DARS1
Aspartate--tRNA ligase, cytoplasmic
Also known as: DARS, SYDC_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P14868
- Gene
- DARS1
- Ensembl
- ENSG00000115866
- Chromosome
- 2
- Canonical length
- 501 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
This gene encodes a member of a multienzyme complex that functions in mediating the attachment of amino acids to their cognate tRNAs. The encoded protein ligates L-aspartate to tRNA(Asp). Mutations in this gene have been found in patients showing hypomyelination with brainstem and spinal cord involvement and leg spasticity. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]
Canonical amino-acid sequenceUniProt
501 residues, UniProt reviewed canonical sequence.
>P14868|DARS1
1 MPSASASRKS QEKPREIMDA AEDYAKERYG ISSMIQSQEK PDRVLVRVRD LTIQKADEVV
61 WVRARVHTSR AKGKQCFLVL RQQQFNVQAL VAVGDHASKQ MVKFAANINK ESIVDVEGVV
121 RKVNQKIGSC TQQDVELHVQ KIYVISLAEP RLPLQLDDAV RPEAEGEEEG RATVNQDTRL
181 DNRVIDLRTS TSQAVFRLQS GICHLFRETL INKGFVEIQT PKIISAASEG GANVFTVSYF
241 KNNAYLAQSP QLYKQMCICA DFEKVFSIGP VFRAEDSNTH RHLTEFVGLD IEMAFNYHYH
301 EVMEEIADTM VQIFKGLQER FQTEIQTVNK QFPCEPFKFL EPTLRLEYCE ALAMLREAGV
361 EMGDEDDLST PNEKLLGHLV KEKYDTDFYI LDKYPLAVRP FYTMPDPRNP KQSNSYDMFM
421 RGEEILSGAQ RIHDPQLLTE RALHHGIDLE KIKAYIDSFR FGAPPHAGGG IGLERVTMLF
481 LGLHNVRQTS MFPRDPKRLT PLocalizationUniProt · AlphaFold · HPA
Whether an antibody against DARS1 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
- 81 nTPM
Expression across tissuesHPA
Tissue
- retina: 81 nTPM
- skeletal muscle: 78 nTPM
- thymus: 59 nTPM
- tongue: 56 nTPM
- tonsil: 52 nTPM
- ovary: 48 nTPM
Single-cell type
- esophageal apical cells: 250 nCPM
- pancreatic acinar cells: 250 nCPM
- extravillous trophoblasts: 236 nCPM
- migrating cytotrophoblasts: 211 nCPM
- syncytiotrophoblasts: 204 nCPM
- esophageal suprabasal cells: 186 nCPM
Immune cell
- memory B-cell: 221 nTPM
- naive B-cell: 200 nTPM
- naive CD4 T-cell: 176 nTPM
- MAIT T-cell: 175 nTPM
- memory CD4 T-cell: 173 nTPM
- NK-cell: 172 nTPM
Brain region
- hypothalamus: 46 nTPM
- medulla oblongata: 46 nTPM
- white matter: 46 nTPM
- spinal cord: 43 nTPM
- cerebellum: 42 nTPM
- pons: 38 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about DARS1.
Disease | AllUniProt
Conditions DARS1 is implicated in, by any mechanism.
- Hypomyelination with brainstem and spinal cord involvement and leg spasticity (HBSL) MIM:615281
Disease | GeneticClinVar
11 pathogenic / likely-pathogenic of 263 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Hypomyelination with brain stem and spinal cord involvement and leg spasticity
- Abnormal brain morphology
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)
- 0.68
- gnomAD pLI
- 0
- DepMap mean gene effect
- -1.91
- 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
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Aspartyl/Asparaginyl-tRNA synthetase, class IIb
- Aminoacyl-tRNA synthetase, class II (D/K/N)
- OB-fold nucleic acid binding domain, AA-tRNA synthetase-type
- Aminoacyl-tRNA synthetase, class II
- Nucleic acid-binding, OB-fold
- Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
- tRNA synthetases class II (D, K and N)
- OB-fold nucleic acid binding domain
- Aspartate-tRNA synthetase, type 2
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of DARS1 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 DARS1 as an antibody target. Whether an autoantibody or antibody against DARS1 could matter depends on whether native DARS1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
DARS1 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.
Annotation status
The present source text does not explicitly label DARS1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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