PGA7_CANAL
ID PGA7_CANAL Reviewed; 219 AA.
AC Q59UT5; A0A1D8PKX9;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=GPI-anchored hemophore PGA7 {ECO:0000303|PubMed:27617569};
DE AltName: Full=Predicted GPI-anchored protein 7 {ECO:0000303|PubMed:12845604};
DE AltName: Full=Repressed by TUP1 protein 6 {ECO:0000303|PubMed:20435697};
DE Flags: Precursor;
GN Name=PGA7 {ECO:0000303|PubMed:12845604};
GN Synonyms=CRW3 {ECO:0000303|PubMed:16151249},
GN RBT6 {ECO:0000303|PubMed:20435697}; OrderedLocusNames=CAALFM_C400120WA;
GN ORFNames=CaO19.13080, CaO19.5635;
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 DOMAIN.
RX PubMed=12633989; DOI=10.1016/s0968-0004(03)00025-2;
RA Kulkarni R.D., Kelkar H.S., Dean R.A.;
RT "An eight-cysteine-containing CFEM domain unique to a group of fungal
RT membrane proteins.";
RL Trends Biochem. Sci. 28:118-121(2003).
RN [5]
RP PREDICTION OF GPI-ANCHOR.
RX PubMed=12845604; DOI=10.1002/yea.1007;
RA De Groot P.W., Hellingwerf K.J., Klis F.M.;
RT "Genome-wide identification of fungal GPI proteins.";
RL Yeast 20:781-796(2003).
RN [6]
RP INDUCTION.
RX PubMed=15554973; DOI=10.1111/j.1365-2958.2004.04350.x;
RA Bensen E.S., Martin S.J., Li M., Berman J., Davis D.A.;
RT "Transcriptional profiling in Candida albicans reveals new adaptive
RT responses to extracellular pH and functions for Rim101p.";
RL Mol. Microbiol. 54:1335-1351(2004).
RN [7]
RP INDUCTION.
RX PubMed=16151249; DOI=10.1128/ec.4.9.1562-1573.2005;
RA Murillo L.A., Newport G., Lan C.Y., Habelitz S., Dungan J., Agabian N.M.;
RT "Genome-wide transcription profiling of the early phase of biofilm
RT formation by Candida albicans.";
RL Eukaryot. Cell 4:1562-1573(2005).
RN [8]
RP INDUCTION.
RX PubMed=15814599; DOI=10.1093/jac/dki105;
RA Lee R.E., Liu T.T., Barker K.S., Lee R.E., Rogers P.D.;
RT "Genome-wide expression profiling of the response to ciclopirox olamine in
RT Candida albicans.";
RL J. Antimicrob. Chemother. 55:655-662(2005).
RN [9]
RP INDUCTION.
RX PubMed=16030247; DOI=10.1091/mbc.e05-05-0435;
RA Hromatka B.S., Noble S.M., Johnson A.D.;
RT "Transcriptional response of Candida albicans to nitric oxide and the role
RT of the YHB1 gene in nitrosative stress and virulence.";
RL Mol. Biol. Cell 16:4814-4826(2005).
RN [10]
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 [11]
RP INDUCTION.
RX PubMed=16455273; DOI=10.1016/j.fgb.2005.12.002;
RA Castillo L., Martinez A.I., Garcera A., Garcia-Martinez J.,
RA Ruiz-Herrera J., Valentin E., Sentandreu R.;
RT "Genomic response programs of Candida albicans following protoplasting and
RT regeneration.";
RL Fungal Genet. Biol. 43:124-134(2006).
RN [12]
RP INDUCTION.
RX PubMed=20435697; DOI=10.1128/ec.00034-10;
RA Rosenbach A., Dignard D., Pierce J.V., Whiteway M., Kumamoto C.A.;
RT "Adaptations of Candida albicans for growth in the mammalian intestinal
RT tract.";
RL Eukaryot. Cell 9:1075-1086(2010).
RN [13]
RP INDUCTION.
RX PubMed=20870877; DOI=10.1128/ec.00159-10;
RA Synnott J.M., Guida A., Mulhern-Haughey S., Higgins D.G., Butler G.;
RT "Regulation of the hypoxic response in Candida albicans.";
RL Eukaryot. Cell 9:1734-1746(2010).
RN [14]
RP INDUCTION.
RX PubMed=21622905; DOI=10.1128/ec.05011-11;
RA Sorgo A.G., Heilmann C.J., Dekker H.L., Bekker M., Brul S., de Koster C.G.,
RA de Koning L.J., Klis F.M.;
RT "Effects of fluconazole on the secretome, the wall proteome, and wall
RT integrity of the clinical fungus Candida albicans.";
RL Eukaryot. Cell 10:1071-1081(2011).
RN [15]
RP INDUCTION.
RX PubMed=21592964; DOI=10.1074/jbc.m111.233569;
RA Singh R.P., Prasad H.K., Sinha I., Agarwal N., Natarajan K.;
RT "Cap2-HAP complex is a critical transcriptional regulator that has dual but
RT contrasting roles in regulation of iron homeostasis in Candida albicans.";
RL J. Biol. Chem. 286:25154-25170(2011).
RN [16]
RP INDUCTION, AND DOMAIN.
RX PubMed=22145027; DOI=10.1371/journal.pone.0028151;
RA Ding C., Vidanes G.M., Maguire S.L., Guida A., Synnott J.M., Andes D.R.,
RA Butler G.;
RT "Conserved and divergent roles of Bcr1 and CFEM proteins in Candida
RT parapsilosis and Candida albicans.";
RL PLoS ONE 6:E28151-E28151(2011).
RN [17]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, HEME-BINDING, DOMAIN,
RP MUTAGENESIS OF ASP-63, AND INTERACTION WITH RBT5.
RX PubMed=25275454; DOI=10.1371/journal.ppat.1004407;
RA Kuznets G., Vigonsky E., Weissman Z., Lalli D., Gildor T., Kauffman S.J.,
RA Turano P., Becker J., Lewinson O., Kornitzer D.;
RT "A relay network of extracellular heme-binding proteins drives C. albicans
RT iron acquisition from hemoglobin.";
RL PLoS Pathog. 10:E1004407-E1004407(2014).
RN [18]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-63.
RX PubMed=27617569; DOI=10.1038/nmicrobiol.2016.156;
RA Nasser L., Weissman Z., Pinsky M., Amartely H., Dvir H., Kornitzer D.;
RT "Structural basis of haem-iron acquisition by fungal pathogens.";
RL Nat. Microbiol. 1:16156-16156(2016).
CC -!- FUNCTION: GPI-linked hyphal surface heme-binding protein involved in
CC heme-iron utilization (PubMed:25275454, PubMed:27617569). Heme transfer
CC occurs between PGA7, RBT5 and CSA2 supporting a model in which the 3
CC CFEM proteins cooperate in a heme-acquisition system and form a cross-
CC cell wall heme-transfer cascade (PubMed:25275454, PubMed:27617569). The
CC ability to acquire iron from host tissues is a major virulence factor
CC of pathogenic microorganisms. Required for biofilm formation
CC (PubMed:25275454). {ECO:0000269|PubMed:25275454,
CC ECO:0000269|PubMed:27617569}.
CC -!- SUBUNIT: Interacts with RBT5. {ECO:0000269|PubMed:25275454}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:25275454}. Cell membrane {ECO:0000305}; Lipid-
CC anchor, GPI-anchor {ECO:0000305}.
CC -!- INDUCTION: Induced by hypoxia, ketoconazole, fluconazole, nitric oxide,
CC ciclopirox olamine, during cell wall regeneration following
CC protoplasting, during adhesion, and during biofilm formation. Regulated
CC by UPC2, BCR1, HAP43, and RIM101. {ECO:0000269|PubMed:15554973,
CC ECO:0000269|PubMed:15814599, ECO:0000269|PubMed:16030247,
CC ECO:0000269|PubMed:16151249, ECO:0000269|PubMed:16455273,
CC ECO:0000269|PubMed:17042758, ECO:0000269|PubMed:20435697,
CC ECO:0000269|PubMed:20870877, ECO:0000269|PubMed:21592964,
CC ECO:0000269|PubMed:21622905, ECO:0000269|PubMed:22145027}.
CC -!- DOMAIN: The CFEM domain is involved in heme-binding and contains 8
CC cysteines and is found in proteins from several pathogenic fungi,
CC including both human and plant pathogens (PubMed:12633989,
CC PubMed:22145027, PubMed:25275454). The CFEM domain adopts a novel
CC helical-basket fold that consists of six alpha-helices, and is uniquely
CC stabilized by four disulfide bonds formed by its 8 signature cysteines
CC (By similarity). {ECO:0000250|UniProtKB:Q5A0X8,
CC ECO:0000269|PubMed:12633989, ECO:0000269|PubMed:22145027,
CC ECO:0000269|PubMed:25275454}.
CC -!- PTM: The GPI-anchor is attached to the protein in the endoplasmic
CC reticulum and serves to target the protein to the cell surface. There,
CC the glucosamine-inositol phospholipid moiety is cleaved off and the
CC GPI-modified mannoprotein is covalently attached via its lipidless GPI
CC glycan remnant to the 1,6-beta-glucan of the outer cell wall layer.
CC {ECO:0000305}.
CC -!- DISRUPTION PHENOTYPE: Leads to defects in hemoglobin utilization as
CC sole source of iron and decreased virulence on a mouse model of
CC systemic candidiasis. {ECO:0000269|PubMed:25275454,
CC ECO:0000269|PubMed:27617569}.
CC -!- SIMILARITY: Belongs to the RBT5 family. {ECO:0000305}.
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DR EMBL; CP017626; AOW28805.1; -; Genomic_DNA.
DR RefSeq; XP_713316.1; XM_708223.1.
DR AlphaFoldDB; Q59UT5; -.
DR SMR; Q59UT5; -.
DR STRING; 237561.Q59UT5; -.
DR GeneID; 3645006; -.
DR KEGG; cal:CAALFM_C400120WA; -.
DR CGD; CAL0000201827; PGA7.
DR VEuPathDB; FungiDB:C4_00120W_A; -.
DR eggNOG; ENOG502SFDE; Eukaryota.
DR HOGENOM; CLU_079397_1_0_1; -.
DR InParanoid; Q59UT5; -.
DR OMA; NCKGEDV; -.
DR OrthoDB; 1627841at2759; -.
DR PHI-base; PHI:3333; -.
DR PRO; PR:Q59UT5; -.
DR Proteomes; UP000000559; Chromosome 4.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IDA:CGD.
DR GO; GO:0005576; C:extracellular region; IBA:GO_Central.
DR GO; GO:0009277; C:fungal-type cell wall; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020037; F:heme binding; IDA:CGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IBA:GO_Central.
DR GO; GO:0044011; P:single-species biofilm formation on inanimate substrate; IMP:CGD.
DR InterPro; IPR008427; Extracellular_membr_CFEM_dom.
DR Pfam; PF05730; CFEM; 1.
DR SMART; SM00747; CFEM; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cell wall; Disulfide bond; Glycoprotein; GPI-anchor; Heme;
KW Iron; Lipoprotein; Membrane; Metal-binding; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..13
FT /evidence="ECO:0000255"
FT CHAIN 14..194
FT /note="GPI-anchored hemophore PGA7"
FT /id="PRO_0000424646"
FT PROPEP 195..219
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000424647"
FT REGION 40..102
FT /note="CFEM"
FT /evidence="ECO:0000269|PubMed:25275454,
FT ECO:0000303|PubMed:12633989"
FT REGION 151..194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 63
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:27617569"
FT LIPID 194
FT /note="GPI-anchor amidated serine"
FT /evidence="ECO:0000255"
FT DISULFID 45..85
FT /evidence="ECO:0000250|UniProtKB:Q5A0X8"
FT DISULFID 49..80
FT /evidence="ECO:0000250|UniProtKB:Q5A0X8"
FT DISULFID 59..66
FT /evidence="ECO:0000250|UniProtKB:Q5A0X8"
FT DISULFID 68..101
FT /evidence="ECO:0000250|UniProtKB:Q5A0X8"
FT MUTAGEN 63
FT /note="D->A: Abolishes heme-binding."
FT /evidence="ECO:0000269|PubMed:25275454"
FT MUTAGEN 63
FT /note="D->H: Impairs the heme transfer within the CFEM
FT proteins cascade."
FT /evidence="ECO:0000269|PubMed:27617569"
SQ SEQUENCE 219 AA; 22420 MW; 6448BFCAED74F433 CRC64;
MHFIFYLILL VSAADYGNFG TYPKVPKTAS INGFADPIYD LLPDCAKECV KFSTSNTPCP
YWDTGCFCVM PQWAGLVGQC VAQKCKGEDV ASARFLATSL CSVVGANTWM MPASISSMLS
TAAGDAKEVT TIEGKTAKSW VTAPGSAAGS VVSETGSASE TGSSESAQST TTGSSSTGSS
STDSSSSSSS SPSSSANFAV LQTGGIGSVI LGFMMYLLV
