ID   PEPA_PENRW              Reviewed;         396 AA.
AC   B6HL60;
DT   05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 1.
DT   03-AUG-2022, entry version 69.
DE   RecName: Full=Penicillopepsin-1 {ECO:0000305};
DE            EC=3.4.23.20 {ECO:0000250|UniProtKB:P00798};
DE   AltName: Full=Aspartic protease pepA;
DE   Flags: Precursor;
GN   Name=pepA; ORFNames=Pc21g03510;
OS   Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS   54-1255) (Penicillium chrysogenum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC   Penicillium chrysogenum species complex.
OX   NCBI_TaxID=500485;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX   PubMed=18820685; DOI=10.1038/nbt.1498;
RA   van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA   Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA   Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA   Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA   van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA   Bovenberg R.A.L.;
RT   "Genome sequencing and analysis of the filamentous fungus Penicillium
RT   chrysogenum.";
RL   Nat. Biotechnol. 26:1161-1168(2008).
CC   -!- FUNCTION: Secreted aspartic endopeptidase that allows assimilation of
CC       proteinaceous substrates. The scissile peptide bond is attacked by a
CC       nucleophilic water molecule activated by two aspartic residues in the
CC       active site. Shows a broad primary substrate specificity. Favors
CC       hydrophobic residues at the P1 and P1' positions, but can also activate
CC       trypsinogen and hydrolyze the B chain of insulin between positions
CC       'Gly-20' and 'Glu-21'. {ECO:0000250|UniProtKB:P00798}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Hydrolysis of proteins with broad specificity similar to that
CC         of pepsin A, preferring hydrophobic residues at P1 and P1', but also
CC         cleaving 20-Gly-|-Glu-21 in the B chain of insulin. Clots milk, and
CC         activates trypsinogen.; EC=3.4.23.20;
CC         Evidence={ECO:0000250|UniProtKB:P00798};
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q12567}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q01972}.
CC   -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000255|PROSITE-
CC       ProRule:PRU01103}.
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DR   EMBL; AM920436; CAP95248.1; -; Genomic_DNA.
DR   RefSeq; XP_002567415.1; XM_002567369.1.
DR   AlphaFoldDB; B6HL60; -.
DR   SMR; B6HL60; -.
DR   STRING; 500485.B6HL60; -.
DR   MEROPS; A01.026; -.
DR   EnsemblFungi; CAP95248; CAP95248; PCH_Pc21g03510.
DR   GeneID; 8313187; -.
DR   KEGG; pcs:Pc21g03510; -.
DR   VEuPathDB; FungiDB:PCH_Pc21g03510; -.
DR   eggNOG; KOG1339; Eukaryota.
DR   HOGENOM; CLU_013253_0_1_1; -.
DR   OMA; GFWEFTA; -.
DR   OrthoDB; 1619495at2759; -.
DR   BioCyc; PCHR:PC21G03510-MON; -.
DR   Proteomes; UP000000724; Contig Pc00c21.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR   GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR   CDD; cd06097; Aspergillopepsin_like; 1.
DR   Gene3D; 2.40.70.10; -; 2.
DR   InterPro; IPR001461; Aspartic_peptidase_A1.
DR   InterPro; IPR001969; Aspartic_peptidase_AS.
DR   InterPro; IPR034163; Aspergillopepsin-like_cat_dom.
DR   InterPro; IPR033121; PEPTIDASE_A1.
DR   InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR   PANTHER; PTHR47966; PTHR47966; 1.
DR   Pfam; PF00026; Asp; 1.
DR   PRINTS; PR00792; PEPSIN.
DR   SUPFAM; SSF50630; SSF50630; 1.
DR   PROSITE; PS00141; ASP_PROTEASE; 2.
DR   PROSITE; PS51767; PEPTIDASE_A1; 1.
PE   3: Inferred from homology;
KW   Aspartyl protease; Disulfide bond; Glycoprotein; Hydrolase; Protease;
KW   Reference proteome; Secreted; Signal; Zymogen.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   PROPEP          21..72
FT                   /note="Activation peptide"
FT                   /evidence="ECO:0000250|UniProtKB:Q12567"
FT                   /id="PRO_0000407054"
FT   CHAIN           73..396
FT                   /note="Penicillopepsin-1"
FT                   /id="PRO_5000409897"
FT   DOMAIN          88..393
FT                   /note="Peptidase A1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        104
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   ACT_SITE        285
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT   CARBOHYD        311
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT   DISULFID        321..356
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
SQ   SEQUENCE   396 AA;  41257 MW;  6F48046B24D64268 CRC64;
     MVVFSKVTAS LACFSAVVSA AAVPVKSPRQ GFSVNQVQKT VTGTRTVNLP GVYANALAKY
     GATVPANVHA AAVSGSAITT PEENDVEYLT PVKIGESTLN LDFDTGSADL WVFSTELSSA
     EQSGHDVYDV SSSGKKLTGA SWSISYGDGS GASGDVYKDT VTVGGVKATG QAVEAAKKIS
     QQFVQDKSND GLLGLAFSSI NTVSPKPQTT FFDTVKSDLD KPLFAVTLKH GAPGTYDFGY
     IDKKKFTGSL TYTDVDNSQG FWSFTADSYK VGTGSAGPSI EGIADTGTTL LLLDDGVVSD
     YYKKVDGAKN NYSAGGYVFP CDADLPDFTV TIGSYDAVVP GKHIKYAPVT TGSSSCFGGI
     QSNSGIGFSI FGDIFLKSQY VVFDAEGPRL GFAAQA