SYSC_MOUSE
ID SYSC_MOUSE Reviewed; 512 AA.
AC P26638; A2AFR8;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 175.
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, Sers;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-283.
RX PubMed=1918033; DOI=10.1016/s0021-9258(18)54975-9;
RA Miseta A., Woodley C.L., Greenberg J.R., Slobin L.I.;
RT "Mammalian seryl-tRNA synthetase associates with mRNA in vivo and has
RT homology to elongation factor 1 alpha.";
RL J. Biol. Chem. 266:19158-19161(1991).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-506, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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; AK075827; BAC35990.1; -; mRNA.
DR EMBL; AL672200; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC008612; AAH08612.1; -; mRNA.
DR EMBL; M74012; AAA40108.1; -; mRNA.
DR CCDS; CCDS57254.1; -.
DR RefSeq; NP_001191908.1; NM_001204979.1.
DR AlphaFoldDB; P26638; -.
DR SMR; P26638; -.
DR BioGRID; 203074; 28.
DR IntAct; P26638; 10.
DR MINT; P26638; -.
DR STRING; 10090.ENSMUSP00000099685; -.
DR iPTMnet; P26638; -.
DR PhosphoSitePlus; P26638; -.
DR SwissPalm; P26638; -.
DR REPRODUCTION-2DPAGE; P26638; -.
DR EPD; P26638; -.
DR jPOST; P26638; -.
DR MaxQB; P26638; -.
DR PaxDb; P26638; -.
DR PeptideAtlas; P26638; -.
DR PRIDE; P26638; -.
DR ProteomicsDB; 254790; -.
DR Antibodypedia; 1608; 241 antibodies from 29 providers.
DR DNASU; 20226; -.
DR Ensembl; ENSMUST00000090553; ENSMUSP00000088041; ENSMUSG00000068739.
DR GeneID; 20226; -.
DR KEGG; mmu:20226; -.
DR UCSC; uc008qzb.2; mouse.
DR CTD; 20226; -.
DR MGI; MGI:102809; Sars.
DR VEuPathDB; HostDB:ENSMUSG00000068739; -.
DR eggNOG; KOG2509; Eukaryota.
DR GeneTree; ENSGT00940000153792; -.
DR InParanoid; P26638; -.
DR UniPathway; UPA00906; UER00895.
DR BioGRID-ORCS; 20226; 23 hits in 72 CRISPR screens.
DR ChiTaRS; Sars; mouse.
DR PRO; PR:P26638; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P26638; protein.
DR Bgee; ENSMUSG00000068739; Expressed in seminal vesicle and 269 other tissues.
DR ExpressionAtlas; P26638; baseline and differential.
DR Genevisible; P26638; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
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:0000049; F:tRNA binding; IBA:GO_Central.
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 DNA-binding; Ligase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Protein biosynthesis; Reference proteome.
FT CHAIN 1..512
FT /note="Serine--tRNA ligase, cytoplasmic"
FT /id="PRO_0000122192"
FT REGION 9..61
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000250|UniProtKB:P49591"
FT REGION 470..512
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..499
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"
FT MOD_RES 506
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT CONFLICT 96
FT /note="A -> R (in Ref. 4; AAA40108)"
FT /evidence="ECO:0000305"
FT CONFLICT 192..199
FT /note="RGYFLKGP -> PGVLPEGA (in Ref. 4; AAA40108)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="E -> A (in Ref. 4; AAA40108)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 512 AA; 58389 MW; 7EF2C68DB20C6FA0 CRC64;
MVLDLDLFRV DKGGDPALIR ETQEKRFKDP GLVDQLVKAD SEWRRCRFRA DNLNKLKNLC
SKTIGEKMKK KEAVGDDESV PENVLNFDDL TADALAALKV SQIKKVRLLI DEAIQKCDGE
RVKLEAERFE NLREIGNLLH PSVPISNDED ADNKVERIWG DCTVRKKYSH VDLVVMVDGF
EGEKGAVVAG SRGYFLKGPL VFLEQALIQY ALRTLGSRGY TPIYTPFFMR KEVMQEVAQL
SQFDEELYKV IGKGSEKSDD NSYDEKYLIA TSEQPIAALH RDEWLRPEDL PIKYAGLSTC
FRQEVGSHGR DTRGIFRVHQ FEKIEQFVYS SPHDNKSWEM FDEMIATAEE FYQSLGIPYH
IVNIVSGSLN HAASKKLDLE AWFPGSGAFR ELVSCSNCTD YQARRLRIRY GQTKKMMDKV
EFVHMLNATM CATTRTICAI LENYQAEKGI AVPEKLREFM PPGLQELIPF VKPAPIDQEP
SKKQKKQHEG SKKKAKEVPL ENQLQSMEVT EA
