SYNC_HUMAN
ID SYNC_HUMAN Reviewed; 548 AA.
AC O43776; B4DG16; Q53GU6;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Asparagine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.22 {ECO:0000269|PubMed:32738225, ECO:0000269|PubMed:32788587, ECO:0000269|PubMed:9421509};
DE AltName: Full=Asparaginyl-tRNA synthetase;
DE Short=AsnRS;
DE AltName: Full=Asparaginyl-tRNA synthetase 1 {ECO:0000312|HGNC:HGNC:7643};
GN Name=NARS1 {ECO:0000312|HGNC:HGNC:7643};
GN Synonyms=NARS, NRS {ECO:0000303|PubMed:30171954};
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 [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, CATALYTIC
RP ACTIVITY, AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=9421509; DOI=10.1093/nar/26.2.521;
RA Beaulande M., Tarbouriech N., Haertlein M.;
RT "Human cytosolic asparaginyl-tRNA synthetase: cDNA sequence, functional
RT expression in Escherichia coli and characterization as human autoantigen.";
RL Nucleic Acids Res. 26:521-524(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9801298; DOI=10.1093/nar/26.22.5045;
RA Shiba K., Motegi H., Yoshida M., Noda T.;
RT "Human asparaginyl-tRNA synthetase: molecular cloning and the inference of
RT the evolutionary history of Asx-tRNA synthetase family.";
RL Nucleic Acids Res. 26:5045-5051(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [7]
RP AUTOANTIBODIES.
RX PubMed=9973509;
RA Hirakata M., Suwa A., Nagai S., Kron M.A., Trieu E.P., Mimori T.,
RA Akizuki M., Targoff I.N.;
RT "Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA
RT synthetase associated with interstitial lung disease.";
RL J. Immunol. 162:2315-2320(1999).
RN [8]
RP FUNCTION.
RX PubMed=12235211; DOI=10.1084/jem.20020186;
RA Howard O.M., Dong H.F., Yang D., Raben N., Nagaraju K., Rosen A.,
RA Casciola-Rosen L., Haertlein M., Kron M., Yang D., Yiadom K., Dwivedi S.,
RA Plotz P.H., Oppenheim J.J.;
RT "Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in
RT myositis, activate chemokine receptors on T lymphocytes and immature
RT dendritic cells.";
RL J. Exp. Med. 196:781-791(2002).
RN [9]
RP PROTEIN SEQUENCE [LARGE SCALE ANALYSIS] OF 2-12.
RC TISSUE=Leukemic T-cell;
RX PubMed=19892738; DOI=10.1073/pnas.0908958106;
RA Xu G., Shin S.B., Jaffrey S.R.;
RT "Global profiling of protease cleavage sites by chemoselective labeling of
RT protein N-termini.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:19310-19315(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-244, 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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
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 [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-61, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
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 [17]
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).
RN [18] {ECO:0007744|PDB:4ZYA, ECO:0007744|PDB:5XIX}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 4-77 AND 98-548, SUBUNIT,
RP FUNCTION, SUBCELLULAR LOCATION, LIGAND-BINDING, AND DOMAIN.
RX PubMed=30171954; DOI=10.1016/j.ijbiomac.2018.08.171;
RA Park J.S., Park M.C., Lee K.Y., Goughnour P.C., Jeong S.J., Kim H.S.,
RA Kim H.J., Lee B.J., Kim S., Han B.W.;
RT "Unique N-terminal extension domain of human asparaginyl-tRNA synthetase
RT elicits CCR3-mediated chemokine activity.";
RL Int. J. Biol. Macromol. 120:835-845(2018).
RN [19]
RP VARIANTS NEDMILG PRO-11; MET-17; GLU-60; 90-ARG--PRO-548 DEL; CYS-132;
RP PRO-350; ALA-356; THR-422; ILE-459 AND CYS-545, VARIANTS NEDMILEG LEU-322;
RP SER-509 AND 534-ARG--PRO-548 DEL, INVOLVEMENT IN NEDMILG, INVOLVEMENT IN
RP NEDMILEG, CHARACTERIZATION OF VARIANT NEDMILG PRO-11, CHARACTERIZATION OF
RP VARIANTS NEDMILEG LEU-322 AND 534-ARG--PRO-548 DEL, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=32738225; DOI=10.1016/j.ajhg.2020.06.016;
RG SYNAPS Study Group;
RA Manole A., Efthymiou S., O'Connor E., Mendes M.I., Jennings M.,
RA Maroofian R., Davagnanam I., Mankad K., Lopez M.R., Salpietro V.,
RA Harripaul R., Badalato L., Walia J., Francklyn C.S.,
RA Athanasiou-Fragkouli A., Sullivan R., Desai S., Baranano K., Zafar F.,
RA Rana N., Ilyas M., Horga A., Kara M., Mattioli F., Goldenberg A.,
RA Griffin H., Piton A., Henderson L.B., Kara B., Aslanger A.D., Raaphorst J.,
RA Pfundt R., Portier R., Shinawi M., Kirby A., Christensen K.M., Wang L.,
RA Rosti R.O., Paracha S.A., Sarwar M.T., Jenkins D., Ahmed J., Santoni F.A.,
RA Ranza E., Iwaszkiewicz J., Cytrynbaum C., Weksberg R., Wentzensen I.M.,
RA Guillen Sacoto M.J., Si Y., Telegrafi A., Andrews M.V., Baldridge D.,
RA Gabriel H., Mohr J., Oehl-Jaschkowitz B., Debard S., Senger B., Fischer F.,
RA van Ravenwaaij C., Fock A.J.M., Stevens S.J.C., Baehler J., Nasar A.,
RA Mantovani J.F., Manzur A., Sarkozy A., Smith D.E.C., Salomons G.S.,
RA Ahmed Z.M., Riazuddin S., Riazuddin S., Usmani M.A., Seibt A., Ansar M.,
RA Antonarakis S.E., Vincent J.B., Ayub M., Grimmel M., Jelsig A.M.,
RA Hjortshoej T.D., Karstensen H.G., Hummel M., Haack T.B., Jamshidi Y.,
RA Distelmaier F., Horvath R., Gleeson J.G., Becker H., Mandel J.L.,
RA Koolen D.A., Houlden H.;
RT "De novo and bi-allelic pathogenic variants in NARS1 cause
RT neurodevelopmental delay due to toxic gain-of-function and partial loss-of-
RT function effects.";
RL Am. J. Hum. Genet. 107:311-324(2020).
RN [20]
RP INVOLVEMENT IN NEDMILG, VARIANTS NEDMILG MET-17; ALA-356 AND CYS-545,
RP CHARACTERIZATION OF VARIANT NEDMILG MET-17, FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=32788587; DOI=10.1038/s41467-020-17454-4;
RA Wang L., Li Z., Sievert D., Smith D.E.C., Mendes M.I., Chen D.Y.,
RA Stanley V., Ghosh S., Wang Y., Kara M., Aslanger A.D., Rosti R.O.,
RA Houlden H., Salomons G.S., Gleeson J.G.;
RT "Loss of NARS1 impairs progenitor proliferation in cortical brain organoids
RT and leads to microcephaly.";
RL Nat. Commun. 11:4038-4038(2020).
RN [21]
RP ERRATUM OF PUBMED:32788587.
RX PubMed=33589599; DOI=10.1038/s41467-021-21448-1;
RA Wang L., Li Z., Sievert D., Smith D.E.C., Mendes M.I., Chen D.Y.,
RA Stanley V., Ghosh S., Wang Y., Kara M., Aslanger A.D., Rosti R.O.,
RA Houlden H., Salomons G.S., Gleeson J.G.;
RL Nat. Commun. 12:1192-1192(2021).
CC -!- FUNCTION: Catalyzes the attachment of asparagine to tRNA(Asn) in a two-
CC step reaction: asparagine is first activated by ATP to form Asn-AMP and
CC then transferred to the acceptor end of tRNA(Asn) (PubMed:9421509,
CC PubMed:32738225, PubMed:32788587). In addition to its essential role in
CC protein synthesis, acts as a signaling molecule that induced migration
CC of CCR3-expressing cells (PubMed:30171954, PubMed:12235211). Has an
CC essential role in the development of the cerebral cortex, being
CC required for proper proliferation of radial glial cells
CC (PubMed:32788587). {ECO:0000269|PubMed:12235211,
CC ECO:0000269|PubMed:30171954, ECO:0000269|PubMed:32738225,
CC ECO:0000269|PubMed:32788587, ECO:0000269|PubMed:9421509}.
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 Evidence={ECO:0000269|PubMed:32738225, ECO:0000269|PubMed:32788587,
CC ECO:0000269|PubMed:9421509};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:30171954}.
CC -!- INTERACTION:
CC O43776; P54253: ATXN1; NbExp=4; IntAct=EBI-373505, EBI-930964;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305|PubMed:9421509}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O43776-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O43776-2; Sequence=VSP_056201, VSP_056202;
CC -!- DOMAIN: The N-terminal domain (1-77) recruits and activates specific
CC immune cells by interacting with CCR3-expressing cells.
CC {ECO:0000269|PubMed:30171954}.
CC -!- DISEASE: Neurodevelopmental disorder with microcephaly, impaired
CC language, and gait abnormalities (NEDMILG) [MIM:619091]: An autosomal
CC recessive neurodevelopmental disorder characterized by global
CC developmental delay apparent in infancy, moderate to profound
CC intellectual disability, poor or absent speech and language, delayed
CC walking with variable gait abnormalities, and progressive microcephaly.
CC Additional variable features include hypotonia, early-onset seizures,
CC and a peripheral demyelinating or axonal peripheral sensorimotor
CC neuropathy. {ECO:0000269|PubMed:32738225, ECO:0000269|PubMed:32788587}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Neurodevelopmental disorder with microcephaly, impaired
CC language, epilepsy, and gait abnormalities (NEDMILEG) [MIM:619092]: An
CC autosomal dominant neurodevelopmental disorder characterized by global
CC developmental delay apparent in infancy, delayed walking, ataxia,
CC spasticity, impaired intellectual development with poor or absent
CC speech and language, progressive microcephaly, and early-onset seizures
CC in most patients. Facial dysmorphism and a demyelinating peripheral
CC neuropathy may also be observed. {ECO:0000269|PubMed:32738225}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- MISCELLANEOUS: Autoantibodies to NARS1, are often detected in sera from
CC patients with interstitial lung disease (ILD).
CC {ECO:0000269|PubMed:9973509}.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC {ECO:0000305}.
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DR EMBL; AJ000334; CAA04008.1; -; mRNA.
DR EMBL; D84273; BAA34600.1; -; mRNA.
DR EMBL; AK294364; BAG57627.1; -; mRNA.
DR EMBL; AC100847; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK222835; BAD96555.1; -; mRNA.
DR EMBL; BC001687; AAH01687.1; -; mRNA.
DR CCDS; CCDS32837.1; -. [O43776-1]
DR RefSeq; NP_004530.1; NM_004539.3. [O43776-1]
DR PDB; 4ZYA; X-ray; 1.65 A; A/B=4-77.
DR PDB; 5XIX; X-ray; 2.25 A; A/B/C/D=98-548.
DR PDBsum; 4ZYA; -.
DR PDBsum; 5XIX; -.
DR AlphaFoldDB; O43776; -.
DR SMR; O43776; -.
DR BioGRID; 110758; 117.
DR IntAct; O43776; 30.
DR MINT; O43776; -.
DR STRING; 9606.ENSP00000256854; -.
DR DrugBank; DB00174; Asparagine.
DR GlyGen; O43776; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O43776; -.
DR MetOSite; O43776; -.
DR PhosphoSitePlus; O43776; -.
DR SwissPalm; O43776; -.
DR BioMuta; NARS; -.
DR EPD; O43776; -.
DR jPOST; O43776; -.
DR MassIVE; O43776; -.
DR MaxQB; O43776; -.
DR PaxDb; O43776; -.
DR PeptideAtlas; O43776; -.
DR PRIDE; O43776; -.
DR ProteomicsDB; 4098; -.
DR ProteomicsDB; 49167; -. [O43776-1]
DR ABCD; O43776; 3 sequenced antibodies.
DR Antibodypedia; 9706; 197 antibodies from 29 providers.
DR DNASU; 4677; -.
DR Ensembl; ENST00000256854.10; ENSP00000256854.4; ENSG00000134440.12. [O43776-1]
DR Ensembl; ENST00000540592.5; ENSP00000442496.1; ENSG00000134440.12. [O43776-2]
DR GeneID; 4677; -.
DR KEGG; hsa:4677; -.
DR MANE-Select; ENST00000256854.10; ENSP00000256854.4; NM_004539.4; NP_004530.1.
DR UCSC; uc002lgs.4; human. [O43776-1]
DR CTD; 4677; -.
DR DisGeNET; 4677; -.
DR GeneCards; NARS1; -.
DR HGNC; HGNC:7643; NARS1.
DR HPA; ENSG00000134440; Low tissue specificity.
DR MalaCards; NARS1; -.
DR MIM; 108410; gene.
DR MIM; 619091; phenotype.
DR MIM; 619092; phenotype.
DR neXtProt; NX_O43776; -.
DR OpenTargets; ENSG00000134440; -.
DR PharmGKB; PA31447; -.
DR VEuPathDB; HostDB:ENSG00000134440; -.
DR eggNOG; KOG0555; Eukaryota.
DR GeneTree; ENSGT01030000234618; -.
DR HOGENOM; CLU_004553_2_10_1; -.
DR InParanoid; O43776; -.
DR OMA; CKQHTVR; -.
DR OrthoDB; 1056670at2759; -.
DR PhylomeDB; O43776; -.
DR TreeFam; TF105664; -.
DR BRENDA; 6.1.1.22; 2681.
DR PathwayCommons; O43776; -.
DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR SignaLink; O43776; -.
DR BioGRID-ORCS; 4677; 808 hits in 1051 CRISPR screens.
DR ChiTaRS; NARS; human.
DR GeneWiki; NARS_(gene); -.
DR GenomeRNAi; 4677; -.
DR Pharos; O43776; Tbio.
DR PRO; PR:O43776; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; O43776; protein.
DR Bgee; ENSG00000134440; Expressed in endothelial cell and 207 other tissues.
DR ExpressionAtlas; O43776; baseline and differential.
DR Genevisible; O43776; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0004816; F:asparagine-tRNA ligase activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0031728; F:CCR3 chemokine receptor binding; IDA:UniProtKB.
DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
DR GO; GO:0046983; F:protein dimerization activity; IDA:UniProtKB.
DR GO; GO:0006421; P:asparaginyl-tRNA aminoacylation; IDA:UniProtKB.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0021987; P:cerebral cortex development; IMP:UniProtKB.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR Gene3D; 2.40.50.140; -; 1.
DR Gene3D; 3.30.930.10; -; 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 3D-structure; Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase;
KW ATP-binding; Cytoplasm; Direct protein sequencing; Disease variant;
KW Epilepsy; Intellectual disability; Ligase; Neurodegeneration;
KW Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW Reference proteome.
FT CHAIN 1..548
FT /note="Asparagine--tRNA ligase, cytoplasmic"
FT /id="PRO_0000176496"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 69..91
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 61
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 244
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 482
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BP47"
FT MOD_RES 490
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BP47"
FT VAR_SEQ 141..173
FT /note="GKNLMFLVLRDGTGYLQCVLADELCQCYNGVLL -> VSVLQWSSLVHGEQC
FT CSVWNAKSYPKGQAGSRW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056201"
FT VAR_SEQ 174..547
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056202"
FT VARIANT 11
FT /note="R -> P (in NEDMILG; unknown pathological
FT significance; decreased protein levels in patient cells;
FT dbSNP:rs771435243)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085100"
FT VARIANT 17
FT /note="T -> M (in NEDMILG; decreased protein levels in
FT patient cells; decreased asparagine-tRNA ligase activity in
FT patient cells; dbSNP:rs148893823)"
FT /evidence="ECO:0000269|PubMed:32738225,
FT ECO:0000269|PubMed:32788587"
FT /id="VAR_085101"
FT VARIANT 60
FT /note="K -> E (in NEDMILG; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085102"
FT VARIANT 90..548
FT /note="Missing (in NEDMILG)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085103"
FT VARIANT 132
FT /note="G -> C (in NEDMILG; unknown pathological
FT significance; dbSNP:rs1402942713)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085104"
FT VARIANT 322
FT /note="R -> L (in NEDMILEG; unable to rescue growth defects
FT in a yeast complementation assay)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085105"
FT VARIANT 350
FT /note="L -> P (in NEDMILG; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085106"
FT VARIANT 356
FT /note="D -> A (in NEDMILG; dbSNP:rs138016359)"
FT /evidence="ECO:0000269|PubMed:32738225,
FT ECO:0000269|PubMed:32788587"
FT /id="VAR_085107"
FT VARIANT 422
FT /note="A -> T (in NEDMILG; unknown pathological
FT significance; dbSNP:rs769070609)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085108"
FT VARIANT 459
FT /note="T -> I (in NEDMILG; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085109"
FT VARIANT 509
FT /note="G -> S (in NEDMILEG; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085110"
FT VARIANT 534..548
FT /note="Missing (in NEDMILEG; decreased asparagine-tRNA
FT ligase activity in patient cells)"
FT /evidence="ECO:0000269|PubMed:32738225"
FT /id="VAR_085111"
FT VARIANT 545
FT /note="R -> C (in NEDMILG; dbSNP:rs770931044)"
FT /evidence="ECO:0000269|PubMed:32738225,
FT ECO:0000269|PubMed:32788587"
FT /id="VAR_085112"
FT CONFLICT 391
FT /note="M -> V (in Ref. 4; BAD96555)"
FT /evidence="ECO:0000305"
FT STRAND 5..8
FT /evidence="ECO:0007829|PDB:4ZYA"
FT TURN 10..12
FT /evidence="ECO:0007829|PDB:4ZYA"
FT TURN 15..17
FT /evidence="ECO:0007829|PDB:4ZYA"
FT STRAND 20..24
FT /evidence="ECO:0007829|PDB:4ZYA"
FT HELIX 29..34
FT /evidence="ECO:0007829|PDB:4ZYA"
FT STRAND 38..40
FT /evidence="ECO:0007829|PDB:4ZYA"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:4ZYA"
FT STRAND 55..57
FT /evidence="ECO:0007829|PDB:4ZYA"
FT HELIX 60..73
FT /evidence="ECO:0007829|PDB:4ZYA"
FT HELIX 117..123
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 126..140
FT /evidence="ECO:0007829|PDB:5XIX"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 144..150
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 155..161
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 163..166
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 168..172
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 178..187
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 198..209
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 226..231
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 233..236
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 240..262
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 272..275
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 286..289
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 292..296
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 301..311
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 312..321
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 333..344
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 347..367
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 371..377
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 389..392
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 393..402
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 421..431
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 435..438
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 455..466
FT /evidence="ECO:0007829|PDB:5XIX"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 470..478
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 482..492
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 497..499
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 500..503
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 504..506
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 513..519
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 520..527
FT /evidence="ECO:0007829|PDB:5XIX"
FT HELIX 533..536
FT /evidence="ECO:0007829|PDB:5XIX"
FT STRAND 537..539
FT /evidence="ECO:0007829|PDB:5XIX"
SQ SEQUENCE 548 AA; 62943 MW; CDD442C4E962CDDB CRC64;
MVLAELYVSD REGSDATGDG TKEKPFKTGL KALMTVGKEP FPTIYVDSQK ENERWNVISK
SQLKNIKKMW HREQMKSESR EKKEAEDSLR REKNLEEAKK ITIKNDPSLP EPKCVKIGAL
EGYRGQRVKV FGWVHRLRRQ GKNLMFLVLR DGTGYLQCVL ADELCQCYNG VLLSTESSVA
VYGMLNLTPK GKQAPGGHEL SCDFWELIGL APAGGADNLI NEESDVDVQL NNRHMMIRGE
NMSKILKARS MVTRCFRDHF FDRGYYEVTP PTLVQTQVEG GATLFKLDYF GEEAFLTQSS
QLYLETCLPA LGDVFCIAQS YRAEQSRTRR HLAEYTHVEA ECPFLTFDDL LNRLEDLVCD
VVDRILKSPA GSIVHELNPN FQPPKRPFKR MNYSDAIVWL KEHDVKKEDG TFYEFGEDIP
EAPERLMTDT INEPILLCRF PVEIKSFYMQ RCPEDSRLTE SVDVLMPNVG EIVGGSMRIF
DSEEILAGYK REGIDPTPYY WYTDQRKYGT CPHGGYGLGL ERFLTWILNR YHIRDVCLYP
RFVQRCTP
