P49589 (SYCC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cysteine--tRNA ligase, cytoplasmic
EC=6.1.1.16

Alternative name(s):
Cysteinyl-tRNA synthetase
Short name=CysRS

Gene names

Name:

CARS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	748 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + L-cysteine + tRNA(Cys) = AMP + diphosphate + L-cysteinyl-tRNA(Cys).
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Monomer By similarity.
Subcellular location	Cytoplasm.
Involvement in disease	Note=A chromosomal aberration involving CARS is associated with inflammatory myofibroblastic tumors (IMTs). Translocation t(2;11)(p23;p15) with ALK.
Sequence similarities	Belongs to the class-I aminoacyl-tRNA synthetase family.
Sequence caution	The sequence AAA73901.1 differs from that shown. Reason: Frameshift at position 619.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Chromosomal rearrangement
Disease	Proto-oncogene
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Aminoacyl-tRNA synthetase Ligase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cysteinyl-tRNA aminoacylation Inferred from direct assay Ref.2. Source: UniProtKB
Cellular component	cytoplasm Non-traceable author statement Ref.2. Source: UniProtKB cytosol Traceable author statement. Source: Reactome
Molecular function	ATP binding Inferred from direct assay. Source: UniProtKB cysteine-tRNA ligase activity Inferred from direct assay Ref.2. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein homodimerization activity Inferred from mutant phenotype. Source: UniProtKB tRNA binding Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P49589-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P49589-2)

The sequence of this isoform differs from the canonical sequence as follows:
     705-748: GLPTHDMEGKELSKGQAKKLKKLFEAQEKLYKEYLQMAQNGSFQ → VSMVCPHMTWRAKSSAKGKPRS

Note: Found in 20% of the mRNAs.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 748	748	Cysteine--tRNA ligase, cytoplasmic		PRO_0000159550
Regions
	Motif	57 – 67	11	"HIGH" region
	Motif	406 – 410	5	"KMSKS" region
Sites
	Metal binding	55	1	Zinc By similarity
	Metal binding	348	1	Zinc By similarity
	Metal binding	373	1	Zinc By similarity
	Metal binding	377	1	Zinc By similarity
	Binding site	409	1	ATP By similarity
Amino acid modifications
	Modified residue	19	1	Phosphoserine Ref.8
	Modified residue	260	1	Phosphotyrosine Ref.6
	Modified residue	307	1	Phosphoserine By similarity
	Modified residue	503	1	N6-acetyllysine Ref.9
	Modified residue	746	1	Phosphoserine Ref.7
Natural variations
	Alternative sequence	705 – 748	44	GLPTH…NGSFQ → VSMVCPHMTWRAKSSAKGKP RS in isoform 2.		VSP_006312

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 31, 2002. Version 3. Checksum: D0B7A29EC03AA87F	FASTA	748	85,473
	10 20 30 40 50 60 MADSSGQQGK GRRVQPQWSP PAGTQPCRLH LYNSLTRNKE VFIPQDGKKV TWYCCGPTVY 70 80 90 100 110 120 DASHMGHARS YISFDILRRV LKDYFKFDVF YCMNITDIDD KIIKRARQNH LFEQYREKRP 130 140 150 160 170 180 EAAQLLEDVQ AALKPFSVKL NETTDPDKKQ MLERIQHAVQ LATEPLEKAV QSRLTGEEVN 190 200 210 220 230 240 SCVEVLLEEA KDLLSDWLDS TLGCDVTDNS IFSKLPKFWE GDFHRDMEAL NVLPPDVLTR 250 260 270 280 290 300 VSEYVPEIVN FVQKIVDNGY GYVSNGSVYF DTAKFASSEK HSYGKLVPEA VGDQKALQEG 310 320 330 340 350 360 EGDLSISADR LSEKRSPNDF ALWKASKPGE PSWPCPWGKG RPGWHIECSA MAGTLLGASM 370 380 390 400 410 420 DIHGGGFDLR FPHHDNELAQ SEAYFENDCW VRYFLHTGHL TIAGCKMSKS LKNFITIKDA 430 440 450 460 470 480 LKKHSARQLR LAFLMHSWKD TLDYSSNTME SALQYEKFLN EFFLNVKDIL RAPVDITGQF 490 500 510 520 530 540 EKWGEEEAEL NKNFYDKKTA IHKALCDNVD TRTVMEEMRA LVSQCNLYMA ARKAVRKRPN 550 560 570 580 590 600 QALLENIALY LTHMLKIFGA VEEDSSLGFP VGGPGTSLSL EATVMPYLQV LSEFREGVRK 610 620 630 640 650 660 IAREQKVPEI LQLSDALRDN ILPELGVRFE DHEGLPTVVK LVDRNTLLKE REEKRRVEEE 670 680 690 700 710 720 KRKKKEEAAR RKQEQEAAKL AKMKIPPSEM FLSETDKYSK FDENGLPTHD MEGKELSKGQ 730 740 AKKLKKLFEA QEKLYKEYLQ MAQNGSFQ
	Isoform 2 [UniParc]. Checksum: 92C51DF9289FE47D	FASTA	726	82,846
	10 20 30 40 50 60 MADSSGQQGK GRRVQPQWSP PAGTQPCRLH LYNSLTRNKE VFIPQDGKKV TWYCCGPTVY 70 80 90 100 110 120 DASHMGHARS YISFDILRRV LKDYFKFDVF YCMNITDIDD KIIKRARQNH LFEQYREKRP 130 140 150 160 170 180 EAAQLLEDVQ AALKPFSVKL NETTDPDKKQ MLERIQHAVQ LATEPLEKAV QSRLTGEEVN 190 200 210 220 230 240 SCVEVLLEEA KDLLSDWLDS TLGCDVTDNS IFSKLPKFWE GDFHRDMEAL NVLPPDVLTR 250 260 270 280 290 300 VSEYVPEIVN FVQKIVDNGY GYVSNGSVYF DTAKFASSEK HSYGKLVPEA VGDQKALQEG 310 320 330 340 350 360 EGDLSISADR LSEKRSPNDF ALWKASKPGE PSWPCPWGKG RPGWHIECSA MAGTLLGASM 370 380 390 400 410 420 DIHGGGFDLR FPHHDNELAQ SEAYFENDCW VRYFLHTGHL TIAGCKMSKS LKNFITIKDA 430 440 450 460 470 480 LKKHSARQLR LAFLMHSWKD TLDYSSNTME SALQYEKFLN EFFLNVKDIL RAPVDITGQF 490 500 510 520 530 540 EKWGEEEAEL NKNFYDKKTA IHKALCDNVD TRTVMEEMRA LVSQCNLYMA ARKAVRKRPN 550 560 570 580 590 600 QALLENIALY LTHMLKIFGA VEEDSSLGFP VGGPGTSLSL EATVMPYLQV LSEFREGVRK 610 620 630 640 650 660 IAREQKVPEI LQLSDALRDN ILPELGVRFE DHEGLPTVVK LVDRNTLLKE REEKRRVEEE 670 680 690 700 710 720 KRKKKEEAAR RKQEQEAAKL AKMKIPPSEM FLSETDKYSK FDENVSMVCP HMTWRAKSSA KGKPRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide and deduced amino acid sequence of human cysteinyl-tRNA synthetase." Cruzen M.E., Arfin S.M. DNA Seq. 4:243-248(1994) [PubMed: 7987009] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Brain.
[2]	"Isolation of two cDNAs encoding functional human cytoplasmic cysteinyl-tRNA synthetase." Davidson E., Caffarella J., Vitseva O., Hou Y.M., King M.P. Biol. Chem. 382:399-406(2001) [PubMed: 11347887] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[5]	"Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor." Cools J., Wlodarska I., Somers R., Mentens N., Pedeutour F., Maes B., De Wolf-Peeters C., Pauwels P., Hagemeijer A., Marynen P. Genes Chromosomes Cancer 34:354-362(2002) [PubMed: 12112524] [Abstract] Cited for: CHROMOSOMAL TRANSLOCATION WITH ALK.
[6]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-260, MASS SPECTROMETRY.
[7]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-746, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[9]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-503, MASS SPECTROMETRY.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	L06845 mRNA. Translation: AAA73901.1. Frameshift. AF288206 mRNA. Translation: AAG00578.1. AF288207 mRNA. Translation: AAG00579.1. BT009913 mRNA. Translation: AAP88915.1. BC002880 mRNA. Translation: AAH02880.1.
IPI	IPI00556365. IPI00939491.
RefSeq	NP_001742.1. NM_001751.5. NP_644802.1. NM_139273.3.
UniGene	Hs.274873.
3D structure databases
ProteinModelPortal	P49589.
SMR	P49589. Positions 27-641.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49589. 4 interactions.
STRING	P49589.
PTM databases
PhosphoSite	P49589.
Polymorphism databases
DMDM	20141641.
Proteomic databases
PRIDE	P49589.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000397111; ENSP00000380300; ENSG00000110619.
GeneID	833.
KEGG	hsa:833.
NMPDR	fig|9606.3.peg.5048.
UCSC	uc001lxg.1. human. uc001lxh.1. human.
Organism-specific databases
CTD	833.
GeneCards	GC11M003022.
HGNC	HGNC:1493. CARS.
HPA	HPA002383. HPA002384.
MIM	123859. gene.
neXtProt	NX_P49589.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17865.
GeneTree	ENSGT00390000006347.
HOVERGEN	HBG002089.
OrthoDB	EOG473PQS.
PhylomeDB	P49589.
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P49589.
Bgee	P49589.
CleanEx	HS_CARS.
Genevestigator	P49589.
GermOnline	ENSG00000110619. Homo sapiens.
Family and domain databases
InterPro	IPR015803. Cys-tRNA-synt. IPR024909. Cys-tRNA/MSH_ligase. IPR014729. Rossmann-like_a/b/a_fold. IPR009080. tRNAsynth_1a_anticodon-bd. [Graphical view]
Gene3D	G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 2 hits.
KO	K01883.
Pfam	PF01406. tRNA-synt_1e. 1 hit. [Graphical view]
PRINTS	PR00983. TRNASYNTHCYS.
SUPFAM	SSF47323. tRNAsyn_1a_bind. 1 hit.
TIGRFAMs	TIGR00435. CysS. 1 hit.
PROSITE	PS00178. AA_TRNA_LIGASE_I. False negative. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00151. L-Cysteine.
NextBio	3450.
SOURCE	Search...

Entry information

Entry name

SYCC_HUMAN

Accession

Primary (citable) accession number: P49589
Secondary accession number(s): Q53XI8, Q9HD24, Q9HD25

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	January 31, 2002
Last modified:	January 25, 2012
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.