P54577 · SYYC_HUMAN
- ProteinTyrosine--tRNA ligase, cytoplasmic
- GeneYARS1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids528 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Tyrosine--tRNA ligase that catalyzes the attachment of tyrosine to tRNA(Tyr) in a two-step reaction: tyrosine is first activated by ATP to form Tyr-AMP and then transferred to the acceptor end of tRNA(Tyr) (Probable) (PubMed:25533949).
Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine--tRNA ligase activity (PubMed:25533949).
Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine--tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949).
Also acts as a positive regulator of poly-ADP-ribosylation in the nucleus, independently of its tyrosine--tRNA ligase activity (PubMed:25533949).
Activity is switched upon resveratrol-binding: resveratrol strongly inhibits the tyrosine--tRNA ligase activity and promotes relocalization to the nucleus, where YARS1 specifically stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949).
Catalytic activity
- ATP + L-tyrosine + tRNA(Tyr) = AMP + diphosphate + H+ + L-tyrosyl-tRNA(Tyr)This reaction proceeds in the forward direction.
Activity regulation
Resveratrol strongly inhibits the tyrosine--tRNA ligase activity.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 39 | L-tyrosine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 39 | trans-resveratrol (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 166 | L-tyrosine (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 170 | L-tyrosine (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 170 | trans-resveratrol (UniProtKB | ChEBI) | ||||
Sequence: Q | ||||||
Binding site | 173 | L-tyrosine (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 173 | trans-resveratrol (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 188 | L-tyrosine (UniProtKB | ChEBI) | ||||
Sequence: Q |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | extracellular space | |
Cellular Component | nuclear body | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | interleukin-8 receptor binding | |
Molecular Function | RNA binding | |
Molecular Function | small molecule binding | |
Molecular Function | tRNA binding | |
Molecular Function | tyrosine-tRNA ligase activity | |
Biological Process | apoptotic process | |
Biological Process | response to starvation | |
Biological Process | tyrosyl-tRNA aminoacylation |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosine--tRNA ligase, cytoplasmic
- EC number
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP54577
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Involvement in disease
Charcot-Marie-Tooth disease, dominant intermediate C (CMTDIC)
- 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. The dominant intermediate type C is 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:608323
Natural variants in CMTDIC
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_026681 | 41 | G>R | in CMTDIC; partial loss of activity; dbSNP:rs121908833 | |
VAR_026682 | 153-156 | missing | in CMTDIC | |
VAR_026684 | 196 | E>K | in CMTDIC; partial loss of activity; dbSNP:rs121908834 |
Neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2 (IMNEPD2)
- Note
- DescriptionAn autosomal recessive disorder with variable clinical manifestations and severity. Main features include cholestatic hepatitis, poor feeding, poor overall growth, and hypoglycemia apparent from infancy. Most patients have variable global developmental delay, sensorineural deafness, retinal abnormalities with visual defects, and hypotonia. Some patients have endocrine abnormalities. Brain imaging often shows dysmyelination, thin corpus callosum, cerebral atrophy, and white matter abnormalities. Death in early childhood may occur.
- See alsoMIM:619418
Natural variants in IMNEPD2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_086001 | 167 | P>T | in IMNEPD2; hypomorphic variant in yeast complementation assays; decreased homodimerization; does not affect localization to the cytoplasm; dbSNP:rs1279417718 | |
VAR_086002 | 213 | P>L | in IMNEPD2; uncertain significance; dbSNP:rs1553123702 | |
VAR_086003 | 269 | F>S | in IMNEPD2; uncertain significance; dbSNP:rs1653248260 | |
VAR_086004 | 525 | G>R | in IMNEPD2; uncertain significance; dbSNP:rs1553122256 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_026681 | 41 | in CMTDIC; partial loss of activity; dbSNP:rs121908833 | |||
Sequence: G → R | ||||||
Natural variant | VAR_026682 | 153-156 | in CMTDIC | |||
Sequence: Missing | ||||||
Natural variant | VAR_086001 | 167 | in IMNEPD2; hypomorphic variant in yeast complementation assays; decreased homodimerization; does not affect localization to the cytoplasm; dbSNP:rs1279417718 | |||
Sequence: P → T | ||||||
Natural variant | VAR_026683 | 170 | in dbSNP:rs2128600 | |||
Sequence: Q → H | ||||||
Natural variant | VAR_026684 | 196 | in CMTDIC; partial loss of activity; dbSNP:rs121908834 | |||
Sequence: E → K | ||||||
Natural variant | VAR_086002 | 213 | in IMNEPD2; uncertain significance; dbSNP:rs1553123702 | |||
Sequence: P → L | ||||||
Mutagenesis | 242-247 | Reduced tyrosine--tRNA ligase activity. | ||||
Sequence: KKKLKK → NNALNA | ||||||
Mutagenesis | 242-247 | Slightly reduced tyrosine--tRNA ligase activity. | ||||
Sequence: KKKLKK → NNKLNA | ||||||
Mutagenesis | 242-247 | Abolished localization to the nucleus. Abolished tyrosine--tRNA ligase activity. Abolished ability to activate PARP1. | ||||
Sequence: KKKLKK → YQFWIN | ||||||
Natural variant | VAR_086003 | 269 | in IMNEPD2; uncertain significance; dbSNP:rs1653248260 | |||
Sequence: F → S | ||||||
Natural variant | VAR_073292 | 274 | found in a patient with hereditary motor and sensory neuropathy; uncertain significance; dbSNP:rs758897498 | |||
Sequence: E → K | ||||||
Natural variant | VAR_087701 | 308 | found in a patient with proximal-predominant motor neuropathy; likely pathogenic; loss of function; dbSNP:rs1207371448 | |||
Sequence: D → Y | ||||||
Natural variant | VAR_086004 | 525 | in IMNEPD2; uncertain significance; dbSNP:rs1553122256 | |||
Sequence: G → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 558 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; alternate | ||||
Sequence: M | |||||||
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000423285 | 1-528 | UniProt | Tyrosine--tRNA ligase, cytoplasmic | |||
Sequence: MGDAPSPEEKLHLITRNLQEVLGEEKLKEILKERELKIYWGTATTGKPHVAYFVPMSKIADFLKAGCEVTILFADLHAYLDNMKAPWELLELRVSYYENVIKAMLESIGVPLEKLKFIKGTDYQLSKEYTLDVYRLSSVVTQHDSKKAGAEVVKQVEHPLLSGLLYPGLQALDEEYLKVDAQFGGIDQRKIFTFAEKYLPALGYSKRVHLMNPMVPGLTGSKMSSSEEESKIDLLDRKEDVKKKLKKAFCEPGNVENNGVLSFIKHVLFPLKSEFVILRDEKWGGNKTYTAYVDLEKDFAAEVVHPGDLKNSVEVALNKLLDPIREKFNTPALKKLASAAYPDPSKQKPMAKGPAKNSEPEEVIPSRLDIRVGKIITVEKHPDADSLYVEKIDVGEAEPRTVVSGLVQFVPKEELQDRLVVVLCNLKPQKMRGVESQGMLLCASIEGINRQVEPLDPPAGSAPGEHVFVKGYEKGQPDEELKPKKKVFEKLQADFKISEECIAQWKQTNFMTKLGSISCKSLKGGNIS | |||||||
Modified residue | 2 | UniProt | N-acetylglycine; in Tyrosine--tRNA ligase, cytoplasmic, N-terminally processed | ||||
Sequence: G | |||||||
Chain | PRO_0000055673 | 2-528 | UniProt | Tyrosine--tRNA ligase, cytoplasmic, N-terminally processed | |||
Sequence: GDAPSPEEKLHLITRNLQEVLGEEKLKEILKERELKIYWGTATTGKPHVAYFVPMSKIADFLKAGCEVTILFADLHAYLDNMKAPWELLELRVSYYENVIKAMLESIGVPLEKLKFIKGTDYQLSKEYTLDVYRLSSVVTQHDSKKAGAEVVKQVEHPLLSGLLYPGLQALDEEYLKVDAQFGGIDQRKIFTFAEKYLPALGYSKRVHLMNPMVPGLTGSKMSSSEEESKIDLLDRKEDVKKKLKKAFCEPGNVENNGVLSFIKHVLFPLKSEFVILRDEKWGGNKTYTAYVDLEKDFAAEVVHPGDLKNSVEVALNKLLDPIREKFNTPALKKLASAAYPDPSKQKPMAKGPAKNSEPEEVIPSRLDIRVGKIITVEKHPDADSLYVEKIDVGEAEPRTVVSGLVQFVPKEELQDRLVVVLCNLKPQKMRGVESQGMLLCASIEGINRQVEPLDPPAGSAPGEHVFVKGYEKGQPDEELKPKKKVFEKLQADFKISEECIAQWKQTNFMTKLGSISCKSLKGGNIS | |||||||
Modified residue | 197 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 205 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 206 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 338 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 358 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 386 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 386 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 474 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 482 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 490 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Interaction
Subunit
Homodimer (PubMed:12427973, PubMed:14671330, PubMed:30304524).
Interacts (when binding to resveratrol) with PARP1; interaction stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949).
Interacts (when binding to resveratrol) with PARP1; interaction stimulates the poly-ADP-ribosyltransferase activity of PARP1 (PubMed:25533949).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for motif, region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 44-52 | 'HIGH' region | ||||
Sequence: TTGKPHVAY | ||||||
Motif | 222-226 | 'KMSKS' region | ||||
Sequence: KMSSS | ||||||
Motif | 242-247 | Nuclear localization signal | ||||
Sequence: KKKLKK | ||||||
Region | 339-363 | Disordered | ||||
Sequence: AAYPDPSKQKPMAKGPAKNSEPEEV | ||||||
Domain | 364-468 | tRNA-binding | ||||
Sequence: IPSRLDIRVGKIITVEKHPDADSLYVEKIDVGEAEPRTVVSGLVQFVPKEELQDRLVVVLCNLKPQKMRGVESQGMLLCASIEGINRQVEPLDPPAGSAPGEHVF |
Domain
The nuclear localization signal, which mediates localization to the nucleus, is also important for interacting with tRNA(Tyr), suggesting that it is sterically blocked when tRNA(Tyr) is bound.
Sequence similarities
Belongs to the class-I aminoacyl-tRNA synthetase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length528
- Mass (Da)59,143
- Last updated2007-01-23 v4
- Checksum00C7E88843905780
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A6Q8PFC1 | A0A6Q8PFC1_HUMAN | YARS1 | 133 | ||
A0A6Q8PFX2 | A0A6Q8PFX2_HUMAN | YARS1 | 479 | ||
A0A6Q8PFX4 | A0A6Q8PFX4_HUMAN | YARS1 | 246 | ||
A0A6Q8PGW2 | A0A6Q8PGW2_HUMAN | YARS1 | 42 | ||
A0A6Q8PF15 | A0A6Q8PF15_HUMAN | YARS1 | 218 | ||
A0A0C4DGZ5 | A0A0C4DGZ5_HUMAN | YARS1 | 225 |
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 143 | in Ref. 4; BAD97328 | ||||
Sequence: H → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U40714 EMBL· GenBank· DDBJ | AAB39406.1 EMBL· GenBank· DDBJ | mRNA | Frameshift | |
U89436 EMBL· GenBank· DDBJ | AAB88409.1 EMBL· GenBank· DDBJ | mRNA | ||
AK125213 EMBL· GenBank· DDBJ | BAG54166.1 EMBL· GenBank· DDBJ | mRNA | ||
AK223608 EMBL· GenBank· DDBJ | BAD97328.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471059 EMBL· GenBank· DDBJ | EAX07506.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471059 EMBL· GenBank· DDBJ | EAX07507.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001933 EMBL· GenBank· DDBJ | AAH01933.1 EMBL· GenBank· DDBJ | mRNA | ||
BC004151 EMBL· GenBank· DDBJ | AAH04151.1 EMBL· GenBank· DDBJ | mRNA | ||
BC016689 EMBL· GenBank· DDBJ | AAH16689.1 EMBL· GenBank· DDBJ | mRNA |