CARP4_CANAL
ID CARP4_CANAL Reviewed; 417 AA.
AC Q5A8N2; A0A1D8PQ73;
DT 13-NOV-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Candidapepsin-4;
DE EC=3.4.23.24;
DE AltName: Full=ACP 4;
DE AltName: Full=Aspartate protease 4;
DE AltName: Full=Secreted aspartic protease 4;
DE Flags: Precursor;
GN Name=SAP4; OrderedLocusNames=CAALFM_C603500CA;
GN ORFNames=CaO19.13139, CaO19.5716;
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 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 [5]
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 [6]
RP ACTIVITY REGULATION.
RX PubMed=12203839; DOI=10.1002/jmr.568;
RA Farley P.C., Christeller J.T., Sullivan M.E., Sullivan P.A., Laing W.A.;
RT "Analysis of the interaction between the aspartic peptidase inhibitor SQAPI
RT and aspartic peptidases using surface plasmon resonance.";
RL J. Mol. Recognit. 15:135-144(2002).
RN [7]
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 [8]
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 [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 INDUCTION.
RX PubMed=22433888;
RA Khodavandi A., Alizadeh F., Harmal N.S., Sidik S.M., Othman F., Sekawi Z.,
RA Chong P.P.;
RT "Expression analysis of SIR2 and SAPs1-4 gene expression in Candida
RT albicans treated with allicin compared to fluconazole.";
RL Trop. Biomed. 28:589-598(2011).
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).
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. Activates host
CC systemic immunity. During infection, plays an important role in
CC penetration into deeper tissues and interaction with host defense.
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:21540243, 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: Activity is inhibited by squash aspartic peptidase
CC inhibitor (SQAPI). {ECO:0000269|PubMed:12203839}.
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. Expression is suppressed by
CC fluconazole. {ECO:0000269|PubMed:15123810, ECO:0000269|PubMed:15731084,
CC ECO:0000269|PubMed:22433888, 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; AOW30280.1; -; Genomic_DNA.
DR RefSeq; XP_718054.1; XM_712961.1.
DR AlphaFoldDB; Q5A8N2; -.
DR SMR; Q5A8N2; -.
DR STRING; 237561.Q5A8N2; -.
DR MEROPS; A01.062; -.
DR GeneID; 3640257; -.
DR KEGG; cal:CAALFM_C603500CA; -.
DR CGD; CAL0000194858; SAP4.
DR VEuPathDB; FungiDB:C6_03500C_A; -.
DR eggNOG; KOG1339; Eukaryota.
DR HOGENOM; CLU_013253_9_1_1; -.
DR InParanoid; Q5A8N2; -.
DR OMA; NEAYVAD; -.
DR OrthoDB; 753343at2759; -.
DR BRENDA; 3.4.23.24; 1096.
DR PHI-base; PHI:6786; -.
DR PHI-base; PHI:6792; -.
DR PHI-base; PHI:6807; -.
DR PHI-base; PHI:6814; -.
DR PRO; PR:Q5A8N2; -.
DR Proteomes; UP000000559; Chromosome 6.
DR GO; GO:0005576; C:extracellular region; 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:0042783; P:evasion of host immune response; IEP: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; 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; Repeat; Secreted;
KW Signal; Virulence; Zymogen.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT PROPEP 19..75
FT /note="Activation peptide"
FT /evidence="ECO:0000250"
FT /id="PRO_0000424296"
FT CHAIN 76..417
FT /note="Candidapepsin-4"
FT /id="PRO_0000424297"
FT DOMAIN 89..403
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10094"
FT ACT_SITE 293
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 293..297
FT /ligand="pepstatin A"
FT /ligand_id="ChEBI:CHEBI:190525"
FT /ligand_note="inhibitor"
FT /evidence="ECO:0000250|UniProtKB:P0CY29"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 122..134
FT /evidence="ECO:0000250"
FT DISULFID 331..369
FT /evidence="ECO:0000250"
SQ SEQUENCE 417 AA; 45332 MW; 796346A4469FB60A CRC64;
MFLQNILSVL AFALLIDAAP VKRSTGFVTL DFNVKRSLVD PKDPTVEVKR SPLFLDIEPT
EIPVDDTGRN DVGKRGPVAV KLDNEIITYS ADITIGSNNQ KLSVIVDTGS SDLWVPDSNA
VCIPKWPGDR GDFCKNNGSY SPAASSTSKN LNTPFEIKYA DGSVAQGNLY QDTVGIGGVS
VRDQLFANVR STSAHKGILG IGFQSNEATR TPYDNLPITL KKQGIISKNA YSLFLNSPEA
SSGQIIFGGI DKAKYSGSLV DLPITSDRTL SVGLRSVNVM GQNVNVNAGV LLDSGTTISY
FTPNIARSII YALGGQVHYD SSGNEAYVAD CKTSGTVDFQ FDRNLKISVP ASEFLYQLYY
TNGEPYPKCE IRVRESEDNI LGDNFMRSAY IVYDLDDRKI SMAQVKYTSQ SNIVAIN
