LOCUS       NM_018060               3530 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens isoleucyl-tRNA synthetase 2, mitochondrial (IARS2),
            mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_018060
VERSION     NM_018060.4
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 3530)
  AUTHORS   Dong,Q., Yin,X., Fan,S., Zhong,S., Yang,W., Chen,K., Wang,Q.,
            Ma,X., Mahlatsi,R.L., Yang,Y., Lyu,J., Fang,H. and Wang,Y.
  TITLE     IARS2 mutations lead to Leigh syndrome with a combined oxidative
            phosphorylation deficiency
  JOURNAL   Orphanet J Rare Dis 19 (1), 305 (2024)
   PUBMED   39169373
  REMARK    GeneRIF: IARS2 mutations lead to Leigh syndrome with a combined
            oxidative phosphorylation deficiency.
            Publication Status: Online-Only
REFERENCE   2  (bases 1 to 3530)
  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   3  (bases 1 to 3530)
  AUTHORS   Barcia,G., Pandithan,D., Ruzzenente,B., Assouline,Z., Pennisi,A.,
            Ormieres,C., Besmond,C., Roux,C.J., Boddaert,N., Desguerre,I.,
            Thorburn,D.R., Bratkovic,D., Munnich,A., Bonnefont,J.P., Rotig,A.
            and Steffann,J.
  TITLE     Biallelic IARS2 mutations presenting as sideroblastic anemia
  JOURNAL   Haematologica 106 (4), 1220-1225 (2021)
   PUBMED   33327715
  REMARK    GeneRIF: Biallelic <i>IARS2</i> mutations presenting as
            sideroblastic anemia.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 3530)
  AUTHORS   Li,H., Tian,Y., Li,X., Wang,B., Zhai,D., Bai,Y., Dong,C. and
            Chao,X.
  TITLE     Knockdown of IARS2 Inhibited Proliferation of Acute Myeloid
            Leukemia Cells by Regulating p53/p21/PCNA/eIF4E Pathway
  JOURNAL   Oncol Res 27 (6), 673-680 (2019)
   PUBMED   30832756
  REMARK    GeneRIF: IARS2 knockdown can inhibit acute myeloid leukemia HL-60
            cell proliferation and cause cell cycle arrest at the G1 phase by
            regulating the p53/p21/PCNA/eIF4E pathways.
REFERENCE   5  (bases 1 to 3530)
  AUTHORS   Jabbour,S. and Harissi-Dagher,M.
  TITLE     Recessive Mutation in a Nuclear-Encoded Mitochondrial tRNA
            Synthetase Associated With Infantile Cataract, Congenital
            Neurotrophic Keratitis, and Orbital Myopathy
  JOURNAL   Cornea 35 (6), 894-896 (2016)
   PUBMED   27078007
  REMARK    GeneRIF: Patients with this very rare mutation present with a
            myriad of ocular findings, including infantile cataract,
            neurotrophic keratitis, corneal opacification, and orbital
            myopathy.
REFERENCE   6  (bases 1 to 3530)
  AUTHORS   Yin,J., Liu,W., Li,R., Liu,J., Zhang,Y., Tang,W. and Wang,K.
  TITLE     IARS2 silencing induces non-small cell lung cancer cells
            proliferation inhibition, cell cycle arrest and promotes cell
            apoptosis
  JOURNAL   Neoplasma 63 (1), 64-71 (2016)
   PUBMED   26639235
  REMARK    GeneRIF: IARS2 silencing induced NSCLC cells growth inhibition,
            cell cycle arrest and promoted cell apoptosis
REFERENCE   7  (bases 1 to 3530)
  AUTHORS   Schwartzentruber,J., Buhas,D., Majewski,J., Sasarman,F.,
            Papillon-Cavanagh,S., Thiffault,I., Sheldon,K.M., Massicotte,C.,
            Patry,L., Simon,M., Zare,A.S., McKernan,K.J., Michaud,J.,
            Boles,R.G., Deal,C.L., Desilets,V., Shoubridge,E.A. and
            Samuels,M.E.
  CONSRTM   FORGE Canada Consortium
  TITLE     Mutation in the nuclear-encoded mitochondrial isoleucyl-tRNA
            synthetase IARS2 in patients with cataracts, growth hormone
            deficiency with short stature, partial sensorineural deafness, and
            peripheral neuropathy or with Leigh syndrome
  JOURNAL   Hum Mutat 35 (11), 1285-1289 (2014)
   PUBMED   25130867
  REMARK    GeneRIF: This study is the first report of clinical findings
            associated with IARS2 mutations.
            Erratum:[Hum Mutat. 2015 Feb;36(2):281. Thiffaut, Isabelle
            [corrected to Thiffault, Isabelle]]
REFERENCE   8  (bases 1 to 3530)
  AUTHORS   Hendrickson,S.L., Lautenberger,J.A., Chinn,L.W., Malasky,M.,
            Sezgin,E., Kingsley,L.A., Goedert,J.J., Kirk,G.D., Gomperts,E.D.,
            Buchbinder,S.P., Troyer,J.L. and O'Brien,S.J.
  TITLE     Genetic variants in nuclear-encoded mitochondrial genes influence
            AIDS progression
  JOURNAL   PLoS One 5 (9), e12862 (2010)
   PUBMED   20877624
  REMARK    GeneRIF: Observational study of gene-disease association. (HuGE
            Navigator)
            Publication Status: Online-Only
REFERENCE   9  (bases 1 to 3530)
  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   10 (bases 1 to 3530)
  AUTHORS   Degoul,F., Brule,H., Cepanec,C., Helm,M., Marsac,C., Leroux,J.,
            Giege,R. and Florentz,C.
  TITLE     Isoleucylation properties of native human mitochondrial tRNAIle and
            tRNAIle transcripts. Implications for cardiomyopathy-related point
            mutations (4269, 4317) in the tRNAIle gene
  JOURNAL   Hum Mol Genet 7 (3), 347-354 (1998)
   PUBMED   9466989
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BI459732.1, BM149097.1 and
            BC040376.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_018060.3.
            
            Summary: Aminoacyl-tRNA synthetases catalyze the aminoacylation of
            tRNA by their cognate amino acid. Because of their central role in
            linking amino acids with nucleotide triplets contained in tRNAS,
            aminoacyl-tRNA synthetases are thought to be among the first
            proteins that appeared in evolution. Two forms of isoleucine-tRNA
            synthetase exist, a cytoplasmic form and a mitochondrial form. This
            gene encodes the mitochondrial isoleucine-tRNA synthetase which
            belongs to the class-I aminoacyl-tRNA synthetase family. [provided
            by RefSeq, Dec 2014].
            
            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 :: SRR1660803.201635.1,
                                           SRR1803613.251205.1 [ECO:0000332]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000366922.3/
                                                  ENSP00000355889.2
            RefSeq Select criteria             :: based on single
                                                  protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-73                BI459732.1         25-97
            74-383              BM149097.1         94-403
            384-3530            BC040376.1         136-3282
FEATURES             Location/Qualifiers
     source          1..3530
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1q41"
     gene            1..3530
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /note="isoleucyl-tRNA synthetase 2, mitochondrial"
                     /db_xref="GeneID:55699"
                     /db_xref="HGNC:HGNC:29685"
                     /db_xref="MIM:612801"
     exon            1..352
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     CDS             86..3124
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /EC_number="6.1.1.5"
                     /note="isoleucine-tRNA synthetase 2, mitochondrial;
                     mitochondrial isoleucine tRNA synthetase; isoleucine tRNA
                     ligase 2, mitochondrial; isoleucyl-tRNA synthetase,
                     mitochondrial"
                     /codon_start=1
                     /product="isoleucine--tRNA ligase, mitochondrial
                     precursor"
                     /protein_id="NP_060530.3"
                     /db_xref="CCDS:CCDS1523.1"
                     /db_xref="GeneID:55699"
                     /db_xref="HGNC:HGNC:29685"
                     /db_xref="MIM:612801"
                     /translation="MRWGLRPRGPGAAALATARSLWGTPRLPCSPGWQGATKRLLVRS
                     VSGASNHQPNSNSGRYRDTVLLPQTSFPMKLLGRQQPDTELEIQQKCGFSELYSWQRE
                     RKVKTEFCLHDGPPYANGDPHVGHALNKILKDIANRFHMMNGSKIHFVPGWDCHGLPI
                     EIKVLSELGREAQNLSAMEIRKKARSFAKAAIEKQKSAFIRWGIMADWNNCYYTFDGK
                     YEAKQLRTFYQMYDKGLVYRSYKPVFWSPSSRTALAEAELEYNPEHVSRSIYVKFPLL
                     KPSPKLASLIDGSSPVSILVWTTQPWTIPANEAVCYMPESKYAVVKCSKSGDLYVLAA
                     DKVASVASTLETTFETISTLSGVDLENGTCSHPLIPDKASPLLPANHVTMAKGTGLVH
                     TAPAHGMEDYGVASQHNLPMDCLVDEDGVFTDVAGPELQNKAVLEEGTDVVIKMLQTA
                     KNLLKEEKLVHSYPYDWRTKKPVVIRASKQWFINITDIKTAAKELLKKVKFIPGSALN
                     GMVEMMDRRPYWCISRQRVWGVPIPVFHHKTKDEYLINSQTTEHIVKLVEQHGSDIWW
                     TLPPEQLLPKEVLSEVGGPDALEYVPGQDILDIWFDSGTSWSYVLPGPDQRADLYLEG
                     KDQLGGWFQSSLLTSVAARKRAPYKTVIVHGFTLGEKGEKMSKSLGNVIHPDVVVNGG
                     QDQSKEPPYGADVLRWWVADSNVFTEVAIGPSVLNAARDDISKLRNTLRFLLGNVADF
                     NPETDSIPVNDMYVIDQYMLHLLQDLANKITELYKQYDFGKVVRLLRTFYTRELSNFY
                     FSIIKDRLYCEKENDPKRRSCQTALVEILDVIVRSFAPILPHLAEEVFQHIPYIKEPK
                     SVFRTGWISTSSIWKKPGLEEAVESACAMRDSFLGSIPGKNAAEYKVITVIEPGLLFE
                     IIEMLQSEETSSTSQLNELMMASESTLLAQEPREMTADVIELKGKFLINLEGGDIREE
                     SSYKVIVMPTTKEKCPRCWKYTAESSDTLCPRCAEVVSGK"
     exon            353..475
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            476..635
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            636..784
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            785..834
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            835..944
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            945..1035
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            1036..1151
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            1152..1321
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            1322..1412
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            1413..1564
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            1565..1725
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            1726..1828
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            1829..1922
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            1923..2031
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            2032..2134
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            2135..2260
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            2261..2392
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            2393..2499
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            2500..2645
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            2646..2836
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            2837..2981
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     exon            2982..3530
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3508..3513
                     /regulatory_class="polyA_signal_sequence"
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /note="hexamer: AATAAA"
     polyA_site      3530
                     /gene="IARS2"
                     /gene_synonym="CAGSSS; ILERS"
                     /note="major polyA site"
ORIGIN      
        1 actcggctcc ccttggtttc ctggggtcct gccccttcaa gctggggcgg gagcggagga
       61 ccccgctctc aggggttgcc ggaccatgcg ttgggggctg cgccctcgcg ggccgggcgc
      121 ggccgccctg gccactgccc gaagtttgtg ggggacgccc cgccttccct gcagcccggg
      181 atggcaaggg gcgacgaaga ggcttctggt gcggtcggtc tccggggcca gtaaccacca
      241 gccgaactcg aatagtggca gataccggga cacggtgctg ctgccgcaga cgagcttccc
      301 catgaagctg ctgggccgcc agcagccgga cacggagctg gagatccagc agaaatgtgg
      361 attttcagaa ctttattcat ggcaaagaga aagaaaagta aagacagaat tttgccttca
      421 tgatggacct ccttatgcaa acggtgaccc tcatgttgga catgctttaa ataagatttt
      481 gaaagacata gccaatcgat tccatatgat gaatggctcc aaaatacatt ttgtgcccgg
      541 ctgggattgt catgggttgc ccattgaaat aaaagtatta tcagaacttg gtagagaagc
      601 tcagaatctt tcagctatgg aaattagaaa gaaagctaga tcatttgcta aagcagccat
      661 tgagaaacag aaatcagcat ttattcgttg gggaataatg gcagattgga ataattgcta
      721 ctatacattt gatgggaagt atgaagccaa acagttgaga actttttacc aaatgtatga
      781 taagggcttg gtttatcgat cttacaaacc tgtgttttgg tctccgtcat ctaggactgc
      841 attggctgaa gcagaacttg aatataatcc tgagcatgtc agtcgttcaa tatatgtaaa
      901 atttcctctc ttaaagcctt ctccaaaatt ggcatctctt atagatggtt catctcctgt
      961 tagtattttg gtctggacca cacaaccttg gacgattcca gccaatgaag ctgtttgcta
     1021 tatgcctgaa tcaaagtatg ctgttgtgaa atgttctaag tctggagacc tctacgtact
     1081 ggcggcagat aaagtagcat ctgttgcttc tactttggaa acaacatttg agactatttc
     1141 aacactttca ggtgtagatt tggaaaatgg tacttgcagt catccattaa ttcctgataa
     1201 agcctctcct cttttacctg caaatcatgt gaccatggca aaaggaacgg gattggttca
     1261 cacagcccca gctcatggta tggaagacta cggtgtagcg tctcagcaca acctgcccat
     1321 ggattgtcta gtggacgaag atggagtttt cacagatgtt gcaggtcctg aacttcaaaa
     1381 caaggctgtc cttgaagagg gaactgatgt ggttataaag atgcttcaga ctgcaaagaa
     1441 tttgttgaaa gaggagaaat tggtgcatag ctatccgtat gactggagga ccaagaaacc
     1501 tgtggttatt cgtgccagca agcagtggtt tataaacatc acggatatta agactgcagc
     1561 caaggaattg ttaaaaaagg tgaaatttat tcctggatca gcactgaatg gcatggttga
     1621 aatgatggac aggcggccat attggtgtat atcaaggcaa agagtttggg gtgttccaat
     1681 tcctgtgttt catcataaga ccaaggatga atacttgatc aacagccaaa ccactgagca
     1741 tattgttaaa ctagtggaac aacacggcag tgatatctgg tggactcttc cccctgaaca
     1801 acttcttcca aaagaagtct tatctgaggt tggtggccct gatgccttgg aatatgtgcc
     1861 aggtcaggat attttggaca tctggtttga tagcggaact tcatggtctt atgttcttcc
     1921 aggtcctgac caaagagcag atttgtactt ggaaggaaaa gaccagctcg ggggttggtt
     1981 tcagtcatcc ttattaacaa gtgtggcagc aaggaagaga gcaccttata agacagtgat
     2041 tgttcatgga tttacccttg gagaaaaggg agaaaagatg tccaagtctc ttgggaatgt
     2101 cattcatcct gatgttgtcg ttaatggagg acaagatcaa agcaaagagc ctccgtatgg
     2161 tgctgatgtc cttcgctggt gggtagctga ttccaatgtc ttcaccgaag ttgcaattgg
     2221 cccatccgtg ctcaatgctg ccagagatga tattagcaag cttaggaata cacttcgctt
     2281 tcttttggga aatgtggctg atttcaaccc agaaacagat tccatccctg taaacgatat
     2341 gtatgtcata gaccagtaca tgctacactt actgcaggat ttggcaaaca agattaccga
     2401 attatacaaa caatatgatt ttggaaaagt tgttcggctg ttacggacgt tttataccag
     2461 agagctctct aacttttatt tcagtataat caaagatagg ctctattgtg aaaaggaaaa
     2521 tgaccccaaa cgacgctctt gtcagactgc attagttgaa attttggatg taatagttcg
     2581 ttcttttgct cccattcttc ctcacctggc tgaagaggtg ttccagcaca taccttatat
     2641 taaagagccc aagagtgttt tccgtactgg gtggattagt actagttcta tctggaaaaa
     2701 gcccgggttg gaagaagctg tggagagtgc gtgtgcaatg cgagactcat ttcttggaag
     2761 catccctggc aaaaatgcag ctgagtacaa ggttatcact gtgatagaac ctggactgct
     2821 ttttgagata atagagatgc tgcagtctga agagacttcc agcacctctc agttgaatga
     2881 attaatgatg gcttctgagt caactttact ggctcaggaa ccacgagaga tgactgcaga
     2941 tgtaatcgag cttaaaggga aattcctcat caacttagaa ggtggtgata ttcgtgaaga
     3001 gtcttcctat aaagtaattg tcatgccgac tacgaaagaa aaatgccccc gttgttggaa
     3061 gtatacagcg gagtcttcag atacactgtg tcctcgatgt gcagaagttg tcagtggaaa
     3121 atagtattaa cagctcactc gagcaagaac cctcctgaca gtactggcta gaagtttgga
     3181 tggattattt acaatatagg aaagaaagcc aagatttagg taatgagtgg atgagtaaat
     3241 ggtggaggat gggagtcaaa atcagaatta tagaagaagt atttcctgta actatagaaa
     3301 gaattatgta tatatacatg cagaaatata tatgtgtgtg tgtatctgtg gatggatata
     3361 tgtatatctc ttcctatata tatccatagt ggacttattc agaacataga tatgtattca
     3421 gcttgtcttc aaatacggcc aagcagaaaa tgttttatat tttataaatc atcttttgac
     3481 tctgtattta aattctatga tactgaaaat aaaggcattc tggaaaaata
//
