RBT5_CANAL
ID RBT5_CANAL Reviewed; 241 AA.
AC Q59UT4; A0A1D8PKY3; Q9HFZ1;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=GPI-anchored hemophore RBT5 {ECO:0000303|PubMed:27617569};
DE AltName: Full=Repressed by TUP1 protein 5 {ECO:0000303|PubMed:10978273};
DE Flags: Precursor;
GN Name=RBT5 {ECO:0000303|PubMed:10978273};
GN OrderedLocusNames=CAALFM_C400130WA; ORFNames=CaO19.13081, CaO19.5636;
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 INDUCTION.
RX PubMed=10978273; DOI=10.1093/genetics/156.1.31;
RA Braun B.R., Head W.S., Wang M.X., Johnson A.D.;
RT "Identification and characterization of TUP1-regulated genes in Candida
RT albicans.";
RL Genetics 156:31-44(2000).
RN [5]
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 [6]
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 [7]
RP FUNCTION, HEME-BINDING, GLYCOSYLATION, INDUCTION, DISRUPTION PHENOTYPE, AND
RP SUBCELLULAR LOCATION.
RX PubMed=15306022; DOI=10.1111/j.1365-2958.2004.04199.x;
RA Weissman Z., Kornitzer D.;
RT "A family of Candida cell surface haem-binding proteins involved in haemin
RT and haemoglobin-iron utilization.";
RL Mol. Microbiol. 53:1209-1220(2004).
RN [8]
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 [9]
RP INDUCTION.
RX PubMed=15387822; DOI=10.1111/j.1365-2958.2004.04214.x;
RA Lan C.Y., Rodarte G., Murillo L.A., Jones T., Davis R.W., Dungan J.,
RA Newport G., Agabian N.;
RT "Regulatory networks affected by iron availability in Candida albicans.";
RL Mol. Microbiol. 53:1451-1469(2004).
RN [10]
RP INDUCTION.
RX PubMed=15917516; DOI=10.1128/aac.49.6.2226-2236.2005;
RA Liu T.T., Lee R.E., Barker K.S., Lee R.E., Wei L., Homayouni R.,
RA Rogers P.D.;
RT "Genome-wide expression profiling of the response to azole, polyene,
RT echinocandin, and pyrimidine antifungal agents in Candida albicans.";
RL Antimicrob. Agents Chemother. 49:2226-2236(2005).
RN [11]
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 [12]
RP FUNCTION.
RX PubMed=17042757; DOI=10.1111/j.1567-1364.2006.00131.x;
RA Perez A., Pedros B., Murgui A., Casanova M., Lopez-Ribot J.L.,
RA Martinez J.P.;
RT "Biofilm formation by Candida albicans mutants for genes coding fungal
RT proteins exhibiting the eight-cysteine-containing CFEM domain.";
RL FEMS Yeast Res. 6:1074-1084(2006).
RN [13]
RP INDUCTION.
RX PubMed=16339080; DOI=10.1091/mbc.e05-06-0501;
RA Enjalbert B., Smith D.A., Cornell M.J., Alam I., Nicholls S., Brown A.J.P.,
RA Quinn J.;
RT "Role of the Hog1 stress-activated protein kinase in the global
RT transcriptional response to stress in the fungal pathogen Candida
RT albicans.";
RL Mol. Biol. Cell 17:1018-1032(2006).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=18227255; DOI=10.1099/mic.0.2007/012617-0;
RA Sosinska G.J., de Groot P.W., Teixeira de Mattos M.J., Dekker H.L.,
RA de Koster C.G., Hellingwerf K.J., Klis F.M.;
RT "Hypoxic conditions and iron restriction affect the cell-wall proteome of
RT Candida albicans grown under vagina-simulative conditions.";
RL Microbiology 154:510-520(2008).
RN [15]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=18466294; DOI=10.1111/j.1365-2958.2008.06277.x;
RA Weissman Z., Shemer R., Conibear E., Kornitzer D.;
RT "An endocytic mechanism for haemoglobin-iron acquisition in Candida
RT albicans.";
RL Mol. Microbiol. 69:201-217(2008).
RN [16]
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 [17]
RP INDUCTION, AND FUNCTION.
RX PubMed=21205162; DOI=10.1111/j.1567-1364.2010.00714.x;
RA Perez A., Ramage G., Blanes R., Murgui A., Casanova M., Martinez J.P.;
RT "Some biological features of Candida albicans mutants for genes coding
RT fungal proteins containing the CFEM domain.";
RL FEMS Yeast Res. 11:273-284(2011).
RN [18]
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 [19]
RP DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION, HEME-BINDING, DOMAIN,
RP MUTAGENESIS OF ASP-72, AND INTERACTION WITH PGA7.
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 [20]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF ASP-72.
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:15306022, PubMed:17042757,
CC PubMed:18466294, PubMed:21205162, PubMed:25275454, PubMed:27617569).
CC Heme transfer occurs between PGA7, RBT5 and CSA2 supporting a model in
CC which the 3 CFEM proteins cooperate in a heme-acquisition system and
CC form a cross-cell wall heme-transfer cascade (PubMed:15306022,
CC PubMed:17042757, PubMed:18466294, PubMed:21205162, PubMed:25275454,
CC PubMed:27617569). The ability to acquire iron from host tissues is a
CC major virulence factor of pathogenic microorganisms. Required for
CC biofilm formation (PubMed:15306022, PubMed:17042757, PubMed:18466294,
CC PubMed:21205162, PubMed:25275454). {ECO:0000269|PubMed:15306022,
CC ECO:0000269|PubMed:17042757, ECO:0000269|PubMed:18466294,
CC ECO:0000269|PubMed:21205162, ECO:0000269|PubMed:25275454,
CC ECO:0000269|PubMed:27617569}.
CC -!- SUBUNIT: Interacts with PGA7. {ECO:0000269|PubMed:25275454}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000269|PubMed:18227255,
CC ECO:0000269|PubMed:18466294, ECO:0000269|PubMed:25275454}. Cell
CC membrane {ECO:0000269|PubMed:15306022, ECO:0000269|PubMed:18466294};
CC Lipid-anchor, GPI-anchor {ECO:0000303|PubMed:12845604}. Note=Found
CC anchored in the cell membrane as well as a covalently-linked GPI-
CC modified cell wall protein (GPI-CWP). {ECO:0000269|PubMed:18466294}.
CC -!- INDUCTION: Induced by iron starvation, hypoxia, amphotericin B, and
CC during hyphal growth. Repressed by ketoconazole and caspofungin.
CC Regulated by BCR1, HOG1, SFU1, TUP1, and UPC2.
CC {ECO:0000269|PubMed:10978273, ECO:0000269|PubMed:15306022,
CC ECO:0000269|PubMed:15387822, ECO:0000269|PubMed:15554973,
CC ECO:0000269|PubMed:15814599, ECO:0000269|PubMed:15917516,
CC ECO:0000269|PubMed:16339080, ECO:0000269|PubMed:18227255,
CC ECO:0000269|PubMed:20870877, ECO:0000269|PubMed:21205162,
CC 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 -!- PTM: Mannosylated. {ECO:0000269|PubMed:15306022}.
CC -!- DISRUPTION PHENOTYPE: Leads to defects in hemin and hemoglobin
CC utilization as sole source of iron. {ECO:0000269|PubMed:15306022,
CC ECO:0000269|PubMed:25275454, ECO:0000269|PubMed:27617569}.
CC -!- SIMILARITY: Belongs to the RBT5 family. {ECO:0000305}.
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DR EMBL; CP017626; AOW28806.1; -; Genomic_DNA.
DR RefSeq; XP_713317.1; XM_708224.2.
DR AlphaFoldDB; Q59UT4; -.
DR SMR; Q59UT4; -.
DR STRING; 237561.Q59UT4; -.
DR GeneID; 3645007; -.
DR KEGG; cal:CAALFM_C400130WA; -.
DR CGD; CAL0000195131; RBT5.
DR VEuPathDB; FungiDB:C4_00130W_A; -.
DR eggNOG; ENOG502SFDE; Eukaryota.
DR HOGENOM; CLU_079397_0_0_1; -.
DR InParanoid; Q59UT4; -.
DR OMA; DVACCIA; -.
DR OrthoDB; 1627841at2759; -.
DR PRO; PR:Q59UT4; -.
DR Proteomes; UP000000559; Chromosome 4.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005576; C:extracellular region; IDA:CGD.
DR GO; GO:0009277; C:fungal-type cell wall; IDA:CGD.
DR GO; GO:0005886; C:plasma membrane; IDA:CGD.
DR GO; GO:0030445; C:yeast-form cell wall; IDA:CGD.
DR GO; GO:0020037; F:heme binding; IDA:CGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043709; P:cell adhesion involved in single-species biofilm formation; IMP:CGD.
DR GO; GO:0006879; P:cellular iron ion homeostasis; IMP:CGD.
DR GO; GO:0020028; P:endocytic hemoglobin import into cell; IMP:CGD.
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..20
FT /evidence="ECO:0000255"
FT CHAIN 21..221
FT /note="GPI-anchored hemophore RBT5"
FT /id="PRO_0000424650"
FT PROPEP 222..241
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000424651"
FT REGION 48..111
FT /note="CFEM"
FT /evidence="ECO:0000269|PubMed:25275454,
FT ECO:0000303|PubMed:12633989"
FT REGION 140..210
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 140..156
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..184
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 195..210
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 72
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 221
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 54..94
FT /evidence="ECO:0000250|UniProtKB:Q5A0X8"
FT DISULFID 58..89
FT /evidence="ECO:0000250|UniProtKB:Q5A0X8"
FT DISULFID 68..75
FT /evidence="ECO:0000250|UniProtKB:Q5A0X8"
FT DISULFID 77..110
FT /evidence="ECO:0000250|UniProtKB:Q5A0X8"
FT MUTAGEN 72
FT /note="D->A: Abolishes heme-binding."
FT /evidence="ECO:0000269|PubMed:25275454"
FT MUTAGEN 72
FT /note="D->H: Impairs the heme transfer within the CFEM
FT proteins cascade."
FT /evidence="ECO:0000269|PubMed:27617569"
SQ SEQUENCE 241 AA; 24173 MW; DE45D24152B15FA4 CRC64;
MLALSLLSIV SIASAAGVTA IPEGDNPYTI FPSVAKTASI NGFADRIYDQ LPECAKECVK
QSTSSTPCPY WDTGCLCVMP QFAGAVGNCV AKNCKGKEVG SVESLATSIC SSAGVWEPYW
MIPSSVSDAL AKAADAAAET TAESTTAEST AAETTKAEET SAKETTAAET SKAAESSAPA
ETSKAEETSK AAETTKAEES SVAQSSSSAA DVASVSVEAA NAGNMPAVAI GGVIAAVAAL
F
