Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine--tRNA ligase, cytoplasmic

Gene

SARS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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:9431993, PubMed:26433229, PubMed:28236339). 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:9431993, PubMed:26433229, PubMed:28236339). 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:19423848, PubMed:19423847, PubMed:24940000).8 Publications

Catalytic activityi

ATP + L-serine + tRNA(Ser) = AMP + diphosphate + L-seryl-tRNA(Ser).5 Publications
ATP + L-serine + tRNA(Sec) = AMP + diphosphate + L-seryl-tRNA(Sec).5 Publications

Pathwayi: selenocysteinyl-tRNA(Sec) biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes L-seryl-tRNA(Sec) from L-serine and tRNA(Sec).
Proteins known to be involved in this subpathway in this organism are:
  1. Serine--tRNA ligase, mitochondrial (SARS2), Serine--tRNA ligase, cytoplasmic (SARS)
This subpathway is part of the pathway selenocysteinyl-tRNA(Sec) biosynthesis, which is itself part of Aminoacyl-tRNA biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-seryl-tRNA(Sec) from L-serine and tRNA(Sec), the pathway selenocysteinyl-tRNA(Sec) biosynthesis and in Aminoacyl-tRNA biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei271L-serineCombined sources1 Publication1
Binding sitei302L-serineCombined sources1 Publication1
Binding sitei325L-serineCombined sources1 Publication1
Binding sitei427L-serineCombined sources1 Publication1
Binding sitei429Important for serine binding1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi302 – 304ATPCombined sources2 Publications3
Nucleotide bindingi318 – 321ATPCombined sources2 Publications4
Nucleotide bindingi391 – 394ATPCombined sources2 Publications4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • core promoter sequence-specific DNA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • RNA binding Source: ProtInc
  • selenocysteine-tRNA ligase activity Source: Reactome
  • serine-tRNA ligase activity Source: UniProtKB

GO - Biological processi

  • negative regulation of angiogenesis Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of vascular endothelial growth factor production Source: UniProtKB
  • selenocysteine metabolic process Source: Reactome
  • selenocysteinyl-tRNA(Sec) biosynthetic process Source: UniProtKB-UniPathway
  • seryl-tRNA aminoacylation Source: UniProtKB
  • translation Source: ProtInc
  • tRNA aminoacylation for protein translation Source: Reactome
  • tRNA processing Source: ProtInc

Keywordsi

Molecular functionAminoacyl-tRNA synthetase, DNA-binding, Ligase
Biological processProtein biosynthesis, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi6.1.1.11. 2681.
ReactomeiR-HSA-2408557. Selenocysteine synthesis.
R-HSA-379716. Cytosolic tRNA aminoacylation.
UniPathwayiUPA00906; UER00895.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine--tRNA ligase, cytoplasmic (EC:6.1.1.115 Publications)
Alternative name(s):
Seryl-tRNA synthetase
Short name:
SerRS
Seryl-tRNA(Ser/Sec) synthetase
Gene namesi
Name:SARS
Synonyms:SERS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000031698.12.
HGNCiHGNC:10537. SARS.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi2 – 14Missing : Abolishes DNA binding. 1 PublicationAdd BLAST13
Mutagenesisi9R → A: Strongly decreased enzyme activity. 1 Publication1
Mutagenesisi44R → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi51D → A: Abolishes enzyme activity. 1 Publication1
Mutagenesisi54N → A: Strongly decreased enzyme activity. 1 Publication1
Mutagenesisi55K → A: Moderately decreased enzyme activity. 1 Publication1
Mutagenesisi58N → A: Moderately decreased enzyme activity. 1 Publication1
Mutagenesisi61S → A: Moderately decreased enzyme activity. 1 Publication1
Mutagenesisi75 – 97Missing : Decreased enzyme activity. Abolishes DNA binding. 2 PublicationsAdd BLAST23
Mutagenesisi104K → A: Moderately decreased enzyme activity. 1 Publication1
Mutagenesisi107R → A: Moderately decreased enzyme activity. 1 Publication1
Mutagenesisi254 – 261Missing : Mildly decreased enzyme activity. Nearly abolishes DNA binding. 2 Publications8
Mutagenesisi378D → R: Retains nuclear location and abolishes enzyme activity; when associated with V-383. 1 Publication1
Mutagenesisi383F → V: Abolishes nuclear location. Decreases enzyme activity. Retains nuclear location and abolishes enzyme activity; when associated with R-378. 1 Publication1
Mutagenesisi413 – 420Missing : Abolishes DNA binding. 1 Publication8
Mutagenesisi429T → A: Catalytically inactive. Loss of serine binding. No effect on nuclear location. 2 Publications1
Mutagenesisi482 – 514Missing : Abolishes nuclear localization. 1 PublicationAdd BLAST33
Mutagenesisi482K → A: Abolishes nuclear localization; when associated with A-485 and A-493. 1 Publication1
Mutagenesisi485K → A: Abolishes nuclear localization; when associated with A-482 and A-493. 1 Publication1
Mutagenesisi493K → A: Abolishes nuclear localization; when associated with A-482 and A-485. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6301.
OpenTargetsiENSG00000031698.
PharmGKBiPA34945.

Chemistry databases

DrugBankiDB00133. L-Serine.

Polymorphism and mutation databases

BioMutaiSARS.
DMDMi19860217.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001221911 – 514Serine--tRNA ligase, cytoplasmicAdd BLAST514

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei241PhosphoserineCombined sources1
Modified residuei323N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP49591.
MaxQBiP49591.
PaxDbiP49591.
PeptideAtlasiP49591.
PRIDEiP49591.

PTM databases

iPTMnetiP49591.
PhosphoSitePlusiP49591.
SwissPalmiP49591.

Miscellaneous databases

PMAP-CutDBiP49591.

Expressioni

Tissue specificityi

Brain.1 Publication

Gene expression databases

BgeeiENSG00000031698.
CleanExiHS_SARS.
ExpressionAtlasiP49591. baseline and differential.
GenevisibleiP49591. HS.

Organism-specific databases

HPAiHPA016939.
HPA064668.

Interactioni

Subunit structurei

Homodimer (PubMed:22353712, PubMed:26433229). The tRNA molecule may bind across the dimer (PubMed:26433229). Interacts with SIRT2 (PubMed:24940000).3 Publications

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi112208. 60 interactors.
DIPiDIP-38215N.
IntActiP49591. 19 interactors.
STRINGi9606.ENSP00000234677.

Structurei

Secondary structure

1514
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi5 – 7Combined sources3
Helixi10 – 12Combined sources3
Helixi16 – 25Combined sources10
Helixi31 – 70Combined sources40
Helixi82 – 84Combined sources3
Beta strandi86 – 89Combined sources4
Helixi92 – 96Combined sources5
Beta strandi100 – 102Combined sources3
Helixi103 – 112Combined sources10
Helixi118 – 131Combined sources14
Helixi132 – 134Combined sources3
Helixi149 – 152Combined sources4
Beta strandi154 – 160Combined sources7
Helixi170 – 176Combined sources7
Helixi183 – 189Combined sources7
Beta strandi195 – 197Combined sources3
Helixi199 – 217Combined sources19
Beta strandi221 – 224Combined sources4
Beta strandi227 – 230Combined sources4
Helixi231 – 237Combined sources7
Helixi240 – 245Combined sources6
Beta strandi249 – 252Combined sources4
Beta strandi254 – 256Combined sources3
Beta strandi266 – 268Combined sources3
Helixi273 – 277Combined sources5
Turni278 – 282Combined sources5
Beta strandi283 – 285Combined sources3
Turni287 – 289Combined sources3
Beta strandi292 – 301Combined sources10
Beta strandi308 – 311Combined sources4
Beta strandi315 – 317Combined sources3
Beta strandi319 – 330Combined sources12
Helixi336 – 354Combined sources19
Beta strandi359 – 363Combined sources5
Helixi366 – 368Combined sources3
Beta strandi374 – 383Combined sources10
Turni384 – 387Combined sources4
Beta strandi388 – 397Combined sources10
Helixi401 – 406Combined sources6
Beta strandi409 – 411Combined sources3
Beta strandi424 – 432Combined sources9
Helixi433 – 444Combined sources12
Beta strandi447 – 451Combined sources5
Helixi454 – 457Combined sources4
Beta strandi464 – 469Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3VBBX-ray2.89A/B/C/D/E/F1-514[»]
4L87X-ray2.90A2-477[»]
4RQEX-ray4.00A/C1-514[»]
4RQFX-ray3.50A/B1-514[»]
ProteinModelPortaliP49591.
SMRiP49591.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni9 – 61Interaction with tRNA1 PublicationAdd BLAST53

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi482 – 494Nuclear localization signal1 PublicationAdd BLAST13

Domaini

Consists of two distinct domains, a catalytic core and a N-terminal extension that is involved in tRNA binding.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2509. Eukaryota.
COG0172. LUCA.
GeneTreeiENSGT00790000123098.
HOGENOMiHOG000035937.
HOVERGENiHBG023172.
InParanoidiP49591.
KOiK01875.
PhylomeDBiP49591.
TreeFamiTF300762.

Family and domain databases

CDDicd00770. SerRS_core. 1 hit.
InterProiView protein in InterPro
IPR002314. aa-tRNA-synt_IIb.
IPR006195. aa-tRNA-synth_II.
IPR002317. Ser-tRNA-ligase_type_1.
IPR015866. Ser-tRNA-synth_1_N.
IPR033729. SerRS_core.
IPR010978. tRNA-bd_arm.
PANTHERiPTHR11778. PTHR11778. 1 hit.
PfamiView protein in Pfam
PF02403. Seryl_tRNA_N. 1 hit.
PF00587. tRNA-synt_2b. 1 hit.
PIRSFiPIRSF001529. Ser-tRNA-synth_IIa. 1 hit.
PRINTSiPR00981. TRNASYNTHSER.
SUPFAMiSSF46589. SSF46589. 2 hits.
TIGRFAMsiTIGR00414. serS. 1 hit.
PROSITEiView protein in PROSITE
PS50862. AA_TRNA_LIGASE_II. 1 hit.

Sequencei

Sequence statusi: Complete.

P49591-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVLDLDLFRV DKGGDPALIR ETQEKRFKDP GLVDQLVKAD SEWRRCRFRA
60 70 80 90 100
DNLNKLKNLC SKTIGEKMKK KEPVGDDESV PENVLSFDDL TADALANLKV
110 120 130 140 150
SQIKKVRLLI DEAILKCDAE RIKLEAERFE NLREIGNLLH PSVPISNDED
160 170 180 190 200
VDNKVERIWG DCTVRKKYSH VDLVVMVDGF EGEKGAVVAG SRGYFLKGVL
210 220 230 240 250
VFLEQALIQY ALRTLGSRGY IPIYTPFFMR KEVMQEVAQL SQFDEELYKV
260 270 280 290 300
IGKGSEKSDD NSYDEKYLIA TSEQPIAALH RDEWLRPEDL PIKYAGLSTC
310 320 330 340 350
FRQEVGSHGR DTRGIFRVHQ FEKIEQFVYS SPHDNKSWEM FEEMITTAEE
360 370 380 390 400
FYQSLGIPYH IVNIVSGSLN HAASKKLDLE AWFPGSGAFR ELVSCSNCTD
410 420 430 440 450
YQARRLRIRY GQTKKMMDKV EFVHMLNATM CATTRTICAI LENYQTEKGI
460 470 480 490 500
TVPEKLKEFM PPGLQELIPF VKPAPIEQEP SKKQKKQHEG SKKKAAARDV
510
TLENRLQNME VTDA
Length:514
Mass (Da):58,777
Last modified:January 23, 2007 - v3
Checksum:iF59DA8E55F193ACB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti54N → S in CAA62635 (PubMed:9431993).Curated1
Sequence conflicti435R → C in AAH09390 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078434172D → N Probable disease-associated mutation found in a family with moderate intellectual disability, microcephaly, ataxia, speech impairment and aggressive behaviour; impaired serine-activation of enzyme resulting in a significant decrease in the first step of the aminoacylation reaction; reduced protein stability; reduced protein expression. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X91257 mRNA. Translation: CAA62635.1.
D49914 mRNA. Translation: BAA95602.1.
AK312771 mRNA. Translation: BAG35636.1.
AL356389 Genomic DNA. No translation available.
CH471122 Genomic DNA. Translation: EAW56369.1.
BC000716 mRNA. Translation: AAH00716.1.
BC009390 mRNA. Translation: AAH09390.1.
CCDSiCCDS795.1.
PIRiG01026.
RefSeqiNP_006504.2. NM_006513.3.
UniGeneiHs.531176.

Genome annotation databases

EnsembliENST00000234677; ENSP00000234677; ENSG00000031698.
GeneIDi6301.
KEGGihsa:6301.
UCSCiuc001dwu.3. human.

Similar proteinsi

Entry informationi

Entry nameiSYSC_HUMAN
AccessioniPrimary (citable) accession number: P49591
Secondary accession number(s): B2R6Y9, Q5T5C8, Q9NSE3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: January 23, 2007
Last modified: September 27, 2017
This is version 166 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Aminoacyl-tRNA synthetases
    List of aminoacyl-tRNA synthetase entries
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  7. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  8. SIMILARITY comments
    Index of protein domains and families