WARS1

Protein identityUniProt · HPA

UniProt accession

P23381

Gene

WARS1

Ensembl

ENSG00000140105

Chromosome

14

Canonical length

471 aa

Protein class

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

Subcellular location

Cytosol

Quaternary structure

Homodimer

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. Two forms of tryptophanyl-tRNA synthetase exist, a cytoplasmic form, named WARS, and a mitochondrial form, named WARS2. Tryptophanyl-tRNA synthetase (WARS) catalyzes the aminoacylation of tRNA(trp) with tryptophan and is induced by interferon. Tryptophanyl-tRNA synthetase belongs to the class I tRNA synthetase family. Four transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

471 residues, UniProt reviewed canonical sequence.

>P23381|WARS1
     1  MPNSEPASLL ELFNSIATQG ELVRSLKAGN ASKDEIDSAV KMLVSLKMSY KAAAGEDYKA
    61  DCPPGNPAPT SNHGPDATEA EEDFVDPWTV QTSSAKGIDY DKLIVRFGSS KIDKELINRI
   121  ERATGQRPHH FLRRGIFFSH RDMNQVLDAY ENKKPFYLYT GRGPSSEAMH VGHLIPFIFT
   181  KWLQDVFNVP LVIQMTDDEK YLWKDLTLDQ AYSYAVENAK DIIACGFDIN KTFIFSDLDY
   241  MGMSSGFYKN VVKIQKHVTF NQVKGIFGFT DSDCIGKISF PAIQAAPSFS NSFPQIFRDR
   301  TDIQCLIPCA IDQDPYFRMT RDVAPRIGYP KPALLHSTFF PALQGAQTKM SASDPNSSIF
   361  LTDTAKQIKT KVNKHAFSGG RDTIEEHRQF GGNCDVDVSF MYLTFFLEDD DKLEQIRKDY
   421  TSGAMLTGEL KKALIEVLQP LIAEHQARRK EVTDEIVKEF MTPRKLSFDF Q

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against WARS1 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)

0.27

Highest tissue expression

305 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about WARS1.

Disease | AllUniProt

Conditions WARS1 is implicated in, by any mechanism.

• Neuronopathy, distal hereditary motor, autosomal dominant 9 (HMND9) MIM:617721
• Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities (NEDMSBA) MIM:620317

Disease | GeneticClinVar

5 pathogenic / likely-pathogenic of 148 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with microcephaly and speech delay, with or without brain abnormalities

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)

0.49

gnomAD pLI

0.3

DepMap mean gene effect

-1.26

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• angiogenesis
• intracellular signal transduction
• negative regulation of cell population proliferation
• regulation of angiogenesis
• translation
• tryptophanyl-tRNA aminoacylation

Molecular functions

• ATP binding
• protein domain specific binding
• protein homodimerization activity
• protein kinase binding
• protein-macromolecule adaptor activity
• tryptophan-tRNA ligase activity

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• nucleus
• protein-containing complex

Protein domainsUniProt · Pfam · InterPro

• WHEP-TRS domain
• Aminoacyl-tRNA synthetase, class I, conserved site
• Aminoacyl-tRNA synthetase, class Ic
• Tryptophan-tRNA ligase
• uS15/NS1, RNA-binding domain superfamily
• Rossmann-like alpha/beta/alpha sandwich fold
• WHEP-TRS domain
• tRNA synthetases class I (W and Y)

KeywordsUniProt

• Aminoacyl-tRNA synthetase
• Angiogenesis
• ATP-binding
• Cytoplasm
• Intellectual disability
• Ligase
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Phosphoprotein
• Protein biosynthesis

InteractionsUniProt · HPA

Protein binding partners of WARS1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• GAPDH