HYR1_CANAL
ID HYR1_CANAL Reviewed; 919 AA.
AC Q5AL03; A0A1D8PFM8; Q5ALC8;
DT 11-DEC-2013, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 2.
DT 03-AUG-2022, entry version 74.
DE RecName: Full=Hyphally regulated cell wall protein 1;
DE AltName: Full=Adhesin-like protein HYR1;
DE Flags: Precursor;
GN Name=HYR1; Synonyms=GPX1; OrderedLocusNames=CAALFM_C113450WA;
GN ORFNames=CaO19.12440, CaO19.4975;
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 IDENTIFICATION, AND INDUCTION.
RX PubMed=8808922; DOI=10.1128/jb.178.18.5353-5360.1996;
RA Bailey D.A., Feldmann P.J.F., Bovey M., Gow N.A.R., Brown A.J.P.;
RT "The Candida albicans HYR1 gene, which is activated in response to hyphal
RT development, belongs to a gene family encoding yeast cell wall proteins.";
RL J. Bacteriol. 178:5353-5360(1996).
RN [5]
RP INDUCTION.
RX PubMed=11532938; DOI=10.1093/emboj/20.17.4742;
RA Murad A.M., Leng P., Straffon M., Wishart J., Macaskill S., MacCallum D.,
RA Schnell N., Talibi D., Marechal D., Tekaia F., d'Enfert C., Gaillardin C.,
RA Odds F.C., Brown A.J.;
RT "NRG1 represses yeast-hypha morphogenesis and hypha-specific gene
RT expression in Candida albicans.";
RL EMBO J. 20:4742-4752(2001).
RN [6]
RP INDUCTION.
RX PubMed=11395474; DOI=10.1128/jb.183.13.4090-4093.2001;
RA Leng P., Lee P.R., Wu H., Brown A.J.;
RT "Efg1, a morphogenetic regulator in Candida albicans, is a sequence-
RT specific DNA binding protein.";
RL J. Bacteriol. 183:4090-4093(2001).
RN [7]
RP INDUCTION.
RX PubMed=11259598; DOI=10.1128/mcb.21.7.2496-2505.2001;
RA Kadosh D., Johnson A.D.;
RT "Rfg1, a protein related to the Saccharomyces cerevisiae hypoxic regulator
RT Rox1, controls filamentous growth and virulence in Candida albicans.";
RL Mol. Cell. Biol. 21:2496-2505(2001).
RN [8]
RP INDUCTION.
RX PubMed=12477786; DOI=10.1128/ec.1.6.856-864.2002;
RA Hazan I., Liu H.;
RT "Hyphal tip-associated localization of Cdc42 is F-actin dependent in
RT Candida albicans.";
RL Eukaryot. Cell 1:856-864(2002).
RN [9]
RP INDUCTION.
RX PubMed=12492856; DOI=10.1046/j.1365-2958.2003.03300.x;
RA Sohn K., Urban C., Brunner H., Rupp S.;
RT "EFG1 is a major regulator of cell wall dynamics in Candida albicans as
RT revealed by DNA microarrays.";
RL Mol. Microbiol. 47:89-102(2003).
RN [10]
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 [11]
RP INDUCTION.
RX PubMed=16839200; DOI=10.1371/journal.ppat.0020063;
RA Nobile C.J., Andes D.R., Nett J.E., Smith F.J., Yue F., Phan Q.T.,
RA Edwards J.E., Filler S.G., Mitchell A.P.;
RT "Critical role of Bcr1-dependent adhesins in C. albicans biofilm formation
RT in vitro and in vivo.";
RL PLoS Pathog. 2:E63-E63(2006).
RN [12]
RP IDENTIFICATION IN THE HYR1/IFF FAMILY.
RX PubMed=17371861; DOI=10.1128/iai.00102-07;
RA Bates S., de la Rosa J.M., MacCallum D.M., Brown A.J., Gow N.A., Odds F.C.;
RT "Candida albicans Iff11, a secreted protein required for cell wall
RT structure and virulence.";
RL Infect. Immun. 75:2922-2928(2007).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND
RP IDENTIFICATION IN A COMPLEX WITH MP65 AND PRA1.
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 [14]
RP FUNCTION, AND INDUCTION.
RX PubMed=20415594; DOI=10.1086/652407;
RA Luo G., Ibrahim A.S., Spellberg B., Nobile C.J., Mitchell A.P., Fu Y.;
RT "Candida albicans Hyr1p confers resistance to neutrophil killing and is a
RT potential vaccine target.";
RL J. Infect. Dis. 201:1718-1728(2010).
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 IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, AND
RP KININOGEN-BINDING.
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 [17]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21283544; DOI=10.1371/journal.pone.0016218;
RA Dwivedi P., Thompson A., Xie Z., Kashleva H., Ganguly S., Mitchell A.P.,
RA Dongari-Bagtzoglou A.;
RT "Role of Bcr1-activated genes Hwp1 and Hyr1 in Candida albicans oral
RT mucosal biofilms and neutrophil evasion.";
RL PLoS ONE 6:E16218-E16218(2011).
RN [18]
RP FUNCTION IN VIRULENCE.
RX PubMed=22028796; DOI=10.1371/journal.pone.0025909;
RA Luo G., Ibrahim A.S., French S.W., Edwards J.E. Jr., Fu Y.;
RT "Active and passive immunization with rHyr1p-N protects mice against
RT hematogenously disseminated candidiasis.";
RL PLoS ONE 6:E25909-E25909(2011).
RN [19]
RP INDUCTION.
RX PubMed=23226409; DOI=10.1371/journal.pone.0050866;
RA Tsang P.W., Bandara H.M., Fong W.P.;
RT "Purpurin suppresses Candida albicans biofilm formation and hyphal
RT development.";
RL PLoS ONE 7:E50866-E50866(2012).
CC -!- FUNCTION: GPI-anchored hyphal cell wall protein required for hyphal
CC growth and virulence. Involved in innate immune cell evasion through
CC confering resistance to neutrophil killing. Binds kininogen, the
CC proteinaceous kinin precursor, and contributes to trigger the kinin-
CC forming cascade on the cell surface. Production of kinins is often
CC involved in the human host defense against microbial infections.
CC {ECO:0000269|PubMed:20415594, ECO:0000269|PubMed:21283544,
CC ECO:0000269|PubMed:22028796}.
CC -!- SUBUNIT: Component of a multiprotein complex of 250 kDa composed of at
CC least HYR1, MP65, and PRA1. {ECO:0000269|PubMed:17277107,
CC ECO:0000269|PubMed:17371861}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000269|PubMed:17277107,
CC ECO:0000269|PubMed:22074954}. Membrane {ECO:0000305}; Lipid-anchor,
CC GPI-anchor {ECO:0000305}.
CC -!- INDUCTION: Induced specifically in response to hyphal growth.
CC Expression is repressed by neutrophils and purpurin. Regulated by RFG1,
CC EFG1, NRG1, TUP1, CYR1, BCR1, and HAP43. {ECO:0000269|PubMed:11259598,
CC ECO:0000269|PubMed:11395474, ECO:0000269|PubMed:11532938,
CC ECO:0000269|PubMed:12477786, ECO:0000269|PubMed:12492856,
CC ECO:0000269|PubMed:16839200, ECO:0000269|PubMed:20415594,
CC ECO:0000269|PubMed:21592964, ECO:0000269|PubMed:23226409,
CC ECO:0000269|PubMed:8808922}.
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 -!- DISRUPTION PHENOTYPE: Leads to attenuated virulence in a mouse oral
CC biofilm model of infection. {ECO:0000269|PubMed:21283544}.
CC -!- SIMILARITY: Belongs to the HYR1/IFF family. {ECO:0000305}.
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DR EMBL; CP017623; AOW26950.1; -; Genomic_DNA.
DR RefSeq; XP_722183.2; XM_717090.2.
DR AlphaFoldDB; Q5AL03; -.
DR BioGRID; 1219162; 11.
DR STRING; 237561.Q5AL03; -.
DR GeneID; 3636226; -.
DR KEGG; cal:CAALFM_C113450WA; -.
DR CGD; CAL0000199501; HYR1.
DR VEuPathDB; FungiDB:C1_13450W_A; -.
DR HOGENOM; CLU_006199_0_0_1; -.
DR OrthoDB; 1483197at2759; -.
DR PRO; PR:Q5AL03; -.
DR Proteomes; UP000000559; Chromosome 1.
DR GO; GO:0031225; C:anchored component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0009986; C:cell surface; IEA:UniProt.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR GO; GO:0009277; C:fungal-type cell wall; IEA:UniProt.
DR InterPro; IPR021031; Hyphal-reg_cell_wall_N.
DR Pfam; PF11765; Hyphal_reg_CWP; 1.
PE 1: Evidence at protein level;
KW Cell wall; Glycoprotein; GPI-anchor; Lipoprotein; Membrane;
KW Reference proteome; Secreted; Signal; Virulence.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..895
FT /note="Hyphally regulated cell wall protein 1"
FT /id="PRO_0000424752"
FT PROPEP 896..919
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000424753"
FT REGION 332..483
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 567..839
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 567..802
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 814..839
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 895
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 236
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 488
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 580
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 585
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 607
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 619
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 631
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 639
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 647
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 693
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 729
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 741
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 755
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 879
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 895
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 919 AA; 91917 MW; 7A53FA025B9DFC48 CRC64;
MKVVSNFIFT ILLTLNLSAA LEVVTSRIDR GGIQGFHGDV KVHSGATWAI LGTTLCSFFG
GLEVEKGASL FIKSDNGPVL ALNVALSTLV RPVINNGVIS LNSKSSTSFS NFDIGGSSFT
NNGEIYLASS GLVKSTAYLY AREWTNNGLI VAYQNQKAAG NIAFGTAYQT ITNNGQICLR
HQDFVPATKI KGTGCVTADE DTWIKLGNTI LSVEPTHNFY LKDSKSSLIV HAVSSNQTFT
VHGFGNGNKL GLTLPLTGNR DHFRFEYYPD TGILQLRAAA LPQYFKIGKG YDSKLFRIVN
SRGLKNAVTY DGPVPNNEIP AVCLIPCTNG PSAPESESDL NTPTTSSIET SSYSSAATES
SVVSESSSAV DSLTSSSLSS KSESSDVVSS TTNIESSSTA IETTMNSESS TDAGSSSISQ
SESSSTAITS SSETSSSESM SASSTTASNT SIETDSGIVS QSESSSNALS STEQSITSSP
GQSTIYVNST VTSTITSCDE NKCTEDVVTI FTTVPCSTDC VPTTGDIPMS TSYTQRTVTS
TITNCDEVSC SQDVVTYTTN VPHTTVDATT TTTTSTGGDN STGGNESGSN HGSGAGSNEG
SQSGPNNGSG SGSEGGSNNG SGSGSDSGSN NGSGSGSNNG SGSGSNNGSG SGSGSTEGSE
GGSGSNEGSN HGSNEGSGSG SGSQTGSGSG SNNGSGSGSQ SGSGSGSQSG SESGSNSGSN
EGSNPGAGNG SNEGSGQGSG NGSEAGSGQG SGPNNGSGSG HNDGSGSGSN QGSNPGAGSG
SGSESGSNAG SHSGSNEGAK TDSIEGFHTE SKPGFNTGAH TDATVTGNSV ANPVTTSTES
DTTISVTVSI TSYMTGFDGK PKPFTTVDVI PVPHSMPSNT TDSSSSVPTI DTNENGSSIV
TGGKSILFGL IVSMVVLFM
