TPCB_ASPFU
ID TPCB_ASPFU Reviewed; 421 AA.
AC Q4WQZ6;
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=Atrochrysone carboxyl ACP thioesterase {ECO:0000250|UniProtKB:Q0CCY4};
DE Short=ACTE {ECO:0000250|UniProtKB:Q0CCY4};
DE EC=3.1.2.- {ECO:0000250|UniProtKB:Q0CCY4};
DE AltName: Full=Trypacidin synthesis protein B {ECO:0000303|PubMed:26242966};
GN Name=tpcB {ECO:0000303|PubMed:26242966};
GN Synonyms=tynB {ECO:0000303|PubMed:26278536}; ORFNames=AFUA_4G14570;
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, DISRUPTION PHENOTYPE, 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: Atrochrysone carboxyl ACP thioesterase; part of the gene
CC cluster that mediates the biosynthesis of trypacidin, a mycotoxin with
CC antiprotozoal activity and that plays a role in the infection process
CC (PubMed:26278536, PubMed:26242966). The pathway begins with the
CC synthesis of atrochrysone thioester by the polyketide synthase (PKS)
CC tpcC (PubMed:26242966). The atrochrysone carboxyl ACP thioesterase tpcB
CC then breaks the thioester bond and releases the atrochrysone carboxylic
CC acid from tpcC (PubMed:26242966). The decarboxylase tpcK converts
CC atrochrysone carboxylic acid to atrochrysone which is further reduced
CC into emodin anthrone (PubMed:26242966). The next step is performed by
CC the emodin anthrone oxygenase tpcL that catalyzes the oxidation of
CC emodin anthrone to emodin (PubMed:26242966). Emodin O-methyltransferase
CC encoded by tpcA catalyzes methylation of the 8-hydroxy group of emodin
CC to form questin (PubMed:26242966). Ring cleavage of questin by questin
CC oxidase tpcI leads to desmethylsulochrin via several intermediates
CC including questin epoxide (By similarity). Another methylation step
CC catalyzed by tpcM leads to the formation of sulochrin which is further
CC converted to monomethylsulfochrin by tpcH. Finally, the tpcJ catalyzes
CC the 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:Q0CCY3,
CC ECO:0000269|PubMed:22319557, ECO:0000269|PubMed:26242966,
CC ECO:0000269|PubMed:26278536}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=atrochrysone carboxyl-[ACP] + H2O = atrochrysone carboxylate +
CC H(+) + holo-[ACP]; Xref=Rhea:RHEA:64236, Rhea:RHEA-COMP:9685,
CC Rhea:RHEA-COMP:16552, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:64479, ChEBI:CHEBI:149712, ChEBI:CHEBI:149713;
CC Evidence={ECO:0000250|UniProtKB:Q0CCY4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64237;
CC Evidence={ECO:0000250|UniProtKB:Q0CCY4};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q988B9};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:Q988B9};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26242966, ECO:0000269|PubMed:26278536}.
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 -!- DISRUPTION PHENOTYPE: Impairs the production of trypacidin and pathway
CC intermediates including questin (PubMed:26278536, PubMed:26242966).
CC {ECO:0000269|PubMed:26242966, ECO:0000269|PubMed:26278536}.
CC -!- SIMILARITY: Belongs to the metallo-beta-lactamase superfamily.
CC {ECO:0000305}.
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DR EMBL; AAHF01000005; EAL89338.1; -; Genomic_DNA.
DR RefSeq; XP_751376.1; XM_746283.1.
DR AlphaFoldDB; Q4WQZ6; -.
DR SMR; Q4WQZ6; -.
DR STRING; 746128.CADAFUBP00006998; -.
DR EnsemblFungi; EAL89338; EAL89338; AFUA_4G14570.
DR GeneID; 3509594; -.
DR KEGG; afm:AFUA_4G14570; -.
DR VEuPathDB; FungiDB:Afu4g14570; -.
DR eggNOG; KOG0813; Eukaryota.
DR HOGENOM; CLU_048478_1_0_1; -.
DR InParanoid; Q4WQZ6; -.
DR OMA; EGGYRQI; -.
DR OrthoDB; 576967at2759; -.
DR Proteomes; UP000002530; Chromosome 4.
DR GO; GO:0016787; F:hydrolase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IMP:AspGD.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.60.15.10; -; 1.
DR InterPro; IPR001279; Metallo-B-lactamas.
DR InterPro; IPR036866; RibonucZ/Hydroxyglut_hydro.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF00753; Lactamase_B; 1.
DR SMART; SM00849; Lactamase_B; 1.
DR SUPFAM; SSF56281; SSF56281; 1.
PE 2: Evidence at transcript level;
KW Hydrolase; Metal-binding; Reference proteome; Zinc.
FT CHAIN 1..421
FT /note="Atrochrysone carboxyl ACP thioesterase"
FT /id="PRO_0000437056"
FT ACT_SITE 211
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000255"
FT BINDING 207
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 209
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 211
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
FT BINDING 212
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q988B9"
SQ SEQUENCE 421 AA; 47062 MW; D7806C9437720360 CRC64;
MLALHQTQRD VPCSEVHDAL GLQGARSIYF GRPTGRSILS DPIRPRPMPT VTVIIYSDIR
FLLEFPSVFL CAYVLPVQRT VIMANEKRGG YRQINQALNI CAWEGYLNEQ HARLPTLEDV
EQISPRVLRV LGQNEGKVRR ADGYYTCSSR LIEGPQFTLQ GTNTYIVGTG RHRLLIDTGQ
GIPEWASLIS STLAGSSIEL SHVLLTHWHG DHTGGVPDLL RMYPDLSDSI YKHTPGKGQK
PISDGQTFRV EGATVRAVHT PGHSHDHMCF ILEEENAMFT GDNVLGHGSS AVEVLSTWMS
SLRMMQSLRC AVGYPAHGAV IRDLPSKLDL ELTQKARRED RVVETLKQMK TETQRNGARG
KGSVTVQQLV TAMHGHDLDE QVRTMALEPF VDEVLRKLAQ DDRVAFEVRG GQKKWFAIEY
T
