P49591 · SYSC_HUMAN

  • Protein
    Serine--tRNA ligase, cytoplasmic
  • Gene
    SARS1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

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.

TypeIDPosition(s)Description
Binding site271L-serine (UniProtKB | ChEBI)
Binding site302L-serine (UniProtKB | ChEBI)
Binding site302-304ATP (UniProtKB | ChEBI)
Binding site318-321ATP (UniProtKB | ChEBI)
Binding site325L-serine (UniProtKB | ChEBI)
Binding site391-394ATP (UniProtKB | ChEBI)
Binding site427L-serine (UniProtKB | ChEBI)
Site429Important for serine binding

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentextracellular exosome
Cellular Componentnucleus
Molecular FunctionATP binding
Molecular Functionenzyme binding
Molecular Functionmolecular adaptor activity
Molecular Functionprotein homodimerization activity
Molecular FunctionRNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Functionselenocysteine-tRNA ligase activity
Molecular Functionserine-tRNA ligase activity
Molecular FunctiontRNA binding
Biological Processcytoplasmic translation
Biological Processnegative regulation of angiogenesis
Biological Processnegative regulation of transcription by RNA polymerase II
Biological Processnegative regulation of vascular endothelial growth factor production
Biological Processselenocysteine incorporation
Biological Processseryl-tRNA aminoacylation
Biological Processtranslation
Biological ProcesstRNA modification

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Serine--tRNA ligase, cytoplasmic
  • EC number
  • Alternative names
    • Seryl-tRNA synthetase (SerRS)
    • Seryl-tRNA(Ser/Sec) synthetase

Gene names

    • Name
      SARS1
    • Synonyms
      SARS, SERS

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    P49591
  • Secondary accessions
    • B2R6Y9
    • Q5T5C8
    • Q9NSE3

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Nucleus
Note: Predominantly cytoplasmic, but a minor proportion is also found in the nucleus.

Keywords

Disease & Variants

Involvement in disease

Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    An 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 also
    MIM:617709
Natural variants in NEDMAS
Variant IDPosition(s)ChangeDescription
VAR_078434172D>Nin 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_087457213R>Lin NEDMAS; reduced protein stability resulting in a significant decrease in cellular enzyme activity; dbSNP:rs539161490
VAR_088480302R>Cin NEDMAS
VAR_088481390R>Cin NEDMAS; dbSNP:rs750961565
  • A splice site deletion resulting in a five amino acid in-frame insertion in SARS1, is associated with autosomal dominant complex spastic paraplegia with ataxia, intellectual disability, developmental delay and seizures, but without microcephaly

Features

Showing features for mutagenesis, natural variant.

TypeIDPosition(s)Description
Mutagenesis2-14Abolishes DNA binding.
Mutagenesis9Strongly decreased enzyme activity.
Mutagenesis44Abolishes enzyme activity.
Mutagenesis51Abolishes enzyme activity.
Mutagenesis54Strongly decreased enzyme activity.
Mutagenesis55Moderately decreased enzyme activity.
Mutagenesis58Moderately decreased enzyme activity.
Mutagenesis61Moderately decreased enzyme activity.
Mutagenesis75-97Decreased enzyme activity. Abolishes DNA binding.
Mutagenesis104Moderately decreased enzyme activity.
Mutagenesis107Moderately decreased enzyme activity.
Natural variantVAR_078434172in 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
Natural variantVAR_087457213in NEDMAS; reduced protein stability resulting in a significant decrease in cellular enzyme activity; dbSNP:rs539161490
Mutagenesis254-261Mildly decreased enzyme activity. Nearly abolishes DNA binding.
Natural variantVAR_088480302in NEDMAS
Mutagenesis378Retains nuclear location and abolishes enzyme activity; when associated with V-383.
Mutagenesis383Abolishes nuclear location. Decreases enzyme activity. Retains nuclear location and abolishes enzyme activity; when associated with R-378.
Natural variantVAR_088481390in NEDMAS; dbSNP:rs750961565
Mutagenesis413-420Abolishes DNA binding.
Mutagenesis429Catalytically inactive. Loss of serine binding. No effect on nuclear location.
Mutagenesis482Abolishes nuclear localization; when associated with A-485 and A-493.
Mutagenesis482-514Abolishes nuclear localization.
Mutagenesis485Abolishes nuclear localization; when associated with A-482 and A-493.
Mutagenesis493Abolishes nuclear localization; when associated with A-482 and A-485.

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.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for modified residue, chain, modified residue (large scale data).

TypeIDPosition(s)SourceDescription
Modified residue1UniProtN-acetylmethionine
ChainPRO_00001221911-514UniProtSerine--tRNA ligase, cytoplasmic
Modified residue241UniProtPhosphoserine
Modified residue323UniProtN6-acetyllysine
Modified residue (large scale data)331PRIDEPhosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Brain.

Gene expression databases

Organism-specific databases

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).

Binary interactions

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, motif.

TypeIDPosition(s)Description
Region9-61Interaction with tRNA
Region473-514Disordered
Compositional bias478-500Basic and acidic residues
Motif482-494Nuclear localization signal

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 status
    Complete
  • Length
    514
  • Mass (Da)
    58,777
  • Last updated
    2007-01-23 v3
  • Checksum
    F59DA8E55F193ACB
MVLDLDLFRVDKGGDPALIRETQEKRFKDPGLVDQLVKADSEWRRCRFRADNLNKLKNLCSKTIGEKMKKKEPVGDDESVPENVLSFDDLTADALANLKVSQIKKVRLLIDEAILKCDAERIKLEAERFENLREIGNLLHPSVPISNDEDVDNKVERIWGDCTVRKKYSHVDLVVMVDGFEGEKGAVVAGSRGYFLKGVLVFLEQALIQYALRTLGSRGYIPIYTPFFMRKEVMQEVAQLSQFDEELYKVIGKGSEKSDDNSYDEKYLIATSEQPIAALHRDEWLRPEDLPIKYAGLSTCFRQEVGSHGRDTRGIFRVHQFEKIEQFVYSSPHDNKSWEMFEEMITTAEEFYQSLGIPYHIVNIVSGSLNHAASKKLDLEAWFPGSGAFRELVSCSNCTDYQARRLRIRYGQTKKMMDKVEFVHMLNATMCATTRTICAILENYQTEKGITVPEKLKEFMPPGLQELIPFVKPAPIEQEPSKKQKKQHEGSKKKAAARDVTLENRLQNMEVTDA

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
Q5T5C7Q5T5C7_HUMANSARS1536

Features

Showing features for sequence conflict, compositional bias.

TypeIDPosition(s)Description
Sequence conflict54in Ref. 1; CAA62635
Sequence conflict435in Ref. 6; AAH09390
Compositional bias478-500Basic and acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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