SYCC_HUMAN
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 03-AUG-2022, entry version 196.
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="http://atlasgeneticsoncology.org/Genes/CARSID484.html";
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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; 77.
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 PRIDE; 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; 242 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 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 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; 528822at2759; -.
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 BioGRID-ORCS; 833; 783 hits in 1087 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; -; 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; PTHR10890; 1.
DR Pfam; PF01406; tRNA-synt_1e; 1.
DR PRINTS; PR00983; TRNASYNTHCYS.
DR SUPFAM; SSF47323; SSF47323; 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
