CARP2_CANAL
ID CARP2_CANAL Reviewed; 398 AA.
AC P0DJ06; A0A1D8PTK5; P28871; P43097; Q59MV8; Q8NKF0; Q8NKF1;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 62.
DE RecName: Full=Candidapepsin-2;
DE EC=3.4.23.24;
DE AltName: Full=ACP 2;
DE AltName: Full=Aspartate protease 2;
DE AltName: Full=Secreted aspartic protease 2;
DE Flags: Precursor;
GN Name=SAP2; Synonyms=PEP11, PRA11, PRA2; OrderedLocusNames=CAALFM_CR07800WA;
GN ORFNames=CaO19.11193, CaO19.3708;
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 [GENOMIC DNA], AND VARIANTS GLY-9 AND LEU-273.
RC STRAIN=SC5314 / CAI4 / ATCC MYA-682;
RX PubMed=12028383; DOI=10.1046/j.1365-2958.2002.02967.x;
RA Staib P., Kretschmar M., Nichterlein T., Hof H., Morschhauser J.;
RT "Host versus in vitro signals and intrastrain allelic differences in the
RT expression of a Candida albicans virulence gene.";
RL Mol. Microbiol. 44:1351-1366(2002).
RN [2]
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 [3]
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 [4]
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 [5]
RP PROTEIN SEQUENCE OF 57-71.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=1879921; DOI=10.1128/iai.59.9.2972-2977.1991;
RA Ganesan K., Banerjee A., Datta A.;
RT "Molecular cloning of the secretory acid proteinase gene from Candida
RT albicans and its use as a species-specific probe.";
RL Infect. Immun. 59:2972-2977(1991).
RN [6]
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 [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 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 [9]
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 [10]
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 [11]
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 [12]
RP FUNCTION, AND INDUCTION.
RX PubMed=15820985; DOI=10.1093/jac/dki088;
RA Copping V.M.S., Barelle C.J., Hube B., Gow N.A.R., Brown A.J.P., Odds F.C.;
RT "Exposure of Candida albicans to antifungal agents affects expression of
RT SAP2 and SAP9 secreted proteinase genes.";
RL J. Antimicrob. Chemother. 55:645-654(2005).
RN [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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).
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:11478679, ECO:0000269|PubMed:12761103,
CC ECO:0000269|PubMed:15820985, 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 squash aspartic peptidase inhibitor
CC (SQAPI). {ECO:0000269|PubMed:12203839}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 4.0. {ECO:0000269|PubMed:21646240,
CC ECO:0000269|PubMed:9043112};
CC -!- SUBUNIT: Monomer.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:9841840}.
CC -!- INDUCTION: Expressed during development of germ tubes, pseudohyphae and
CC true hyphae. Expressed in greater amounts in the mature biofilms
CC compared to early biofilms during inflammatory disorder of the palatal
CC mucosa among denture wearers. Induced by fluconazole.
CC {ECO:0000269|PubMed:15820985, ECO:0000269|PubMed:22302440,
CC ECO:0000269|PubMed:23484407}.
CC -!- PTM: O-glycosylated.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; AF481100; AAM21050.1; -; Genomic_DNA.
DR EMBL; AF481101; AAM21051.1; -; Genomic_DNA.
DR EMBL; CP017630; AOW31471.1; -; Genomic_DNA.
DR PIR; A45280; A45280.
DR RefSeq; XP_711047.1; XM_705955.2.
DR AlphaFoldDB; P0DJ06; -.
DR SMR; P0DJ06; -.
DR STRING; 237561.P0DJ06; -.
DR DrugBank; DB03241; 1-Amino-1-Carbonyl Pentane.
DR DrugBank; DB04387; 1-Hydroxy-2-Amino-3-Cyclohexylpropane.
DR DrugBank; DB04451; 4-Methylpiperazin-1-Yl Carbonyl Group.
DR DrugBank; DB03659; Butylamine.
DR DrugBank; DB03090; Ethylaminobenzylmethylcarbonyl Group.
DR MEROPS; A01.060; -.
DR GeneID; 3647354; -.
DR KEGG; cal:CAALFM_CR07800WA; -.
DR CGD; CAL0000196689; SAP2.
DR VEuPathDB; FungiDB:CR_07800W_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; P0DJ06; -.
DR OMA; LWVPDVN; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR EvolutionaryTrace; P0DJ06; -.
DR PHI-base; PHI:6784; -.
DR PHI-base; PHI:6790; -.
DR PHI-base; PHI:6812; -.
DR PHI-base; PHI:72; -.
DR PRO; PR:P0DJ06; -.
DR Proteomes; UP000000559; Chromosome R.
DR GO; GO:0005576; C:extracellular region; IDA:CGD.
DR GO; GO:1903561; C:extracellular vesicle; 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:0006807; P:nitrogen compound metabolic process; IMP:CGD.
DR GO; GO:0030163; P:protein catabolic process; IDA: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 Aspartyl protease; Cleavage on pair of basic residues;
KW Direct protein sequencing; Disulfide bond; Glycoprotein; Hydrolase;
KW Protease; Reference proteome; Secreted; Signal; Virulence; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..56
FT /note="Activation peptide"
FT /evidence="ECO:0000269|PubMed:1879921"
FT /id="PRO_0000413048"
FT CHAIN 57..398
FT /note="Candidapepsin-2"
FT /id="PRO_0000413049"
FT DOMAIN 70..384
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 88
FT ACT_SITE 274
FT BINDING 88..90
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 141..142
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 274..278
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT CARBOHYD 313
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 103..115
FT DISULFID 312..350
FT VARIANT 9
FT /note="A -> G (in allele SAP2-1)"
FT /evidence="ECO:0000269|PubMed:12028383"
FT VARIANT 273
FT /note="V -> L (in allele SAP2-1)"
FT /evidence="ECO:0000269|PubMed:12028383"
SQ SEQUENCE 398 AA; 42316 MW; 53F2AF1ADDBFADAA CRC64;
MFLKNIFIAL AIALLVDATP TTTKRSAGFV ALDFSVVKTP KAFPVTNGQE GKTSKRQAVP
VTLHNEQVTY AADITVGSNN QKLNVIVDTG SSDLWVPDVN VDCQVTYSDQ TADFCKQKGT
YDPSGSSASQ DLNTPFKIGY GDGSSSQGTL YKDTVGFGGV SIKNQVLADV DSTSIDQGIL
GVGYKTNEAG GSYDNVPVTL KKQGVIAKNA YSLYLNSPDA ATGQIIFGGV DNAKYSGSLI
ALPVTSDREL RISLGSVEVS GKTINTDNVD VLVDSGTTIT YLQQDLADQI IKAFNGKLTQ
DSNGNSFYEV DCNLSGDVVF NFSKNAKISV PASEFAASLQ GDDGQPYDKC QLLFDVNDAN
ILGDNFLRSA YIVYDLDDNE ISLAQVKYTS ASSISALT
