CARP7_CANAL
ID CARP7_CANAL Reviewed; 588 AA.
AC Q59VH7; A0A1D8PDF9;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 2.
DT 03-AUG-2022, entry version 108.
DE RecName: Full=Candidapepsin-7;
DE EC=3.4.23.24;
DE AltName: Full=ACP 7;
DE AltName: Full=Aspartate protease 7;
DE AltName: Full=Secreted aspartic protease 7;
DE Flags: Precursor;
GN Name=SAP7; OrderedLocusNames=CAALFM_C104870WA;
GN ORFNames=CaO19.756, CaO19.8376;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP INDUCTION.
RX PubMed=16177393; DOI=10.1128/iai.73.10.7061-7063.2005;
RA Taylor B.N., Hannemann H., Sehnal M., Biesemeier A., Schweizer A.,
RA Rollinghoff M., Schroppel K.;
RT "Induction of SAP7 correlates with virulence in an intravenous infection
RT model of candidiasis but not in a vaginal infection model in mice.";
RL Infect. Immun. 73:7061-7063(2005).
RN [5]
RP INDUCTION.
RX PubMed=15814841; DOI=10.1091/mbc.e05-01-0071;
RA Garcia-Sanchez S., Mavor A.L., Russell C.L., Argimon S., Dennison P.,
RA Enjalbert B., Brown A.J.;
RT "Global roles of Ssn6 in Tup1- and Nrg1-dependent gene regulation in the
RT fungal pathogen, Candida albicans.";
RL Mol. Biol. Cell 16:2913-2925(2005).
RN [6]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=21646240; DOI=10.1093/jb/mvr073;
RA Aoki W., Kitahara N., Miura N., Morisaka H., Yamamoto Y., Kuroda K.,
RA Ueda M.;
RT "Comprehensive characterization of secreted aspartic proteases encoded by a
RT virulence gene family in Candida albicans.";
RL J. Biochem. 150:431-438(2011).
RN [7]
RP GLYCOSYLATION, CATALYTIC ACTIVITY, ACTIVE SITE, PROPEPTIDE, AND MUTAGENESIS
RP OF MET-242; ASP-244; ASP-464 AND THR-467.
RX PubMed=22384266; DOI=10.1371/journal.pone.0032513;
RA Aoki W., Kitahara N., Miura N., Morisaka H., Yamamoto Y., Kuroda K.,
RA Ueda M.;
RT "Candida albicans possesses Sap7 as a pepstatin A-insensitive secreted
RT aspartic protease.";
RL PLoS ONE 7:E32513-E32513(2012).
CC -!- FUNCTION: Secreted aspartic peptidases (SAPs) are a group of ten acidic
CC hydrolases considered as key virulence factors. These enzymes supply
CC the fungus with nutrient amino acids as well as are able to degrade the
CC selected host's proteins involved in the immune defense.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Preferential cleavage at the carboxyl of hydrophobic amino
CC acids, but fails to cleave 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17 and 24-
CC Phe-|-Phe-25 of insulin B chain. Activates trypsinogen, and degrades
CC keratin.; EC=3.4.23.24; Evidence={ECO:0000269|PubMed:21646240,
CC ECO:0000269|PubMed:22384266};
CC -!- ACTIVITY REGULATION: Contrary to other SAPs, SAP7 is insensitive to
CC pepstatin A inhibition, which is due restriction of the accessibility
CC of pepstatin A to the active site by Met-242 and Thr-467.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.5. {ECO:0000269|PubMed:21646240};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- INDUCTION: Expression is regulated by SSN6 and induced during host
CC infection. {ECO:0000269|PubMed:15814841, ECO:0000269|PubMed:16177393}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:22384266}.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CP017623; AOW26160.1; -; Genomic_DNA.
DR RefSeq; XP_713566.2; XM_708473.2.
DR AlphaFoldDB; Q59VH7; -.
DR SMR; Q59VH7; -.
DR STRING; 237561.Q59VH7; -.
DR MEROPS; A01.065; -.
DR GeneID; 3644783; -.
DR KEGG; cal:CAALFM_C104870WA; -.
DR CGD; CAL0000192370; SAP7.
DR VEuPathDB; FungiDB:C1_04870W_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; Q59VH7; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR PHI-base; PHI:480; -.
DR PRO; PR:Q59VH7; -.
DR Proteomes; UP000000559; Chromosome 1.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0009277; C:fungal-type cell wall; IBA:GO_Central.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IBA:GO_Central.
DR GO; GO:0031505; P:fungal-type cell wall organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; IBA:GO_Central.
DR CDD; cd05474; SAP_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR InterPro; IPR033876; SAP-like.
DR PANTHER; PTHR47965; PTHR47965; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW Aspartyl protease; Cleavage on pair of basic residues; Glycoprotein;
KW Hydrolase; Protease; Reference proteome; Secreted; Signal; Virulence;
KW Zymogen.
FT SIGNAL 1..16
FT /evidence="ECO:0000255"
FT PROPEP 17..143
FT /note="Activation peptide"
FT /id="PRO_0000424300"
FT CHAIN 144..588
FT /note="Candidapepsin-7"
FT /id="PRO_0000424301"
FT DOMAIN 226..574
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT REGION 83..126
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 145..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 244
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094,
FT ECO:0000269|PubMed:22384266"
FT ACT_SITE 464
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094,
FT ECO:0000269|PubMed:22384266"
FT BINDING 244..246
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 295..296
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 464..468
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 308
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 327
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 423
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 445
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 486
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 242
FT /note="M->A: Abolishes pepstatin A insensitivity."
FT /evidence="ECO:0000269|PubMed:22384266"
FT MUTAGEN 244
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:22384266"
FT MUTAGEN 464
FT /note="D->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:22384266"
FT MUTAGEN 467
FT /note="T->A: Abolishes pepstatin A insensitivity."
FT /evidence="ECO:0000269|PubMed:22384266"
SQ SEQUENCE 588 AA; 62526 MW; 8EEA8515C6EC4C38 CRC64;
MQRVLELLLL SSTALAVIGD GFIALPVHKL QAGEGSAHFP NRLPIFDVVN GVAKSVEDDV
NQIIQPIFGN GIFSGGSIQG THSGNGHSVK YEVSLPSSSS QKGSNGPSST DNKDTDPSKT
GFSLDDLMNS IPTDFWNLIG LNKAPTSSDN GSKDADFTPS AVSQVEQPTS KSVESTAPGP
ASSASSSSSS EAASSSQPSE DSQPSSSANK KTGAFFLSLD NTQTLYTATL KVGSPAQEVQ
VMIDTGSSDL WFISSGNSQC KVNGGSIDCD KYGVFDKSKS STWHDNKTDY SISYYDGDKA
SGTMGQDNIT FADGFSIENA NFAVIDNTTS SIGVFGVGYP ELEAVKSKYT NLPFAMKEQN
LIAKVAYSLY LDSRDAVQGY ILFGGIDHAK YTGDLKAFDI VQSNDKYVYS QIPLTSVASS
LNNYTNAYGL PAGSNHPKVG AVIYNGTDSF NGGVDLKDTP TLLDTGTTYS YLSKDQVESI
VGLYGNVTYN DAGKAYEVPC WVGNPGNYLE FNFKNEQYIK VPTSEFVISV GTYASGAELC
VFGILPGTHS ILGDNFMRSV YAVFDLEDHV ISIAQAAYND NHAVVPIE
