PRA1_CANAL
ID PRA1_CANAL Reviewed; 299 AA.
AC P87020; A0A1D8PMQ8; P78598; Q5A0Y5; Q5A156;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 3.
DT 25-MAY-2022, entry version 97.
DE RecName: Full=pH-regulated antigen PRA1;
DE AltName: Full=58 kDa fibrinogen-binding mannoprotein;
DE Flags: Precursor;
GN Name=PRA1; Synonyms=FBP1; OrderedLocusNames=CAALFM_C406980WA;
GN ORFNames=CaO19.10623, CaO19.3111;
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], INDUCTION, FUNCTION, DISRUPTION
RP PHENOTYPE, SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=9440517; DOI=10.1128/jb.180.2.282-289.1998;
RA Sentandreu M., Elorza M.V., Sentandreu R., Fonzi W.A.;
RT "Cloning and characterization of PRA1, a gene encoding a novel pH-regulated
RT antigen of Candida albicans.";
RL J. Bacteriol. 180:282-289(1998).
RN [2]
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 [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 NUCLEOTIDE SEQUENCE [MRNA] OF 8-299.
RC STRAIN=ATCC 26555;
RX PubMed=9435108; DOI=10.1111/j.1574-6968.1997.tb12784.x;
RA Lopez-Ribot J.L., Sepulveda P., Cervera A.M., Roig P., Gozalbo D.,
RA Martinez J.P.;
RT "Cloning of a cDNA fragment encoding part of the protein moiety of the 58-
RT kDa fibrinogen-binding mannoprotein of Candida albicans.";
RL FEMS Microbiol. Lett. 157:273-278(1997).
RN [6]
RP IDENTIFICATION, SUBCELLULAR LOCATION, GLYCOSYLATION, AND
RP FIBRINOGEN-BINDING.
RX PubMed=1398933; DOI=10.1128/iai.60.10.4221-4229.1992;
RA Casanova M., Lopez-Ribot J.L., Monteagudo C., Llombart-Bosch A.,
RA Sentandreu R., Martinez J.P.;
RT "Identification of a 58-kilodalton cell surface fibrinogen-binding
RT mannoprotein from Candida albicans.";
RL Infect. Immun. 60:4221-4229(1992).
RN [7]
RP SUBCELLULAR LOCATION.
RX PubMed=8300229; DOI=10.1128/iai.62.2.709-712.1994;
RA Martinez J.P., Lopez-Ribot J.L., Chaffin W.L.;
RT "Heterogeneous surface distribution of the fibrinogen-binding protein on
RT Candida albicans.";
RL Infect. Immun. 62:709-712(1994).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=7768591; DOI=10.1128/iai.63.6.2126-2132.1995;
RA Lopez-Ribot J.L., Martinez J.P., Chaffin W.L.;
RT "Comparative study of the C3d receptor and 58-kilodalton fibrinogen-binding
RT mannoproteins of Candida albicans.";
RL Infect. Immun. 63:2126-2132(1995).
RN [9]
RP SUBCELLULAR LOCATION.
RX PubMed=8759797; DOI=10.1111/j.1574-6968.1996.tb08417.x;
RA Lopez-Ribot J.L., Monteagudo C., Sepulveda P., Casanova M., Martinez J.P.,
RA Chaffin W.L.;
RT "Expression of the fibrinogen binding mannoprotein and the laminin receptor
RT of Candida albicans in vitro and in infected tissues.";
RL FEMS Microbiol. Lett. 142:117-122(1996).
RN [10]
RP INDUCTION.
RX PubMed=10629054; DOI=10.1128/mcb.20.3.971-978.2000;
RA Davis D.A., Wilson R.B., Mitchell A.P.;
RT "RIM101-dependent and -independent pathways govern pH responses in Candida
RT albicans.";
RL Mol. Cell. Biol. 20:971-978(2000).
RN [11]
RP IDENTIFICATION AS A DOMINANT ANTIGEN.
RX PubMed=11292706; DOI=10.1128/iai.69.5.2909-2919.2001;
RA Viudes A., Perea S., Lopez-Ribot J.L.;
RT "Identification of continuous B-cell epitopes on the protein moiety of the
RT 58-kiloDalton cell wall mannoprotein of Candida albicans belonging to a
RT family of immunodominant fungal antigens.";
RL Infect. Immun. 69:2909-2919(2001).
RN [12]
RP INDUCTION.
RX PubMed=17042758; DOI=10.1111/j.1567-1364.2006.00130.x;
RA Sohn K., Senyurek I., Fertey J., Konigsdorfer A., Joffroy C., Hauser N.,
RA Zelt G., Brunner H., Rupp S.;
RT "An in vitro assay to study the transcriptional response during adherence
RT of Candida albicans to different human epithelia.";
RL FEMS Yeast Res. 6:1085-1093(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RX PubMed=17905924; DOI=10.1128/ec.00285-07;
RA Hiller E., Heine S., Brunner H., Rupp S.;
RT "Candida albicans Sun41p, a putative glycosidase, is involved in
RT morphogenesis, cell wall biogenesis, and biofilm formation.";
RL Eukaryot. Cell 6:2056-2065(2007).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, IDENTIFICATION
RP IN A COMPLEX WITH MP65 AND HYR1, AND INTERACTION WITH HUMAN INTEGRIN
RP ALPHA-M/BETA-2.
RX PubMed=17277107; DOI=10.4049/jimmunol.178.4.2038;
RA Soloviev D.A., Fonzi W.A., Sentandreu R., Pluskota E., Forsyth C.B.,
RA Yadav S., Plow E.F.;
RT "Identification of pH-regulated antigen 1 released from Candida albicans as
RT the major ligand for leukocyte integrin alphaMbeta2.";
RL J. Immunol. 178:2038-2046(2007).
RN [15]
RP SUBCELLULAR LOCATION, AND GLYCOSYLATION.
RX PubMed=19098294; DOI=10.1093/jac/dkn515;
RA Pierce C.G., Thomas D.P., Lopez-Ribot J.L.;
RT "Effect of tunicamycin on Candida albicans biofilm formation and
RT maintenance.";
RL J. Antimicrob. Chemother. 63:473-479(2009).
RN [16]
RP FUNCTION, AND INTERACTION WITH HUMAN CFH; CFHR1 AND PLG.
RX PubMed=19850343; DOI=10.1016/j.molimm.2009.07.017;
RA Luo S., Poltermann S., Kunert A., Rupp S., Zipfel P.F.;
RT "Immune evasion of the human pathogenic yeast Candida albicans: Pra1 is a
RT Factor H, FHL-1 and plasminogen binding surface protein.";
RL Mol. Immunol. 47:541-550(2009).
RN [17]
RP FUNCTION.
RX PubMed=20504767; DOI=10.1074/jbc.m110.142703;
RA Agarwal V., Asmat T.M., Luo S., Jensch I., Zipfel P.F., Hammerschmidt S.;
RT "Complement regulator Factor H mediates a two-step uptake of Streptococcus
RT pneumoniae by human cells.";
RL J. Biol. Chem. 285:23486-23495(2010).
RN [18]
RP FUNCTION, AND INTERACTION WITH HUMAN COMPLEMENT C3.
RX PubMed=20644161; DOI=10.4049/jimmunol.1001011;
RA Luo S., Hartmann A., Dahse H.M., Skerka C., Zipfel P.F.;
RT "Secreted pH-regulated antigen 1 of Candida albicans blocks activation and
RT conversion of complement C3.";
RL J. Immunol. 185:2164-2173(2010).
RN [19]
RP FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH HUMAN INTEGRIN
RP ALPHA-M/BETA-2.
RX PubMed=21245270; DOI=10.1128/iai.00650-10;
RA Soloviev D.A., Jawhara S., Fonzi W.A.;
RT "Regulation of innate immune response to Candida albicans infections by
RT alphaMbeta2-Pra1p interaction.";
RL Infect. Immun. 79:1546-1558(2011).
RN [20]
RP FUNCTION, AND INTERACTION WITH HUMAN C4BPA.
RX PubMed=21212281; DOI=10.1074/jbc.m110.130138;
RA Luo S., Blom A.M., Rupp S., Hipler U.C., Hube B., Skerka C., Zipfel P.F.;
RT "The pH-regulated antigen 1 of Candida albicans binds the human complement
RT inhibitor C4b-binding protein and mediates fungal complement evasion.";
RL J. Biol. Chem. 286:8021-8029(2011).
RN [21]
RP FUNCTION.
RX PubMed=21820180; DOI=10.1016/j.molimm.2011.07.007;
RA Losse J., Svobodova E., Heyken A., Hube B., Zipfel P.F., Jozsi M.;
RT "Role of pH-regulated antigen 1 of Candida albicans in the fungal
RT recognition and antifungal response of human neutrophils.";
RL Mol. Immunol. 48:2135-2143(2011).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=22074954; DOI=10.1016/j.peptides.2011.10.021;
RA Karkowska-Kuleta J., Kedracka-Krok S., Rapala-Kozik M., Kamysz W.,
RA Bielinska S., Karafova A., Kozik A.;
RT "Molecular determinants of the interaction between human high molecular
RT weight kininogen and Candida albicans cell wall: Identification of
RT kininogen-binding proteins on fungal cell wall and mapping the cell wall-
RT binding regions on kininogen molecule.";
RL Peptides 32:2488-2496(2011).
RN [23]
RP FUNCTION.
RX PubMed=22844116; DOI=10.4049/jimmunol.1200524;
RA Jawhara S., Pluskota E., Verbovetskiy D., Skomorovska-Prokvolit O.,
RA Plow E.F., Soloviev D.A.;
RT "Integrin alphaXbeta(2) is a leukocyte receptor for Candida albicans and is
RT essential for protection against fungal infections.";
RL J. Immunol. 189:2468-2477(2012).
RN [24]
RP FUNCTION.
RX PubMed=22761575; DOI=10.1371/journal.ppat.1002777;
RA Citiulo F., Jacobsen I.D., Miramon P., Schild L., Brunke S., Zipfel P.,
RA Brock M., Hube B., Wilson D.;
RT "Candida albicans scavenges host zinc via Pra1 during endothelial
RT invasion.";
RL PLoS Pathog. 8:E1002777-E1002777(2012).
CC -!- FUNCTION: Cell surface protein involved in the host-parasite
CC interaction during candidal infection. With MP65, represents a major
CC component of the biofilm matrix. Sequesters zinc from host tissue and
CC mediates leukocyte adhesion and migration. As a surface protein, binds
CC the two human complement regulators CFH and CFHR1, as well as
CC plasminogen PLG, mediates complement evasion and extra-cellular matrix
CC interaction and/or degradation. As a released protein, enhances
CC complement control in direct vicinity of the yeast and thus generates
CC an additional protective layer which controls host complement attack,
CC assisting the fungus in escaping host surveillance. Binds to host
CC fluid-phase C3 and blocks cleavage of C3 to C3a and C3b, leading to
CC inhibition of complement activation. Mediates also human complement
CC control and complement evasion through binding to C4BPA, another human
CC complement inhibitor, as well as through binding to host integrin
CC alpha-M/beta-2. Decreases complement-mediated adhesion, as well as
CC uptake of C.albicans by human macrophages.
CC {ECO:0000269|PubMed:19850343, ECO:0000269|PubMed:20504767,
CC ECO:0000269|PubMed:20644161, ECO:0000269|PubMed:21212281,
CC ECO:0000269|PubMed:21245270, ECO:0000269|PubMed:21820180,
CC ECO:0000269|PubMed:22074954, ECO:0000269|PubMed:22761575,
CC ECO:0000269|PubMed:22844116, ECO:0000269|PubMed:9440517}.
CC -!- SUBUNIT: Component of a multiprotein complex of 250 kDa composed of at
CC least HYR1, MP65, and PRA1. Interacts with host Integrin alpha-M/beta-2
CC heterodimer. Binds also human factor H (CFH), CFHR1, plasminogen (PLG),
CC complement C3, and C4BPA. {ECO:0000269|PubMed:17277107,
CC ECO:0000269|PubMed:19850343, ECO:0000269|PubMed:20644161,
CC ECO:0000269|PubMed:21212281, ECO:0000269|PubMed:21245270}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:1398933,
CC ECO:0000269|PubMed:17277107, ECO:0000269|PubMed:17905924,
CC ECO:0000269|PubMed:19098294, ECO:0000269|PubMed:22074954,
CC ECO:0000269|PubMed:7768591, ECO:0000269|PubMed:8300229,
CC ECO:0000269|PubMed:8759797, ECO:0000269|PubMed:9440517}. Note=Found
CC primarily on the cell surface of filamentous forms and enriched at
CC hyphal tips.
CC -!- INDUCTION: Differentially expressed in response to changes in the pH
CC with aximal expression at neutral pH and no expression detected below
CC pH 6.0. Expression is controlled by RIM101. Expression is also
CC increased during adhesion onto human epithelia.
CC {ECO:0000269|PubMed:10629054, ECO:0000269|PubMed:17042758,
CC ECO:0000269|PubMed:9440517}.
CC -!- PTM: N- and O-glycosylated. The N- and 0-glycosidically linked
CC carbohydrates represent 18 to 20 percent and 3 to 4 percent,
CC respectively, of the molecular mass of PRA1. 0-linked sugar residues
CC may be involved in the interaction with fibrinogen. Contributes highly
CC to the carbohydrate component of the matrix. Treatment with tunicamycin
CC impairs glycosylation. {ECO:0000269|PubMed:1398933,
CC ECO:0000269|PubMed:19098294, ECO:0000269|PubMed:9440517}.
CC -!- DISRUPTION PHENOTYPE: Impairs hypha formation. Protects the fungus
CC against leukocyte killing in vitro and in vivo, impedes the innate
CC immune response to the infection, and increases fungal virulence and
CC organ invasion in vivo. {ECO:0000269|PubMed:21245270,
CC ECO:0000269|PubMed:9440517}.
CC -!- SIMILARITY: Belongs to the ZPS1 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; U84261; AAC00525.1; -; Genomic_DNA.
DR EMBL; CP017626; AOW29419.1; -; Genomic_DNA.
DR EMBL; U83997; AAC49898.1; -; mRNA.
DR RefSeq; XP_715420.2; XM_710327.2.
DR AlphaFoldDB; P87020; -.
DR SMR; P87020; -.
DR BioGRID; 1225932; 5.
DR STRING; 237561.P87020; -.
DR TCDB; 2.A.5.1.15; the zinc (zn(2+))-iron (fe(2+)) permease (zip) family.
DR GeneID; 3642969; -.
DR KEGG; cal:CAALFM_C406980WA; -.
DR CGD; CAL0000174610; PRA1.
DR VEuPathDB; FungiDB:C4_06980W_A; -.
DR eggNOG; ENOG502RTN8; Eukaryota.
DR HOGENOM; CLU_048223_0_0_1; -.
DR InParanoid; P87020; -.
DR OrthoDB; 1207536at2759; -.
DR PRO; PR:P87020; -.
DR Proteomes; UP000000559; Chromosome 4.
DR GO; GO:0009986; C:cell surface; IDA:CGD.
DR GO; GO:0005576; C:extracellular region; IDA:CGD.
DR GO; GO:0009277; C:fungal-type cell wall; IDA:CGD.
DR GO; GO:0030446; C:hyphal cell wall; IDA:CGD.
DR GO; GO:0001411; C:hyphal tip; IDA:CGD.
DR GO; GO:0070051; F:fibrinogen binding; IDA:CGD.
DR GO; GO:0030985; F:high molecular weight kininogen binding; IDA:CGD.
DR GO; GO:0005178; F:integrin binding; IDA:CGD.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IDA:CGD.
DR GO; GO:0044406; P:adhesion of symbiont to host; IDA:CGD.
DR GO; GO:0042783; P:evasion of host immune response; IPI:CGD.
DR GO; GO:0007159; P:leukocyte cell-cell adhesion; IDA:CGD.
DR GO; GO:0052155; P:modulation by symbiont of host cell-mediated immune response; IDA:CGD.
DR GO; GO:0045916; P:negative regulation of complement activation; IDA:CGD.
DR GO; GO:0032119; P:sequestering of zinc ion; IMP:CGD.
DR GO; GO:0052085; P:suppression by symbiont of host T-cell mediated immune response; IDA:CGD.
DR CDD; cd11307; M35_Asp_f2_like; 1.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR029482; HRXXH.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR039124; PRA1-like.
DR PANTHER; PTHR39399; PTHR39399; 1.
DR Pfam; PF13933; HRXXH; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..15
FT /evidence="ECO:0000255"
FT CHAIN 16..299
FT /note="pH-regulated antigen PRA1"
FT /id="PRO_0000041750"
FT REGION 253..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..288
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 48
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 89
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 135
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 208
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 8
FT /note="L -> F (in Ref. 5; AAC49898)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="D -> N (in Ref. 1; AAC00525)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="E -> D (in Ref. 1; AAC00525)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="D -> E (in Ref. 1; AAC00525 and 5; AAC49898)"
FT /evidence="ECO:0000305"
FT CONFLICT 105
FT /note="G -> D (in Ref. 5; AAC49898)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="T -> S (in Ref. 1; AAC00525 and 5; AAC49898)"
FT /evidence="ECO:0000305"
FT CONFLICT 159
FT /note="S -> G (in Ref. 1; AAC00525 and 5; AAC49898)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 299 AA; 33159 MW; 5DF3AC42FE495E73 CRC64;
MNYLLFCLFF AFSVAAPVTV TRFVDASPTG YDWRADWVKG FPIDSSCNAT QYNQLSTGLQ
EAQLLAEHAR DHTLRFGSKS PFFRKYFGNE TASAEVVGHF DNVVGADKSS ILFLCDDLDD
KCKNDGWAGY WRGSNHSDQT IICDLSFVTR RYLTQLCSSG YTVSKSKTNI FWAGDLLHRF
WHLKSIGQLV IEHYADTYEE VLELAQENST YAVRNSNSLI YYALDVYAYD VTIPGEGCNG
DGTSYKKSDF SSFEDSDSGS DSGASSTASS SHQHTDSNPS ATTDANSHCH THADGEVHC
