondrial; probable glutamate--tRNA ligase,
                     mitochondrial; mitochondrial glutamyl-tRNA synthetase;
                     glutamate--tRNA(Gln) ligase EARS2, mitochondrial;
                     nondiscriminating glutamyl-tRNA synthetase EARS2,
                     mitochondrial"
                     /codon_start=1
                     /product="nondiscriminating glutamyl-tRNA synthetase
                     EARS2, mitochondrial isoform 1"
                     /protein_id="NP_001077083.1"
                     /db_xref="CCDS:CCDS42132.1"
                     /db_xref="GeneID:124454"
                     /db_xref="HGNC:HGNC:29419"
                     /db_xref="MIM:612799"
                     /translation="MAALLRRLLQRERPSAASGRPVGRREANLGTDAGVAVRVRFAPS
                     PTGFLHLGGLRTALYNYIFAKKYQGSFILRLEDTDQTRVVPGAAENIEDMLEWAGIPP
                     DESPRRGGPAGPYQQSQRLELYAQATEALLKTGAAYPCFCSPQRLELLKKEALRNHQT
                     PRYDNRCRNMSQEQVAQKLAKDPKPAIRFRLEQVVPAFQDLVYGWNRHEVASVEGDPV
                     IMKSDGFPTYHLACVVDDHHMGISHVLRGSEWLVSTAKHLLLYQALGWQPPHFAHLPL
                     LLNRDGSKLSKRQGDVFLEHFAADGFLPDSLLDIITNCGSGFAENQMGRTLPELITQF
                     NLTQVTCHSALLDLEKLPEFNRLHLQRLVSNESQRRQLVGKLQVLVEEAFGCQLQNRD
                     VLNPVYVERILLLRQGHICRLQDLVSPVYSYLWTRPAVGRAQLDAISEKVDVIAKRVL
                     GLLERSSMSLTQDMLNGELKKLSEGLEGTKYSNVMKLLRMALSGQQQGPPVAEMMLAL
                     GPKEVRERIQKVVSS"
     exon            147..302
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     exon            303..492
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     exon            493..965
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     exon            966..1074
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1075..1228
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1229..1359
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1360..1495
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1496..5196
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3912..3917
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /note="hexamer: AGTAAA"
     polyA_site      3934
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /note="major polyA site"
     regulatory      5172..5177
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
                     /note="hexamer: AATAAA"
     polyA_site      5196
                     /gene="EARS2"
                     /gene_synonym="COXPD12; gluRS; MSE1; mtGlnRS; mtGluRS"
ORIGIN      
        1 atcccacatg gcggcgctcc tgaggagact gctgcagcgc gagaggcctt cggcggcctc
       61 tggccgcccc gtaggacggc gcgaggccaa cctgggcact gatgccgggg ttgcggtgcg
      121 agtgcggttc gctcccagcc ccacaggctt cttgcacctg ggtggcctcc gcactgcctt
      181 gtacaactac atctttgcta agaagtacca ggggagcttc atcctgaggc tagaggacac
      241 agatcagact cgcgttgtgc ctggggcagc ggagaatatt gaggacatgc tggagtgggc
      301 aggcatcccg cctgatgaga gcccccgccg gggcggtcct gctgggccct accagcaatc
      361 tcagcggttg gagctgtatg cccaggccac agaagcgctg ctgaagaccg gagctgctta
      421 cccctgtttc tgctcacccc agcggctgga gctcctgaag aaggaggcct tgcggaacca
      481 ccagacgccc cggtatgaca atcggtgcag gaacatgagc caggagcagg tggcccagaa
      541 gctggccaag gaccccaagc ctgcgatccg cttccgcctg gagcaggtgg tgccagcctt
      601 ccaggacctg gtctatggct ggaataggca tgaagtggcc agcgtggagg gagacccagt
      661 catcatgaag agcgacggct tccccacata ccacctggcc tgcgtggtgg acgaccacca
      721 catgggcatc agccacgtgc tgcgaggctc tgagtggctc gtctccactg ccaagcacct
      781 gctcctctac caggccctgg gctggcagcc accccacttc gcccacctgc ccctgctcct
      841 caacagggat ggcagcaagc tctccaagag gcaaggggac gttttcctgg agcactttgc
      901 tgctgatggc ttcctgcccg attccttgtt ggacatcatc accaactgtg gctcaggttt
      961 tgcagagaac caaatgggca ggaccctgcc ggagctgatc acacagttca acctgacaca
     1021 ggtcacctgt cactcagccc tgctggacct ggagaagctc ccagaattca acagactgca
     1081 cctccagcgg ctggtgagca atgagagcca gaggcgccag ctggtgggga agctgcaggt
     1141 ccttgtggag gaggcctttg gttgccagct gcaaaacagg gatgtcctca acccagtcta
     1201 cgtggagagg atcctcctgc tgagacaggg tcacatttgc cgcctgcagg acttggtgtc
     1261 cccagtatac tcttacctgt ggactcgccc tgcagtaggt cgagcacagc tggacgccat
     1321 ctcggagaag gtggatgtga ttgccaagcg tgtgctgggg cttctagaaa gatctagtat
     1381 gagcttaact caggatatgc tgaatggaga actgaagaag ctatcagaag gtctggaagg
     1441 caccaagtac agtaatgtga tgaaactcct tcggatggcc ctcagtggac agcagcaagg
     1501 acctcctgta gctgagatga tgttggcctt gggaccaaag gaagtacggg aacggatcca
     1561 gaaggtggtt tccagctagg gagaggatgt ttcgggcagt ggagatcgcc ctaagaacct
     1621 gtgagcttag aaacagcttt cagagaccag aaggaggcct ggggcccgtc gggaagtttg
     1681 ctgaaggaac taagagtgga aacaatctct gactgcacac aagtgcattt gtgatccacc
     1741 acaggcacgt ttttgtcaat tggctgggga agcccaaccc atctaacctc ctggactctg
     1801 gaaaggcatt ctccgggtct ggtttctcac acattacaca gcagaggttt ggagttagtt
     1861 cacagaaaag ttaacatccc ggaacagtgc agaaggcttg ggtttcagtt tgctagggcc
     1921 cccataacaa aatgccacag aaccaggtgg tttaaacaac agagatttat tttctcacat
     1981 ttggaggcta gaagttcaag atcaaggtgt cagcaggcct ggtttttcct agaggcctct
     2041 tttgttggct tgcagacagc tgtcttctca ctgtgtcctt gtgcggtctt ccctccatgc
     2101 acacacatct ctaagtttca ttatgtgccc aacgttcctc ttctaagaac accagttgga
     2161 ctggatttta actttaacca gcctcattta agttaatcac ctctttaaat gctcaatctc
     2221 caagtacagt ctcattctga ggttccaggg gtttctcaac gtaagaattt agggggacag
     2281 aattcagccc gtagcagctg ggcagcagga ctcatgggtc ccagttctca ggccccaagg
     2341 actcagagca gcaaaggata cgtgacacaa gcagggctga actggacacc agactttctt
     2401 tggggttgta aaaggagaag tgtgactcca ctgccaaggg taagcactct tgtcttatgc
     2461 taccctttat tcttgaacct tggggcagcc tgtgtctccc ttccctaaac gtcatctgtt
     2521 ccgtttttcc agtcttccag acctggtcct tggactggag accttcaccc ttcctatttt
     2581 gtggctttct cttcaaatcc acctcgtcct tcctccatga cttataagtc atcatctctg
     2641 ctggtttctg aaatgagata tgcttcttgg ggtcttcagt gaagaggaat agcaagtgaa
     2701 aggaggatgg tggcagggta catgaacccc taccaggctt ctaggcttcc cctgcatggc
     2761 agccagcctc taagttggcc cccaaccatc cctgccttct tctattcaca cccttgtgtg
     2821 gttccttccc acattgaata ggcctgactt gtgtaaccac tacactattg aagaaatgag
     2881 agtttgactt ctgagggtaa gtcataaaat acatcgtggc ttctgtcttg ttttctttga
     2941 tcgcttactt tgggggaagc cagcttccag gtcatgaaaa tactcaagca gccttatgga
     3001 gtgctccaca tgacaaggga tcgaggcctc ccaccaatag ccatgggagt gtgcaatctt
     3061 gaaagctggt ccttcaattc cagccaagca ttcacatgac cgcaatccta gctgatctcg
     3121 cttgtgacct ctatgggaga ccctaagcca gaaccactca gagaagctgc tccggaacgt
     3181 cagacacaca tgaactgtga gatagtaaac gtttattgtt taaagctact tggtttgggg
     3241 ataatttgcg tttcagcagt agacaatata tttattttgt ccaggggagt ggaaaggcga
     3301 ttacagagtt tgttgagccc catagagtcc tagtctttgc ttaaagaaat ataccagttc
     3361 tttctaatac agaatccatt aagttcgttg gttgcaaaca atagaaacca actctgcctc
     3421 acttatgttt attggaggcc ataagagagc cacagcatct accaaaaagc caaaaaaaaa
     3481 acaggttttg gaaaagacag gaactagcta caggagctaa tggccaatct tgtctgagtt
     3541 ctttgatggc gacacatgaa ctacagccgt tttgttgttg ttaatttctc cgtgttttcc
     3601 cctcagtttt ggatgactct gctcaaggtt cagattctga ggagcaagta tctgttgggc
     3661 tatctgaggt cctgctacca ttccttggcc agtaataggt agtttcacag ggattatatg
     3721 caatggagga aaagttgttc tcaaggaaaa ctagggagct ttctccagaa gatgatgtaa
     3781 tggcagaaac aacaggtggt tgaccacaga aggggacaat aataatactt gtaatttatt
     3841 gtgcgcttat atgagcctca ccctctccca ggtgtcagat aatgctcgta aatgccttag
     3901 tccatcatct cagtaaattt tttttataac actatgagag aagcagtatt ttttttttct
     3961 gttacagata tggaaaccga ggttctgaaa agttaactaa aacttccgag gttatagtac
     4021 gaggcaaaac caagatttaa actcagatct gtgccgatcc agagtccaag cttaactctg
     4081 atctactgag tgttgtcaga gcatctgttt ctaagacatt aagaatggtt aaaaggagct
     4141 tcttggctca tggtcaagtg agtgttttta acaaagtgag tggtcaaaat actaagtcga
     4201 ttctggtata tctacaacat ggatgaacct ctaggacttc atgctaaatg aaatgtcagt
     4261 cacaaaagga caaatacgtc ctaatgcttt gtgaggcaaa ggtggtaggc ttgtcaaagg
     4321 ccaggagttt ggagaccagc ctgggcaaca tagtgagatc ctgtctctac aaaaaattta
     4381 aaaattagcc aggtgaggtg acatatgcct gtagtcccag ctacttggga gactaaggta
     4441 ggaggatcac ttgagctgag gcgttaaggc tgcagtgagc tatgaatgca ctactgcact
     4501 ctaacctggg caacagagca agatcctgtg tctaaaaaaa aaaaaatgaa taaaataaag
     4561 ttaaaaggat agatactgta agattctact tatttgaatt acttaaaata atcaaaatta
     4621 tacaggcaga aaataagatg gtggttgtca gacttgggga ggcagaaatg ggaagttact
     4681 gtttagggta tagagtttca gttttgcaag atgtagttac aggggtcaat ggtggtgata
     4741 attgcacaac attataaaga tacgtaatgc cgctgaactg tatatttaaa aatgactgag
     4801 atggtaaatt ttatattttt ctgtatttta ccacagtttt taaaaaatac taaattagag
     4861 ctgggcctgg tggctcacac ctagaatccc aacattttgg gaggccaagg caggcagatc
     4921 acttgaggcc gggagttcaa gaccagcctg gccaacatgg tgaaacccca tctctactaa
     4981 aagtacaaaa attagccagg tgtggtggta catacctata atcccagcta cttgggtggc
     5041 tgaggcacag gaattacttg aacccccaca gaacgggagg ttgcagtgag ccaagatcac
     5101 accattgtac tccagcctgg ggaacagagc gacactctgt ctcaacaaga aattaataaa
     5161 aaagcgaaat taataaagct gttgctactt cctcaa
//
