CARP8_CANAL
ID CARP8_CANAL Reviewed; 405 AA.
AC Q5AEM6; A0A1D8PJG6;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Candidapepsin-8;
DE EC=3.4.23.24;
DE AltName: Full=ACP 8;
DE AltName: Full=Aspartate protease 8;
DE AltName: Full=Secreted aspartic protease 8;
DE Flags: Precursor;
GN Name=SAP8; OrderedLocusNames=CAALFM_C302510CA;
GN ORFNames=CaO19.242, CaO19.7872;
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=9802014; DOI=10.1099/00221287-144-10-2731;
RA Monod M., Hube B., Hess D., Sanglard D.;
RT "Differential regulation of SAP8 and SAP9, which encode two new members of
RT the secreted aspartic proteinase family in Candida albicans.";
RL Microbiology 144:2731-2737(1998).
RN [5]
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 [6]
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 [7]
RP FUNCTION.
RX PubMed=23139737; DOI=10.1371/journal.pone.0046020;
RA Puri S., Kumar R., Chadha S., Tati S., Conti H.R., Hube B., Cullen P.J.,
RA Edgerton M.;
RT "Secreted aspartic protease cleavage of Candida albicans Msb2 activates
RT Cek1 MAPK signaling affecting biofilm formation and oropharyngeal
RT candidiasis.";
RL PLoS ONE 7:E46020-E46020(2012).
RN [8]
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. Serves as a
CC major regulator of MSB2-processing which activates CEK1 MAPK-signaling
CC affecting biofilm formation and oropharyngeal candidiasis. Moreover,
CC acts toward human hemoglobin though limited proteolysis to generate a
CC variety of antimicrobial hemocidins, enabling to compete with the other
CC microorganisms of the same physiological niche using the microbicidal
CC peptides generated from the host protein. {ECO:0000269|PubMed:22302440,
CC ECO:0000269|PubMed:23139737, 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 -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 2.5. {ECO:0000269|PubMed:21646240};
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- INDUCTION: Expressed in greater amounts in the mature biofilms compared
CC to early biofilms during inflammatory disorder of the palatal mucosa
CC among denture wearers. {ECO:0000269|PubMed:22302440,
CC ECO:0000269|PubMed:9802014}.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; CP017625; AOW28286.1; -; Genomic_DNA.
DR RefSeq; XP_719941.1; XM_714848.2.
DR AlphaFoldDB; Q5AEM6; -.
DR SMR; Q5AEM6; -.
DR STRING; 237561.Q5AEM6; -.
DR MEROPS; A01.066; -.
DR GeneID; 3638371; -.
DR KEGG; cal:CAALFM_C302510CA; -.
DR CGD; CAL0000190503; SAP8.
DR VEuPathDB; FungiDB:C3_02510C_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; Q5AEM6; -.
DR OMA; EDNHILC; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR PRO; PR:Q5AEM6; -.
DR Proteomes; UP000000559; Chromosome 3.
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:CGD.
DR GO; GO:0031505; P:fungal-type cell wall organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; 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; 1.
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..23
FT /evidence="ECO:0000255"
FT PROPEP 24..75
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000424302"
FT CHAIN 76..405
FT /note="Candidapepsin-8"
FT /id="PRO_0000424303"
FT DOMAIN 89..392
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT REGION 52..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 292
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT BINDING 107..109
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 160..161
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT BINDING 292..296
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT DISULFID 122..134
FT /evidence="ECO:0000250"
FT DISULFID 327..358
FT /evidence="ECO:0000250"
SQ SEQUENCE 405 AA; 43037 MW; A667BD901C6860A1 CRC64;
MVSIITFTKN VLVTLAFALL AQGLAIPEDI DKRAEKVVSL DFTVTRKPFN ATAHGQHHQS
QQQQQQQQQQ PAQKRGTVQT SLINEGPSYA ATITVGSNKQ QQTVIVDTGS SDLWVVDSAA
VCQVTYPGQS PTFCKQDGTY KPSSSTTSQN LGKAFSIRYE DGSSSQGTVY KDTVGLGGAS
ITNQQFADVT TTSVDQGILG IGFTGDESSP TYDNVPVTLK KQGIINKNAY SLYLNSASAS
SGTIIFGGVD NAKYTGSLTA LPITSSNELR VQLSTINIAG TTVSASTTPV LDSGTTLTYF
SQTIADKLAA AVGAKWNSYY QLYTSSCNLA GNIVFNFAKG VTISVPLSEF VLQDGNSCYF
GVSRDSATIL GDNFLRRAYA VYDLDGNTIS LAQVKYTTSS SISTL
