Q15046 · SYK_HUMAN
- ProteinLysine--tRNA ligase
- GeneKARS1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids597 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
When secreted, acts as a signaling molecule that induces immune response through the activation of monocyte/macrophages (PubMed:15851690).
Catalyzes the synthesis of the signaling molecule diadenosine tetraphosphate (Ap4A), and thereby mediates disruption of the complex between HINT1 and MITF and the concomitant activation of MITF transcriptional activity (PubMed:14975237, PubMed:19524539, PubMed:23159739, PubMed:5338216).
Miscellaneous
Catalytic activity
- ATP + L-lysine + tRNA(Lys) = AMP + diphosphate + L-lysyl-tRNA(Lys)
Activity regulation
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
1.19 μM | tRNA(Lys) |
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 277 | substrate | ||||
Sequence: G | ||||||
Binding site | 301 | substrate | ||||
Sequence: E | ||||||
Binding site | 323-325 | ATP (UniProtKB | ChEBI) | ||||
Sequence: RNE | ||||||
Binding site | 331-332 | ATP (UniProtKB | ChEBI) | ||||
Sequence: HN | ||||||
Binding site | 339 | substrate | ||||
Sequence: E | ||||||
Binding site | 341 | substrate | ||||
Sequence: Y | ||||||
Binding site | 494-495 | ATP (UniProtKB | ChEBI) | ||||
Sequence: EI | ||||||
Binding site | 497 | substrate | ||||
Sequence: N | ||||||
Binding site | 501 | substrate | ||||
Sequence: E | ||||||
Binding site | 550-553 | ATP (UniProtKB | ChEBI) | ||||
Sequence: GIDR |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLysine--tRNA ligase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ15046
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Isoform Cytoplasmic
Isoform Mitochondrial
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Charcot-Marie-Tooth disease, recessive intermediate B (CMTRIB)
- Note
- DescriptionA form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Recessive intermediate forms of Charcot-Marie-Tooth disease are characterized by clinical and pathologic features intermediate between demyelinating and axonal peripheral neuropathies, and motor median nerve conduction velocities ranging from 25 to 45 m/sec.
- See alsoMIM:613641
Natural variants in CMTRIB
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_064911 | 105 | L>H | in CMTRIB; severely affects enzyme activity; dbSNP:rs267607194 | |
VAR_064912 | 274 | I>M | in CMTRIB; dbSNP:rs146955132 |
Deafness, autosomal recessive, 89 (DFNB89)
- Note
- DescriptionA form of non-syndromic deafness characterized by bilateral, prelingual, moderate to severe hearing loss affecting all frequencies.
- See alsoMIM:613916
Natural variants in DFNB89
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_070233 | 145 | Y>H | in DFNB89; dbSNP:rs397514745 | |
VAR_070234 | 349 | D>N | in DFNB89; dbSNP:rs397514746 |
Deafness, congenital, and adult-onset progressive leukoencephalopathy (DEAPLE)
- Note
- DescriptionAn autosomal recessive, complex neurodegenerative disorder characterized by congenital sensorineural deafness, and progressive motor and cognitive decline apparent in young adulthood. Brain imaging shows diffuse white matter abnormalities affecting various brain regions, consistent with a progressive leukoencephalopathy. More variable additional features may include visual impairment and axonal peripheral neuropathy. Premature death may occurr in some patients.
- See alsoMIM:619196
Natural variants in DEAPLE
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_085386 | 80 | R>H | in DEAPLE; uncertain significance; dbSNP:rs369114426 | |
VAR_085388 | 200 | P>L | in DEAPLE and LEPID; reduces interaction with AIMP2. Reduces tRNA-lysine aminoacylation; dbSNP:rs201650281 | |
VAR_085389 | 263 | F>V | in DEAPLE; reduces interaction with AIMP2. Reduces tRNA-lysine aminoacylation; dbSNP:rs772410450 | |
VAR_085390 | 448 | V>F | in DEAPLE; uncertain significance | |
VAR_079744 | 477 | R>H | in DEAPLE and LEPID; decreases tRNA-lysine aminoacylation; induces protein aggregation; releases from the subunit complex; no effect on cytoplasmic location; no effect on oligomerization; dbSNP:rs778748895 | |
VAR_079745 | 505 | P>S | in DEAPLE; decreases tRNA-lysine aminoacylation; slightly induces protein aggregation; no effect on cytoplasmic location; no effect on oligomerization; dbSNP:rs1555512658 |
Leukoencephalopathy, progressive, infantile-onset, with or without deafness (LEPID)
- Note
- DescriptionAn autosomal recessive, complex neurodegenerative disorder apparent from infancy. LEPID is characterized by early-onset progressive leukoencephalopathy with brainstem and spinal cord calcifications, sensorineural deafness in most patients, global developmental delay with cognitive impairment and poor or absent speech, developmental regression, and neurologic deterioration. Additional more variable features may include poor overall growth with microcephaly, seizures, visual loss, microcytic anemia, and hepatic enlargement or abnormal liver enzymes. Premature death is common.
- See alsoMIM:619147
Natural variants in LEPID
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_085387 | 189 | G>D | in LEPID; does not rescue the developmental defects caused by KARS1 depletion in xenopus | |
VAR_085388 | 200 | P>L | in DEAPLE and LEPID; reduces interaction with AIMP2. Reduces tRNA-lysine aminoacylation; dbSNP:rs201650281 | |
VAR_079743 | 438 | R>W | in LEPID; uncertain significance; dbSNP:rs761527468 | |
VAR_079744 | 477 | R>H | in DEAPLE and LEPID; decreases tRNA-lysine aminoacylation; induces protein aggregation; releases from the subunit complex; no effect on cytoplasmic location; no effect on oligomerization; dbSNP:rs778748895 | |
VAR_079746 | 525 | E>K | in LEPID; uncertain significance; dbSNP:rs770522582 | |
VAR_085391 | 568 | L>F | in LEPID; decreases tRNA-lysine aminoacylation activity of both the mitochondrial and cytosolic forms. Does not rescue the developmental defects caused by KARS1 depletion in xenopus; dbSNP:rs768349236 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1-65 | Loss of nuclear localization, but no effect on packaging into HIV-1. | ||||
Sequence: Missing | ||||||
Natural variant | VAR_085386 | 80 | in DEAPLE; uncertain significance; dbSNP:rs369114426 | |||
Sequence: R → H | ||||||
Mutagenesis | 101 | Disrupts interaction with AIMP2 and the multisynthase complex. | ||||
Sequence: V → D, R, or W | ||||||
Natural variant | VAR_064911 | 105 | in CMTRIB; severely affects enzyme activity; dbSNP:rs267607194 | |||
Sequence: L → H | ||||||
Natural variant | VAR_070233 | 145 | in DFNB89; dbSNP:rs397514745 | |||
Sequence: Y → H | ||||||
Natural variant | VAR_052640 | 179 | in dbSNP:rs11557665 | |||
Sequence: G → A | ||||||
Natural variant | VAR_085387 | 189 | in LEPID; does not rescue the developmental defects caused by KARS1 depletion in xenopus | |||
Sequence: G → D | ||||||
Natural variant | VAR_085388 | 200 | in DEAPLE and LEPID; reduces interaction with AIMP2. Reduces tRNA-lysine aminoacylation; dbSNP:rs201650281 | |||
Sequence: P → L | ||||||
Mutagenesis | 207 | Strongly reduced production of diadenosine tetraphosphate (Ap4A). Reduced protein phosphorylation. | ||||
Sequence: S → A | ||||||
Mutagenesis | 207 | Phosphomimetic mutant that strongly enhances translocation into the nucleus and production of diadenosine tetraphosphate (Ap4A). Almost complete loss of tRNA ligase activity. | ||||
Sequence: S → D | ||||||
Mutagenesis | 207 | Strongly decreased tRNA ligase activity. | ||||
Sequence: S → R | ||||||
Mutagenesis | 207 | Almost complete loss of tRNA ligase activity. | ||||
Sequence: S → Y | ||||||
Natural variant | VAR_085389 | 263 | in DEAPLE; reduces interaction with AIMP2. Reduces tRNA-lysine aminoacylation; dbSNP:rs772410450 | |||
Sequence: F → V | ||||||
Natural variant | VAR_064912 | 274 | in CMTRIB; dbSNP:rs146955132 | |||
Sequence: I → M | ||||||
Mutagenesis | 346 | Induces protein aggregation. Releases from the subunit complex. | ||||
Sequence: D → R | ||||||
Natural variant | VAR_070234 | 349 | in DFNB89; dbSNP:rs397514746 | |||
Sequence: D → N | ||||||
Natural variant | VAR_079741 | 350 | found in a patient with hypertrophic cardiomyopathy and mild intellectual disability together with proximal muscle weakness; uncertain significance | |||
Sequence: L → H | ||||||
Natural variant | VAR_079742 | 390 | found in a patient with hypertrophic cardiomyopathy and mild intellectual disability together with proximal muscle weakness; uncertain significance | |||
Sequence: P → R | ||||||
Natural variant | VAR_079743 | 438 | in LEPID; uncertain significance; dbSNP:rs761527468 | |||
Sequence: R → W | ||||||
Natural variant | VAR_085390 | 448 | in DEAPLE; uncertain significance | |||
Sequence: V → F | ||||||
Natural variant | VAR_079744 | 477 | in DEAPLE and LEPID; decreases tRNA-lysine aminoacylation; induces protein aggregation; releases from the subunit complex; no effect on cytoplasmic location; no effect on oligomerization; dbSNP:rs778748895 | |||
Sequence: R → H | ||||||
Natural variant | VAR_079745 | 505 | in DEAPLE; decreases tRNA-lysine aminoacylation; slightly induces protein aggregation; no effect on cytoplasmic location; no effect on oligomerization; dbSNP:rs1555512658 | |||
Sequence: P → S | ||||||
Natural variant | VAR_079746 | 525 | in LEPID; uncertain significance; dbSNP:rs770522582 | |||
Sequence: E → K | ||||||
Mutagenesis | 540 | Disrupts interaction with AIMP2 and the multisynthase complex. Increases production of diadenosine tetraphosphate (Ap4A). Almost complete loss of tRNA ligase activity. | ||||
Sequence: G → Y | ||||||
Natural variant | VAR_085391 | 568 | in LEPID; decreases tRNA-lysine aminoacylation activity of both the mitochondrial and cytosolic forms. Does not rescue the developmental defects caused by KARS1 depletion in xenopus; dbSNP:rs768349236 | |||
Sequence: L → F | ||||||
Natural variant | VAR_016105 | 595 | in dbSNP:rs6834 | |||
Sequence: T → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 879 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000152765 | 2-597 | UniProt | Lysine--tRNA ligase | |||
Sequence: AAVQAAEVKVDGSEPKLSKNELKRRLKAEKKVAEKEAKQKELSEKQLSQATAAATNHTTDNGVGPEEESVDPNQYYKIRSQAIHQLKVNGEDPYPHKFHVDISLTDFIQKYSHLQPGDHLTDITLKVAGRIHAKRASGGKLIFYDLRGEGVKLQVMANSRNYKSEEEFIHINNKLRRGDIIGVQGNPGKTKKGELSIIPYEITLLSPCLHMLPHLHFGLKDKETRYRQRYLDLILNDFVRQKFIIRSKIITYIRSFLDELGFLEIETPMMNIIPGGAVAKPFITYHNELDMNLYMRIAPELYHKMLVVGGIDRVYEIGRQFRNEGIDLTHNPEFTTCEFYMAYADYHDLMEITEKMVSGMVKHITGSYKVTYHPDGPEGQAYDVDFTPPFRRINMVEELEKALGMKLPETNLFETEETRKILDDICVAKAVECPPPRTTARLLDKLVGEFLEVTCINPTFICDHPQIMSPLAKWHRSKEGLTERFELFVMKKEICNAYTELNDPMRQRQLFEEQAKAKAAGDDEAMFIDENFCTALEYGLPPTAGWGMGIDRVAMFLTDSNNIKEVLLFPAMKPEDKKENVATTDTLESTTVGTSV | |||||||
Modified residue | 88 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 141 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 207 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 470 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 584 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 585 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 587 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 590 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 591 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 596 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 596 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Part of the multisynthetase complex (MSC), a multisubunit complex that groups tRNA ligases for Arg (RARS), Asp (DARS), Gln (QARS), Ile (IARS), Leu (LARS), Lys (KARS), Met (MARS) the bifunctional ligase for Glu and Pro (EPRS) and the auxiliary subunits AIMP1/p43, AIMP2/p38 and EEF1E1/p18 (PubMed:19131329, PubMed:19289464, PubMed:23159739, PubMed:24312579).
Interacts with AIMP2 (via N-terminus) and MITF (PubMed:14975237, PubMed:15220430, PubMed:23159739, PubMed:26074468, PubMed:31116475, PubMed:9878398).
Interacts with TARSL2 (PubMed:24312579).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q15046 | AIMP2 Q13155 | 23 | EBI-356367, EBI-745226 | |
BINARY | Q15046 | EPRS1 P07814 | 6 | EBI-356367, EBI-355315 | |
BINARY | Q15046 | KARS1 Q15046 | 6 | EBI-356367, EBI-356367 | |
BINARY | Q15046 | RPSA P08865 | 9 | EBI-356367, EBI-354112 | |
BINARY | Q15046 | SOD1 P00441 | 3 | EBI-356367, EBI-990792 | |
BINARY | Q15046-1 | AIMP2 Q13155 | 2 | EBI-21457670, EBI-745226 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-71 | Disordered | ||||
Sequence: MAAVQAAEVKVDGSEPKLSKNELKRRLKAEKKVAEKEAKQKELSEKQLSQATAAATNHTTDNGVGPEEESV | ||||||
Compositional bias | 13-44 | Basic and acidic residues | ||||
Sequence: GSEPKLSKNELKRRLKAEKKVAEKEAKQKELS | ||||||
Compositional bias | 45-64 | Polar residues | ||||
Sequence: EKQLSQATAAATNHTTDNGV |
Domain
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q15046-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameCytoplasmic
- Length597
- Mass (Da)68,048
- Last updated2002-04-16 v3
- ChecksumE7770953332D905D
Q15046-2
- NameMitochondrial
- NoteMitochondrial precursor. Contains a mitochondrial transit peptide at positions 1-16.
- Differences from canonical
- 1-21: MAAVQAAEVKVDGSEPKLSKN → MLTQAAVRLVRGSLRKTSWAEWGHRELRLGQLAPFTAPHKDKSFSDQRS
Computationally mapped potential isoform sequences
There are 7 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_038481 | 1-21 | in isoform Mitochondrial | |||
Sequence: MAAVQAAEVKVDGSEPKLSKN → MLTQAAVRLVRGSLRKTSWAEWGHRELRLGQLAPFTAPHKDKSFSDQRS | ||||||
Compositional bias | 13-44 | Basic and acidic residues | ||||
Sequence: GSEPKLSKNELKRRLKAEKKVAEKEAKQKELS | ||||||
Compositional bias | 45-64 | Polar residues | ||||
Sequence: EKQLSQATAAATNHTTDNGV | ||||||
Sequence conflict | 48 | In isoform Q15046-2; in Ref. 2; AAG30114 | ||||
Sequence: R → G |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D32053 EMBL· GenBank· DDBJ | BAA22084.1 EMBL· GenBank· DDBJ | mRNA | ||
AF285758 EMBL· GenBank· DDBJ | AAG30114.1 EMBL· GenBank· DDBJ | mRNA | ||
D31890 EMBL· GenBank· DDBJ | BAA06688.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AC025287 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471114 EMBL· GenBank· DDBJ | EAW95622.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471114 EMBL· GenBank· DDBJ | EAW95624.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC004132 EMBL· GenBank· DDBJ | AAH04132.1 EMBL· GenBank· DDBJ | mRNA |