ID   ANEH_ASPA1              Reviewed;         448 AA.
AC   A0A1L9WUM2;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2017, sequence version 1.
DT   03-AUG-2022, entry version 20.
DE   RecName: Full=Proline iminopeptidase aneH {ECO:0000303|PubMed:31618514};
DE            Short=PIP {ECO:0000303|PubMed:31618514};
DE            EC=3.4.11.5 {ECO:0000250|UniProtKB:P52279};
DE   AltName: Full=Aculenes biosynthesis cluster protein HA {ECO:0000303|PubMed:31618514};
GN   Name=aneH {ECO:0000303|PubMed:31618514}; ORFNames=ASPACDRAFT_43554;
OS   Aspergillus aculeatus (strain ATCC 16872 / CBS 172.66 / WB 5094).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=690307;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 16872 / CBS 172.66 / WB 5094;
RX   PubMed=28196534; DOI=10.1186/s13059-017-1151-0;
RA   de Vries R.P., Riley R., Wiebenga A., Aguilar-Osorio G., Amillis S.,
RA   Uchima C.A., Anderluh G., Asadollahi M., Askin M., Barry K., Battaglia E.,
RA   Bayram O., Benocci T., Braus-Stromeyer S.A., Caldana C., Canovas D.,
RA   Cerqueira G.C., Chen F., Chen W., Choi C., Clum A., Dos Santos R.A.,
RA   Damasio A.R., Diallinas G., Emri T., Fekete E., Flipphi M., Freyberg S.,
RA   Gallo A., Gournas C., Habgood R., Hainaut M., Harispe M.L., Henrissat B.,
RA   Hilden K.S., Hope R., Hossain A., Karabika E., Karaffa L., Karanyi Z.,
RA   Krasevec N., Kuo A., Kusch H., LaButti K., Lagendijk E.L., Lapidus A.,
RA   Levasseur A., Lindquist E., Lipzen A., Logrieco A.F., MacCabe A.,
RA   Maekelae M.R., Malavazi I., Melin P., Meyer V., Mielnichuk N., Miskei M.,
RA   Molnar A.P., Mule G., Ngan C.Y., Orejas M., Orosz E., Ouedraogo J.P.,
RA   Overkamp K.M., Park H.-S., Perrone G., Piumi F., Punt P.J., Ram A.F.,
RA   Ramon A., Rauscher S., Record E., Riano-Pachon D.M., Robert V., Roehrig J.,
RA   Ruller R., Salamov A., Salih N.S., Samson R.A., Sandor E., Sanguinetti M.,
RA   Schuetze T., Sepcic K., Shelest E., Sherlock G., Sophianopoulou V.,
RA   Squina F.M., Sun H., Susca A., Todd R.B., Tsang A., Unkles S.E.,
RA   van de Wiele N., van Rossen-Uffink D., Oliveira J.V., Vesth T.C.,
RA   Visser J., Yu J.-H., Zhou M., Andersen M.R., Archer D.B., Baker S.E.,
RA   Benoit I., Brakhage A.A., Braus G.H., Fischer R., Frisvad J.C.,
RA   Goldman G.H., Houbraken J., Oakley B., Pocsi I., Scazzocchio C.,
RA   Seiboth B., vanKuyk P.A., Wortman J., Dyer P.S., Grigoriev I.V.;
RT   "Comparative genomics reveals high biological diversity and specific
RT   adaptations in the industrially and medically important fungal genus
RT   Aspergillus.";
RL   Genome Biol. 18:RESEARCH28.1-RESEARCH28.45(2017).
RN   [2]
RP   FUNCTION, AND PATHWAY.
RX   PubMed=31618514; DOI=10.1002/anie.201910200;
RA   Lee C.F., Chen L.X., Chiang C.Y., Lai C.Y., Lin H.C.;
RT   "The biosynthesis of norsesquiterpene aculenes requires three cytochrome
RT   P450 enzymes to catalyze a stepwise demethylation process.";
RL   Angew. Chem. Int. Ed. 58:18414-18418(2019).
CC   -!- FUNCTION: Proline iminopeptidase; part of the gene cluster that
CC       mediates the biosynthesis of aculenes, a unique type of
CC       norsesquiterpenes that contain a nordaucane skeleton linked to an L-
CC       proline moiety and are of mixed biosynthetic origin (PubMed:31618514).
CC       The pathway begins with the synthesis of dauca-4,7-diene by the terpene
CC       cyclase aneC using farnesyl pyrophosphate (FPP) as substrate
CC       (PubMed:31618514). The cytochrome P450 monooxygenase aneF then performs
CC       the initial oxidation at C-12 of dauca-4,7-diene to yield asperaculane
CC       D (PubMed:31618514). Asperaculane D is substrate of the cytochrome P450
CC       monooxygenase aneD for C-10 hydroxylation to yield asperaculane E
CC       (PubMed:31618514). The cytochrome P450 monooxygenase aneG then converts
CC       asperaculane E into aculene D via C-2 oxidation (PubMed:31618514). The
CC       monomodular nonribosomal peptide synthtase aneB adenylates L-proline
CC       and the thiohydrolase aneE transfers this activated L-proline
CC       derivative to aculenes D and C to produce respectively aculenes B and A
CC       (PubMed:31618514). The dioxygenase aneA converts aculene D into aculene
CC       C, and aculene B into aculene A by introducing the 5,6-alkene moiety
CC       (PubMed:31618514). Asperculanes A, B, C and F, as well as 14-prolyl
CC       asperculane C, might be shunt products of the pathway
CC       (PubMed:31618514). {ECO:0000269|PubMed:31618514}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Release of N-terminal proline from a peptide.; EC=3.4.11.5;
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000305|PubMed:31618514}.
CC   -!- SUBUNIT: Homooligomer. {ECO:0000250|UniProtKB:P52279}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P52279}.
CC   -!- SIMILARITY: Belongs to the peptidase S33 family. {ECO:0000305}.
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DR   EMBL; KV878977; OJJ99919.1; -; Genomic_DNA.
DR   RefSeq; XP_020056259.1; XM_020201280.1.
DR   AlphaFoldDB; A0A1L9WUM2; -.
DR   SMR; A0A1L9WUM2; -.
DR   EnsemblFungi; OJJ99919; OJJ99919; ASPACDRAFT_43554.
DR   GeneID; 30975094; -.
DR   VEuPathDB; FungiDB:ASPACDRAFT_43554; -.
DR   OrthoDB; 1061420at2759; -.
DR   Proteomes; UP000184546; Unassembled WGS sequence.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0004177; F:aminopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   Gene3D; 3.40.50.1820; -; 1.
DR   InterPro; IPR029058; AB_hydrolase.
DR   InterPro; IPR000073; AB_hydrolase_1.
DR   InterPro; IPR002410; Peptidase_S33.
DR   Pfam; PF00561; Abhydrolase_1; 1.
DR   PRINTS; PR00793; PROAMNOPTASE.
DR   SUPFAM; SSF53474; SSF53474; 1.
PE   3: Inferred from homology;
KW   Aminopeptidase; Cytoplasm; Hydrolase; Protease; Reference proteome.
FT   CHAIN           1..448
FT                   /note="Proline iminopeptidase aneH"
FT                   /id="PRO_0000449097"
FT   DOMAIN          64..191
FT                   /note="AB hydrolase-1"
FT                   /evidence="ECO:0000255"
FT   ACT_SITE        164
FT                   /note="Nucleophile"
FT                   /evidence="ECO:0000250|UniProtKB:P52279"
FT   ACT_SITE        397
FT                   /evidence="ECO:0000250|UniProtKB:P52279"
FT   ACT_SITE        425
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:P52279"
SQ   SEQUENCE   448 AA;  50390 MW;  FD6A225B825371E7 CRC64;
     MAVEQNIAPA KLIDRFSHDG PGKCRTSEWR FEVPLNHSKP DEGTVRLFAR SIHCVLGVDD
     PELPWMLYLQ GGPGLGCKTP LEYAWLPSIL EKGYRVLFLD ERGTGQSSPI TAKTLAQQGD
     HKKQADLLKR FRADNIVRDC EAVRKHLYQD APADQSKWSV MAASFGGFCA ISYVSMFPNS
     LVEVFIGGGP CPMVNEPGQV IPRLFAVAAR RNEVYYKKYP EDVGRVKRII KYLKENKVAL
     SKGTLTPERF QQLGVMLGLH GGIDYIHGVV QRTDNDLDMF KFLTAPTLDL IENSGMAHNV
     IYSLLQEPMY CQGKAGGWCA DKCRKADPRF SLNERNAQIW FTGEAIFSDM FESYDELKDL
     KPVAELLARS SDWGQLYNEA QLARNEVPVY VATAVEDMYV SYDLGCHTAS KVKNLQQVVN
     NTWYHDAVET KASEVMPALF ALKEDRID