Information on EC 6.1.1.21 - histidine-tRNA ligase and Organism(s) Homo sapiens and UniProt Accession P12081

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Homo sapiens
UNIPROT: P12081
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The expected taxonomic range for this enzyme is: Archaea, Bacteria, Eukaryota


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
6.1.1.21
-
RECOMMENDED NAME
GeneOntology No.
histidine-tRNA ligase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Aminoacylation
-
-
esterification
-
-
Aminoacylation
esterification
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
tRNA charging
-
-
histidine metabolism
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-
Aminoacyl-tRNA biosynthesis
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-
SYSTEMATIC NAME
IUBMB Comments
L-histidine:tRNAHis ligase (AMP-forming)
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CAS REGISTRY NUMBER
COMMENTARY hide
9068-78-4
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
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mutations in histidyl-tRNA synthetase cause the dominant axonal peripheral neuropathy Charcot-Marie-Tooth disease type 2W
physiological function
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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
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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
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
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 SUBSTRATES
NATURAL PRODUCTS
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
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
?
-
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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+
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-
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Myositis-specific anti-Jo-1 autoantibody
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-
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
Hematin
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can substitute for hemoglobin in stimulation
hemoglobin
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2 mg/ml, stimulates
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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
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
57400
x * 57400, amino acid sequence determination
55000
2 * 55000, dimeric quarternary structure
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 57400, amino acid sequence determination
homodimer
-
-
?
-
x * 55000, SDS-PAGE
dimer
2 * 55000, dimeric quarternary structure
homodimer
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
proteolytic modification
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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
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TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
51.7
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melting temperature
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
hemoglobin partially preserves the enzyme activity of preparations during storage at -80°C
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hemoglobin, 2 mg/ml, partially restores the activity of the enzyme stored at low concentrations, below 0.01 mg/ml
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stabilization of the isolated enzyme by hemoglobin and hematin
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, and Superdex 200 gel filtration
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Ni-NTA column chromatography
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Ni-NTA column chromatography and Superdex 200 gel filtration
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Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli BL21(DE3) cells
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determination of DNA sequence, genomic organization, and chromosome mapping to 5q31.3
expressed in Escherichia coli BL21(DE3) cells
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expression as enzyme-green fluorescent protein or as green fluorescent protein-enzyme construct
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expression in Cos-1 cells
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expression of C-terminally epitope-tagged wild-type and mutant HARS2 in 293T cells mitochondria
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ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D175E
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the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
D364Y
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the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
D48A
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site-directed mutagenesis, the mutant is cleaved by caspase-6, but not by granzyme B
L200V
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naturally occuring mutations in HARS2 involved in the Perrault syndrome, the mutant shows reduced activity compared to wild-type enzyme
P134H
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the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
R137Q
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the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
S356N
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the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
T132I
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the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
V155G
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the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
V368L
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naturally occuring mutations in HARS2 involved in the Perrault syndrome, the mutant shows reduced activity compared to wild-type enzyme
Y330C
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the mutant with reduced aminoacylation activity is associated with Charcot-Marie-Tooth disease type 2W
Y454S
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the mutation is associated with childhood deafness, blindness, and episodic hallucinations during acute illness
additional information
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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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