VPS4_CANAL
ID VPS4_CANAL Reviewed; 439 AA.
AC Q5AG40; A0A1D8PNL7; Q5AGH7;
DT 04-FEB-2015, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Vacuolar protein sorting-associated protein 4 {ECO:0000305};
GN Name=VPS4 {ECO:0000303|PubMed:15590834};
GN OrderedLocusNames=CAALFM_C503090WA; ORFNames=CaO19.11814, CaO19.4339;
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 FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=15590834; DOI=10.1128/ec.3.6.1609-1618.2004;
RA Kullas A.L., Li M., Davis D.A.;
RT "Snf7p, a component of the ESCRT-III protein complex, is an upstream member
RT of the RIM101 pathway in Candida albicans.";
RL Eukaryot. Cell 3:1609-1618(2004).
RN [5]
RP INDUCTION.
RX PubMed=16215176; DOI=10.1128/ec.4.10.1687-1696.2005;
RA Tournu H., Tripathi G., Bertram G., Macaskill S., Mavor A., Walker L.,
RA Odds F.C., Gow N.A., Brown A.J.;
RT "Global role of the protein kinase Gcn2 in the human pathogen Candida
RT albicans.";
RL Eukaryot. Cell 4:1687-1696(2005).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=17506830; DOI=10.1111/j.1567-1364.2007.00253.x;
RA Lee S.A., Jones J., Khalique Z., Kot J., Alba M., Bernardo S., Seghal A.,
RA Wong B.;
RT "A functional analysis of the Candida albicans homolog of Saccharomyces
RT cerevisiae VPS4.";
RL FEMS Yeast Res. 7:973-985(2007).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19819358; DOI=10.1016/j.jprot.2009.10.003;
RA Thomas D.P., Lopez-Ribot J.L., Lee S.A.;
RT "A proteomic analysis of secretory proteins of a pre-vacuolar mutant of
RT Candida albicans.";
RL J. Proteomics 73:342-351(2009).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18814053; DOI=10.1007/s11046-008-9155-7;
RA Lee S.A., Jones J., Hardison S., Kot J., Khalique Z., Bernardo S.M.,
RA Lazzell A., Monteagudo C., Lopez-Ribot J.;
RT "Candida albicans VPS4 is required for secretion of aspartyl proteases and
RT in vivo virulence.";
RL Mycopathologia 167:55-63(2009).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20581294; DOI=10.1128/ec.00056-10;
RA Wolf J.M., Johnson D.J., Chmielewski D., Davis D.A.;
RT "The Candida albicans ESCRT pathway makes Rim101-dependent and -independent
RT contributions to pathogenesis.";
RL Eukaryot. Cell 9:1203-1215(2010).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20026677; DOI=10.1534/genetics.109.112029;
RA Wolf J.M., Davis D.A.;
RT "Mutational analysis of Candida albicans SNF7 reveals genetically separable
RT Rim101 and ESCRT functions and demonstrates divergence in bro1-domain
RT protein interactions.";
RL Genetics 184:673-694(2010).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=22427429; DOI=10.1128/ec.05211-11;
RA Gomez-Raja J., Davis D.A.;
RT "The beta-arrestin-like protein Rim8 is hyperphosphorylated and complexes
RT with Rim21 and Rim101 to promote adaptation to neutral-alkaline pH.";
RL Eukaryot. Cell 11:683-693(2012).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25483774; DOI=10.4161/21505594.2014.956648;
RA Rane H.S., Hardison S., Botelho C., Bernardo S.M., Wormley F. Jr.,
RA Lee S.A.;
RT "Candida albicans VPS4 contributes differentially to epithelial and mucosal
RT pathogenesis.";
RL Virulence 5:810-818(2014).
CC -!- FUNCTION: Pre-vacuolar protein sorting protein involved in the
CC transport of biosynthetic membrane proteins from the
CC prevacuolar/endosomal compartment to the vacuole. Required for
CC multivesicular body (MVB) protein sorting. Catalyzes the ATP-dependent
CC dissociation of class E VPS proteins from endosomal membranes, such as
CC the disassembly of the ESCRT-III complex. Required for extracellular
CC secretion of the secreted aspartyl proteases SAP2, SAP4, SAP5, and
CC SAP6. Its regulation of the pre-vacuolar secretory pathway is critical
CC for virulence. {ECO:0000269|PubMed:15590834,
CC ECO:0000269|PubMed:17506830, ECO:0000269|PubMed:18814053,
CC ECO:0000269|PubMed:19819358, ECO:0000269|PubMed:20026677,
CC ECO:0000269|PubMed:20581294, ECO:0000269|PubMed:22427429,
CC ECO:0000269|PubMed:25483774}.
CC -!- SUBUNIT: Monomer or homodimer (in nucleotide-free form). Decamer,
CC dodecamer or tetradecamer of two stacked respective homooligomeric
CC rings (when bound to ATP); the dodecameric form seems to be
CC predominant. {ECO:0000250|UniProtKB:P52917}.
CC -!- SUBCELLULAR LOCATION: Endosome membrane {ECO:0000250|UniProtKB:P52917};
CC Peripheral membrane protein {ECO:0000305}.
CC -!- INDUCTION: Expression is regulated by GCN2 and GCN4.
CC {ECO:0000269|PubMed:16215176}.
CC -!- DISRUPTION PHENOTYPE: Leads to defects in endocytosis. Displays a
CC characteristic class E vacuolar morphology and multilamellar structures
CC consistent with an aberrant prevacuolar compartment. Missorts several
CC vacuolar proteins to the extracellular space, including
CC carboxypeptidase (CPY), vacuolar protease A (PrA), and vacuolar
CC protease B (PrB). In addition, certain soluble secretory proteins, such
CC as invertase and acid phosphatase, are missorted from the pre-vacuolar
CC compartment (PVC) to the general secretory pathway prior to exocytosis.
CC Results also in a decrease of canonically secreted proteins. Shows
CC increased biofilm formation. Causes reduced tissue damage in an in
CC vitro oral epithelial model (OEM) of tissue invasion, and defects in
CC macrophage killing in vitro. Shows also attenuated virulence in an in
CC vivo Caenorhabditis elegans model representative of intestinal
CC epithelial infection. {ECO:0000269|PubMed:15590834,
CC ECO:0000269|PubMed:17506830, ECO:0000269|PubMed:18814053,
CC ECO:0000269|PubMed:19819358, ECO:0000269|PubMed:20026677,
CC ECO:0000269|PubMed:20581294, ECO:0000269|PubMed:22427429,
CC ECO:0000269|PubMed:25483774}.
CC -!- SIMILARITY: Belongs to the AAA ATPase family. {ECO:0000305}.
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DR EMBL; CP017627; AOW29729.1; -; Genomic_DNA.
DR RefSeq; XP_720644.1; XM_715551.2.
DR AlphaFoldDB; Q5AG40; -.
DR SMR; Q5AG40; -.
DR STRING; 237561.Q5AG40; -.
DR GeneID; 3637703; -.
DR KEGG; cal:CAALFM_C503090WA; -.
DR CGD; CAL0000180282; VPS4.
DR VEuPathDB; FungiDB:C5_03090W_A; -.
DR eggNOG; KOG0739; Eukaryota.
DR HOGENOM; CLU_000688_21_2_1; -.
DR InParanoid; Q5AG40; -.
DR OrthoDB; 787710at2759; -.
DR PHI-base; PHI:2553; -.
DR PRO; PR:Q5AG40; -.
DR Proteomes; UP000000559; Chromosome 5.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0071285; P:cellular response to lithium ion; IMP:CGD.
DR GO; GO:0016197; P:endosomal transport; IBA:GO_Central.
DR GO; GO:0030447; P:filamentous growth; IMP:CGD.
DR GO; GO:0044182; P:filamentous growth of a population of unicellular organisms; IMP:CGD.
DR GO; GO:0030448; P:hyphal growth; IMP:CGD.
DR GO; GO:0045324; P:late endosome to vacuole transport; IMP:CGD.
DR GO; GO:0009306; P:protein secretion; IMP:CGD.
DR GO; GO:0006623; P:protein targeting to vacuole; IMP:CGD.
DR GO; GO:0007033; P:vacuole organization; IMP:CGD.
DR CDD; cd02678; MIT_VPS4; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR003593; AAA+_ATPase.
DR InterPro; IPR003959; ATPase_AAA_core.
DR InterPro; IPR003960; ATPase_AAA_CS.
DR InterPro; IPR007330; MIT_dom.
DR InterPro; IPR036181; MIT_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR015415; Vps4_C.
DR InterPro; IPR045253; VPS4_MIT.
DR Pfam; PF00004; AAA; 1.
DR Pfam; PF04212; MIT; 1.
DR Pfam; PF09336; Vps4_C; 1.
DR SMART; SM00382; AAA; 1.
DR SMART; SM00745; MIT; 1.
DR SUPFAM; SSF116846; SSF116846; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS00674; AAA; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Endosome; Membrane; Nucleotide-binding; Reference proteome;
KW Virulence.
FT CHAIN 1..439
FT /note="Vacuolar protein sorting-associated protein 4"
FT /id="PRO_0000431935"
FT DOMAIN 8..75
FT /note="MIT"
FT /evidence="ECO:0000255"
FT REGION 76..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 81..100
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 175..182
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00136"
FT VARIANT 4
FT /note="A -> V (in allele: CaO19.11814)"
FT VARIANT 102
FT /note="G -> S (in allele: CaO19.11814)"
SQ SEQUENCE 439 AA; 48437 MW; 316CB3263A8F6DEE CRC64;
MSGASDFLSK GIDLVQKAID ADTATRYEEA YKLYYNGLDY LMLAIKYEKN PKSKELVKSK
FTEYLTRAEQ LKDHLEKQAQ NKSTAESSVN GSTKAKKSNG DGNGSGDDND DADTKKLRGA
LAGAILSEKP NVKWSDIAGL DAAKEALKEA VILPVKFPQL FVGNRKPTSG ILLYGPPGTG
KSYLAKAVAT EANSTFFSVS SSDLVSKWMG ESERLVKQLF TMARENKPSI IFIDEVDALC
GPRGEGESEA SRRIKTELLV QMNGVGNDSQ GVLVLGATNI PWQLDAAVRR RFERRIYIAL
PDVEARTRMF EINIGDVPCE CTPHDYRTLA EMTDGYSGHD VAVVVRDALM QPIRKIQQAT
HFKPVIDETD GKEKLTPCSP GDEGAREMNW MDLATDELKE PPLTIKDFIK AIKNNRPTVN
EADIAQHVKF TEDFGQEGN
