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SYWC_HUMAN
ID   SYWC_HUMAN              Reviewed;         471 AA.
AC   P23381; A6NGN1; A6NID3; P78535; Q502Y0; Q53XB6; Q9UDI5; Q9UDL3;
DT   01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-1992, sequence version 2.
DT   03-AUG-2022, entry version 214.
DE   RecName: Full=Tryptophan--tRNA ligase, cytoplasmic {ECO:0000305};
DE            EC=6.1.1.2 {ECO:0000269|PubMed:1761529, ECO:0000269|PubMed:28369220};
DE   AltName: Full=Interferon-induced protein 53;
DE            Short=IFP53;
DE   AltName: Full=Tryptophanyl-tRNA synthetase;
DE            Short=TrpRS;
DE            Short=hWRS;
DE   Contains:
DE     RecName: Full=T1-TrpRS;
DE   Contains:
DE     RecName: Full=T2-TrpRS;
GN   Name=WARS1 {ECO:0000312|HGNC:HGNC:12729}; Synonyms=IFI53, WARS, WRS;
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] (ISOFORM 1), AND CATALYTIC ACTIVITY.
RX   PubMed=1761529; DOI=10.1016/s0021-9258(18)54219-8;
RA   Rubin B.Y., Anderson S.L., Xing L., Powell R.J., Tate W.P.;
RT   "Interferon induces tryptophanyl-tRNA synthetase expression in human
RT   fibroblasts.";
RL   J. Biol. Chem. 266:24245-24248(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=1763065; DOI=10.1073/pnas.88.24.11520;
RA   Fleckner J., Rasmussen H.H., Justesen J.;
RT   "Human interferon gamma potently induces the synthesis of a 55-kDa protein
RT   (gamma 2) highly homologous to rabbit peptide chain release factor and
RT   bovine tryptophanyl-tRNA synthetase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:11520-11524(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=1765274; DOI=10.1016/0378-1119(91)90624-k;
RA   Frolova L.Y., Sudomoina M.A., Grigorieva A.Y., Zinovieva O.L.,
RA   Kisselev L.L.;
RT   "Cloning and nucleotide sequence of the structural gene encoding for human
RT   tryptophanyl-tRNA synthetase.";
RL   Gene 109:291-296(1991).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=1537332; DOI=10.1002/j.1460-2075.1992.tb05079.x;
RA   Buwitt U., Flohr T., Boettger E.C.;
RT   "Molecular cloning and characterization of an interferon induced human cDNA
RT   with sequence homology to a mammalian peptide chain release factor.";
RL   EMBO J. 11:489-496(1992).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Fetal liver;
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Teratocarcinoma;
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   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [8]
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   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Blood, and Lymph;
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   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-13.
RX   PubMed=8724762;
RA   Sokolova I.V., Narovlianskii A.N., Amchenkova A.M., Turpaev K.T.;
RT   "Alternative splicing of 5'-terminal exons of the human tryptophanyl-tRNA
RT   synthetase gene.";
RL   Mol. Biol. (Mosk.) 30:319-329(1996).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-141 AND 182-471.
RC   TISSUE=Sperm;
RX   PubMed=7685728; DOI=10.1016/0378-1119(93)90568-n;
RA   Frolova L.Y., Grigorieva A.Y., Sudomoina M.A., Kisselev L.L.;
RT   "The human gene encoding tryptophanyl-tRNA synthetase: interferon-response
RT   elements and exon-intron organization.";
RL   Gene 128:237-245(1993).
RN   [12]
RP   PROTEIN SEQUENCE OF 2-19; 142-162; 205-220; 278-298; 350-366 AND 433-448,
RP   AND INDUCTION.
RC   TISSUE=Keratinocyte;
RX   PubMed=8496617; DOI=10.1111/1523-1747.ep12476463;
RA   Reano A., Richard M.H., Denoroy L., Viac J., Benedetto J.P., Schmitt D.;
RT   "Gamma interferon potently induces tryptophanyl-tRNA synthetase expression
RT   in human keratinocytes.";
RL   J. Invest. Dermatol. 100:775-779(1993).
RN   [13]
RP   PROTEIN SEQUENCE OF 2-24; 97-106; 433-448 AND 465-471, CLEAVAGE OF
RP   INITIATOR METHIONINE, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Colon carcinoma;
RA   Bienvenut W.V., Heiserich L., Gottlieb E.;
RL   Submitted (MAR-2008) to UniProtKB.
RN   [14]
RP   PROTEIN SEQUENCE OF 71-75 AND 91-98, PROTEOLYTIC CLEAVAGE, AND FUNCTION.
RX   PubMed=11773626; DOI=10.1073/pnas.012602099;
RA   Wakasugi K., Slike B.M., Hood J., Otani A., Ewalt K.L., Friedlander M.,
RA   Cheresh D.A., Schimmel P.;
RT   "A human aminoacyl-tRNA synthetase as a regulator of angiogenesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:173-177(2002).
RN   [15]
RP   PROTEIN SEQUENCE OF 265-276; 278-296; 299-317 AND 350-365.
RC   TISSUE=Keratinocyte;
RX   PubMed=1286667; DOI=10.1002/elps.11501301199;
RA   Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA   Vandekerckhove J.;
RT   "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT   database of normal human epidermal keratinocytes.";
RL   Electrophoresis 13:960-969(1992).
RN   [16]
RP   FUNCTION.
RX   PubMed=1373391; DOI=10.1016/0014-5793(92)80187-l;
RA   Bange F.-C., Flohr T., Buwitt U., Boettger E.C.;
RT   "An interferon-induced protein with release factor activity is a
RT   tryptophanyl-tRNA synthetase.";
RL   FEBS Lett. 300:162-166(1992).
RN   [17]
RP   ALTERNATIVE SPLICING.
RX   PubMed=7814400; DOI=10.1074/jbc.270.1.397;
RA   Tolstrup A.B., Bejder A., Fleckner J., Justesen J.;
RT   "Transcriptional regulation of the interferon-gamma-inducible tryptophanyl-
RT   tRNA synthetase includes alternative splicing.";
RL   J. Biol. Chem. 270:397-403(1995).
RN   [18]
RP   FUNCTION.
RX   PubMed=11773625; DOI=10.1073/pnas.012601899;
RA   Otani A., Slike B.M., Dorrell M.I., Hood J., Kinder K., Ewalt K.L.,
RA   Cheresh D., Schimmel P., Friedlander M.;
RT   "A fragment of human TrpRS as a potent antagonist of ocular angiogenesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:178-183(2002).
RN   [19]
RP   FUNCTION.
RX   PubMed=14630953; DOI=10.1073/pnas.2436330100;
RA   Tzima E., Reader J.S., Irani-Tehrani M., Ewalt K.L., Schwartz M.A.,
RA   Schimmel P.;
RT   "Biologically active fragment of a human tRNA synthetase inhibits fluid
RT   shear stress-activated responses of endothelial cells.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:14903-14907(2003).
RN   [20]
RP   INTERACTION WITH GAPDH.
RX   PubMed=15628863; DOI=10.1021/bi048313k;
RA   Wakasugi K., Nakano T., Morishima I.;
RT   "Oxidative stress-responsive intracellular regulation specific for the
RT   angiostatic form of human tryptophanyl-tRNA synthetase.";
RL   Biochemistry 44:225-232(2005).
RN   [21]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [22]
RP   IDENTIFICATION BY MASS 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   [23]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [24]
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   [25]
RP   CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA   Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA   Giglione C.;
RT   "Comparative large-scale characterisation of plant vs. mammal proteins
RT   reveals similar and idiosyncratic N-alpha acetylation features.";
RL   Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN   [26]
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   [27]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-351, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [28]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, INVOLVEMENT IN HMN9, VARIANT HMN9
RP   ARG-257, VARIANT SER-443, AND CHARACTERIZATION OF VARIANT HMN9 ARG-257.
RX   PubMed=28369220; DOI=10.1093/brain/awx058;
RA   Tsai P.C., Soong B.W., Mademan I., Huang Y.H., Liu C.R., Hsiao C.T.,
RA   Wu H.T., Liu T.T., Liu Y.T., Tseng Y.T., Lin K.P., Yang U.C., Chung K.W.,
RA   Choi B.O., Nicholson G.A., Kennerson M.L., Chan C.C., De Jonghe P.,
RA   Cheng T.H., Liao Y.C., Zuechner S., Baets J., Lee Y.C.;
RT   "A recurrent WARS mutation is a novel cause of autosomal dominant distal
RT   hereditary motor neuropathy.";
RL   Brain 140:1252-1266(2017).
RN   [29]
RP   X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1-466.
RX   PubMed=14671330; DOI=10.1073/pnas.2136794100;
RA   Yang X.-L., Otero F.J., Skene R.J., McRee D.E., Schimmel P.,
RA   Ribas de Pouplana L.;
RT   "Crystal structures that suggest late development of genetic code
RT   components for differentiating aromatic side chains.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:15376-15380(2003).
RN   [30]
RP   X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 94-471.
RX   PubMed=14660560; DOI=10.1074/jbc.m311284200;
RA   Yu Y., Liu Y., Shen N., Xu X., Xu F., Jia J., Jin Y., Arnold E., Ding J.;
RT   "Crystal structure of human tryptophanyl-tRNA synthetase catalytic
RT   fragment: insights into substrate recognition, tRNA binding, and
RT   angiogenesis activity.";
RL   J. Biol. Chem. 279:8378-8388(2004).
RN   [31]
RP   VARIANT [LARGE SCALE ANALYSIS] ASP-455.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Isoform 1, isoform 2 and T1-TrpRS have aminoacylation
CC       activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS
CC       possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS
CC       inhibits fluid shear stress-activated responses of endothelial cells.
CC       Regulates ERK, Akt, and eNOS activation pathways that are associated
CC       with angiogenesis, cytoskeletal reorganization and shear stress-
CC       responsive gene expression. {ECO:0000269|PubMed:11773625,
CC       ECO:0000269|PubMed:11773626, ECO:0000269|PubMed:1373391,
CC       ECO:0000269|PubMed:14630953, ECO:0000269|PubMed:28369220}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + L-tryptophan + tRNA(Trp) = AMP + diphosphate + H(+) + L-
CC         tryptophanyl-tRNA(Trp); Xref=Rhea:RHEA:24080, Rhea:RHEA-COMP:9671,
CC         Rhea:RHEA-COMP:9705, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:57912, ChEBI:CHEBI:78442,
CC         ChEBI:CHEBI:78535, ChEBI:CHEBI:456215; EC=6.1.1.2;
CC         Evidence={ECO:0000269|PubMed:1761529, ECO:0000269|PubMed:28369220};
CC   -!- SUBUNIT: Homodimer (PubMed:28369220). Isoform 1 and isoform 2 interact
CC       with an oxidized form of GAPDH. GAPDH stimulates the aminoacylation
CC       activity of isoform 2 (PubMed:15628863). {ECO:0000269|PubMed:15628863,
CC       ECO:0000269|PubMed:28369220}.
CC   -!- INTERACTION:
CC       P23381; P33151: CDH5; NbExp=4; IntAct=EBI-721244, EBI-2903122;
CC       P23381; P54274: TERF1; NbExp=2; IntAct=EBI-721244, EBI-710997;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P23381-1; Sequence=Displayed;
CC       Name=2; Synonyms=mini TrpRS;
CC         IsoId=P23381-2; Sequence=VSP_038221;
CC   -!- INDUCTION: By IFNG/IFN-gamma. {ECO:0000269|PubMed:8496617}.
CC   -!- PTM: Proteolytic cleavage generates 2 forms; T1-TrpRS and T2-TrpRS.
CC       {ECO:0000269|PubMed:11773626}.
CC   -!- DISEASE: Neuronopathy, distal hereditary motor, 9 (HMN9) [MIM:617721]:
CC       An autosomal dominant neurologic disorder characterized by juvenile
CC       onset of slowly progressive distal muscle weakness and atrophy
CC       affecting both the lower and upper limbs.
CC       {ECO:0000269|PubMed:28369220}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase family.
CC       {ECO:0000305}.
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DR   EMBL; M77804; AAA67324.1; -; mRNA.
DR   EMBL; X59892; CAA42545.1; -; mRNA.
DR   EMBL; M61715; AAA61298.1; -; mRNA.
DR   EMBL; X62570; CAA44450.1; -; mRNA.
DR   EMBL; BX248006; CAD62335.1; -; mRNA.
DR   EMBL; AK056100; BAG51626.1; -; mRNA.
DR   EMBL; AK291141; BAF83830.1; -; mRNA.
DR   EMBL; AL157871; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471061; EAW81700.1; -; Genomic_DNA.
DR   EMBL; BC017489; AAH17489.1; -; mRNA.
DR   EMBL; BC095453; AAH95453.1; -; mRNA.
DR   EMBL; S82905; AAB39381.1; -; Genomic_DNA.
DR   EMBL; X67920; CAB94198.1; -; Genomic_DNA.
DR   EMBL; X67921; CAB94198.1; JOINED; Genomic_DNA.
DR   EMBL; X67922; CAB94198.1; JOINED; Genomic_DNA.
DR   EMBL; X67923; CAB94199.1; -; Genomic_DNA.
DR   EMBL; X67924; CAB94199.1; JOINED; Genomic_DNA.
DR   EMBL; X67925; CAB94199.1; JOINED; Genomic_DNA.
DR   EMBL; X67926; CAB94199.1; JOINED; Genomic_DNA.
DR   EMBL; X67927; CAB94199.1; JOINED; Genomic_DNA.
DR   EMBL; X67928; CAB94199.1; JOINED; Genomic_DNA.
DR   CCDS; CCDS9960.1; -. [P23381-1]
DR   CCDS; CCDS9961.1; -. [P23381-2]
DR   PIR; A41633; A41706.
DR   RefSeq; NP_004175.2; NM_004184.3. [P23381-1]
DR   RefSeq; NP_776049.1; NM_173701.1. [P23381-1]
DR   RefSeq; NP_998810.1; NM_213645.1. [P23381-2]
DR   RefSeq; NP_998811.1; NM_213646.1. [P23381-2]
DR   RefSeq; XP_005268101.1; XM_005268044.3. [P23381-1]
DR   RefSeq; XP_006720312.1; XM_006720249.3. [P23381-1]
DR   RefSeq; XP_011535435.1; XM_011537133.2. [P23381-1]
DR   RefSeq; XP_011535437.1; XM_011537135.2.
DR   RefSeq; XP_011535438.1; XM_011537136.2. [P23381-2]
DR   RefSeq; XP_016877116.1; XM_017021627.1. [P23381-1]
DR   RefSeq; XP_016877117.1; XM_017021628.1.
DR   RefSeq; XP_016877118.1; XM_017021629.1. [P23381-1]
DR   PDB; 1O5T; X-ray; 2.50 A; A=94-471.
DR   PDB; 1R6T; X-ray; 2.10 A; A/B=1-466.
DR   PDB; 1R6U; X-ray; 2.00 A; A/B=48-471.
DR   PDB; 1ULH; X-ray; 2.31 A; A/B=82-471.
DR   PDB; 2AKE; X-ray; 3.10 A; A=94-471.
DR   PDB; 2AZX; X-ray; 2.80 A; A/B=1-471.
DR   PDB; 2DR2; X-ray; 3.00 A; A=94-471.
DR   PDB; 2QUH; X-ray; 2.40 A; A/B=1-471.
DR   PDB; 2QUI; X-ray; 2.40 A; A/B=1-471.
DR   PDB; 2QUJ; X-ray; 2.42 A; A/B=1-471.
DR   PDB; 2QUK; X-ray; 2.80 A; A=1-471.
DR   PDB; 5UJI; X-ray; 2.79 A; A/B=97-471.
DR   PDB; 5UJJ; X-ray; 2.10 A; A/B=1-471.
DR   PDBsum; 1O5T; -.
DR   PDBsum; 1R6T; -.
DR   PDBsum; 1R6U; -.
DR   PDBsum; 1ULH; -.
DR   PDBsum; 2AKE; -.
DR   PDBsum; 2AZX; -.
DR   PDBsum; 2DR2; -.
DR   PDBsum; 2QUH; -.
DR   PDBsum; 2QUI; -.
DR   PDBsum; 2QUJ; -.
DR   PDBsum; 2QUK; -.
DR   PDBsum; 5UJI; -.
DR   PDBsum; 5UJJ; -.
DR   AlphaFoldDB; P23381; -.
DR   SMR; P23381; -.
DR   BioGRID; 113292; 93.
DR   DIP; DIP-29493N; -.
DR   IntAct; P23381; 20.
DR   MINT; P23381; -.
DR   STRING; 9606.ENSP00000347495; -.
DR   DrugBank; DB00150; Tryptophan.
DR   DrugBank; DB04537; Tryptophanamide.
DR   DrugBank; DB01831; Tryptophanyl-5'amp.
DR   MoonProt; P23381; -.
DR   GlyGen; P23381; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P23381; -.
DR   MetOSite; P23381; -.
DR   PhosphoSitePlus; P23381; -.
DR   SwissPalm; P23381; -.
DR   BioMuta; WARS; -.
DR   DMDM; 135191; -.
DR   OGP; P23381; -.
DR   EPD; P23381; -.
DR   jPOST; P23381; -.
DR   MassIVE; P23381; -.
DR   MaxQB; P23381; -.
DR   PaxDb; P23381; -.
DR   PeptideAtlas; P23381; -.
DR   PRIDE; P23381; -.
DR   ProteomicsDB; 54085; -. [P23381-1]
DR   ProteomicsDB; 54086; -. [P23381-2]
DR   ABCD; P23381; 4 sequenced antibodies.
DR   Antibodypedia; 27522; 269 antibodies from 30 providers.
DR   DNASU; 7453; -.
DR   Ensembl; ENST00000344102.9; ENSP00000339485.5; ENSG00000140105.18. [P23381-2]
DR   Ensembl; ENST00000355338.6; ENSP00000347495.2; ENSG00000140105.18. [P23381-1]
DR   Ensembl; ENST00000358655.8; ENSP00000351481.4; ENSG00000140105.18. [P23381-2]
DR   Ensembl; ENST00000392882.7; ENSP00000376620.2; ENSG00000140105.18. [P23381-1]
DR   Ensembl; ENST00000556645.5; ENSP00000451887.1; ENSG00000140105.18. [P23381-2]
DR   Ensembl; ENST00000557135.5; ENSP00000451460.1; ENSG00000140105.18. [P23381-1]
DR   GeneID; 7453; -.
DR   KEGG; hsa:7453; -.
DR   MANE-Select; ENST00000392882.7; ENSP00000376620.2; NM_004184.4; NP_004175.2.
DR   UCSC; uc001yhg.3; human. [P23381-1]
DR   CTD; 7453; -.
DR   DisGeNET; 7453; -.
DR   GeneCards; WARS1; -.
DR   GeneReviews; WARS1; -.
DR   HGNC; HGNC:12729; WARS1.
DR   HPA; ENSG00000140105; Tissue enhanced (placenta).
DR   MalaCards; WARS1; -.
DR   MIM; 191050; gene.
DR   MIM; 617721; phenotype.
DR   neXtProt; NX_P23381; -.
DR   OpenTargets; ENSG00000140105; -.
DR   PharmGKB; PA37340; -.
DR   VEuPathDB; HostDB:ENSG00000140105; -.
DR   eggNOG; KOG2145; Eukaryota.
DR   GeneTree; ENSGT00940000153724; -.
DR   HOGENOM; CLU_032621_0_1_1; -.
DR   InParanoid; P23381; -.
DR   OMA; SIYHRFM; -.
DR   PhylomeDB; P23381; -.
DR   TreeFam; TF105669; -.
DR   BRENDA; 6.1.1.2; 2681.
DR   PathwayCommons; P23381; -.
DR   Reactome; R-HSA-379716; Cytosolic tRNA aminoacylation.
DR   SignaLink; P23381; -.
DR   BioGRID-ORCS; 7453; 760 hits in 1092 CRISPR screens.
DR   ChiTaRS; WARS; human.
DR   EvolutionaryTrace; P23381; -.
DR   GeneWiki; WARS_(gene); -.
DR   GenomeRNAi; 7453; -.
DR   Pharos; P23381; Tbio.
DR   PRO; PR:P23381; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; P23381; protein.
DR   Bgee; ENSG00000140105; Expressed in monocyte and 202 other tissues.
DR   ExpressionAtlas; P23381; baseline and differential.
DR   Genevisible; P23381; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:CAFA.
DR   GO; GO:0032991; C:protein-containing complex; IMP:CAFA.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0019210; F:kinase inhibitor activity; IDA:CAFA.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
DR   GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR   GO; GO:0019901; F:protein kinase binding; IPI:CAFA.
DR   GO; GO:0004830; F:tryptophan-tRNA ligase activity; IMP:UniProtKB.
DR   GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; TAS:ProtInc.
DR   GO; GO:0006469; P:negative regulation of protein kinase activity; IDA:CAFA.
DR   GO; GO:0001933; P:negative regulation of protein phosphorylation; IDA:CAFA.
DR   GO; GO:0010628; P:positive regulation of gene expression; IDA:CAFA.
DR   GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IMP:CAFA.
DR   GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
DR   GO; GO:0010835; P:regulation of protein ADP-ribosylation; IDA:CAFA.
DR   GO; GO:0006412; P:translation; TAS:ProtInc.
DR   GO; GO:0006436; P:tryptophanyl-tRNA aminoacylation; IBA:GO_Central.
DR   CDD; cd00806; TrpRS_core; 1.
DR   Gene3D; 3.40.50.620; -; 1.
DR   InterPro; IPR001412; aa-tRNA-synth_I_CS.
DR   InterPro; IPR002305; aa-tRNA-synth_Ic.
DR   InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR   InterPro; IPR009068; S15_NS1_RNA-bd.
DR   InterPro; IPR002306; Trp-tRNA-ligase.
DR   InterPro; IPR000738; WHEP-TRS_dom.
DR   Pfam; PF00579; tRNA-synt_1b; 1.
DR   Pfam; PF00458; WHEP-TRS; 1.
DR   PRINTS; PR01039; TRNASYNTHTRP.
DR   SMART; SM00991; WHEP-TRS; 1.
DR   SUPFAM; SSF47060; SSF47060; 1.
DR   TIGRFAMs; TIGR00233; trpS; 1.
DR   PROSITE; PS00178; AA_TRNA_LIGASE_I; 1.
DR   PROSITE; PS00762; WHEP_TRS_1; 1.
DR   PROSITE; PS51185; WHEP_TRS_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Aminoacyl-tRNA synthetase;
KW   Angiogenesis; ATP-binding; Cytoplasm; Direct protein sequencing;
KW   Disease variant; Ligase; Neurodegeneration; Neuropathy; Nucleotide-binding;
KW   Phosphoprotein; Protein biosynthesis; Reference proteome.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|PubMed:8496617, ECO:0000269|Ref.13,
FT                   ECO:0007744|PubMed:22223895"
FT   CHAIN           2..471
FT                   /note="Tryptophan--tRNA ligase, cytoplasmic"
FT                   /id="PRO_0000136738"
FT   CHAIN           71..471
FT                   /note="T1-TrpRS"
FT                   /id="PRO_0000386461"
FT   CHAIN           94..471
FT                   /note="T2-TrpRS"
FT                   /id="PRO_0000386462"
FT   DOMAIN          8..64
FT                   /note="WHEP-TRS"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00531"
FT   REGION          59..79
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           164..173
FT                   /note="'HIGH' region"
FT   MOTIF           349..353
FT                   /note="'KMSKS' region"
FT   MOD_RES         154
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P32921"
FT   MOD_RES         351
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   VAR_SEQ         1..41
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_038221"
FT   VARIANT         54
FT                   /note="A -> S (in dbSNP:rs2234521)"
FT                   /id="VAR_052406"
FT   VARIANT         257
FT                   /note="H -> R (in HMN9; decreased tryptophan-tRNA ligase
FT                   activity; dominant negative effect; decreased general
FT                   protein synthesis; decreased cell viability; no effect on
FT                   homodimerization)"
FT                   /evidence="ECO:0000269|PubMed:28369220"
FT                   /id="VAR_080407"
FT   VARIANT         443
FT                   /note="A -> S (in dbSNP:rs139914390)"
FT                   /evidence="ECO:0000269|PubMed:28369220"
FT                   /id="VAR_080408"
FT   VARIANT         455
FT                   /note="E -> D (in a breast cancer sample; somatic
FT                   mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036466"
FT   CONFLICT        213..214
FT                   /note="SY -> GD (in Ref. 3; AAA61298)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        310
FT                   /note="A -> V (in Ref. 9; AAH95453)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        424
FT                   /note="A -> R (in Ref. 4; CAA44450)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        439
FT                   /note="Q -> L (in Ref. 9; AAH95453)"
FT                   /evidence="ECO:0000305"
FT   HELIX           8..28
FT                   /evidence="ECO:0007829|PDB:1R6T"
FT   HELIX           33..53
FT                   /evidence="ECO:0007829|PDB:1R6T"
FT   STRAND          54..56
FT                   /evidence="ECO:0007829|PDB:1R6T"
FT   STRAND          84..86
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          89..91
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   TURN            100..102
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           103..106
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           114..124
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           130..133
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          136..142
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           143..150
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   TURN            151..153
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          156..162
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          166..168
FT                   /evidence="ECO:0007829|PDB:5UJJ"
FT   HELIX           171..187
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          191..195
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           197..203
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           208..223
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   TURN            224..226
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           229..231
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          232..236
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           237..240
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           241..243
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           247..256
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           260..267
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          271..274
FT                   /evidence="ECO:0007829|PDB:1ULH"
FT   HELIX           275..285
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           286..288
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           290..292
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           294..297
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          304..310
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           311..313
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           314..323
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           324..327
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          333..337
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          345..349
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          354..357
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          360..362
FT                   /evidence="ECO:0007829|PDB:2AZX"
FT   HELIX           365..374
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          379..381
FT                   /evidence="ECO:0007829|PDB:5UJI"
FT   HELIX           384..390
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   TURN            394..396
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           398..406
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           410..422
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   STRAND          423..425
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           430..450
FT                   /evidence="ECO:0007829|PDB:1R6U"
FT   HELIX           454..460
FT                   /evidence="ECO:0007829|PDB:1R6U"
SQ   SEQUENCE   471 AA;  53165 MW;  E96344449053A0D0 CRC64;
     MPNSEPASLL ELFNSIATQG ELVRSLKAGN ASKDEIDSAV KMLVSLKMSY KAAAGEDYKA
     DCPPGNPAPT SNHGPDATEA EEDFVDPWTV QTSSAKGIDY DKLIVRFGSS KIDKELINRI
     ERATGQRPHH FLRRGIFFSH RDMNQVLDAY ENKKPFYLYT GRGPSSEAMH VGHLIPFIFT
     KWLQDVFNVP LVIQMTDDEK YLWKDLTLDQ AYSYAVENAK DIIACGFDIN KTFIFSDLDY
     MGMSSGFYKN VVKIQKHVTF NQVKGIFGFT DSDCIGKISF PAIQAAPSFS NSFPQIFRDR
     TDIQCLIPCA IDQDPYFRMT RDVAPRIGYP KPALLHSTFF PALQGAQTKM SASDPNSSIF
     LTDTAKQIKT KVNKHAFSGG RDTIEEHRQF GGNCDVDVSF MYLTFFLEDD DKLEQIRKDY
     TSGAMLTGEL KKALIEVLQP LIAEHQARRK EVTDEIVKEF MTPRKLSFDF Q
 
 
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