Full text data of WARS
WARS
(IFI53, WRS)
[Confidence: low (only semi-automatic identification from reviews)]
Tryptophan--tRNA ligase, cytoplasmic; 6.1.1.2 (Interferon-induced protein 53; IFP53; Tryptophanyl-tRNA synthetase; TrpRS; hWRS; T1-TrpRS; T2-TrpRS)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Tryptophan--tRNA ligase, cytoplasmic; 6.1.1.2 (Interferon-induced protein 53; IFP53; Tryptophanyl-tRNA synthetase; TrpRS; hWRS; T1-TrpRS; T2-TrpRS)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P23381
ID SYWC_HUMAN Reviewed; 471 AA.
AC P23381; A6NGN1; A6NID3; P78535; Q502Y0; Q53XB6; Q9UDI5; Q9UDL3;
read moreDT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Tryptophan--tRNA ligase, cytoplasmic;
DE EC=6.1.1.2;
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=WARS; Synonyms=IFI53, WRS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1761529;
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
RT protein (gamma 2) highly homologous to rabbit peptide chain release
RT factor and 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
RT human tryptophanyl-tRNA synthetase.";
RL Gene 109:291-296(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1537332;
RA Buwitt U., Flohr T., Boettger E.C.;
RT "Molecular cloning and characterization of an interferon induced human
RT cDNA with sequence homology to a mammalian peptide chain release
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA 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.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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-
RT tRNA 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-
RT response 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
RP 433-448, 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.,
RA Schmitt D.;
RT "Gamma interferon potently induces tryptophanyl-tRNA synthetase
RT expression 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 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
RP FUNCTION.
RX PubMed=11773626; DOI=10.1073/pnas.012602099;
RA Wakasugi K., Slike B.M., Hood J., Otani A., Ewalt K.L.,
RA Friedlander M., 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
RT protein 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
RT tryptophanyl-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
RT 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
RT fluid 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.,
RA Walther T.C., 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
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 [27]
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.,
RA 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 [28]
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.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT 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
CC cells. Regulates ERK, Akt, and eNOS activation pathways that are
CC associated with angiogenesis, cytoskeletal reorganization and
CC shear stress-responsive gene expression.
CC -!- CATALYTIC ACTIVITY: ATP + L-tryptophan + tRNA(Trp) = AMP +
CC diphosphate + L-tryptophyl-tRNA(Trp).
CC -!- SUBUNIT: Homodimer. Isoform 1 and isoform 2 interact with an
CC oxidized form of GAPDH. GAPDH stimulates the aminoacylation
CC activity of isoform 2.
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.
CC -!- PTM: Proteolytic cleavage generates 2 forms; T1-TrpRS and T2-
CC TrpRS.
CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase
CC family.
CC -!- SIMILARITY: Contains 1 WHEP-TRS domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAF83830.1; Type=Erroneous initiation;
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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; ALT_INIT; 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 PIR; A41633; A41706.
DR RefSeq; NP_004175.2; NM_004184.3.
DR RefSeq; NP_776049.1; NM_173701.1.
DR RefSeq; NP_998810.1; NM_213645.1.
DR RefSeq; NP_998811.1; NM_213646.1.
DR RefSeq; XP_005268099.1; XM_005268042.1.
DR RefSeq; XP_005268100.1; XM_005268043.1.
DR RefSeq; XP_005268101.1; XM_005268044.1.
DR UniGene; Hs.497599; -.
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 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 ProteinModelPortal; P23381; -.
DR SMR; P23381; 82-471.
DR DIP; DIP-29493N; -.
DR IntAct; P23381; 5.
DR MINT; MINT-1408962; -.
DR STRING; 9606.ENSP00000347495; -.
DR DrugBank; DB00150; L-Tryptophan.
DR PhosphoSite; P23381; -.
DR DMDM; 135191; -.
DR OGP; P23381; -.
DR PaxDb; P23381; -.
DR PeptideAtlas; P23381; -.
DR PRIDE; P23381; -.
DR Ensembl; ENST00000344102; ENSP00000339485; ENSG00000140105.
DR Ensembl; ENST00000355338; ENSP00000347495; ENSG00000140105.
DR Ensembl; ENST00000358655; ENSP00000351481; ENSG00000140105.
DR Ensembl; ENST00000392882; ENSP00000376620; ENSG00000140105.
DR Ensembl; ENST00000556645; ENSP00000451887; ENSG00000140105.
DR Ensembl; ENST00000557135; ENSP00000451460; ENSG00000140105.
DR GeneID; 7453; -.
DR KEGG; hsa:7453; -.
DR UCSC; uc001yhg.2; human.
DR CTD; 7453; -.
DR GeneCards; GC14M100800; -.
DR HGNC; HGNC:12729; WARS.
DR MIM; 191050; gene.
DR neXtProt; NX_P23381; -.
DR PharmGKB; PA37340; -.
DR eggNOG; COG0180; -.
DR HOVERGEN; HBG002325; -.
DR InParanoid; P23381; -.
DR KO; K01867; -.
DR OMA; KPETAIY; -.
DR OrthoDB; EOG7T4MK3; -.
DR PhylomeDB; P23381; -.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; WARS; human.
DR EvolutionaryTrace; P23381; -.
DR GeneWiki; WARS_(gene); -.
DR GenomeRNAi; 7453; -.
DR NextBio; 29178; -.
DR PRO; PR:P23381; -.
DR ArrayExpress; P23381; -.
DR Bgee; P23381; -.
DR CleanEx; HS_WARS; -.
DR Genevestigator; P23381; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004830; F:tryptophan-tRNA ligase activity; NAS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0006436; P:tryptophanyl-tRNA aminoacylation; NAS:UniProtKB.
DR Gene3D; 1.10.287.10; -; 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.
DR PANTHER; PTHR10055; PTHR10055; 1.
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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Ligase; Nucleotide-binding; Polymorphism;
KW Protein biosynthesis; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 471 Tryptophan--tRNA ligase, cytoplasmic.
FT /FTId=PRO_0000136738.
FT CHAIN 71 471 T1-TrpRS.
FT /FTId=PRO_0000386461.
FT CHAIN 94 471 T2-TrpRS.
FT /FTId=PRO_0000386462.
FT DOMAIN 8 64 WHEP-TRS.
FT MOTIF 164 173 "HIGH" region.
FT MOTIF 349 353 "KMSKS" region.
FT VAR_SEQ 1 47 Missing (in isoform 2).
FT /FTId=VSP_038221.
FT VARIANT 54 54 A -> S (in dbSNP:rs2234521).
FT /FTId=VAR_052406.
FT VARIANT 455 455 E -> D (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036466.
FT CONFLICT 213 214 SY -> GD (in Ref. 3; AAA61298).
FT CONFLICT 310 310 A -> V (in Ref. 9; AAH95453).
FT CONFLICT 424 424 A -> R (in Ref. 4; CAA44450).
FT CONFLICT 439 439 Q -> L (in Ref. 9; AAH95453).
FT HELIX 8 28
FT HELIX 33 53
FT STRAND 54 56
FT STRAND 84 86
FT STRAND 89 91
FT TURN 100 102
FT HELIX 103 106
FT HELIX 114 124
FT HELIX 130 133
FT STRAND 136 142
FT HELIX 143 150
FT TURN 151 153
FT STRAND 156 162
FT HELIX 171 187
FT STRAND 191 195
FT HELIX 197 203
FT HELIX 208 223
FT TURN 224 226
FT HELIX 229 231
FT STRAND 232 236
FT HELIX 237 240
FT HELIX 241 243
FT HELIX 247 256
FT HELIX 260 267
FT STRAND 271 274
FT HELIX 275 285
FT HELIX 286 288
FT HELIX 290 292
FT HELIX 294 297
FT STRAND 304 310
FT HELIX 311 313
FT HELIX 314 323
FT HELIX 324 327
FT STRAND 333 337
FT STRAND 345 349
FT STRAND 354 357
FT STRAND 360 362
FT HELIX 365 374
FT HELIX 384 390
FT TURN 394 396
FT HELIX 398 406
FT HELIX 410 422
FT STRAND 423 425
FT HELIX 430 450
FT HELIX 454 460
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
//
ID SYWC_HUMAN Reviewed; 471 AA.
AC P23381; A6NGN1; A6NID3; P78535; Q502Y0; Q53XB6; Q9UDI5; Q9UDL3;
read moreDT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 2.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Tryptophan--tRNA ligase, cytoplasmic;
DE EC=6.1.1.2;
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=WARS; Synonyms=IFI53, WRS;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1761529;
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
RT protein (gamma 2) highly homologous to rabbit peptide chain release
RT factor and 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
RT human tryptophanyl-tRNA synthetase.";
RL Gene 109:291-296(1991).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1537332;
RA Buwitt U., Flohr T., Boettger E.C.;
RT "Molecular cloning and characterization of an interferon induced human
RT cDNA with sequence homology to a mammalian peptide chain release
RT 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA 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.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., 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.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA 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
RT project: 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-
RT tRNA 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-
RT response 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
RP 433-448, 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.,
RA Schmitt D.;
RT "Gamma interferon potently induces tryptophanyl-tRNA synthetase
RT expression 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 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
RP FUNCTION.
RX PubMed=11773626; DOI=10.1073/pnas.012602099;
RA Wakasugi K., Slike B.M., Hood J., Otani A., Ewalt K.L.,
RA Friedlander M., 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
RT protein 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
RT tryptophanyl-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
RT 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
RT fluid 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.,
RA Walther T.C., 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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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 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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
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 [27]
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.,
RA 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 [28]
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.,
RA Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal
RT 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
CC cells. Regulates ERK, Akt, and eNOS activation pathways that are
CC associated with angiogenesis, cytoskeletal reorganization and
CC shear stress-responsive gene expression.
CC -!- CATALYTIC ACTIVITY: ATP + L-tryptophan + tRNA(Trp) = AMP +
CC diphosphate + L-tryptophyl-tRNA(Trp).
CC -!- SUBUNIT: Homodimer. Isoform 1 and isoform 2 interact with an
CC oxidized form of GAPDH. GAPDH stimulates the aminoacylation
CC activity of isoform 2.
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.
CC -!- PTM: Proteolytic cleavage generates 2 forms; T1-TrpRS and T2-
CC TrpRS.
CC -!- SIMILARITY: Belongs to the class-I aminoacyl-tRNA synthetase
CC family.
CC -!- SIMILARITY: Contains 1 WHEP-TRS domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAF83830.1; Type=Erroneous initiation;
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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; ALT_INIT; 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 PIR; A41633; A41706.
DR RefSeq; NP_004175.2; NM_004184.3.
DR RefSeq; NP_776049.1; NM_173701.1.
DR RefSeq; NP_998810.1; NM_213645.1.
DR RefSeq; NP_998811.1; NM_213646.1.
DR RefSeq; XP_005268099.1; XM_005268042.1.
DR RefSeq; XP_005268100.1; XM_005268043.1.
DR RefSeq; XP_005268101.1; XM_005268044.1.
DR UniGene; Hs.497599; -.
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 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 ProteinModelPortal; P23381; -.
DR SMR; P23381; 82-471.
DR DIP; DIP-29493N; -.
DR IntAct; P23381; 5.
DR MINT; MINT-1408962; -.
DR STRING; 9606.ENSP00000347495; -.
DR DrugBank; DB00150; L-Tryptophan.
DR PhosphoSite; P23381; -.
DR DMDM; 135191; -.
DR OGP; P23381; -.
DR PaxDb; P23381; -.
DR PeptideAtlas; P23381; -.
DR PRIDE; P23381; -.
DR Ensembl; ENST00000344102; ENSP00000339485; ENSG00000140105.
DR Ensembl; ENST00000355338; ENSP00000347495; ENSG00000140105.
DR Ensembl; ENST00000358655; ENSP00000351481; ENSG00000140105.
DR Ensembl; ENST00000392882; ENSP00000376620; ENSG00000140105.
DR Ensembl; ENST00000556645; ENSP00000451887; ENSG00000140105.
DR Ensembl; ENST00000557135; ENSP00000451460; ENSG00000140105.
DR GeneID; 7453; -.
DR KEGG; hsa:7453; -.
DR UCSC; uc001yhg.2; human.
DR CTD; 7453; -.
DR GeneCards; GC14M100800; -.
DR HGNC; HGNC:12729; WARS.
DR MIM; 191050; gene.
DR neXtProt; NX_P23381; -.
DR PharmGKB; PA37340; -.
DR eggNOG; COG0180; -.
DR HOVERGEN; HBG002325; -.
DR InParanoid; P23381; -.
DR KO; K01867; -.
DR OMA; KPETAIY; -.
DR OrthoDB; EOG7T4MK3; -.
DR PhylomeDB; P23381; -.
DR Reactome; REACT_71; Gene Expression.
DR ChiTaRS; WARS; human.
DR EvolutionaryTrace; P23381; -.
DR GeneWiki; WARS_(gene); -.
DR GenomeRNAi; 7453; -.
DR NextBio; 29178; -.
DR PRO; PR:P23381; -.
DR ArrayExpress; P23381; -.
DR Bgee; P23381; -.
DR CleanEx; HS_WARS; -.
DR Genevestigator; P23381; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004830; F:tryptophan-tRNA ligase activity; NAS:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0008285; P:negative regulation of cell proliferation; TAS:ProtInc.
DR GO; GO:0045765; P:regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0006436; P:tryptophanyl-tRNA aminoacylation; NAS:UniProtKB.
DR Gene3D; 1.10.287.10; -; 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.
DR PANTHER; PTHR10055; PTHR10055; 1.
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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Ligase; Nucleotide-binding; Polymorphism;
KW Protein biosynthesis; Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 471 Tryptophan--tRNA ligase, cytoplasmic.
FT /FTId=PRO_0000136738.
FT CHAIN 71 471 T1-TrpRS.
FT /FTId=PRO_0000386461.
FT CHAIN 94 471 T2-TrpRS.
FT /FTId=PRO_0000386462.
FT DOMAIN 8 64 WHEP-TRS.
FT MOTIF 164 173 "HIGH" region.
FT MOTIF 349 353 "KMSKS" region.
FT VAR_SEQ 1 47 Missing (in isoform 2).
FT /FTId=VSP_038221.
FT VARIANT 54 54 A -> S (in dbSNP:rs2234521).
FT /FTId=VAR_052406.
FT VARIANT 455 455 E -> D (in a breast cancer sample;
FT somatic mutation).
FT /FTId=VAR_036466.
FT CONFLICT 213 214 SY -> GD (in Ref. 3; AAA61298).
FT CONFLICT 310 310 A -> V (in Ref. 9; AAH95453).
FT CONFLICT 424 424 A -> R (in Ref. 4; CAA44450).
FT CONFLICT 439 439 Q -> L (in Ref. 9; AAH95453).
FT HELIX 8 28
FT HELIX 33 53
FT STRAND 54 56
FT STRAND 84 86
FT STRAND 89 91
FT TURN 100 102
FT HELIX 103 106
FT HELIX 114 124
FT HELIX 130 133
FT STRAND 136 142
FT HELIX 143 150
FT TURN 151 153
FT STRAND 156 162
FT HELIX 171 187
FT STRAND 191 195
FT HELIX 197 203
FT HELIX 208 223
FT TURN 224 226
FT HELIX 229 231
FT STRAND 232 236
FT HELIX 237 240
FT HELIX 241 243
FT HELIX 247 256
FT HELIX 260 267
FT STRAND 271 274
FT HELIX 275 285
FT HELIX 286 288
FT HELIX 290 292
FT HELIX 294 297
FT STRAND 304 310
FT HELIX 311 313
FT HELIX 314 323
FT HELIX 324 327
FT STRAND 333 337
FT STRAND 345 349
FT STRAND 354 357
FT STRAND 360 362
FT HELIX 365 374
FT HELIX 384 390
FT TURN 394 396
FT HELIX 398 406
FT HELIX 410 422
FT STRAND 423 425
FT HELIX 430 450
FT HELIX 454 460
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
//
MIM
191050
*RECORD*
*FIELD* NO
191050
*FIELD* TI
*191050 TRYPTOPHANYL-tRNA SYNTHETASE; WARS
;;TRYPTOPHANYL-tRNA SYNTHETASE, CYTOPLASMIC
read more*FIELD* TX
DESCRIPTION
Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis.
Human tyrosyl-tRNA synthetase (YARS; 603623) can be split into 2
fragments having distinct cytokine activities, thereby linking protein
synthesis to cytokine signaling pathways. Tryptophanyl-tRNA synthetase
(WARS) is a close homolog of tyrosyl-tRNA synthetase. It catalyzes the
aminoacylation of tRNA(trp) with tryptophan, an essential function of
the cell's protein synthesis machinery.
CLONING
Frolova et al. (1991) cloned the human gene and reported its nucleotide
sequence. Shimizu et al. (1976) and Denney et al. (1978) located the
structural gene for tryptophanyl-tRNA synthetase on chromosome 14.
GENE FUNCTION
In normal cells, human tryptophanyl-tRNA synthetase exists in 2 forms.
The major form is the full-length protein, and the other is a truncated
form in which most of the extra-NH2-terminal domain is deleted because
of alternative splicing of the pre-mRNA (Tolstrup et al., 1995; Turpaev
et al., 1996), with met48 being deduced as the NH2-terminal residue of
the truncated form. The expression of the short form of WARS is highly
stimulated in human cells by the addition of interferon-gamma (IFNG;
147570).
Wakasugi et al. (2002) showed that the truncated form of WARS is
angiostatic in several different systems and assays, whereas the
full-length enzyme is inactive. Thus, protein synthesis may be linked to
the regulation of angiogenesis by a natural fragment of
tryptophanyl-tRNA synthetase.
Otani et al. (2002) showed that a recombinant form of a COOH-terminal
fragment of tryptophanyl-tRNA synthetase is a potent antagonist of
vascular endothelial growth factor (VEGF; 192240)-induced angiogenesis
in a mouse model and of naturally occurring retinal angiogenesis in the
neonatal mouse. Angiostatic activity was dose-dependent in both systems.
The full-length protein was inactive as an antagonist of angiogenesis.
The results suggested that fragments of tryptophanyl-tRNA synthetase, as
naturally occurring and potentially nonimmunogenic anti-angiogenics, can
be used for the treatment of neovascular eye diseases.
MAPPING
Francke et al. (1977) assigned WARS to 14q21-qter. Graphodatsky et al.
(1993) confirmed the assignment to chromosome 14 and regionalized it by
isotopic in situ hybridization to 14q23-q31. The gene may be in the
14q24 band where one-third of the grains were localized.
Borglum et al. (1996) mapped a cDNA probe of the WARS gene by a
combination of somatic cell hybrid analysis, fluorescence in situ
hybridization (FISH), and linkage analysis. Both FISH and linkage
analysis independently supported a more distal position of WARS than had
been previously reported. FISH mapping indicated the most likely
position to be 14q32.31.
Jensen et al. (2001) found that a pseudogene of the NDUFB3 gene
(603839), designated NDUFB3P4, is positioned in intron 2 of the WARS
gene in the opposite direction.
*FIELD* RF
1. Borglum, A. D.; Flint, T.; Tommerup, N.; Fleckner, J.; Justesen,
J.; Kruse, T. A.: Assignment of the human tryptophanyl-tRNA synthetase
gene (WARS) to chromosome 14q32.2-q32.32. Cytogenet. Cell Genet. 73:
99-103, 1996.
2. Denney, R. M.; Borgaonkar, D.; Ruddle, F. H.: Order of genes for
NP and TRPRS on chromosome 14. Cytogenet. Cell Genet. 22: 493-497,
1978.
3. Francke, U.; Denney, R. M.; Ruddle, F. H.: Intrachromosomal gene
mapping in man: the gene for tryptophanyl-tRNA synthetase maps in
region q21-qter of chromosome 14. Somat. Cell Genet. 3: 381-389,
1977.
4. Frolova, L. Y.; Sudomoina, M. A.; Grigorieva, A. Y.; Zinovieva,
O. L.; Kisselev, L. L.: Cloning and nucleotide sequence of the structural
gene encoding for human tryptophanyl-tRNA synthetase. Gene 109:
291-296, 1991.
5. Graphodatsky, A.; Frolova, L.; Biltueva, L.; Eremina, V.; Lushnikova,
T.; Sudomoina, M.; Zinovieva, O.; Kisselev, L.: Localization of the
tryptophanyl tRNA synthetase gene (WARS) on human and bovine chromosomes
by in situ hybridization. Mammalian Genome 4: 183-184, 1993.
6. Jensen, L. L.; Nielsen, M. M.; Justesen, J.; Hansen, L. L.: Assignment
of human NADH dehydrogenase (ubiquinone) 1 beta subcomplex 3 (NDUFB3)
and of its four pseudogenes to human chromosomes 2q31.3, 1p13.3-p13.1,
9q32-q34.1, 14q22.3-q23.1 and 14q32.2 by radiation hybrid mapping. Cytogenet.
Cell Genet. 93: 147-150, 2001.
7. Otani, A.; Slike, B. M.; Dorrell, M. I.; Hood, J.; Kinder, K.;
Ewalt, K. L.; Cheresh, D.; Schimmel, P.; Friedlander, M.: A fragment
of human TrpRS as a potent antagonist of ocular angiogenesis. Proc.
Nat. Acad. Sci. 99: 178-183, 2002.
8. Shimizu, N.; Kucherlapati, R. S.; Ruddle, F. H.: Assignment of
a human gene for tryptophanyl-tRNA synthetase to chromosome 14 using
human-mouse somatic cell hybrids. Somat. Cell Genet. 2: 345-357,
1976.
9. Tolstrup, A. B.; Bejder, A.; Fleckner, J.; Justesen, J.: Transcriptional
regulation of the interferon-gamma-inducible tryptophanyl-tRNA synthetase
includes alternative splicing. J. Biol. Chem. 270: 397-403, 1995.
10. Turpaev, K. T.; Zakhariev, V. M.; Sokolova, I. V.; Narovlyansky,
A. N.; Amchenkova, A. M.; Justesen, J.; Frolova, L. Y.: Alternative
processing of the tryptophanyl-tRNA synthetase mRNA from interferon-treated
human cells. Europ. J. Biochem. 240: 732-737, 1996.
11. Wakasugi, K.; Slike, B. M.; Hood, J.; Otani, A.; Ewalt, K. L.;
Friedlander, M.; Cheresh, D. A.; Schimmel, P.: A human aminoacyl-tRNA
synthetase as a regulator of angiogenesis. Proc. Nat. Acad. Sci. 99:
173-177, 2002.
*FIELD* CN
Victor A. McKusick - updated: 1/31/2002
Carol A. Bocchini - updated: 8/28/2001
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 03/08/2002
carol: 2/18/2002
mcapotos: 2/7/2002
mcapotos: 2/6/2002
terry: 1/31/2002
carol: 8/28/2001
psherman: 3/23/2000
terry: 9/18/1996
marlene: 8/15/1996
carol: 3/25/1993
carol: 4/21/1992
supermim: 3/19/1992
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989
*RECORD*
*FIELD* NO
191050
*FIELD* TI
*191050 TRYPTOPHANYL-tRNA SYNTHETASE; WARS
;;TRYPTOPHANYL-tRNA SYNTHETASE, CYTOPLASMIC
read more*FIELD* TX
DESCRIPTION
Aminoacyl-tRNA synthetases catalyze the first step of protein synthesis.
Human tyrosyl-tRNA synthetase (YARS; 603623) can be split into 2
fragments having distinct cytokine activities, thereby linking protein
synthesis to cytokine signaling pathways. Tryptophanyl-tRNA synthetase
(WARS) is a close homolog of tyrosyl-tRNA synthetase. It catalyzes the
aminoacylation of tRNA(trp) with tryptophan, an essential function of
the cell's protein synthesis machinery.
CLONING
Frolova et al. (1991) cloned the human gene and reported its nucleotide
sequence. Shimizu et al. (1976) and Denney et al. (1978) located the
structural gene for tryptophanyl-tRNA synthetase on chromosome 14.
GENE FUNCTION
In normal cells, human tryptophanyl-tRNA synthetase exists in 2 forms.
The major form is the full-length protein, and the other is a truncated
form in which most of the extra-NH2-terminal domain is deleted because
of alternative splicing of the pre-mRNA (Tolstrup et al., 1995; Turpaev
et al., 1996), with met48 being deduced as the NH2-terminal residue of
the truncated form. The expression of the short form of WARS is highly
stimulated in human cells by the addition of interferon-gamma (IFNG;
147570).
Wakasugi et al. (2002) showed that the truncated form of WARS is
angiostatic in several different systems and assays, whereas the
full-length enzyme is inactive. Thus, protein synthesis may be linked to
the regulation of angiogenesis by a natural fragment of
tryptophanyl-tRNA synthetase.
Otani et al. (2002) showed that a recombinant form of a COOH-terminal
fragment of tryptophanyl-tRNA synthetase is a potent antagonist of
vascular endothelial growth factor (VEGF; 192240)-induced angiogenesis
in a mouse model and of naturally occurring retinal angiogenesis in the
neonatal mouse. Angiostatic activity was dose-dependent in both systems.
The full-length protein was inactive as an antagonist of angiogenesis.
The results suggested that fragments of tryptophanyl-tRNA synthetase, as
naturally occurring and potentially nonimmunogenic anti-angiogenics, can
be used for the treatment of neovascular eye diseases.
MAPPING
Francke et al. (1977) assigned WARS to 14q21-qter. Graphodatsky et al.
(1993) confirmed the assignment to chromosome 14 and regionalized it by
isotopic in situ hybridization to 14q23-q31. The gene may be in the
14q24 band where one-third of the grains were localized.
Borglum et al. (1996) mapped a cDNA probe of the WARS gene by a
combination of somatic cell hybrid analysis, fluorescence in situ
hybridization (FISH), and linkage analysis. Both FISH and linkage
analysis independently supported a more distal position of WARS than had
been previously reported. FISH mapping indicated the most likely
position to be 14q32.31.
Jensen et al. (2001) found that a pseudogene of the NDUFB3 gene
(603839), designated NDUFB3P4, is positioned in intron 2 of the WARS
gene in the opposite direction.
*FIELD* RF
1. Borglum, A. D.; Flint, T.; Tommerup, N.; Fleckner, J.; Justesen,
J.; Kruse, T. A.: Assignment of the human tryptophanyl-tRNA synthetase
gene (WARS) to chromosome 14q32.2-q32.32. Cytogenet. Cell Genet. 73:
99-103, 1996.
2. Denney, R. M.; Borgaonkar, D.; Ruddle, F. H.: Order of genes for
NP and TRPRS on chromosome 14. Cytogenet. Cell Genet. 22: 493-497,
1978.
3. Francke, U.; Denney, R. M.; Ruddle, F. H.: Intrachromosomal gene
mapping in man: the gene for tryptophanyl-tRNA synthetase maps in
region q21-qter of chromosome 14. Somat. Cell Genet. 3: 381-389,
1977.
4. Frolova, L. Y.; Sudomoina, M. A.; Grigorieva, A. Y.; Zinovieva,
O. L.; Kisselev, L. L.: Cloning and nucleotide sequence of the structural
gene encoding for human tryptophanyl-tRNA synthetase. Gene 109:
291-296, 1991.
5. Graphodatsky, A.; Frolova, L.; Biltueva, L.; Eremina, V.; Lushnikova,
T.; Sudomoina, M.; Zinovieva, O.; Kisselev, L.: Localization of the
tryptophanyl tRNA synthetase gene (WARS) on human and bovine chromosomes
by in situ hybridization. Mammalian Genome 4: 183-184, 1993.
6. Jensen, L. L.; Nielsen, M. M.; Justesen, J.; Hansen, L. L.: Assignment
of human NADH dehydrogenase (ubiquinone) 1 beta subcomplex 3 (NDUFB3)
and of its four pseudogenes to human chromosomes 2q31.3, 1p13.3-p13.1,
9q32-q34.1, 14q22.3-q23.1 and 14q32.2 by radiation hybrid mapping. Cytogenet.
Cell Genet. 93: 147-150, 2001.
7. Otani, A.; Slike, B. M.; Dorrell, M. I.; Hood, J.; Kinder, K.;
Ewalt, K. L.; Cheresh, D.; Schimmel, P.; Friedlander, M.: A fragment
of human TrpRS as a potent antagonist of ocular angiogenesis. Proc.
Nat. Acad. Sci. 99: 178-183, 2002.
8. Shimizu, N.; Kucherlapati, R. S.; Ruddle, F. H.: Assignment of
a human gene for tryptophanyl-tRNA synthetase to chromosome 14 using
human-mouse somatic cell hybrids. Somat. Cell Genet. 2: 345-357,
1976.
9. Tolstrup, A. B.; Bejder, A.; Fleckner, J.; Justesen, J.: Transcriptional
regulation of the interferon-gamma-inducible tryptophanyl-tRNA synthetase
includes alternative splicing. J. Biol. Chem. 270: 397-403, 1995.
10. Turpaev, K. T.; Zakhariev, V. M.; Sokolova, I. V.; Narovlyansky,
A. N.; Amchenkova, A. M.; Justesen, J.; Frolova, L. Y.: Alternative
processing of the tryptophanyl-tRNA synthetase mRNA from interferon-treated
human cells. Europ. J. Biochem. 240: 732-737, 1996.
11. Wakasugi, K.; Slike, B. M.; Hood, J.; Otani, A.; Ewalt, K. L.;
Friedlander, M.; Cheresh, D. A.; Schimmel, P.: A human aminoacyl-tRNA
synthetase as a regulator of angiogenesis. Proc. Nat. Acad. Sci. 99:
173-177, 2002.
*FIELD* CN
Victor A. McKusick - updated: 1/31/2002
Carol A. Bocchini - updated: 8/28/2001
*FIELD* CD
Victor A. McKusick: 6/2/1986
*FIELD* ED
terry: 03/08/2002
carol: 2/18/2002
mcapotos: 2/7/2002
mcapotos: 2/6/2002
terry: 1/31/2002
carol: 8/28/2001
psherman: 3/23/2000
terry: 9/18/1996
marlene: 8/15/1996
carol: 3/25/1993
carol: 4/21/1992
supermim: 3/19/1992
supermim: 3/16/1992
supermim: 3/20/1990
ddp: 10/27/1989