SYSC_MACFA
ID SYSC_MACFA Reviewed; 514 AA.
AC Q4R4U9;
DT 09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 97.
DE RecName: Full=Serine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.11 {ECO:0000250|UniProtKB:P49591};
DE AltName: Full=Seryl-tRNA synthetase;
DE Short=SerRS;
DE AltName: Full=Seryl-tRNA(Ser/Sec) synthetase;
GN Name=SARS1; Synonyms=SARS; ORFNames=QccE-14020;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the attachment of serine to tRNA(Ser) in a two-step
CC reaction: serine is first activated by ATP to form Ser-AMP and then
CC transferred to the acceptor end of tRNA(Ser). Is probably also able to
CC aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-
CC seryl-tRNA(Sec), which will be further converted into selenocysteinyl-
CC tRNA(Sec). In the nucleus, binds to the VEGFA core promoter and
CC prevents MYC binding and transcriptional activation by MYC. Recruits
CC SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at
CC 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and
CC sprouting angiogenesis mediated by VEGFA.
CC {ECO:0000250|UniProtKB:P49591}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-serine + tRNA(Ser) = AMP + diphosphate + H(+) + L-
CC seryl-tRNA(Ser); Xref=Rhea:RHEA:12292, Rhea:RHEA-COMP:9669,
CC Rhea:RHEA-COMP:9703, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:33384, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78533, ChEBI:CHEBI:456215; EC=6.1.1.11;
CC Evidence={ECO:0000250|UniProtKB:P49591};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-serine + tRNA(Sec) = AMP + diphosphate + H(+) + L-
CC seryl-tRNA(Sec); Xref=Rhea:RHEA:42580, Rhea:RHEA-COMP:9742,
CC Rhea:RHEA-COMP:10128, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:33384, ChEBI:CHEBI:78442,
CC ChEBI:CHEBI:78533, ChEBI:CHEBI:456215; EC=6.1.1.11;
CC Evidence={ECO:0000250|UniProtKB:P49591};
CC -!- PATHWAY: Aminoacyl-tRNA biosynthesis; selenocysteinyl-tRNA(Sec)
CC biosynthesis; L-seryl-tRNA(Sec) from L-serine and tRNA(Sec): step 1/1.
CC -!- SUBUNIT: Homodimer. The tRNA molecule may bind across the dimer.
CC Interacts with SIRT2. Interacts with METTL6; interaction is required
CC for the tRNA N(3)-methylcytidine methyltransferase activity of METTL6.
CC {ECO:0000250|UniProtKB:P49591}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P49591}. Nucleus
CC {ECO:0000250|UniProtKB:P49591}. Note=Predominantly cytoplasmic, but a
CC minor proportion is also found in the nucleus.
CC {ECO:0000250|UniProtKB:P49591}.
CC -!- DOMAIN: Consists of two distinct domains, a catalytic core and a N-
CC terminal extension that is involved in tRNA binding.
CC {ECO:0000250|UniProtKB:P49591}.
CC -!- SIMILARITY: Belongs to the class-II aminoacyl-tRNA synthetase family.
CC Type-1 seryl-tRNA synthetase subfamily. {ECO:0000305}.
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DR EMBL; AB169795; BAE01876.1; -; mRNA.
DR RefSeq; NP_001270308.1; NM_001283379.1.
DR AlphaFoldDB; Q4R4U9; -.
DR SMR; Q4R4U9; -.
DR STRING; 9541.XP_005558926.1; -.
DR GeneID; 101866794; -.
DR KEGG; mcf:101866794; -.
DR CTD; 6301; -.
DR eggNOG; KOG2509; Eukaryota.
DR OrthoDB; 726296at2759; -.
DR UniPathway; UPA00906; UER00895.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0004828; F:serine-tRNA ligase activity; ISS:UniProtKB.
DR GO; GO:0016525; P:negative regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:1904046; P:negative regulation of vascular endothelial growth factor production; ISS:UniProtKB.
DR GO; GO:0097056; P:selenocysteinyl-tRNA(Sec) biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006434; P:seryl-tRNA aminoacylation; ISS:UniProtKB.
DR CDD; cd00770; SerRS_core; 1.
DR Gene3D; 1.10.287.40; -; 1.
DR Gene3D; 3.30.930.10; -; 1.
DR InterPro; IPR002314; aa-tRNA-synt_IIb.
DR InterPro; IPR006195; aa-tRNA-synth_II.
DR InterPro; IPR045864; aa-tRNA-synth_II/BPL/LPL.
DR InterPro; IPR002317; Ser-tRNA-ligase_type_1.
DR InterPro; IPR015866; Ser-tRNA-synth_1_N.
DR InterPro; IPR042103; SerRS_1_N_sf.
DR InterPro; IPR033729; SerRS_core.
DR InterPro; IPR010978; tRNA-bd_arm.
DR PANTHER; PTHR11778; PTHR11778; 1.
DR Pfam; PF02403; Seryl_tRNA_N; 1.
DR Pfam; PF00587; tRNA-synt_2b; 1.
DR PIRSF; PIRSF001529; Ser-tRNA-synth_IIa; 1.
DR PRINTS; PR00981; TRNASYNTHSER.
DR SUPFAM; SSF46589; SSF46589; 1.
DR SUPFAM; SSF55681; SSF55681; 1.
DR TIGRFAMs; TIGR00414; serS; 1.
DR PROSITE; PS50862; AA_TRNA_LIGASE_II; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm;
KW DNA-binding; Ligase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Protein biosynthesis; Reference proteome.
FT CHAIN 1..514
FT /note="Serine--tRNA ligase, cytoplasmic"
FT /id="PRO_0000270763"
FT REGION 9..61
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT REGION 471..514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 482..494
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT COMPBIAS 478..500
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 271
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT BINDING 302..304
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT BINDING 302
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT BINDING 318..321
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT BINDING 325
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT BINDING 391..394
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT BINDING 427
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT SITE 429
FT /note="Important for serine binding"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT MOD_RES 323
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P49591"
SQ SEQUENCE 514 AA; 58765 MW; 81C2068AF066B393 CRC64;
MVLDLDLFRV DKGGDPALIR ETQEKRFKDP GLVDQLVKAD SEWRRCRFRA DNLNKLKNLC
SKTIGEKMKK KEPVEDDESV PENVLNFDDL TADALANLKV SQIKKVRLLI DEAILKCDAE
RIKLEAERFE NLREIGNLLH PSVPISNDED ADNKVERIWG DCTVRKKYSH VDLVVMVDGF
EGEKGAVVAG SRGYFLKGVL VFLEQALIQY ALRTLGSRGY TPIYTPFFMR KEVMQEVAQL
SQFDEELYKV IGKGSEKSDD NSYDEKYLIA TSEQPIAALH RDEWLRPEDL PIKYAGLSTC
FRQEVGSHGR DTRGIFRVHQ FEKIEQFVYS SPHDNKSWEM FEEMITTAEE FYQSLGIPYH
IVNIVSGSLN HAASKKLDLE AWFPGSGAFR ELVSCSNCTD YQARRLRIRY GQTKKMMDKV
EFVHMLNATM CATTRTICAI LENYQTEKGI TVPEKLKEFM PPGLQELIPF VKPAPIDQEP
SKKQKKQHEG SKKKAAARDV ALESRLQNME VTDA
