ID SYQ_HUMAN Reviewed; 775 AA. AC P47897; B4DWJ2; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 23-FEB-2022, entry version 209. DE RecName: Full=Glutamine--tRNA ligase; DE EC=6.1.1.18 {ECO:0000269|PubMed:24656866, ECO:0000269|PubMed:26869582}; DE AltName: Full=Glutaminyl-tRNA synthetase; DE Short=GlnRS {ECO:0000303|PubMed:25288775, ECO:0000303|PubMed:26869582}; GN Name=QARS1 {ECO:0000312|HGNC:HGNC:9751}; Synonyms=QARS; 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). RC TISSUE=Brain, and Liver; RX PubMed=8078941; DOI=10.1073/pnas.91.18.8670; RA Lamour V., Quevillon S., Diriong S., N'Guyen V.C., Lipinski M., Mirande M.; RT "Evolution of the Glx-tRNA synthetase family: the glutaminyl enzyme as a RT case of horizontal gene transfer."; RL Proc. Natl. Acad. Sci. U.S.A. 91:8670-8674(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Mammary gland; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung, Ovary, and Placenta; 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 [5] RP PROTEIN SEQUENCE OF 2-19; 206-225; 377-391 AND 602-616, CLEAVAGE OF RP INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Hepatoma; RA Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W.; RL Submitted (JUL-2007) to UniProtKB. RN [6] RP SUBCELLULAR LOCATION. RX PubMed=10791971; DOI=10.1083/jcb.149.3.567; RA Ko Y.G., Kang Y.S., Kim E.K., Park S.G., Kim S.; RT "Nucleolar localization of human methionyl-tRNA synthetase and its role in RT ribosomal RNA synthesis."; RL J. Cell Biol. 149:567-574(2000). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=Lymphoblast; RX PubMed=14654843; DOI=10.1038/nature02166; RA Andersen J.S., Wilkinson C.J., Mayor T., Mortensen P., Nigg E.A., Mann M.; RT "Proteomic characterization of the human centrosome by protein correlation RT profiling."; RL Nature 426:570-574(2003). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-70, AND IDENTIFICATION BY RP 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 [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [10] RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY. RX PubMed=19131329; DOI=10.1074/jbc.m809636200; RA Kaminska M., Havrylenko S., Decottignies P., Gillet S., Le Marechal P., RA Negrutskii B., Mirande M.; RT "Dissection of the structural organization of the aminoacyl-tRNA synthetase RT complex."; RL J. Biol. Chem. 284:6053-6060(2009). RN [11] RP SUBCELLULAR LOCATION, AND SUBUNIT. RX PubMed=19289464; DOI=10.1074/jbc.m900480200; RA Kaminska M., Havrylenko S., Decottignies P., Le Marechal P., Negrutskii B., RA Mirande M.; RT "Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the RT Cytoplasm of Human Cells."; RL J. Biol. Chem. 284:13746-13754(2009). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-309, 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 [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 ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [17] RP FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INTERACTION WITH RARS1, RP VARIANTS MSCCA VAL-45; HIS-57; TRP-403 AND TRP-515, AND CHARACTERIZATION OF RP VARIANTS MSCCA VAL-45; HIS-57; TRP-403 AND TRP-515. RX PubMed=24656866; DOI=10.1016/j.ajhg.2014.03.003; RA Zhang X., Ling J., Barcia G., Jing L., Wu J., Barry B.J., Mochida G.H., RA Hill R.S., Weimer J.M., Stein Q., Poduri A., Partlow J.N., Ville D., RA Dulac O., Yu T.W., Lam A.T., Servattalab S., Rodriguez J., Boddaert N., RA Munnich A., Colleaux L., Zon L.I., Soll D., Walsh C.A., Nabbout R.; RT "Mutations in QARS, encoding glutaminyl-tRNA synthetase, cause progressive RT microcephaly, cerebral-cerebellar atrophy, and intractable seizures."; RL Am. J. Hum. Genet. 94:547-558(2014). RN [18] 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 [19] {ECO:0007744|PDB:4R3Z} RP X-RAY CRYSTALLOGRAPHY (4.03 ANGSTROMS) IN COMPLEX WITH RARS1 AND AIMP1. RX PubMed=25288775; DOI=10.1073/pnas.1408836111; RA Fu Y., Kim Y., Jin K.S., Kim H.S., Kim J.H., Wang D., Park M., Jo C.H., RA Kwon N.H., Kim D., Kim M.H., Jeon Y.H., Hwang K.Y., Kim S., Cho Y.; RT "Structure of the ArgRS-GlnRS-AIMP1 complex and its implications for RT mammalian translation."; RL Proc. Natl. Acad. Sci. U.S.A. 111:15084-15089(2014). RN [20] {ECO:0007744|PDB:4YE6, ECO:0007744|PDB:4YE8, ECO:0007744|PDB:4YE9} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF WILD-TYPE AND VARIANTS MSCCA RP VAL-45 AND HIS-57, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, MUTAGENESIS OF RP HIS-175, AND CHARACTERIZATION OF VARIANTS MSCCA VAL-45; HIS-57; TRP-403 AND RP TRP-515. RX PubMed=26869582; DOI=10.1093/nar/gkw082; RA Ognjenovic J., Wu J., Matthies D., Baxa U., Subramaniam S., Ling J., RA Simonovic M.; RT "The crystal structure of human GlnRS provides basis for the development of RT neurological disorders."; RL Nucleic Acids Res. 44:3420-3431(2016). CC -!- FUNCTION: Glutamine--tRNA ligase (PubMed:26869582). Plays a critical CC role in brain development (PubMed:24656866). CC {ECO:0000269|PubMed:24656866, ECO:0000269|PubMed:26869582}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-glutamine + tRNA(Gln) = AMP + diphosphate + L- CC glutaminyl-tRNA(Gln); Xref=Rhea:RHEA:20121, Rhea:RHEA-COMP:9662, CC Rhea:RHEA-COMP:9681, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:58359, ChEBI:CHEBI:78442, ChEBI:CHEBI:78521, CC ChEBI:CHEBI:456215; EC=6.1.1.18; CC Evidence={ECO:0000269|PubMed:24656866}; CC -!- SUBUNIT: Monomer (PubMed:26869582). Part of a multisubunit complex that CC groups tRNA ligases for Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile CC (IARS1), Leu (LARS1), Lys (KARS1), Met (MARS1) the bifunctional ligase CC for Glu and Pro (EPRS1) and the auxiliary subunits AIMP1/p43, AIMP2/p38 CC and EEF1E1/p18 (PubMed:19131329, PubMed:19289464). Interacts with RARS1 CC (PubMed:24656866). Part of a complex composed of RARS1, QARS1 and AIMP1 CC (PubMed:25288775). {ECO:0000269|PubMed:19131329, CC ECO:0000269|PubMed:19289464, ECO:0000269|PubMed:24656866, CC ECO:0000269|PubMed:25288775, ECO:0000269|PubMed:26869582}. CC -!- INTERACTION: CC P47897; P35609: ACTN2; NbExp=3; IntAct=EBI-347462, EBI-77797; CC P47897; Q9BPU9: B9D2; NbExp=3; IntAct=EBI-347462, EBI-6958971; CC P47897; Q96CA5: BIRC7; NbExp=3; IntAct=EBI-347462, EBI-517623; CC P47897; Q13137: CALCOCO2; NbExp=3; IntAct=EBI-347462, EBI-739580; CC P47897; Q9Y2V7: COG6; NbExp=3; IntAct=EBI-347462, EBI-3866319; CC P47897; P56545-3: CTBP2; NbExp=3; IntAct=EBI-347462, EBI-10171902; CC P47897; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-347462, EBI-11988027; CC P47897; P50570: DNM2; NbExp=3; IntAct=EBI-347462, EBI-346547; CC P47897; Q96F86: EDC3; NbExp=3; IntAct=EBI-347462, EBI-997311; CC P47897; Q5JST6: EFHC2; NbExp=3; IntAct=EBI-347462, EBI-2349927; CC P47897; Q96DF8: ESS2; NbExp=3; IntAct=EBI-347462, EBI-3928124; CC P47897; Q3B820: FAM161A; NbExp=3; IntAct=EBI-347462, EBI-719941; CC P47897; Q86UY5: FAM83A; NbExp=3; IntAct=EBI-347462, EBI-1384254; CC P47897; Q86WP2: GPBP1; NbExp=3; IntAct=EBI-347462, EBI-2349758; CC P47897; P28799: GRN; NbExp=3; IntAct=EBI-347462, EBI-747754; CC P47897; O43708: GSTZ1; NbExp=3; IntAct=EBI-347462, EBI-748043; CC P47897; Q9BYE0: HES7; NbExp=3; IntAct=EBI-347462, EBI-12163087; CC P47897; Q9NP66: HMG20A; NbExp=3; IntAct=EBI-347462, EBI-740641; CC P47897; P49639: HOXA1; NbExp=3; IntAct=EBI-347462, EBI-740785; CC P47897; P04792: HSPB1; NbExp=3; IntAct=EBI-347462, EBI-352682; CC P47897; P42858: HTT; NbExp=6; IntAct=EBI-347462, EBI-466029; CC P47897; Q13123: IK; NbExp=3; IntAct=EBI-347462, EBI-713456; CC P47897; Q13422-7: IKZF1; NbExp=3; IntAct=EBI-347462, EBI-11522367; CC P47897; O60333-2: KIF1B; NbExp=3; IntAct=EBI-347462, EBI-10975473; CC P47897; Q6P597: KLC3; NbExp=3; IntAct=EBI-347462, EBI-1643885; CC P47897; O76013-2: KRT36; NbExp=3; IntAct=EBI-347462, EBI-11958506; CC P47897; Q3B8N2: LGALS9B; NbExp=3; IntAct=EBI-347462, EBI-10240775; CC P47897; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-347462, EBI-9088829; CC P47897; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-347462, EBI-739832; CC P47897; Q9Y250: LZTS1; NbExp=3; IntAct=EBI-347462, EBI-1216080; CC P47897; Q9BRK4: LZTS2; NbExp=6; IntAct=EBI-347462, EBI-741037; CC P47897; P59942: MCCD1; NbExp=3; IntAct=EBI-347462, EBI-11987923; CC P47897; Q14696: MESD; NbExp=3; IntAct=EBI-347462, EBI-6165891; CC P47897; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-347462, EBI-10172526; CC P47897; Q15742: NAB2; NbExp=3; IntAct=EBI-347462, EBI-8641936; CC P47897; O76041: NEBL; NbExp=3; IntAct=EBI-347462, EBI-2880203; CC P47897; Q8NI38: NFKBID; NbExp=3; IntAct=EBI-347462, EBI-10271199; CC P47897; Q86UR1-2: NOXA1; NbExp=3; IntAct=EBI-347462, EBI-12025760; CC P47897; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-347462, EBI-79165; CC P47897; Q7Z5V6-2: PPP1R32; NbExp=3; IntAct=EBI-347462, EBI-12000762; CC P47897; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-347462, EBI-11320284; CC P47897; Q16825: PTPN21; NbExp=3; IntAct=EBI-347462, EBI-2860264; CC P47897; Q04864-2: REL; NbExp=3; IntAct=EBI-347462, EBI-10829018; CC P47897; Q9Y3C5: RNF11; NbExp=10; IntAct=EBI-347462, EBI-396669; CC P47897; Q15427: SF3B4; NbExp=3; IntAct=EBI-347462, EBI-348469; CC P47897; Q8IYI0: SHLD1; NbExp=3; IntAct=EBI-347462, EBI-2560428; CC P47897; Q13239-3: SLA; NbExp=3; IntAct=EBI-347462, EBI-17630587; CC P47897; O60504: SORBS3; NbExp=3; IntAct=EBI-347462, EBI-741237; CC P47897; Q8TDD2: SP7; NbExp=5; IntAct=EBI-347462, EBI-10713842; CC P47897; Q9H0A9-2: SPATC1L; NbExp=3; IntAct=EBI-347462, EBI-11995806; CC P47897; A6NLX3: SPDYE4; NbExp=3; IntAct=EBI-347462, EBI-12047907; CC P47897; Q7Z698: SPRED2; NbExp=3; IntAct=EBI-347462, EBI-7082156; CC P47897; O75478: TADA2A; NbExp=3; IntAct=EBI-347462, EBI-742268; CC P47897; Q99081: TCF12; NbExp=4; IntAct=EBI-347462, EBI-722877; CC P47897; Q96PF1: TGM7; NbExp=3; IntAct=EBI-347462, EBI-12029034; CC P47897; Q08117: TLE5; NbExp=3; IntAct=EBI-347462, EBI-717810; CC P47897; Q12933: TRAF2; NbExp=3; IntAct=EBI-347462, EBI-355744; CC P47897; Q9BUZ4: TRAF4; NbExp=6; IntAct=EBI-347462, EBI-3650647; CC P47897; P14373: TRIM27; NbExp=3; IntAct=EBI-347462, EBI-719493; CC P47897; Q9UPQ4-2: TRIM35; NbExp=4; IntAct=EBI-347462, EBI-17716262; CC P47897; Q15645: TRIP13; NbExp=6; IntAct=EBI-347462, EBI-358993; CC P47897; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-347462, EBI-739895; CC P47897; Q9H9H4: VPS37B; NbExp=3; IntAct=EBI-347462, EBI-4400866; CC P47897; O76024: WFS1; NbExp=3; IntAct=EBI-347462, EBI-720609; CC P47897; P98170: XIAP; NbExp=3; IntAct=EBI-347462, EBI-517127; CC P47897; Q9H0C1: ZMYND12; NbExp=5; IntAct=EBI-347462, EBI-12030590; CC P47897; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-347462, EBI-527853; CC P47897-2; Q86UW9: DTX2; NbExp=3; IntAct=EBI-10209725, EBI-740376; CC P47897-2; Q6P597: KLC3; NbExp=3; IntAct=EBI-10209725, EBI-1643885; CC P47897-2; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-10209725, EBI-741037; CC P47897-2; Q99081: TCF12; NbExp=3; IntAct=EBI-10209725, EBI-722877; CC P47897-2; Q08117: TLE5; NbExp=3; IntAct=EBI-10209725, EBI-717810; CC P47897-2; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-10209725, EBI-3650647; CC P47897-2; Q15645: TRIP13; NbExp=3; IntAct=EBI-10209725, EBI-358993; CC P47897-2; Q9H9H4: VPS37B; NbExp=3; IntAct=EBI-10209725, EBI-4400866; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:19289464}. CC Cytoplasm {ECO:0000269|PubMed:10791971, ECO:0000269|PubMed:24656866}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P47897-1; Sequence=Displayed; CC Name=2; CC IsoId=P47897-2; Sequence=VSP_055107; CC -!- TISSUE SPECIFICITY: Highly expressed in fetal cerebral cortex, CC particularly in the ventricular zone, inner subventricular zone, outer CC subventricular zone, and cortical plate. {ECO:0000269|PubMed:24656866}. CC -!- DISEASE: Microcephaly, progressive, with seizures and cerebral and CC cerebellar atrophy (MSCCA) [MIM:615760]: A severe, autosomal recessive, CC neurodevelopmental and neurodegenerative disorder characterized by CC progressive microcephaly, severe seizures in infancy, atrophy of the CC cerebral cortex and cerebellar vermis, and mild atrophy of the CC cerebellar hemispheres, resulting in profoundly delayed development and CC hypotonia. {ECO:0000269|PubMed:24656866, ECO:0000269|PubMed:26869582}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; X76013; CAA53600.1; -; mRNA. DR EMBL; AK301559; BAG63054.1; -; mRNA. DR EMBL; AC135506; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000394; AAH00394.1; -; mRNA. DR EMBL; BC001567; AAH01567.1; -; mRNA. DR EMBL; BC029739; AAH29739.1; -; mRNA. DR CCDS; CCDS2788.1; -. [P47897-1] DR CCDS; CCDS63633.1; -. [P47897-2] DR PIR; I37422; I37422. DR RefSeq; NP_001259002.1; NM_001272073.1. [P47897-2] DR RefSeq; NP_005042.1; NM_005051.2. [P47897-1] DR PDB; 4R3Z; X-ray; 4.03 A; C=1-775. DR PDB; 4YE6; X-ray; 2.40 A; A=1-775. DR PDB; 4YE8; X-ray; 3.30 A; A=1-775. DR PDB; 4YE9; X-ray; 2.70 A; A=1-775. DR PDBsum; 4R3Z; -. DR PDBsum; 4YE6; -. DR PDBsum; 4YE8; -. DR PDBsum; 4YE9; -. DR SMR; P47897; -. DR BioGRID; 111797; 311. DR CORUM; P47897; -. DR IntAct; P47897; 139. DR MINT; P47897; -. DR STRING; 9606.ENSP00000307567; -. DR BindingDB; P47897; -. DR ChEMBL; CHEMBL3054; -. DR DrugBank; DB00130; L-Glutamine. DR MoonProt; P47897; -. DR GlyGen; P47897; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P47897; -. DR MetOSite; P47897; -. DR PhosphoSitePlus; P47897; -. DR SwissPalm; P47897; -. DR BioMuta; QARS; -. DR DMDM; 1351170; -. DR CPTAC; CPTAC-123; -. DR CPTAC; CPTAC-124; -. DR EPD; P47897; -. DR jPOST; P47897; -. DR MassIVE; P47897; -. DR MaxQB; P47897; -. DR PaxDb; P47897; -. DR PeptideAtlas; P47897; -. DR PRIDE; P47897; -. DR ProteomicsDB; 5345; -. DR ProteomicsDB; 55816; -. [P47897-1] DR Antibodypedia; 30393; 144 antibodies from 26 providers. DR DNASU; 5859; -. DR Ensembl; ENST00000306125; ENSP00000307567; ENSG00000172053. DR Ensembl; ENST00000414533; ENSP00000390015; ENSG00000172053. [P47897-2] DR GeneID; 5859; -. DR KEGG; hsa:5859; -. DR MANE-Select; ENST00000306125.12; ENSP00000307567.6; NM_005051.3; NP_005042.1. DR UCSC; uc003cvx.5; human. [P47897-1] DR CTD; 5859; -. DR DisGeNET; 5859; -. DR GeneCards; QARS1; -. DR HGNC; HGNC:9751; QARS1. DR HPA; ENSG00000172053; Low tissue specificity. DR MalaCards; QARS1; -. DR MIM; 603727; gene. DR MIM; 615760; phenotype. DR neXtProt; NX_P47897; -. DR OpenTargets; ENSG00000172053; -. DR Orphanet; 404437; Diffuse cerebral and cerebellar atrophy-intractable seizures-progressive microcephaly syndrome. DR Orphanet; 423306; Microcephaly-short stature-intellectual disability-facial dysmorphism syndrome. DR PharmGKB; PA34093; -. DR VEuPathDB; HostDB:ENSG00000172053; -. DR eggNOG; KOG1148; Eukaryota. DR GeneTree; ENSGT00550000074972; -. DR HOGENOM; CLU_001882_2_3_1; -. DR InParanoid; P47897; -. DR OMA; INNFCAQ; -. DR PhylomeDB; P47897; -. DR TreeFam; TF105683; -. DR BRENDA; 6.1.1.18; 2681. DR PathwayCommons; P47897; -. DR Reactome; R-HSA-2408522; Selenoamino acid metabolism. DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation. DR Reactome; R-HSA-379726; Mitochondrial tRNA aminoacylation. DR SignaLink; P47897; -. DR BioGRID-ORCS; 5859; 795 hits in 1052 CRISPR screens. DR ChiTaRS; QARS; human. DR GeneWiki; QARS; -. DR GenomeRNAi; 5859; -. DR Pharos; P47897; Tchem. DR PRO; PR:P47897; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P47897; protein. DR Bgee; ENSG00000172053; Expressed in left lobe of thyroid gland and 247 other tissues. DR ExpressionAtlas; P47897; baseline and differential. DR Genevisible; P47897; HS. DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0032991; C:protein-containing complex; IMP:CAFA. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004819; F:glutamine-tRNA ligase activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:CAFA. DR GO; GO:0004860; F:protein kinase inhibitor activity; IMP:CAFA. DR GO; GO:0007420; P:brain development; IMP:UniProtKB. DR GO; GO:0006425; P:glutaminyl-tRNA aminoacylation; IDA:UniProtKB. DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IDA:CAFA. DR GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:CAFA. DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; IDA:CAFA. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:CAFA. DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome. DR Gene3D; 1.10.10.2420; -; 1. DR Gene3D; 1.10.8.1290; -; 1. DR Gene3D; 2.40.240.10; -; 2. DR Gene3D; 3.40.50.620; -; 1. DR InterPro; IPR001412; aa-tRNA-synth_I_CS. DR InterPro; IPR004514; Gln-tRNA-synth. DR InterPro; IPR007638; Gln-tRNA-synth_Ib_RNA-bd_2. DR InterPro; IPR007639; Gln-tRNA-synth_Ib_RNA-bd_N. DR InterPro; IPR042558; Gln-tRNA-synth_Ib_RNA-bd_N_1. DR InterPro; IPR042559; Gln-tRNA-synth_Ib_RNA-bd_N_2. DR InterPro; IPR000924; Glu/Gln-tRNA-synth. DR InterPro; IPR020058; Glu/Gln-tRNA-synth_Ib_cat-dom. DR InterPro; IPR020059; Glu/Gln-tRNA-synth_Ib_codon-bd. DR InterPro; IPR020056; Rbsml_L25/Gln-tRNA_synth_N. DR InterPro; IPR011035; Ribosomal_L25/Gln-tRNA_synth. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR Pfam; PF00749; tRNA-synt_1c; 1. DR Pfam; PF03950; tRNA-synt_1c_C; 1. DR Pfam; PF04558; tRNA_synt_1c_R1; 1. DR Pfam; PF04557; tRNA_synt_1c_R2; 1. DR PRINTS; PR00987; TRNASYNTHGLU. DR SUPFAM; SSF50715; SSF50715; 1. DR TIGRFAMs; TIGR00440; glnS; 1. DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 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; Ligase; Nucleotide-binding; Phosphoprotein; Primary microcephaly; KW Protein biosynthesis; Reference proteome. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..775 FT /note="Glutamine--tRNA ligase" FT /id="PRO_0000195860" FT NP_BIND 271..273 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P00962" FT NP_BIND 277..283 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P00962" FT NP_BIND 486..487 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P00962" FT NP_BIND 494..496 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P00962" FT MOTIF 270..280 FT /note="'HIGH' region" FT /evidence="ECO:0000305|PubMed:26869582" FT MOTIF 493..497 FT /note="'KMSKS' region" FT /evidence="ECO:0000305|PubMed:26869582" FT BINDING 303 FT /note="L-glutamine" FT /evidence="ECO:0000250|UniProtKB:P00962" FT BINDING 438 FT /note="L-glutamine" FT /evidence="ECO:0000250|UniProtKB:P00962" FT BINDING 457 FT /note="ATP" FT /evidence="ECO:0000250|UniProtKB:P00962" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000269|Ref.5, ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 70 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 309 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 495 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 78..89 FT /note="SKKIHTEPQLSA -> T (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055107" FT VARIANT 45 FT /note="G -> V (in MSCCA; results in reduced glutaminyl-tRNA FT aminoacylation activity; does not affect interaction with FT RARS1; dbSNP:rs587777331)" FT /evidence="ECO:0000269|PubMed:24656866, FT ECO:0000269|PubMed:26869582" FT /id="VAR_071189" FT VARIANT 57 FT /note="Y -> H (in MSCCA; results in reduced glutaminyl-tRNA FT aminoacylation activity; does not affect interaction with FT RARS1; dbSNP:rs587777333)" FT /evidence="ECO:0000269|PubMed:24656866, FT ECO:0000269|PubMed:26869582" FT /id="VAR_071190" FT VARIANT 403 FT /note="R -> W (in MSCCA; results in loss of glutaminyl-tRNA FT aminoacylation activity; impairs protein folding; does not FT interact with RARS1; results in reduced protein solubility; FT dbSNP:rs587777332)" FT /evidence="ECO:0000269|PubMed:24656866, FT ECO:0000269|PubMed:26869582" FT /id="VAR_071191" FT VARIANT 515 FT /note="R -> W (in MSCCA; results in loss of glutaminyl-tRNA FT aminoacylation activity; impairs protein folding; results FT in reduced protein solubility; dbSNP:rs587777334)" FT /evidence="ECO:0000269|PubMed:24656866, FT ECO:0000269|PubMed:26869582" FT /id="VAR_071192" FT MUTAGEN 175 FT /note="H->A: Decreases catalytic efficiency about 60-fold." FT /evidence="ECO:0000269|PubMed:26869582" FT HELIX 6..12 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 17..25 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 27..42 FT /evidence="ECO:0007829|PDB:4YE6" FT TURN 43..45 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 50..62 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 66..68 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 69..77 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 84..94 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 104..110 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 119..140 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 141..143 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 147..154 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 162..177 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 220..223 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 226..229 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 237..239 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 249..260 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 265..268 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 278..293 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 297..302 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 312..324 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 330..334 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 335..338 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 339..351 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 354..358 FT /evidence="ECO:0007829|PDB:4YE6" FT TURN 374..377 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 380..391 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 401..404 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 416..420 FT /evidence="ECO:0007829|PDB:4YE6" FT TURN 426..428 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 433..436 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 438..448 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 452..457 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 464..473 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 480..484 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 487..489 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 496..504 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 507..510 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 519..524 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 529..539 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 546..548 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 551..564 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 570..576 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 578..581 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 592..594 FT /evidence="ECO:0007829|PDB:4YE6" FT HELIX 599..601 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 603..606 FT /evidence="ECO:0007829|PDB:4YE9" FT STRAND 613..615 FT /evidence="ECO:0007829|PDB:4YE6" FT TURN 616..618 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 647..650 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 654..656 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 661..663 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 681..683 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 685..692 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 695..700 FT /evidence="ECO:0007829|PDB:4YE6" FT TURN 702..705 FT /evidence="ECO:0007829|PDB:4YE6" FT TURN 711..714 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 720..722 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 725..728 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 732..734 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 740..743 FT /evidence="ECO:0007829|PDB:4YE6" FT TURN 744..746 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 747..751 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 757..759 FT /evidence="ECO:0007829|PDB:4YE6" FT STRAND 761..766 FT /evidence="ECO:0007829|PDB:4YE6" SQ SEQUENCE 775 AA; 87799 MW; ADDE23E6C442FF73 CRC64; MAALDSLSLF TSLGLSEQKA RETLKNSALS AQLREAATQA QQTLGSTIDK ATGILLYGLA SRLRDTRRLS FLVSYIASKK IHTEPQLSAA LEYVRSHPLD PIDTVDFERE CGVGVIVTPE QIEEAVEAAI NRHRPQLLVE RYHFNMGLLM GEARAVLKWA DGKMIKNEVD MQVLHLLGPK LEADLEKKFK VAKARLEETD RRTAKDVVEN GETADQTLSL MEQLRGEALK FHKPGENYKT PGYVVTPHTM NLLKQHLEIT GGQVRTRFPP EPNGILHIGH AKAINFNFGY AKANNGICFL RFDDTNPEKE EAKFFTAICD MVAWLGYTPY KVTYASDYFD QLYAWAVELI RRGLAYVCHQ RGEELKGHNT LPSPWRDRPM EESLLLFEAM RKGKFSEGEA TLRMKLVMED GKMDPVAYRV KYTPHHRTGD KWCIYPTYDY THCLCDSIEH ITHSLCTKEF QARRSSYFWL CNALDVYCPV QWEYGRLNLH YAVVSKRKIL QLVATGAVRD WDDPRLFTLT ALRRRGFPPE AINNFCARVG VTVAQTTMEP HLLEACVRDV LNDTAPRAMA VLESLRVIIT NFPAAKSLDI QVPNFPADET KGFHQVPFAP IVFIERTDFK EEPEPGFKRL AWGQPVGLRH TGYVIELQHV VKGPSGCVES LEVTCRRADA GEKPKAFIHW VSQPLMCEVR LYERLFQHKN PEDPTEVPGG FLSDLNLASL HVVDAALVDC SVALAKPFDK FQFERLGYFS VDPDSHQGKL VFNRTVTLKE DPGKV //