LOCUS       NM_002109               1948 bp    mRNA    linear   PRI 08-OCT-2024
DEFINITION  Homo sapiens histidyl-tRNA synthetase 1 (HARS1), transcript variant
            1, mRNA.
ACCESSION   NM_002109
VERSION     NM_002109.6
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 1948)
  AUTHORS   Adams,R.A., Fernandes-Cerqueira,C., Notarnicola,A., Mertsching,E.,
            Xu,Z., Lo,W.S., Ogilvie,K., Chiang,K.P., Ampudia,J., Rosengren,S.,
            Cubitt,A., King,D.J., Mendlein,J.D., Yang,X.L., Nangle,L.A.,
            Lundberg,I.E., Jakobsson,P.J. and Schimmel,P.
  TITLE     Serum-circulating His-tRNA synthetase inhibits organ-targeted
            immune responses
  JOURNAL   Cell Mol Immunol 18 (6), 1463-1475 (2021)
   PUBMED   31797905
  REMARK    GeneRIF: Serum-circulating His-tRNA synthetase inhibits
            organ-targeted immune responses.
REFERENCE   2  (bases 1 to 1948)
  AUTHORS   Galatolo,D., Kuo,M.E., Mullen,P., Meyer-Schuman,R., Doccini,S.,
            Battini,R., Lieto,M., Tessa,A., Filla,A., Francklyn,C.,
            Antonellis,A. and Santorelli,F.M.
  TITLE     Bi-allelic mutations in HARS1 severely impair histidyl-tRNA
            synthetase expression and enzymatic activity causing a novel
            multisystem ataxic syndrome
  JOURNAL   Hum Mutat 41 (7), 1232-1237 (2020)
   PUBMED   32333447
  REMARK    GeneRIF: Bi-allelic mutations in HARS1 severely impair
            histidyl-tRNA synthetase expression and enzymatic activity causing
            a novel multisystem ataxic syndrome.
REFERENCE   3  (bases 1 to 1948)
  AUTHORS   Huang,H.L., Lin,W.C., Yeh,C.C. and Sun,Y.T.
  TITLE     Serological risk factors for concomitant interstitial lung disease
            in patients with idiopathic inflammatory myopathy
  JOURNAL   J Clin Neurosci 74, 32-35 (2020)
   PUBMED   31982271
  REMARK    GeneRIF: Serological risk factors for concomitant interstitial lung
            disease in patients with idiopathic inflammatory myopathy.
REFERENCE   4  (bases 1 to 1948)
  AUTHORS   Abbott,J.A., Meyer-Schuman,R., Lupo,V., Feely,S., Mademan,I.,
            Oprescu,S.N., Griffin,L.B., Alberti,M.A., Casasnovas,C.,
            Aharoni,S., Basel-Vanagaite,L., Zuchner,S., De Jonghe,P., Baets,J.,
            Shy,M.E., Espinos,C., Demeler,B., Antonellis,A. and Francklyn,C.
  TITLE     Substrate interaction defects in histidyl-tRNA synthetase linked to
            dominant axonal peripheral neuropathy
  JOURNAL   Hum Mutat 39 (3), 415-432 (2018)
   PUBMED   29235198
  REMARK    GeneRIF: the first biochemical analysis of
            Charcot-Marie-Tooth-associated HARS mutations and underscores how
            loss of the primary aminoacylation function can contribute to
            disease pathology.
REFERENCE   5  (bases 1 to 1948)
  AUTHORS   Abbott,J.A., Guth,E., Kim,C., Regan,C., Siu,V.M., Rupar,C.A.,
            Demeler,B., Francklyn,C.S. and Robey-Bond,S.M.
  TITLE     The Usher Syndrome Type IIIB Histidyl-tRNA Synthetase Mutation
            Confers Temperature Sensitivity
  JOURNAL   Biochemistry 56 (28), 3619-3631 (2017)
   PUBMED   28632987
  REMARK    GeneRIF: Despite the similar kinetics, differential scanning
            fluorimetry revealed that Y454S is less thermally stable than Wild
            Type HARS, and cells from Y454S patients grown at elevated
            temperatures demonstrate diminished levels of protein synthesis
            compared to those of Wild Type cells. The thermal sensitivity
            associated with the Y454S mutation represents a biochemical basis
            for understanding Usher Syndrome Type IIIB.
REFERENCE   6  (bases 1 to 1948)
  AUTHORS   Bird,T.D.
  TITLE     Charcot-Marie-Tooth Neuropathy Type 2 - 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   20301462
REFERENCE   7  (bases 1 to 1948)
  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
REFERENCE   8  (bases 1 to 1948)
  AUTHORS   Shi,M.H., Tsui,F.W. and Rubin,L.A.
  TITLE     Cellular localization of the target structures recognized by the
            anti-Jo-1 antibody: immunofluorescence studies on cultured human
            myoblasts
  JOURNAL   J Rheumatol 18 (2), 252-258 (1991)
   PUBMED   2023220
REFERENCE   9  (bases 1 to 1948)
  AUTHORS   Wasmuth,J.J. and Carlock,L.R.
  TITLE     Chromosomal localization of human gene for histidyl-tRNA
            synthetase: clustering of genes encoding aminoacyl-tRNA synthetases
            on human chromosome 5
  JOURNAL   Somat Cell Mol Genet 12 (5), 513-517 (1986)
   PUBMED   3464104
REFERENCE   10 (bases 1 to 1948)
  AUTHORS   Carlock,L.R., Skarecky,D., Dana,S.L. and Wasmuth,J.J.
  TITLE     Deletion mapping of human chromosome 5 using chromosome-specific
            DNA probes
  JOURNAL   Am J Hum Genet 37 (5), 839-852 (1985)
   PUBMED   2996334
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from Z11518.1 and AK225776.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 22, 2018 this sequence version replaced NM_002109.5.
            
            Summary: Aminoacyl-tRNA synthetases are a class of enzymes that
            charge tRNAs with their cognate amino acids. The protein encoded by
            this gene is a cytoplasmic enzyme which belongs to the class II
            family of aminoacyl-tRNA synthetases. The enzyme is responsible for
            the synthesis of histidyl-transfer RNA, which is essential for the
            incorporation of histidine into proteins. The gene is located in a
            head-to-head orientation with HARSL on chromosome five, where the
            homologous genes share a bidirectional promoter. The gene product
            is a frequent target of autoantibodies in the human autoimmune
            disease polymyositis/dermatomyositis. Several transcript variants
            encoding different isoforms have been found for this gene.
            [provided by RefSeq, Apr 2012].
            
            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 :: SRR3476690.38063.1,
                                           SRR1660803.160355.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000504156.7/ ENSP00000425634.1
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-1786              Z11518.1           493-2278
            1787-1948           AK225776.1         1734-1895
FEATURES             Location/Qualifiers
     source          1..1948
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="5"
                     /map="5q31.3"
     gene            1..1948
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /note="histidyl-tRNA synthetase 1"
                     /db_xref="GeneID:3035"
                     /db_xref="HGNC:HGNC:4816"
                     /db_xref="MIM:142810"
     exon            1..156
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     CDS             67..1596
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /EC_number="6.1.1.21"
                     /note="isoform 1 is encoded by transcript variant 1;
                     HisRS; histidine--tRNA ligase, cytoplasmic; histidine
                     translase; Jo-1 antigen"
                     /codon_start=1
                     /product="histidine--tRNA ligase, cytoplasmic isoform 1"
                     /protein_id="NP_002100.2"
                     /db_xref="CCDS:CCDS4237.1"
                     /db_xref="GeneID:3035"
                     /db_xref="HGNC:HGNC:4816"
                     /db_xref="MIM:142810"
                     /translation="MAERAALEELVKLQGERVRGLKQQKASAELIEEEVAKLLKLKAQ
                     LGPDESKQKFVLKTPKGTRDYSPRQMAVREKVFDVIIRCFKRHGAEVIDTPVFELKET
                     LMGKYGEDSKLIYDLKDQGGELLSLRYDLTVPFARYLAMNKLTNIKRYHIAKVYRRDN
                     PAMTRGRYREFYQCDFDIAGNFDPMIPDAECLKIMCEILSSLQIGDFLVKVNDRRILD
                     GMFAICGVSDSKFRTICSSVDKLDKVSWEEVKNEMVGEKGLAPEVADRIGDYVQQHGG
                     VSLVEQLLQDPKLSQNKQALEGLGDLKLLFEYLTLFGIDDKISFDLSLARGLDYYTGV
                     IYEAVLLQTPAQAGEEPLGVGSVAAGGRYDGLVGMFDPKGRKVPCVGLSIGVERIFSI
                     VEQRLEALEEKIRTTETQVLVASAQKKLLEERLKLVSELWDAGIKAELLYKKNPKLLN
                     QLQYCEEAGIPLVAIIGEQELKDGVIKLRSVTSREEVDVRREDLVEEIKRRTGQPLCI
                     C"
     exon            157..246
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            247..366
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            367..462
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            463..588
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            589..696
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            697..795
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            796..889
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            890..1017
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            1018..1260
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            1261..1377
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            1378..1524
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     exon            1525..1948
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1927..1932
                     /regulatory_class="polyA_signal_sequence"
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /note="hexamer: AATAAA"
     polyA_site      1948
                     /gene="HARS1"
                     /gene_synonym="CMT2W; HARS; HRS; USH3B"
                     /note="major polyA site"
ORIGIN      
        1 atccttgctg aggctggggc aaccaccgca ggtcgagaca gcaggcggct caagtggaca
       61 gccgggatgg cagagcgtgc ggcgctggag gagctggtga aacttcaggg agagcgcgtg
      121 cgaggcctca agcagcagaa ggccagcgcc gagctgatcg aggaggaggt ggcgaaactc
      181 ctgaaactga aggcacagct gggtcctgat gaaagcaaac agaaatttgt gctcaaaacc
      241 cccaagggca caagagacta tagtccccgg cagatggcag ttcgcgagaa ggtgtttgac
      301 gtaatcatcc gttgcttcaa gcgccacggt gcagaagtca ttgatacacc tgtatttgaa
      361 ctaaaggaaa cactgatggg aaagtatggg gaagactcca agcttatcta tgacctgaag
      421 gaccagggcg gggagctcct gtcccttcgc tatgacctca ctgttccttt tgctcggtat
      481 ttggcaatga ataaactgac caacattaaa cgctaccaca tagcaaaggt atatcggcgg
      541 gataacccag ccatgacccg tggccgatac cgggaattct accagtgtga ttttgacatt
      601 gctgggaact ttgatcccat gatccctgat gcagagtgcc tgaagatcat gtgcgagatc
      661 ctgagttcac ttcagatagg cgacttcctg gtcaaggtaa acgatcgacg cattctagat
      721 gggatgtttg ctatctgtgg tgtttctgac agcaagttcc gtaccatctg ctcctcagta
      781 gacaagctgg acaaggtgtc ctgggaagag gtgaagaatg agatggtggg agagaagggc
      841 cttgcacctg aggtggctga ccgcattggg gactatgtcc agcaacatgg tggggtatcc
      901 ctggtggaac agctgctcca ggatcctaaa ctatcccaaa acaagcaggc cttggagggc
      961 ctgggagacc tgaagttgct ctttgagtac ctgaccctat ttggcattga tgacaaaatc
     1021 tcctttgacc tgagccttgc tcgagggctg gattactaca ctggggtgat ctatgaggca
     1081 gtgctgctac agaccccagc ccaggcaggg gaagagcccc tgggtgtggg cagtgtggct
     1141 gctggaggac gctatgatgg gctagtgggc atgttcgacc ccaaagggcg caaggtgcca
     1201 tgtgtggggc tcagcattgg ggtggagcgg attttctcca tcgtggaaca gagactagag
     1261 gctttggagg agaagatacg gaccacggag acacaggtgc ttgtggcatc tgcacagaag
     1321 aagctgctag aggaaagact aaagcttgtc tcagaactgt gggatgctgg gatcaaggct
     1381 gagctgctgt acaagaagaa cccaaagcta ctgaaccagt tacagtactg tgaggaggca
     1441 ggcatcccac tggtggctat catcggcgag caggaactca aggatggggt catcaagctc
     1501 cgttcagtga cgagcaggga agaggtggat gtccgaagag aagaccttgt ggaggaaatc
     1561 aaaaggagaa caggccagcc cctctgcatc tgctgaactg aacaaactat cagaggaaag
     1621 gaagtgggac tggcactatt tgaggttaag acaaactgca tatgtacttc aattgctttg
     1681 cacttttccg tttcagcgga agacctgaag agtggtcaga acagagcctt tgatttttat
     1741 tatggttatt ttattgatta ttactggcaa aaacggccag gtacaacacc tttttcatac
     1801 aaggcccagg aggcttagtc cagtctgtgc tcctgggcta caaggaccca gcctgagatg
     1861 gtcccatctg cagggccccg caccagttgg agcagatgcc tccccaccac caattgccaa
     1921 aggtccaata aaatgcctca accacgga
//
