SYIC_HUMAN
ID SYIC_HUMAN Reviewed; 1262 AA.
AC P41252; A8KAE9; Q5TCD0; Q7Z3T4; Q9H588;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 16-JUN-2009, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Isoleucine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.5 {ECO:0000269|PubMed:8052601};
DE AltName: Full=Isoleucyl-tRNA synthetase;
DE Short=IRS;
DE Short=IleRS;
GN Name=IARS1 {ECO:0000312|HGNC:HGNC:5330}; Synonyms=IARS;
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], FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8052601; DOI=10.1073/pnas.91.16.7435;
RA Shiba K., Suzuki N., Shigesada K., Schimmel P., Noda T.;
RT "Human cytoplasmic isoleucyl-tRNA synthetase: selective divergence of the
RT anticodon-binding domain and acquisition of a new structural unit.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:7435-7439(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION,
RP AND VARIANT ILE-769.
RC TISSUE=Liver;
RX PubMed=7721108; DOI=10.1016/0378-1119(94)00634-5;
RA Nichols R.C., Raben N., Boerkoel C.F., Plotz P.H.;
RT "Human isoleucyl-tRNA synthetase: sequence of the cDNA, alternative mRNA
RT splicing, and the characteristics of an unusually long C-terminal
RT extension.";
RL Gene 155:299-304(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLU-1182.
RC TISSUE=Colon endothelium;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047, 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 [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=19131329; DOI=10.1074/jbc.m809636200;
RA Kaminska M., Havrylenko S., Decottignies P., Gillet S., Le Marechal P.,
RA Negrutskii B., Mirande M.;
RT "Dissection of the structural organization of the aminoacyl-tRNA synthetase
RT complex.";
RL J. Biol. Chem. 284:6053-6060(2009).
RN [10]
RP SUBCELLULAR LOCATION, AND SUBUNIT.
RX PubMed=19289464; DOI=10.1074/jbc.m900480200;
RA Kaminska M., Havrylenko S., Decottignies P., Le Marechal P., Negrutskii B.,
RA Mirande M.;
RT "Dynamic Organization of Aminoacyl-tRNA Synthetase Complexes in the
RT Cytoplasm of Human Cells.";
RL J. Biol. Chem. 284:13746-13754(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047 AND SER-1049, AND
RP IDENTIFICATION BY MASS 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 [12]
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 [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1047 AND THR-1058, 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 [15]
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 [16]
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).
RN [17]
RP VARIANTS TYR-302 AND THR-1188.
RX PubMed=24706940; DOI=10.1136/jmedgenet-2013-102218;
RG FORGE Canada Consortium;
RA Smith A.C., Mears A.J., Bunker R., Ahmed A., MacKenzie M.,
RA Schwartzentruber J.A., Beaulieu C.L., Ferretti E., Majewski J.,
RA Bulman D.E., Celik F.C., Boycott K.M., Graham G.E.;
RT "Mutations in the enzyme glutathione peroxidase 4 cause Sedaghatian-type
RT spondylometaphyseal dysplasia.";
RL J. Med. Genet. 51:470-474(2014).
RN [18]
RP INVOLVEMENT IN GRIDHH, VARIANTS GRIDHH GLY-370; LEU-437; ASP-992 AND
RP ASN-1174, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=27426735; DOI=10.1016/j.ajhg.2016.05.027;
RA Kopajtich R., Murayama K., Janecke A.R., Haack T.B., Breuer M.,
RA Knisely A.S., Harting I., Ohashi T., Okazaki Y., Watanabe D., Tokuzawa Y.,
RA Kotzaeridou U., Koelker S., Sauer S., Carl M., Straub S., Entenmann A.,
RA Gizewski E., Feichtinger R.G., Mayr J.A., Lackner K., Strom T.M.,
RA Meitinger T., Mueller T., Ohtake A., Hoffmann G.F., Prokisch H.,
RA Staufner C.;
RT "Biallelic IARS mutations cause growth retardation with prenatal onset,
RT intellectual disability, muscular hypotonia, and infantile hepatopathy.";
RL Am. J. Hum. Genet. 99:414-422(2016).
CC -!- FUNCTION: Catalyzes the specific attachment of an amino acid to its
CC cognate tRNA in a 2 step reaction: the amino acid (AA) is first
CC activated by ATP to form AA-AMP and then transferred to the acceptor
CC end of the tRNA. {ECO:0000269|PubMed:8052601}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-
CC isoleucyl-tRNA(Ile); Xref=Rhea:RHEA:11060, Rhea:RHEA-COMP:9666,
CC Rhea:RHEA-COMP:9695, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:58045, ChEBI:CHEBI:78442, ChEBI:CHEBI:78528,
CC ChEBI:CHEBI:456215; EC=6.1.1.5;
CC Evidence={ECO:0000269|PubMed:8052601};
CC -!- SUBUNIT: Part of a multisubunit complex that groups tRNA ligases for
CC Arg (RARS1), Asp (DARS1), Gln (QARS1), Ile (IARS1), Leu (LARS1), Lys
CC (KARS1), Met (MARS1) the bifunctional ligase for Glu and Pro (EPRS1)
CC and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18
CC (PubMed:19131329, PubMed:19289464). {ECO:0000269|PubMed:19131329,
CC ECO:0000269|PubMed:19289464}.
CC -!- INTERACTION:
CC P41252; P07814: EPRS1; NbExp=7; IntAct=EBI-355303, EBI-355315;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:27426735,
CC ECO:0000269|PubMed:7721108}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:19289464}.
CC -!- TISSUE SPECIFICITY: Expressed in liver and muscle (at protein level).
CC {ECO:0000269|PubMed:27426735}.
CC -!- DISEASE: Growth retardation, impaired intellectual development,
CC hypotonia, and hepatopathy (GRIDHH) [MIM:617093]: An autosomal
CC recessive disorder characterized by severe growth retardation with
CC prenatal onset, intellectual disability, muscular hypotonia, and
CC hepatic dysfunction. {ECO:0000269|PubMed:27426735}. Note=The disease is
CC caused by variants 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=BAA05835.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D28473; BAA05835.1; ALT_INIT; mRNA.
DR EMBL; U04953; AAA80153.1; -; mRNA.
DR EMBL; AK293014; BAF85703.1; -; mRNA.
DR EMBL; BX537429; CAD97671.1; -; mRNA.
DR EMBL; AL136097; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471089; EAW62813.1; -; Genomic_DNA.
DR CCDS; CCDS6694.1; -.
DR PIR; I59314; I59314.
DR RefSeq; NP_002152.2; NM_002161.5.
DR RefSeq; NP_038203.2; NM_013417.3.
DR AlphaFoldDB; P41252; -.
DR SMR; P41252; -.
DR BioGRID; 109605; 281.
DR CORUM; P41252; -.
DR IntAct; P41252; 61.
DR MINT; P41252; -.
DR STRING; 9606.ENSP00000364794; -.
DR BindingDB; P41252; -.
DR ChEMBL; CHEMBL3235; -.
DR DrugBank; DB00167; Isoleucine.
DR DrugCentral; P41252; -.
DR CarbonylDB; P41252; -.
DR GlyGen; P41252; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P41252; -.
DR MetOSite; P41252; -.
DR PhosphoSitePlus; P41252; -.
DR SwissPalm; P41252; -.
DR BioMuta; IARS; -.
DR DMDM; 239938717; -.
DR EPD; P41252; -.
DR jPOST; P41252; -.
DR MassIVE; P41252; -.
DR MaxQB; P41252; -.
DR PaxDb; P41252; -.
DR PeptideAtlas; P41252; -.
DR PRIDE; P41252; -.
DR ProteomicsDB; 55454; -.
DR Antibodypedia; 28131; 137 antibodies from 21 providers.
DR DNASU; 3376; -.
DR Ensembl; ENST00000375643.7; ENSP00000364794.3; ENSG00000196305.19.
DR Ensembl; ENST00000443024.7; ENSP00000406448.4; ENSG00000196305.19.
DR Ensembl; ENST00000683565.1; ENSP00000507144.1; ENSG00000196305.19.
DR GeneID; 3376; -.
DR KEGG; hsa:3376; -.
DR MANE-Select; ENST00000443024.7; ENSP00000406448.4; NM_002161.6; NP_002152.2.
DR UCSC; uc004art.4; human.
DR CTD; 3376; -.
DR DisGeNET; 3376; -.
DR GeneCards; IARS1; -.
DR HGNC; HGNC:5330; IARS1.
DR HPA; ENSG00000196305; Low tissue specificity.
DR MalaCards; IARS1; -.
DR MIM; 600709; gene.
DR MIM; 617093; phenotype.
DR neXtProt; NX_P41252; -.
DR OpenTargets; ENSG00000196305; -.
DR Orphanet; 541423; Growth delay-intellectual disability-hepatopathy syndrome.
DR PharmGKB; PA29580; -.
DR VEuPathDB; HostDB:ENSG00000196305; -.
DR eggNOG; KOG0434; Eukaryota.
DR GeneTree; ENSGT00550000074921; -.
DR InParanoid; P41252; -.
DR OMA; KMMAPFT; -.
DR OrthoDB; 59501at2759; -.
DR PhylomeDB; P41252; -.
DR PathwayCommons; P41252; -.
DR Reactome; R-HSA-2408522; Selenoamino acid metabolism.
DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR SignaLink; P41252; -.
DR BioGRID-ORCS; 3376; 763 hits in 1049 CRISPR screens.
DR ChiTaRS; IARS; human.
DR GeneWiki; IARS; -.
DR GenomeRNAi; 3376; -.
DR Pharos; P41252; Tchem.
DR PRO; PR:P41252; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P41252; protein.
DR Bgee; ENSG00000196305; Expressed in cartilage tissue and 209 other tissues.
DR ExpressionAtlas; P41252; baseline and differential.
DR Genevisible; P41252; HS.
DR GO; GO:0017101; C:aminoacyl-tRNA synthetase multienzyme complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:CAFA.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0002161; F:aminoacyl-tRNA editing activity; IEA:InterPro.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051020; F:GTPase binding; IPI:UniProtKB.
DR GO; GO:0004822; F:isoleucine-tRNA ligase activity; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR GO; GO:0006428; P:isoleucyl-tRNA aminoacylation; IDA:UniProtKB.
DR GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB.
DR GO; GO:0006418; P:tRNA aminoacylation for protein translation; TAS:Reactome.
DR CDD; cd07961; Anticodon_Ia_Ile_ABEc; 1.
DR Gene3D; 3.40.50.620; -; 2.
DR HAMAP; MF_02003; Ile_tRNA_synth_type2; 1.
DR InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR InterPro; IPR002300; aa-tRNA-synth_Ia.
DR InterPro; IPR033709; Anticodon_Ile_ABEc.
DR InterPro; IPR002301; Ile-tRNA-ligase.
DR InterPro; IPR023586; Ile-tRNA-ligase_type2.
DR InterPro; IPR013155; M/V/L/I-tRNA-synth_anticd-bd.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR009080; tRNAsynth_Ia_anticodon-bd.
DR InterPro; IPR009008; Val/Leu/Ile-tRNA-synth_edit.
DR PANTHER; PTHR42780; PTHR42780; 1.
DR Pfam; PF08264; Anticodon_1; 1.
DR Pfam; PF00133; tRNA-synt_1; 1.
DR PRINTS; PR00984; TRNASYNTHILE.
DR SUPFAM; SSF47323; SSF47323; 1.
DR SUPFAM; SSF50677; SSF50677; 1.
DR TIGRFAMs; TIGR00392; ileS; 1.
DR PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
PE 1: Evidence at protein level;
KW Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm;
KW Direct protein sequencing; Disease variant; Intellectual disability;
KW Ligase; Nucleotide-binding; Phosphoprotein; Protein biosynthesis;
KW Reference proteome.
FT CHAIN 1..1262
FT /note="Isoleucine--tRNA ligase, cytoplasmic"
FT /id="PRO_0000098597"
FT MOTIF 48..58
FT /note="'HIGH' region"
FT MOTIF 600..604
FT /note="'KMSKS' region"
FT BINDING 603
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 1047
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 1049
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 1058
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 302
FT /note="N -> Y (in dbSNP:rs140666586)"
FT /evidence="ECO:0000269|PubMed:24706940"
FT /id="VAR_071387"
FT VARIANT 370
FT /note="V -> G (in GRIDHH; dbSNP:rs886037876)"
FT /evidence="ECO:0000269|PubMed:27426735"
FT /id="VAR_077055"
FT VARIANT 437
FT /note="P -> L (in GRIDHH; dbSNP:rs886037874)"
FT /evidence="ECO:0000269|PubMed:27426735"
FT /id="VAR_077056"
FT VARIANT 684
FT /note="T -> M (in dbSNP:rs2070053)"
FT /id="VAR_058300"
FT VARIANT 769
FT /note="M -> I"
FT /evidence="ECO:0000269|PubMed:7721108"
FT /id="VAR_057951"
FT VARIANT 992
FT /note="N -> D (in GRIDHH; dbSNP:rs886037877)"
FT /evidence="ECO:0000269|PubMed:27426735"
FT /id="VAR_077057"
FT VARIANT 1174
FT /note="I -> N (in GRIDHH; dbSNP:rs886037873)"
FT /evidence="ECO:0000269|PubMed:27426735"
FT /id="VAR_077058"
FT VARIANT 1182
FT /note="K -> E (in dbSNP:rs556155)"
FT /evidence="ECO:0000269|PubMed:17974005"
FT /id="VAR_057952"
FT VARIANT 1188
FT /note="M -> T (in dbSNP:rs201071417)"
FT /evidence="ECO:0000269|PubMed:24706940"
FT /id="VAR_071388"
FT CONFLICT 658
FT /note="N -> S (in Ref. 4; CAD97671)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1262 AA; 144498 MW; 73CB3967A6868005 CRC64;
MLQQVPENIN FPAEEEKILE FWTEFNCFQE CLKQSKHKPK FTFYDGPPFA TGLPHYGHIL
AGTIKDIVTR YAHQSGFHVD RRFGWDCHGL PVEYEIDKTL GIRGPEDVAK MGITEYNNQC
RAIVMRYSAE WKSTVSRLGR WIDFDNDYKT LYPQFMESVW WVFKQLYDKG LVYRGVKVMP
FSTACNTPLS NFESHQNYKD VQDPSVFVTF PLEEDETVSL VAWTTTPWTL PSNLAVCVNP
EMQYVKIKDV ARGRLLILME ARLSALYKLE SDYEILERFP GAYLKGKKYR PLFDYFLKCK
ENGAFTVLVD NYVKEEEGTG VVHQAPYFGA EDYRVCMDFN IIRKDSLPVC PVDASGCFTT
EVTDFAGQYV KDADKSIIRT LKEQGRLLVA TTFTHSYPFC WRSDTPLIYK AVPSWFVRVE
NMVDQLLRNN DLCYWVPELV REKRFGNWLK DARDWTISRN RYWGTPIPLW VSDDFEEVVC
IGSVAELEEL SGAKISDLHR ESVDHLTIPS RCGKGSLHRI SEVFDCWFES GSMPYAQVHY
PFENKREFED AFPADFIAEG IDQTRGWFYT LLVLATALFG QPPFKNVIVN GLVLASDGQK
MSKRKKNYPD PVSIIQKYGA DALRLYLINS PVVRAENLRF KEEGVRDVLK DVLLPWYNAY
RFLIQNVLRL QKEEEIEFLY NENTVRESPN ITDRWILSFM QSLIGFFETE MAAYRLYTVV
PRLVKFVDIL TNWYVRMNRR RLKGENGMED CVMALETLFS VLLSLCRLMA PYTPFLTELM
YQNLKVLIDP VSVQDKDTLS IHYLMLPRVR EELIDKKTES AVSQMQSVIE LGRVIRDRKT
IPIKYPLKEI VVIHQDPEAL KDIKSLEKYI IEELNVRKVT LSTDKNKYGI RLRAEPDHMV
LGKRLKGAFK AVMTSIKQLS SEELEQFQKT GTIVVEGHEL HDEDIRLMYT FDQATGGTAQ
FEAHSDAQAL VLLDVTPDQS MVDEGMAREV INRIQKLRKK CNLVPTDEIT VYYKAKSEGT
YLNSVIESHT EFIFTTIKAP LKPYPVSPSD KVLIQEKTQL KGSELEITLT RGSSLPGPAC
AYVNLNICAN GSEQGGVLLL ENPKGDNRLD LLKLKSVVTS IFGVKNTELA VFHDETEIQN
QTDLLSLSGK TLCVTAGSAP SLINSSSTLL CQYINLQLLN AKPQECLMGT VGTLLLENPL
GQNGLTHQGL LYEAAKVFGL RSRKLKLFLN ETQTQEITED IPVKTLNMKT VYVSVLPTTA
DF
