SYSC_HUMAN
ID SYSC_HUMAN Reviewed; 514 AA.
AC P49591; B2R6Y9; Q5T5C8; Q9NSE3;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Serine--tRNA ligase, cytoplasmic;
DE EC=6.1.1.11 {ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058, ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:9431993};
DE AltName: Full=Seryl-tRNA synthetase;
DE Short=SerRS;
DE AltName: Full=Seryl-tRNA(Ser/Sec) synthetase;
GN Name=SARS1 {ECO:0000312|HGNC:HGNC:10537}; Synonyms=SARS, SERS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC TISSUE=Brain;
RX PubMed=9431993; DOI=10.1111/j.1432-1033.1997.00077.x;
RA Vincent C., Tarbouriech N., Haertlein M.;
RT "Genomic organization, cDNA sequence, bacterial expression, and
RT purification of human seryl-tRNA synthase.";
RL Eur. J. Biochem. 250:77-84(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Shiba K., Yu R., Motegi H., Martinis S., Noda T.;
RT "Isolation and characterization of human seryl-tRNA synthetase cDNA.";
RL Submitted (MAR-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Placenta;
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP FUNCTION.
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 [10]
RP FUNCTION.
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 [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-323, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [14]
RP FUNCTION, DNA BINDING, INTERACTION WITH SIRT2, AND MUTAGENESIS OF
RP 2-VAL--GLY-14; 75-GLY--ASN-97; 254-GLY--SER-261 AND 413-THR--VAL-420.
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).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [16]
RP INTERACTION WITH METTL6.
RX PubMed=28655767; DOI=10.1074/jbc.m117.798298;
RA Xu L., Liu X., Sheng N., Oo K.S., Liang J., Chionh Y.H., Xu J., Ye F.,
RA Gao Y.G., Dedon P.C., Fu X.Y.;
RT "Three distinct 3-methylcytidine (m3C) methyltransferases modify tRNA and
RT mRNA in mice and humans.";
RL J. Biol. Chem. 292:14695-14703(2017).
RN [17]
RP INTERACTION WITH METTL6.
RX PubMed=34268557; DOI=10.1093/nar/gkab603;
RA Mao X.L., Li Z.H., Huang M.H., Wang J.T., Zhou J.B., Li Q.R., Xu H.,
RA Wang X.J., Zhou X.L.;
RT "Mutually exclusive substrate selection strategy by human m3C RNA
RT transferases METTL2A and METTL6.";
RL Nucleic Acids Res. 49:8309-8323(2021).
RN [18] {ECO:0007744|PDB:3VBB}
RP X-RAY CRYSTALLOGRAPHY (2.89 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-378; PHE-383;
RP THR-429; 482-LYS--ALA-514; LYS-482; LYS-485 AND LYS-493.
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 [19] {ECO:0007744|PDB:4L87}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 2-477 IN COMPLEX WITH
RP SERINE-ADENYLATE ANALOG, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP 75-GLY--ASN-97 AND 254-GLY--SER-261.
RX PubMed=24095058; DOI=10.1016/j.str.2013.08.021;
RA Xu X., Shi Y., Yang X.L.;
RT "Crystal structure of human Seryl-tRNA synthetase and Ser-SA complex
RT reveals a molecular lever specific to higher eukaryotes.";
RL Structure 21:2078-2086(2013).
RN [20] {ECO:0007744|PDB:4RQE, ECO:0007744|PDB:4RQF}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) IN COMPLEX WITH SERINE; ATP ANALOG
RP AND TRNA, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, AND MUTAGENESIS OF ARG-9;
RP ARG-44; ASP-51; ASN-54; LYS-55; ASN-58; SER-61; LYS-104 AND ARG-107.
RX PubMed=26433229; DOI=10.1093/nar/gkv996;
RA Wang C., Guo Y., Tian Q., Jia Q., Gao Y., Zhang Q., Zhou C., Xie W.;
RT "SerRS-tRNASec complex structures reveal mechanism of the first step in
RT selenocysteine biosynthesis.";
RL Nucleic Acids Res. 43:10534-10545(2015).
RN [21]
RP VARIANT NEDMAS ASN-172, CHARACTERIZATION OF VARIANT NEDMAS ASN-172,
RP INVOLVEMENT IN NEDMAS, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF THR-429.
RX PubMed=28236339; DOI=10.1002/humu.23205;
RA Musante L., Puettmann L., Kahrizi K., Garshasbi M., Hu H., Stehr H.,
RA Lipkowitz B., Otto S., Jensen L.R., Tzschach A., Jamali P., Wienker T.,
RA Najmabadi H., Ropers H.H., Kuss A.W.;
RT "Mutations of the aminoacyl-tRNA-synthetases SARS and WARS2 are implicated
RT in the aetiology of autosomal recessive intellectual disability.";
RL Hum. Mutat. 38:621-636(2017).
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:22353712,
CC PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339). 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:9431993, PubMed:26433229,
CC PubMed:28236339). In the nucleus, binds to the VEGFA core promoter and
CC prevents MYC binding and transcriptional activation by MYC
CC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting
CC deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the
CC production of VEGFA and sprouting angiogenesis mediated by VEGFA
CC (PubMed:19423848, PubMed:19423847, PubMed:24940000).
CC {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848,
CC ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058,
CC ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229,
CC ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:9431993}.
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:22353712, ECO:0000269|PubMed:24095058,
CC ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339,
CC ECO:0000269|PubMed:9431993};
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:22353712, ECO:0000269|PubMed:24095058,
CC ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339,
CC ECO:0000269|PubMed:9431993};
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 (PubMed:22353712, PubMed:26433229). The tRNA
CC molecule may bind across the dimer (PubMed:26433229). Interacts with
CC SIRT2 (PubMed:24940000). Interacts with METTL6; interaction is required
CC for the tRNA N(3)-methylcytidine methyltransferase activity of METTL6
CC (PubMed:28655767, PubMed:34268557). {ECO:0000269|PubMed:22353712,
CC ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229,
CC ECO:0000269|PubMed:28655767, ECO:0000269|PubMed:34268557}.
CC -!- INTERACTION:
CC P49591; Q6DHV7-2: ADAL; NbExp=3; IntAct=EBI-1053431, EBI-18899653;
CC P49591; Q6LES2: ANXA4; NbExp=3; IntAct=EBI-1053431, EBI-10250835;
CC P49591; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-1053431, EBI-9089489;
CC P49591; Q8TAB7: CCDC26; NbExp=3; IntAct=EBI-1053431, EBI-10271580;
CC P49591; P38936: CDKN1A; NbExp=3; IntAct=EBI-1053431, EBI-375077;
CC P49591; Q9Y4F5-3: CEP170B; NbExp=3; IntAct=EBI-1053431, EBI-12950757;
CC P49591; A0A024RCP2: DOM3Z; NbExp=3; IntAct=EBI-1053431, EBI-25847826;
CC P49591; A0A0C4DGV4: LAMTOR5; NbExp=3; IntAct=EBI-1053431, EBI-10173304;
CC P49591; Q92615: LARP4B; NbExp=3; IntAct=EBI-1053431, EBI-1052558;
CC P49591; A6NJ78-4: METTL15; NbExp=3; IntAct=EBI-1053431, EBI-10174029;
CC P49591; Q8N2H9-4: PELI3; NbExp=3; IntAct=EBI-1053431, EBI-25852006;
CC P49591; O15534: PER1; NbExp=3; IntAct=EBI-1053431, EBI-2557276;
CC P49591; Q14181: POLA2; NbExp=3; IntAct=EBI-1053431, EBI-712752;
CC P49591; P79522: PRR3; NbExp=3; IntAct=EBI-1053431, EBI-2803328;
CC P49591; Q9NS23-4: RASSF1; NbExp=3; IntAct=EBI-1053431, EBI-438710;
CC P49591; Q9NUC0: SERTAD4; NbExp=3; IntAct=EBI-1053431, EBI-1773811;
CC P49591; O14544: SOCS6; NbExp=3; IntAct=EBI-1053431, EBI-3929549;
CC P49591; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-1053431, EBI-10696971;
CC P49591; Q496A3: SPATS1; NbExp=3; IntAct=EBI-1053431, EBI-3923692;
CC P49591; Q9UH65: SWAP70; NbExp=3; IntAct=EBI-1053431, EBI-310749;
CC P49591; Q7Z7C8-2: TAF8; NbExp=3; IntAct=EBI-1053431, EBI-9089028;
CC P49591; Q8N0U2: TMEM61; NbExp=3; IntAct=EBI-1053431, EBI-25830583;
CC P49591; Q9NX94: WBP1L; NbExp=3; IntAct=EBI-1053431, EBI-10316321;
CC P49591; Q9BRR0: ZKSCAN3; NbExp=3; IntAct=EBI-1053431, EBI-1965777;
CC P49591; Q9BYN7-2: ZNF341; NbExp=3; IntAct=EBI-1053431, EBI-16435478;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:22353712,
CC ECO:0000269|PubMed:28236339}. Nucleus {ECO:0000269|PubMed:22353712}.
CC Note=Predominantly cytoplasmic, but a minor proportion is also found in
CC the nucleus. {ECO:0000269|PubMed:22353712}.
CC -!- TISSUE SPECIFICITY: Brain. {ECO:0000269|PubMed:28236339}.
CC -!- DOMAIN: Consists of two distinct domains, a catalytic core and a N-
CC terminal extension that is involved in tRNA binding.
CC {ECO:0000269|PubMed:26433229}.
CC -!- DISEASE: Neurodevelopmental disorder with microcephaly, ataxia, and
CC seizures (NEDMAS) [MIM:617709]: An autosomal recessive disorder
CC characterized by delayed psychomotor development, intellectual
CC disability, seizures apparent in infancy, impaired speech, and
CC aggressive behavior. Additional features include microcephaly, ataxia,
CC and muscle weakness. {ECO:0000269|PubMed:28236339}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
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; X91257; CAA62635.1; -; mRNA.
DR EMBL; D49914; BAA95602.1; -; mRNA.
DR EMBL; AK312771; BAG35636.1; -; mRNA.
DR EMBL; AL356389; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471122; EAW56369.1; -; Genomic_DNA.
DR EMBL; BC000716; AAH00716.1; -; mRNA.
DR EMBL; BC009390; AAH09390.1; -; mRNA.
DR CCDS; CCDS795.1; -.
DR PIR; G01026; G01026.
DR RefSeq; NP_006504.2; NM_006513.3.
DR PDB; 3VBB; X-ray; 2.89 A; A/B/C/D/E/F=1-514.
DR PDB; 4L87; X-ray; 2.90 A; A=2-477.
DR PDB; 4RQE; X-ray; 4.00 A; A/C=1-514.
DR PDB; 4RQF; X-ray; 3.50 A; A/B=1-514.
DR PDBsum; 3VBB; -.
DR PDBsum; 4L87; -.
DR PDBsum; 4RQE; -.
DR PDBsum; 4RQF; -.
DR AlphaFoldDB; P49591; -.
DR SMR; P49591; -.
DR BioGRID; 112208; 92.
DR DIP; DIP-38215N; -.
DR IntAct; P49591; 48.
DR MINT; P49591; -.
DR STRING; 9606.ENSP00000234677; -.
DR BindingDB; P49591; -.
DR ChEMBL; CHEMBL4523232; -.
DR DrugBank; DB00133; Serine.
DR GlyConnect; 1738; 4 N-Linked glycans (1 site).
DR GlyGen; P49591; 2 sites, 4 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; P49591; -.
DR MetOSite; P49591; -.
DR PhosphoSitePlus; P49591; -.
DR SwissPalm; P49591; -.
DR BioMuta; SARS; -.
DR DMDM; 19860217; -.
DR CPTAC; CPTAC-438; -.
DR CPTAC; CPTAC-439; -.
DR EPD; P49591; -.
DR jPOST; P49591; -.
DR MassIVE; P49591; -.
DR MaxQB; P49591; -.
DR PaxDb; P49591; -.
DR PeptideAtlas; P49591; -.
DR PRIDE; P49591; -.
DR ProteomicsDB; 56027; -.
DR ABCD; P49591; 3 sequenced antibodies.
DR Antibodypedia; 1608; 241 antibodies from 29 providers.
DR DNASU; 6301; -.
DR Ensembl; ENST00000234677.7; ENSP00000234677.2; ENSG00000031698.13.
DR GeneID; 6301; -.
DR KEGG; hsa:6301; -.
DR MANE-Select; ENST00000234677.7; ENSP00000234677.2; NM_006513.4; NP_006504.2.
DR UCSC; uc001dwu.3; human.
DR CTD; 6301; -.
DR DisGeNET; 6301; -.
DR GeneCards; SARS1; -.
DR HGNC; HGNC:10537; SARS1.
DR HPA; ENSG00000031698; Low tissue specificity.
DR MalaCards; SARS1; -.
DR MIM; 607529; gene.
DR MIM; 617709; phenotype.
DR neXtProt; NX_P49591; -.
DR OpenTargets; ENSG00000031698; -.
DR Orphanet; 88616; Autosomal recessive non-syndromic intellectual disability.
DR PharmGKB; PA34945; -.
DR VEuPathDB; HostDB:ENSG00000031698; -.
DR eggNOG; KOG2509; Eukaryota.
DR GeneTree; ENSGT00940000153792; -.
DR HOGENOM; CLU_023797_0_0_1; -.
DR InParanoid; P49591; -.
DR OMA; SPCFRRE; -.
DR PhylomeDB; P49591; -.
DR TreeFam; TF300762; -.
DR BRENDA; 6.1.1.11; 2681.
DR PathwayCommons; P49591; -.
DR Reactome; R-HSA-2408557; Selenocysteine synthesis.
DR Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR SignaLink; P49591; -.
DR SIGNOR; P49591; -.
DR UniPathway; UPA00906; UER00895.
DR BioGRID-ORCS; 6301; 809 hits in 1088 CRISPR screens.
DR ChiTaRS; SARS; human.
DR GeneWiki; SARS_(gene); -.
DR GenomeRNAi; 6301; -.
DR Pharos; P49591; Tbio.
DR PRO; PR:P49591; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P49591; protein.
DR Bgee; ENSG00000031698; Expressed in islet of Langerhans and 203 other tissues.
DR ExpressionAtlas; P49591; baseline and differential.
DR Genevisible; P49591; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0003723; F:RNA binding; TAS:ProtInc.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA: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:0016525; P:negative regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:1904046; P:negative regulation of vascular endothelial growth factor production; IDA:UniProtKB.
DR GO; GO:0097056; P:selenocysteinyl-tRNA(Sec) biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006434; P:seryl-tRNA aminoacylation; IDA:UniProtKB.
DR GO; GO:0006412; P:translation; TAS:ProtInc.
DR GO; GO:0008033; P:tRNA processing; TAS:ProtInc.
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 3D-structure; Acetylation; Aminoacyl-tRNA synthetase; ATP-binding;
KW Cytoplasm; Disease variant; DNA-binding; Epilepsy; Intellectual disability;
KW Ligase; Nucleotide-binding; Nucleus; Phosphoprotein; Protein biosynthesis;
KW Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..514
FT /note="Serine--tRNA ligase, cytoplasmic"
FT /id="PRO_0000122191"
FT REGION 9..61
FT /note="Interaction with tRNA"
FT /evidence="ECO:0000269|PubMed:26433229"
FT REGION 473..514
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 482..494
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:22353712"
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:0000269|PubMed:24095058,
FT ECO:0007744|PDB:4L87"
FT BINDING 302..304
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24095058,
FT ECO:0000269|PubMed:26433229, ECO:0007744|PDB:4L87"
FT BINDING 302
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000269|PubMed:24095058,
FT ECO:0007744|PDB:4L87"
FT BINDING 318..321
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24095058,
FT ECO:0000269|PubMed:26433229, ECO:0007744|PDB:4L87"
FT BINDING 325
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000269|PubMed:24095058,
FT ECO:0007744|PDB:4L87"
FT BINDING 391..394
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:24095058,
FT ECO:0000269|PubMed:26433229, ECO:0007744|PDB:4L87"
FT BINDING 427
FT /ligand="L-serine"
FT /ligand_id="ChEBI:CHEBI:33384"
FT /evidence="ECO:0000269|PubMed:24095058,
FT ECO:0007744|PDB:4L87"
FT SITE 429
FT /note="Important for serine binding"
FT /evidence="ECO:0000269|PubMed:28236339"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17525332"
FT MOD_RES 323
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VARIANT 172
FT /note="D -> N (in NEDMAS; impaired serine-activation of
FT enzyme resulting in a significant decrease in the first
FT step of the aminoacylation reaction; reduced protein
FT stability; reduced protein expression; dbSNP:rs1553178049)"
FT /evidence="ECO:0000269|PubMed:28236339"
FT /id="VAR_078434"
FT MUTAGEN 2..14
FT /note="Missing: Abolishes DNA binding."
FT /evidence="ECO:0000269|PubMed:24940000"
FT MUTAGEN 9
FT /note="R->A: Strongly decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 44
FT /note="R->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 51
FT /note="D->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 54
FT /note="N->A: Strongly decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 55
FT /note="K->A: Moderately decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 58
FT /note="N->A: Moderately decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 61
FT /note="S->A: Moderately decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 75..97
FT /note="Missing: Decreased enzyme activity. Abolishes DNA
FT binding."
FT /evidence="ECO:0000269|PubMed:24095058,
FT ECO:0000269|PubMed:24940000"
FT MUTAGEN 104
FT /note="K->A: Moderately decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 107
FT /note="R->A: Moderately decreased enzyme activity."
FT /evidence="ECO:0000269|PubMed:26433229"
FT MUTAGEN 254..261
FT /note="Missing: Mildly decreased enzyme activity. Nearly
FT abolishes DNA binding."
FT /evidence="ECO:0000269|PubMed:24095058,
FT ECO:0000269|PubMed:24940000"
FT MUTAGEN 378
FT /note="D->R: Retains nuclear location and abolishes enzyme
FT activity; when associated with V-383."
FT /evidence="ECO:0000269|PubMed:22353712"
FT MUTAGEN 383
FT /note="F->V: Abolishes nuclear location. Decreases enzyme
FT activity. Retains nuclear location and abolishes enzyme
FT activity; when associated with R-378."
FT /evidence="ECO:0000269|PubMed:22353712"
FT MUTAGEN 413..420
FT /note="Missing: Abolishes DNA binding."
FT /evidence="ECO:0000269|PubMed:24940000"
FT MUTAGEN 429
FT /note="T->A: Catalytically inactive. Loss of serine
FT binding. No effect on nuclear location."
FT /evidence="ECO:0000269|PubMed:22353712,
FT ECO:0000269|PubMed:28236339"
FT MUTAGEN 482..514
FT /note="Missing: Abolishes nuclear localization."
FT /evidence="ECO:0000269|PubMed:22353712"
FT MUTAGEN 482
FT /note="K->A: Abolishes nuclear localization; when
FT associated with A-485 and A-493."
FT /evidence="ECO:0000269|PubMed:22353712"
FT MUTAGEN 485
FT /note="K->A: Abolishes nuclear localization; when
FT associated with A-482 and A-493."
FT /evidence="ECO:0000269|PubMed:22353712"
FT MUTAGEN 493
FT /note="K->A: Abolishes nuclear localization; when
FT associated with A-482 and A-485."
FT /evidence="ECO:0000269|PubMed:22353712"
FT CONFLICT 54
FT /note="N -> S (in Ref. 1; CAA62635)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="R -> C (in Ref. 6; AAH09390)"
FT /evidence="ECO:0000305"
FT HELIX 5..7
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 10..12
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 16..25
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 31..70
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 92..96
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 100..102
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 103..112
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 118..131
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 132..134
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 149..152
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 154..160
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 170..176
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 183..189
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 199..217
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 221..224
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 227..230
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 231..237
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 240..245
FT /evidence="ECO:0007829|PDB:4L87"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 254..256
FT /evidence="ECO:0007829|PDB:4L87"
FT STRAND 266..268
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 273..277
FT /evidence="ECO:0007829|PDB:3VBB"
FT TURN 278..282
FT /evidence="ECO:0007829|PDB:4L87"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:4L87"
FT TURN 287..289
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 292..301
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 308..311
FT /evidence="ECO:0007829|PDB:4L87"
FT STRAND 315..317
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 319..330
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 336..354
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 359..363
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 366..368
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 374..383
FT /evidence="ECO:0007829|PDB:3VBB"
FT TURN 384..387
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 388..397
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 401..406
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 424..432
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 433..444
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 447..451
FT /evidence="ECO:0007829|PDB:3VBB"
FT HELIX 454..457
FT /evidence="ECO:0007829|PDB:3VBB"
FT STRAND 464..469
FT /evidence="ECO:0007829|PDB:3VBB"
SQ SEQUENCE 514 AA; 58777 MW; F59DA8E55F193ACB CRC64;
MVLDLDLFRV DKGGDPALIR ETQEKRFKDP GLVDQLVKAD SEWRRCRFRA DNLNKLKNLC
SKTIGEKMKK KEPVGDDESV PENVLSFDDL TADALANLKV SQIKKVRLLI DEAILKCDAE
RIKLEAERFE NLREIGNLLH PSVPISNDED VDNKVERIWG DCTVRKKYSH VDLVVMVDGF
EGEKGAVVAG SRGYFLKGVL VFLEQALIQY ALRTLGSRGY IPIYTPFFMR KEVMQEVAQL
SQFDEELYKV IGKGSEKSDD NSYDEKYLIA TSEQPIAALH RDEWLRPEDL PIKYAGLSTC
FRQEVGSHGR DTRGIFRVHQ FEKIEQFVYS SPHDNKSWEM FEEMITTAEE FYQSLGIPYH
IVNIVSGSLN HAASKKLDLE AWFPGSGAFR ELVSCSNCTD YQARRLRIRY GQTKKMMDKV
EFVHMLNATM CATTRTICAI LENYQTEKGI TVPEKLKEFM PPGLQELIPF VKPAPIEQEP
SKKQKKQHEG SKKKAAARDV TLENRLQNME VTDA
