TPCA_ASPFU
ID TPCA_ASPFU Reviewed; 482 AA.
AC Q4WQZ7;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=O-methyltransferase tpcA {ECO:0000303|PubMed:26242966};
DE EC=2.1.1.- {ECO:0000305|PubMed:26242966};
DE AltName: Full=Trypacidin synthesis protein A {ECO:0000303|PubMed:26242966};
GN Name=tpcA {ECO:0000303|PubMed:26242966};
GN Synonyms=tynA {ECO:0000303|PubMed:26278536}; ORFNames=AFUA_4G14580;
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 DISRUPTION PHENOTYPE.
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: O-methyltransferase; 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:Q0CCX9,
CC ECO:0000269|PubMed:22319557, ECO:0000269|PubMed:26242966,
CC ECO:0000269|PubMed:26278536}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26242966}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in conidia
CC (PubMed:22319557). {ECO:0000305|PubMed:22319557}.
CC -!- DISRUPTION PHENOTYPE: Resulted in loss of trypacidin production
CC (PubMed:26242966). {ECO:0000269|PubMed:26242966}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. Cation-independent O-methyltransferase family.
CC {ECO:0000305}.
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DR EMBL; AAHF01000005; EAL89337.1; -; Genomic_DNA.
DR RefSeq; XP_751375.1; XM_746282.1.
DR AlphaFoldDB; Q4WQZ7; -.
DR SMR; Q4WQZ7; -.
DR STRING; 746128.CADAFUBP00006999; -.
DR EnsemblFungi; EAL89337; EAL89337; AFUA_4G14580.
DR GeneID; 3509593; -.
DR KEGG; afm:AFUA_4G14580; -.
DR VEuPathDB; FungiDB:Afu4g14580; -.
DR eggNOG; KOG3178; Eukaryota.
DR HOGENOM; CLU_005533_0_1_1; -.
DR InParanoid; Q4WQZ7; -.
DR OMA; CRGLVWI; -.
DR OrthoDB; 817726at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0008171; F:O-methyltransferase activity; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IGC:AspGD.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR016461; COMT-like.
DR InterPro; IPR001077; O_MeTrfase_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00891; Methyltransf_2; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR PROSITE; PS51683; SAM_OMT_II; 1.
PE 2: Evidence at transcript level;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..482
FT /note="O-methyltransferase tpcA"
FT /id="PRO_0000437066"
FT ACT_SITE 368
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 293..294
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 316
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01020"
FT BINDING 348..349
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
FT BINDING 364
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:O04385"
SQ SEQUENCE 482 AA; 53244 MW; 1185091D74E0701D CRC64;
MERQPKSLCD ATQLLETANI ISDTVQTIIA EWSAEAKAPQ GSGKQNAPML PSRELFDAQR
TILAAVGKLT ELVSDPSARI LEVATQFQES RSLYIAAERR IPDLLAAGDE GGVHIDQISQ
KAKIEPRKLA RILRYLCSIG IFKQTGPDTF ANNRISAALV SNEPLRAYVQ LVNSEGFTAS
DRLPHTLLHP DTGPSYDVAK TAWQNAVCTK KTRWEWLEER VAPEQLLESG GHYPGIPSLV
MGLPPREDDG LVARPELEIM GLSMVGGGRV FGTAHVYDFP WASLGDALVV DVGGGVGGFP
LQLSKVYPQL RFIVQDRGPV VKQGLEKVWP RENPEALHQG RVQFVEHSFF DTNPTEGADI
YFLRYVLHDW SDDYCVRILA AIRSSMAAHS RLLICDQVMN TTIGDPDLDS APSPLPANYG
YHTRFSHSRD ITMMSCINGI ERTPAEFKGL LQAAGLKLKK IWDCRSQVSL IEAVLPEMNG
FR
