LOCUS       NM_012208               2468 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens histidyl-tRNA synthetase 2, mitochondrial (HARS2),
            transcript variant 1, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_012208
VERSION     NM_012208.4
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 2468)
  AUTHORS   Lei,Y.B., Sun,S.P., Mao,L., Xu,H.E., Tang,W.X., Pan,Z.Y. and Lu,W.
  TITLE     [Analysis of perrault syndrome caused by pathogenic variants in
            LARS2 and HARS2 genes]
  JOURNAL   Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 58 (12), 1191-1197
            (2023)
   PUBMED   38186093
  REMARK    GeneRIF: [Analysis of perrault syndrome caused by pathogenic
            variants in LARS2 and HARS2 genes].
REFERENCE   2  (bases 1 to 2468)
  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 2468)
  AUTHORS   Yu,J., Jiang,W., Cao,L., Na,X. and Yang,J.
  TITLE     Two novel likely pathogenic variants of HARS2 identified in a
            Chinese family with sensorineural hearing loss
  JOURNAL   Hereditas 157 (1), 47 (2020)
   PUBMED   33228777
  REMARK    GeneRIF: Two novel likely pathogenic variants of HARS2 identified
            in a Chinese family with sensorineural hearing loss.
            Publication Status: Online-Only
REFERENCE   4  (bases 1 to 2468)
  AUTHORS   Demain,L.A.M., Gerkes,E.H., Smith,R.J.H., Molina-Ramirez,L.P.,
            O'Keefe,R.T. and Newman,W.G.
  TITLE     A recurrent missense variant in HARS2 results in variable
            sensorineural hearing loss in three unrelated families
  JOURNAL   J Hum Genet 65 (3), 305-311 (2020)
   PUBMED   31827252
  REMARK    GeneRIF: A recurrent missense variant in HARS2 results in variable
            sensorineural hearing loss in three unrelated families.
REFERENCE   5  (bases 1 to 2468)
  AUTHORS   Gong,S., Wang,X., Meng,F., Cui,L., Yi,Q., Zhao,Q., Cang,X., Cai,Z.,
            Mo,J.Q., Liang,Y. and Guan,M.X.
  TITLE     Overexpression of mitochondrial histidyl-tRNA synthetase restores
            mitochondrial dysfunction caused by a deafness-associated tRNAHis
            mutation
  JOURNAL   J Biol Chem 295 (4), 940-954 (2020)
   PUBMED   31819004
  REMARK    GeneRIF: Overexpression of mitochondrial histidyl-tRNA synthetase
            restores mitochondrial dysfunction caused by a deafness-associated
            tRNA(His) mutation.
REFERENCE   6  (bases 1 to 2468)
  AUTHORS   Lama,J. and Trono,D.
  TITLE     Human immunodeficiency virus type 1 matrix protein interacts with
            cellular protein HO3
  JOURNAL   J Virol 72 (2), 1671-1676 (1998)
   PUBMED   9445076
REFERENCE   7  (bases 1 to 2468)
  AUTHORS   O'Hanlon,T.P., Raben,N. and Miller,F.W.
  TITLE     A novel gene oriented in a head-to-head configuration with the
            human histidyl-tRNA synthetase (HRS) gene encodes an mRNA that
            predicts a polypeptide homologous to HRS
  JOURNAL   Biochem Biophys Res Commun 210 (2), 556-566 (1995)
   PUBMED   7755634
REFERENCE   8  (bases 1 to 2468)
  AUTHORS   Tsui,H.W., Mok,S., de Souza,L., Martin,A. and Tsui,F.W.
  TITLE     Transcriptional analyses of the gene region that encodes human
            histidyl-tRNA synthetase: identification of a novel bidirectional
            regulatory element
  JOURNAL   Gene 131 (2), 201-208 (1993)
   PUBMED   8406012
REFERENCE   9  (bases 1 to 2468)
  AUTHORS   Newman,W.G., Friedman,T.B., Conway,G.S. and Demain,L.A.M.
  TITLE     Perrault Syndrome
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   25254289
REFERENCE   10 (bases 1 to 2468)
  AUTHORS   Raben,N., Borriello,F., Amin,J., Horwitz,R., Fraser,D. and Plotz,P.
  TITLE     Human histidyl-tRNA synthetase: recognition of amino acid signature
            regions in class 2a aminoacyl-tRNA synthetases
  JOURNAL   Nucleic Acids Res 20 (5), 1075-1081 (1992)
   PUBMED   1549469
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA150729.1 and BC014982.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_012208.3.
            
            Summary: Aminoacyl-tRNA synthetases are a class of enzymes that
            charge tRNAs with their cognate amino acids. The protein encoded by
            this gene is an enzyme belonging to the class II family of
            aminoacyl-tRNA synthetases. Functioning in the synthesis of
            histidyl-transfer RNA, the enzyme plays an accessory role in the
            regulation of protein biosynthesis. The gene is located in a
            head-to-head orientation with HARS on chromosome five, where the
            homologous genes likely share a bidirectional promoter. Mutations
            in this gene are associated with the pathogenesis of Perrault
            syndrome, which involves ovarian dysgenesis and sensorineural
            hearing loss. Alternative splicing results in multiple transcript
            variants of this gene. [provided by RefSeq, Jul 2013].
            
            Transcript Variant: This variant (1) represents the longest
            transcript and encodes the longest isoform (1).
            
            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 :: SRR1660805.11907.1,
                                           SRR1803614.250150.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000230771.9/
                                                  ENSP00000230771.3
            RefSeq Select criteria             :: based on conservation,
                                                  expression
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-7                 DA150729.1         30-36
            8-2468              BC014982.1         1-2461
FEATURES             Location/Qualifiers
     source          1..2468
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q31.3"
     gene            1..2468
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /note="histidyl-tRNA synthetase 2, mitochondrial"
                     /db_xref="GeneID:23438"
                     /db_xref="HGNC:HGNC:4817"
                     /db_xref="MIM:600783"
     exon            1..302
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     CDS             195..1715
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /EC_number="6.1.1.21"
                     /note="isoform 1 precursor is encoded by transcript
                     variant 1; HARS-related; histidyl-tRNA synthetase 2,
                     mitochondrial (putative); histidine tRNA ligase 2,
                     mitochondrial (putative); histidine-tRNA ligase homolog;
                     histidine translase; probable histidyl-tRNA synthetase,
                     mitochondrial; histidyl-tRNA synthetase 2, mitochondrial,
                     hisRS; probable histidine--tRNA ligase, mitochondrial"
                     /codon_start=1
                     /product="histidine--tRNA ligase, mitochondrial isoform 1
                     precursor"
                     /protein_id="NP_036340.1"
                     /db_xref="CCDS:CCDS4238.1"
                     /db_xref="GeneID:23438"
                     /db_xref="HGNC:HGNC:4817"
                     /db_xref="MIM:600783"
                     /translation="MPLLGLLPRRAWASLLSQLLRPPCASCTGAVRCQSQVAEAVLTS
                     QLKAHQEKPNFIIKTPKGTRDLSPQHMVVREKILDLVISCFKRHGAKGMDTPAFELKE
                     TLTEKYGEDSGLMYDLKDQGGELLSLRYDLTVPFARYLAMNKVKKMKRYHVGKVWRRE
                     SPTIVQGRYREFCQCDFDIAGQFDPMIPDAECLKIMCEILSGLQLGDFLIKVNDRRIV
                     DGMFAVCGVPESKFRAICSSIDKLDKMAWKDVRHEMVVKKGLAPEVADRIGDYVQCHG
                     GVSLVEQMFQDPRLSQNKQALEGLGDLKLLFEYLTLFGIADKISFDLSLARGLDYYTG
                     VIYEAVLLQTPTQAGEEPLNVGSVAAGGRYDGLVGMFDPKGHKVPCVGLSIGVERIFY
                     IVEQRMKTKGEKVRTTETQVFVATPQKNFLQERLKLIAELWDSGIKAEMLYKNNPKLL
                     TQLHYCESTGIPLVVIIGEQELKEGVIKIRSVASREEVAIKRENFVAEIQKRLSES"
     exon            303..377
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            378..497
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            498..593
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            594..719
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            720..827
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            828..926
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            927..1020
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1021..1148
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1149..1391
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1392..1508
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1509..1655
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     exon            1656..2468
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2451..2456
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /note="hexamer: AATAAA"
     polyA_site      2468
                     /gene="HARS2"
                     /gene_synonym="HARSL; HARSR; HisRS; HO3; PRLTS2"
                     /note="major polyA site"
ORIGIN      
        1 gccgaagctg gctactaagg gaacttggga ggatcccacc tcagccttcg tgactagtga
       61 ggtgcgcaaa cgcccgagtt ttccctggtg cgcgggttcc gcctttgcag tgccctccac
      121 ccttcctggt gtctgacccg cctccttccc aggccttttg ttcctgtccc ggaaagccgg
      181 cgtcctgccg cgcgatgccc ctgctcggac ttcttcccag gagggcctgg gcttcgctgc
      241 tcagccagct cctgcgaccg ccctgcgctt cgtgcaccgg ggcggtccgt tgccaaagcc
      301 aggttgcaga ggcagtgtta acatcccaac tgaaagcaca tcaagagaaa ccaaatttta
      361 ttatcaagac cccaaagggt accagggatc ttagtcctca gcatatggtt gtgagggaga
      421 aaattcttga tttggttatc agctgcttta aacgtcatgg agcaaagggg atggacaccc
      481 cagcatttga gctgaaggaa accctgactg agaagtatgg agaggactct gggctcatgt
      541 atgatctgaa ggatcaaggt ggagagctgt tgtccctccg ctatgacctt actgttccct
      601 ttgctcgtta tctggccatg aataaggtga agaagatgaa acgttatcat gttggaaagg
      661 tgtggcggcg agagagccca accatagtcc aaggccgtta tagggagttc tgccagtgtg
      721 attttgacat tgctggtcag tttgacccta tgatccccga tgcagagtgt ttgaagatca
      781 tgtgtgaaat cctaagtgga ttgcagttgg gagactttct cattaaggta aatgaccggc
      841 ggattgtgga tgggatgttt gctgtctgtg gtgttcctga aagcaagttc cgtgccatct
      901 gctcctccat agataaacta gacaagatgg cttggaaaga tgtgagacat gagatggtgg
      961 tgaagaaagg cctggctcct gaggtggctg atcgaattgg ggactatgtc cagtgtcatg
     1021 gtggggtatc cctagtagag caaatgtttc aggatcccag actatcccag aacaagcagg
     1081 ccctggaggg cctgggagac ctaaagctgc tatttgaata cctgacttta tttggaattg
     1141 ctgataagat ctcctttgac ctcagcctgg ctcggggcct agactactat acaggagtga
     1201 tctatgaagc agtgctgctg cagaccccaa ctcaggctgg ggaggagccc ctgaatgtgg
     1261 gcagtgtggc tgctggtggg cgctatgatg ggctggtggg catgtttgac cccaagggcc
     1321 acaaggtgcc atgtgtggga ctcagcattg gggttgagcg aatcttctac attgtggagc
     1381 agaggatgaa gaccaaaggt gagaaggtgc ggactacaga gactcaagtg tttgtggcca
     1441 caccacagaa gaactttctc caagaacggt tgaagcttat tgcagagctt tgggattctg
     1501 gaatcaaggc agagatgcta tacaagaaca accccaaact attaacccag ctgcactatt
     1561 gtgagagcac aggcattcca ctggtggtca ttattggtga gcaagaactg aaagaagggg
     1621 tcatcaagat ccgttcagtg gccagcagag aggaggtggc cattaaacgg gaaaattttg
     1681 tggctgaaat tcagaagcga ctgtctgagt cttgatcctt gcctgattcc catctgctgc
     1741 tctttgtaga aaaggtttcc tctagaactg aattcctctg gaattgagtg atggacttca
     1801 caacaactag ccaggaaggg tgacaagtac cttctgcctc ctccattctt cctgggtgca
     1861 gaactgtaga agaccctgag gactcctggg ctagtgtgag cagctattct gcatgggtgc
     1921 agatggctgg atgtgaaaga gacatgctct agctgcagag gcaaatttga agtgccacgg
     1981 aacgttgtca agaggtagtg agattgttgc tgtgagcaag gctctgggag agtcacctca
     2041 ggctcaggat tctgaaccat tgagatcaga aaccagatac ttagccttct actgtagcta
     2101 cggaaccaga ttctggtgaa tttgtccaca atcagccatt ggcctgtctg gggagttttt
     2161 ggaagacagc aaagaggggc aatggctgct ttcagctttg aggacagatg ctatcctaag
     2221 ggcatggcag tacccatgtt gatttgacat ctctctagcc catccattgc ttacagtaga
     2281 agagtggggc tgtatgcttg ataatcttga acattgaact taatagatga cttgacaagg
     2341 tagagatctg atattttgag attttggaga ccatttcctg tgccagaatc actgctctat
     2401 tccataccgt gccatggagg ctgttttaga agtggttgga taacatgtta aataaaatat
     2461 taagtgta
//
