PEPA_ASPPH
ID PEPA_ASPPH Reviewed; 394 AA.
AC Q12567;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Aspergillopepsin-1 {ECO:0000305};
DE EC=3.4.23.18 {ECO:0000269|PubMed:21699};
DE AltName: Full=Aspartic protease pepA;
DE AltName: Full=Aspergillopepsin I {ECO:0000303|PubMed:8142467};
DE AltName: Full=Aspergillopeptidase A;
DE AltName: Full=Protease type XIII;
DE Flags: Precursor;
GN Name=pepA;
OS Aspergillus phoenicis (Aspergillus saitoi).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=5063;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 70-91; 93-112;
RP 134-152; 158-168; 176-194; 204-242; 249-253; 291-299; 335-339 AND 376-394,
RP AND MUTAGENESIS OF ASP-145.
RC STRAIN=ATCC 14332 / BCRC 34164 / R-3813;
RX PubMed=8142467; DOI=10.1016/0167-4838(94)90016-7;
RA Shintani T., Ichishima E.;
RT "Primary structure of aspergillopepsin I deduced from nucleotide sequence
RT of the gene and aspartic acid-76 is an essential active site of the enzyme
RT for trypsinogen activation.";
RL Biochim. Biophys. Acta 1204:257-264(1994).
RN [2]
RP FUNCTION.
RX PubMed=13702766; DOI=10.1016/0006-3002(60)90786-1;
RA Gabeloteau C., Desnuelle P.;
RT "On the activation of bovine trypsinogen by a crystallized protease from
RT Aspergillus saitoi.";
RL Biochim. Biophys. Acta 42:230-237(1960).
RN [3]
RP SUBUNIT.
RX PubMed=5886141; DOI=10.1038/207525a0;
RA Ichishima E., Yoshida F.;
RT "Molecular weight of acid proteinase of Aspergillus saitoi.";
RL Nature 207:525-526(1965).
RN [4]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX DOI=10.1016/0076-6879(70)19029-X;
RA Ichishima E.;
RT "Purification and mode of assay for acid proteinase of Aspergillus
RT saitoi.";
RL Methods Enzymol. 19:379-406(1970).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=21699; DOI=10.1016/0005-2744(77)90176-0;
RA Tanaka N., Takeuchi M., Ichishima E.;
RT "Purification of an acid proteinase from Aspergillus saitoi and
RT determination of peptide bond specificity.";
RL Biochim. Biophys. Acta 485:406-416(1977).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.14 ANGSTROMS) OF 70-394, DISULFIDE BOND, AND
RP GLYCOSYLATION AT SER-129 AND SER-304.
RX PubMed=11418762; DOI=10.1107/s0907444901005972;
RA Cho S.W., Kim N., Choi M.U., Shin W.;
RT "Structure of aspergillopepsin I from Aspergillus phoenicis: variations of
RT the S1'-S2 subsite in aspartic proteinases.";
RL Acta Crystallogr. D 57:948-956(2001).
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. {ECO:0000269|PubMed:13702766,
CC ECO:0000269|PubMed:21699, ECO:0000269|Ref.4}.
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:21699};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 2.9-3.3. {ECO:0000269|Ref.4};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:5886141}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|Ref.4}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01103}.
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DR EMBL; D25318; BAA04988.1; -; Genomic_DNA.
DR PDB; 1IBQ; X-ray; 2.14 A; A/B=70-394.
DR PDBsum; 1IBQ; -.
DR AlphaFoldDB; Q12567; -.
DR SMR; Q12567; -.
DR Allergome; 8264; Asp sa AP.
DR MEROPS; A01.016; -.
DR iPTMnet; Q12567; -.
DR EvolutionaryTrace; Q12567; -.
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 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Protease; Secreted; Signal; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..69
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:8142467"
FT /id="PRO_0000025924"
FT CHAIN 70..394
FT /note="Aspergillopepsin-1"
FT /id="PRO_0000025925"
FT DOMAIN 85..391
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 101
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CARBOHYD 129
FT /note="O-linked (Man...) serine"
FT /evidence="ECO:0000269|PubMed:11418762"
FT CARBOHYD 304
FT /note="O-linked (Man...) serine"
FT /evidence="ECO:0000269|PubMed:11418762"
FT DISULFID 319..354
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103,
FT ECO:0000269|PubMed:11418762"
FT MUTAGEN 145
FT /note="D->S: Changes specificity toward basic substrates."
FT /evidence="ECO:0000269|PubMed:8142467"
FT STRAND 72..78
FT /evidence="ECO:0007829|PDB:1IBQ"
FT TURN 80..82
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 85..92
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 94..101
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 107..110
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 116..119
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 148..160
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 163..176
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 178..181
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 208..212
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 216..226
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 229..237
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 260..263
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 265..268
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 288..291
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 293..300
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 310..314
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 316..318
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 333..337
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 339..342
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 343..348
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 352..360
FT /evidence="ECO:0007829|PDB:1IBQ"
FT TURN 362..364
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 366..369
FT /evidence="ECO:0007829|PDB:1IBQ"
FT HELIX 371..374
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 377..382
FT /evidence="ECO:0007829|PDB:1IBQ"
FT TURN 383..386
FT /evidence="ECO:0007829|PDB:1IBQ"
FT STRAND 387..393
FT /evidence="ECO:0007829|PDB:1IBQ"
SQ SEQUENCE 394 AA; 41298 MW; 70FC32D747101551 CRC64;
MVVFSKTAAL VLGLSTAVSA APAPTRKGFT INQIARPANK TRTVNLPGLY ARSLAKFGGT
VPQSVKEAAS KGSAVTTPQN NDEEYLTPVT VGKSTLHLDF DTGSADLWVF SDELPSSEQT
GHDLYTPSSS ATKLSGYSWD ISYGDGSSAS GDVYRDTVTV GGVTTNKQAV EAASKISSEF
VQDTANDGLL GLAFSSINTV QPKAQTTFFD TVKSQLDSPL FAVQLKHDAP GVYDFGYIDD
SKYTGSITYT DADSSQGYWG FSTDGYSIGD GSSSSSGFSA IADTGTTLIL LDDEIVSAYY
EQVSGAQESY EAGGYVFSCS TDLPDFTVVI GDYKAVVPGK YINYAPVSTG SSTCYGGIQS
NSGLGLSILG DVFLKSQYVV FNSEGPKLGF AAQA
