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Protein

Hyphal wall protein 1

Gene

HWP1

Organism
Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Major hyphal cell wall protein which plays a role of adhesin and is required for mating, normal hyphal development, cell-to-cell adhesive functions necessary for biofilm integrity, attachment to host, and virulence. Promotes interactions with host and bacterial molecules, thus leading to effective colonization within polymicrobial communities. Plays a crucial role in gastrointestinal colonization, in mucosal symptomatic and asymptomatic infections, in vaginitis, as well as in lethal oroesophageal candidiasis, caused by the combined action of fungal virulence factors and host inflammatory responses when protective immunity is absent.16 Publications

Miscellaneous

As a major cell surface protein expressed during infection, HWP1 detection can be used for diagnosis of invasive candidiasis. HWP1 epitopes can also be used to develop vaccines for protection against candidiasis.

GO - Molecular functioni

  • cell adhesion molecule binding Source: CGD

GO - Biological processi

  • adhesion of symbiont to host Source: CGD
  • cell adhesion Source: CGD
  • cell adhesion involved in biofilm formation Source: CGD
  • cell adhesion involved in single-species biofilm formation in or on host organism Source: CGD
  • fungal-type cell wall organization Source: CGD
  • growth of symbiont in host Source: CGD
  • pathogenesis Source: CGD
  • single organismal cell-cell adhesion Source: CGD
  • single-species biofilm formation on inanimate substrate Source: CGD

Keywordsi

Biological processCell adhesion, Virulence

Names & Taxonomyi

Protein namesi
Recommended name:
Hyphal wall protein 1
Alternative name(s):
Cell elongation protein 2
Gene namesi
Name:HWP1
Synonyms:ECE2
Ordered Locus Names:CAALFM_C403570WA
ORF Names:CaO19.1321, CaO19.8901
OrganismiCandida albicans (strain SC5314 / ATCC MYA-2876) (Yeast)
Taxonomic identifieri237561 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaAscomycotaSaccharomycotinaSaccharomycetesSaccharomycetalesDebaryomycetaceaeCandida/Lodderomyces cladeCandida
Proteomesi
  • UP000000559 Componenti: Chromosome 4

Organism-specific databases

CGDiCAL0000200504. HWP1.

Subcellular locationi

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • cell surface Source: CGD
  • extracellular region Source: UniProtKB-KW
  • fungal-type cell wall Source: CGD
  • hyphal cell wall Source: CGD
  • mating projection Source: CGD

Keywords - Cellular componenti

Cell wall, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

Reduces the overall mating frequency in both liquid and solid media. Impairs stable attachments to human buccal epithelial cells and reduces capacity to cause systemic candidiasis in mice. Produces a thin biofilm that lacks much of the hyphal mass found in the wild type cell.6 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi613G → D, N or S: Still allows localization to the cell surface. 1 Publication1
Mutagenesisi613G → E, Q, R or T: Impairs cell surface localization and localizes exclusively to internal ER-like structures. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000008409728 – 613Hyphal wall protein 1Add BLAST586
PropeptideiPRO_0000425596614 – 634Removed in mature formAdd BLAST21

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi241N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi286N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi601N-linked (GlcNAc...) asparagineSequence analysis1
Lipidationi613GPI-anchor amidated glycine1 Publication1

Post-translational modificationi

The GPI-anchor is attached to the protein in the endoplasmic reticulum and serves to target the protein to the cell surface. There, the glucosamine-inositol phospholipid moiety is cleaved off and the GPI-modified mannoprotein is covalently attached via its lipidless GPI glycan remnant to the 1,6-beta-glucan of the outer cell wall layer.
Serves as a substrate for mammalian transglutaminases which are necessary for cross-linking between HWP1 and host epithelial cells. Also predicted to be a substrate for cleavage by KEX2.
N- and O-glycosylated.2 Publications

Keywords - PTMi

Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

PRIDEiP46593.

Expressioni

Developmental stagei

Found in hyphal but not yeast forms.

Inductioni

The promoter contains a 368 bp region, the HWP1 control region (HCR), which is target of transcription factors and is critical for activation under hypha-inducing conditions. Expression is positively regulated by BCR1, EFG1, FLO8, GPA2, GPR1, MSS11, RBF1, and RFG1; and negatively regulated by NRG1 and TUP1. Transcription is induced in an adhesion-dependent manner and in presence of human serum or hemoglobin. Expression is down-regulated by hypoxic conditions, allicine, ethylenediaminetetra-acetic acid (EDTA), farnesol, linalool, riccardin D, purpurin, filastatin, phorbasin H, Ocimum sanctum essential oil (OSEO), as well as many substances belonging to chemical classes such as methyl aryl-oxazoline carboxylates, dihydrobenzo-d-isoxazolones, and thiazolo-4,5-e-benzoisoxazoles. Moreover, the competitors Saccharomyces boulardii or Streptococcus mutans secrete respectively capric acid and trans-2-decenoic acid (SDSF) which also suppress HWP1 expression.35 Publications

Interactioni

GO - Molecular functioni

  • cell adhesion molecule binding Source: CGD

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati46 – 581; approximateAdd BLAST13
Repeati59 – 692; approximateAdd BLAST11
Repeati70 – 813; approximateAdd BLAST12
Repeati82 – 91410
Repeati92 – 101510
Repeati102 – 111610
Repeati112 – 121710
Repeati122 – 131810
Repeati132 – 141910
Repeati142 – 1511010
Repeati152 – 1611110
Repeati162 – 1711210
Repeati172 – 17913; truncated8
Repeati180 – 18714; truncated8

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni46 – 18714 X 10 AA tandem repeats of [EVIQ]-P-[CDT]-D-[YNW]-P-[PQ]-[QI]-[QP]-[QDN]Add BLAST142

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi53 – 58Poly-Gln6
Compositional biasi65 – 69Poly-Gln5
Compositional biasi204 – 207Poly-Thr4
Compositional biasi208 – 220Poly-SerAdd BLAST13
Compositional biasi291 – 294Poly-Thr4
Compositional biasi304 – 307Poly-Thr4
Compositional biasi398 – 401Poly-Val4

Sequence similaritiesi

Belongs to the HWP1 family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

InParanoidiP46593.
OrthoDBiEOG092C4VN7.

Family and domain databases

InterProiView protein in InterPro
IPR025928. Flocculin_t3_rpt.
PfamiView protein in Pfam
PF13928. Flocculin_t3. 2 hits.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P46593-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRLSTAQLIA IAYYMLSIGA TVPQVDGQGE TEEALIQKRS YDYYQEPCDD
60 70 80 90 100
YPQQQQQQEP CDYPQQQQQE EPCDYPQQQP QEPCDYPQQP QEPCDYPQQP
110 120 130 140 150
QEPCDYPQQP QEPCDNPPQP DVPCDNPPQP DVPCDNPPQP DVPCDNPPQP
160 170 180 190 200
DVPCDNPPQP DQPDDNPPIP NIPTDWIPNI PTDWIPDIPE KPTTPATTPN
210 220 230 240 250
IPATTTTSES SSSSSSSSSS TTPKTSASTT PESSVPATTP NTSVPTTSSE
260 270 280 290 300
STTPATSPES SVPVTSGSSI LATTSESSSA PATTPNTSVP TTTTEAKSSS
310 320 330 340 350
TPLTTTTEHD TTVVTVTSCS NSVCTESEVT TGVIVITSKD TIYTTYCPLT
360 370 380 390 400
ETTPVSTAPA TETPTGTVST STEQSTTVIT VTSCSESSCT ESEVTTGVVV
410 420 430 440 450
VTSEETVYTT FCPLTENTPG TDSTPEASIP PMETIPAGSE PSMPAGETSP
460 470 480 490 500
AVPKSDVPAT ESAPVPEMTP AGSQPSIPAG ETSPAVPKSD VSATESAPAP
510 520 530 540 550
EMTPAGTETK PAAPKSSAPA TEPSPVAPGT ESAPAGPGAS SSPKSSVLAS
560 570 580 590 600
ETSPIAPGAE TAPAGSSGAI TIPESSAVVS TTEGAIPTTL ESVPLMQPSA
610 620 630
NYSSVAPIST FEGAGNNMRL TFGAAIIGIA AFLI
Length:634
Mass (Da):65,314
Last modified:March 15, 2017 - v5
Checksum:iD48F1FD5C659EAC1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti142V → I in AAC96368 (PubMed:9639315).Curated1
Sequence conflicti142V → I in AAB64014 (PubMed:10464197).Curated1
Sequence conflicti142V → VPCDNPPQPDI in AAC49209 (PubMed:8626424).Curated1
Sequence conflicti152V → I in AAC96368 (PubMed:9639315).Curated1
Sequence conflicti152V → I in AAB64014 (PubMed:10464197).Curated1
Sequence conflicti152V → I in AAC49209 (PubMed:8626424).Curated1
Sequence conflicti296A → T in AAC96368 (PubMed:9639315).Curated1
Sequence conflicti441P → S in AAC96368 (PubMed:9639315).Curated1
Sequence conflicti492S → P in AAC96368 (PubMed:9639315).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U64206 Genomic DNA. Translation: AAC96368.1.
AF001978 Genomic DNA. Translation: AAB64014.1.
CP017626 Genomic DNA. Translation: AOW29115.1.
U29369 mRNA. Translation: AAC49209.1.
RefSeqiXP_709961.2. XM_704869.2.

Genome annotation databases

EnsemblFungiiEAK93836; EAK93836; CaO19.8901.
EAK93868; EAK93868; CaO19.1321.
GeneIDi3645372.
KEGGical:CAALFM_C403570WA.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U64206 Genomic DNA. Translation: AAC96368.1.
AF001978 Genomic DNA. Translation: AAB64014.1.
CP017626 Genomic DNA. Translation: AOW29115.1.
U29369 mRNA. Translation: AAC49209.1.
RefSeqiXP_709961.2. XM_704869.2.

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Proteomic databases

PRIDEiP46593.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblFungiiEAK93836; EAK93836; CaO19.8901.
EAK93868; EAK93868; CaO19.1321.
GeneIDi3645372.
KEGGical:CAALFM_C403570WA.

Organism-specific databases

CGDiCAL0000200504. HWP1.

Phylogenomic databases

InParanoidiP46593.
OrthoDBiEOG092C4VN7.

Family and domain databases

InterProiView protein in InterPro
IPR025928. Flocculin_t3_rpt.
PfamiView protein in Pfam
PF13928. Flocculin_t3. 2 hits.
ProtoNetiSearch...

Entry informationi

Entry nameiHWP1_CANAL
AccessioniPrimary (citable) accession number: P46593
Secondary accession number(s): A0A1D8PLV3
, O13424, P87019, Q59TL7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: March 15, 2017
Last modified: May 10, 2017
This is version 71 of the entry and version 5 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Candida albicans
    Candida albicans: entries and gene names
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.