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Information on EC 6.1.1.21 - histidine-tRNA ligase and Organism(s) Homo sapiens and UniProt Accession P49590

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Homo sapiens
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
histidyl-trna synthetase, hisrs, hars2, jo-1 antigen, histidyl trna synthetase, histidyl-transfer rna synthetase, class ii histidyl-trna synthetase, hars1, histidine-trna ligase, mitochondrial histidyl trna synthetase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Histidine translase
-
histidine-tRNA ligase
-
histidine-tRNA ligase homolog
-
Histidyl-transfer ribonucleate synthetase
-
Histidyl-tRNA synthetase
-
Jo-1 antigen
-
Synthetase, histidyl-transfer ribonucleate
-
antihistidyl-tRNA synthetase
-
-
HARS2
-
-
HisRS
Histidine translase
Histidine--tRNA ligase
-
-
-
-
Histidine--tRNA ligase homolog
-
-
-
-
histidine-tRNA ligase
histidine-tRNA ligase homolog
histidyl tRNA synthetase
-
-
Histidyl-transfer ribonucleate synthetase
histidyl-transfer RNA synthetase
-
-
Histidyl-tRNA synthetase
Jo-1 antigen
mitochondrial histidyl tRNA synthetase
-
-
Synthetase, histidyl-transfer ribonucleate
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
esterification
Aminoacylation
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
L-histidine:tRNAHis ligase (AMP-forming)
-
CAS REGISTRY NUMBER
COMMENTARY hide
9068-78-4
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
ATP + L-histidine + tRNAHis
AMP + diphosphate + L-histidyl-tRNAHis
show the reaction diagram
phylogenetic and evolutionary development
-
?
ATP + L-histidine + tRNAHis
AMP + diphosphate + L-histidinyl-tRNAHis
show the reaction diagram
ATP + L-histidine + tRNAHis
AMP + diphosphate + L-histidyl-tRNAHis
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
ATP + L-histidine + tRNAHis
AMP + diphosphate + L-histidyl-tRNAHis
show the reaction diagram
phylogenetic and evolutionary development
-
?
ATP + L-histidine + tRNAHis
AMP + diphosphate + L-histidinyl-tRNAHis
show the reaction diagram
-
strong association of autoantibodies, specificity recognizing the enzyme's granzyme B binding site of the lung enzyme, to HisRS with interstitial lung disease in patients with myositis
-
-
?
ATP + L-histidine + tRNAHis
AMP + diphosphate + L-histidyl-tRNAHis
show the reaction diagram
additional information
?
-
-
determination of enzyme-induced chemotactic activity of human cells, e.g. leukocytes and primary neutrophils, to the enzyme
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
-
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Myositis-specific anti-Jo-1 autoantibody
-
-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Hematin
-
can substitute for hemoglobin in stimulation
hemoglobin
-
2 mg/ml, stimulates
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0442 - 1.763
ATP
0.008 - 0.6872
L-histidine
0.000199 - 0.000979
tRNAHis
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.48 - 5.8
ATP
0.39 - 4.1
L-histidine
0.3 - 5.4
tRNAHis
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.15 - 130
ATP
3 - 500
L-histidine
1500 - 6900
tRNAHis
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
mutations in histidyl-tRNA synthetase cause the dominant axonal peripheral neuropathy Charcot-Marie-Tooth disease type 2W
physiological function
-
the enzyme induces muscle inflammation in B6.TLR2 and B6.TLR4 knockout mice. The enzyme induces interleukin 8 production in toll-like-receptor-transfected HEK-293 cells
additional information
-
in idiopathic inflammatory myopathy, the aminoacyl-transfer RNA synthetases are targets of the autoimmune response. Among these antigens, antibodies against histidyl-transfer RNA synthetase are by far the most prominent found in 15-20% of myositis patients, and more strikingly, are detected in about 70% of patients with myositis and interstitial lung disease. Strong association of HisRS with interstitial lung disease in humans
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
SYHM_HUMAN
506
0
56888
Swiss-Prot
Mitochondrion (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
55000
2 * 55000, dimeric quarternary structure
57400
x * 57400, amino acid sequence determination
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
dimer
2 * 55000, dimeric quarternary structure
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
-
lung HisRS cleavage by the cytotoxic lymphocyte serine protease granzyme B in vitro at LGPD48, caspase 6, which shares a tetrapeptide specificity similar to that of granzyme B, cleaves HisRS, producing a fragment of similar size, but cleavage sites are nonoverlapping
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
vapor diffusion method, using 0.1 M Tris pH 8.5, 0.2 M MgCl2 and 25% (w/v) PEG 3350
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D175E
-
the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
D364Y
-
the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
D48A
-
site-directed mutagenesis, the mutant is cleaved by caspase-6, but not by granzyme B
L200V
-
naturally occuring mutations in HARS2 involved in the Perrault syndrome, the mutant shows reduced activity compared to wild-type enzyme
P134H
-
the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
R137Q
-
the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
S356N
-
the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
T132I
-
the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
V155G
-
the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
V368L
-
naturally occuring mutations in HARS2 involved in the Perrault syndrome, the mutant shows reduced activity compared to wild-type enzyme
Y330C
-
the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
Y454S
-
the mutation is associated with childhood deafness, blindness, and episodic hallucinations during acute illness
additional information
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
51.7
-
melting temperature
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
stabilization of the isolated enzyme by hemoglobin and hematin
hemoglobin partially preserves the enzyme activity of preparations during storage at -80°C
-
hemoglobin, 2 mg/ml, partially restores the activity of the enzyme stored at low concentrations, below 0.01 mg/ml
-
OXIDATION STABILITY
ORGANISM
UNIPROT
LITERATURE
the tRNA aminoacylation activity of the enzyme is increased upon oxidative modification by hydrogen peroxide
-
726891
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
Ni-NTA column chromatography
-
Ni-NTA column chromatography and Superdex 200 gel filtration
-
Ni-NTA column chromatography, and Superdex 200 gel filtration
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
determination of DNA sequence, genomic organization, and chromosome mapping to 5q31.3
expressed in Escherichia coli BL21(DE3) cells
expression as enzyme-green fluorescent protein or as green fluorescent protein-enzyme construct
-
expression in Cos-1 cells
-
expression of C-terminally epitope-tagged wild-type and mutant HARS2 in 293T cells mitochondria
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
-
patients suffering from autoimmune-disease myositis develop antibodies against a histidyl-tRNA synthetase. Cytoplasm is the sole localization of enzyme-green fluorescent protein or green fluorescent protein-enzyme construct in T24 cell, HeLa cell and L6 cell
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Vazquez-Abad, D.; Carson, J.H.; Rothfield, N.
Localization of histidyl-tRNA synthetase (Jo-1) in human laryngeal epithelial carcinoma cell line HEp-2 cells)
Cell Tissue Res.
286
487-491
1996
Homo sapiens
Manually annotated by BRENDA team
Yang, D.C.H.; Dang, C.V.; Arnett, F.C.
Rat liver histidyl-tRNA synthetase. Purification and inhibition by the myositis-specific anti-Jo-1 autoantibody
Biochem. Biophys. Res. Commun.
120
15-21
1984
Homo sapiens, Rattus norvegicus
Manually annotated by BRENDA team
Tsui, F.W.L.; Siminovitch, L.
Isolation, structure and expression of mammalian genes for histidyl-tRNA synthetase
Nucleic Acids Res.
15
3349-3367
1987
Homo sapiens
Manually annotated by BRENDA team
Biswas, T.; Miller, F.W.; Plotz, P.H.
Stimulation and partial stabilization of human histidyl-tRNA synthetase by hemoglobin
FEBS Lett.
229
203-205
1988
Homo sapiens
Manually annotated by BRENDA team
O'Hanlon, T.P.; Miller, F.W.
Genomic organization, transcriptional mapping, and evolutionary implications of the human bi-directional histidyl-tRNA synthetase locus (HARS/HARSL)
Biochem. Biophys. Res. Commun.
294
609-614
2002
Homo sapiens (P12081), Homo sapiens (P49590), Homo sapiens
Manually annotated by BRENDA team
Freist, W.; Verhey, J.F.; Ruhlmann, A.; Gauss, D.H.; Arnez, J.G.
Histidyl-tRNA synthetase
Biol. Chem.
380
623-646
1999
Archaeoglobus fulgidus (O28631), Salmonella enterica subsp. enterica serovar Typhimurium (O52765), Mesocricetus auratus (P07178), Saccharomyces cerevisiae (P07263), Homo sapiens (P12081), Homo sapiens (P49590), Streptococcus dysgalactiae subsp. equisimilis (P30053), Caenorhabditis elegans (P34183), Haemophilus influenzae (P43823), Mycobacterium leprae (P46696), Mycoplasma genitalium (P47281), Porphyra purpurea (P51348), Thermus thermophilus (P56194), Thermus thermophilus, Helicobacter pylori (P56455), Escherichia coli (P60906), Escherichia coli, Takifugu rubripes (P70076), Mycoplasma pneumoniae (P75069), Oryza sativa (P93422), Mycobacterium tuberculosis (P9WFV5), Synechococcus sp. (Q55267), Synechocystis sp. (Q55653), Methanocaldococcus jannaschii (Q58406), Mus musculus (Q61035), Mycobacterium tuberculosis H37Rv (P9WFV5)
Manually annotated by BRENDA team
Howard, O.M.; Dong, H.F.; Yang, D.; Raben, N.; Nagaraju, K.; Rosen, A.; Casciola-Rosen, L.; Hartlein, M.; Kron, M.; Yiadom, K.; Dwivedi, S.; Plotz, P.H.; Oppenheim, J.J.
Histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, autoantigens in myositis, activate chemokine receptors on T lymphocytes and immature dendritic cells
J. Exp. Med.
196
781-791
2002
Homo sapiens
Manually annotated by BRENDA team
Kamei, H.
Intracellular localization of histidyl-tRNA synthetase/Jo-1 antigen in T24 cells and some other cells
J. Autoimmun.
22
201-210
2004
Homo sapiens
Manually annotated by BRENDA team
Levine, S.M.; Raben, N.; Xie, D.; Askin, F.B.; Tuder, R.; Mullins, M.; Rosen, A.; Casciola-Rosen, L.A.
Novel conformation of histidyl-transfer RNA synthetase in the lung: the target tissue in Jo-1 autoantibody-associated myositis
Arthritis Rheum.
56
2729-2739
2007
Homo sapiens
Manually annotated by BRENDA team
Wegner, N.; Wait, R.; Venables, P.J.
Evolutionarily conserved antigens in autoimmune disease: Implications for an infective aetiology
Int. J. Biochem. Cell Biol.
41
390-397
2008
Homo sapiens
Manually annotated by BRENDA team
Polosa, R.; Di Mauro, C.; Spampinato, B.; Castelli, L.; DAmico, G.; Edwards, C.J.; Russo, C.
A patient with antihistidyl-tRNA synthetase positive polymyositis presenting as acute respiratory distress syndrome
J. Clin. Rheumatol.
14
219-221
2008
Homo sapiens
Manually annotated by BRENDA team
Casciola-Rosen, L.
Histidyl-transfer RNA synthetase: A key participant in idiopathic inflammatory myopathies
Arthritis Rheum.
63
331-333
2011
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Pierce, S.B.; Chisholm, K.M.; Lynch, E.D.; Lee, M.K.; Walsh, T.; Opitz, J.M.; Li, W.; Klevit, R.E.; King, M.C.
Mutations in mitochondrial histidyl tRNA synthetase HARS2 cause ovarian dysgenesis and sensorineural hearing loss of Perrault syndrome
Proc. Natl. Acad. Sci. USA
108
6543-6548
2011
Caenorhabditis elegans, Homo sapiens
Manually annotated by BRENDA team
van Dooren, S.H.; Raijmakers, R.; Pluk, H.; Lokate, A.M.; Koemans, T.S.; Spanjers, R.E.; Heck, A.J.; Boelens, W.C.; van Venrooij, W.J.; Pruijn, G.J.
Oxidative stress-induced modifications of histidyl-tRNA synthetase affect its tRNA aminoacylation activity but not its immunoreactivity
Biochem. Cell Biol.
89
545-553
2011
Homo sapiens
Manually annotated by BRENDA team
Fernandez, I.; Harlow, L.; Zang, Y.; Liu-Bryan, R.; Ridgway, W.M.; Clemens, P.R.; Ascherman, D.P.
Functional redundancy of MyD88-dependent signaling pathways in a murine model of histidyl-transfer RNA synthetase-induced myositis
J. Immunol.
191
1865-1872
2013
Homo sapiens
Manually annotated by BRENDA team
Abbott, J.A.; Guth, E.; Kim, C.; Regan, C.; Siu, V.M.; Rupar, C.A.; Demeler, B.; Francklyn, C.S.; Robey-Bond, S.M.
The Usher Syndrome Type IIIB histidyl-tRNA synthetase mutation confers temperature sensitivity
Biochemistry
56
3619-3631
2017
Homo sapiens
Manually annotated by BRENDA team
Koh, C.Y.; Wetzel, A.B.; de van der Schueren, W.J.; Hol, W.G.
Comparison of histidine recognition in human and trypanosomatid histidyl-tRNA synthetases
Biochimie
106
111-120
2014
Homo sapiens (P12081), Homo sapiens, Trypanosoma brucei (Q4DA54), Trypanosoma brucei, Trypanosoma brucei CL Brener (Q4DA54)
Manually annotated by BRENDA team
Lee, Y.H.; Chang, C.P.; Cheng, Y.J.; Kuo, Y.Y.; Lin, Y.S.; Wang, C.C.
Evolutionary gain of highly divergent tRNA specificities by two isoforms of human histidyl-tRNA synthetase
Cell. Mol. Life Sci.
74
2663-2677
2017
Bacillus subtilis, Saccharomyces cerevisiae, Homo sapiens
Manually annotated by BRENDA team
Abbott, J.A.; Meyer-Schuman, R.; Lupo, V.; Feely, S.; Mademan, I.; Oprescu, S.N.; Griffin, L.B.; Alberti, M.A.; Casasnovas, C.; Aharoni, S.; Basel-Vanagaite, L.; Zuechner, S.; De Jonghe, P.; Baets, J.; Shy, M.E.; Espinos, C.; Demeler, B.; Antonellis, A.; Francklyn, C.
Substrate interaction defects in histidyl-tRNA synthetase linked to dominant axonal peripheral neuropathy
Hum. Mutat.
39
415-432
2018
Homo sapiens
Manually annotated by BRENDA team
Zhou, J.J.; Wang, F.; Xu, Z.; Lo, W.S.; Lau, C.F.; Chiang, K.P.; Nangle, L.A.; Ashlock, M.A.; Mendlein, J.D.; Yang, X.L.; Zhang, M.; Schimmel, P.
Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis
J. Biol. Chem.
289
19269-19275
2014
Homo sapiens
Manually annotated by BRENDA team