SYCM_HUMAN
ID SYCM_HUMAN Reviewed; 564 AA.
AC Q9HA77; Q8NI84; Q96IV4;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Probable cysteine--tRNA ligase, mitochondrial;
DE EC=6.1.1.16;
DE AltName: Full=Cysteinyl-tRNA synthetase;
DE Short=CysRS;
DE Flags: Precursor;
GN Name=CARS2; ORFNames=OK/SW-cl.10;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-555.
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-564.
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that recognized by tumor-reactive CTL
RT generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP IDENTIFICATION.
RX PubMed=15779907; DOI=10.1021/bi047527z;
RA Bonnefond L., Fender A., Rudinger-Thirion J., Giege R., Florentz C.,
RA Sissler M.;
RT "Toward the full set of human mitochondrial aminoacyl-tRNA synthetases:
RT characterization of AspRS and TyrRS.";
RL Biochemistry 44:4805-4816(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP INVOLVEMENT IN COXPD27, AND VARIANT COXPD27 191-GLY--PRO-218 DEL.
RX PubMed=25361775; DOI=10.1212/wnl.0000000000001055;
RA Hallmann K., Zsurka G., Moskau-Hartmann S., Kirschner J., Korinthenberg R.,
RA Ruppert A.K., Ozdemir O., Weber Y., Becker F., Lerche H., Elger C.E.,
RA Thiele H., Nuernberg P., Sander T., Kunz W.S.;
RT "A homozygous splice-site mutation in CARS2 is associated with progressive
RT myoclonic epilepsy.";
RL Neurology 83:2183-2187(2014).
RN [8]
RP INVOLVEMENT IN COXPD27, AND VARIANTS COXPD27 GLU-217 DEL AND LEU-251.
RX PubMed=25787132; DOI=10.1136/jmedgenet-2015-103049;
RA Coughlin C.R. II, Scharer G.H., Friederich M.W., Yu H.C., Geiger E.A.,
RA Creadon-Swindell G., Collins A.E., Vanlander A.V., Coster R.V.,
RA Powell C.A., Swanson M.A., Minczuk M., Van Hove J.L., Shaikh T.H.;
RT "Mutations in the mitochondrial cysteinyl-tRNA synthase gene, CARS2, lead
RT to a severe epileptic encephalopathy and complex movement disorder.";
RL J. Med. Genet. 52:532-540(2015).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-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 -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix {ECO:0000250}.
CC -!- DISEASE: Combined oxidative phosphorylation deficiency 27 (COXPD27)
CC [MIM:616672]: An autosomal recessive mitochondrial disorder
CC characterized by multiple mitochondrial respiratory-chain-complex
CC deficiencies causing neurological regression, progressive cognitive
CC decline, complex movement disorder, epileptic encephalopathy,
CC progressive spastic tetraparesis, and progressive impairment of vision
CC and hearing. {ECO:0000269|PubMed:25361775,
CC ECO:0000269|PubMed:25787132}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB93499.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AK022180; BAB13978.1; -; mRNA.
DR EMBL; AL157820; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL139385; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007220; AAH07220.1; -; mRNA.
DR EMBL; AB062436; BAB93499.1; ALT_INIT; mRNA.
DR CCDS; CCDS9514.1; -.
DR RefSeq; NP_078813.1; NM_024537.3.
DR AlphaFoldDB; Q9HA77; -.
DR SMR; Q9HA77; -.
DR BioGRID; 122730; 94.
DR IntAct; Q9HA77; 12.
DR MINT; Q9HA77; -.
DR STRING; 9606.ENSP00000257347; -.
DR DrugBank; DB00151; Cysteine.
DR GlyGen; Q9HA77; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9HA77; -.
DR PhosphoSitePlus; Q9HA77; -.
DR SwissPalm; Q9HA77; -.
DR BioMuta; CARS2; -.
DR DMDM; 74761587; -.
DR EPD; Q9HA77; -.
DR jPOST; Q9HA77; -.
DR MassIVE; Q9HA77; -.
DR MaxQB; Q9HA77; -.
DR PaxDb; Q9HA77; -.
DR PeptideAtlas; Q9HA77; -.
DR PRIDE; Q9HA77; -.
DR ProteomicsDB; 81383; -.
DR Antibodypedia; 42558; 33 antibodies from 17 providers.
DR DNASU; 79587; -.
DR Ensembl; ENST00000257347.9; ENSP00000257347.4; ENSG00000134905.17.
DR GeneID; 79587; -.
DR KEGG; hsa:79587; -.
DR MANE-Select; ENST00000257347.9; ENSP00000257347.4; NM_024537.4; NP_078813.1.
DR UCSC; uc001vrd.3; human.
DR CTD; 79587; -.
DR DisGeNET; 79587; -.
DR GeneCards; CARS2; -.
DR HGNC; HGNC:25695; CARS2.
DR HPA; ENSG00000134905; Low tissue specificity.
DR MalaCards; CARS2; -.
DR MIM; 612800; gene.
DR MIM; 616672; phenotype.
DR neXtProt; NX_Q9HA77; -.
DR OpenTargets; ENSG00000134905; -.
DR Orphanet; 477774; Combined oxidative phosphorylation defect type 27.
DR PharmGKB; PA162381083; -.
DR VEuPathDB; HostDB:ENSG00000134905; -.
DR eggNOG; KOG2007; Eukaryota.
DR GeneTree; ENSGT00390000006347; -.
DR HOGENOM; CLU_013528_0_3_1; -.
DR InParanoid; Q9HA77; -.
DR OMA; HAWPASE; -.
DR OrthoDB; 528822at2759; -.
DR PhylomeDB; Q9HA77; -.
DR TreeFam; TF300384; -.
DR BRENDA; 6.1.1.16; 2681.
DR PathwayCommons; Q9HA77; -.
DR Reactome; R-HSA-379726; Mitochondrial tRNA aminoacylation.
DR SignaLink; Q9HA77; -.
DR BioGRID-ORCS; 79587; 228 hits in 1038 CRISPR screens.
DR ChiTaRS; CARS2; human.
DR GenomeRNAi; 79587; -.
DR Pharos; Q9HA77; Tbio.
DR PRO; PR:Q9HA77; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q9HA77; protein.
DR Bgee; ENSG00000134905; Expressed in monocyte and 184 other tissues.
DR ExpressionAtlas; Q9HA77; baseline and differential.
DR Genevisible; Q9HA77; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IBA:GO_Central.
DR GO; GO:0004817; F:cysteine-tRNA ligase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006423; P:cysteinyl-tRNA aminoacylation; IBA:GO_Central.
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 Aminoacyl-tRNA synthetase; ATP-binding; Disease variant; Ligase;
KW Metal-binding; Mitochondrion; Nucleotide-binding;
KW Primary mitochondrial disease; Protein biosynthesis; Reference proteome;
KW Transit peptide; Zinc.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..564
FT /note="Probable cysteine--tRNA ligase, mitochondrial"
FT /id="PRO_0000250741"
FT MOTIF 80..90
FT /note="'HIGH' region"
FT MOTIF 317..321
FT /note="'KMSKS' region"
FT BINDING 78
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 257
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 282
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 286
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 320
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT VARIANT 191..218
FT /note="Missing (in COXPD27)"
FT /evidence="ECO:0000269|PubMed:25361775"
FT /id="VAR_075667"
FT VARIANT 217
FT /note="Missing (in COXPD27; dbSNP:rs753472937)"
FT /evidence="ECO:0000269|PubMed:25787132"
FT /id="VAR_075668"
FT VARIANT 251
FT /note="P -> L (in COXPD27; dbSNP:rs557671802)"
FT /evidence="ECO:0000269|PubMed:25787132"
FT /id="VAR_075669"
FT VARIANT 440
FT /note="E -> K (in dbSNP:rs965189)"
FT /id="VAR_034523"
FT VARIANT 555
FT /note="Q -> P (in dbSNP:rs1043886)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_034524"
FT CONFLICT 182..202
FT /note="RGNAYSTAKGNVYFDLKSRGD -> SWERLFNGKRQCLLRSESLEET (in
FT Ref. 4; BAB93499)"
FT /evidence="ECO:0000305"
FT CONFLICT 207..223
FT /note="LVGVVPGPVGEPADSDK -> IGRRGPWSSPETSGLLTS (in Ref. 4;
FT BAB93499)"
FT /evidence="ECO:0000305"
FT CONFLICT 227
FT /note="S -> N (in Ref. 4; BAB93499)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 564 AA; 62224 MW; 92F8B615E6657D50 CRC64;
MLRTTRGPGL GPPLLQAALG LGRAGWHWPA GRAASGGRGR AWLQPTGRET GVQVYNSLTG
RKEPLIVAHA EAASWYSCGP TVYDHAHLGH ACSYVRFDII RRILTKVFGC SIVMVMGITD
VDDKIIKRAN EMNISPASLA SLYEEDFKQD MAALKVLPPT VYLRVTENIP QIISFIEGII
ARGNAYSTAK GNVYFDLKSR GDKYGKLVGV VPGPVGEPAD SDKRHASDFA LWKAAKPQEV
FWASPWGPGR PGWHIECSAI ASMVFGSQLD IHSGGIDLAF PHHENEIAQC EVFHQCEQWG
NYFLHSGHLH AKGKEEKMSK SLKNYITIKD FLKTFSPDVF RFFCLRSSYR SAIDYSDSAM
LQAQQLLLGL GSFLEDARAY MKGQLACGSV REAMLWERLS STKRAVKAAL ADDFDTPRVV
DAILGLAHHG NGQLRASLKE PEGPRSPAVF GAIISYFEQF FETVGISLAN QQYVSGDGSE
ATLHGVVDEL VRFRQKVRQF ALAMPEATGD ARRQQLLERQ PLLEACDTLR RGLTAHGINI
KDRSSTTSTW ELLDQRTKDQ KSAG
