TPCJ_ASPFU
ID TPCJ_ASPFU Reviewed; 609 AA.
AC Q4WQY8;
DT 07-SEP-2016, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2005, sequence version 1.
DT 25-MAY-2022, entry version 99.
DE RecName: Full=Oxidoreductase tpcJ {ECO:0000303|PubMed:26242966};
DE EC=1.-.-.- {ECO:0000305|PubMed:26242966};
DE AltName: Full=Trypacidin synthesis protein J {ECO:0000303|PubMed:26242966};
DE Flags: Precursor;
GN Name=tpcJ {ECO:0000303|PubMed:26242966};
GN Synonyms=tynJ {ECO:0000303|PubMed:26278536}; ORFNames=AFUA_4G14490;
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: Oxidoreductase; 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:26242966}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in conidia
CC (PubMed:22319557). {ECO:0000305|PubMed:22319557}.
CC -!- SIMILARITY: Belongs to the multicopper oxidase family. {ECO:0000305}.
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DR EMBL; AAHF01000005; EAL89346.1; -; Genomic_DNA.
DR RefSeq; XP_751384.1; XM_746291.1.
DR AlphaFoldDB; Q4WQY8; -.
DR SMR; Q4WQY8; -.
DR STRING; 746128.CADAFUBP00006991; -.
DR EnsemblFungi; EAL89346; EAL89346; AFUA_4G14490.
DR GeneID; 3509608; -.
DR KEGG; afm:AFUA_4G14490; -.
DR VEuPathDB; FungiDB:Afu4g14490; -.
DR eggNOG; KOG1263; Eukaryota.
DR HOGENOM; CLU_006504_7_2_1; -.
DR InParanoid; Q4WQY8; -.
DR OMA; TFWIDGH; -.
DR OrthoDB; 454773at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0005507; F:copper ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IGC:AspGD.
DR Gene3D; 2.60.40.420; -; 3.
DR InterPro; IPR001117; Cu-oxidase.
DR InterPro; IPR011706; Cu-oxidase_C.
DR InterPro; IPR045087; Cu-oxidase_fam.
DR InterPro; IPR011707; Cu-oxidase_N.
DR InterPro; IPR033138; Cu_oxidase_CS.
DR InterPro; IPR002355; Cu_oxidase_Cu_BS.
DR InterPro; IPR008972; Cupredoxin.
DR PANTHER; PTHR11709; PTHR11709; 1.
DR Pfam; PF00394; Cu-oxidase; 1.
DR Pfam; PF07731; Cu-oxidase_2; 1.
DR Pfam; PF07732; Cu-oxidase_3; 1.
DR SUPFAM; SSF49503; SSF49503; 3.
DR PROSITE; PS00079; MULTICOPPER_OXIDASE1; 1.
DR PROSITE; PS00080; MULTICOPPER_OXIDASE2; 1.
PE 2: Evidence at transcript level;
KW Copper; Glycoprotein; Metal-binding; Oxidoreductase; Reference proteome;
KW Repeat; Signal.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT CHAIN 17..609
FT /note="Oxidoreductase tpcJ"
FT /id="PRO_5004246590"
FT DOMAIN 66..186
FT /note="Plastocyanin-like 1"
FT /evidence="ECO:0000255"
FT DOMAIN 196..351
FT /note="Plastocyanin-like 2"
FT /evidence="ECO:0000255"
FT DOMAIN 429..567
FT /note="Plastocyanin-like 3"
FT /evidence="ECO:0000255"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 471
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 601
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 609 AA; 69043 MW; 8FE6014B1F6E0F30 CRC64;
MITVIKWLVS GCCALAAVTT RAPLPKDCRN TPNSRGCWKD GFDILTDYTD PKRAPPGKLV
EYNLTVSQQV IAPDGYEKLG MVANGQFPGP TIEADWGDTI RISVYNNFTD NNNGSAIHWH
GLRQFENNVQ DGVPGVTQCP SKPGETQVYE FRATQYGTSW YHSHFSLQCE CPLNGLFGPI
VIHGPSSMDW DEDLGPWLLH DWYHDDVFSL LWVGETKNRG AIPESTILNG KGKFDCNHHN
DTRCTGTGGE YFEVNFRKGV RYKFTIANTG TLLEYMFWID GHNLTVIAAD FVPIEPYVTD
VVNVAMGQRY EIIVEANADF THGSNFWIYA QYCDEVDLLP HKAVGIVRYD EQDRQDPRTP
PLSDQHRDFG CEDPDLDNLV PVVQQSVGRR VNRMEMKDYL RMGQEGYPDP MNFDGDLHKW
VLGDVPMFVD WKNPSLKKLA VDEHPDFPPE TVPILLDFDT GDWVHFVITN NYTFEKVHFP
RNLTPVMHPM HLHGHDFAIL AQGRGEFDPS IVPKLDNPPR RDVVNVDTGS YVWIAFQVNN
PGAWLLHCHI AFHVSSGLSL QFIEQPKKVK PLMEAAGVLG EFHDRCAKWT EYYDSVNIPD
NHTIDDSGI
