IARS1
Isoleucine--tRNA ligase, cytoplasmic
Also known as: IARS, ILRS, SYIC_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P41252
- Gene
- IARS1
- Ensembl
- ENSG00000196305
- Chromosome
- 9
- Canonical length
- 1262 aa
- Protein class
- Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins
- Subcellular location
- Nucleoplasm,Cytosol
OverviewNCBI Gene
Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Isoleucine-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family and has been identified as a target of autoantibodies in the autoimmune disease polymyositis/dermatomyositis. Alternatively spliced transcript variants have been found. [provided by RefSeq, Nov 2012]
Canonical amino-acid sequenceUniProt
1262 residues, UniProt reviewed canonical sequence.
>P41252|IARS1
1 MLQQVPENIN FPAEEEKILE FWTEFNCFQE CLKQSKHKPK FTFYDGPPFA TGLPHYGHIL
61 AGTIKDIVTR YAHQSGFHVD RRFGWDCHGL PVEYEIDKTL GIRGPEDVAK MGITEYNNQC
121 RAIVMRYSAE WKSTVSRLGR WIDFDNDYKT LYPQFMESVW WVFKQLYDKG LVYRGVKVMP
181 FSTACNTPLS NFESHQNYKD VQDPSVFVTF PLEEDETVSL VAWTTTPWTL PSNLAVCVNP
241 EMQYVKIKDV ARGRLLILME ARLSALYKLE SDYEILERFP GAYLKGKKYR PLFDYFLKCK
301 ENGAFTVLVD NYVKEEEGTG VVHQAPYFGA EDYRVCMDFN IIRKDSLPVC PVDASGCFTT
361 EVTDFAGQYV KDADKSIIRT LKEQGRLLVA TTFTHSYPFC WRSDTPLIYK AVPSWFVRVE
421 NMVDQLLRNN DLCYWVPELV REKRFGNWLK DARDWTISRN RYWGTPIPLW VSDDFEEVVC
481 IGSVAELEEL SGAKISDLHR ESVDHLTIPS RCGKGSLHRI SEVFDCWFES GSMPYAQVHY
541 PFENKREFED AFPADFIAEG IDQTRGWFYT LLVLATALFG QPPFKNVIVN GLVLASDGQK
601 MSKRKKNYPD PVSIIQKYGA DALRLYLINS PVVRAENLRF KEEGVRDVLK DVLLPWYNAY
661 RFLIQNVLRL QKEEEIEFLY NENTVRESPN ITDRWILSFM QSLIGFFETE MAAYRLYTVV
721 PRLVKFVDIL TNWYVRMNRR RLKGENGMED CVMALETLFS VLLSLCRLMA PYTPFLTELM
781 YQNLKVLIDP VSVQDKDTLS IHYLMLPRVR EELIDKKTES AVSQMQSVIE LGRVIRDRKT
841 IPIKYPLKEI VVIHQDPEAL KDIKSLEKYI IEELNVRKVT LSTDKNKYGI RLRAEPDHMV
901 LGKRLKGAFK AVMTSIKQLS SEELEQFQKT GTIVVEGHEL HDEDIRLMYT FDQATGGTAQ
961 FEAHSDAQAL VLLDVTPDQS MVDEGMAREV INRIQKLRKK CNLVPTDEIT VYYKAKSEGT
1021 YLNSVIESHT EFIFTTIKAP LKPYPVSPSD KVLIQEKTQL KGSELEITLT RGSSLPGPAC
1081 AYVNLNICAN GSEQGGVLLL ENPKGDNRLD LLKLKSVVTS IFGVKNTELA VFHDETEIQN
1141 QTDLLSLSGK TLCVTAGSAP SLINSSSTLL CQYINLQLLN AKPQECLMGT VGTLLLENPL
1201 GQNGLTHQGL LYEAAKVFGL RSRKLKLFLN ETQTQEITED IPVKTLNMKT VYVSVLPTTA
1261 DFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against IARS1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.24
- Highest tissue expression
- 50 nTPM
Expression across tissuesHPA
Tissue
- thyroid gland: 50 nTPM
- parathyroid gland: 45 nTPM
- tongue: 42 nTPM
- smooth muscle: 35 nTPM
- skeletal muscle: 35 nTPM
- tonsil: 31 nTPM
Single-cell type
- erythrocyte progenitors: 249 nCPM
- basal keratinocytes: 205 nCPM
- epididymal principal cells: 182 nCPM
- suprabasal keratinocytes: 165 nCPM
- megakaryocyte-erythroid progenitors: 145 nCPM
- podocytes: 137 nCPM
Immune cell
- MAIT T-cell: 9.6 nTPM
- NK-cell: 8.7 nTPM
- memory CD8 T-cell: 7.7 nTPM
- naive CD4 T-cell: 7.5 nTPM
- naive CD8 T-cell: 7.3 nTPM
- myeloid DC: 7.1 nTPM
Brain region
- choroid plexus: 17 nTPM
- hypothalamus: 12 nTPM
- pons: 11 nTPM
- medulla oblongata: 10 nTPM
- cerebral cortex: 10 nTPM
- basal ganglia: 9.4 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about IARS1.
Disease | AllUniProt
Conditions IARS1 is implicated in, by any mechanism.
- Growth retardation, impaired intellectual development, hypotonia, and hepatopathy (GRIDHH) MIM:617093
Disease | GeneticClinVar
37 pathogenic / likely-pathogenic of 529 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Growth retardation, intellectual developmental disorder, hypotonia, and hepatopathy
- Microcephaly
- Global developmental delay
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.77
- gnomAD pLI
- 0
- DepMap mean gene effect
- -1.88
- DepMap dependency class
- pan
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
Molecular functions
- aminoacyl-tRNA deacylase activity
- ATP binding
- GTPase binding
- isoleucine-tRNA ligase activity
- tRNA binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Aminoacyl-tRNA synthetase, class I, conserved site
- Aminoacyl-tRNA synthetase, class Ia
- Isoleucine-tRNA ligase
- Valyl/Leucyl/Isoleucyl-tRNA synthetase, editing domain
- Aminoacyl-tRNA synthetase, class Ia, anticodon-binding
- Methionyl/Valyl/Leucyl/Isoleucyl-tRNA synthetase, anticodon-binding
- Rossmann-like alpha/beta/alpha sandwich fold
- tRNA synthetases class I (I, L, M and V)
- Anticodon-binding domain of tRNA ligase
- Isoleucine-tRNA ligase, type 2
- Isoleucyl tRNA synthetase type 2, anticodon-binding domain
- Isoleucine--tRNA ligase, cytoplasmic, ubiquitin-like domain
- Domain of unknown function (DUF5915)
- Isoleucine--tRNA ligase, cytoplasmic, ubiquitin-like
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of IARS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads IARS1 as an antibody target. Whether an autoantibody or antibody against IARS1 could matter depends on whether native IARS1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
IARS1 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Source-annotated serology context
The source annotations explicitly mention antibody, autoantibody, autoantigen, or autoimmune context. This is biological context, not study-specific reactivity.
- Isoleucine-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family and has been identified as a target of autoantibodies in the autoimmune disease polymyositis/dermatomyositis.
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