CARP1_CANAL
ID CARP1_CANAL Reviewed; 391 AA.
AC P0CY27; A0A1D8PQ68; P28872; Q5A8N4;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 68.
DE RecName: Full=Candidapepsin-1;
DE EC=3.4.23.24;
DE AltName: Full=ACP 1;
DE AltName: Full=Aspartate protease 1;
DE AltName: Full=Secreted aspartic protease 1;
DE Flags: Precursor;
GN Name=SAP1; Synonyms=PEP1, PEP10, PRA10, PRA3;
GN OrderedLocusNames=CAALFM_C603490CA; ORFNames=CaO19.13137, CaO19.5714;
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=1620110; DOI=10.1128/mcb.12.7.2997-3005.1992;
RA Morrow B., Srikantha T., Soll D.R.;
RT "Transcription of the gene for a pepsinogen, PEP1, is regulated by white-
RT opaque switching in Candida albicans.";
RL Mol. Cell. Biol. 12:2997-3005(1992).
RN [5]
RP CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=9043112; DOI=10.1099/00221287-143-2-349;
RA Smolenski G., Sullivan P.A., Cutfield S.M., Cutfield J.F.;
RT "Analysis of secreted aspartic proteinases from Candida albicans:
RT purification and characterization of individual Sap1, Sap2 and Sap3
RT isoenzymes.";
RL Microbiology 143:349-356(1997).
RN [6]
RP INDUCTION, AND FUNCTION.
RX PubMed=10569787; DOI=10.1128/iai.67.12.6652-6662.1999;
RA Kvaal C., Lachke S.A., Srikantha T., Daniels K., McCoy J., Soll D.R.;
RT "Misexpression of the opaque-phase-specific gene PEP1 (SAP1) in the white
RT phase of Candida albicans confers increased virulence in a mouse model of
RT cutaneous infection.";
RL Infect. Immun. 67:6652-6662(1999).
RN [7]
RP SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX PubMed=9841840; DOI=10.1086/314546;
RA De Bernardis F., Arancia S., Morelli L., Hube B., Sanglard D., Schafer W.,
RA Cassone A.;
RT "Evidence that members of the secretory aspartyl proteinase gene family, in
RT particular SAP2, are virulence factors for Candida vaginitis.";
RL J. Infect. Dis. 179:201-208(1999).
RN [8]
RP SUBCELLULAR LOCATION, AND PROPEPTIDE.
RX PubMed=11065355; DOI=10.1099/00221287-146-11-2765;
RA Beggah S., Lechenne B., Reichard U., Foundling S., Monod M.;
RT "Intra- and intermolecular events direct the propeptide-mediated maturation
RT of the Candida albicans secreted aspartic proteinase Sap1p.";
RL Microbiology 146:2765-2773(2000).
RN [9]
RP FUNCTION.
RX PubMed=11478679; DOI=10.1099/0022-1317-50-8-743;
RA Schaller M., Januschke E., Schackert C., Woerle B., Korting H.C.;
RT "Different isoforms of secreted aspartyl proteinases (Sap) are expressed by
RT Candida albicans during oral and cutaneous candidosis in vivo.";
RL J. Med. Microbiol. 50:743-747(2001).
RN [10]
RP ACTIVITY REGULATION.
RX PubMed=12203839; DOI=10.1002/jmr.568;
RA Farley P.C., Christeller J.T., Sullivan M.E., Sullivan P.A., Laing W.A.;
RT "Analysis of the interaction between the aspartic peptidase inhibitor SQAPI
RT and aspartic peptidases using surface plasmon resonance.";
RL J. Mol. Recognit. 15:135-144(2002).
RN [11]
RP INDUCTION.
RX PubMed=14555467; DOI=10.1128/ec.2.5.847-855.2003;
RA Lockhart S.R., Zhao R., Daniels K.J., Soll D.R.;
RT "Alpha-pheromone-induced 'shmooing' and gene regulation require white-
RT opaque switching during Candida albicans mating.";
RL Eukaryot. Cell 2:847-855(2003).
RN [12]
RP FUNCTION.
RX PubMed=12761103; DOI=10.1128/iai.71.6.3227-3234.2003;
RA Schaller M., Bein M., Korting H.C., Baur S., Hamm G., Monod M.,
RA Beinhauer S., Hube B.;
RT "The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an
RT in vitro model of vaginal candidiasis based on reconstituted human vaginal
RT epithelium.";
RL Infect. Immun. 71:3227-3234(2003).
RN [13]
RP FUNCTION.
RX PubMed=15845479; DOI=10.1128/iai.73.5.2758-2765.2005;
RA Schaller M., Korting H.C., Borelli C., Hamm G., Hube B.;
RT "Candida albicans-secreted aspartic proteinases modify the epithelial
RT cytokine response in an in vitro model of vaginal candidiasis.";
RL Infect. Immun. 73:2758-2765(2005).
RN [14]
RP FUNCTION.
RX PubMed=19880183; DOI=10.1016/j.molimm.2009.08.019;
RA Gropp K., Schild L., Schindler S., Hube B., Zipfel P.F., Skerka C.;
RT "The yeast Candida albicans evades human complement attack by secretion of
RT aspartic proteases.";
RL Mol. Immunol. 47:465-475(2009).
RN [15]
RP FUNCTION.
RX PubMed=20713630; DOI=10.1128/iai.00789-10;
RA Pietrella D., Rachini A., Pandey N., Schild L., Netea M., Bistoni F.,
RA Hube B., Vecchiarelli A.;
RT "The Inflammatory response induced by aspartic proteases of Candida
RT albicans is independent of proteolytic activity.";
RL Infect. Immun. 78:4754-4762(2010).
RN [16]
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 [17]
RP FUNCTION, AND INDUCTION.
RX PubMed=22302440; DOI=10.1007/s11046-012-9522-2;
RA Ramage G., Coco B., Sherry L., Bagg J., Lappin D.F.;
RT "In vitro Candida albicans biofilm induced proteinase activity and SAP8
RT expression correlates with in vivo denture stomatitis severity.";
RL Mycopathologia 174:11-19(2012).
RN [18]
RP INDUCTION.
RX PubMed=23484407;
RA Staniszewska M., Bondaryk M., Siennicka K., Kurek A., Orlowski J.,
RA Schaller M., Kurzatkowski W.;
RT "In vitro study of secreted aspartyl proteinases Sap1 to Sap3 and Sap4 to
RT Sap6 expression in Candida albicans pleomorphic forms.";
RL Pol. J. Microbiol. 61:247-256(2012).
RN [19]
RP ACTIVITY REGULATION.
RX PubMed=23262278; DOI=10.1016/j.bcp.2012.12.008;
RA Cadicamo C.D., Mortier J., Wolber G., Hell M., Heinrich I.E., Michel D.,
RA Semlin L., Berger U., Korting H.C., Holtje H.D., Koksch B., Borelli C.;
RT "Design, synthesis, inhibition studies, and molecular modeling of pepstatin
RT analogues addressing different secreted aspartic proteinases of Candida
RT albicans.";
RL Biochem. Pharmacol. 85:881-887(2013).
RN [20]
RP FUNCTION.
RX PubMed=23927842; DOI=10.1016/j.peptides.2013.07.023;
RA Bochenska O., Rapala-Kozik M., Wolak N., Bras G., Kozik A., Dubin A.,
RA Aoki W., Ueda M., Mak P.;
RT "Secreted aspartic peptidases of Candida albicans liberate bactericidal
RT hemocidins from human hemoglobin.";
RL Peptides 48:49-58(2013).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 51-391.
RX PubMed=18384081; DOI=10.1002/prot.22021;
RA Borelli C., Ruge E., Lee J.H., Schaller M., Vogelsang A., Monod M.,
RA Korting H.C., Huber R., Maskos K.;
RT "X-ray structures of Sap1 and Sap5: structural comparison of the secreted
RT aspartic proteinases from Candida albicans.";
RL Proteins 72:1308-1319(2008).
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. Induces host
CC inflammatory cytokine production in a proteolytic activity-independent
CC way. Plays a role in tissue damage during superficial infection.
CC Moreover, acts toward human hemoglobin though limited proteolysis to
CC generate a variety of antimicrobial hemocidins, enabling to compete
CC with the other microorganisms of the same physiological niche using the
CC microbicidal peptides generated from the host protein.
CC {ECO:0000269|PubMed:10569787, ECO:0000269|PubMed:11478679,
CC ECO:0000269|PubMed:12761103, ECO:0000269|PubMed:15845479,
CC ECO:0000269|PubMed:19880183, ECO:0000269|PubMed:20713630,
CC ECO:0000269|PubMed:22302440, ECO:0000269|PubMed:23927842}.
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:9043112, ECO:0000269|PubMed:9841840};
CC -!- ACTIVITY REGULATION: Inhibited by pepstatin A analogs and squash
CC aspartic peptidase inhibitor (SQAPI). {ECO:0000269|PubMed:12203839,
CC ECO:0000269|PubMed:23262278}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 5.0. {ECO:0000269|PubMed:21646240,
CC ECO:0000269|PubMed:9043112};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11065355,
CC ECO:0000269|PubMed:9841840}.
CC -!- INDUCTION: Expressed during development of germ tubes, pseudohyphae,
CC true hyphae and opaque cells. Expressed in greater amounts in the
CC mature biofilms compared to early biofilms during inflammatory disorder
CC of the palatal mucosa among denture wearers. Regulated by growth phase
CC and alpha-pheromones. {ECO:0000269|PubMed:10569787,
CC ECO:0000269|PubMed:14555467, ECO:0000269|PubMed:1620110,
CC ECO:0000269|PubMed:22302440, ECO:0000269|PubMed:23484407}.
CC -!- PTM: O-glycosylated.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; CP017628; AOW30279.1; -; Genomic_DNA.
DR RefSeq; XP_718053.2; XM_712960.2.
DR PDB; 2QZW; X-ray; 2.05 A; A/B=51-391.
DR PDBsum; 2QZW; -.
DR AlphaFoldDB; P0CY27; -.
DR SMR; P0CY27; -.
DR STRING; 237561.P0CY27; -.
DR MEROPS; A01.014; -.
DR GeneID; 3640256; -.
DR KEGG; cal:CAALFM_C603490CA; -.
DR CGD; CAL0000189556; SAP1.
DR VEuPathDB; FungiDB:C6_03490C_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; P0CY27; -.
DR OMA; GIGYKTN; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR EvolutionaryTrace; P0CY27; -.
DR PHI-base; PHI:6783; -.
DR PHI-base; PHI:6789; -.
DR PHI-base; PHI:6811; -.
DR PRO; PR:P0CY27; -.
DR Proteomes; UP000000559; Chromosome 6.
DR GO; GO:0005576; C:extracellular region; IDA:CGD.
DR GO; GO:0009277; C:fungal-type cell wall; IBA:GO_Central.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0044406; P:adhesion of symbiont to host; IMP:CGD.
DR GO; GO:0031505; P:fungal-type cell wall organization; IBA:GO_Central.
DR GO; GO:0052391; P:induction by symbiont of defense-related host calcium ion flux; IDA:CGD.
DR GO; GO:0044416; P:induction by symbiont of host defense response; IDA:CGD.
DR GO; GO:0052559; P:induction by symbiont of host immune response; IDA:CGD.
DR GO; GO:0006807; P:nitrogen compound metabolic process; IMP:CGD.
DR GO; GO:0030163; P:protein catabolic process; IMP:CGD.
DR GO; GO:0019538; P:protein metabolic process; IDA:CGD.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0006465; P:signal peptide processing; IDA:CGD.
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; 2.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; Cleavage on pair of basic residues;
KW Disulfide bond; Glycoprotein; Hydrolase; Protease; Reference proteome;
KW Secreted; Signal; Virulence; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..50
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000413044"
FT CHAIN 51..391
FT /note="Candidapepsin-1"
FT /id="PRO_0000413045"
FT DOMAIN 64..377
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 82
FT ACT_SITE 267
FT BINDING 82..84
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 135..136
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 267..271
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT CARBOHYD 40
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 97..109
FT DISULFID 305..343
FT STRAND 53..59
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 64..70
FT /evidence="ECO:0007829|PDB:2QZW"
FT TURN 71..74
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 75..82
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 88..97
FT /evidence="ECO:0007829|PDB:2QZW"
FT TURN 106..109
FT /evidence="ECO:0007829|PDB:2QZW"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 124..133
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 139..151
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 154..171
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 173..175
FT /evidence="ECO:0007829|PDB:2QZW"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:2QZW"
FT HELIX 190..196
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 199..208
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 215..221
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 234..237
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 241..243
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 245..253
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 256..266
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 271..275
FT /evidence="ECO:0007829|PDB:2QZW"
FT HELIX 277..287
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 290..292
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 295..297
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 300..303
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 310..316
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 320..324
FT /evidence="ECO:0007829|PDB:2QZW"
FT HELIX 325..328
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 347..349
FT /evidence="ECO:0007829|PDB:2QZW"
FT HELIX 357..360
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 363..368
FT /evidence="ECO:0007829|PDB:2QZW"
FT TURN 369..372
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 373..379
FT /evidence="ECO:0007829|PDB:2QZW"
FT STRAND 387..389
FT /evidence="ECO:0007829|PDB:2QZW"
SQ SEQUENCE 391 AA; 41602 MW; CF88C56943BCCCA9 CRC64;
MFLKNIFIAL AIALLVDASP AKRSPGFVTL DFDVIKTPVN ATGQEGKVKR QAIPVTLNNE
HVSYAADITI GSNKQKFNVI VDTGSSDLWV PDASVTCDKP RPGQSADFCK GKGIYTPKSS
TTSQNLGTPF YIGYGDGSSS QGTLYKDTVG FGGASITKQV FADITKTSIP QGILGIGYKT
NEAAGDYDNV PVTLKNQGVI AKNAYSLYLN SPNAATGQII FGGVDKAKYS GSLIAVPVTS
DRELRITLNS LKAVGKNING NIDVLLDSGT TITYLQQDVA QDIIDAFQAE LKSDGQGHTF
YVTDCQTSGT VDFNFDNNAK ISVPASEFTA PLSYANGQPY PKCQLLLGIS DANILGDNFL
RSAYLVYDLD DDKISLAQVK YTSASNIAAL T
