PEPA_ASPOR
ID PEPA_ASPOR Reviewed; 404 AA.
AC Q06902; Q00249; Q2U5X3;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 02-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Aspergillopepsin-1 {ECO:0000305};
DE EC=3.4.23.18 {ECO:0000269|PubMed:8138};
DE AltName: Full=Acid protease A2 {ECO:0000303|PubMed:8138};
DE AltName: Full=Aspartic protease pepA;
DE AltName: Full=Aspergillopepsin I;
DE AltName: Full=Aspergillopepsin O {ECO:0000303|PubMed:8462873};
DE Short=PEPO;
DE AltName: Full=Aspergillopeptidase A;
DE Short=PEPA;
DE Flags: Precursor;
GN Name=pepA {ECO:0000303|PubMed:7763981};
GN Synonyms=pepO {ECO:0000303|PubMed:8462873}; ORFNames=AO090120000474;
OS Aspergillus oryzae (strain ATCC 42149 / RIB 40) (Yellow koji mold).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=510516;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 237-249 AND
RP 386-404.
RC STRAIN=ATCC 42149 / RIB 40;
RX PubMed=7763981; DOI=10.1271/bbb.57.1095;
RA Gomi K., Arikawa K., Kamiya N., Kitamoto K., Kumagai C.;
RT "Cloning and nucleotide sequence of the acid protease-encoding gene (pepA)
RT from Aspergillus oryzae.";
RL Biosci. Biotechnol. Biochem. 57:1095-1100(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8462873; DOI=10.1016/0378-1119(93)90328-z;
RA Berka R.M., Carmona C.L., Kirk H.J., Thompson S.A., Ward M.;
RT "Isolation and characterization of the Aspergillus oryzae gene encoding
RT aspergillopepsin O.";
RL Gene 125:195-198(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 42149 / RIB 40;
RX PubMed=16372010; DOI=10.1038/nature04300;
RA Machida M., Asai K., Sano M., Tanaka T., Kumagai T., Terai G., Kusumoto K.,
RA Arima T., Akita O., Kashiwagi Y., Abe K., Gomi K., Horiuchi H.,
RA Kitamoto K., Kobayashi T., Takeuchi M., Denning D.W., Galagan J.E.,
RA Nierman W.C., Yu J., Archer D.B., Bennett J.W., Bhatnagar D.,
RA Cleveland T.E., Fedorova N.D., Gotoh O., Horikawa H., Hosoyama A.,
RA Ichinomiya M., Igarashi R., Iwashita K., Juvvadi P.R., Kato M., Kato Y.,
RA Kin T., Kokubun A., Maeda H., Maeyama N., Maruyama J., Nagasaki H.,
RA Nakajima T., Oda K., Okada K., Paulsen I., Sakamoto K., Sawano T.,
RA Takahashi M., Takase K., Terabayashi Y., Wortman J.R., Yamada O.,
RA Yamagata Y., Anazawa H., Hata Y., Koide Y., Komori T., Koyama Y.,
RA Minetoki T., Suharnan S., Tanaka A., Isono K., Kuhara S., Ogasawara N.,
RA Kikuchi H.;
RT "Genome sequencing and analysis of Aspergillus oryzae.";
RL Nature 438:1157-1161(2005).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=239702; DOI=10.1042/bj1470045;
RA Davidson R., Gertler A., Hofmann T.;
RT "Aspergillus oryzae acid proteinase. Purification and properties, and
RT formation of pi-chymotrypsin.";
RL Biochem. J. 147:45-53(1975).
RN [5]
RP BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION, AND SUBCELLULAR
RP LOCATION.
RX PubMed=8138; DOI=10.1016/0005-2744(76)90172-8;
RA Tsujita Y., Endo A.;
RT "Purification and characterization of the two molecular forms of
RT Aspergillus oryzae acid protease.";
RL Biochim. Biophys. Acta 445:194-204(1976).
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 also accepts a
CC lysine residue in the P1 position, leading to the activation of
CC trypsinogen and chymotrypsinogen A. Hydrolyzes bovine chymotrysinogen A
CC between positions 'Arg-15' and 'Ile-16'. {ECO:0000269|PubMed:239702}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins with broad specificity. Generally
CC favors hydrophobic residues in P1 and P1', but also accepts Lys in
CC P1, which leads to activation of trypsinogen. Does not clot milk.;
CC EC=3.4.23.18; Evidence={ECO:0000269|PubMed:8138};
CC -!- ACTIVITY REGULATION: Inhibited by sodium lauryl sulfonate.
CC {ECO:0000269|PubMed:8138}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.064 mM for Z-His-Phe-Phe-OEt {ECO:0000269|PubMed:239702};
CC KM=0.037 mM for Z-Ala-Ala-Phe-Phe-OPy4Pr {ECO:0000269|PubMed:239702};
CC KM=0.1 mM for bovine trypsinogen {ECO:0000269|PubMed:239702};
CC KM=0.18 mM for bovine chymotrysinogen A {ECO:0000269|PubMed:239702};
CC Note=kcat is 1.65 sec(-1) with Z-His-Phe-Phe-OEt as substrate, 0.35
CC sec(-1) with Z-Ala-Ala-Phe-Phe-OPy4Pr as substrate, 13 sec(-1) with
CC bovine trypsinogen as substrate and 1.14 sec(-1) with bovine
CC chymotrysinogen A as substrate. {ECO:0000269|PubMed:239702};
CC pH dependence:
CC Optimum pH is 3.0-4.2. {ECO:0000269|PubMed:8138};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:8138}.
CC -!- PTM: Two isozymes of this enzyme exist which differ only by their non-
CC covalent association with carbohydrate. {ECO:0000305|PubMed:8138}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01103}.
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DR EMBL; D13894; BAA02994.1; -; Genomic_DNA.
DR EMBL; M92927; AAA32704.1; -; Genomic_DNA.
DR EMBL; AP007166; BAE63042.1; -; Genomic_DNA.
DR PIR; JN0630; JN0630.
DR RefSeq; XP_001824175.1; XM_001824123.2.
DR AlphaFoldDB; Q06902; -.
DR SMR; Q06902; -.
DR MEROPS; A01.026; -.
DR EnsemblFungi; BAE63042; BAE63042; AO090120000474.
DR GeneID; 5996434; -.
DR KEGG; aor:AO090120000474; -.
DR VEuPathDB; FungiDB:AO090120000474; -.
DR HOGENOM; CLU_013253_0_1_1; -.
DR OMA; YGSGNAK; -.
DR BRENDA; 3.4.23.18; 522.
DR Proteomes; UP000006564; Chromosome 5.
DR GO; GO:0005576; C:extracellular region; IDA:AspGD.
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 1: Evidence at protein level;
KW Aspartyl protease; Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Hydrolase; Protease; Reference proteome; Secreted; Signal; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..77
FT /note="Activation peptide"
FT /evidence="ECO:0000250|UniProtKB:Q12567"
FT /id="PRO_0000025922"
FT CHAIN 78..404
FT /note="Aspergillopepsin-1"
FT /id="PRO_0000025923"
FT DOMAIN 95..401
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 293
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 329..364
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CONFLICT 289
FT /note="T -> S (in Ref. 1; BAA02994)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 404 AA; 42313 MW; BFC21C29EC0A24DF CRC64;
MVILSKVAAV AVGLSTVASA LPTGPSHSPH ARRGFTINQI TRQTARVGPK TASFPAIYSR
ALAKYGGTVP AHLKSAVASG HGTVVTSPEP NDIEYLTPVN IGGTTLNLDF DTGSADLWVF
SEELPKSEQT GHDVYKPSGN ASKIAGASWD ISYGDGSSAS GDVYQDTVTV GGVTAQGQAV
EAASKISDQF VQDKNNDGLL GLAFSSINTV KPKPQTTFFD TVKDQLDAPL FAVTLKYHAP
GSYDFGFIDK SKFTGELAYA DVDDSQGFWQ FTADGYSVGK GDAQKAPITG IADTGTTLVM
LDDEIVDAYY KQVQGAKNDA SAGGYVFPCE TELPEFTVVI GSYNAVIPGK HINYAPLQEG
SSTCVGGIQS NSGLGLSILG DVFLKSQYVV FDSQGPRLGF AAQA
