LOCUS       NM_152268               2356 bp    mRNA    linear   PRI 09-FEB-2025
DEFINITION  Homo sapiens prolyl-tRNA synthetase 2, mitochondrial (PARS2), mRNA;
            nuclear gene for mitochondrial product.
ACCESSION   NM_152268
VERSION     NM_152268.4
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 2356)
  AUTHORS   Hu,X., Guo,R., Hao,C. and Hao,L.
  TITLE     Novel mutation in PARS2 revealed highly variable phenotype of
            developmental and epileptic encephalopathy-75
  JOURNAL   Gene 894, 147985 (2024)
   PUBMED   37956963
  REMARK    GeneRIF: Novel mutation in PARS2 revealed highly variable phenotype
            of developmental and epileptic encephalopathy-75.
REFERENCE   2  (bases 1 to 2356)
  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 2356)
  AUTHORS   Yin,X., Tang,B., Mao,X., Peng,J., Zeng,S., Wang,Y., Jiang,H. and
            Li,N.
  TITLE     The genotypic and phenotypic spectrum of PARS2-related
            infantile-onset encephalopathy
  JOURNAL   J Hum Genet 63 (9), 971-980 (2018)
   PUBMED   29915213
  REMARK    GeneRIF: study provides further evidence for validating the role of
            PARS2 in the pathology of related infantile-onset encephalopathy,
            contributing to the phenotypic features of this condition, and
            providing clinical and molecular insight for the diagnosis of this
            disease entity.
REFERENCE   4  (bases 1 to 2356)
  AUTHORS   Ciara,E., Rokicki,D., Lazniewski,M., Mierzewska,H., Jurkiewicz,E.,
            Bekiesinska-Figatowska,M., Piekutowska-Abramczuk,D.,
            Iwanicka-Pronicka,K., Szymanska,E., Stawinski,P., Kosinska,J.,
            Pollak,A., Pronicki,M., Plewczynski,D., Ploski,R. and Pronicka,E.
  TITLE     Clinical and molecular characteristics of newly reported
            mitochondrial disease entity caused by biallelic PARS2 mutations
  JOURNAL   J Hum Genet 63 (4), 473-485 (2018)
   PUBMED   29410512
  REMARK    GeneRIF: Depending on available data of six patients from three
            families, we describe a phenotype linked to PARS2 pathological
            variants. This phenotype includes: early epileptic encephalopathy,
            infantile spasms, and Alpers-like brain MRI changes with
            predominance of frontal cerebral volume loss (FCVL-AS).
REFERENCE   5  (bases 1 to 2356)
  AUTHORS   Mizuguchi,T., Nakashima,M., Kato,M., Yamada,K., Okanishi,T.,
            Ekhilevitch,N., Mandel,H., Eran,A., Toyono,M., Sawaishi,Y.,
            Motoi,H., Shiina,M., Ogata,K., Miyatake,S., Miyake,N., Saitsu,H.
            and Matsumoto,N.
  TITLE     PARS2 and NARS2 mutations in infantile-onset neurodegenerative
            disorder
  JOURNAL   J Hum Genet 62 (5), 525-529 (2017)
   PUBMED   28077841
  REMARK    GeneRIF: The individuals with PARS2 and NARS2 mutations demonstrate
            similar neurological features as those previously reported, with
            diversity in clinical presentation such as hearing loss and seizure
            type.
            Erratum:[J Hum Genet. 2017 Apr;62(5):587. doi:
            10.1038/jhg.2017.13.. PMID: 28202951]
REFERENCE   6  (bases 1 to 2356)
  AUTHORS   Henmyr,V., Lind-Hallden,C., Hallden,C., Sall,T., Carlberg,D.,
            Bachert,C. and Cardell,L.O.
  TITLE     Chronic Rhinosinusitis Patients Show Accumulation of Genetic
            Variants in PARS2
  JOURNAL   PLoS One 11 (6), e0158202 (2016)
   PUBMED   27348859
  REMARK    GeneRIF: The PARS2 gene produced a significant association signal
            in a recent replication study of all known CRS-associations and is
            now the first human gene to be re-sequenced within CRS research.
            PARS2 showed an accumulation of low-frequency variants in CRS
            patients compared to background populations.
            Publication Status: Online-Only
REFERENCE   7  (bases 1 to 2356)
  AUTHORS   Sofou,K., Kollberg,G., Holmstrom,M., Davila,M., Darin,N.,
            Gustafsson,C.M., Holme,E., Oldfors,A., Tulinius,M. and
            Asin-Cayuela,J.
  TITLE     Whole exome sequencing reveals mutations in NARS2 and PARS2,
            encoding the mitochondrial asparaginyl-tRNA synthetase and
            prolyl-tRNA synthetase, in patients with Alpers syndrome
  JOURNAL   Mol Genet Genomic Med 3 (1), 59-68 (2015)
   PUBMED   25629079
REFERENCE   8  (bases 1 to 2356)
  AUTHORS   Zhou,H., Sun,L., Yang,X.L. and Schimmel,P.
  TITLE     ATP-directed capture of bioactive herbal-based medicine on human
            tRNA synthetase
  JOURNAL   Nature 494 (7435), 121-124 (2013)
   PUBMED   23263184
  REMARK    GeneRIF: unusual 2.0 A structure showing that ATP directly locks
            onto and orients two parts of halofuginone (HF) onto human ProRS,
            so that one part of HF mimics bound proline and the other mimics
            the 3' end of bound tRNA.
REFERENCE   9  (bases 1 to 2356)
  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
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DB004072.1 and BC011758.2.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Nov 23, 2018 this sequence version replaced NM_152268.3.
            
            Summary: This gene encodes a putative member of the class II family
            of aminoacyl-tRNA synthetases. These enzymes play a critical role
            in protein biosynthesis by charging tRNAs with their cognate amino
            acids. This protein is encoded by the nuclear genome but is likely
            to be imported to the mitochondrion where it is thought to catalyze
            the ligation of proline to tRNA molecules. Mutations have been
            found in this gene in some patients with Alpers syndrome. [provided
            by RefSeq, Mar 2015].
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC011758.2, SRR1803615.230915.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1968189
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            MANE Ensembl match                 :: ENST00000371279.4/
                                                  ENSP00000360327.3
            RefSeq Select criteria             :: based on single
                                                  protein-coding transcript
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-9                 DB004072.1         31-39
            10-2356             BC011758.2         1-2347
FEATURES             Location/Qualifiers
     source          1..2356
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="1"
                     /map="1p32.3"
     gene            1..2356
                     /gene="PARS2"
                     /gene_synonym="DEE75; EIEE75; MT-PRORS; proRS"
                     /note="prolyl-tRNA synthetase 2, mitochondrial"
                     /db_xref="GeneID:25973"
                     /db_xref="HGNC:HGNC:30563"
                     /db_xref="MIM:612036"
     exon            1..63
                     /gene="PARS2"
                     /gene_synonym="DEE75; EIEE75; MT-PRORS; proRS"
                     /inference="alignment:Splign:2.1.0"
     exon            64..2356
                     /gene="PARS2"
                     /gene_synonym="DEE75; EIEE75; MT-PRORS; proRS"
                     /inference="alignment:Splign:2.1.0"
     CDS             93..1520
                     /gene="PARS2"
                     /gene_synonym="DEE75; EIEE75; MT-PRORS; proRS"
                     /EC_number="6.1.1.15"
                     /note="proline tRNA ligase 2, mitochondrial (putative);
                     prolyl-tRNA synthetase 2, mitochondrial (putative)"
                     /codon_start=1
                     /product="probable proline--tRNA ligase, mitochondrial
                     precursor"
                     /protein_id="NP_689481.2"
                     /db_xref="CCDS:CCDS597.1"
                     /db_xref="GeneID:25973"
                     /db_xref="HGNC:HGNC:30563"
                     /db_xref="MIM:612036"
                     /translation="MEGLLTRCRALPALATCSRQLSGYVPCRFHHCAPRRGRRLLLSR
                     VFQPQNLREDRVLSLQDKSDDLTCKSQRLMLQVGLIYPASPGCYHLLPYTVRAMEKLV
                     RVIDQEMQAIGGQKVNMPSLSPAELWQATNRWDLMGKELLRLRDRHGKEYCLGPTHEE
                     AITALIASQKKLSYKQLPFLLYQVTRKFRDEPRPRFGLLRGREFYMKDMYTFDSSPEA
                     AQQTYSLVCDAYCSLFNKLGLPFVKVQADVGTIGGTVSHEFQLPVDIGEDRLAICPRC
                     SFSANMETLDLSQMNCPACQGPLTKTKGIEVGHTFYLGTKYSSIFNAQFTNVCGKPTL
                     AEMGCYGLGVTRILAAAIEVLSTEDCVRWPSLLAPYQACLIPPKKGSKEQAASELIGQ
                     LYDHITEAVPQLHGEVLLDDRTHLTIGNRLKDANKFGYPFVIIAGKRALEDPAHFEVW
                     CQNTGEVAFLTKDGVMDLLTPVQTV"
     regulatory      2336..2341
                     /regulatory_class="polyA_signal_sequence"
                     /gene="PARS2"
                     /gene_synonym="DEE75; EIEE75; MT-PRORS; proRS"
                     /note="hexamer: AATAAA"
     polyA_site      2356
                     /gene="PARS2"
                     /gene_synonym="DEE75; EIEE75; MT-PRORS; proRS"
                     /note="major polyA site"
ORIGIN      
        1 gaggcgcaag cgcgctggcc cggcacggcg gtggtcttgc gggaggcgtg ggctgggatt
       61 gcggtgcctg tgcttcccgg tgccagggtg tcatggaagg gctgctgaca agatgcagag
      121 cattgcccgc cctggccacc tgcagccgcc agctctctgg gtatgttcct tgcaggtttc
      181 accactgtgc cccaagaaga gggcggcgcc tgctgctgtc tcgtgtgttc cagccacaga
      241 accttcggga agaccgggtg ctctccctgc aggacaaatc tgatgacctg acctgtaaga
      301 gccagcggct gatgctgcag gtgggcctga tctacccagc aagccccggc tgttaccacc
      361 tcctgccata taccgtccgt gccatggaga agctcgtgcg agtgatagac caggagatgc
      421 aggccatcgg gggccagaaa gtcaacatgc ccagcctcag cccggcagag ctctggcaag
      481 ccaccaaccg gtgggacttg atgggcaaag agctgctaag acttagagac aggcatggca
      541 aggaatactg cttaggacca actcacgagg aagccattac ggccttaatt gcctcccaga
      601 agaaactgtc ctacaagcag cttcccttcc tgctgtacca agtgacaagg aagtttcggg
      661 atgagcccag gccccgcttt ggtcttctcc gtggccgaga gttttacatg aaggatatgt
      721 acacctttga ctcctcccca gaggctgccc agcagaccta cagcctggtg tgtgatgcct
      781 actgcagcct gttcaacaag ctagggctgc catttgtcaa ggtccaggcc gatgtgggca
      841 ccatcggggg cacagtgtct catgagttcc agctcccagt ggatattgga gaggaccggc
      901 ttgccatctg tccccgctgc agcttctcag ccaacatgga gacactagac ttgtcacaaa
      961 tgaactgccc tgcttgccag ggcccattga ctaaaaccaa aggcattgag gtggggcaca
     1021 cattttacct gggtaccaag tactcatcca ttttcaatgc ccagtttacc aatgtctgtg
     1081 gcaaaccaac cctggctgaa atggggtgct atggcttggg tgtgacacgg atcttggctg
     1141 ctgccattga agtcctctct acagaagact gtgtccgctg gcccagccta ctggcccctt
     1201 accaagcctg cctcatcccc cctaagaagg gcagtaagga gcaggcggcc tccgagctca
     1261 tagggcagct gtacgaccac atcacagagg cagtgcctca gcttcacggg gaggtgctcc
     1321 tggacgacag gacccatctg accatcggaa acagactgaa agatgccaac aagtttggct
     1381 acccctttgt gataatcgct ggcaagaggg ccctggagga ccctgcacat tttgaggttt
     1441 ggtgtcagaa cactggtgag gtggccttcc tcaccaaaga tggagtcatg gatttactga
     1501 ccccagtgca gactgtctaa atgcccccag cccacccctg cccccatttg cagccttggt
     1561 gttcgttcta acactgcatt ttcctacacc cctttcctgg actgctctct ccagaaacag
     1621 cacagctcat ggagggtgag atcatgttag ggaaatcaat ttttatctag tcatttgttc
     1681 agattatttg tatttaaagt cattaacttg atccctttct ccagactggc catgccgcca
     1741 tatacctttc cttttgtatt ccattgtgga agcttctagg aggctgagaa gcaggagatc
     1801 caagctccag tcctgggtgt taccctgagg ggggaagtca cttcccttct ctcagctgag
     1861 tttttcacgt gtaagatgag aatggctgat ggctgagagc ccaccaacct tccccacccc
     1921 gtatcagttt gaccacgggc cttttgctac attctatcca gagagcaggc ctgccagccc
     1981 ctctccactg agaagttggg ctgagagtat ggggaaaaga atcaagagac ctgactgccg
     2041 ccaactcact agtgacttag atacatcccc tccccctgct ggggcctcag tttccccatc
     2101 tgtaacttga gaaaatagaa ctagatctgt aaagtctgga actagatctg taacgtcctt
     2161 ataggtgtca ctagggggtt ccatgagagg tgtgtgacag gcagtctgat tcctctcatt
     2221 ctccatagtc tgtttcctgg aaagtcgatg taattaactg atggcccaaa aactacctca
     2281 agagacctgg ccctgttaag acggcttaac cactgagatc ccgttctatt gatttaataa
     2341 agtcaaacta ttggaa
//
