CARP5_CANAL
ID CARP5_CANAL Reviewed; 418 AA.
AC P43094; A0A1D8PQ36; Q5ABW5;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Candidapepsin-5;
DE EC=3.4.23.24;
DE AltName: Full=ACP 5;
DE AltName: Full=Aspartate protease 5;
DE AltName: Full=Secreted aspartic protease 5;
DE Flags: Precursor;
GN Name=SAP5; OrderedLocusNames=CAALFM_C603030WA;
GN ORFNames=CaO19.13032, CaO19.5585;
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].
RC STRAIN=C74;
RX PubMed=7984113; DOI=10.1111/j.1365-2958.1994.tb00429.x;
RA Monod M., Togni G., Hube B., Sanglard D.;
RT "Multiplicity of genes encoding secreted aspartic proteinases in Candida
RT species.";
RL Mol. Microbiol. 13:357-368(1994).
RN [2]
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 [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 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 INDUCTION.
RX PubMed=15731084; DOI=10.1128/iai.73.3.1828-1835.2005;
RA Taylor B.N., Staib P., Binder A., Biesemeier A., Sehnal M., Rollinghoff M.,
RA Morschhauser J., Schroppel K.;
RT "Profile of Candida albicans-secreted aspartic proteinase elicited during
RT vaginal infection.";
RL Infect. Immun. 73:1828-1835(2005).
RN [7]
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 [8]
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 [9]
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 [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. During
CC infection, plays an important role in penetration into deeper tissues
CC and interaction with host defense. Moreover, acts toward human
CC hemoglobin though limited proteolysis to generate a variety of
CC 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:11478679,
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 -!- 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 -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- INDUCTION: Expressed during development of germ tubes, pseudohyphae and
CC true hyphae. Induced during host infection.
CC {ECO:0000269|PubMed:15123810, ECO:0000269|PubMed:15731084,
CC 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; Z30191; CAA82923.1; -; Genomic_DNA.
DR EMBL; CP017628; AOW30234.1; -; Genomic_DNA.
DR PIR; S49056; S42072.
DR RefSeq; XP_719147.1; XM_714054.1.
DR PDB; 2QZX; X-ray; 2.50 A; A/B=77-418.
DR PDBsum; 2QZX; -.
DR AlphaFoldDB; P43094; -.
DR SMR; P43094; -.
DR STRING; 237561.P43094; -.
DR ChEMBL; CHEMBL6019; -.
DR MEROPS; A01.063; -.
DR GeneID; 3639268; -.
DR KEGG; cal:CAALFM_C603030WA; -.
DR CGD; CAL0000193807; SAP5.
DR VEuPathDB; FungiDB:C6_03030W_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; P43094; -.
DR OMA; TKKYKGD; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR EvolutionaryTrace; P43094; -.
DR PHI-base; PHI:126; -.
DR PHI-base; PHI:6787; -.
DR PHI-base; PHI:6793; -.
DR PHI-base; PHI:6808; -.
DR PHI-base; PHI:6815; -.
DR PRO; PR:P43094; -.
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:0031505; P:fungal-type cell wall organization; IBA:GO_Central.
DR GO; GO:0006508; P:proteolysis; 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 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..76
FT /note="Activation peptide"
FT /evidence="ECO:0000255"
FT /id="PRO_0000025856"
FT CHAIN 77..418
FT /note="Candidapepsin-5"
FT /id="PRO_0000025857"
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 DISULFID 123..135
FT /evidence="ECO:0000250"
FT DISULFID 332..370
FT /evidence="ECO:0000250"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 90..96
FT /evidence="ECO:0007829|PDB:2QZX"
FT TURN 97..100
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 101..108
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 114..123
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:2QZX"
FT HELIX 134..136
FT /evidence="ECO:0007829|PDB:2QZX"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 150..159
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 165..177
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 180..193
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 195..197
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:2QZX"
FT HELIX 205..207
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:2QZX"
FT HELIX 217..223
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 226..235
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 242..248
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 250..252
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 255..258
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 268..270
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 272..280
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 283..293
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:2QZX"
FT HELIX 304..314
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 317..320
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 326..330
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 337..342
FT /evidence="ECO:0007829|PDB:2QZX"
FT TURN 343..345
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 346..351
FT /evidence="ECO:0007829|PDB:2QZX"
FT HELIX 352..355
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 368..376
FT /evidence="ECO:0007829|PDB:2QZX"
FT HELIX 384..387
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 390..395
FT /evidence="ECO:0007829|PDB:2QZX"
FT TURN 396..399
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 400..406
FT /evidence="ECO:0007829|PDB:2QZX"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:2QZX"
SQ SEQUENCE 418 AA; 45649 MW; 185B00E6BA4AD1E6 CRC64;
MFLKNILSVL AFALLIDAAP VKRSPGFVTL DFNVKRSLVD PDDPTVEAKR SPLFLEFTPS
EFPVDETGRD GDVDKRGPVA VTLHNEAITY TADITVGSDN QKLNVIVDTG SSDLWIPDSN
VICIPKWRGD KGDFCKSAGS YSPASSRTSQ NLNTRFDIKY GDGSYAKGKL YKDTVGIGGV
SVRDQLFANV WSTSARKGIL GIGFQSGEAT EFDYDNLPIS LRNQGIIGKA AYSLYLNSAE
ASTGQIIFGG IDKAKYSGSL VDLPITSEKK LTVGLRSVNV RGRNVDANTN VLLDSGTTIS
YFTRSIVRNI LYAIGAQMKF DSAGNKVYVA DCKTSGTIDF QFGNNLKISV PVSEFLFQTY
YTSGKPFPKC EVRIRESEDN ILGDNFLRSA YVVYNLDDKK ISMAPVKYTS ESDIVAIN
