ID   VPS34_CANAX             Reviewed;        1020 AA.
AC   Q92213;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1997, sequence version 1.
DT   27-MAR-2024, entry version 106.
DE   RecName: Full=Phosphatidylinositol 3-kinase VPS34 {ECO:0000303|PubMed:10870104};
DE            Short=PI3-kinase VPS34 {ECO:0000303|PubMed:10870104};
DE            Short=PI3K VPS34 {ECO:0000303|PubMed:10870104};
DE            Short=PtdIns-3-kinase VPS34 {ECO:0000303|PubMed:10870104};
DE            EC=2.7.1.137 {ECO:0000269|PubMed:10870104, ECO:0000269|PubMed:15632428};
DE   AltName: Full=Vacuolar protein sorting-associated protein 34 {ECO:0000303|PubMed:10870104};
GN   Name=VPS34 {ECO:0000303|PubMed:10870104};
OS   Candida albicans (Yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX   NCBI_TaxID=5476;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, FUNCTION, AND CATALYTIC
RP   ACTIVITY.
RC   STRAIN=3153A;
RX   PubMed=10870104;
RX   DOI=10.1002/1097-0061(200007)16:10<933::aid-yea591>3.0.co;2-c;
RA   Eck R., Bruckmann A., Wetzker R., Kunkel W.;
RT   "A phosphatidylinositol 3-kinase of Candida albicans: molecular cloning and
RT   characterization.";
RL   Yeast 16:933-944(2000).
RN   [2]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=11223944;
RX   DOI=10.1002/1097-0061(20010315)18:4<343::aid-yea675>3.0.co;2-z;
RA   Bruckmann A., Kuenkel W., Augsten K., Wetzker R., Eck R.;
RT   "The deletion of CaVPS34 in the human pathogenic yeast Candida albicans
RT   causes defects in vesicle-mediated protein sorting and nuclear
RT   segregation.";
RL   Yeast 18:343-353(2001).
RN   [3]
RP   FUNCTION, DISRUPTION PHENOTYPE, AND INTERACTION WITH VMA7.
RX   PubMed=15861817; DOI=10.1016/j.ijmm.2004.12.007;
RA   Eck R., Nguyen M., Guenther J., Kuenkel W., Zipfel P.F.;
RT   "The phosphatidylinositol 3-kinase Vps34p of the human pathogenic yeast
RT   Candida albicans is a multifunctional protein that interacts with the
RT   putative vacuolar H+ -ATPase subunit Vma7p.";
RL   Int. J. Med. Microbiol. 295:57-66(2005).
RN   [4]
RP   FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION, MUTAGENESIS OF
RP   902-ASP--PRO-907, AND DISRUPTION PHENOTYPE.
RX   PubMed=15632428; DOI=10.1099/mic.0.27333-0;
RA   Guenther J., Nguyen M., Haertl A., Kuenkel W., Zipfel P.F., Eck R.;
RT   "Generation and functional in vivo characterization of a lipid kinase
RT   defective phosphatidylinositol 3-kinase Vps34p of Candida albicans.";
RL   Microbiology 151:81-89(2005).
CC   -!- FUNCTION: Multifunctional phosphatidylinositol 3-kinase involved in
CC       acidification of vacuoles, pH-dependent cell growth, and
CC       autophagocytosis (PubMed:15861817, PubMed:15632428). Plays an important
CC       role in protein transport and virulence (PubMed:11223944,
CC       PubMed:15632428). Component of the autophagy-specific VPS34 PI3-kinase
CC       complex I essential to recruit the ATG8-phosphatidylinositol conjugate
CC       and the ATG12-ATG5 conjugate to the pre-autophagosomal structure (By
CC       similarity). Also involved in endosome-to-Golgi retrograde transport as
CC       part of the VPS34 PI3-kinase complex II (By similarity). This second
CC       complex is required for the endosome-to-Golgi retrieval of PEP1 and
CC       KEX2, and the recruitment of VPS5 and VPS7, two components of the
CC       retromer complex, to endosomal membranes (probably through the
CC       synthesis of a specific pool of phosphatidylinositol 3-phosphate
CC       recruiting the retromer to the endosomes) (By similarity). Finally, it
CC       might also be involved in ethanol tolerance and cell wall integrity (By
CC       similarity). {ECO:0000250|UniProtKB:P22543,
CC       ECO:0000269|PubMed:11223944, ECO:0000269|PubMed:15632428,
CC       ECO:0000269|PubMed:15861817}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a
CC         1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP +
CC         H(+); Xref=Rhea:RHEA:12709, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:57880, ChEBI:CHEBI:58088, ChEBI:CHEBI:456216;
CC         EC=2.7.1.137; Evidence={ECO:0000269|PubMed:10870104,
CC         ECO:0000269|PubMed:15632428};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC         Evidence={ECO:0000269|PubMed:10870104, ECO:0000269|PubMed:15632428};
CC   -!- SUBUNIT: Component of the autophagy-specific VPS34 PI3-kinase complex I
CC       composed of at least VPS15, VPS30, VPS34, and of the VPS34 PI3-kinase
CC       complex II composed of VPS15, VPS30, VPS34 and VPS38 (By similarity).
CC       Interacts with VMNA7 (PubMed:15861817). {ECO:0000250|UniProtKB:P22543,
CC       ECO:0000269|PubMed:15861817}.
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network membrane
CC       {ECO:0000250|UniProtKB:P22543}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P22543}. Endosome membrane
CC       {ECO:0000250|UniProtKB:P22543}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:P22543}.
CC   -!- INDUCTION: Expression is increased up to 12-fold during exponential
CC       growth, followed by a decline upon entry into stationary phase.
CC       {ECO:0000269|PubMed:10870104}.
CC   -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:15632428}.
CC   -!- DISRUPTION PHENOTYPE: Leads to defective acidification of the vacuoles
CC       and a lack of growth at pH 8.0 (PubMed:15861817). Vacuoles are
CC       considerably enlarged and electron-transparent (PubMed:11223944). Shows
CC       aberrant patch-like accumulation of vesicles, which are localized in
CC       the periplasm close to the plasma membrane (PubMed:11223944). Shows a
CC       staining of punctuate structures, possibly multivesicular bodies (MVB),
CC       that are scattered all over the cell, the result of a late block in
CC       endocytic vesicle transport (PubMed:11223944). Results in significantly
CC       lower carboxypeptidase Y activity (PubMed:11223944). Causes disturbance
CC       of normal nuclear migration (PubMed:11223944). Leads also to avirulence
CC       in mice (PubMed:15632428). {ECO:0000269|PubMed:11223944,
CC       ECO:0000269|PubMed:15632428, ECO:0000269|PubMed:15861817}.
CC   -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC       ProRule:PRU00880}.
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DR   EMBL; Y09043; CAA70254.1; -; Genomic_DNA.
DR   PIR; T18260; T18260.
DR   AlphaFoldDB; Q92213; -.
DR   SMR; Q92213; -.
DR   VEuPathDB; FungiDB:C1_06680W_A; -.
DR   VEuPathDB; FungiDB:CAWG_00745; -.
DR   BRENDA; 2.7.1.137; 1096.
DR   PHI-base; PHI:195; -.
DR   GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0000329; C:fungal-type vacuole membrane; IEA:EnsemblFungi.
DR   GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR   GO; GO:0071561; C:nucleus-vacuole junction; IEA:EnsemblFungi.
DR   GO; GO:0005777; C:peroxisome; IEA:EnsemblFungi.
DR   GO; GO:0000407; C:phagophore assembly site; IEA:EnsemblFungi.
DR   GO; GO:0034271; C:phosphatidylinositol 3-kinase complex, class III, type I; IEA:EnsemblFungi.
DR   GO; GO:0034272; C:phosphatidylinositol 3-kinase complex, class III, type II; IEA:EnsemblFungi.
DR   GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IEA:UniProtKB-EC.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004672; F:protein kinase activity; IEA:EnsemblFungi.
DR   GO; GO:0032120; P:ascospore-type prospore membrane formation; IEA:EnsemblFungi.
DR   GO; GO:0000425; P:pexophagy; IEA:EnsemblFungi.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0032968; P:positive regulation of transcription elongation by RNA polymerase II; IEA:EnsemblFungi.
DR   CDD; cd08397; C2_PI3K_class_III; 1.
DR   CDD; cd00896; PI3Kc_III; 1.
DR   Gene3D; 2.60.40.150; C2 domain; 1.
DR   Gene3D; 1.10.1070.11; Phosphatidylinositol 3-/4-kinase, catalytic domain; 1.
DR   Gene3D; 1.25.40.70; Phosphatidylinositol 3-kinase, accessory domain (PIK); 1.
DR   InterPro; IPR016024; ARM-type_fold.
DR   InterPro; IPR035892; C2_domain_sf.
DR   InterPro; IPR011009; Kinase-like_dom_sf.
DR   InterPro; IPR000403; PI3/4_kinase_cat_dom.
DR   InterPro; IPR036940; PI3/4_kinase_cat_sf.
DR   InterPro; IPR018936; PI3/4_kinase_CS.
DR   InterPro; IPR002420; PI3K-type_C2_dom.
DR   InterPro; IPR001263; PI3K_accessory_dom.
DR   InterPro; IPR042236; PI3K_accessory_sf.
DR   InterPro; IPR008290; PI3K_Vps34.
DR   InterPro; IPR015433; PI_Kinase.
DR   PANTHER; PTHR10048:SF7; PHOSPHATIDYLINOSITOL 3-KINASE CATALYTIC SUBUNIT TYPE 3; 1.
DR   PANTHER; PTHR10048; PHOSPHATIDYLINOSITOL KINASE; 1.
DR   Pfam; PF00454; PI3_PI4_kinase; 1.
DR   Pfam; PF00792; PI3K_C2; 1.
DR   Pfam; PF00613; PI3Ka; 2.
DR   PIRSF; PIRSF000587; PI3K_Vps34; 1.
DR   SMART; SM00142; PI3K_C2; 1.
DR   SMART; SM00145; PI3Ka; 1.
DR   SMART; SM00146; PI3Kc; 1.
DR   SUPFAM; SSF48371; ARM repeat; 1.
DR   SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   PROSITE; PS51547; C2_PI3K; 1.
DR   PROSITE; PS00915; PI3_4_KINASE_1; 1.
DR   PROSITE; PS00916; PI3_4_KINASE_2; 1.
DR   PROSITE; PS50290; PI3_4_KINASE_3; 1.
DR   PROSITE; PS51545; PIK_HELICAL; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Endosome; Golgi apparatus; Kinase; Membrane;
KW   Nucleotide-binding; Transferase.
FT   CHAIN           1..1020
FT                   /note="Phosphatidylinositol 3-kinase VPS34"
FT                   /id="PRO_0000088816"
FT   DOMAIN          49..210
FT                   /note="C2 PI3K-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT   DOMAIN          331..577
FT                   /note="PIK helical"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT   DOMAIN          666..1004
FT                   /note="PI3K/PI4K catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          672..678
FT                   /note="G-loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          873..881
FT                   /note="Catalytic loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   REGION          892..913
FT                   /note="Activation loop"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT   MUTAGEN         902..907
FT                   /note="DPKPFP->AILREKYPERV: Lacks lipid kinase activity but
FT                   retains autophosphorylation activity."
FT                   /evidence="ECO:0000269|PubMed:15632428"
SQ   SEQUENCE   1020 AA;  117401 MW;  FF798F55AD2C8231 CRC64;
     MATLSQPQSA LPKTKIATTF GLSKDLKSPI SVKVCYLECT RNNVSLVPLS TKFEDPTVFK
     KLSQIYKNSD LFVEIRVYDG KNNNLISTPV RTSYKAFNNK GRTWNQQLKL NIDYNQISID
     AYLKFSICEI IDTKPSVFGV SYLSLFSHDS STLRSGSHKI PVFMEDDPQY SKNIQYGTLI
     GLTDLEKRLI DYENGKYPRL NWLDKMVLPK VDATFLKTNN KDHDYYLYIE LPQFEFPIVY
     SDIIYQIPTI EPITETTSKI PPDDTLNSNI IINSIDIPMA TSHDPSIMKV YDPDFHITAN
     NHLNPNATTF DPVELKYRKL ERNIDNNTIL DKELKPTPQL RDELLRIMIK PSNAESTDNE
     KNLIWKFRYY FSKNNSGNDP SNKSVKSFLP KFLRSINWEN DYELDHTFKE IIPFYWNVDK
     LQIGDALELL GDYFNPYTLG KPTYQDDSMT SKSSKMKSDE KRFIKIYNNV CFLRKLAVER
     LKLANSEELL LYLLQLVQAL KYEALIYEKS PPFCERSDQI EDNASSTLKS PLADFLIERA
     VENEKLGNFF YWYVKVENED QLNNPHIDGP IKIYMDILNR YIELLKAHCH ENRLPYYKHL
     KHQIWFIKKL TSLVELLRAS FKKNEATAKK VEYLREYLAN SGNELLKFPE PFPLPLDPSV
     MICGCYPEES SVFKSSLAPL KITLKTIEKK KHGHATSQLF GKRSRYGKYP LMFKIGDDLR
     QDQLVIQIID LMDQLLKNEN LDLKLTPYKI LATSPISGLI QFVPNETLDS ILSKTYPTSV
     TYSGGGETSD GPPSVSNNGI LNYLRLHSQE QQSEEPISKS ILSTNTSQSN TEIPVLPRQP
     KPTITSDLGV SPILMDNYVK SCAGYCVITY ILGVGDRHLD NLLLSPNGKF WHADFGYILG
     RDPKPFPPLM KLPIQVIDGM GGLHHENYNV FKSYCFITYT TLRKNSNLIL NLFQLMLDAN
     IPDIQFDPSR VIEKVQEKFC LQMTEEEAIL HFQNLINDSV NAFLPVVIDR LHSLAQYWRA
//