ID SYCC_HUMAN Reviewed; 748 AA. AC P49589; Q53XI8; Q5HYE4; Q9HD24; Q9HD25; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 31-JAN-2002, sequence version 3. DT 28-JUN-2023, entry version 201. DE RecName: Full=Cysteine--tRNA ligase, cytoplasmic; DE EC=6.1.1.16 {ECO:0000269|PubMed:11347887, ECO:0000269|PubMed:30824121}; DE AltName: Full=Cysteinyl-tRNA synthetase; DE Short=CysRS; GN Name=CARS1 {ECO:0000312|HGNC:HGNC:1493}; Synonyms=CARS; 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 2). RC TISSUE=Brain; RX PubMed=7987009; DOI=10.3109/10425179409020847; RA Cruzen M.E., Arfin S.M.; RT "Nucleotide and deduced amino acid sequence of human cysteinyl-tRNA RT synthetase."; RL DNA Seq. 4:243-248(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, CATALYTIC RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT. RX PubMed=11347887; DOI=10.1515/bc.2001.049; RA Davidson E., Caffarella J., Vitseva O., Hou Y.M., King M.P.; RT "Isolation of two cDNAs encoding functional human cytoplasmic cysteinyl- RT tRNA synthetase."; RL Biol. Chem. 382:399-406(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Testis; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Cervix; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton 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 [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Lung; 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 [9] RP CHROMOSOMAL TRANSLOCATION WITH ALK. RX PubMed=12112524; DOI=10.1002/gcc.10033; RA Cools J., Wlodarska I., Somers R., Mentens N., Pedeutour F., Maes B., RA De Wolf-Peeters C., Pauwels P., Hagemeijer A., Marynen P.; RT "Identification of novel fusion partners of ALK, the anaplastic lymphoma RT kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic RT tumor."; RL Genes Chromosomes Cancer 34:354-362(2002). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-746, 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 [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-503, 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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-746, PHOSPHORYLATION [LARGE RP SCALE ANALYSIS] AT SER-79 (ISOFORM 3), AND IDENTIFICATION BY MASS RP 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 [14] 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 [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-19 AND SER-307, AND RP IDENTIFICATION BY 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 [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19; SER-305 AND SER-307, AND 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 [18] RP VARIANTS MDBH HIS-341; LEU-359; 380-GLN--GLN-748 DEL AND GLN-400, RP CHARACTERIZATION OF VARIANTS MDBH HIS-341; LEU-359; 380-GLN--GLN-748 DEL RP AND GLN-400, FUNCTION, CATALYTIC ACTIVITY, INVOLVEMENT IN MDBH, AND RP SUBCELLULAR LOCATION. RX PubMed=30824121; DOI=10.1016/j.ajhg.2019.01.006; RA Kuo M.E., Theil A.F., Kievit A., Malicdan M.C., Introne W.J., Christian T., RA Verheijen F.W., Smith D.E.C., Mendes M.I., Hussaarts-Odijk L., RA van der Meijden E., van Slegtenhorst M., Wilke M., Vermeulen W., Raams A., RA Groden C., Shimada S., Meyer-Schuman R., Hou Y.M., Gahl W.A., RA Antonellis A., Salomons G.S., Mancini G.M.S.; RT "Cysteinyl-tRNA synthetase mutations cause a multi-system, recessive RT disease that includes microcephaly, developmental delay, and brittle hair RT and nails."; RL Am. J. Hum. Genet. 104:520-529(2019). CC -!- FUNCTION: Catalyzes the ATP-dependent ligation of cysteine to CC tRNA(Cys). {ECO:0000269|PubMed:11347887, ECO:0000269|PubMed:30824121}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-cysteine + tRNA(Cys) = AMP + diphosphate + L- CC cysteinyl-tRNA(Cys); Xref=Rhea:RHEA:17773, Rhea:RHEA-COMP:9661, CC Rhea:RHEA-COMP:9679, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, CC ChEBI:CHEBI:35235, ChEBI:CHEBI:78442, ChEBI:CHEBI:78517, CC ChEBI:CHEBI:456215; EC=6.1.1.16; CC Evidence={ECO:0000269|PubMed:11347887, ECO:0000269|PubMed:30824121}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17774; CC Evidence={ECO:0000305|PubMed:11347887}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000250|UniProtKB:P21888}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:P21888}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 1]: CC Kinetic parameters: CC KM=1.4 uM for tRNA(Cys) {ECO:0000269|PubMed:11347887}; CC Vmax=18000 pmol/sec/mg enzyme for tRNA(Cys) CC {ECO:0000269|PubMed:11347887}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 2]: CC Kinetic parameters: CC KM=1.4 uM for tRNA(Cys) {ECO:0000269|PubMed:11347887}; CC Vmax=4000 pmol/sec/mg enzyme for tRNA(Cys) CC {ECO:0000269|PubMed:11347887}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11347887}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:30824121}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P49589-1; Sequence=Displayed; CC Name=2; CC IsoId=P49589-2; Sequence=VSP_006312; CC Name=3; CC IsoId=P49589-3; Sequence=VSP_043571; CC -!- DISEASE: Microcephaly, developmental delay, and brittle hair syndrome CC (MDBH) [MIM:618891]: An autosomal recessive disorder characterized by CC developmental delay, motor and cognitive disabilities, brittle hair and CC nails, failure to thrive, and short stature. CC {ECO:0000269|PubMed:30824121}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Note=A chromosomal aberration involving CARS is associated CC with inflammatory myofibroblastic tumors (IMTs). Translocation CC t(2;11)(p23;p15) with ALK. CC -!- MISCELLANEOUS: [Isoform 2]: Found in 20% of the mRNAs. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAA73901.1; Type=Frameshift; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/484/CARS"; 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; L06845; AAA73901.1; ALT_FRAME; mRNA. DR EMBL; AF288206; AAG00578.1; -; mRNA. DR EMBL; AF288207; AAG00579.1; -; mRNA. DR EMBL; BT009913; AAP88915.1; -; mRNA. DR EMBL; AK302644; BAG63885.1; -; mRNA. DR EMBL; BX647906; CAI46108.1; -; mRNA. DR EMBL; AC108448; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC131971; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471158; EAX02541.1; -; Genomic_DNA. DR EMBL; BC002880; AAH02880.1; -; mRNA. DR CCDS; CCDS41600.1; -. [P49589-3] DR CCDS; CCDS41602.1; -. [P49589-2] DR CCDS; CCDS7742.1; -. [P49589-1] DR RefSeq; NP_001014437.1; NM_001014437.2. [P49589-3] DR RefSeq; NP_001742.1; NM_001751.5. [P49589-1] DR RefSeq; NP_644802.1; NM_139273.3. [P49589-2] DR AlphaFoldDB; P49589; -. DR SMR; P49589; -. DR BioGRID; 107283; 107. DR IntAct; P49589; 21. DR MINT; P49589; -. DR STRING; 9606.ENSP00000369897; -. DR ChEMBL; CHEMBL4105937; -. DR DrugBank; DB00151; Cysteine. DR GlyGen; P49589; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P49589; -. DR MetOSite; P49589; -. DR PhosphoSitePlus; P49589; -. DR SwissPalm; P49589; -. DR BioMuta; CARS; -. DR DMDM; 20141641; -. DR EPD; P49589; -. DR jPOST; P49589; -. DR MassIVE; P49589; -. DR MaxQB; P49589; -. DR PaxDb; P49589; -. DR PeptideAtlas; P49589; -. DR ProteomicsDB; 56023; -. [P49589-1] DR ProteomicsDB; 56024; -. [P49589-2] DR ProteomicsDB; 56025; -. [P49589-3] DR ABCD; P49589; 1 sequenced antibody. DR Antibodypedia; 1044; 265 antibodies from 30 providers. DR DNASU; 833; -. DR Ensembl; ENST00000278224.13; ENSP00000278224.9; ENSG00000110619.18. [P49589-2] DR Ensembl; ENST00000380525.9; ENSP00000369897.4; ENSG00000110619.18. [P49589-3] DR Ensembl; ENST00000397111.9; ENSP00000380300.5; ENSG00000110619.18. [P49589-1] DR Ensembl; ENST00000612826.3; ENSP00000482336.1; ENSG00000278191.4. [P49589-3] DR Ensembl; ENST00000632612.1; ENSP00000487923.1; ENSG00000278191.4. [P49589-2] DR Ensembl; ENST00000633248.1; ENSP00000488657.1; ENSG00000278191.4. [P49589-1] DR GeneID; 833; -. DR KEGG; hsa:833; -. DR MANE-Select; ENST00000380525.9; ENSP00000369897.4; NM_001014437.3; NP_001014437.1. [P49589-3] DR UCSC; uc001lxf.4; human. [P49589-1] DR AGR; HGNC:1493; -. DR CTD; 833; -. DR DisGeNET; 833; -. DR GeneCards; CARS1; -. DR HGNC; HGNC:1493; CARS1. DR HPA; ENSG00000110619; Low tissue specificity. DR MalaCards; CARS1; -. DR MIM; 123859; gene. DR MIM; 618891; phenotype. DR neXtProt; NX_P49589; -. DR OpenTargets; ENSG00000110619; -. DR Orphanet; 178342; Inflammatory myofibroblastic tumor. DR Orphanet; 33364; Trichothiodystrophy. DR PharmGKB; PA26079; -. DR VEuPathDB; HostDB:ENSG00000110619; -. DR eggNOG; KOG1668; Eukaryota. DR eggNOG; KOG2007; Eukaryota. DR GeneTree; ENSGT00390000006347; -. DR HOGENOM; CLU_013528_3_3_1; -. DR InParanoid; P49589; -. DR OMA; FHNDMKS; -. DR OrthoDB; 2140072at2759; -. DR PhylomeDB; P49589; -. DR TreeFam; TF300384; -. DR PathwayCommons; P49589; -. DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation. DR Reactome; R-HSA-9725370; Signaling by ALK fusions and activated point mutants. DR SignaLink; P49589; -. DR SIGNOR; P49589; -. DR BioGRID-ORCS; 833; 817 hits in 1175 CRISPR screens. DR ChiTaRS; CARS; human. DR GenomeRNAi; 833; -. DR Pharos; P49589; Tchem. DR PRO; PR:P49589; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P49589; protein. DR Bgee; ENSG00000110619; Expressed in olfactory segment of nasal mucosa and 94 other tissues. DR ExpressionAtlas; P49589; baseline and differential. DR Genevisible; P49589; HS. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB. DR GO; GO:0004817; F:cysteine-tRNA ligase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0000049; F:tRNA binding; IDA:UniProtKB. DR GO; GO:0006423; P:cysteinyl-tRNA aminoacylation; IDA:UniProtKB. DR CDD; cd00672; CysRS_core; 1. DR Gene3D; 3.40.50.620; HUPs; 1. DR HAMAP; MF_00041; Cys_tRNA_synth; 1. DR InterPro; IPR015803; Cys-tRNA-ligase. DR InterPro; IPR024909; Cys-tRNA/MSH_ligase. DR InterPro; IPR014729; Rossmann-like_a/b/a_fold. DR InterPro; IPR032678; tRNA-synt_1_cat_dom. DR InterPro; IPR009080; tRNAsynth_Ia_anticodon-bd. DR PANTHER; PTHR10890:SF3; CYSTEINE--TRNA LIGASE, CYTOPLASMIC; 1. DR PANTHER; PTHR10890; CYSTEINYL-TRNA SYNTHETASE; 1. DR Pfam; PF01406; tRNA-synt_1e; 1. DR PRINTS; PR00983; TRNASYNTHCYS. DR SUPFAM; SSF47323; Anticodon-binding domain of a subclass of class I aminoacyl-tRNA synthetases; 1. DR SUPFAM; SSF52374; Nucleotidylyl transferase; 1. DR TIGRFAMs; TIGR00435; cysS; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Aminoacyl-tRNA synthetase; ATP-binding; KW Chromosomal rearrangement; Cytoplasm; Disease variant; Dwarfism; Ligase; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Protein biosynthesis; KW Proto-oncogene; Reference proteome; Zinc. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..748 FT /note="Cysteine--tRNA ligase, cytoplasmic" FT /id="PRO_0000159550" FT REGION 1..25 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 653..686 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 57..67 FT /note="'HIGH' region" FT MOTIF 406..410 FT /note="'KMSKS' region" FT COMPBIAS 1..22 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 653..679 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 55 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P21888" FT BINDING 348 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P21888" FT BINDING 373 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P21888" FT BINDING 377 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000250|UniProtKB:P21888" FT BINDING 409 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 19 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 305 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 307 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 503 FT /note="N6-acetyllysine" FT /evidence="ECO:0007744|PubMed:19608861" FT MOD_RES 746 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231" FT VAR_SEQ 9 FT /note="G -> APDYRSILSISDEAARAQALNEHLSTRSYVQGYSLSQADVDAFRQLS FT APPADPQLFHVARWFRHIEALLGSPCGKGQPCRLQAS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:17974005" FT /id="VSP_043571" FT VAR_SEQ 705..748 FT /note="GLPTHDMEGKELSKGQAKKLKKLFEAQEKLYKEYLQMAQNGSFQ -> VSMV FT CPHMTWRAKSSAKGKPRS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11347887, FT ECO:0000303|PubMed:7987009" FT /id="VSP_006312" FT VARIANT 341 FT /note="R -> H (in MDBH; 50% reduction of cysteine-tRNA FT ligase activity)" FT /evidence="ECO:0000269|PubMed:30824121" FT /id="VAR_084305" FT VARIANT 359 FT /note="S -> L (in MDBH; 84% reduction of cysteine-tRNA FT ligase activity)" FT /evidence="ECO:0000269|PubMed:30824121" FT /id="VAR_084306" FT VARIANT 380..748 FT /note="Missing (in MDBH; undetectable mutant protein in FT patient cells; loss-of-function variant unable to rescue FT viability defects in a yeast complementation assay)" FT /evidence="ECO:0000269|PubMed:30824121" FT /id="VAR_084307" FT VARIANT 400 FT /note="L -> Q (in MDBH; loss-of-function variant unable to FT rescue viability defects in a yeast complementation assay)" FT /evidence="ECO:0000269|PubMed:30824121" FT /id="VAR_084308" FT MOD_RES P49589-3:79 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" SQ SEQUENCE 748 AA; 85473 MW; D0B7A29EC03AA87F CRC64; MADSSGQQGK GRRVQPQWSP PAGTQPCRLH LYNSLTRNKE VFIPQDGKKV TWYCCGPTVY DASHMGHARS YISFDILRRV LKDYFKFDVF YCMNITDIDD KIIKRARQNH LFEQYREKRP EAAQLLEDVQ AALKPFSVKL NETTDPDKKQ MLERIQHAVQ LATEPLEKAV QSRLTGEEVN SCVEVLLEEA KDLLSDWLDS TLGCDVTDNS IFSKLPKFWE GDFHRDMEAL NVLPPDVLTR VSEYVPEIVN FVQKIVDNGY GYVSNGSVYF DTAKFASSEK HSYGKLVPEA VGDQKALQEG EGDLSISADR LSEKRSPNDF ALWKASKPGE PSWPCPWGKG RPGWHIECSA MAGTLLGASM DIHGGGFDLR FPHHDNELAQ SEAYFENDCW VRYFLHTGHL TIAGCKMSKS LKNFITIKDA LKKHSARQLR LAFLMHSWKD TLDYSSNTME SALQYEKFLN EFFLNVKDIL RAPVDITGQF EKWGEEEAEL NKNFYDKKTA IHKALCDNVD TRTVMEEMRA LVSQCNLYMA ARKAVRKRPN QALLENIALY LTHMLKIFGA VEEDSSLGFP VGGPGTSLSL EATVMPYLQV LSEFREGVRK IAREQKVPEI LQLSDALRDN ILPELGVRFE DHEGLPTVVK LVDRNTLLKE REEKRRVEEE KRKKKEEAAR RKQEQEAAKL AKMKIPPSEM FLSETDKYSK FDENGLPTHD MEGKELSKGQ AKKLKKLFEA QEKLYKEYLQ MAQNGSFQ //