CARP9_CANAL
ID CARP9_CANAL Reviewed; 544 AA.
AC Q59SU1; A0A1D8PJX2;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 2.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Candidapepsin-9;
DE EC=3.4.23.24;
DE AltName: Full=ACP 9;
DE AltName: Full=Aspartate protease 9;
DE AltName: Full=Secreted aspartic protease 9;
DE Flags: Precursor;
GN Name=SAP9; Synonyms=YPS1; OrderedLocusNames=CAALFM_C303870CA;
GN ORFNames=CaO19.14190, CaO19.6928;
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 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 [6]
RP GLYCOSYLATION, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=16269404; DOI=10.1074/jbc.m509297200;
RA Albrecht A., Felk A., Pichova I., Naglik J.R., Schaller M., de Groot P.,
RA Maccallum D., Odds F.C., Schafer W., Klis F., Monod M., Hube B.;
RT "Glycosylphosphatidylinositol-anchored proteases of Candida albicans target
RT proteins necessary for both cellular processes and host-pathogen
RT interactions.";
RL J. Biol. Chem. 281:688-694(2006).
RN [7]
RP FUNCTION.
RX PubMed=19805528; DOI=10.1128/iai.00723-09;
RA Hornbach A., Heyken A., Schild L., Hube B., Loffler J., Kurzai O.;
RT "The glycosylphosphatidylinositol-anchored protease Sap9 modulates the
RT interaction of Candida albicans with human neutrophils.";
RL Infect. Immun. 77:5216-5224(2009).
RN [8]
RP SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=21622905; DOI=10.1128/ec.05011-11;
RA Sorgo A.G., Heilmann C.J., Dekker H.L., Bekker M., Brul S., de Koster C.G.,
RA de Koning L.J., Klis F.M.;
RT "Effects of fluconazole on the secretome, the wall proteome, and wall
RT integrity of the clinical fungus Candida albicans.";
RL Eukaryot. Cell 10:1071-1081(2011).
RN [9]
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 [10]
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. Involved in
CC triggering host polymorphonuclear neutrophils chemotaxis toward germ
CC tubes. Moreover, acts toward human hemoglobin though limited
CC proteolysis to generate a variety of antimicrobial hemocidins, enabling
CC to compete with the other microorganisms of the same physiological
CC niche using the microbicidal peptides generated from the host protein.
CC Required for cell surface integrity and cell separation during budding.
CC {ECO:0000269|PubMed:15820985, ECO:0000269|PubMed:16269404,
CC ECO:0000269|PubMed:19805528, 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 5.5. {ECO:0000269|PubMed:21646240};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Lipid-anchor, GPI-
CC anchor {ECO:0000305}. Secreted, cell wall {ECO:0000269|PubMed:16269404,
CC ECO:0000269|PubMed:21622905}.
CC -!- INDUCTION: Induced by fluconazole. Expression is regulated by growth
CC phase, temperature, and white-opaque switch.
CC {ECO:0000269|PubMed:15820985, ECO:0000269|PubMed:21622905,
CC ECO:0000269|PubMed:9802014}.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
CC -!- PTM: The GPI-anchor is attached to the protein in the endoplasmic
CC reticulum and serves to target the protein to the cell surface. There,
CC the glucosamine-inositol phospholipid moiety is cleaved off and the
CC GPI-modified mannoprotein is covalently attached via its lipidless GPI
CC glycan remnant to the 1,6-beta-glucan of the outer cell wall layer.
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; CP017625; AOW28414.1; -; Genomic_DNA.
DR RefSeq; XP_712729.2; XM_707636.2.
DR AlphaFoldDB; Q59SU1; -.
DR SMR; Q59SU1; -.
DR STRING; 237561.Q59SU1; -.
DR MEROPS; A01.067; -.
DR PRIDE; Q59SU1; -.
DR GeneID; 3645625; -.
DR KEGG; cal:CAALFM_C303870CA; -.
DR CGD; CAL0000194661; SAP9.
DR VEuPathDB; FungiDB:C3_03870C_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; Q59SU1; -.
DR OMA; IWGYDDV; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR PRO; PR:Q59SU1; -.
DR Proteomes; UP000000559; Chromosome 3.
DR GO; GO:0031225; C:anchored component of membrane; IDA:CGD.
DR GO; GO:0046658; C:anchored component of plasma membrane; IDA:CGD.
DR GO; GO:0009986; C:cell surface; IDA:CGD.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:1903561; C:extracellular vesicle; IDA:CGD.
DR GO; GO:0009277; C:fungal-type cell wall; IDA:CGD.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IDA:CGD.
DR GO; GO:0044406; P:adhesion of symbiont to host; IMP:CGD.
DR GO; GO:0031505; P:fungal-type cell wall organization; IMP:CGD.
DR GO; GO:0052155; P:modulation by symbiont of host cell-mediated immune response; IMP:CGD.
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; 2.
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; Cell membrane; Cell wall;
KW Cleavage on pair of basic residues; Disulfide bond; Glycoprotein;
KW GPI-anchor; Hydrolase; Lipoprotein; Membrane; Protease; Reference proteome;
KW Repeat; Secreted; Signal; Transmembrane; Transmembrane helix; Virulence;
KW Zymogen.
FT SIGNAL 1..17
FT /evidence="ECO:0000255"
FT CHAIN 18..520
FT /note="Candidapepsin-9"
FT /id="PRO_0000424304"
FT PROPEP 521..544
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000424305"
FT TRANSMEM 524..544
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 65..479
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT REGION 31..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 500..519
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 31..49
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 83
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 371
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT LIPID 520
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT CARBOHYD 212
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 252
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 422
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 499
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 98..195
FT /evidence="ECO:0000250"
SQ SEQUENCE 544 AA; 58483 MW; 4EC6144F27F97B47 CRC64;
MRLNSVALLS LVATALAAKA PFKIDFEVRR GESKDDLSPE DDSNPRFVKR DGSLDMTLTN
KQTFYMATLK IGSNEDENRV LVDTGSSDLW VMSHDLKCVS APNSKRNERS FGHGTGVKLN
ERELMQKRKN LYQPSRTIET DEEKEASEKI HNKLFGFGSI YSTVYITEGP GAYSTFSPFV
GTEGGSGGSG GSNTCTSYGS FNTENSDTFK KNNTNDFEIQ YADDTSAIGI WGYDDVTISN
VTVKDLSFAI ANETSSDVGV LGIGLPGLEV TTQYGYTYQN LPLKLKADGI IAKSLYSLYL
NTADAKAGSI LFGAIDHAKY QGDLVTVKMM RTYSQISYPV RIQVPVSKID VESSSGSTTN
ILSSTTGVVL DTGSTLSYVF SDTLQSLGKA LNGQYSNSVG AYVVNCNLAD SSRTVDIEFG
GNKTIKVPIS DLVLQASKST CILGVMQQSS SSSYMLFGDN ILRSAYIVYD LDDYEVSLAQ
VSYTNKESIE VIGASGITNS SGSGTTSSSG TSTSTSTRHS AGSIISKPVY GLLLSLLISC
YVLV
