TPCL_ASPFU
ID TPCL_ASPFU Reviewed; 161 AA.
AC Q4WQY6;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 17-APR-2007, sequence version 2.
DT 25-MAY-2022, entry version 62.
DE RecName: Full=Anthrone oxygenase tpcL {ECO:0000303|PubMed:26242966};
DE EC=1.10.3.- {ECO:0000305|PubMed:26242966};
DE AltName: Full=Trypacidin synthesis protein L {ECO:0000303|PubMed:26242966};
GN Name=tpcL {ECO:0000303|PubMed:26242966};
GN Synonyms=tynL {ECO:0000303|PubMed:26278536}; ORFNames=AFUA_4G14480;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
RN [2]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22319557; DOI=10.1371/journal.pone.0029906;
RA Gauthier T., Wang X., Sifuentes Dos Santos J., Fysikopoulos A., Tadrist S.,
RA Canlet C., Artigot M.P., Loiseau N., Oswald I.P., Puel O.;
RT "Trypacidin, a spore-borne toxin from Aspergillus fumigatus, is cytotoxic
RT to lung cells.";
RL PLoS ONE 7:E29906-E29906(2012).
RN [3]
RP FUNCTION.
RX PubMed=26278536; DOI=10.1007/s00253-015-6898-1;
RA Mattern D.J., Schoeler H., Weber J., Novohradska S., Kraibooj K.,
RA Dahse H.M., Hillmann F., Valiante V., Figge M.T., Brakhage A.A.;
RT "Identification of the antiphagocytic trypacidin gene cluster in the human-
RT pathogenic fungus Aspergillus fumigatus.";
RL Appl. Microbiol. Biotechnol. 99:10151-10161(2015).
RN [4]
RP FUNCTION, AND INDUCTION.
RX PubMed=26242966; DOI=10.1111/1462-2920.13007;
RA Throckmorton K., Lim F.Y., Kontoyiannis D.P., Zheng W., Keller N.P.;
RT "Redundant synthesis of a conidial polyketide by two distinct secondary
RT metabolite clusters in Aspergillus fumigatus.";
RL Environ. Microbiol. 18:246-259(2016).
CC -!- FUNCTION: Anthrone oxygenase; part of the gene cluster that mediates
CC the biosynthesis of trypacidin, a mycotoxin with antiprotozoal activity
CC and that plays a role in the infection process (PubMed:26278536,
CC PubMed:26242966). The pathway begins with the synthesis of atrochrysone
CC thioester by the polyketide synthase (PKS) tpcC (PubMed:26242966). The
CC atrochrysone carboxyl ACP thioesterase tpcB then breaks the thioester
CC bond and releases the atrochrysone carboxylic acid from tpcC
CC (PubMed:26242966). The decarboxylase tpcK converts atrochrysone
CC carboxylic acid to atrochrysone which is further reduced into emodin
CC anthrone (PubMed:26242966). The next step is performed by the emodin
CC anthrone oxygenase tpcL that catalyzes the oxidation of emodinanthrone
CC to emodin (PubMed:26242966). Emodin O-methyltransferase encoded by tpcA
CC catalyzes methylation of the 8-hydroxy group of emodin to form questin
CC (PubMed:26242966). Ring cleavage of questin by questin oxidase tpcI
CC leads to desmethylsulochrin via several intermediates including questin
CC epoxide (By similarity). Another methylation step catalyzed by tpcM
CC leads to the formation of sulochrin which is further converted to
CC monomethylsulfochrin by tpcH. Finally, the tpcJ catalyzes the
CC conversion of monomethylsulfochrin to trypacidin (PubMed:26242966).
CC Trypacidin is toxic for human pulmonary and bronchial epithelial cells
CC by initiating the intracellular formation of nitric oxide (NO) and
CC hydrogen peroxide (H(2)O(2)), thus triggering host necrotic cell death
CC (PubMed:22319557). The trypacidin pathway is also able to produce
CC endocrocin via a distinct route from the endocrocin Enc pathway
CC (PubMed:26242966). {ECO:0000250|UniProtKB:Q0CCX8,
CC ECO:0000269|PubMed:22319557, ECO:0000269|PubMed:26242966,
CC ECO:0000269|PubMed:26278536}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=emodin anthrone + O2 = emodin + H(+) + H2O;
CC Xref=Rhea:RHEA:64268, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:77659, ChEBI:CHEBI:150013;
CC Evidence={ECO:0000305|PubMed:26242966};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64269;
CC Evidence={ECO:0000305|PubMed:26242966};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26242966}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in conidia
CC (PubMed:22319557). {ECO:0000305|PubMed:22319557}.
CC -!- INDUCTION: Expression is positively regulated by the transcription
CC factors brlA and laeA (PubMed:26242966). {ECO:0000269|PubMed:26242966}.
CC -!- SIMILARITY: Belongs to the anthrone oxygenase family. {ECO:0000305}.
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DR EMBL; AAHF01000005; EAL89348.2; -; Genomic_DNA.
DR RefSeq; XP_751386.2; XM_746293.2.
DR AlphaFoldDB; Q4WQY6; -.
DR STRING; 746128.CADAFUBP00006989; -.
DR EnsemblFungi; EAL89348; EAL89348; AFUA_4G14480.
DR GeneID; 3509610; -.
DR KEGG; afm:AFUA_4G14480; -.
DR VEuPathDB; FungiDB:Afu4g14480; -.
DR eggNOG; ENOG502SBMN; Eukaryota.
DR HOGENOM; CLU_105974_0_0_1; -.
DR InParanoid; Q4WQY6; -.
DR OMA; RMYHYGH; -.
DR OrthoDB; 1517224at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IGC:AspGD.
PE 2: Evidence at transcript level;
KW Glycoprotein; Membrane; Monooxygenase; Oxidoreductase; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..161
FT /note="Anthrone oxygenase tpcL"
FT /id="PRO_0000437098"
FT TRANSMEM 15..35
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 56..74
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 87..107
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 136..155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 4
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 161 AA; 17361 MW; 4EF73E3BB7043B9E CRC64;
MPQNASVIIT QATAVITGSF LSGLMMGLSV VDIPVVLDTA TQASQLLQHF TRLYDIGHKM
MPSLAVTTCL LYGYTASSTR TTGGSGLPHI IAAVTTISMV PFTWLVMAPT NNALFRMHAN
PAAANLGEVR RLLVRWAQLH AVRSLFPLMG SVLGLRQILR E
