WARS2

Protein identityUniProt · HPA

UniProt accession

Q9UGM6

Gene

WARS2

Ensembl

ENSG00000116874

Chromosome

1

Canonical length

360 aa

Protein class

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

Subcellular location

Mitochondria

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. This gene encodes the mitochondrial tryptophanyl-tRNA synthetase. Two alternative transcripts encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

360 residues, UniProt reviewed canonical sequence.

>Q9UGM6|WARS2
     1  MALHSMRKAR ERWSFIRALH KGSAAAPALQ KDSKKRVFSG IQPTGILHLG NYLGAIESWV
    61  RLQDEYDSVL YSIVDLHSIT VPQDPAVLRQ SILDMTAVLL ACGINPEKSI LFQQSQVSEH
   121  TQLSWILSCM VRLPRLQHLH QWKAKTTKQK HDGTVGLLTY PVLQAADILL YKSTHVPVGE
   181  DQVQHMELVQ DLAQGFNKKY GEFFPVPESI LTSMKKVKSL RDPSAKMSKS DPDKLATVRI
   241  TDSPEEIVQK FRKAVTDFTS EVTYDPAGRA GVSNIVAVHA AVTGLSVEEV VRRSAGMNTA
   301  RYKLAVADAV IEKFAPIKRE IEKLKLDKDH LEKVLQIGSA KAKELAYTVC QEVKKLVGFL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against WARS2 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)

0.29

Highest tissue expression

9.6 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about WARS2.

Disease | AllUniProt

Conditions WARS2 is implicated in, by any mechanism.

• Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures (NEMMLAS) MIM:617710
• Parkinsonism-dystonia 3, childhood-onset (PKDYS3) MIM:619738

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 180 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures
• Parkinsonism-dystonia 3, childhood-onset
• WARS2-related disorder
• Inborn genetic diseases

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)

0.67

gnomAD pLI

0.05

gnomAD missense Z

0.9

DepMap mean gene effect

-0.44

DepMap dependency class

selective

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

• positive regulation of angiogenesis
• tRNA aminoacylation for protein translation
• vasculogenesis
• mitochondrial tryptophanyl-tRNA aminoacylation

Molecular functions

• ATP binding
• tryptophan-tRNA ligase activity

Cellular components

• mitochondrial matrix
• mitochondrion
• nucleoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Aminoacyl-tRNA synthetase, class I, conserved site
• Aminoacyl-tRNA synthetase, class Ic
• Tryptophan-tRNA ligase
• Rossmann-like alpha/beta/alpha sandwich fold
• tRNA synthetases class I (W and Y)
• Tryptophan-tRNA ligase, bacterial-type
• Tryptophan--tRNA ligase

KeywordsUniProt

• Aminoacyl-tRNA synthetase
• ATP-binding
• Dystonia
• Ligase
• Mitochondrion
• Nucleotide-binding
• Parkinsonism
• Primary mitochondrial disease
• Protein biosynthesis
• Transit peptide