SYSC_RABIT
ID SYSC_RABIT Reviewed; 514 AA.
AC P13642; G1TXX6;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2017, sequence version 2.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Serine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.11 {ECO:0000250|UniProtKB:P49591};
DE AltName: Full=62 kDa RNA-binding protein;
DE AltName: Full=Seryl-tRNA synthetase;
DE Short=SerRS;
DE AltName: Full=Seryl-tRNA(Ser/Sec) synthetase;
GN Name=SARS1; Synonyms=SARS, SERS;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1] {ECO:0000312|Ensembl:ENSOCUP00000021931, ECO:0000312|Proteomes:UP000001811}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thorbecke {ECO:0000312|Proteomes:UP000001811};
RX PubMed=21993624; DOI=10.1038/nature10530;
RA Lindblad-Toh K., Garber M., Zuk O., Lin M.F., Parker B.J., Washietl S.,
RA Kheradpour P., Ernst J., Jordan G., Mauceli E., Ward L.D., Lowe C.B.,
RA Holloway A.K., Clamp M., Gnerre S., Alfoldi J., Beal K., Chang J.,
RA Clawson H., Cuff J., Di Palma F., Fitzgerald S., Flicek P., Guttman M.,
RA Hubisz M.J., Jaffe D.B., Jungreis I., Kent W.J., Kostka D., Lara M.,
RA Martins A.L., Massingham T., Moltke I., Raney B.J., Rasmussen M.D.,
RA Robinson J., Stark A., Vilella A.J., Wen J., Xie X., Zody M.C., Baldwin J.,
RA Bloom T., Chin C.W., Heiman D., Nicol R., Nusbaum C., Young S.,
RA Wilkinson J., Worley K.C., Kovar C.L., Muzny D.M., Gibbs R.A., Cree A.,
RA Dihn H.H., Fowler G., Jhangiani S., Joshi V., Lee S., Lewis L.R.,
RA Nazareth L.V., Okwuonu G., Santibanez J., Warren W.C., Mardis E.R.,
RA Weinstock G.M., Wilson R.K., Delehaunty K., Dooling D., Fronik C.,
RA Fulton L., Fulton B., Graves T., Minx P., Sodergren E., Birney E.,
RA Margulies E.H., Herrero J., Green E.D., Haussler D., Siepel A., Goldman N.,
RA Pollard K.S., Pedersen J.S., Lander E.S., Kellis M.;
RT "A high-resolution map of human evolutionary constraint using 29 mammals.";
RL Nature 478:476-482(2011).
RN [2]
RP PROTEIN SEQUENCE OF 2-40.
RX PubMed=2452088; DOI=10.1111/j.1432-1033.1988.tb13999.x;
RA Slobin L.I., Greenberg J.R.;
RT "Purification and properties of a protein component of messenger
RT ribonucleoprotein particles that shares a common epitope with eucaryotic
RT elongation factor Tu.";
RL Eur. J. Biochem. 173:305-310(1988).
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}.
CC -!- CAUTION: Was originally thought to function in mRNA expression.
CC {ECO:0000305|PubMed:2452088}.
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DR EMBL; AAGW02000971; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAGW02000972; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; S00490; S00490.
DR RefSeq; XP_002715855.1; XM_002715809.3.
DR AlphaFoldDB; P13642; -.
DR SMR; P13642; -.
DR STRING; 9986.ENSOCUP00000007455; -.
DR Ensembl; ENSOCUT00000026819; ENSOCUP00000021931; ENSOCUG00000008625.
DR GeneID; 100339002; -.
DR CTD; 6301; -.
DR eggNOG; KOG2509; Eukaryota.
DR GeneTree; ENSGT00940000153792; -.
DR InParanoid; P13642; -.
DR UniPathway; UPA00906; UER00895.
DR Proteomes; UP000001811; Chromosome 13.
DR Bgee; ENSOCUG00000008625; Expressed in autopod skin and 17 other tissues.
DR ExpressionAtlas; P13642; baseline.
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 1: Evidence at protein level;
KW Acetylation; Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm;
KW Direct protein sequencing; DNA-binding; Ligase; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Protein biosynthesis; Reference proteome.
FT CHAIN 1..514
FT /note="Serine--tRNA ligase, cytoplasmic"
FT /id="PRO_0000122193"
FT REGION 9..61
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT REGION 472..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; 58891 MW; D6A1093EA27BC421 CRC64;
MVLDLDLFRV DKGGDPALIR ETQEKRFKDP GLVDQLVKAD SEWRRCRFRA DNLNKLKNLC
SKTIGEKMKK KEPVGDDESI PENVLNFDDV TADTLTNLKV SQIKKVRLLI DEAILKCDAE
RIKLEAERFE SLREIGNLLH PSVPISNDED ADNKVERIWG DCTVRKKYSH VDLVVMVDGF
EGEKGAVVAG SRGYFLKGVL VFLEQALIQY ALRTLRNRGY TPIYTPFFMR KEVMQEVAQL
SQFDEELYKV IGKGSEKSDD NSYDEKYLIA TSEQPIAALH RDEWLRPEDL PIKYAGLSTC
FRQEVGSHGR DTRGIFRVHQ FEKIEQFVYS SPHDNKSWEM FEEMIATAEE FYQSLGIPYH
IVNIVSGSLN HAASKKLDLE AWFPGSGAFR ELVSCSNCTD YQARRLRIRY GQTKKMMDKV
EFVHMLNATM CATTRTICAI LENYQTEKGI IVPEKLKEFM PPGLQELIPF VKPAPIDQEP
SKKQKKQHEG SKKKAAARDV TLENRLQNME VTDA
