LOCUS       NM_006567               1679 bp    mRNA    linear   PRI 11-OCT-2024
DEFINITION  Homo sapiens phenylalanyl-tRNA synthetase 2, mitochondrial (FARS2),
            transcript variant 2, mRNA; nuclear gene for mitochondrial product.
ACCESSION   NM_006567
VERSION     NM_006567.5
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 1679)
  AUTHORS   Li,B., Liu,F., Chen,X., Chen,T., Zhang,J., Liu,Y., Yao,Y., Hu,W.,
            Zhang,M., Wang,B., Liu,L., Chen,K. and Wu,Y.
  TITLE     FARS2 Deficiency Causes Cardiomyopathy by Disrupting Mitochondrial
            Homeostasis and the Mitochondrial Quality Control System
  JOURNAL   Circulation 149 (16), 1268-1284 (2024)
   PUBMED   38362779
  REMARK    GeneRIF: FARS2 Deficiency Causes Cardiomyopathy by Disrupting
            Mitochondrial Homeostasis and the Mitochondrial Quality Control
            System.
REFERENCE   2  (bases 1 to 1679)
  AUTHORS   Li,L., Ma,J., Wang,J., Dong,L. and Liu,S.
  TITLE     Two Chinese siblings of combined oxidative phosphorylation
            deficiency 14 caused by compound heterozygous variants in FARS2
  JOURNAL   Eur J Med Res 27 (1), 184 (2022)
   PUBMED   36155627
  REMARK    GeneRIF: Two Chinese siblings of combined oxidative phosphorylation
            deficiency 14 caused by compound heterozygous variants in FARS2.
            Publication Status: Online-Only
REFERENCE   3  (bases 1 to 1679)
  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   4  (bases 1 to 1679)
  AUTHORS   Roux,C.J., Barcia,G., Schiff,M., Sissler,M., Levy,R.,
            Dangouloff-Ros,V., Desguerre,I., Edvardson,S., Elpeleg,O.,
            Rotig,A., Munnich,A. and Boddaert,N.
  TITLE     Phenotypic diversity of brain MRI patterns in mitochondrial
            aminoacyl-tRNA synthetase mutations
  JOURNAL   Mol Genet Metab 133 (2), 222-229 (2021)
   PUBMED   33972171
  REMARK    GeneRIF: Phenotypic diversity of brain MRI patterns in
            mitochondrial aminoacyl-tRNA synthetase mutations.
REFERENCE   5  (bases 1 to 1679)
  AUTHORS   Huttlin,E.L., Bruckner,R.J., Navarrete-Perea,J., Cannon,J.R.,
            Baltier,K., Gebreab,F., Gygi,M.P., Thornock,A., Zarraga,G., Tam,S.,
            Szpyt,J., Gassaway,B.M., Panov,A., Parzen,H., Fu,S., Golbazi,A.,
            Maenpaa,E., Stricker,K., Guha Thakurta,S., Zhang,T., Rad,R.,
            Pan,J., Nusinow,D.P., Paulo,J.A., Schweppe,D.K., Vaites,L.P.,
            Harper,J.W. and Gygi,S.P.
  TITLE     Dual proteome-scale networks reveal cell-specific remodeling of the
            human interactome
  JOURNAL   Cell 184 (11), 3022-3040 (2021)
   PUBMED   33961781
REFERENCE   6  (bases 1 to 1679)
  AUTHORS   Klipcan,L., Levin,I., Kessler,N., Moor,N., Finarov,I. and Safro,M.
  TITLE     The tRNA-induced conformational activation of human mitochondrial
            phenylalanyl-tRNA synthetase
  JOURNAL   Structure 16 (7), 1095-1104 (2008)
   PUBMED   18611382
  REMARK    GeneRIF: Formation of the PheRS-tRNAPhe complex in human
            mitochondria must be accompanied by considerable rearrangement of
            the anticodon binding domain upon tRNA binding.
REFERENCE   7  (bases 1 to 1679)
  AUTHORS   Levin,I., Kessler,N., Moor,N., Klipcan,L., Koc,E., Templeton,P.,
            Spremulli,L. and Safro,M.
  TITLE     Purification, crystallization and preliminary X-ray
            characterization of a human mitochondrial phenylalanyl-tRNA
            synthetase
  JOURNAL   Acta Crystallogr Sect F Struct Biol Cryst Commun 63 (Pt 9), 761-764
            (2007)
   PUBMED   17768348
  REMARK    GeneRIF: The recombinant human enzyme has been purified to
            homogeneity and crystallized in complex with phenylalanine and ATP.
REFERENCE   8  (bases 1 to 1679)
  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
REFERENCE   9  (bases 1 to 1679)
  AUTHORS   Bullard,J.M., Cai,Y.C., Demeler,B. and Spremulli,L.L.
  TITLE     Expression and characterization of a human mitochondrial
            phenylalanyl-tRNA synthetase
  JOURNAL   J Mol Biol 288 (4), 567-577 (1999)
   PUBMED   10329163
REFERENCE   10 (bases 1 to 1679)
  AUTHORS   Almannai,M., Faqeih,E., El-Hattab,A.W. and Wong,L.J.C.
  TITLE     FARS2 Deficiency
  JOURNAL   (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE and
            Amemiya A (Eds.);
            GENEREVIEWS(R);
            (1993)
   PUBMED   30869852
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from DA516347.1, BC020239.1,
            AF097441.1 and CA432122.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jun 2, 2019 this sequence version replaced NM_006567.4.
            
            Summary: This gene encodes a protein that transfers phenylalanine
            to its cognate tRNA. This protein localizes to the mitochondrion
            and plays a role in mitochondrial protein translation. Mutations in
            this gene can cause combined oxidative phosphorylation deficiency
            14 (Alpers encephalopathy). Alternative splicing results in
            multiple transcript variants. [provided by RefSeq, Jan 2016].
            
            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 :: SRR3476690.1078338.1,
                                           SRR5189664.8259.1 [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                 :: ENST00000274680.9/
                                                  ENSP00000274680.4
            RefSeq Select criteria             :: based on manual assertion,
                                                  conservation, expression,
                                                  longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-13                DA516347.1         140-152
            14-774              BC020239.1         1-761
            775-1676            AF097441.1         618-1519
            1677-1679           CA432122.1         27-29               c
FEATURES             Location/Qualifiers
     source          1..1679
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="6"
                     /map="6p25.1"
     gene            1..1679
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /note="phenylalanyl-tRNA synthetase 2, mitochondrial"
                     /db_xref="GeneID:10667"
                     /db_xref="HGNC:HGNC:21062"
                     /db_xref="MIM:611592"
     exon            1..148
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /inference="alignment:Splign:2.1.0"
     exon            149..781
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /inference="alignment:Splign:2.1.0"
     CDS             170..1525
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /EC_number="6.1.1.20"
                     /note="isoform 1 is encoded by transcript variant 2;
                     phenylalanine-tRNA synthetase 1 (mitochondrial);
                     phenylalanine tRNA ligase 2, mitochondrial; phenylalanine
                     translase; dJ236A3.1 (phenylalanine-tRNA synthetase);
                     dJ520B18.2 (FARS1 (phenylalanine-tRNA synthetase));
                     mitochondrial PHERS"
                     /codon_start=1
                     /product="phenylalanine--tRNA ligase, mitochondrial
                     isoform 1"
                     /protein_id="NP_006558.1"
                     /db_xref="CCDS:CCDS4494.1"
                     /db_xref="GeneID:10667"
                     /db_xref="HGNC:HGNC:21062"
                     /db_xref="MIM:611592"
                     /translation="MVGSALRRGAHAYVYLVSKASHISRGHQHQAWGSRPPAAECATQ
                     RAPGSVVELLGKSYPQDDHSNLTRKVLTRVGRNLHNQQHHPLWLIKERVKEHFYKQYV
                     GRFGTPLFSVYDNLSPVVTTWQNFDSLLIPADHPSRKKGDNYYLNRTHMLRAHTSAHQ
                     WDLLHAGLDAFLVVGDVYRRDQIDSQHYPIFHQLEAVRLFSKHELFAGIKDGESLQLF
                     EQSSRSAHKQETHTMEAVKLVEFDLKQTLTRLMAHLFGDELEIRWVDCYFPFTHPSFE
                     MEINFHGEWLEVLGCGVMEQQLVNSAGAQDRIGWAFGLGLERLAMILYDIPDIRLFWC
                     EDERFLKQFCVSNINQKVKFQPLSKYPAVINDISFWLPSENYAENDFYDLVRTIGGDL
                     VEKVDLIDKFVHPKTHKTSHCYRITYRHMERTLSQREVRHIHQALQEAAVQLLGVEGR
                     F"
     exon            782..941
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /inference="alignment:Splign:2.1.0"
     exon            942..1073
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /inference="alignment:Splign:2.1.0"
     exon            1074..1234
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /inference="alignment:Splign:2.1.0"
     exon            1235..1386
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /inference="alignment:Splign:2.1.0"
     exon            1387..1679
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /inference="alignment:Splign:2.1.0"
     regulatory      1655..1660
                     /regulatory_class="polyA_signal_sequence"
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /note="hexamer: AATAAA"
     polyA_site      1679
                     /gene="FARS2"
                     /gene_synonym="COXPD14; FARS1; HSPC320; mtPheRS; PheRS;
                     SPG77"
                     /note="major polyA site"
ORIGIN      
        1 aggcccgctt tctgtcaaaa tggcagcgcc cagcgtgcgc gggtatctct gaagttgggg
       61 tttaagattc ttgcccgtga gagcgaacga gcctgccgta cttctgattt tgaaacacct
      121 gggtctgggc ttcccgggcg agcggtggaa cctgtgagaa gtttctacaa tggtgggctc
      181 agctctcagg agaggtgccc atgcatatgt ctacctggtg agtaaggcca gtcacatctc
      241 cagaggccat cagcaccagg cctggggatc gaggcctcct gcagcagagt gtgccaccca
      301 aagagctcca ggcagtgtgg tggagctgct gggcaaatcc taccctcagg acgaccacag
      361 caacctcacc cggaaggtcc tcaccagagt tggcaggaac ctgcacaacc agcagcatca
      421 ccctctgtgg ctgatcaagg agagggtgaa ggagcacttc tacaagcagt atgtgggccg
      481 ctttgggacc ccgttgttct cggtctacga caacctttct ccagtggtca cgacctggca
      541 gaactttgac agcctgctca tcccagctga tcaccccagc aggaagaagg gggacaacta
      601 ttacctgaat cggactcaca tgctgagagc gcacacgtct gcacaccagt gggacttgct
      661 gcacgcggga ctggatgcct tcctggtggt gggtgatgtc tacaggcgtg accagatcga
      721 ctcccagcac taccctattt tccaccagct ggaggccgtg cggctcttct ccaagcatga
      781 gttatttgct ggtataaagg atggagaaag cctgcagctc tttgaacaaa gttctcgctc
      841 tgcgcataaa caagagacac acaccatgga ggccgtgaag cttgtagagt ttgatcttaa
      901 gcaaacgctt accaggctca tggcacatct ttttggagat gagctggaga taagatgggt
      961 agactgctac ttccctttta cacatccttc ctttgagatg gagatcaact ttcatggaga
     1021 atggctggaa gttcttggct gcggggtgat ggaacaacaa ctggtcaatt cagctggtgc
     1081 tcaagaccga atcggctggg cttttggcct aggattagaa aggctagcca tgatcctcta
     1141 cgacatccct gatatccgtc tcttctggtg tgaggacgag cgcttcctga agcagttctg
     1201 tgtatccaac attaatcaga aggtgaagtt tcagcctctt agcaaatatc cggctgtgat
     1261 caatgatatt tcattctggt tgccctctga gaattacgca gaaaatgatt tctatgactt
     1321 agtccgaaca attggaggag acctggtgga aaaggttgat ctcatagaca agtttgtaca
     1381 tccaaagacg cacaagacca gccactgcta ccgcatcacg taccgccaca tggaacggac
     1441 tctgtcccag agagaggtca ggcacatcca ccaggccttg caggaggctg cagtccagct
     1501 gttgggtgtg gagggcaggt tctgatgtca ccacttcact caggctgcag ccctcttggg
     1561 gctccaggat ttgctgaaag agaaaaagat atggtttgtg aactggggca tcaatcatct
     1621 tttgataaat ggatcagttt taggactttc agaaaataaa agatcgctct tgaaaagct
//
