CARP6_CANAL
ID CARP6_CANAL Reviewed; 418 AA.
AC Q5AC08; A0A1D8PPY9; Q5ACC9;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Candidapepsin-6;
DE EC=3.4.23.24;
DE AltName: Full=ACP 6;
DE AltName: Full=Aspartate protease 6;
DE AltName: Full=Secreted aspartic protease 6;
DE Flags: Precursor;
GN Name=SAP6; OrderedLocusNames=CAALFM_C602710CA;
GN ORFNames=CaO19.12988, CaO19.5542;
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], AND INDUCTION.
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 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 [5]
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 [6]
RP FUNCTION.
RX PubMed=12065511; DOI=10.1128/iai.70.7.3689-3700.2002;
RA Felk A., Kretschmar M., Albrecht A., Schaller M., Beinhauer S.,
RA Nichterlein T., Sanglard D., Korting H.C., Schafer W., Hube B.;
RT "Candida albicans hyphal formation and the expression of the Efg1-regulated
RT proteinases Sap4 to Sap6 are required for the invasion of parenchymal
RT organs.";
RL Infect. Immun. 70:3689-3700(2002).
RN [7]
RP FUNCTION.
RX PubMed=17652724; DOI=10.1167/iovs.07-0114;
RA Jackson B.E., Wilhelmus K.R., Hube B.;
RT "The role of secreted aspartyl proteinases in Candida albicans keratitis.";
RL Invest. Ophthalmol. Vis. Sci. 48:3559-3565(2007).
RN [8]
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 [9]
RP FUNCTION.
RX PubMed=21540243; DOI=10.1242/dmm.006627;
RA Glittenberg M.T., Kounatidis I., Christensen D., Kostov M., Kimber S.,
RA Roberts I., Ligoxygakis P.;
RT "Pathogen and host factors are needed to provoke a systemic host response
RT to gastrointestinal infection of Drosophila larvae by Candida albicans.";
RL Dis. Model. Mech. 4:515-525(2011).
RN [10]
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 [11]
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 [12]
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 [13]
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 [14]
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. During
CC infection, plays an important role in penetration into deeper tissues
CC and interaction with host defense. Activates host systemic immunity and
CC induces host inflammatory cytokine production in a proteolytic
CC activity-independent way. Contributes to corneal pathogenicity.
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:12065511,
CC ECO:0000269|PubMed:17652724, ECO:0000269|PubMed:20713630,
CC ECO:0000269|PubMed:21540243, ECO:0000269|PubMed:22302440,
CC 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};
CC -!- ACTIVITY REGULATION: Inhibited by pepstatin A analogs.
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:0000250}.
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. {ECO:0000269|PubMed:15123810,
CC ECO:0000269|PubMed:22302440, ECO:0000269|PubMed:23484407}.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; CP017628; AOW30203.1; -; Genomic_DNA.
DR RefSeq; XP_719105.1; XM_714012.1.
DR AlphaFoldDB; Q5AC08; -.
DR SMR; Q5AC08; -.
DR STRING; 237561.Q5AC08; -.
DR MEROPS; A01.064; -.
DR GeneID; 3639229; -.
DR KEGG; cal:CAALFM_C602710CA; -.
DR CGD; CAL0000179762; SAP6.
DR VEuPathDB; FungiDB:C6_02710C_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; Q5AC08; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR PHI-base; PHI:6788; -.
DR PHI-base; PHI:6794; -.
DR PHI-base; PHI:6809; -.
DR PHI-base; PHI:6816; -.
DR PRO; PR:Q5AC08; -.
DR Proteomes; UP000000559; Chromosome 6.
DR GO; GO:0005576; C:extracellular region; IDA:CGD.
DR GO; GO:0062040; C:fungal biofilm matrix; IDA:CGD.
DR GO; GO:0009277; C:fungal-type cell wall; IBA:GO_Central.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:CGD.
DR GO; GO:0002253; P:activation of immune response; 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:0019538; P:protein metabolic process; IDA:CGD.
DR GO; GO:0006508; P:proteolysis; IDA:CGD.
DR GO; GO:0006465; P:signal peptide processing; IDA:CGD.
DR GO; GO:0044010; P:single-species biofilm formation; IMP: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; Disulfide bond;
KW Glycoprotein; Hydrolase; Protease; Reference proteome; Secreted; Signal;
KW Virulence; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..76
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000424298"
FT CHAIN 77..418
FT /note="Candidapepsin-6"
FT /id="PRO_0000424299"
FT DOMAIN 90..404
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 108
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 294
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT BINDING 108..110
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 161..162
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 294..298
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT CARBOHYD 138
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 123..135
FT /evidence="ECO:0000250"
FT DISULFID 332..370
FT /evidence="ECO:0000250"
SQ SEQUENCE 418 AA; 45432 MW; 8ED0F1C0240FF989 CRC64;
MLLKNILSVL AFALLIDAAP VKRSPGFVTL DFNVKRSLVD PDDPTVESKR SPLFLDLDPT
KIPVDDTGRN DGVDKRGPVA VKLDNEIITY SADITVGSNN QKLSVIVDTG SSDLWIPDSK
AICIPKWRGD RGDFCKNNGS YSPAASSTSK NLNTRFEIKY ADGSYAKGNL YQDTVGIGGA
SVKNQLFANV WSTSAHKGIL GIGFQANEAT RTPYDNLPIS LKKQGIIAKN AYSLFLNSPE
ASSGQIIFGG IDKAKYSGSL VELPITSDRT LSVGLRSVNV MGRNVNVNAG VLLDSGTTIS
YFTPSIARSI IYALGGQVHF DSAGNKAYVA DCKTSGTVDF QFDKNLKISV PASEFLYQLY
YTNGKPYPKC EIRVRESEDN ILGDNFMRSA YIVYDLDDKK ISMAQVKYTS ESNIVAIN
