LARS1

Protein identityUniProt · HPA

UniProt accession

Q9P2J5

Gene

LARS1

Ensembl

ENSG00000133706

Chromosome

5

Canonical length

1176 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nuclear bodies,Cytosol

OverviewNCBI Gene

This gene encodes a cytosolic leucine-tRNA synthetase, a member of the class I aminoacyl-tRNA synthetase family. The encoded enzyme catalyzes the ATP-dependent ligation of L-leucine to tRNA(Leu). It is found in the cytoplasm as part of a multisynthetase complex and interacts with the arginine tRNA synthetase through its C-terminal domain. A mutation in this gene was found in affected individuals with infantile liver failure syndrome 1. Alternatively spliced transcript variants of this gene have been observed. [provided by RefSeq, Dec 2015]

Canonical amino-acid sequenceUniProt

1176 residues, UniProt reviewed canonical sequence.

>Q9P2J5|LARS1
     1  MAERKGTAKV DFLKKIEKEI QQKWDTERVF EVNASNLEKQ TSKGKYFVTF PYPYMNGRLH
    61  LGHTFSLSKC EFAVGYQRLK GKCCLFPFGL HCTGMPIKAC ADKLKREIEL YGCPPDFPDE
   121  EEEEEETSVK TEDIIIKDKA KGKKSKAAAK AGSSKYQWGI MKSLGLSDEE IVKFSEAEHW
   181  LDYFPPLAIQ DLKRMGLKVD WRRSFITTDV NPYYDSFVRW QFLTLRERNK IKFGKRYTIY
   241  SPKDGQPCMD HDRQTGEGVG PQEYTLLKLK VLEPYPSKLS GLKGKNIFLV AATLRPETMF
   301  GQTNCWVRPD MKYIGFETVN GDIFICTQKA ARNMSYQGFT KDNGVVPVVK ELMGEEILGA
   361  SLSAPLTSYK VIYVLPMLTI KEDKGTGVVT SVPSDSPDDI AALRDLKKKQ ALRAKYGIRD
   421  DMVLPFEPVP VIEIPGFGNL SAVTICDELK IQSQNDREKL AEAKEKIYLK GFYEGIMLVD
   481  GFKGQKVQDV KKTIQKKMID AGDALIYMEP EKQVMSRSSD ECVVALCDQW YLDYGEENWK
   541  KQTSQCLKNL ETFCEETRRN FEATLGWLQE HACSRTYGLG THLPWDEQWL IESLSDSTIY
   601  MAFYTVAHLL QGGNLHGQAE SPLGIRPQQM TKEVWDYVFF KEAPFPKTQI AKEKLDQLKQ
   661  EFEFWYPVDL RVSGKDLVPN HLSYYLYNHV AMWPEQSDKW PTAVRANGHL LLNSEKMSKS
   721  TGNFLTLTQA IDKFSADGMR LALADAGDTV EDANFVEAMA DAGILRLYTW VEWVKEMVAN
   781  WDSLRSGPAS TFNDRVFASE LNAGIIKTDQ NYEKMMFKEA LKTGFFEFQA AKDKYRELAV
   841  EGMHRELVFR FIEVQTLLLA PFCPHLCEHI WTLLGKPDSI MNASWPVAGP VNEVLIHSSQ
   901  YLMEVTHDLR LRLKNYMMPA KGKKTDKQPL QKPSHCTIYV AKNYPPWQHT TLSVLRKHFE
   961  ANNGKLPDNK VIASELGSMP ELKKYMKKVM PFVAMIKENL EKMGPRILDL QLEFDEKAVL
  1021  MENIVYLTNS LELEHIEVKF ASEAEDKIRE DCCPGKPLNV FRIEPGVSVS LVNPQPSNGH
  1081  FSTKIEIRQG DNCDSIIRRL MKMNRGIKDL SKVKLMRFDD PLLGPRRVPV LGKEYTEKTP
  1141  ISEHAVFNVD LMSKKIHLTE NGIRVDIGDT IIYLVH

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against LARS1 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

64 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about LARS1.

Disease | AllUniProt

Conditions LARS1 is implicated in, by any mechanism.

• Infantile liver failure syndrome 1 (ILFS1) MIM:615438

Disease | GeneticClinVar

29 pathogenic / likely-pathogenic of 606 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins
• Infantile liver failure syndrome 1
• LARS1-related disorder

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)

0.53

gnomAD pLI

0

DepMap mean gene effect

-1.65

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to amino acid starvation
• cellular response to amino acid stimulus
• cellular response to L-leucine
• cellular response to leucine starvation
• glutaminyl-tRNA aminoacylation
• leucyl-tRNA aminoacylation
• positive regulation of TORC1 signaling
• tRNA aminoacylation for protein translation

Molecular functions

• aminoacyl-tRNA deacylase activity
• ATP binding
• glutamine-tRNA ligase activity
• GTPase activator activity
• leucine-tRNA ligase activity

Cellular components

• aminoacyl-tRNA synthetase multienzyme complex
• cytoplasm
• cytosol
• endomembrane system
• endoplasmic reticulum
• lysosome
• nuclear body

Protein domainsUniProt · Pfam · InterPro

• Aminoacyl-tRNA synthetase, class I, conserved site
• Aminoacyl-tRNA synthetase, class Ia
• 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
• Leucyl-tRNA synthetase, class Ia, archaeal/eukaryotic cytosolic
• Leucine--tRNA ligase, ubiquitin-like domain
• Leucine--tRNA ligase, RagD-binding domain
• Leucine--tRNA ligase, ubiquitin-like domain
• Leucine--tRNA ligase, RagD-binding domain

KeywordsUniProt

• Acetylation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Cytoplasm
• Ligase
• Nucleotide-binding
• Phosphoprotein
• Protein biosynthesis

InteractionsUniProt · HPA

Protein binding partners of LARS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AIMP1
• AIMP2
• DARS1
• EEF1E1
• EPRS1
• IARS1
• MARS1
• QARS1
• RARS1