CSA2_CANAL
ID CSA2_CANAL Reviewed; 147 AA.
AC Q5A0X8; A0A1D8PMP6;
DT 07-JAN-2015, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Secreted hemophore CSA2 {ECO:0000303|PubMed:27617569};
DE AltName: Full=Surface antigen protein 2 {ECO:0000305};
DE Flags: Precursor;
GN Name=CSA2; Synonyms=CRW1; OrderedLocusNames=CAALFM_C406920CA;
GN ORFNames=CaO19.10629, CaO19.3117;
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=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 [5]
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 [6]
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 [7]
RP INDUCTION.
RX PubMed=16102003; DOI=10.1111/j.1365-2958.2005.04771.x;
RA Urban C., Xiong X., Sohn K., Schroppel K., Brunner H., Rupp S.;
RT "The moonlighting protein Tsa1p is implicated in oxidative stress response
RT and in cell wall biogenesis in Candida albicans.";
RL Mol. Microbiol. 57:1318-1341(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=20641015; DOI=10.1002/yea.1775;
RA Sorgo A.G., Heilmann C.J., Dekker H.L., Brul S., de Koster C.G., Klis F.M.;
RT "Mass spectrometric analysis of the secretome of Candida albicans.";
RL Yeast 27:661-672(2010).
RN [9]
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 [10]
RP INDUCTION.
RX PubMed=23563485; DOI=10.1128/ec.00071-13;
RA Srikantha T., Daniels K.J., Pujol C., Kim E., Soll D.R.;
RT "Identification of genes upregulated by the transcription factor Bcr1 that
RT are involved in impermeability, impenetrability, and drug resistance of
RT Candida albicans a/alpha biofilms.";
RL Eukaryot. Cell 12:875-888(2013).
RN [11]
RP DISRUPTION PHENOTYPE, FUNCTION, AND HEME-BINDING.
RX PubMed=24796871; DOI=10.1111/1567-1364.12160;
RA Okamoto-Shibayama K., Kikuchi Y., Kokubu E., Sato Y., Ishihara K.;
RT "Csa2, a member of the Rbt5 protein family, is involved in the utilization
RT of iron from human hemoglobin during Candida albicans hyphal growth.";
RL FEMS Yeast Res. 14:674-677(2014).
RN [12]
RP BIOTECHNOLOGY.
RX PubMed=25001939;
RA Liu L., Cai J., Liu C., Guo Y., Pan Y., Wang Y., Che X.;
RT "Establishment and evaluation of a double antibody sandwich ELISA to detect
RT Csa2 protein of Candida albicans.";
RL Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 30:732-735(2014).
RN [13] {ECO:0007744|PDB:4Y7S}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 34-144 IN COMPLEX WITH HEME,
RP SUBUNIT, FUNCTION, DISRUPTION PHENOTYPE, DOMAIN, DISULFIDE BOND, AND
RP MUTAGENESIS OF ASP-80.
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: Secreted heme-binding protein involved in the utilization of
CC iron from human hemoglobin during hyphal growth (PubMed:24796871,
CC PubMed:27617569). May also play a role in non-hemoglobin iron
CC utilization (PubMed:24796871). Heme transfer occurs between PGA7, RBT5
CC and CSA2 supporting a model in which the 3 CFEM proteins cooperate in a
CC heme-acquisition system and form a cross-cell wall heme-transfer
CC cascade (PubMed:27617569). The ability to acquire iron from host
CC tissues is a major virulence factor of pathogenic microorganisms
CC (PubMed:24796871). {ECO:0000269|PubMed:24796871,
CC ECO:0000269|PubMed:27617569}.
CC -!- SUBUNIT: Homodimer (PubMed:27617569). The possibility of a transient
CC honotrimer assembly of the holo protein is not ruled out
CC (PubMed:27617569). {ECO:0000269|PubMed:27617569}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:20641015}.
CC -!- INDUCTION: Expression is induced during hyphal growth, by ketoconazole,
CC and nitric oxide. Expression is also regulated by RIM101, TSA1, HAP43
CC and BCR1. {ECO:0000269|PubMed:15554973, ECO:0000269|PubMed:15917516,
CC ECO:0000269|PubMed:16030247, ECO:0000269|PubMed:16102003,
CC ECO:0000269|PubMed:20641015, ECO:0000269|PubMed:21592964,
CC ECO:0000269|PubMed:23563485}.
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:27617569). The CFEM
CC domain adopts a novel helical-basket fold that consists of six alpha-
CC helices, and is uniquely stabilized by four disulfide bonds formed by
CC its 8 signature cysteines (PubMed:27617569).
CC {ECO:0000269|PubMed:27617569}.
CC -!- DISRUPTION PHENOTYPE: Leads to defects in hemoglobin utilization as
CC sole source of iron. {ECO:0000269|PubMed:24796871}.
CC -!- BIOTECHNOLOGY: CSA2 could be used as a new diagnostic marker of Candida
CC albicans infection. {ECO:0000269|PubMed:25001939}.
CC -!- SIMILARITY: Belongs to the RBT5 family. {ECO:0000305}.
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DR EMBL; CP017626; AOW29413.1; -; Genomic_DNA.
DR RefSeq; XP_715426.1; XM_710333.1.
DR PDB; 4Y7S; X-ray; 2.00 A; A/B/C=34-144.
DR PDBsum; 4Y7S; -.
DR AlphaFoldDB; Q5A0X8; -.
DR SMR; Q5A0X8; -.
DR GeneID; 3642930; -.
DR KEGG; cal:CAALFM_C406920CA; -.
DR CGD; CAL0000201350; CSA2.
DR VEuPathDB; FungiDB:C4_06920C_A; -.
DR HOGENOM; CLU_147526_0_0_1; -.
DR InParanoid; Q5A0X8; -.
DR OMA; CKSAGVW; -.
DR OrthoDB; 1627841at2759; -.
DR PRO; PR:Q5A0X8; -.
DR Proteomes; UP000000559; Chromosome 4.
DR GO; GO:0005576; C:extracellular region; IDA:CGD.
DR GO; GO:0009277; C:fungal-type cell wall; IBA:GO_Central.
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; IMP:CGD.
DR GO; GO:0035351; P:heme transmembrane transport; IDA: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 3D-structure; Disulfide bond; Heme; Iron; Metal-binding;
KW Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..147
FT /note="Secreted hemophore CSA2"
FT /id="PRO_0000431444"
FT REGION 56..119
FT /note="CFEM"
FT /evidence="ECO:0000305|PubMed:27617569"
FT BINDING 80
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 ECO:0007744|PDB:4Y7S"
FT DISULFID 62..102
FT /evidence="ECO:0000269|PubMed:27617569"
FT DISULFID 66..97
FT /evidence="ECO:0000269|PubMed:27617569"
FT DISULFID 76..83
FT /evidence="ECO:0000269|PubMed:27617569"
FT DISULFID 85..118
FT /evidence="ECO:0000269|PubMed:27617569"
FT MUTAGEN 80
FT /note="D->H: Impairs the heme transfer within the CFEM
FT proteins cascade."
FT /evidence="ECO:0000269|PubMed:27617569"
FT HELIX 35..38
FT /evidence="ECO:0007829|PDB:4Y7S"
FT HELIX 52..55
FT /evidence="ECO:0007829|PDB:4Y7S"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:4Y7S"
FT HELIX 61..63
FT /evidence="ECO:0007829|PDB:4Y7S"
FT HELIX 65..68
FT /evidence="ECO:0007829|PDB:4Y7S"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:4Y7S"
FT HELIX 81..86
FT /evidence="ECO:0007829|PDB:4Y7S"
FT HELIX 88..101
FT /evidence="ECO:0007829|PDB:4Y7S"
FT HELIX 105..120
FT /evidence="ECO:0007829|PDB:4Y7S"
FT HELIX 132..143
FT /evidence="ECO:0007829|PDB:4Y7S"
SQ SEQUENCE 147 AA; 15078 MW; 0E339D80F96CC52C CRC64;
MKFSTILAIP FAIAFANAAA APAVTAAPAP AADNPYTIYP PVPKTASING FADRIYDQIP
KCAQECVKQS TSSTPCPYWD TGCLCVIPNF TGAVGNCVAS KCRGADVTNF RKLAVGACAA
AGVWDPYWII PASVSSALDA AATATGN
