LOCUS       NM_004539               2762 bp    mRNA    linear   PRI 04-MAR-2025
DEFINITION  Homo sapiens asparaginyl-tRNA synthetase 1 (NARS1), mRNA.
ACCESSION   NM_004539
VERSION     NM_004539.4
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 2762)
  AUTHORS   Haenig,C., Atias,N., Taylor,A.K., Mazza,A., Schaefer,M.H., Russ,J.,
            Riechers,S.P., Jain,S., Coughlin,M., Fontaine,J.F., Freibaum,B.D.,
            Brusendorf,L., Zenkner,M., Porras,P., Stroedicke,M., Schnoegl,S.,
            Arnsburg,K., Boeddrich,A., Pigazzini,L., Heutink,P., Taylor,J.P.,
            Kirstein,J., Andrade-Navarro,M.A., Sharan,R. and Wanker,E.E.
  TITLE     Interactome Mapping Provides a Network of Neurodegenerative Disease
            Proteins and Uncovers Widespread Protein Aggregation in Affected
            Brains
  JOURNAL   Cell Rep 32 (7), 108050 (2020)
   PUBMED   32814053
REFERENCE   2  (bases 1 to 2762)
  AUTHORS   Wang,L., Li,Z., Sievert,D., Smith,D.E.C., Mendes,M.I., Chen,D.Y.,
            Stanley,V., Ghosh,S., Wang,Y., Kara,M., Aslanger,A.D., Rosti,R.O.,
            Houlden,H., Salomons,G.S. and Gleeson,J.G.
  TITLE     Loss of NARS1 impairs progenitor proliferation in cortical brain
            organoids and leads to microcephaly
  JOURNAL   Nat Commun 11 (1), 4038 (2020)
   PUBMED   32788587
  REMARK    GeneRIF: Loss of NARS1 impairs progenitor proliferation in cortical
            brain organoids and leads to microcephaly.
            Erratum:[Nat Commun. 2021 Feb 15;12(1):1192. doi:
            10.1038/s41467-021-21448-1. PMID: 33589599]
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 2762)
  AUTHORS   Manole,A., Efthymiou,S., O'Connor,E., Mendes,M.I., Jennings,M.,
            Maroofian,R., Davagnanam,I., Mankad,K., Lopez,M.R., Salpietro,V.,
            Harripaul,R., Badalato,L., Walia,J., Francklyn,C.S.,
            Athanasiou-Fragkouli,A., Sullivan,R., Desai,S., Baranano,K.,
            Zafar,F., Rana,N., Ilyas,M., Horga,A., Kara,M., Mattioli,F.,
            Goldenberg,A., Griffin,H., Piton,A., Henderson,L.B., Kara,B.,
            Aslanger,A.D., Raaphorst,J., Pfundt,R., Portier,R., Shinawi,M.,
            Kirby,A., Christensen,K.M., Wang,L., Rosti,R.O., Paracha,S.A.,
            Sarwar,M.T., Jenkins,D., Ahmed,J., Santoni,F.A., Ranza,E.,
            Iwaszkiewicz,J., Cytrynbaum,C., Weksberg,R., Wentzensen,I.M.,
            Guillen Sacoto,M.J., Si,Y., Telegrafi,A., Andrews,M.V.,
            Baldridge,D., Gabriel,H., Mohr,J., Oehl-Jaschkowitz,B., Debard,S.,
            Senger,B., Fischer,F., van Ravenwaaij,C., Fock,A.J.M.,
            Stevens,S.J.C., Bahler,J., Nasar,A., Mantovani,J.F., Manzur,A.,
            Sarkozy,A., Smith,D.E.C., Salomons,G.S., Ahmed,Z.M., Riazuddin,S.,
            Riazuddin,S., Usmani,M.A., Seibt,A., Ansar,M., Antonarakis,S.E.,
            Vincent,J.B., Ayub,M., Grimmel,M., Jelsig,A.M., Hjortshoj,T.D.,
            Karstensen,H.G., Hummel,M., Haack,T.B., Jamshidi,Y.,
            Distelmaier,F., Horvath,R., Gleeson,J.G., Becker,H., Mandel,J.L.,
            Koolen,D.A. and Houlden,H.
  CONSRTM   SYNAPS Study Group
  TITLE     De Novo and Bi-allelic Pathogenic Variants in NARS1 Cause
            Neurodevelopmental Delay Due to Toxic Gain-of-Function and Partial
            Loss-of-Function Effects
  JOURNAL   Am J Hum Genet 107 (2), 311-324 (2020)
   PUBMED   32738225
REFERENCE   4  (bases 1 to 2762)
  AUTHORS   Park,J.S., Park,M.C., Lee,K.Y., Goughnour,P.C., Jeong,S.J.,
            Kim,H.S., Kim,H.J., Lee,B.J., Kim,S. and Han,B.W.
  TITLE     Unique N-terminal extension domain of human asparaginyl-tRNA
            synthetase elicits CCR3-mediated chemokine activity
  JOURNAL   Int J Biol Macromol 120 (Pt A), 835-845 (2018)
   PUBMED   30171954
  REMARK    GeneRIF: The chemokine activity of UNE-N was significantly reduced
            by suppressing CCR3 expression with CCR3-targeting siRNA, and the
            loop3 region of UNE-N was shown to interact mainly with the
            extracellular domains of CCR3 in nuclear magnetic resonance
            perturbation experiments. Based on these results, evolutionarily
            acquired UNE-N elicits chemokine activities that would promote
            NRS-CCR3-mediated proinflammatory signaling in ILD.
REFERENCE   5  (bases 1 to 2762)
  AUTHORS   Hsu,C.H., Hsu,C.W., Hsueh,C., Wang,C.L., Wu,Y.C., Wu,C.C.,
            Liu,C.C., Yu,J.S., Chang,Y.S. and Yu,C.J.
  TITLE     Identification and Characterization of Potential Biomarkers by
            Quantitative Tissue Proteomics of Primary Lung Adenocarcinoma
  JOURNAL   Mol Cell Proteomics 15 (7), 2396-2410 (2016)
   PUBMED   27161446
  REMARK    GeneRIF: Study shows that ERO1L and NARS expression level are
            up-regulated in primary lung adenocarcinoma and identifies them
            with a potential to promote tumor metastasis and growth of cancer
            cells.
REFERENCE   6  (bases 1 to 2762)
  AUTHORS   Lehner,B. and Sanderson,C.M.
  TITLE     A protein interaction framework for human mRNA degradation
  JOURNAL   Genome Res 14 (7), 1315-1323 (2004)
   PUBMED   15231747
REFERENCE   7  (bases 1 to 2762)
  AUTHORS   Shiba,K., Motegi,H., Yoshida,M. and Noda,T.
  TITLE     Human asparaginyl-tRNA synthetase: molecular cloning and the
            inference of the evolutionary history of Asx-tRNA synthetase family
  JOURNAL   Nucleic Acids Res 26 (22), 5045-5051 (1998)
   PUBMED   9801298
REFERENCE   8  (bases 1 to 2762)
  AUTHORS   Beaulande,M., Tarbouriech,N. and Hartlein,M.
  TITLE     Human cytosolic asparaginyl-tRNA synthetase: cDNA sequence,
            functional expression in Escherichia coli and characterization as
            human autoantigen
  JOURNAL   Nucleic Acids Res 26 (2), 521-524 (1998)
   PUBMED   9421509
REFERENCE   9  (bases 1 to 2762)
  AUTHORS   Efthymiou,S., Nagy,S., Aynekin,B. and Houlden,H.
  TITLE     NARS1-Related Neurologic Disorders
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   40014750
REFERENCE   10 (bases 1 to 2762)
  AUTHORS   Cirullo,R.E., Arredondo-Vega,F.X., Smith,M. and Wasmuth,J.J.
  TITLE     Isolation and characterization of interspecific heat-resistant
            hybrids between a temperature-sensitive chinese hamster cell
            asparaginyl-tRNA synthetase mutant and normal human leukocytes:
            assignment of human asnS gene to chromosome 18
  JOURNAL   Somatic Cell Genet 9 (2), 215-233 (1983)
   PUBMED   6836455
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            DC302277.1, BC001687.1, U79254.1 and AC100847.2.
            
            On Nov 22, 2018 this sequence version replaced NM_004539.3.
            
            Summary:  Aminoacyl-tRNA synthetases are a class of enzymes that
            charge tRNAs with their cognate amino acids.  Asparaginyl-tRNA
            synthetase is localized to the cytoplasm and belongs to the class
            II family of tRNA synthetases.  The N-terminal domain represents
            the signature sequence for the eukaryotic asparaginyl-tRNA
            synthetases. [provided by RefSeq, Jul 2008].
            
            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 :: BC001687.1, D84273.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000256854.10/ ENSP00000256854.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-51                DC302277.1         110-160
            52-2163             BC001687.1         10-2121
            2164-2759           U79254.1           566-1161
            2760-2762           AC100847.2         28856-28858
FEATURES             Location/Qualifiers
     source          1..2762
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="18"
                     /map="18q21.31"
     gene            1..2762
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /note="asparaginyl-tRNA synthetase 1"
                     /db_xref="GeneID:4677"
                     /db_xref="HGNC:HGNC:7643"
                     /db_xref="MIM:108410"
     exon            1..129
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     CDS             120..1766
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /EC_number="6.1.1.22"
                     /note="asparagine tRNA ligase 1, cytoplasmic;
                     asparaginyl-tRNA synthetase, cytoplasmic"
                     /codon_start=1
                     /product="asparagine--tRNA ligase, cytoplasmic"
                     /protein_id="NP_004530.1"
                     /db_xref="CCDS:CCDS32837.1"
                     /db_xref="GeneID:4677"
                     /db_xref="HGNC:HGNC:7643"
                     /db_xref="MIM:108410"
                     /translation="MVLAELYVSDREGSDATGDGTKEKPFKTGLKALMTVGKEPFPTI
                     YVDSQKENERWNVISKSQLKNIKKMWHREQMKSESREKKEAEDSLRREKNLEEAKKIT
                     IKNDPSLPEPKCVKIGALEGYRGQRVKVFGWVHRLRRQGKNLMFLVLRDGTGYLQCVL
                     ADELCQCYNGVLLSTESSVAVYGMLNLTPKGKQAPGGHELSCDFWELIGLAPAGGADN
                     LINEESDVDVQLNNRHMMIRGENMSKILKARSMVTRCFRDHFFDRGYYEVTPPTLVQT
                     QVEGGATLFKLDYFGEEAFLTQSSQLYLETCLPALGDVFCIAQSYRAEQSRTRRHLAE
                     YTHVEAECPFLTFDDLLNRLEDLVCDVVDRILKSPAGSIVHELNPNFQPPKRPFKRMN
                     YSDAIVWLKEHDVKKEDGTFYEFGEDIPEAPERLMTDTINEPILLCRFPVEIKSFYMQ
                     RCPEDSRLTESVDVLMPNVGEIVGGSMRIFDSEEILAGYKREGIDPTPYYWYTDQRKY
                     GTCPHGGYGLGLERFLTWILNRYHIRDVCLYPRFVQRCTP"
     exon            130..212
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            213..371
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            372..461
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            462..540
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            541..611
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            612..698
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            699..920
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            921..1120
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            1121..1256
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            1257..1370
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            1371..1502
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            1503..1634
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     exon            1635..2762
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /inference="alignment:Splign:2.1.0"
     regulatory      2742..2747
                     /regulatory_class="polyA_signal_sequence"
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /note="hexamer: AATGAA"
     polyA_site      2762
                     /gene="NARS1"
                     /gene_synonym="ASNRS; NARS; NEDMILEG; NEDMILG"
                     /note="major polyA site"
ORIGIN      
        1 agatctacgc tctctgatgc aacgccggaa tcgcggaaac cgccggtgca cgttggagtc
       61 ataagacggc gtcggtgttg cagtctgtgt ccttggaggt gaccagggcc actgcaggca
      121 tggtgctagc agagctgtac gtctctgacc gagagggaag cgatgccacg ggagatggaa
      181 ccaaggagaa accatttaaa acaggtctaa aggctttgat gacagtaggg aaagaaccat
      241 ttcctaccat ttacgtagat tcacaaaaag aaaatgagag gtggaatgtt atttctaaat
      301 cacagttgaa gaacattaaa aagatgtggc atagggaaca aatgaagagt gaatcccggg
      361 aaaagaaaga ggcagaagat agtttacgaa gagaaaagaa cctggaagaa gcaaagaaga
      421 ttaccattaa aaatgatcca agtctcccag agccaaaatg tgtgaagatt ggtgcgttag
      481 aaggatatag aggccaaaga gtaaaggtgt ttggctgggt ccacaggctg cgcaggcaag
      541 gaaagaattt aatgtttctg gtgttgcgag atggtacagg ttatcttcag tgtgtcttgg
      601 cggatgagtt gtgtcagtgc tacaatggag ttctcttgtc cacggagagc agtgttgcag
      661 tgtatggaat gctaaatctt accccaaagg gcaagcaggc tccaggtggc catgagctga
      721 gttgtgactt ctgggaacta attgggttgg cccctgctgg aggagctgac aacctgatca
      781 atgaggagtc tgacgttgat gtccagctca acaacagaca catgatgatc cgaggagaaa
      841 acatgtccaa aatcctaaaa gcacgatcca tggtcaccag gtgctttaga gatcacttct
      901 ttgatagggg gtactatgaa gttactcctc caacattagt gcaaacacaa gtagaaggtg
      961 gtgccacact cttcaagctt gactattttg gggaagaggc atttttgact caatcctctc
     1021 agttgtactt ggagacctgc ctcccagccc tgggagatgt tttttgtatt gctcagtcat
     1081 accgggcaga gcagtccaga acacgaaggc acctggctga gtacactcac gtggaagctg
     1141 agtgtccttt cctgactttt gacgacctcc tgaaccggtt ggaggacttg gtttgtgatg
     1201 tggtagatcg aatattgaag tcacctgcag ggagcatagt gcatgagctc aacccgaact
     1261 ttcagccccc caaacggcct ttcaaacgga tgaactattc agatgctatc gtttggctaa
     1321 aagaacatga tgtaaagaaa gaagatggaa ctttctatga atttggagaa gatatcccag
     1381 aagctcctga gagactgatg acagacacca ttaatgaacc aatcttgctg tgtcgatttc
     1441 ctgtggagat caagtccttc tacatgcagc gatgtcctga ggattcccgt cttactgaat
     1501 ctgtcgacgt gttgatgccc aatgttggtg agattgtggg aggctcaatg cgtatctttg
     1561 atagtgaaga aatactggca ggttataaaa gggaagggat tgaccccact ccctattact
     1621 ggtatacgga tcagagaaaa tacggtacat gtccccatgg aggatatggc ttgggcttgg
     1681 aacgattctt aacgtggatt ctgaataggt atcacatccg agacgtgtgc ttataccctc
     1741 gatttgtcca gcgttgcacg ccataaccat tttctccaga agcgtggagg aaagattatg
     1801 aaaggaacag gctctttaaa aaagaaaaca aaaagccaga atcttccttt ttttgtttca
     1861 ttggggtttc tctttctgtt tttctttcta ctaccataaa aactatctca aatcacctga
     1921 acatcaagtg atattaaggt tgtcatctta agaaaaaata tccatttttt tcttaagttc
     1981 gggaaacaaa gttcggggaa aatacctggc atgaaactgt agttagggat acatttcagc
     2041 attttactca ctttatccaa gttattcatt ttattcaagt tatatgtatg tataattcaa
     2101 caattttaga ttatggtgta agatactcca gtaacttatc tttctgtcct tttaagtgta
     2161 ccttgaattc tttgatttat tttattgcat caatgaatta aaacaaaaat cttgggggaa
     2221 gaaattggca atatcgtata aaaatctgct catattagaa cacagtataa ttcagcagta
     2281 aacactagaa tcaaatgaat agccttttgt atcagttatt aatcttttct aactctgctt
     2341 agctgctaat aatcctgagg catagaaatt gaagaatttg taaaaataga attgccttaa
     2401 aggatttgaa gtaagaacat aattttgggg agagtttttt agtgattcac agtatccctc
     2461 ttagcattaa tttaaggtaa agaggcagat tgattttccc tctttcctgg taattcctaa
     2521 gtaattaaga ataaataagt tccaaaagaa attgtagctg gaatcttaat aacaattgtg
     2581 agtggctgtt tgagttgccc ccaccatgtc cttagatcta atctgtgcta ccttattaac
     2641 tcacagcagg cttactgaat ggcttcattt cagatttagt tgatttctcc accaaatgca
     2701 tgtcatgtat tctcaatagg ctgtattccc agcagtcaat aaatgaacac ccgtaaaaac
     2761 tc
//
