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P0CY27 (CARP1_CANAL) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 20. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Candidapepsin-1

EC=3.4.23.24
Alternative name(s):
ACP 1
Aspartate protease 1
Secreted aspartic protease 1
Gene names
Name:SAP1
Synonyms:PEP1, PEP10, PRA10, PRA3
ORF Names:CaO19.13137, CaO19.5714
OrganismCandida albicans (strain SC5314 / ATCC MYA-2876) (Yeast) [Reference proteome]
Taxonomic identifier237561 [NCBI]
Taxonomic lineageEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesmitosporic SaccharomycetalesCandida

Protein attributes

Sequence length391 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Secreted aspartic peptidases (SAPs) are a group of ten acidic hydrolases considered as key virulence factors. These enzymes supply the fungus with nutrient amino acids as well as are able to degrade the selected host's proteins involved in the immune defense. Induces host inflammatory cytokine production in a proteolytic activity-independent way. Plays a role in tissue damage during superficial infection. Moreover, acts toward human hemoglobin though limited proteolysis to generate a variety of antimicrobial hemocidins, enabling to compete with the other microorganisms of the same physiological niche using the microbicidal peptides generated from the host protein. Ref.4 Ref.7 Ref.10 Ref.11 Ref.12 Ref.13 Ref.15 Ref.18

Catalytic activity

Preferential cleavage at the carboxyl of hydrophobic amino acids, but fails to cleave 15-Leu-|-Tyr-16, 16-Tyr-|-Leu-17 and 24-Phe-|-Phe-25 of insulin B chain. Activates trypsinogen, and degrades keratin. Ref.3 Ref.5 Ref.14

Enzyme regulation

Inhibited by pepstatin A analogs and squash aspartic peptidase inhibitor (SQAPI). Ref.8 Ref.17

Subcellular location

Secreted Ref.5 Ref.6.

Induction

Expressed during development of germ tubes, pseudohyphae, true hyphae and opaque cells. Expressed in greater amounts in the mature biofilms compared to early biofilms during inflammatory disorder of the palatal mucosa among denture wearers. Regulated by growth phase and alpha-pheromones. Ref.2 Ref.4 Ref.8 Ref.9 Ref.15 Ref.16 Ref.17

Post-translational modification

O-glycosylated.

Sequence similarities

Belongs to the peptidase A1 family.

Biophysicochemical properties

pH dependence:

Optimum pH is 5.0. Ref.3 Ref.14

Ontologies

Keywords
   Biological processVirulence
   Cellular componentSecreted
   DomainSignal
   Molecular functionAspartyl protease
Hydrolase
Protease
   PTMCleavage on pair of basic residues
Disulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadhesion to host

Inferred from mutant phenotype PubMed 16269404PubMed 9485603. Source: CGD

fungal-type cell wall organization

Inferred from mutant phenotype PubMed 21097664. Source: CGD

induction by symbiont of defense-related host calcium ion flux

Inferred from direct assay Ref.13. Source: CGD

induction by symbiont of host defense response

Inferred from direct assay PubMed 11506465. Source: CGD

induction by symbiont of host immune response

Inferred from direct assay Ref.13. Source: CGD

nitrogen compound metabolic process

Inferred from mutant phenotype PubMed 9284116. Source: CGD

pathogenesis

Inferred from mutant phenotype PubMed 10540295Ref.10Ref.11PubMed 9284116Ref.5. Source: CGD

protein catabolic process

Inferred from mutant phenotype PubMed 9284116. Source: CGD

protein metabolic process

Inferred from direct assay PubMed 11004559. Source: CGD

proteolysis

Inferred from direct assay Ref.14. Source: CGD

signal peptide processing

Inferred from direct assay PubMed 11004559. Source: CGD

   Cellular_componentanchored component of plasma membrane

Inferred from direct assay PubMed 16269404. Source: CGD

cell surface

Inferred from direct assay PubMed 16269404. Source: CGD

extracellular region

Inferred from direct assay PubMed 20641015PubMed 8407785. Source: CGD

fungal-type cell wall

Inferred from direct assay PubMed 16269404. Source: CGD

   Molecular_functionaspartic-type endopeptidase activity

Inferred from direct assay PubMed 11004559PubMed 21097664Ref.14PubMed 8540363Ref.3. Source: CGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Propeptide19 – 5032Activation peptide By similarity
PRO_0000413044
Chain51 – 391341Candidapepsin-1
PRO_0000413045

Regions

Region82 – 843Inhibitor binding By similarity
Region135 – 1362Inhibitor binding By similarity
Region267 – 2715Inhibitor binding By similarity

Sites

Active site821
Active site2671

Amino acid modifications

Glycosylation401N-linked (GlcNAc...) Potential
Disulfide bond97 ↔ 109
Disulfide bond305 ↔ 343

Secondary structure

...................................................................... 391
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P0CY27 [UniParc].

Last modified October 19, 2011. Version 1.
Checksum: CF88C56943BCCCA9

FASTA39141,602
        10         20         30         40         50         60 
MFLKNIFIAL AIALLVDASP AKRSPGFVTL DFDVIKTPVN ATGQEGKVKR QAIPVTLNNE 

        70         80         90        100        110        120 
HVSYAADITI GSNKQKFNVI VDTGSSDLWV PDASVTCDKP RPGQSADFCK GKGIYTPKSS 

       130        140        150        160        170        180 
TTSQNLGTPF YIGYGDGSSS QGTLYKDTVG FGGASITKQV FADITKTSIP QGILGIGYKT 

       190        200        210        220        230        240 
NEAAGDYDNV PVTLKNQGVI AKNAYSLYLN SPNAATGQII FGGVDKAKYS GSLIAVPVTS 

       250        260        270        280        290        300 
DRELRITLNS LKAVGKNING NIDVLLDSGT TITYLQQDVA QDIIDAFQAE LKSDGQGHTF 

       310        320        330        340        350        360 
YVTDCQTSGT VDFNFDNNAK ISVPASEFTA PLSYANGQPY PKCQLLLGIS DANILGDNFL 

       370        380        390 
RSAYLVYDLD DDKISLAQVK YTSASNIAAL T 

« Hide

References

« Hide 'large scale' references
[1]"The diploid genome sequence of Candida albicans."
Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B., Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W., Scherer S.
Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: SC5314 / ATCC MYA-2876.
[2]"Transcription of the gene for a pepsinogen, PEP1, is regulated by white-opaque switching in Candida albicans."
Morrow B., Srikantha T., Soll D.R.
Mol. Cell. Biol. 12:2997-3005(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[3]"Analysis of secreted aspartic proteinases from Candida albicans: purification and characterization of individual Sap1, Sap2 and Sap3 isoenzymes."
Smolenski G., Sullivan P.A., Cutfield S.M., Cutfield J.F.
Microbiology 143:349-356(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[4]"Misexpression of the opaque-phase-specific gene PEP1 (SAP1) in the white phase of Candida albicans confers increased virulence in a mouse model of cutaneous infection."
Kvaal C., Lachke S.A., Srikantha T., Daniels K., McCoy J., Soll D.R.
Infect. Immun. 67:6652-6662(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION, FUNCTION.
[5]"Evidence that members of the secretory aspartyl proteinase gene family, in particular SAP2, are virulence factors for Candida vaginitis."
De Bernardis F., Arancia S., Morelli L., Hube B., Sanglard D., Schafer W., Cassone A.
J. Infect. Dis. 179:201-208(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
[6]"Intra- and intermolecular events direct the propeptide-mediated maturation of the Candida albicans secreted aspartic proteinase Sap1p."
Beggah S., Lechenne B., Reichard U., Foundling S., Monod M.
Microbiology 146:2765-2773(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PROPEPTIDE.
[7]"Different isoforms of secreted aspartyl proteinases (Sap) are expressed by Candida albicans during oral and cutaneous candidosis in vivo."
Schaller M., Januschke E., Schackert C., Woerle B., Korting H.C.
J. Med. Microbiol. 50:743-747(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[8]"Analysis of the interaction between the aspartic peptidase inhibitor SQAPI and aspartic peptidases using surface plasmon resonance."
Farley P.C., Christeller J.T., Sullivan M.E., Sullivan P.A., Laing W.A.
J. Mol. Recognit. 15:135-144(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[9]"Alpha-pheromone-induced 'shmooing' and gene regulation require white-opaque switching during Candida albicans mating."
Lockhart S.R., Zhao R., Daniels K.J., Soll D.R.
Eukaryot. Cell 2:847-855(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[10]"The secreted aspartyl proteinases Sap1 and Sap2 cause tissue damage in an in vitro model of vaginal candidiasis based on reconstituted human vaginal epithelium."
Schaller M., Bein M., Korting H.C., Baur S., Hamm G., Monod M., Beinhauer S., Hube B.
Infect. Immun. 71:3227-3234(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Candida albicans-secreted aspartic proteinases modify the epithelial cytokine response in an in vitro model of vaginal candidiasis."
Schaller M., Korting H.C., Borelli C., Hamm G., Hube B.
Infect. Immun. 73:2758-2765(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[12]"The yeast Candida albicans evades human complement attack by secretion of aspartic proteases."
Gropp K., Schild L., Schindler S., Hube B., Zipfel P.F., Skerka C.
Mol. Immunol. 47:465-475(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[13]"The Inflammatory response induced by aspartic proteases of Candida albicans is independent of proteolytic activity."
Pietrella D., Rachini A., Pandey N., Schild L., Netea M., Bistoni F., Hube B., Vecchiarelli A.
Infect. Immun. 78:4754-4762(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[14]"Comprehensive characterization of secreted aspartic proteases encoded by a virulence gene family in Candida albicans."
Aoki W., Kitahara N., Miura N., Morisaka H., Yamamoto Y., Kuroda K., Ueda M.
J. Biochem. 150:431-438(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES.
[15]"In vitro Candida albicans biofilm induced proteinase activity and SAP8 expression correlates with in vivo denture stomatitis severity."
Ramage G., Coco B., Sherry L., Bagg J., Lappin D.F.
Mycopathologia 174:11-19(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION.
[16]"In vitro study of secreted aspartyl proteinases Sap1 to Sap3 and Sap4 to Sap6 expression in Candida albicans pleomorphic forms."
Staniszewska M., Bondaryk M., Siennicka K., Kurek A., Orlowski J., Schaller M., Kurzatkowski W.
Pol. J. Microbiol. 61:247-256(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INDUCTION.
[17]"Design, synthesis, inhibition studies, and molecular modeling of pepstatin analogues addressing different secreted aspartic proteinases of Candida albicans."
Cadicamo C.D., Mortier J., Wolber G., Hell M., Heinrich I.E., Michel D., Semlin L., Berger U., Korting H.C., Holtje H.D., Koksch B., Borelli C.
Biochem. Pharmacol. 85:881-887(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[18]"Secreted aspartic peptidases of Candida albicans liberate bactericidal hemocidins from human hemoglobin."
Bochenska O., Rapala-Kozik M., Wolak N., Bras G., Kozik A., Dubin A., Aoki W., Ueda M., Mak P.
Peptides 48:49-58(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[19]"X-ray structures of Sap1 and Sap5: structural comparison of the secreted aspartic proteinases from Candida albicans."
Borelli C., Ruge E., Lee J.H., Schaller M., Vogelsang A., Monod M., Korting H.C., Huber R., Maskos K.
Proteins 72:1308-1319(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 51-391.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AACQ01000047 Genomic DNA. Translation: EAK99043.1.
AACQ01000046 Genomic DNA. Translation: EAK99117.1.
RefSeqXP_717987.1. XM_712894.1.
XP_718053.1. XM_712960.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2QZWX-ray2.05A/B51-391[»]
ProteinModelPortalP0CY27.
SMRP0CY27. Positions 51-391.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID3640256.
3640364.
KEGGcal:CaO19.13137.
cal:CaO19.5714.

Phylogenomic databases

KOK06005.
OrthoDBEOG71VT34.

Enzyme and pathway databases

BRENDA3.4.23.24. 1124.

Family and domain databases

Gene3D2.40.70.10. 2 hits.
InterProIPR001461. Aspartic_peptidase.
IPR001969. Aspartic_peptidase_AS.
IPR021109. Peptidase_aspartic_dom.
[Graphical view]
PANTHERPTHR13683. PTHR13683. 1 hit.
PfamPF00026. Asp. 1 hit.
[Graphical view]
PRINTSPR00792. PEPSIN.
SUPFAMSSF50630. SSF50630. 1 hit.
PROSITEPS00141. ASP_PROTEASE. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP0CY27.

Entry information

Entry nameCARP1_CANAL
AccessionPrimary (citable) accession number: P0CY27
Secondary accession number(s): P28872, Q5A8N4
Entry history
Integrated into UniProtKB/Swiss-Prot: October 19, 2011
Last sequence update: October 19, 2011
Last modified: April 16, 2014
This is version 20 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Candida albicans

Candida albicans: entries and gene names