PEPA_ASPFU
ID PEPA_ASPFU Reviewed; 395 AA.
AC P41748; Q12547; Q4WVU0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 10-JAN-2006, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=Aspergillopepsin-1 {ECO:0000305};
DE EC=3.4.23.18 {ECO:0000269|PubMed:7558282};
DE AltName: Full=Aspartic protease pepA;
DE AltName: Full=Aspergillopepsin F {ECO:0000303|PubMed:7558282};
DE AltName: Full=Aspergillopepsin I;
DE AltName: Full=Aspergillopeptidase A;
DE Flags: Precursor;
GN Name=pepA; ORFNames=AFUA_5G13300;
OS Neosartorya fumigata (strain ATCC MYA-4609 / Af293 / CBS 101355 / FGSC
OS A1100) (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=330879;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBCELLULAR LOCATION.
RX PubMed=7558282; DOI=10.1128/iai.63.10.3796-3803.1995;
RA Lee J.D., Kolattukudy P.E.;
RT "Molecular cloning of the cDNA and gene for an elastinolytic aspartic
RT proteinase from Aspergillus fumigatus and evidence of its secretion by the
RT fungus during invasion of the host lung.";
RL Infect. Immun. 63:3796-3803(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=D141;
RX PubMed=7557298; DOI=10.1111/j.1574-6968.1995.tb07700.x;
RA Reichard U., Monod M., Ruechel R.;
RT "Molecular cloning and sequencing of the gene encoding an extracellular
RT aspartic proteinase from Aspergillus fumigatus.";
RL FEMS Microbiol. Lett. 130:69-74(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC MYA-4609 / Af293 / CBS 101355 / FGSC A1100;
RX PubMed=16372009; DOI=10.1038/nature04332;
RA Nierman W.C., Pain A., Anderson M.J., Wortman J.R., Kim H.S., Arroyo J.,
RA Berriman M., Abe K., Archer D.B., Bermejo C., Bennett J.W., Bowyer P.,
RA Chen D., Collins M., Coulsen R., Davies R., Dyer P.S., Farman M.L.,
RA Fedorova N., Fedorova N.D., Feldblyum T.V., Fischer R., Fosker N.,
RA Fraser A., Garcia J.L., Garcia M.J., Goble A., Goldman G.H., Gomi K.,
RA Griffith-Jones S., Gwilliam R., Haas B.J., Haas H., Harris D.E.,
RA Horiuchi H., Huang J., Humphray S., Jimenez J., Keller N., Khouri H.,
RA Kitamoto K., Kobayashi T., Konzack S., Kulkarni R., Kumagai T., Lafton A.,
RA Latge J.-P., Li W., Lord A., Lu C., Majoros W.H., May G.S., Miller B.L.,
RA Mohamoud Y., Molina M., Monod M., Mouyna I., Mulligan S., Murphy L.D.,
RA O'Neil S., Paulsen I., Penalva M.A., Pertea M., Price C., Pritchard B.L.,
RA Quail M.A., Rabbinowitsch E., Rawlins N., Rajandream M.A., Reichard U.,
RA Renauld H., Robson G.D., Rodriguez de Cordoba S., Rodriguez-Pena J.M.,
RA Ronning C.M., Rutter S., Salzberg S.L., Sanchez M., Sanchez-Ferrero J.C.,
RA Saunders D., Seeger K., Squares R., Squares S., Takeuchi M., Tekaia F.,
RA Turner G., Vazquez de Aldana C.R., Weidman J., White O., Woodward J.R.,
RA Yu J.-H., Fraser C.M., Galagan J.E., Asai K., Machida M., Hall N.,
RA Barrell B.G., Denning D.W.;
RT "Genomic sequence of the pathogenic and allergenic filamentous fungus
RT Aspergillus fumigatus.";
RL Nature 438:1151-1156(2005).
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 (By similarity). Can catalyze
CC hydrolysis of the major structural proteins of basement membrane,
CC elastin, collagen, and laminin. Thought to play a significant role in
CC virulence (PubMed:7558282). {ECO:0000250|UniProtKB:Q12567,
CC ECO:0000269|PubMed:7558282}.
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:7558282};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5.0. {ECO:0000269|PubMed:7558282};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7558282}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01103}.
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DR EMBL; L31490; AAB07619.1; -; Genomic_DNA.
DR EMBL; X85092; CAA59419.1; -; Genomic_DNA.
DR EMBL; AAHF01000003; EAL91286.1; -; Genomic_DNA.
DR RefSeq; XP_753324.1; XM_748231.1.
DR AlphaFoldDB; P41748; -.
DR SMR; P41748; -.
DR STRING; 746128.CADAFUBP00005960; -.
DR Allergome; 3108; Asp f 10.0101.
DR Allergome; 63; Asp f 10.
DR MEROPS; A01.026; -.
DR EnsemblFungi; EAL91286; EAL91286; AFUA_5G13300.
DR GeneID; 3510846; -.
DR KEGG; afm:AFUA_5G13300; -.
DR VEuPathDB; FungiDB:Afu5g13300; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_0_1_1; -.
DR InParanoid; P41748; -.
DR OMA; GFWEFTA; -.
DR OrthoDB; 1619495at2759; -.
DR Proteomes; UP000002530; Chromosome 5.
DR GO; GO:0005576; C:extracellular region; IDA:AspGD.
DR GO; GO:0000329; C:fungal-type vacuole membrane; IBA:GO_Central.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0004175; F:endopeptidase activity; IDA:AspGD.
DR GO; GO:0006508; P:proteolysis; IMP:AspGD.
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; Disulfide bond; Hydrolase; Protease; Reference proteome;
KW Secreted; Signal; Virulence; Zymogen.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT PROPEP 30..70
FT /note="Activation peptide"
FT /evidence="ECO:0000250|UniProtKB:Q12567"
FT /id="PRO_0000025926"
FT CHAIN 71..395
FT /note="Aspergillopepsin-1"
FT /id="PRO_0000025927"
FT DOMAIN 86..392
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 102
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 284
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT DISULFID 320..355
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CONFLICT 19..27
FT /note="SAVPVVQPR -> MLSLWSSRA (in Ref. 1; AAB07619)"
FT /evidence="ECO:0000305"
FT CONFLICT 33..34
FT /note="NQ -> FL (in Ref. 1; AAB07619)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="V -> G (in Ref. 1; AAB07619)"
FT /evidence="ECO:0000305"
FT CONFLICT 204..211
FT /note="RPQTTFFD -> SDYFLY (in Ref. 1; AAB07619)"
FT /evidence="ECO:0000305"
FT CONFLICT 276
FT /note="S -> T (in Ref. 1; AAB07619)"
FT /evidence="ECO:0000305"
FT CONFLICT 348..359
FT /note="VTDGSSTCYGGI -> SLTQLYLLRRH (in Ref. 1; AAB07619)"
FT /evidence="ECO:0000305"
FT CONFLICT 393..395
FT /note="PQA -> LRH (in Ref. 1)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 395 AA; 41613 MW; F3D1CCC0C6814BA9 CRC64;
MVVFSKVTAV VVGLSTIVSA VPVVQPRKGF TINQVARPVT NKKTVNLPAV YANALTKYGG
TVPDSVKAAA SSGSAVTTPE QYDSEYLTPV KVGGTTLNLD FDTGSADLWV FSSELSASQS
SGHAIYKPSA NAQKLNGYTW KIQYGDGSSA SGDVYKDTVT VGGVTAQSQA VEAASHISSQ
FVQDKDNDGL LGLAFSSINT VSPRPQTTFF DTVKSQLDSP LFAVTLKYHA PGTYDFGYID
NSKFQGELTY TDVDSSQGFW MFTADGYGVG NGAPNSNSIS GIADTGTTLL LLDDSVVADY
YRQVSGAKNS NQYGGYVFPC STKLPSFTTV IGGYNAVVPG EYINYAPVTD GSSTCYGGIQ
SNSGLGFSIF GDIFLKSQYV VFDSQGPRLG FAPQA
