P41252 (SYIC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Isoleucine--tRNA ligase, cytoplasmic
EC=6.1.1.5

Alternative name(s):
Isoleucyl-tRNA synthetase
Short name=IRS
Short name=IleRS

Gene names

Name:

IARS

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	1262 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-isoleucyl-tRNA(Ile).
Subunit structure	Part of a multisubunit complex that groups tRNA ligases for Arg, Asp, Glu, Gln, Ile, Leu, Lys, Met and Pro.
Subcellular location	Cytoplasm Ref.2.
Sequence similarities	Belongs to the class-I aminoacyl-tRNA synthetase family.
Sequence caution	The sequence BAA05835.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Protein biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Aminoacyl-tRNA synthetase Ligase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	isoleucyl-tRNA aminoacylation Inferred from electronic annotation. Source: InterPro
Cellular component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA soluble fraction Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW isoleucine-tRNA ligase activity Traceable author statement. Source: Reactome protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EPRS	P07814	4	EBI-355303,EBI-355315

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1262	1262	Isoleucine--tRNA ligase, cytoplasmic		PRO_0000098597
Regions
	Motif	48 – 58	11	"HIGH" region
	Motif	600 – 604	5	"KMSKS" region
Sites
	Binding site	603	1	ATP By similarity
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.9
	Modified residue	844	1	N6-acetyllysine Ref.10
	Modified residue	1047	1	Phosphoserine Ref.7 Ref.8 Ref.9
Natural variations
	Natural variant	684	1	T → M. Corresponds to variant rs2070053 [ dbSNP | Ensembl ].		VAR_058300
	Natural variant	769	1	M → I. Ref.2 Corresponds to variant rs1136054 [ dbSNP | Ensembl ].		VAR_057951
	Natural variant	1182	1	K → E. Ref.4 Corresponds to variant rs556155 [ dbSNP | Ensembl ].		VAR_057952
Experimental info
	Sequence conflict	658	1	N → S in CAD97671. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P41252 [UniParc]. Last modified June 16, 2009. Version 2. Checksum: 73CB3967A6868005	FASTA	1,262	144,498
	10 20 30 40 50 60 MLQQVPENIN FPAEEEKILE FWTEFNCFQE CLKQSKHKPK FTFYDGPPFA TGLPHYGHIL 70 80 90 100 110 120 AGTIKDIVTR YAHQSGFHVD RRFGWDCHGL PVEYEIDKTL GIRGPEDVAK MGITEYNNQC 130 140 150 160 170 180 RAIVMRYSAE WKSTVSRLGR WIDFDNDYKT LYPQFMESVW WVFKQLYDKG LVYRGVKVMP 190 200 210 220 230 240 FSTACNTPLS NFESHQNYKD VQDPSVFVTF PLEEDETVSL VAWTTTPWTL PSNLAVCVNP 250 260 270 280 290 300 EMQYVKIKDV ARGRLLILME ARLSALYKLE SDYEILERFP GAYLKGKKYR PLFDYFLKCK 310 320 330 340 350 360 ENGAFTVLVD NYVKEEEGTG VVHQAPYFGA EDYRVCMDFN IIRKDSLPVC PVDASGCFTT 370 380 390 400 410 420 EVTDFAGQYV KDADKSIIRT LKEQGRLLVA TTFTHSYPFC WRSDTPLIYK AVPSWFVRVE 430 440 450 460 470 480 NMVDQLLRNN DLCYWVPELV REKRFGNWLK DARDWTISRN RYWGTPIPLW VSDDFEEVVC 490 500 510 520 530 540 IGSVAELEEL SGAKISDLHR ESVDHLTIPS RCGKGSLHRI SEVFDCWFES GSMPYAQVHY 550 560 570 580 590 600 PFENKREFED AFPADFIAEG IDQTRGWFYT LLVLATALFG QPPFKNVIVN GLVLASDGQK 610 620 630 640 650 660 MSKRKKNYPD PVSIIQKYGA DALRLYLINS PVVRAENLRF KEEGVRDVLK DVLLPWYNAY 670 680 690 700 710 720 RFLIQNVLRL QKEEEIEFLY NENTVRESPN ITDRWILSFM QSLIGFFETE MAAYRLYTVV 730 740 750 760 770 780 PRLVKFVDIL TNWYVRMNRR RLKGENGMED CVMALETLFS VLLSLCRLMA PYTPFLTELM 790 800 810 820 830 840 YQNLKVLIDP VSVQDKDTLS IHYLMLPRVR EELIDKKTES AVSQMQSVIE LGRVIRDRKT 850 860 870 880 890 900 IPIKYPLKEI VVIHQDPEAL KDIKSLEKYI IEELNVRKVT LSTDKNKYGI RLRAEPDHMV 910 920 930 940 950 960 LGKRLKGAFK AVMTSIKQLS SEELEQFQKT GTIVVEGHEL HDEDIRLMYT FDQATGGTAQ 970 980 990 1000 1010 1020 FEAHSDAQAL VLLDVTPDQS MVDEGMAREV INRIQKLRKK CNLVPTDEIT VYYKAKSEGT 1030 1040 1050 1060 1070 1080 YLNSVIESHT EFIFTTIKAP LKPYPVSPSD KVLIQEKTQL KGSELEITLT RGSSLPGPAC 1090 1100 1110 1120 1130 1140 AYVNLNICAN GSEQGGVLLL ENPKGDNRLD LLKLKSVVTS IFGVKNTELA VFHDETEIQN 1150 1160 1170 1180 1190 1200 QTDLLSLSGK TLCVTAGSAP SLINSSSTLL CQYINLQLLN AKPQECLMGT VGTLLLENPL 1210 1220 1230 1240 1250 1260 GQNGLTHQGL LYEAAKVFGL RSRKLKLFLN ETQTQEITED IPVKTLNMKT VYVSVLPTTA DF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human cytoplasmic isoleucyl-tRNA synthetase: selective divergence of the anticodon-binding domain and acquisition of a new structural unit." Shiba K., Suzuki N., Shigesada K., Schimmel P., Noda T. Proc. Natl. Acad. Sci. U.S.A. 91:7435-7439(1994) [PubMed: 8052601] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Human isoleucyl-tRNA synthetase: sequence of the cDNA, alternative mRNA splicing, and the characteristics of an unusually long C-terminal extension." Nichols R.C., Raben N., Boerkoel C.F., Plotz P.H. Gene 155:299-304(1995) [PubMed: 7721108] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, VARIANT ILE-769. Tissue: Liver.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Trachea.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-1182. Tissue: Colon endothelium.
[5]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed: 15164053] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra." Yu L.-R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D. J. Proteome Res. 6:4150-4162(2007) [PubMed: 17924679] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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-1047, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[9]	"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: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[10]	"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-844, MASS SPECTROMETRY.
[11]	"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.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D28473 mRNA. Translation: BAA05835.1. Different initiation. U04953 mRNA. Translation: AAA80153.1. AK293014 mRNA. Translation: BAF85703.1. BX537429 mRNA. Translation: CAD97671.1. AL136097 Genomic DNA. Translation: CAI16202.2. CH471089 Genomic DNA. Translation: EAW62813.1.
IPI	IPI00644127.
PIR	I59314.
RefSeq	NP_002152.2. NM_002161.4. NP_038203.2. NM_013417.2.
UniGene	Hs.445403.
3D structure databases
ProteinModelPortal	P41252.
SMR	P41252. Positions 554-612.
ModBase	Search...
Protein-protein interaction databases
IntAct	P41252. 3 interactions.
MINT	MINT-141153.
STRING	P41252.
PTM databases
PhosphoSite	P41252.
Polymorphism databases
DMDM	239938717.
Proteomic databases
PRIDE	P41252.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375643; ENSP00000364794; ENSG00000196305. ENST00000375660; ENSP00000364811; ENSG00000196305. ENST00000443024; ENSP00000406448; ENSG00000196305. ENST00000447699; ENSP00000415020; ENSG00000196305.
GeneID	3376.
KEGG	hsa:3376.
Organism-specific databases
CTD	3376.
GeneCards	GC09M094972.
H-InvDB	HIX0008163.
HGNC	HGNC:5330. IARS.
HPA	HPA029806.
MIM	600709. gene.
neXtProt	NX_P41252.
PharmGKB	PA29580.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG14733.
HOVERGEN	HBG013511.
InParanoid	P41252.
OrthoDB	EOG4FBHS2.
PhylomeDB	P41252.
Enzyme and pathway databases
Reactome	REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P41252.
Bgee	P41252.
CleanEx	HS_IARS.
Genevestigator	P41252.
GermOnline	ENSG00000196305. Homo sapiens.
Family and domain databases
InterPro	IPR001412. aa-tRNA-synth_I_CS. IPR002300. aa-tRNA-synth_Ia. IPR002301. Ile-tRNA-synt. IPR023586. Ile-tRNA-synt_type2. IPR014729. Rossmann-like_a/b/a_fold. IPR009080. tRNAsynth_1a_anticodon-bd. IPR013155. V/L/I-tRNA-synth_anticodon-bd. IPR009008. Val/Leu/Ile-tRNA-synth_edit. [Graphical view]
Gene3D	G3DSA:3.90.740.10. G3DSA:3.90.740.10. 1 hit. G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 2 hits.
KO	K01870.
Pfam	PF08264. Anticodon_1. 1 hit. PF00133. tRNA-synt_1. 1 hit. [Graphical view]
PRINTS	PR00984. TRNASYNTHILE.
SUPFAM	SSF47323. tRNAsyn_1a_bind. 1 hit. SSF50677. ValRS_IleRS_edit. 1 hit.
TIGRFAMs	TIGR00392. IleS. 1 hit.
PROSITE	PS00178. AA_TRNA_LIGASE_I. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00167. L-Isoleucine.
PMAP-CutDB	P41252.
SOURCE	Search...

Entry information

Entry name

SYIC_HUMAN

Accession

Primary (citable) accession number: P41252
Secondary accession number(s): A8KAE9 , Q5TCD0, Q7Z3T4, Q9H588

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	June 16, 2009
Last modified:	January 25, 2012
This is version 116 of the entry and version 2 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.