SYSC_DANRE
ID SYSC_DANRE Reviewed; 515 AA.
AC Q6DRC0;
DT 27-SEP-2017, integrated into UniProtKB/Swiss-Prot.
DT 16-AUG-2004, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Serine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.11 {ECO:0000269|PubMed:19423848};
DE AltName: Full=Seryl-tRNA synthetase;
DE Short=SerRS;
GN Name=sars1; Synonyms=sars {ECO:0000312|ZFIN:ZDB-GENE-040831-1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1] {ECO:0000312|EMBL:BAI44434.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF THR-429.
RX PubMed=19423848; DOI=10.1161/circresaha.108.191189;
RA Fukui H., Hanaoka R., Kawahara A.;
RT "Noncanonical activity of seryl-tRNA synthetase is involved in vascular
RT development.";
RL Circ. Res. 104:1253-1259(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RX PubMed=15256591; DOI=10.1073/pnas.0403929101;
RA Amsterdam A., Nissen R.M., Sun Z., Swindell E.C., Farrington S.,
RA Hopkins N.;
RT "Identification of 315 genes essential for early zebrafish development.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:12792-12797(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (SEP-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, AND MUTAGENESIS OF PHE-383.
RX PubMed=19423847; DOI=10.1161/circresaha.108.191718;
RA Herzog W., Mueller K., Huisken J., Stainier D.Y.;
RT "Genetic evidence for a noncanonical function of seryl-tRNA synthetase in
RT vascular development.";
RL Circ. Res. 104:1260-1266(2009).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22353712; DOI=10.1038/ncomms1686;
RA Xu X., Shi Y., Zhang H.M., Swindell E.C., Marshall A.G., Guo M., Kishi S.,
RA Yang X.L.;
RT "Unique domain appended to vertebrate tRNA synthetase is essential for
RT vascular development.";
RL Nat. Commun. 3:681-681(2012).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24940000; DOI=10.7554/elife.02349;
RA Shi Y., Xu X., Zhang Q., Fu G., Mo Z., Wang G.S., Kishi S., Yang X.L.;
RT "tRNA synthetase counteracts c-Myc to develop functional vasculature.";
RL Elife 3:E02349-E02349(2014).
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) (PubMed:19423848). Is
CC probably also able to aminoacylate tRNA(Sec) with serine, to form the
CC misacylated tRNA L-seryl-tRNA(Sec), which will be further converted
CC into selenocysteinyl-tRNA(Sec) (PubMed:19423848). In the nucleus, binds
CC to the vegfa core promoter and prevents myc binding and transcriptional
CC activation by myc (PubMed:24940000). Thereby inhibits the production of
CC vegfa and sprouting angiogenesis mediated by vegfa (PubMed:19423848,
CC PubMed:19423847, PubMed:22353712, PubMed:24940000).
CC {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848,
CC ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24940000}.
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:0000269|PubMed:19423848};
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:0000269|PubMed:19423848};
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 -!- DISRUPTION PHENOTYPE: Morpholino knockdown causes aberrant angiogenesis
CC with excessive intersegmental vessel branching, due to excessive
CC expression of vegfa. {ECO:0000269|PubMed:19423848,
CC ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24940000}.
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; AB453157; BAI44434.1; -; mRNA.
DR EMBL; AY648839; AAT68157.1; -; mRNA.
DR EMBL; AL954678; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC081608; AAH81608.1; -; mRNA.
DR RefSeq; NP_001003882.1; NM_001003882.2.
DR AlphaFoldDB; Q6DRC0; -.
DR SMR; Q6DRC0; -.
DR STRING; 7955.ENSDARP00000015775; -.
DR PaxDb; Q6DRC0; -.
DR PRIDE; Q6DRC0; -.
DR Ensembl; ENSDART00000003296; ENSDARP00000015775; ENSDARG00000008237.
DR GeneID; 445405; -.
DR KEGG; dre:445405; -.
DR CTD; 6301; -.
DR ZFIN; ZDB-GENE-040831-1; sars1.
DR eggNOG; KOG2509; Eukaryota.
DR GeneTree; ENSGT00940000153792; -.
DR HOGENOM; CLU_023797_0_0_1; -.
DR InParanoid; Q6DRC0; -.
DR OMA; SPCFRRE; -.
DR OrthoDB; 726296at2759; -.
DR PhylomeDB; Q6DRC0; -.
DR TreeFam; TF300762; -.
DR BRENDA; 6.1.1.11; 928.
DR PRO; PR:Q6DRC0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 23.
DR Bgee; ENSDARG00000008237; Expressed in tail and 35 other tissues.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IMP:ZFIN.
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; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IBA:GO_Central.
DR GO; GO:0001525; P:angiogenesis; IMP:ZFIN.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IMP:ZFIN.
DR GO; GO:0061300; P:cerebellum vasculature development; IMP:ZFIN.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:1903671; P:negative regulation of sprouting angiogenesis; IMP: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; IDA:UniProtKB.
DR GO; GO:1901342; P:regulation of vasculature development; IGI:ZFIN.
DR GO; GO:0006434; P:seryl-tRNA aminoacylation; IDA:UniProtKB.
DR GO; GO:0001944; P:vasculature development; IMP:ZFIN.
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 Aminoacyl-tRNA synthetase; ATP-binding; Cytoplasm; DNA-binding; Ligase;
KW Nucleotide-binding; Nucleus; Protein biosynthesis; Reference proteome.
FT CHAIN 1..515
FT /note="Serine--tRNA ligase, cytoplasmic"
FT /id="PRO_0000441403"
FT REGION 9..61
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT REGION 475..515
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 493..509
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 MUTAGEN 383
FT /note="F->V: In sars-s277; pronounced dilatation of the
FT aortic arch vasculature at 72 hpf and subsequent aberrant
FT branching of the hindbrain capillary network."
FT /evidence="ECO:0000269|PubMed:19423847"
FT MUTAGEN 429
FT /note="T->A: Abolishes tRNA ligase activity. No effect on
FT ability to regulate sprouting angiogenesis."
FT /evidence="ECO:0000269|PubMed:19423848"
SQ SEQUENCE 515 AA; 58718 MW; 383122F24E2287B7 CRC64;
MVLDLDLFRT DKGGDPEIIR ETQRKRFKDV SLVDKLVQAD TEWRKCRFTA DNLNKAKNLC
SKSIGEKMKK KEPVGDDDTL PEEAQNLEAL TAETLSPLTV TQIKKVRVLV DEAVQKTDSD
RLKLEAERFE YLREIGNLLH PSVPISNDED ADNKVERTWG DCTVQKKYSH VDLVVMVDGY
EGEKGAIVAG SRGYFLKGPL VFLEQALINY ALRILYSKNY NLLYTPFFMR KEVMQEVAQL
SQFDEELYKV IGKGSEKSDD NTVDEKYLIA TSEQPIAAFL RDEWLKPEEL PIRYAGLSTC
FRQEVGSHGR DTRGIFRVHQ FEKIEQFVYA SPHDGKSWEM FDEMIGTAES FYQTLGIPYR
IVNIVSGALN HAASKKLDLE AWFPGSQAFR ELVSCSNCTD YQARRLRIRY GQTKKMMDKA
EFVHMLNATM CATTRVICAI LENFQTEEGI IVPEPLKAFM PPGLTEIIKF VKPAPIDQET
TKKQKKQQEG GKKKKHQGGD ADLENKVENM SVNDS
