HARS1

Protein identityUniProt · HPA

UniProt accession

P12081

Gene

HARS1

Ensembl

ENSG00000170445

Chromosome

5

Canonical length

509 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 are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

Canonical amino-acid sequenceUniProt

509 residues, UniProt reviewed canonical sequence.

>P12081|HARS1
     1  MAERAALEEL VKLQGERVRG LKQQKASAEL IEEEVAKLLK LKAQLGPDES KQKFVLKTPK
    61  GTRDYSPRQM AVREKVFDVI IRCFKRHGAE VIDTPVFELK ETLMGKYGED SKLIYDLKDQ
   121  GGELLSLRYD LTVPFARYLA MNKLTNIKRY HIAKVYRRDN PAMTRGRYRE FYQCDFDIAG
   181  NFDPMIPDAE CLKIMCEILS SLQIGDFLVK VNDRRILDGM FAICGVSDSK FRTICSSVDK
   241  LDKVSWEEVK NEMVGEKGLA PEVADRIGDY VQQHGGVSLV EQLLQDPKLS QNKQALEGLG
   301  DLKLLFEYLT LFGIDDKISF DLSLARGLDY YTGVIYEAVL LQTPAQAGEE PLGVGSVAAG
   361  GRYDGLVGMF DPKGRKVPCV GLSIGVERIF SIVEQRLEAL EEKIRTTETQ VLVASAQKKL
   421  LEERLKLVSE LWDAGIKAEL LYKKNPKLLN QLQYCEEAGI PLVAIIGEQE LKDGVIKLRS
   481  VTSREEVDVR REDLVEEIKR RTGQPLCIC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HARS1 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

78 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HARS1.

Disease | AllUniProt

Conditions HARS1 is implicated in, by any mechanism.

• Usher syndrome 3B (USH3B) MIM:614504
• Charcot-Marie-Tooth disease, axonal, type 2W (CMT2W) MIM:616625

Disease | GeneticClinVar

10 pathogenic / likely-pathogenic of 683 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autosomal dominant Charcot-Marie-Tooth disease type 2W
• Spastic ataxia
• 10 conditions
• 11 conditions
• HARS1-related multi-system ataxia syndrome

Disease | AutoantibodyPubMed

Conditions in which antibodies against HARS1 are reported. Each links to that disease's full target list.

• Myositis 200
• Lung Diseases, Interstitial 104
• Dermatomyositis 91
• Polymyositis 80
• Pulmonary Fibrosis 29
• Arthritis 24
• Arthritis, Rheumatoid 15
• Scleroderma, Systemic 14
• Lupus Erythematosus, Systemic 13
• Raynaud Disease 13
• Sjogren's Syndrome 13
• Muscle Weakness 7
• Calcinosis 6

Showing 13 of 19 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for HARS1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

0.76

gnomAD pLI

0

DepMap mean gene effect

-1.48

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

• histidyl-tRNA aminoacylation
• translation
• tRNA aminoacylation for protein translation

Molecular functions

• ATP binding
• histidine-tRNA ligase activity
• identical protein binding
• protein homodimerization activity
• RNA binding

Cellular components

• cytosol

Protein domainsUniProt · Pfam · InterPro

• WHEP-TRS domain
• Anticodon-binding
• Histidine-tRNA ligase/ATP phosphoribosyltransferase regulatory subunit
• Aminoacyl-tRNA synthetase, class II
• uS15/NS1, RNA-binding domain superfamily
• Histidine-tRNA ligase
• Histidyl-anticodon-binding
• Anticodon-binding domain superfamily
• Class II Histidinyl-tRNA synthetase (HisRS)-like catalytic core domain
• Class II Aminoacyl-tRNA synthetase/Biotinyl protein ligase (BPL) and lipoyl protein ligase (LPL)
• WHEP-TRS domain
• Anticodon binding domain
• Histidyl-tRNA synthetase

KeywordsUniProt

• Acetylation
• Aminoacyl-tRNA synthetase
• ATP-binding
• Charcot-Marie-Tooth disease
• Cytoplasm
• Deafness
• Ligase
• Neurodegeneration
• Neuropathy
• Nucleotide-binding
• Phosphoprotein
• Protein biosynthesis
• Retinitis pigmentosa
• Usher syndrome