Catalyzes the ATP-dependent ligation of histidine to the 3'-end of its cognate tRNA, via the formation of an aminoacyl-adenylate intermediate (His-AMP) (PubMed:29235198). Plays a role in axon guidance (PubMed:26072516). (updated: Feb. 26, 2020)
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
No sequence conservation computed yet.
Total structural coverage: 91%
No model available.
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The reference OMIM entry for this protein is 142810
Histidyl-trna synthetase; hars
Hrs
Hisrs
DESCRIPTION
HARS catalyzes the covalent ligation of histidine to its cognate tRNA as an early step in protein biosynthesis (O'Hanlon and Miller, 2002).
CLONING
O'Hanlon et al. (1995) noted that HARS and HARS2 (
600783), which they called HO3, are oriented in a head-to-head configuration and share a bidirectional promoter. They reported that the deduced 509-amino acid HARS protein shares 72% amino acid identity with HARS2. Both proteins contain 3 motifs conserved among class II aminoacyl-tRNA synthetases and 2 signature regions of histidyl-tRNA synthetases. However, HARS and HARS2 have divergent N-terminal domains that are encoded by the first 2 exons of each gene. HARS has a calculated molecular mass of 57.4 kD. Northern blot analysis detected a 2.0-kb HARS transcript that was highly expressed in heart, brain, liver, and kidney. Using 5-prime RACE with a human kidney cDNA library, O'Hanlon and Miller (2002) identified several HARS transcripts that differed only in the lengths of their 5-prime UTRs. O'Hanlon and Miller (2002) noted that pufferfish and human HARS proteins share 84% amino acid homology, suggesting a high degree of conservation. Lo et al. (2014) reported the discovery of a large number of natural catalytic nulls for each human aminoacyl tRNA synthetase. Splicing events retain noncatalytic domains while ablating the catalytic domain to create catalytic nulls with diverse functions. Each synthetase is converted into several new signaling proteins with biologic activities 'orthogonal' to that of the catalytic parent. The recombinant aminoacyl tRNA synthetase variants had specific biologic activities across a spectrum of cell-based assays: about 46% across all species affect transcriptional regulation, 22% cell differentiation, 10% immunomodulation, 10% cytoprotection, and 4% each for proliferation, adipogenesis/cholesterol transport, and inflammatory response. Lo et al. (2014) identified in-frame splice variants of cytoplasmic aminoacyl tRNA synthetases. They identified 8 catalytic-null splice variants for HisRS.
GENE STRUCTURE
O'Hanlon and Miller (2002) determined that the HARS gene contains 13 exons and spans approximately 17.4 kb. The HARS and HARS2 genes share a bidirectional promoter that lacks TATA and CAAT boxes. Both genes use multiple transcriptional start sites. HARS also uses a second, more distal promoter that overlaps the first exons of the HARS2 gene.
MAPPING
Carlock et al. (1985) used a Chinese hamster ovary (CHO) cell line with mutations in 3 genes, HARS, RPS14 (
130620) and CHR (
118840), in interspecies cell hybridization experiments, to assign the HARS gene to chromosome 5. Wasmuth and Carlock (1986) assigned the HARS gene to chromosome 5 by use of human-Chinese hamster ovary cell hybrids. By genomic sequence analysis, O'Hanlon and Miller (2002) mapped the HARS and HARS2 genes to chromosome 5q31.3. HARS and HARS2 exhibit a head-to-head orientation, with 344 bp separating their ORFs.
MOLECULAR GENETICS
- Usher Syndrome Type III In 2 patients from Old Order Amish families in Pennsylvania with Usher syndrome type III mapping to chromosome 5q (USH3B;
614504), Puffenberger et al. (2012) identified homozygosity for a missense mutation in the HARS gene (Y454S;
142810.0001) that was not found in dbSNP 129 or the 1000 Genomes Project. In addition, an Old Order Amish patient from an unrelated deme in Ontario, Canada, had an identical phenotype and was homozygous for ...
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Subscribe to this protein entry history
March 3, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 142810 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).