CARP3_CANAL
ID CARP3_CANAL Reviewed; 398 AA.
AC P0CY29; A0A1D8PKC8; P43092; Q5ANA2;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Candidapepsin-3;
DE EC=3.4.23.24;
DE AltName: Full=ACP 3;
DE AltName: Full=Aspartate protease 3;
DE AltName: Full=Secreted aspartic protease 3;
DE Flags: Precursor;
GN Name=SAP3; OrderedLocusNames=CAALFM_C305230WA;
GN ORFNames=CaO19.13422, CaO19.6001;
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 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 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 [6]
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 [7]
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 [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 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 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 [11]
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 [12]
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 [13] {ECO:0007744|PDB:2H6S, ECO:0007744|PDB:2H6T}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 59-396 IN COMPLEXES WITH ZINC AND
RP PEPSTATIN A INHIBITOR.
RX PubMed=17510964; DOI=10.1002/prot.21425;
RA Borelli C., Ruge E., Schaller M., Monod M., Korting H.C., Huber R.,
RA Maskos K.;
RT "The crystal structure of the secreted aspartic proteinase 3 from Candida
RT albicans and its complex with pepstatin A.";
RL Proteins 68:738-748(2007).
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:19880183,
CC ECO:0000269|PubMed:20713630, 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.
CC {ECO:0000269|PubMed:23262278}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 3.0. {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. {ECO:0000269|PubMed:23484407}.
CC -!- PTM: O-glycosylated. {ECO:0000250}.
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; AOW28538.1; -; Genomic_DNA.
DR RefSeq; XP_723210.1; XM_718117.1.
DR PDB; 2H6S; X-ray; 2.20 A; A=59-398.
DR PDB; 2H6T; X-ray; 1.90 A; A=59-398.
DR PDBsum; 2H6S; -.
DR PDBsum; 2H6T; -.
DR AlphaFoldDB; P0CY29; -.
DR SMR; P0CY29; -.
DR STRING; 237561.P0CY29; -.
DR MEROPS; A01.061; -.
DR GeneID; 3635197; -.
DR KEGG; cal:CAALFM_C305230WA; -.
DR CGD; CAL0000201569; SAP3.
DR VEuPathDB; FungiDB:C3_05230W_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; P0CY29; -.
DR OMA; MHRIDIQ; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR EvolutionaryTrace; P0CY29; -.
DR PHI-base; PHI:6785; -.
DR PHI-base; PHI:6791; -.
DR PHI-base; PHI:6813; -.
DR PRO; PR:P0CY29; -.
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: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: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..58
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000413052"
FT CHAIN 59..398
FT /note="Candidapepsin-3"
FT /id="PRO_0000413053"
FT DOMAIN 72..384
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT REGION 103..139
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 90
FT ACT_SITE 274
FT BINDING 90..92
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:17510964,
FT ECO:0007744|PDB:2H6T"
FT BINDING 140..143
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:17510964,
FT ECO:0007744|PDB:2H6T"
FT BINDING 274..278
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000269|PubMed:17510964,
FT ECO:0007744|PDB:2H6T"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 313
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 105..116
FT DISULFID 312..350
FT STRAND 61..67
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 69..78
FT /evidence="ECO:0007829|PDB:2H6T"
FT TURN 79..82
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 83..90
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 96..105
FT /evidence="ECO:0007829|PDB:2H6T"
FT HELIX 115..117
FT /evidence="ECO:0007829|PDB:2H6T"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 131..140
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 146..158
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 161..174
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:2H6T"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:2H6T"
FT HELIX 197..203
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 206..215
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 222..228
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 230..232
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 235..244
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 248..250
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 252..260
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 263..273
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 278..282
FT /evidence="ECO:0007829|PDB:2H6T"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 297..300
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 306..310
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 316..323
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 327..331
FT /evidence="ECO:0007829|PDB:2H6T"
FT HELIX 332..335
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 336..340
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 346..356
FT /evidence="ECO:0007829|PDB:2H6T"
FT HELIX 364..367
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 370..375
FT /evidence="ECO:0007829|PDB:2H6T"
FT TURN 376..379
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 380..386
FT /evidence="ECO:0007829|PDB:2H6T"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:2H6T"
SQ SEQUENCE 398 AA; 42806 MW; D9A8687FBAD4C448 CRC64;
MFLKNIFIAL AIALLADATP TTFNNSPGFV ALNFDVIKTH KNVTGPQGEI NTNVNVKRQT
VPVKLINEQV SYASDITVGS NKQKLTVVID TGSSDLWVPD SQVSCQAGQG QDPNFCKNEG
TYSPSSSSSS QNLNSPFSIE YGDGTTSQGT WYKDTIGFGG ISITKQQFAD VTSTSVDQGI
LGIGYKTHEA EGNYDNVPVT LKNQGIISKN AYSLYLNSRQ ATSGQIIFGG VDNAKYSGTL
IALPVTSDNE LRIHLNTVKV AGQSINADVD VLLDSGTTIT YLQQGVADQV ISAFNGQETY
DANGNLFYLV DCNLSGSVDF AFDKNAKISV PASEFTAPLY TEDGQVYDQC QLLFGTSDYN
ILGDNFLRSA YIVYDLDDNE ISLAQVKYTT ASNIAALT
