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Showing Protein Oxidoreductase tpcJ (HMDBP12605)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP12605
Secondary Accession Numbers None
Name Oxidoreductase tpcJ
Synonyms
  1. Trypacidin synthesis protein J
Gene Name TPCJ
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Oxidoreductase; part of the gene cluster that mediates the biosynthesis of trypacidin, a mycotoxin with antiprotozoal activity and that plays a role in the infection process (PubMed:26278536, PubMed:26242966). The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase (PKS) tpcC (PubMed:26242966). The atrochrysone carboxyl ACP thioesterase tpcB then breaks the thioester bond and releases the atrochrysone carboxylic acid from tpcC (PubMed:26242966). The decarboxylase tpcK converts atrochrysone carboxylic acid to atrochrysone which is further reduced into emodin anthrone (PubMed:26242966). The next step is performed by the emodin anthrone oxygenase tpcL that catalyzes the oxidation of emodinanthrone to emodin (PubMed:26242966). Emodin O-methyltransferase encoded by tpcA catalyzes methylation of the 8-hydroxy group of emodin to form questin (PubMed:26242966). Ring cleavage of questin by questin oxidase tpcI leads to desmethylsulochrin via several intermediates including questin epoxide (By similarity). Another methylation step catalyzed by tpcM leads to the formation of sulochrin which is further converted to monomethylsulfochrin by tpcH. Finally, the tpcJ catalyzes the conversion of monomethylsulfochrin to trypacidin (PubMed:26242966). Trypacidin is toxic for human pulmonary and bronchial epithelial cells by initiating the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)), thus triggering host necrotic cell death (PubMed:22319557). The trypacidin pathway is also able to produce endocrocin via a distinct route from the endocrocin Enc pathway (PubMed:26242966).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
secondary metabolite biosynthetic process
Molecular Function
oxidoreductase activity
copper ion binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 609
Molecular Weight 69042.22
Theoretical pI 5.329
Pfam Domain Function
Signals
  • 1-16;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q4WQY8
UniProtKB/Swiss-Prot Entry Name TPCJ_ASPFU
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Arroyo J, Berriman M, Abe K, Archer DB, Bermejo C, Bennett J, Bowyer P, Chen D, Collins M, Coulsen R, Davies R, Dyer PS, Farman M, Fedorova N, Fedorova N, Feldblyum TV, Fischer R, Fosker N, Fraser A, Garcia JL, Garcia MJ, Goble A, Goldman GH, Gomi K, Griffith-Jones S, Gwilliam R, Haas B, Haas H, Harris D, Horiuchi H, Huang J, Humphray S, Jimenez J, Keller N, Khouri H, Kitamoto K, Kobayashi T, Konzack S, Kulkarni R, Kumagai T, Lafon A, Latge JP, Li W, Lord A, Lu C, Majoros WH, May GS, Miller BL, Mohamoud Y, Molina M, Monod M, Mouyna I, Mulligan S, Murphy L, O'Neil S, Paulsen I, Penalva MA, Pertea M, Price C, Pritchard BL, Quail MA, Rabbinowitsch E, Rawlins N, Rajandream MA, Reichard U, Renauld H, Robson GD, Rodriguez de Cordoba S, Rodriguez-Pena JM, Ronning CM, Rutter S, Salzberg SL, Sanchez M, Sanchez-Ferrero JC, Saunders D, Seeger K, Squares R, Squares S, Takeuchi M, Tekaia F, Turner G, Vazquez de Aldana CR, Weidman J, White O, Woodward J, Yu JH, Fraser C, Galagan JE, Asai K, Machida M, Hall N, Barrell B, Denning DW: Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature. 2005 Dec 22;438(7071):1151-6. doi: 10.1038/nature04332. [PubMed:16372009 ]
  2. Gauthier T, Wang X, Sifuentes Dos Santos J, Fysikopoulos A, Tadrist S, Canlet C, Artigot MP, Loiseau N, Oswald IP, Puel O: Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic to lung cells. PLoS One. 2012;7(2):e29906. doi: 10.1371/journal.pone.0029906. Epub 2012 Feb 3. [PubMed:22319557 ]
  3. Mattern DJ, Schoeler H, Weber J, Novohradska S, Kraibooj K, Dahse HM, Hillmann F, Valiante V, Figge MT, Brakhage AA: Identification of the antiphagocytic trypacidin gene cluster in the human-pathogenic fungus Aspergillus fumigatus. Appl Microbiol Biotechnol. 2015 Dec;99(23):10151-61. doi: 10.1007/s00253-015-6898-1. Epub 2015 Aug 18. [PubMed:26278536 ]
  4. Throckmorton K, Lim FY, Kontoyiannis DP, Zheng W, Keller NP: Redundant synthesis of a conidial polyketide by two distinct secondary metabolite clusters in Aspergillus fumigatus. Environ Microbiol. 2016 Jan;18(1):246-59. doi: 10.1111/1462-2920.13007. Epub 2015 Sep 3. [PubMed:26242966 ]