TPCM_ASPFU
ID TPCM_ASPFU Reviewed; 319 AA.
AC Q4WQY5;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=Methyltransferase tpcM {ECO:0000303|PubMed:26242966};
DE EC=2.1.1.- {ECO:0000269|PubMed:26242966};
DE AltName: Full=Geodin synthesis protein G {ECO:0000303|PubMed:26242966};
GN Name=tpcM {ECO:0000303|PubMed:26242966};
GN Synonyms=tynM {ECO:0000303|PubMed:26278536}; ORFNames=AFUA_4G14460;
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.
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: Methyltransferase; part of the gene cluster that mediates the
CC biosynthesis of trypacidin, a mycotoxin with antiprotozoal activity and
CC 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 -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000305|PubMed:26278536}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in conidia
CC (PubMed:22319557). {ECO:0000305|PubMed:22319557}.
CC -!- SIMILARITY: Belongs to the methyltransferase superfamily.
CC {ECO:0000305}.
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DR EMBL; AAHF01000005; EAL89349.1; -; Genomic_DNA.
DR RefSeq; XP_751387.1; XM_746294.1.
DR AlphaFoldDB; Q4WQY5; -.
DR SMR; Q4WQY5; -.
DR STRING; 746128.CADAFUBP00006988; -.
DR EnsemblFungi; EAL89349; EAL89349; AFUA_4G14460.
DR GeneID; 3509494; -.
DR KEGG; afm:AFUA_4G14460; -.
DR VEuPathDB; FungiDB:Afu4g14460; -.
DR eggNOG; ENOG502SJ7Q; Eukaryota.
DR HOGENOM; CLU_049344_0_1_1; -.
DR InParanoid; Q4WQY5; -.
DR OMA; SKFQHVI; -.
DR OrthoDB; 899118at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IGC:AspGD.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR013216; Methyltransf_11.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR Pfam; PF08241; Methyltransf_11; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
PE 2: Evidence at transcript level;
KW Methyltransferase; Reference proteome; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..319
FT /note="Methyltransferase tpcM"
FT /id="PRO_0000437071"
FT REGION 63..155
FT /note="Methyltransferase domain"
FT /evidence="ECO:0000255"
SQ SEQUENCE 319 AA; 35534 MW; 68BE9E493A3D5182 CRC64;
MAVPQSIPPP TAAPIESKDQ VFARSKAFWD NYLRGRPQVP PSFFQRIYRY HREHGGRFGT
VHDVGAGIGP YAGELRSQFP HVIVSDIVPK NVQLAEAHLG RDGFRYRAAP VEVADDLPPG
SVDLAFATNV MHFADQHAAM QAIATQLRPG GTFACAGFGP ARFDDPDIQD VWERISQQGG
RILLGMAEHP PDTINVMSRS SKEYNVAPLE PQWFRPGALR IRLNMAQGGI TGLLPPERQQ
EVTDPDFAGP RDVVVYETNE EWRFETDWEG FLQHFRSFPH AGADPAAFTG LLQELKDLLD
EGRCLRGCWP ATLILATRR
