ID   USTP_ASPFN              Reviewed;         480 AA.
AC   B8NM69;
DT   05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT   03-MAR-2009, sequence version 1.
DT   03-AUG-2022, entry version 54.
DE   RecName: Full=Peptidase S41 family protein ustP {ECO:0000303|PubMed:24841822};
DE            EC=3.4.-.- {ECO:0000305|PubMed:24841822};
DE   AltName: Full=Ustiloxin B biosynthesis protein P {ECO:0000303|PubMed:24841822};
GN   Name=ustP {ECO:0000303|PubMed:27166860}; ORFNames=AFLA_095010;
OS   Aspergillus flavus (strain ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357
OS   / JCM 12722 / SRRC 167).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=332952;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 200026 / FGSC A1120 / IAM 13836 / NRRL 3357 / JCM 12722 / SRRC
RC   167;
RX   PubMed=25883274; DOI=10.1128/genomea.00168-15;
RA   Nierman W.C., Yu J., Fedorova-Abrams N.D., Losada L., Cleveland T.E.,
RA   Bhatnagar D., Bennett J.W., Dean R., Payne G.A.;
RT   "Genome sequence of Aspergillus flavus NRRL 3357, a strain that causes
RT   aflatoxin contamination of food and feed.";
RL   Genome Announc. 3:E0016815-E0016815(2015).
RN   [2]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND CATALYTIC ACTIVITY.
RX   PubMed=24841822; DOI=10.1016/j.fgb.2014.04.011;
RA   Umemura M., Nagano N., Koike H., Kawano J., Ishii T., Miyamura Y.,
RA   Kikuchi M., Tamano K., Yu J., Shin-ya K., Machida M.;
RT   "Characterization of the biosynthetic gene cluster for the ribosomally
RT   synthesized cyclic peptide ustiloxin B in Aspergillus flavus.";
RL   Fungal Genet. Biol. 68:23-30(2014).
RN   [3]
RP   FUNCTION.
RX   PubMed=27166860; DOI=10.1002/anie.201602611;
RA   Ye Y., Minami A., Igarashi Y., Izumikawa M., Umemura M., Nagano N.,
RA   Machida M., Kawahara T., Shin-Ya K., Gomi K., Oikawa H.;
RT   "Unveiling the biosynthetic pathway of the ribosomally synthesized and
RT   post-translationally modified peptide ustiloxin B in filamentous fungi.";
RL   Angew. Chem. Int. Ed. 55:8072-8075(2016).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=26703898; DOI=10.1016/j.fgb.2015.12.010;
RA   Nagano N., Umemura M., Izumikawa M., Kawano J., Ishii T., Kikuchi M.,
RA   Tomii K., Kumagai T., Yoshimi A., Machida M., Abe K., Shin-ya K., Asai K.;
RT   "Class of cyclic ribosomal peptide synthetic genes in filamentous fungi.";
RL   Fungal Genet. Biol. 86:58-70(2016).
CC   -!- FUNCTION: Peptidase S41 family protein; part of the gene cluster that
CC       mediates the biosynthesis of the secondary metabolite ustiloxin B, an
CC       antimitotic tetrapeptide (PubMed:24841822, PubMed:27166860,
CC       PubMed:26703898). First, ustA is processed by the subtilisin-like
CC       endoprotease Kex2 that is outside the ustiloxin B gene cluster, at the
CC       C-terminal side of Arg-Lys, after transfer to Golgi apparatus through
CC       the endoplasmic reticulum (ER) (PubMed:24841822). Cleavage by KEX2
CC       generates 16 peptides YAIG-I to YAIG-XVI (PubMed:24841822). To process
CC       the precursor peptide further, at least two peptidases are necessary to
CC       cleave the N-terminal and C-terminal sides of the Tyr-Ala-Ile-Gly core
CC       peptide which serves as backbone for the synthesis of ustiloxin B,
CC       through cyclization and modification of the tyrosine with a non-protein
CC       coding amino acid, norvaline (PubMed:24841822). One of the two
CC       peptidases must be the serine peptidase ustP; and the other pepdidase
CC       is probably ustH (PubMed:24841822). Macrocyclization of the core
CC       peptide derived from ustA requires the tyrosinase ustQ, as well as the
CC       homologous oxidases ustYa and ustYb, and leads to the production of the
CC       first cyclization product N-desmethylustiloxin F (PubMed:27166860,
CC       PubMed:26703898). For the formation of N-desmethylustiloxin F, three
CC       oxidation steps are required, hydroxylation at the benzylic position,
CC       hydroxylation at either the aromatic ring of Tyr or beta-position of
CC       Ile, and oxidative cyclization (PubMed:27166860). UstQ may catalyze the
CC       oxidation of a phenol moiety, whereas the ustYa and ustYb are most
CC       likely responsible for the remaining two-step oxidations
CC       (PubMed:27166860). N-desmethylustiloxin F is then methylated by ustM to
CC       yield ustiloxin F which in turn substrate of the cytochrome P450
CC       monooxygenase ustC which catalyzes the formation of S-deoxyustiloxin H
CC       (PubMed:27166860). The flavoprotein monooxygenases ustF1 and ustF2 then
CC       participate in the modification of the side chain of S-deoxyustiloxin
CC       H, leading to the synthesis of an oxime intermediate, via ustiloxin H
CC       (PubMed:27166860). Finally, carboxylative dehydration performed by the
CC       cysteine desulfurase-like protein ustD yields ustiloxin B
CC       (PubMed:27166860). {ECO:0000269|PubMed:24841822,
CC       ECO:0000269|PubMed:26703898, ECO:0000269|PubMed:27166860}.
CC   -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:26703898}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of ustiloxin B and its
CC       intermediate ustiloxin F (PubMed:24841822, PubMed:26703898).
CC       {ECO:0000269|PubMed:24841822, ECO:0000269|PubMed:26703898}.
CC   -!- SIMILARITY: Belongs to the peptidase S41A family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; EQ963480; EED49420.1; -; Genomic_DNA.
DR   RefSeq; XP_002381321.1; XM_002381280.1.
DR   AlphaFoldDB; B8NM69; -.
DR   EnsemblFungi; EED49420; EED49420; AFLA_095010.
DR   VEuPathDB; FungiDB:AFLA_095010; -.
DR   eggNOG; ENOG502S18W; Eukaryota.
DR   HOGENOM; CLU_014251_1_1_1; -.
DR   OMA; VSTCAFF; -.
DR   Proteomes; UP000001875; Unassembled WGS sequence.
DR   GO; GO:0008236; F:serine-type peptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   InterPro; IPR029045; ClpP/crotonase-like_dom_sf.
DR   InterPro; IPR005151; Tail-specific_protease.
DR   Pfam; PF03572; Peptidase_S41; 1.
DR   SUPFAM; SSF52096; SSF52096; 1.
PE   1: Evidence at protein level;
KW   Hydrolase; Protease; Serine protease.
FT   CHAIN           1..480
FT                   /note="Peptidase S41 family protein ustP"
FT                   /id="PRO_0000437296"
FT   REGION          78..97
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          134..336
FT                   /note="Peptidase S41 domain"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   480 AA;  52630 MW;  EC06904C3F595234 CRC64;
     MANVQSRYNH LFPSPAAAFS GMYTGGLWTN NLGSWPGKAN QTVEFSNGTK MTVETTASVM
     LDRGLDFSSG ESLFQTACMP NKKSRPPDPR PSLAVGKPPY SIPLGGPSMY PDPIIHHKKD
     FVRGYYLHEE RLEDVAVLQL PTFRLIGESP VSLARVAVQF LERARKDGKE KLIIDLSNNM
     GGDINLGFNL FRILFPDKPI YTATRFPSTE LIGLMGRVFS TSQGNEAVEH DNTLDLPLVF
     QNAVTPDHRH SFGSWEKLFG PVEIAGQNMS HLHATYNFTT ASTEDNPISG YGGIEFGPST
     QLFHAENIII MTNGICASTC TILARLLKQQ GVRSIVFGGR PRAAPMQLLG GSKGGQYWSL
     VTISHYIKKA REIAVNASGA GSPILSEDEL ARFLELAPPP LTGFPIRIDS RGGSGVNFRN
     EYDEKDPTTP LQFVYEAADC RLFWTAENYV FPESSWVAAA DAMFGDASCV EESDGHHITP