LOCUS       NM_018122               3336 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens aspartyl-tRNA synthetase 2, mitochondrial (DARS2),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_018122
VERSION     NM_018122.5
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 3336)
  AUTHORS   Bostanova,F.M., Tsygankova,P.G., Larshina,E.A., Nagornov,I.O.,
            Evseeva,Y.V., Krutikhina,I.L., Dzhentemirova,M.E., Kashlakova,M.N.,
            Petukhova,M.S., Sharkova,I.V. and Zakharova,E.Y.
  TITLE     Identification of a Novel Indel Variant in the DARS2 Gene in
            Russian Patients with Leukoencephalopathy with Brainstem and Spinal
            Cord Involvement and Lactate Elevation
  JOURNAL   Genes (Basel) 15 (5), 615 (2024)
   PUBMED   38790244
  REMARK    GeneRIF: Identification of a Novel Indel Variant in the DARS2 Gene
            in Russian Patients with Leukoencephalopathy with Brainstem and
            Spinal Cord Involvement and Lactate Elevation.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3336)
  AUTHORS   Liu,X.S., Liu,Z.Y., Zeng,D.B., Hu,J., Chen,X.L., Gu,J.L., Gao,Y.
            and Pei,Z.J.
  TITLE     Functional enrichment analysis reveals the involvement of DARS2 in
            multiple biological pathways and its potential as a therapeutic
            target in esophageal carcinoma
  JOURNAL   Aging (Albany NY) 16 (4), 3934-3954 (2024)
   PUBMED   38382106
  REMARK    GeneRIF: Functional enrichment analysis reveals the involvement of
            DARS2 in multiple biological pathways and its potential as a
            therapeutic target in esophageal carcinoma.
REFERENCE   3  (bases 1 to 3336)
  AUTHORS   Fang,T., Jiang,J., Yu,W., Li,R. and Tian,H.
  TITLE     DARS2 promotes the occurrence of lung adenocarcinoma via the
            ERK/c-Myc signaling pathway
  JOURNAL   Thorac Cancer 14 (36), 3511-3521 (2023)
   PUBMED   37950542
  REMARK    GeneRIF: DARS2 promotes the occurrence of lung adenocarcinoma via
            the ERK/c-Myc signaling pathway.
REFERENCE   4  (bases 1 to 3336)
  AUTHORS   Liu,X.S., Yuan,L.L., Gao,Y., Ming,X., Zhang,Y.H., Zhang,Y.,
            Liu,Z.Y., Yang,Y. and Pei,Z.J.
  TITLE     DARS2 overexpression is associated with PET/CT metabolic parameters
            and affects glycolytic activity in lung adenocarcinoma
  JOURNAL   J Transl Med 21 (1), 574 (2023)
   PUBMED   37626419
  REMARK    GeneRIF: DARS2 overexpression is associated with PET/CT metabolic
            parameters and affects glycolytic activity in lung adenocarcinoma.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 3336)
  AUTHORS   Isohanni,P., Linnankivi,T., Buzkova,J., Lonnqvist,T., Pihko,H.,
            Valanne,L., Tienari,P.J., Elovaara,I., Pirttila,T., Reunanen,M.,
            Koivisto,K., Marjavaara,S. and Suomalainen,A.
  TITLE     DARS2 mutations in mitochondrial leucoencephalopathy and multiple
            sclerosis
  JOURNAL   J Med Genet 47 (1), 66-70 (2010)
   PUBMED   19592391
  REMARK    GeneRIF: DARS2 mutations cause childhood-to-adolescence onset
            leucoencephalopathy, but they do not seem to be associated with
            multiple sclerosis.
REFERENCE   6  (bases 1 to 3336)
  AUTHORS   Reiling,E., van Vliet-Ostaptchouk,J.V., van 't Riet,E., van
            Haeften,T.W., Arp,P.A., Hansen,T., Kremer,D., Groenewoud,M.J., van
            Hove,E.C., Romijn,J.A., Smit,J.W., Nijpels,G., Heine,R.J.,
            Uitterlinden,A.G., Pedersen,O., Slagboom,P.E., Maassen,J.A.,
            Hofker,M.H., 't Hart,L.M. and Dekker,J.M.
  TITLE     Genetic association analysis of 13 nuclear-encoded mitochondrial
            candidate genes with type II diabetes mellitus: the DAMAGE study
  JOURNAL   Eur J Hum Genet 17 (8), 1056-1062 (2009)
   PUBMED   19209188
  REMARK    GeneRIF: Meta-analysis of gene-disease association. (HuGE
            Navigator)
REFERENCE   7  (bases 1 to 3336)
  AUTHORS   Scheper,G.C., van der Klok,T., van Andel,R.J., van Berkel,C.G.,
            Sissler,M., Smet,J., Muravina,T.I., Serkov,S.V., Uziel,G.,
            Bugiani,M., Schiffmann,R., Krageloh-Mann,I., Smeitink,J.A.,
            Florentz,C., Van Coster,R., Pronk,J.C. and van der Knaap,M.S.
  TITLE     Mitochondrial aspartyl-tRNA synthetase deficiency causes
            leukoencephalopathy with brain stem and spinal cord involvement and
            lactate elevation
  JOURNAL   Nat Genet 39 (4), 534-539 (2007)
   PUBMED   17384640
  REMARK    GeneRIF: Mutations in DARS2, which encodes mitochondrial
            aspartyl-tRNA synthetase, in affected individuals with
            leukoencephalopathy with brain stem and spinal cord involvement and
            lactate elevation.
REFERENCE   8  (bases 1 to 3336)
  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
  REMARK    GeneRIF: The gene for mitochondrial aspartyl-tRNA synthetase is
            described and the initial characterization of the enzyme is
            reported. Genes for the remaining missing human synthetases have
            also been found with the exception of glutaminyl-tRNA synthetase.
REFERENCE   9  (bases 1 to 3336)
  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
REFERENCE   10 (bases 1 to 3336)
  AUTHORS   Engelen,M., Abbink,T.E.M., Salomons,G.S. and van der Knaap,M.S.
  TITLE     Leukoencephalopathy with Brain Stem and Spinal Cord Involvement and
            Lactate Elevation
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   20506600
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AL519850.3, BC045173.2,
            AK022754.1 and AL109921.21.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Aug 7, 2018 this sequence version replaced NM_018122.4.
            
            Summary: The protein encoded by this gene belongs to the class-II
            aminoacyl-tRNA synthetase family. It is a mitochondrial enzyme that
            specifically aminoacylates aspartyl-tRNA. Mutations in this gene
            are associated with leukoencephalopathy with brainstem and spinal
            cord involvement and lactate elevation (LBSL). [provided by RefSeq,
            Nov 2009].
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR1803612.201082.1,
                                           SRR1660809.181326.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000649689.2/
                                                  ENSP00000497569.1
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-29                AL519850.3         74-102
            30-2702             BC045173.2         23-2695
            2703-3334           AK022754.1         1722-2353
            3335-3336           AL109921.21        133117-133118
FEATURES             Location/Qualifiers
     source          1..3336
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q25.1"
     gene            1..3336
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /note="aspartyl-tRNA synthetase 2, mitochondrial"
                     /db_xref="GeneID:55157"
                     /db_xref="HGNC:HGNC:25538"
                     /db_xref="MIM:610956"
     exon            1..684
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     CDS             558..2495
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /EC_number="6.1.1.12"
                     /note="isoform 1 is encoded by transcript variant 1;
                     aspartate tRNA ligase 2, mitochondrial; aspartyl-tRNA
                     synthetase, mitochondrial; aspartate--tRNA ligase,
                     mitochondrial"
                     /codon_start=1
                     /product="aspartate--tRNA ligase, mitochondrial isoform 1"
                     /protein_id="NP_060592.2"
                     /db_xref="CCDS:CCDS1311.1"
                     /db_xref="GeneID:55157"
                     /db_xref="HGNC:HGNC:25538"
                     /db_xref="MIM:610956"
                     /translation="MYFPSWLSQLYRGLSRPIRRTTQPIWGSLYRSLLQSSQRRIPEF
                     SSFVVRTNTCGELRSSHLGQEVTLCGWIQYRRQNTFLVLRDFDGLVQVIIPQDESAAS
                     VKKILCEAPVESVVQVSGTVISRPAGQENPKMPTGEIEIKVKTAELLNACKKLPFEIK
                     NFVKKTEALRLQYRYLDLRSFQMQYNLRLRSQMVMKMREYLCNLHGFVDIETPTLFKR
                     TPGGAKEFLVPSREPGKFYSLPQSPQQFKQLLMVGGLDRYFQVARCYRDEGSRPDRQP
                     EFTQIDIEMSFVDQTGIQSLIEGLLQYSWPNDKDPVVVPFPTMTFAEVLATYGTDKPD
                     TRFGMKIIDISDVFRNTEIGFLQDALSKPHGTVKAICIPEGAKYLKRKDIESIRNFAA
                     DHFNQEILPVFLNANRNWNSPVANFIMESQRLELIRLMETQEEDVVLLTAGEHNKACS
                     LLGKLRLECADLLETRGVVLRDPTLFSFLWVVDFPLFLPKEENPRELESAHHPFTAPH
                     PSDIHLLYTEPKKARSQHYDLVLNGNEIGGGSIRIHNAELQRYILATLLKEDVKMLSH
                     LLQALDYGAPPHGGIALGLDRLICLVTGSPSIRDVIAFPKSFRGHDLMSNTPDSVPPE
                     ELKPYHIRVSKPTDSKAERAH"
     exon            685..784
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            785..851
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            852..953
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            954..1049
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1050..1173
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1174..1220
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1221..1327
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1328..1397
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1398..1577
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1578..1685
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1686..1748
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1749..1901
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            1902..2120
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2121..2231
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2232..2307
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     exon            2308..3336
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2650..2655
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /note="hexamer: GATAAA"
     polyA_site      2676
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /note="major polyA site"
     regulatory      3190..3195
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /note="hexamer: AATAAA"
     polyA_site      3212
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /note="major polyA site"
     regulatory      3313..3318
                     /regulatory_class="polyA_signal_sequence"
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
                     /note="hexamer: AGTAAA"
     polyA_site      3336
                     /gene="DARS2"
                     /gene_synonym="ASPRS; LBSL; MT-ASPRS; mtAspRS"
ORIGIN      
        1 gaagggcgct tggaccccag cggcgatctg tgtttgggtt cgcgctctgg gagaattttg
       61 gctttgctcg ccttcctctt tcagaagact cgaaatcggc cagcaggtct gcgagatttg
      121 aaacgcgact gttactcctt gttttccggt tctggccgcg ggagcctctc gagaagcgtg
      181 gaaagaggag aagggcgtat accttgtgac cgcctctggt tgtcttgggc tcgcgcctgg
      241 cgccgctacg tggagtcgct ctctcgtcgt cacttttggc tgccgacttg ttgagtagaa
      301 gtgcagactg atgctttaag actcagggag aggtctttcc cttatctcca ccccagcaag
      361 caccccagag accttggaga tttgtcttgt ttctagacac gtgtactcca atgttgtgcg
      421 gaggaggcct taaatattcg agaagagagt gggaactcct ggaattttaa gggatttctg
      481 tgtatttcca aaactgactt ttaactaccg gcagcgtggg atttcgtgat tgtttttcgc
      541 catcgtgtgg ctccaacatg tacttccctt cttggttaag tcagctgtac aggggtttat
      601 ccagacccat cagaaggacc acccaaccga tctggggttc tctctacaga agtctgttgc
      661 agagttcaca gaggagaatt ccagaattca gtagctttgt tgtccggacc aacacatgtg
      721 gagagttgcg ttcgtctcac ttaggccaag aagtcacctt gtgtggatgg attcagtacc
      781 gaaggcaaaa cacattcttg gtcctaagag atttcgatgg gcttgttcaa gttatcattc
      841 cccaggatga gtcggcagcc tctgtgaaga agattttatg tgaagcccct gtggaatctg
      901 tggtgcaagt gtctggtaca gtcatttccc gtcctgcagg acaagagaat ccaaaaatgc
      961 caacaggtga gattgaaatc aaagttaaaa cagctgagct tctgaatgcc tgcaagaagc
     1021 tgccctttga aattaagaac ttcgtgaaga aaacagaggc tcttcggttg cagtatcgct
     1081 acttagactt gcgtagtttc caaatgcagt ataacctgcg actgaggtcc cagatggtca
     1141 tgaaaatgcg ggaatatctc tgtaatctgc atgggtttgt ggatatagaa acccccacat
     1201 tgtttaagag gaccccaggg ggtgccaaag agtttttagt accatccagg gaacctggaa
     1261 agttttattc tctccctcag agtcctcaac agtttaagca acttctgatg gttggcggtt
     1321 tagacagata ttttcaggtt gcccgatgtt atcgagatga aggttcaaga ccagacagac
     1381 agcctgagtt tactcagatt gacatagaga tgtcatttgt agaccagact gggatccaga
     1441 gtttaattga gggtttgctc cagtattcct ggcccaatga caaagatcct gtggttgttc
     1501 cttttcctac tatgactttt gctgaggtgc tggccaccta tggaactgat aaacctgaca
     1561 ctcgctttgg aatgaagatt atagatatca gtgatgtgtt tagaaacaca gagattggat
     1621 ttcttcaaga tgcacttagt aagccccatg gaactgtgaa agccatatgt atccctgaag
     1681 gagcaaaata cttaaaaagg aaagacattg aatccattag aaactttgca gctgaccatt
     1741 ttaatcagga aatcttacct gtattcctta acgccaatag aaactggaat tctccagttg
     1801 ctaatttcat aatggagtca caaagactgg aattaatcag actaatggag acccaagagg
     1861 aagatgtggt cctactaact gctggagagc acaataaagc atgctctttg ttaggaaaat
     1921 tacgactgga atgtgctgac cttctagaaa caagaggagt ggtgctccgt gaccccactc
     1981 tgttctcttt cctttgggtg gtagatttcc cactcttcct gcccaaggag gaaaatccca
     2041 gagagctgga atcggcccac cacccattta ctgctcccca ccccagtgac atacatctcc
     2101 tgtacactga gcccaaaaag gcccgtagcc aacactatga cttggtttta aatggcaatg
     2161 aaataggagg tggttcaatt cgaattcaca atgcagagct gcagcgttat atcctggcaa
     2221 ccttactaaa ggaggatgtg aaaatgctct cccatctgct ccaggcttta gattatgggg
     2281 caccccctca tggaggaatt gccttagggt tagacagact gatatgcctt gtcactggat
     2341 ctccaagcat cagagatgtc atagccttcc caaagtcctt ccggggacat gacctcatga
     2401 gcaatacccc agattctgtc cctcctgagg aactgaagcc ctatcatatc cgagtctcca
     2461 agccaacaga ctccaaagca gaaagagctc attgaatcat gcataccatg cagaaagttg
     2521 agcttttagg ttttgtcctc tttgcttccc caaggctaaa gtcagatcta gagttctgcc
     2581 acaggtctaa caatcaagtc tttagatgga aggaatccag gcaacattct tcaccacaac
     2641 gaagaaacag ataaaagata cccaattttg acttgatttc atgcatcatt tggatttttt
     2701 ttggttagga ctttttttga agttcctttt tacttaggtg tgaaagatgg ttctttgttg
     2761 aaataatata gtggtttagt gttttcaaat catgtttctc atacccagat agtagattat
     2821 tcacttagga cagaggtaat caaattatgt gtgaaatgta ggaaaatgct tgcccctgta
     2881 aactagtgag ttgatggagc atttgcttca tcatcctcat caagagaatc atataaatta
     2941 agctttataa tgacatttca accatcaaca taatatagtg aggagtagca taatattttt
     3001 taataatgca gaaaacatca ctgaaatgag agtcacaaat ttttcttcag tgtttcagcc
     3061 tgagtaagtt acataaacct cgcttagcct cccttcctgc taatgtgtaa aatacatact
     3121 tgccctggct acctcaccgg gctgttattg ctggaatcag aggagataac atatatggaa
     3181 gataaagtga ataaaagtac tttgaaaaac tataaagcat tccacaaata tgagatgatg
     3241 gtattatcca tccataaata ggtagatata tctctatttt atagtttcag attaaacaaa
     3301 actgatatca atagtaaaag tcattttact tatcaa
//
