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Protein

Isoleucine--tRNA ligase, cytoplasmic

Gene

IARS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.1 Publication

Catalytic activityi

ATP + L-isoleucine + tRNA(Ile) = AMP + diphosphate + L-isoleucyl-tRNA(Ile).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei603ATPBy similarity1

GO - Molecular functioni

  • aminoacyl-tRNA editing activity Source: InterPro
  • ATP binding Source: UniProtKB-KW
  • GTPase binding Source: UniProtKB
  • isoleucine-tRNA ligase activity Source: UniProtKB
  • tRNA binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionAminoacyl-tRNA synthetase, Ligase
Biological processProtein biosynthesis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-2408517 SeMet incorporation into proteins
R-HSA-379716 Cytosolic tRNA aminoacylation

Names & Taxonomyi

Protein namesi
Recommended name:
Isoleucine--tRNA ligase, cytoplasmic (EC:6.1.1.51 Publication)
Alternative name(s):
Isoleucyl-tRNA synthetase
Short name:
IRS
Short name:
IleRS
Gene namesi
Name:IARS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000196305.17
HGNCiHGNC:5330 IARS
MIMi600709 gene
neXtProtiNX_P41252

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy (GRIDHH)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by severe growth retardation with prenatal onset, intellectual disability, muscular hypotonia, and hepatic dysfunction.
See also OMIM:617093
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077055370V → G in GRIDHH. 1 PublicationCorresponds to variant dbSNP:rs886037876EnsemblClinVar.1
Natural variantiVAR_077056437P → L in GRIDHH. 1 PublicationCorresponds to variant dbSNP:rs886037874EnsemblClinVar.1
Natural variantiVAR_077057992N → D in GRIDHH. 1 PublicationCorresponds to variant dbSNP:rs886037877EnsemblClinVar.1
Natural variantiVAR_0770581174I → N in GRIDHH. 1 PublicationCorresponds to variant dbSNP:rs886037873EnsemblClinVar.1

Keywords - Diseasei

Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi3376
MalaCardsiIARS
MIMi617093 phenotype
OpenTargetsiENSG00000196305
PharmGKBiPA29580

Chemistry databases

ChEMBLiCHEMBL3235
DrugBankiDB00167 L-Isoleucine

Polymorphism and mutation databases

DMDMi239938717

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000985971 – 1262Isoleucine--tRNA ligase, cytoplasmicAdd BLAST1262

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei1047PhosphoserineCombined sources1
Modified residuei1049PhosphoserineCombined sources1
Modified residuei1058PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP41252
MaxQBiP41252
PaxDbiP41252
PeptideAtlasiP41252
PRIDEiP41252
ProteomicsDBi55454

PTM databases

CarbonylDBiP41252
iPTMnetiP41252
PhosphoSitePlusiP41252
SwissPalmiP41252

Miscellaneous databases

PMAP-CutDBiP41252

Expressioni

Tissue specificityi

Expressed in liver and muscle (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000196305 Expressed in 238 organ(s), highest expression level in middle temporal gyrus
CleanExiHS_IARS
ExpressionAtlasiP41252 baseline and differential
GenevisibleiP41252 HS

Organism-specific databases

HPAiHPA029806

Interactioni

Subunit structurei

Part of a multisubunit complex that groups tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:19131329, PubMed:19289464).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EPRSP078146EBI-355303,EBI-355315

GO - Molecular functioni

Protein-protein interaction databases

BioGridi109605, 188 interactors
CORUMiP41252
IntActiP41252, 37 interactors
MINTiP41252
STRINGi9606.ENSP00000364794

Chemistry databases

BindingDBiP41252

Structurei

3D structure databases

ProteinModelPortaliP41252
SMRiP41252
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi48 – 58"HIGH" regionAdd BLAST11
Motifi600 – 604"KMSKS" region5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0434 Eukaryota
COG0060 LUCA
GeneTreeiENSGT00550000074921
HOGENOMiHOG000246403
HOVERGENiHBG013511
InParanoidiP41252
KOiK01870
OMAiGYRVMPY
OrthoDBiEOG091G01AQ
PhylomeDBiP41252

Family and domain databases

CDDicd07961 Anticodon_Ia_Ile_ABEc, 1 hit
Gene3Di3.40.50.620, 1 hit
3.90.740.10, 1 hit
HAMAPiMF_02003 Ile_tRNA_synth_type2, 1 hit
InterProiView protein in InterPro
IPR001412 aa-tRNA-synth_I_CS
IPR002300 aa-tRNA-synth_Ia
IPR033709 Anticodon_Ile_ABEc
IPR002301 Ile-tRNA-ligase
IPR023586 Ile-tRNA-ligase_type2
IPR013155 M/V/L/I-tRNA-synth_anticd-bd
IPR014729 Rossmann-like_a/b/a_fold
IPR009080 tRNAsynth_Ia_anticodon-bd
IPR009008 Val/Leu/Ile-tRNA-synth_edit
PfamiView protein in Pfam
PF08264 Anticodon_1, 1 hit
PF00133 tRNA-synt_1, 1 hit
PRINTSiPR00984 TRNASYNTHILE
SUPFAMiSSF47323 SSF47323, 1 hit
SSF50677 SSF50677, 1 hit
TIGRFAMsiTIGR00392 ileS, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 5 potential isoforms that are computationally mapped.Show allAlign All

P41252-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLQQVPENIN FPAEEEKILE FWTEFNCFQE CLKQSKHKPK FTFYDGPPFA
60 70 80 90 100
TGLPHYGHIL AGTIKDIVTR YAHQSGFHVD RRFGWDCHGL PVEYEIDKTL
110 120 130 140 150
GIRGPEDVAK MGITEYNNQC RAIVMRYSAE WKSTVSRLGR WIDFDNDYKT
160 170 180 190 200
LYPQFMESVW WVFKQLYDKG LVYRGVKVMP FSTACNTPLS NFESHQNYKD
210 220 230 240 250
VQDPSVFVTF PLEEDETVSL VAWTTTPWTL PSNLAVCVNP EMQYVKIKDV
260 270 280 290 300
ARGRLLILME ARLSALYKLE SDYEILERFP GAYLKGKKYR PLFDYFLKCK
310 320 330 340 350
ENGAFTVLVD NYVKEEEGTG VVHQAPYFGA EDYRVCMDFN IIRKDSLPVC
360 370 380 390 400
PVDASGCFTT EVTDFAGQYV KDADKSIIRT LKEQGRLLVA TTFTHSYPFC
410 420 430 440 450
WRSDTPLIYK AVPSWFVRVE NMVDQLLRNN DLCYWVPELV REKRFGNWLK
460 470 480 490 500
DARDWTISRN RYWGTPIPLW VSDDFEEVVC IGSVAELEEL SGAKISDLHR
510 520 530 540 550
ESVDHLTIPS RCGKGSLHRI SEVFDCWFES GSMPYAQVHY PFENKREFED
560 570 580 590 600
AFPADFIAEG IDQTRGWFYT LLVLATALFG QPPFKNVIVN GLVLASDGQK
610 620 630 640 650
MSKRKKNYPD PVSIIQKYGA DALRLYLINS PVVRAENLRF KEEGVRDVLK
660 670 680 690 700
DVLLPWYNAY RFLIQNVLRL QKEEEIEFLY NENTVRESPN ITDRWILSFM
710 720 730 740 750
QSLIGFFETE MAAYRLYTVV PRLVKFVDIL TNWYVRMNRR RLKGENGMED
760 770 780 790 800
CVMALETLFS VLLSLCRLMA PYTPFLTELM YQNLKVLIDP VSVQDKDTLS
810 820 830 840 850
IHYLMLPRVR EELIDKKTES AVSQMQSVIE LGRVIRDRKT IPIKYPLKEI
860 870 880 890 900
VVIHQDPEAL KDIKSLEKYI IEELNVRKVT LSTDKNKYGI RLRAEPDHMV
910 920 930 940 950
LGKRLKGAFK AVMTSIKQLS SEELEQFQKT GTIVVEGHEL HDEDIRLMYT
960 970 980 990 1000
FDQATGGTAQ FEAHSDAQAL VLLDVTPDQS MVDEGMAREV INRIQKLRKK
1010 1020 1030 1040 1050
CNLVPTDEIT VYYKAKSEGT YLNSVIESHT EFIFTTIKAP LKPYPVSPSD
1060 1070 1080 1090 1100
KVLIQEKTQL KGSELEITLT RGSSLPGPAC AYVNLNICAN GSEQGGVLLL
1110 1120 1130 1140 1150
ENPKGDNRLD LLKLKSVVTS IFGVKNTELA VFHDETEIQN QTDLLSLSGK
1160 1170 1180 1190 1200
TLCVTAGSAP SLINSSSTLL CQYINLQLLN AKPQECLMGT VGTLLLENPL
1210 1220 1230 1240 1250
GQNGLTHQGL LYEAAKVFGL RSRKLKLFLN ETQTQEITED IPVKTLNMKT
1260
VYVSVLPTTA DF
Length:1,262
Mass (Da):144,498
Last modified:June 16, 2009 - v2
Checksum:i73CB3967A6868005
GO

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0A0MSX9A0A0A0MSX9_HUMAN
Isoleucine--tRNA ligase, cytoplasmi...
IARS
1,242Annotation score:
J3KR24J3KR24_HUMAN
Isoleucine--tRNA ligase, cytoplasmi...
IARS hCG_31137
1,152Annotation score:
Q5TCD1Q5TCD1_HUMAN
Isoleucine--tRNA ligase, cytoplasmi...
IARS
330Annotation score:
Q5TCC9Q5TCC9_HUMAN
Isoleucine--tRNA ligase, cytoplasmi...
IARS
72Annotation score:
Q5TCC6Q5TCC6_HUMAN
Isoleucine--tRNA ligase, cytoplasmi...
IARS
174Annotation score:

Sequence cautioni

The sequence BAA05835 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti658N → S in CAD97671 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_071387302N → Y1 PublicationCorresponds to variant dbSNP:rs140666586Ensembl.1
Natural variantiVAR_077055370V → G in GRIDHH. 1 PublicationCorresponds to variant dbSNP:rs886037876EnsemblClinVar.1
Natural variantiVAR_077056437P → L in GRIDHH. 1 PublicationCorresponds to variant dbSNP:rs886037874EnsemblClinVar.1
Natural variantiVAR_058300684T → M. Corresponds to variant dbSNP:rs2070053Ensembl.1
Natural variantiVAR_057951769M → I1 Publication1
Natural variantiVAR_077057992N → D in GRIDHH. 1 PublicationCorresponds to variant dbSNP:rs886037877EnsemblClinVar.1
Natural variantiVAR_0770581174I → N in GRIDHH. 1 PublicationCorresponds to variant dbSNP:rs886037873EnsemblClinVar.1
Natural variantiVAR_0579521182K → E1 PublicationCorresponds to variant dbSNP:rs556155Ensembl.1
Natural variantiVAR_0713881188M → T1 PublicationCorresponds to variant dbSNP:rs201071417Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
CH471089 Genomic DNA Translation: EAW62813.1
CCDSiCCDS6694.1
PIRiI59314
RefSeqiNP_002152.2, NM_002161.5
NP_038203.2, NM_013417.3
UniGeneiHs.445403

Genome annotation databases

EnsembliENST00000375643; ENSP00000364794; ENSG00000196305
GeneIDi3376
KEGGihsa:3376
UCSCiuc004art.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
CH471089 Genomic DNA Translation: EAW62813.1
CCDSiCCDS6694.1
PIRiI59314
RefSeqiNP_002152.2, NM_002161.5
NP_038203.2, NM_013417.3
UniGeneiHs.445403

3D structure databases

ProteinModelPortaliP41252
SMRiP41252
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109605, 188 interactors
CORUMiP41252
IntActiP41252, 37 interactors
MINTiP41252
STRINGi9606.ENSP00000364794

Chemistry databases

BindingDBiP41252
ChEMBLiCHEMBL3235
DrugBankiDB00167 L-Isoleucine

PTM databases

CarbonylDBiP41252
iPTMnetiP41252
PhosphoSitePlusiP41252
SwissPalmiP41252

Polymorphism and mutation databases

DMDMi239938717

Proteomic databases

EPDiP41252
MaxQBiP41252
PaxDbiP41252
PeptideAtlasiP41252
PRIDEiP41252
ProteomicsDBi55454

Protocols and materials databases

DNASUi3376
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375643; ENSP00000364794; ENSG00000196305
GeneIDi3376
KEGGihsa:3376
UCSCiuc004art.4 human

Organism-specific databases

CTDi3376
DisGeNETi3376
EuPathDBiHostDB:ENSG00000196305.17
GeneCardsiIARS
HGNCiHGNC:5330 IARS
HPAiHPA029806
MalaCardsiIARS
MIMi600709 gene
617093 phenotype
neXtProtiNX_P41252
OpenTargetsiENSG00000196305
PharmGKBiPA29580
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0434 Eukaryota
COG0060 LUCA
GeneTreeiENSGT00550000074921
HOGENOMiHOG000246403
HOVERGENiHBG013511
InParanoidiP41252
KOiK01870
OMAiGYRVMPY
OrthoDBiEOG091G01AQ
PhylomeDBiP41252

Enzyme and pathway databases

ReactomeiR-HSA-2408517 SeMet incorporation into proteins
R-HSA-379716 Cytosolic tRNA aminoacylation

Miscellaneous databases

ChiTaRSiIARS human
GeneWikiiIARS
GenomeRNAii3376
PMAP-CutDBiP41252
PROiPR:P41252
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000196305 Expressed in 238 organ(s), highest expression level in middle temporal gyrus
CleanExiHS_IARS
ExpressionAtlasiP41252 baseline and differential
GenevisibleiP41252 HS

Family and domain databases

CDDicd07961 Anticodon_Ia_Ile_ABEc, 1 hit
Gene3Di3.40.50.620, 1 hit
3.90.740.10, 1 hit
HAMAPiMF_02003 Ile_tRNA_synth_type2, 1 hit
InterProiView protein in InterPro
IPR001412 aa-tRNA-synth_I_CS
IPR002300 aa-tRNA-synth_Ia
IPR033709 Anticodon_Ile_ABEc
IPR002301 Ile-tRNA-ligase
IPR023586 Ile-tRNA-ligase_type2
IPR013155 M/V/L/I-tRNA-synth_anticd-bd
IPR014729 Rossmann-like_a/b/a_fold
IPR009080 tRNAsynth_Ia_anticodon-bd
IPR009008 Val/Leu/Ile-tRNA-synth_edit
PfamiView protein in Pfam
PF08264 Anticodon_1, 1 hit
PF00133 tRNA-synt_1, 1 hit
PRINTSiPR00984 TRNASYNTHILE
SUPFAMiSSF47323 SSF47323, 1 hit
SSF50677 SSF50677, 1 hit
TIGRFAMsiTIGR00392 ileS, 1 hit
PROSITEiView protein in PROSITE
PS00178 AA_TRNA_LIGASE_I, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSYIC_HUMAN
AccessioniPrimary (citable) accession number: P41252
Secondary accession number(s): A8KAE9
, Q5TCD0, Q7Z3T4, Q9H588
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: June 16, 2009
Last modified: November 7, 2018
This is version 188 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  6. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
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