PEPA2_PENJA
ID PEPA2_PENJA Reviewed; 394 AA.
AC P78735;
DT 05-APR-2011, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 83.
DE RecName: Full=Penicillopepsin-2 {ECO:0000305};
DE EC=3.4.23.20 {ECO:0000269|PubMed:10850809};
DE AltName: Full=Aspartic protease pepA;
DE AltName: Full=Penicillopepsin-JT2 {ECO:0000303|PubMed:10850809};
DE Flags: Precursor;
GN Name=pepA {ECO:0000303|PubMed:10850809};
OS Penicillium janthinellum (Penicillium vitale).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5079;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF N-TERMINUS,
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=NRRL905;
RX PubMed=10850809; DOI=10.1110/ps.9.5.991;
RA Cao Q.N., Stubbs M., Ngo K.Q., Ward M., Cunningham A., Pai E.F., Tu G.C.,
RA Hofmann T.;
RT "Penicillopepsin-JT2, a recombinant enzyme from Penicillium janthinellum
RT and the contribution of a hydrogen bond in subsite S3 to k(cat).";
RL Protein Sci. 9:991-1001(2000).
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:0000269|PubMed:10850809}.
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:0000269|PubMed:10850809};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.4 mM for Ac-Lys-p-nitrophenylalanyl-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.4 mM for Ac-Ala-Lys-p-nitrophenylalanyl-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.5 mM for Ac-Ala-Ala-Lys-p-nitrophenylalanyl-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.59 mM for Ac-Lys-p-nitrophenylalanyl-Ala-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.5 mM for Ac-Ala-Lys-p-nitrophenylalanyl-Ala-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.35 mM for Ac-Ala-Ala-Lys-p-nitrophenylalanyl-Ala-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.21 mM for Ac-Lys-p-nitrophenylalanyl-Ala-Ala-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.41 mM for Ac-Ala-Lys-p-nitrophenylalanyl-Ala-Ala-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.32 mM for Ac-Ala-Ala-Lys-p-nitrophenylalanyl-Ala-Ala-amide
CC {ECO:0000269|PubMed:10850809};
CC KM=0.46 mM for Ac-Ala-Ala-Ala-Lys-p-nitrophenylalanyl-Ala-Ala-amide
CC {ECO:0000269|PubMed:10850809};
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}.
CC -!- CAUTION: PubMed:10850809 has identified a second propeptide cleavage
CC site after Lys-68 and both possible mature proteins were found in equal
CC quantities in a heterologous expression system in Aspergillus awamori.
CC {ECO:0000305}.
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DR EMBL; U81483; AAB63942.1; -; Genomic_DNA.
DR AlphaFoldDB; P78735; -.
DR SMR; P78735; -.
DR MEROPS; A01.026; -.
DR BRENDA; 3.4.23.20; 4621.
DR SABIO-RK; P78735; -.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
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; Secreted; Signal; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..71
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:10850809"
FT /id="PRO_0000407055"
FT CHAIN 72..394
FT /note="Penicillopepsin-2"
FT /id="PRO_5000145200"
FT DOMAIN 87..391
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CARBOHYD 132
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 319..354
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
SQ SEQUENCE 394 AA; 40840 MW; FCFE8246FFAD31F4 CRC64;
MVVFSKITVV LAGLATVASA VPTGTSRKST FTVNQKARPV AQAKAINLPG MYASALSKYG
AAVPASVKAA AESGTAVTTP EANDVEYLTP VNVGGTTLNL DFDTGSADLW VFSSELSSSE
STGHSLYKPS SNATKLAGYS WSITYGDQSS ASGDVYKDFV VVGGVKASPQ AVEAASQISQ
QFVNDKNNDG LLGLAFSSIN TVKPKSQTTF FDTVKGQLDS PLFAVTLKHN APGTYDFGFV
DKNKYTGSLT YAQVDSSQGF WSFTADGYKI GSKSGGSIQG IADTGTTLLL LPDNVVSDYY
GQVSGAQQDS SAGGYTVPCS AQLPDFTVTI GSYNAVVPGS LINYAPLQSG SSTCFGGIQS
NSGLGFSIFG DIFLKSQYVV FDANGPRLGF APQA
