P49591 · SYSC_HUMAN
- ProteinSerine--tRNA ligase, cytoplasmic
- GeneSARS1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids514 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser-AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:36041817, PubMed:9431993).
Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:9431993).
In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000).
Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423847, PubMed:19423848, PubMed:24940000).
Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:26433229, PubMed:28236339, PubMed:34570399, PubMed:9431993).
In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000).
Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423847, PubMed:19423848, PubMed:24940000).
Catalytic activity
- ATP + L-serine + tRNA(Ser) = AMP + diphosphate + H+ + L-seryl-tRNA(Ser)
Pathway
Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec) biosynthesis; L-seryl-tRNA(Sec) from L-serine and tRNA(Sec): step 1/1.
Features
Showing features for binding site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 271 | L-serine (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 302 | L-serine (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 302-304 | ATP (UniProtKB | ChEBI) | ||||
Sequence: RQE | ||||||
Binding site | 318-321 | ATP (UniProtKB | ChEBI) | ||||
Sequence: VHQF | ||||||
Binding site | 325 | L-serine (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 391-394 | ATP (UniProtKB | ChEBI) | ||||
Sequence: ELVS | ||||||
Binding site | 427 | L-serine (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Site | 429 | Important for serine binding | ||||
Sequence: T |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | enzyme binding | |
Molecular Function | molecular adaptor activity | |
Molecular Function | protein homodimerization activity | |
Molecular Function | RNA polymerase II cis-regulatory region sequence-specific DNA binding | |
Molecular Function | selenocysteine-tRNA ligase activity | |
Molecular Function | serine-tRNA ligase activity | |
Molecular Function | tRNA binding | |
Biological Process | cytoplasmic translation | |
Biological Process | negative regulation of angiogenesis | |
Biological Process | negative regulation of transcription by RNA polymerase II | |
Biological Process | negative regulation of vascular endothelial growth factor production | |
Biological Process | selenocysteine incorporation | |
Biological Process | seryl-tRNA aminoacylation | |
Biological Process | translation | |
Biological Process | tRNA modification |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine--tRNA ligase, cytoplasmic
- 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 accessionP49591
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Involvement in disease
Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS)
- Note
- DescriptionAn autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness.
- See alsoMIM:617709
Natural variants in NEDMAS
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_078434 | 172 | D>N | in NEDMAS; impaired serine-activation of enzyme resulting in a significant decrease in the first step of the aminoacylation reaction; reduced protein stability; reduced protein expression; dbSNP:rs1553178049 | |
VAR_087457 | 213 | R>L | in NEDMAS; reduced protein stability resulting in a significant decrease in cellular enzyme activity; dbSNP:rs539161490 | |
VAR_088480 | 302 | R>C | in NEDMAS | |
VAR_088481 | 390 | R>C | in NEDMAS; dbSNP:rs750961565 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 2-14 | Abolishes DNA binding. | ||||
Sequence: Missing | ||||||
Mutagenesis | 9 | Strongly decreased enzyme activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 44 | Abolishes enzyme activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 51 | Abolishes enzyme activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 54 | Strongly decreased enzyme activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 55 | Moderately decreased enzyme activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 58 | Moderately decreased enzyme activity. | ||||
Sequence: N → A | ||||||
Mutagenesis | 61 | Moderately decreased enzyme activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 75-97 | Decreased enzyme activity. Abolishes DNA binding. | ||||
Sequence: Missing | ||||||
Mutagenesis | 104 | Moderately decreased enzyme activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 107 | Moderately decreased enzyme activity. | ||||
Sequence: R → A | ||||||
Natural variant | VAR_078434 | 172 | in NEDMAS; impaired serine-activation of enzyme resulting in a significant decrease in the first step of the aminoacylation reaction; reduced protein stability; reduced protein expression; dbSNP:rs1553178049 | |||
Sequence: D → N | ||||||
Natural variant | VAR_087457 | 213 | in NEDMAS; reduced protein stability resulting in a significant decrease in cellular enzyme activity; dbSNP:rs539161490 | |||
Sequence: R → L | ||||||
Mutagenesis | 254-261 | Mildly decreased enzyme activity. Nearly abolishes DNA binding. | ||||
Sequence: Missing | ||||||
Natural variant | VAR_088480 | 302 | in NEDMAS | |||
Sequence: R → C | ||||||
Mutagenesis | 378 | Retains nuclear location and abolishes enzyme activity; when associated with V-383. | ||||
Sequence: D → R | ||||||
Mutagenesis | 383 | Abolishes nuclear location. Decreases enzyme activity. Retains nuclear location and abolishes enzyme activity; when associated with R-378. | ||||
Sequence: F → V | ||||||
Natural variant | VAR_088481 | 390 | in NEDMAS; dbSNP:rs750961565 | |||
Sequence: R → C | ||||||
Mutagenesis | 413-420 | Abolishes DNA binding. | ||||
Sequence: Missing | ||||||
Mutagenesis | 429 | Catalytically inactive. Loss of serine binding. No effect on nuclear location. | ||||
Sequence: T → A | ||||||
Mutagenesis | 482 | Abolishes nuclear localization; when associated with A-485 and A-493. | ||||
Sequence: K → A | ||||||
Mutagenesis | 482-514 | Abolishes nuclear localization. | ||||
Sequence: Missing | ||||||
Mutagenesis | 485 | Abolishes nuclear localization; when associated with A-482 and A-493. | ||||
Sequence: K → A | ||||||
Mutagenesis | 493 | Abolishes nuclear localization; when associated with A-482 and A-485. | ||||
Sequence: K → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 447 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 modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000122191 | 1-514 | UniProt | Serine--tRNA ligase, cytoplasmic | |||
Sequence: MVLDLDLFRVDKGGDPALIRETQEKRFKDPGLVDQLVKADSEWRRCRFRADNLNKLKNLCSKTIGEKMKKKEPVGDDESVPENVLSFDDLTADALANLKVSQIKKVRLLIDEAILKCDAERIKLEAERFENLREIGNLLHPSVPISNDEDVDNKVERIWGDCTVRKKYSHVDLVVMVDGFEGEKGAVVAGSRGYFLKGVLVFLEQALIQYALRTLGSRGYIPIYTPFFMRKEVMQEVAQLSQFDEELYKVIGKGSEKSDDNSYDEKYLIATSEQPIAALHRDEWLRPEDLPIKYAGLSTCFRQEVGSHGRDTRGIFRVHQFEKIEQFVYSSPHDNKSWEMFEEMITTAEEFYQSLGIPYHIVNIVSGSLNHAASKKLDLEAWFPGSGAFRELVSCSNCTDYQARRLRIRYGQTKKMMDKVEFVHMLNATMCATTRTICAILENYQTEKGITVPEKLKEFMPPGLQELIPFVKPAPIEQEPSKKQKKQHEGSKKKAAARDVTLENRLQNMEVTDA | |||||||
Modified residue | 241 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 323 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 331 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homodimer (PubMed:22353712, PubMed:26433229).
The tRNA molecule may bind across the dimer (PubMed:26433229).
Interacts with SIRT2 (PubMed:24940000).
Interacts with METTL6; interaction is required for the tRNA N3-methylcytidine methyltransferase activity of METTL6 (PubMed:28655767, PubMed:34268557).
The tRNA molecule may bind across the dimer (PubMed:26433229).
Interacts with SIRT2 (PubMed:24940000).
Interacts with METTL6; interaction is required for the tRNA N3-methylcytidine methyltransferase activity of METTL6 (PubMed:28655767, PubMed:34268557).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 9-61 | Interaction with tRNA | ||||
Sequence: RVDKGGDPALIRETQEKRFKDPGLVDQLVKADSEWRRCRFRADNLNKLKNLCS | ||||||
Region | 473-514 | Disordered | ||||
Sequence: PAPIEQEPSKKQKKQHEGSKKKAAARDVTLENRLQNMEVTDA | ||||||
Compositional bias | 478-500 | Basic and acidic residues | ||||
Sequence: QEPSKKQKKQHEGSKKKAAARDV | ||||||
Motif | 482-494 | Nuclear localization signal | ||||
Sequence: KKQKKQHEGSKKK |
Domain
Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length514
- Mass (Da)58,777
- Last updated2007-01-23 v3
- ChecksumF59DA8E55F193ACB
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q5T5C7 | Q5T5C7_HUMAN | SARS1 | 536 |
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 54 | in Ref. 1; CAA62635 | ||||
Sequence: N → S | ||||||
Sequence conflict | 435 | in Ref. 6; AAH09390 | ||||
Sequence: R → C | ||||||
Compositional bias | 478-500 | Basic and acidic residues | ||||
Sequence: QEPSKKQKKQHEGSKKKAAARDV |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X91257 EMBL· GenBank· DDBJ | CAA62635.1 EMBL· GenBank· DDBJ | mRNA | ||
D49914 EMBL· GenBank· DDBJ | BAA95602.1 EMBL· GenBank· DDBJ | mRNA | ||
AK312771 EMBL· GenBank· DDBJ | BAG35636.1 EMBL· GenBank· DDBJ | mRNA | ||
AL356389 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471122 EMBL· GenBank· DDBJ | EAW56369.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC000716 EMBL· GenBank· DDBJ | AAH00716.1 EMBL· GenBank· DDBJ | mRNA | ||
BC009390 EMBL· GenBank· DDBJ | AAH09390.1 EMBL· GenBank· DDBJ | mRNA |