SYNM_HUMAN
ID SYNM_HUMAN Reviewed; 477 AA.
AC Q96I59; G3V178;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Probable asparagine--tRNA ligase, mitochondrial;
DE EC=6.1.1.22;
DE AltName: Full=Asparaginyl-tRNA synthetase;
DE Short=AsnRS;
DE Flags: Precursor;
GN Name=NARS2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-87.
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP IDENTIFICATION.
RX PubMed=15779907; DOI=10.1021/bi047527z;
RA Bonnefond L., Fender A., Rudinger-Thirion J., Giege R., Florentz C.,
RA Sissler M.;
RT "Toward the full set of human mitochondrial aminoacyl-tRNA synthetases:
RT characterization of AspRS and TyrRS.";
RL Biochemistry 44:4805-4816(2005).
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-353, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [8]
RP INVOLVEMENT IN COXPD24.
RX PubMed=25385316; DOI=10.1002/humu.22728;
RA Vanlander A.V., Menten B., Smet J., De Meirleir L., Sante T., De Paepe B.,
RA Seneca S., Pearce S.F., Powell C.A., Vergult S., Michotte A., De Latter E.,
RA Vantomme L., Minczuk M., Van Coster R.;
RT "Two siblings with homozygous pathogenic splice-site variant in
RT mitochondrial asparaginyl-tRNA synthetase (NARS2).";
RL Hum. Mutat. 36:222-231(2015).
RN [9]
RP INVOLVEMENT IN COXPD24, AND VARIANT COXPD24 LEU-214.
RX PubMed=25629079; DOI=10.1002/mgg3.115;
RA Sofou K., Kollberg G., Holmstroem M., Davila M., Darin N., Gustafsson C.M.,
RA Holme E., Oldfors A., Tulinius M., Asin-Cayuela J.;
RT "Whole exome sequencing reveals mutations in NARS2 and PARS2, encoding the
RT mitochondrial asparaginyl-tRNA synthetase and prolyl-tRNA synthetase, in
RT patients with Alpers syndrome.";
RL Mol. Genet. Genomic Med. 3:59-68(2015).
RN [10]
RP SUBCELLULAR LOCATION, SUBUNIT, INVOLVEMENT IN COXPD24, INVOLVEMENT IN
RP DFNB94, VARIANTS COXPD24 323-TYR--LEU-477 DEL AND SER-381, VARIANT DFNB94
RP PHE-213, CHARACTERIZATION OF VARIANT DFNB94 PHE-213, AND CHARACTERIZATION
RP OF VARIANT COXPD24 SER-381.
RX PubMed=25807530; DOI=10.1371/journal.pgen.1005097;
RA Simon M., Richard E.M., Wang X., Shahzad M., Huang V.H., Qaiser T.A.,
RA Potluri P., Mahl S.E., Davila A., Nazli S., Hancock S., Yu M., Gargus J.,
RA Chang R., Al-Sheqaih N., Newman W.G., Abdenur J., Starr A., Hegde R.,
RA Dorn T., Busch A., Park E., Wu J., Schwenzer H., Flierl A., Florentz C.,
RA Sissler M., Khan S.N., Li R., Guan M.X., Friedman T.B., Wu D.K.,
RA Procaccio V., Riazuddin S., Wallace D.C., Ahmed Z.M., Huang T.,
RA Riazuddin S.;
RT "Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA
RT synthetase, cause nonsyndromic deafness and Leigh syndrome.";
RL PLoS Genet. 11:E1005097-E1005097(2015).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-asparagine + tRNA(Asn) = AMP + diphosphate + H(+) + L-
CC asparaginyl-tRNA(Asn); Xref=Rhea:RHEA:11180, Rhea:RHEA-COMP:9659,
CC Rhea:RHEA-COMP:9674, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:58048, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78515, ChEBI:CHEBI:456215; EC=6.1.1.22;
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:25807530}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}. Mitochondrion
CC {ECO:0000269|PubMed:25807530}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96I59-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96I59-2; Sequence=VSP_054120;
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 24 (COXPD24)
CC [MIM:616239]: An autosomal recessive mitochondrial disorder with wide
CC phenotypic variability. Some patients have a milder form affecting only
CC skeletal muscle, whereas others may have a more severe disorder,
CC reminiscent of Alpers syndrome. Alpers syndrome is a progressive
CC neurodegenerative disorder that presents in infancy or early childhood
CC and is characterized by diffuse degeneration of cerebral gray matter.
CC {ECO:0000269|PubMed:25385316, ECO:0000269|PubMed:25629079,
CC ECO:0000269|PubMed:25807530}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Deafness, autosomal recessive, 94 (DFNB94) [MIM:618434]: A
CC form of non-syndromic, sensorineural deafness characterized by
CC prelingual, profound, bilateral hearing impairment. Sensorineural
CC deafness results from damage to the neural receptors of the inner ear,
CC the nerve pathways to the brain, or the area of the brain that receives
CC sound information. {ECO:0000269|PubMed:25807530}. Note=The disease may
CC be caused by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC {ECO:0000305}.
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DR EMBL; AP003086; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003110; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW75061.1; -; Genomic_DNA.
DR EMBL; BC007800; AAH07800.2; -; mRNA.
DR CCDS; CCDS58164.1; -. [Q96I59-2]
DR CCDS; CCDS8261.1; -. [Q96I59-1]
DR RefSeq; NP_001230180.1; NM_001243251.1. [Q96I59-2]
DR RefSeq; NP_078954.4; NM_024678.5. [Q96I59-1]
DR RefSeq; XP_016873792.1; XM_017018303.1. [Q96I59-2]
DR AlphaFoldDB; Q96I59; -.
DR SMR; Q96I59; -.
DR BioGRID; 122846; 74.
DR IntAct; Q96I59; 35.
DR STRING; 9606.ENSP00000281038; -.
DR DrugBank; DB00174; Asparagine.
DR iPTMnet; Q96I59; -.
DR PhosphoSitePlus; Q96I59; -.
DR BioMuta; NARS2; -.
DR DMDM; 296452944; -.
DR EPD; Q96I59; -.
DR jPOST; Q96I59; -.
DR MassIVE; Q96I59; -.
DR MaxQB; Q96I59; -.
DR PaxDb; Q96I59; -.
DR PeptideAtlas; Q96I59; -.
DR PRIDE; Q96I59; -.
DR ProteomicsDB; 32283; -.
DR ProteomicsDB; 76813; -. [Q96I59-1]
DR Antibodypedia; 17519; 191 antibodies from 26 providers.
DR DNASU; 79731; -.
DR Ensembl; ENST00000281038.10; ENSP00000281038.5; ENSG00000137513.10. [Q96I59-1]
DR Ensembl; ENST00000528850.5; ENSP00000432635.1; ENSG00000137513.10. [Q96I59-2]
DR GeneID; 79731; -.
DR KEGG; hsa:79731; -.
DR MANE-Select; ENST00000281038.10; ENSP00000281038.5; NM_024678.6; NP_078954.4.
DR UCSC; uc001ozi.3; human. [Q96I59-1]
DR CTD; 79731; -.
DR DisGeNET; 79731; -.
DR GeneCards; NARS2; -.
DR HGNC; HGNC:26274; NARS2.
DR HPA; ENSG00000137513; Low tissue specificity.
DR MalaCards; NARS2; -.
DR MIM; 612803; gene.
DR MIM; 616239; phenotype.
DR MIM; 618434; phenotype.
DR neXtProt; NX_Q96I59; -.
DR OpenTargets; ENSG00000137513; -.
DR Orphanet; 90636; Autosomal recessive non-syndromic sensorineural deafness type DFNB.
DR Orphanet; 444458; Combined oxidative phosphorylation defect type 24.
DR PharmGKB; PA143485554; -.
DR VEuPathDB; HostDB:ENSG00000137513; -.
DR eggNOG; KOG0554; Eukaryota.
DR GeneTree; ENSGT01030000234618; -.
DR HOGENOM; CLU_004553_2_0_1; -.
DR InParanoid; Q96I59; -.
DR OMA; DNMDLAE; -.
DR OrthoDB; 1056670at2759; -.
DR PhylomeDB; Q96I59; -.
DR TreeFam; TF315088; -.
DR BRENDA; 6.1.1.22; 2681.
DR PathwayCommons; Q96I59; -.
DR Reactome; R-HSA-379726; Mitochondrial tRNA aminoacylation.
DR SignaLink; Q96I59; -.
DR BioGRID-ORCS; 79731; 239 hits in 1098 CRISPR screens.
DR ChiTaRS; NARS2; human.
DR GenomeRNAi; 79731; -.
DR Pharos; Q96I59; Tbio.
DR PRO; PR:Q96I59; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q96I59; protein.
DR Bgee; ENSG00000137513; Expressed in secondary oocyte and 200 other tissues.
DR ExpressionAtlas; Q96I59; baseline and differential.
DR Genevisible; Q96I59; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0004816; F:asparagine-tRNA ligase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0006421; P:asparaginyl-tRNA aminoacylation; ISS:UniProtKB.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR HAMAP; MF_00534; Asn_tRNA_synth; 1.
DR InterPro; IPR004364; Aa-tRNA-synt_II.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR004522; Asn-tRNA-ligase.
DR InterPro; IPR002312; Asp/Asn-tRNA-synth_IIb.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR004365; NA-bd_OB_tRNA.
DR Pfam; PF00152; tRNA-synt_2; 1.
DR Pfam; PF01336; tRNA_anti-codon; 1.
DR PRINTS; PR01042; TRNASYNTHASP.
DR SUPFAM; SSF50249; SSF50249; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00457; asnS; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding;
KW Deafness; Disease variant; Leigh syndrome; Ligase; Mitochondrion;
KW Non-syndromic deafness; Nucleotide-binding; Primary mitochondrial disease;
KW Protein biosynthesis; Reference proteome; Transit peptide.
FT TRANSIT 1..14
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 15..477
FT /note="Probable asparagine--tRNA ligase, mitochondrial"
FT /id="PRO_0000250722"
FT MOD_RES 353
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 1..227
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_054120"
FT VARIANT 87
FT /note="N -> T (in dbSNP:rs10501429)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_052636"
FT VARIANT 213
FT /note="V -> F (in DFNB94; probable loss-of-function
FT variant; unable to rescue mitochondrial respiratory chain
FT defects in NARS2 null fibroblasts; does not affect
FT homodimerization; does not affect localization to
FT mitochondrion; dbSNP:rs756725793)"
FT /evidence="ECO:0000269|PubMed:25807530"
FT /id="VAR_073723"
FT VARIANT 214
FT /note="P -> L (in COXPD24; dbSNP:rs730882155)"
FT /evidence="ECO:0000269|PubMed:25629079"
FT /id="VAR_073250"
FT VARIANT 323..477
FT /note="Missing (in COXPD24)"
FT /evidence="ECO:0000269|PubMed:25807530"
FT /id="VAR_082311"
FT VARIANT 381
FT /note="N -> S (in COXPD24; does not form homodimers; does
FT not affect localization to mitochondrion;
FT dbSNP:rs1565216037)"
FT /evidence="ECO:0000269|PubMed:25807530"
FT /id="VAR_073724"
SQ SEQUENCE 477 AA; 54090 MW; 1F4C78E0B6F5500C CRC64;
MLGVRCLLRS VRFCSSAPFP KHKPSAKLSV RDALGAQNAS GERIKIQGWI RSVRSQKEVL
FLHVNDGSSL ESLQVVADSG LDSRELNFGS SVEVQGQLIK SPSKRQNVEL KAEKIKVIGN
CDAKDFPIKY KERHPLEYLR QYPHFRCRTN VLGSILRIRS EATAAIHSFF KDSGFVHIHT
PIITSNDSEG AGELFQLEPS GKLKVPEENF FNVPAFLTVS GQLHLEVMSG AFTQVFTFGP
TFRAENSQSR RHLAEFYMIE AEISFVDSLQ DLMQVIEELF KATTMMVLSK CPEDVELCHK
FIAPGQKDRL EHMLKNNFLI ISYTEAVEIL KQASQNFTFT PEWGADLRTE HEKYLVKHCG
NIPVFVINYP LTLKPFYMRD NEDGPQHTVA AVDLLVPGVG ELFGGGLREE RYHFLEERLA
RSGLTEVYQW YLDLRRFGSV PHGGFGMGFE RYLQCILGVD NIKDVIPFPR FPHSCLL
