You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Identification
HMDB Protein ID HMDBP00574
Secondary Accession Numbers
  • 5846
Name Tryptophan--tRNA ligase, cytoplasmic
Synonyms
  1. IFP53
  2. Interferon-induced protein 53
  3. T1-TrpRS
  4. T2-TrpRS
  5. TrpRS
  6. Tryptophan--tRNA ligase
  7. hWRS
  8. Tryptophanyl-tRNA synthetase
Gene Name WARS
Protein Type Enzyme
Biological Properties
General Function Involved in nucleotide binding
Specific Function Isoform 1, isoform 2 and T1-TrpRS have aminoacylation activity while T2-TrpRS lacks it. Isoform 2, T1-TrpRS and T2-TrpRS possess angiostatic activity whereas isoform 1 lacks it. T2-TrpRS inhibits fluid shear stress-activated responses of endothelial cells. Regulates ERK, Akt, and eNOS activation pathways that are associated with angiogenesis, cytoskeletal reorganization and shear stress-responsive gene expression.
Pathways
  • Aminoacyl-tRNA biosynthesis
  • Tryptophan Metabolism
Reactions
Adenosine triphosphate + L-Tryptophan + tRNA(Trp) → Adenosine monophosphate + Pyrophosphate + L-tryptophyl-tRNA(Trp) details
Adenosine triphosphate + L-Tryptophan + tRNA(Trp) → Adenosine monophosphate + Pyrophosphate + L-Tryptophanyl-tRNA(Trp) details
GO Classification
Biological Process
regulation of angiogenesis
angiogenesis
tryptophanyl-tRNA aminoacylation
negative regulation of cell proliferation
Cellular Component
cytosol
Component
cell part
intracellular part
cytoplasm
Function
binding
nucleotide binding
catalytic activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
tryptophan-trna ligase activity
ligase activity
ligase activity, forming carbon-oxygen bonds
ligase activity, forming aminoacyl-trna and related compounds
aminoacyl-trna ligase activity
Molecular Function
ATP binding
tryptophan-tRNA ligase activity
Process
rna metabolic process
ncrna metabolic process
trna metabolic process
trna aminoacylation
trna aminoacylation for protein translation
macromolecule biosynthetic process
cellular macromolecule biosynthetic process
translation
metabolic process
macromolecule metabolic process
cellular macromolecule metabolic process
tryptophanyl-trna aminoacylation
biosynthetic process
Cellular Location
  1. Cytoplasm
Gene Properties
Chromosome Location 14
Locus 14q32.31
SNPs WARS
Gene Sequence
>1416 bp
ATGCCCAACAGTGAGCCCGCATCTCTGCTGGAGCTGTTCAACAGCATCGCCACACAAGGG
GAGCTCGTAAGGTCCCTCAAAGCGGGAAATGCGTCAAAGGATGAAATTGATTCTGCAGTA
AAGATGTTGGTGTCATTAAAAATGAGCTACAAAGCTGCCGCGGGGGAGGATTACAAGGCT
GACTGTCCTCCAGGGAACCCAGCACCTACCAGTAATCATGGCCCAGATGCCACAGAAGCT
GAAGAGGATTTTGTGGACCCATGGACAGTACAGACAAGCAGTGCAAAAGGCATAGACTAC
GATAAGCTCATTGTTCGGTTTGGAAGTAGTAAAATTGACAAAGAGCTAATAAACCGAATA
GAGAGAGCCACCGGCCAAAGACCACACCACTTCCTGCGCAGAGGCATCTTCTTCTCACAC
AGAGATATGAATCAGGTTCTTGATGCCTATGAAAATAAGAAGCCATTTTATCTGTACACG
GGCCGGGGCCCCTCTTCTGAAGCAATGCATGTAGGTCACCTCATTCCATTTATTTTCACA
AAGTGGCTCCAGGATGTATTTAACGTGCCCTTGGTGATCCAGATGACGGATGACGAGAAG
TATCTGTGGAAGGACCTGACCCTGGACCAGGCCTATAGCTATGCTGTGGAGAATGCCAAG
GACATCATCGCCTGTGGCTTTGACATCAACAAGACTTTCATATTCTCTGACCTGGACTAC
ATGGGGATGAGCTCAGGTTTCTACAAAAATGTGGTGAAGATTCAAAAGCATGTTACCTTC
AACCAAGTGAAAGGCATTTTCGGCTTCACTGACAGCGACTGCATTGGGAAGATCAGTTTT
CCTGCCATCCAGGCTGCTCCCTCCTTCAGCAACTCATTCCCACAGATCTTCCGAGACAGG
ACGGATATCCAGTGCCTTATCCCATGTGCCATTGACCAGGATCCTTACTTTAGAATGACA
AGGGACGTCGCCCCCAGGATCGGCTATCCTAAACCAGCCCTGTTGCACTCCACCTTCTTC
CCAGCCCTGCAGGGCGCCCAGACCAAAATGAGTGCCAGCGACCCCAACTCCTCCATCTTC
CTCACCGACACGGCCAAGCAGATCAAAACCAAGGTCAATAAGCATGCGTTTTCTGGAGGG
AGAGACACCATCGAGGAGCACAGGCAGTTTGGGGGCAACTGTGATGTGGACGTGTCTTTC
ATGTACCTGACCTTCTTCCTCGAGGACGACGACAAGCTCGAGCAGATCAGGAAGGATTAC
ACCAGCGGAGCCATGCTCACCGGTGAGCTCAAGAAGGCACTCATAGAGGTTCTGCAGCCC
TTGATCGCAGAGCACCAGGCCCGGCGCAAGGAGGTCACGGATGAGATAGTGAAAGAGTTC
ATGACTCCCCGGAAGCTGTCCTTCGACTTTCAGTAG
Protein Properties
Number of Residues 471
Molecular Weight 53164.91
Theoretical pI 6.232
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Tryptophanyl-tRNA synthetase, cytoplasmic
MPNSEPASLLELFNSIATQGELVRSLKAGNASKDEIDSAVKMLVSLKMSYKAAAGEDYKA
DCPPGNPAPTSNHGPDATEAEEDFVDPWTVQTSSAKGIDYDKLIVRFGSSKIDKELINRI
ERATGQRPHHFLRRGIFFSHRDMNQVLDAYENKKPFYLYTGRGPSSEAMHVGHLIPFIFT
KWLQDVFNVPLVIQMTDDEKYLWKDLTLDQAYSYAVENAKDIIACGFDINKTFIFSDLDY
MGMSSGFYKNVVKIQKHVTFNQVKGIFGFTDSDCIGKISFPAIQAAPSFSNSFPQIFRDR
TDIQCLIPCAIDQDPYFRMTRDVAPRIGYPKPALLHSTFFPALQGAQTKMSASDPNSSIF
LTDTAKQIKTKVNKHAFSGGRDTIEEHRQFGGNCDVDVSFMYLTFFLEDDDKLEQIRKDY
TSGAMLTGELKKALIEVLQPLIAEHQARRKEVTDEIVKEFMTPRKLSFDFQ
GenBank ID Protein 184657
UniProtKB/Swiss-Prot ID P23381
UniProtKB/Swiss-Prot Entry Name SYWC_HUMAN
PDB IDs
GenBank Gene ID M77804
GeneCard ID WARS
GenAtlas ID WARS
HGNC ID HGNC:12729
References
General References
  1. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [PubMed:14702039 ]
  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  5. Heilig R, Eckenberg R, Petit JL, Fonknechten N, Da Silva C, Cattolico L, Levy M, Barbe V, de Berardinis V, Ureta-Vidal A, Pelletier E, Vico V, Anthouard V, Rowen L, Madan A, Qin S, Sun H, Du H, Pepin K, Artiguenave F, Robert C, Cruaud C, Bruls T, Jaillon O, Friedlander L, Samson G, Brottier P, Cure S, Segurens B, Aniere F, Samain S, Crespeau H, Abbasi N, Aiach N, Boscus D, Dickhoff R, Dors M, Dubois I, Friedman C, Gouyvenoux M, James R, Madan A, Mairey-Estrada B, Mangenot S, Martins N, Menard M, Oztas S, Ratcliffe A, Shaffer T, Trask B, Vacherie B, Bellemere C, Belser C, Besnard-Gonnet M, Bartol-Mavel D, Boutard M, Briez-Silla S, Combette S, Dufosse-Laurent V, Ferron C, Lechaplais C, Louesse C, Muselet D, Magdelenat G, Pateau E, Petit E, Sirvain-Trukniewicz P, Trybou A, Vega-Czarny N, Bataille E, Bluet E, Bordelais I, Dubois M, Dumont C, Guerin T, Haffray S, Hammadi R, Muanga J, Pellouin V, Robert D, Wunderle E, Gauguet G, Roy A, Sainte-Marthe L, Verdier J, Verdier-Discala C, Hillier L, Fulton L, McPherson J, Matsuda F, Wilson R, Scarpelli C, Gyapay G, Wincker P, Saurin W, Quetier F, Waterston R, Hood L, Weissenbach J: The DNA sequence and analysis of human chromosome 14. Nature. 2003 Feb 6;421(6923):601-7. Epub 2003 Jan 1. [PubMed:12508121 ]
  6. Kim JE, Tannenbaum SR, White FM: Global phosphoproteome of HT-29 human colon adenocarcinoma cells. J Proteome Res. 2005 Jul-Aug;4(4):1339-46. [PubMed:16083285 ]
  7. Rubin BY, Anderson SL, Xing L, Powell RJ, Tate WP: Interferon induces tryptophanyl-tRNA synthetase expression in human fibroblasts. J Biol Chem. 1991 Dec 25;266(36):24245-8. [PubMed:1761529 ]
  8. Fleckner J, Rasmussen HH, Justesen J: Human interferon gamma potently induces the synthesis of a 55-kDa protein (gamma 2) highly homologous to rabbit peptide chain release factor and bovine tryptophanyl-tRNA synthetase. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11520-4. [PubMed:1763065 ]
  9. Frolova LYu, Sudomoina MA, Grigorieva AYu, Zinovieva OL, Kisselev LL: Cloning and nucleotide sequence of the structural gene encoding for human tryptophanyl-tRNA synthetase. Gene. 1991 Dec 30;109(2):291-6. [PubMed:1765274 ]
  10. Buwitt U, Flohr T, Bottger EC: Molecular cloning and characterization of an interferon induced human cDNA with sequence homology to a mammalian peptide chain release factor. EMBO J. 1992 Feb;11(2):489-96. [PubMed:1537332 ]
  11. Sokolova IV, Narovlianskii AN, Amchenkova AM, Turpaev KT: [Alternative splicing of 5'-terminal exons of the human tryptophanyl-tRNA synthetase gene]. Mol Biol (Mosk). 1996 Mar-Apr;30(2):319-29. [PubMed:8724762 ]
  12. Frolova LY, Grigorieva AY, Sudomoina MA, Kisselev LL: The human gene encoding tryptophanyl-tRNA synthetase: interferon-response elements and exon-intron organization. Gene. 1993 Jun 30;128(2):237-45. [PubMed:7685728 ]
  13. Reano A, Richard MH, Denoroy L, Viac J, Benedetto JP, Schmitt D: Gamma interferon potently induces tryptophanyl-tRNA synthetase expression in human keratinocytes. J Invest Dermatol. 1993 Jun;100(6):775-9. [PubMed:8496617 ]
  14. Wakasugi K, Slike BM, Hood J, Otani A, Ewalt KL, Friedlander M, Cheresh DA, Schimmel P: A human aminoacyl-tRNA synthetase as a regulator of angiogenesis. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):173-7. Epub 2002 Jan 2. [PubMed:11773626 ]
  15. Rasmussen HH, van Damme J, Puype M, Gesser B, Celis JE, Vandekerckhove J: Microsequences of 145 proteins recorded in the two-dimensional gel protein database of normal human epidermal keratinocytes. Electrophoresis. 1992 Dec;13(12):960-9. [PubMed:1286667 ]
  16. Bange FC, Flohr T, Buwitt U, Bottger EC: An interferon-induced protein with release factor activity is a tryptophanyl-tRNA synthetase. FEBS Lett. 1992 Mar 30;300(2):162-6. [PubMed:1373391 ]
  17. Tolstrup AB, Bejder A, Fleckner J, Justesen J: Transcriptional regulation of the interferon-gamma-inducible tryptophanyl-tRNA synthetase includes alternative splicing. J Biol Chem. 1995 Jan 6;270(1):397-403. [PubMed:7814400 ]
  18. Otani A, Slike BM, Dorrell MI, Hood J, Kinder K, Ewalt KL, Cheresh D, Schimmel P, Friedlander M: A fragment of human TrpRS as a potent antagonist of ocular angiogenesis. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):178-83. Epub 2002 Jan 2. [PubMed:11773625 ]
  19. Tzima E, Reader JS, Irani-Tehrani M, Ewalt KL, Schwartz MA, Schimmel P: Biologically active fragment of a human tRNA synthetase inhibits fluid shear stress-activated responses of endothelial cells. Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14903-7. Epub 2003 Nov 20. [PubMed:14630953 ]
  20. Wakasugi K, Nakano T, Morishima I: Oxidative stress-responsive intracellular regulation specific for the angiostatic form of human tryptophanyl-tRNA synthetase. Biochemistry. 2005 Jan 11;44(1):225-32. [PubMed:15628863 ]
  21. Yang XL, Otero FJ, Skene RJ, McRee DE, Schimmel P, Ribas de Pouplana L: Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15376-80. Epub 2003 Dec 11. [PubMed:14671330 ]
  22. Yu Y, Liu Y, Shen N, Xu X, Xu F, Jia J, Jin Y, Arnold E, Ding J: Crystal structure of human tryptophanyl-tRNA synthetase catalytic fragment: insights into substrate recognition, tRNA binding, and angiogenesis activity. J Biol Chem. 2004 Feb 27;279(9):8378-88. Epub 2003 Dec 5. [PubMed:14660560 ]