PK3C3_HUMAN
ID PK3C3_HUMAN Reviewed; 887 AA.
AC Q8NEB9; Q15134;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Phosphatidylinositol 3-kinase catalytic subunit type 3;
DE Short=PI3-kinase type 3;
DE Short=PI3K type 3;
DE Short=PtdIns-3-kinase type 3;
DE EC=2.7.1.137 {ECO:0000269|PubMed:7628435};
DE AltName: Full=Phosphatidylinositol 3-kinase p100 subunit;
DE AltName: Full=Phosphoinositide-3-kinase class 3;
DE AltName: Full=hVps34;
GN Name=PIK3C3 {ECO:0000312|HGNC:HGNC:8974}; Synonyms=VPS34 {ECO:0000305};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, COFACTOR,
RP SUBUNIT, TISSUE SPECIFICITY, AND INTERACTION WITH PIK3R4.
RX PubMed=7628435; DOI=10.1002/j.1460-2075.1995.tb07340.x;
RA Volinia S., Dhand R., Vanhaesebroeck B., MacDougall L.K., Zvelebil M.J.,
RA Domin J., Panaretou C., Waterfield M.D.;
RT "A human phosphatidylinositol 3-kinase complex related to the yeast Vps34p-
RT Vps15p protein sorting system.";
RL EMBO J. 14:3339-3348(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH RAB7A AND PIK3R4, AND SUBCELLULAR LOCATION.
RX PubMed=14617358; DOI=10.1034/j.1600-0854.2003.00133.x;
RA Stein M.P., Feng Y., Cooper K.L., Welford A.M., Wandinger-Ness A.;
RT "Human VPS34 and p150 are Rab7 interacting partners.";
RL Traffic 4:754-771(2003).
RN [4]
RP INTERACTION WITH NCKAP1L.
RX PubMed=16417406; DOI=10.1371/journal.pbio.0040038;
RA Weiner O.D., Rentel M.C., Ott A., Brown G.E., Jedrychowski M., Yaffe M.B.,
RA Gygi S.P., Cantley L.C., Bourne H.R., Kirschner M.W.;
RT "Hem-1 complexes are essential for Rac activation, actin polymerization,
RT and myosin regulation during neutrophil chemotaxis.";
RL PLoS Biol. 4:E38-E38(2006).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [6]
RP INTERACTION WITH BECN1 AND ATG14.
RX PubMed=19050071; DOI=10.1073/pnas.0810452105;
RA Sun Q., Fan W., Chen K., Ding X., Chen S., Zhong Q.;
RT "Identification of Barkor as a mammalian autophagy-specific factor for
RT Beclin 1 and class III phosphatidylinositol 3-kinase.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:19211-19216(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [8]
RP FUNCTION, AND SUBUNIT.
RX PubMed=20643123; DOI=10.1016/j.yexcr.2010.07.008;
RA Thoresen S.B., Pedersen N.M., Liestol K., Stenmark H.;
RT "A phosphatidylinositol 3-kinase class III sub-complex containing VPS15,
RT VPS34, Beclin 1, UVRAG and BIF-1 regulates cytokinesis and degradative
RT endocytic traffic.";
RL Exp. Cell Res. 316:3368-3378(2010).
RN [9]
RP INTERACTION WITH BECN1; RUBCN; ATG14; PIK3R4 AND UVRAG.
RX PubMed=19270696; DOI=10.1038/ncb1846;
RA Matsunaga K., Saitoh T., Tabata K., Omori H., Satoh T., Kurotori N.,
RA Maejima I., Shirahama-Noda K., Ichimura T., Isobe T., Akira S., Noda T.,
RA Yoshimori T.;
RT "Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate
RT autophagy at different stages.";
RL Nat. Cell Biol. 11:385-396(2009).
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=20208530; DOI=10.1038/ncb2036;
RA Sagona A.P., Nezis I.P., Pedersen N.M., Liestol K., Poulton J.,
RA Rusten T.E., Skotheim R.I., Raiborg C., Stenmark H.;
RT "PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of
RT FYVE-CENT to the midbody.";
RL Nat. Cell Biol. 12:362-371(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP INTERACTION WITH SLAMF1.
RX PubMed=22493499; DOI=10.1074/jbc.m112.367060;
RA Ma C., Wang N., Detre C., Wang G., O'Keeffe M., Terhorst C.;
RT "Receptor signaling lymphocyte-activation molecule family 1 (Slamf1)
RT regulates membrane fusion and NADPH oxidase 2 (NOX2) activity by recruiting
RT a Beclin-1/Vps34/ultraviolet radiation resistance-associated gene (UVRAG)
RT complex.";
RL J. Biol. Chem. 287:18359-18365(2012).
RN [13]
RP INTERACTION WITH BECN1P1/BECN2.
RX PubMed=23954414; DOI=10.1016/j.cell.2013.07.035;
RA He C., Wei Y., Sun K., Li B., Dong X., Zou Z., Liu Y., Kinch L.N., Khan S.,
RA Sinha S., Xavier R.J., Grishin N.V., Xiao G., Eskelinen E.L., Scherer P.E.,
RA Whistler J.L., Levine B.;
RT "Beclin 2 functions in autophagy, degradation of G protein-coupled
RT receptors, and metabolism.";
RL Cell 154:1085-1099(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-282, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP INTERACTION WITH BECN1.
RX PubMed=23878393; DOI=10.1128/mcb.00079-13;
RA Fogel A.I., Dlouhy B.J., Wang C., Ryu S.W., Neutzner A., Hasson S.A.,
RA Sideris D.P., Abeliovich H., Youle R.J.;
RT "Role of membrane association and Atg14-dependent phosphorylation in
RT beclin-1-mediated autophagy.";
RL Mol. Cell. Biol. 33:3675-3688(2013).
RN [16]
RP RECONSTITUTION OF THE PI3K COMPLEX I, AND ELECTRON MICROSCOPY OF THE PI3K
RP COMPLEX I.
RX PubMed=25490155; DOI=10.7554/elife.05115;
RA Baskaran S., Carlson L.A., Stjepanovic G., Young L.N., Kim do J., Grob P.,
RA Stanley R.E., Nogales E., Hurley J.H.;
RT "Architecture and dynamics of the autophagic phosphatidylinositol 3-kinase
RT complex.";
RL Elife 3:0-0(2014).
RN [17]
RP INTERACTION WITH ATG14.
RX PubMed=31806350; DOI=10.1016/j.molcel.2019.10.035;
RA Miao G., Zhang Y., Chen D., Zhang H.;
RT "The ER-Localized Transmembrane Protein TMEM39A/SUSR2 Regulates Autophagy
RT by Controlling the Trafficking of the PtdIns(4)P Phosphatase SAC1.";
RL Mol. Cell 0:0-0(2019).
RN [18]
RP FUNCTION, AND INTERACTION WITH STEEP1.
RX PubMed=32690950; DOI=10.1038/s41590-020-0730-5;
RA Zhang B.C., Nandakumar R., Reinert L.S., Huang J., Laustsen A., Gao Z.L.,
RA Sun C.L., Jensen S.B., Troldborg A., Assil S., Berthelsen M.F.,
RA Scavenius C., Zhang Y., Windross S.J., Olagnier D., Prabakaran T.,
RA Bodda C., Narita R., Cai Y., Zhang C.G., Stenmark H., Doucet C.M., Noda T.,
RA Guo Z., Goldbach-Mansky R., Hartmann R., Chen Z.J., Enghild J.J., Bak R.O.,
RA Thomsen M.K., Paludan S.R.;
RT "STEEP mediates STING ER exit and activation of signaling.";
RL Nat. Immunol. 21:868-879(2020).
RN [19]
RP ERRATUM OF PUBMED:32690950.
RX PubMed=32929276; DOI=10.1038/s41590-020-0803-5;
RA Zhang B.C., Nandakumar R., Reinert L.S., Huang J., Laustsen A., Gao Z.L.,
RA Sun C.L., Jensen S.B., Troldborg A., Assil S., Berthelsen M.F.,
RA Scavenius C., Zhang Y., Windross S.J., Olagnier D., Prabakaran T.,
RA Bodda C., Narita R., Cai Y., Zhang C.G., Stenmark H., Doucet C.M., Noda T.,
RA Guo Z., Goldbach-Mansky R., Hartmann R., Chen Z.J., Enghild J.J., Bak R.O.,
RA Thomsen M.K., Paludan S.R.;
RL Nat. Immunol. 21:1468-1469(2020).
RN [20]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=34320401; DOI=10.1016/j.celrep.2021.109479;
RA Williams C.G., Jureka A.S., Silvas J.A., Nicolini A.M., Chvatal S.A.,
RA Carlson-Stevermer J., Oki J., Holden K., Basler C.F.;
RT "Inhibitors of VPS34 and fatty-acid metabolism suppress SARS-CoV-2
RT replication.";
RL Cell Rep. 36:109479-109479(2021).
RN [21]
RP INTERACTION WITH YWHAG.
RX PubMed=33473107; DOI=10.1038/s41467-020-20780-2;
RA Wang W., Li J., Tan J., Wang M., Yang J., Zhang Z.M., Li C.,
RA Basnakian A.G., Tang H.W., Perrimon N., Zhou Q.;
RT "Endonuclease G promotes autophagy by suppressing mTOR signaling and
RT activating the DNA damage response.";
RL Nat. Commun. 12:476-476(2021).
RN [22]
RP FUNCTION, UBIQUITINATION, AND DEUBIQUITINATION.
RX PubMed=33637724; DOI=10.1038/s41467-021-21715-1;
RA Chen Y.H., Huang T.Y., Lin Y.T., Lin S.Y., Li W.H., Hsiao H.J., Yan R.L.,
RA Tang H.W., Shen Z.Q., Chen G.C., Wu K.P., Tsai T.F., Chen R.H.;
RT "VPS34 K29/K48 branched ubiquitination governed by UBE3C and TRABID
RT regulates autophagy, proteostasis and liver metabolism.";
RL Nat. Commun. 12:1322-1322(2021).
CC -!- FUNCTION: Catalytic subunit of the PI3K complex that mediates formation
CC of phosphatidylinositol 3-phosphate; different complex forms are
CC believed to play a role in multiple membrane trafficking pathways:
CC PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in
CC maturation of autophagosomes and endocytosis (PubMed:14617358,
CC PubMed:7628435, PubMed:33637724). As part of PI3KC3-C1, promotes
CC endoplasmic reticulum membrane curvature formation prior to vesicle
CC budding (PubMed:32690950). Involved in regulation of degradative
CC endocytic trafficking and required for the abcission step in
CC cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20208530,
CC PubMed:20643123). Involved in the transport of lysosomal enzyme
CC precursors to lysosomes (By similarity). Required for transport from
CC early to late endosomes (By similarity). {ECO:0000250|UniProtKB:O88763,
CC ECO:0000269|PubMed:14617358, ECO:0000269|PubMed:20208530,
CC ECO:0000269|PubMed:20643123, ECO:0000269|PubMed:32690950,
CC ECO:0000269|PubMed:33637724, ECO:0000269|PubMed:7628435}.
CC -!- FUNCTION: (Microbial infection) Kinase activity is required for SARS
CC coronavirus-2/SARS-CoV-2 replication. {ECO:0000269|PubMed:34320401}.
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:7628435};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000305|PubMed:7628435};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:7628435};
CC -!- SUBUNIT: Component of the PI3K (PI3KC3/PI3K-III/class III
CC phosphatidylinositol 3-kinase) complex the core of which is composed of
CC the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1
CC associating with additional regulatory/auxilliary subunits to form
CC alternative complex forms. Alternative complex forms containing a forth
CC regulatory subunit in a mutually exclusive manner are: the PI3K complex
CC I (PI3KC3-C1) containing ATG14, and the PI3K complex II (PI3KC3-C2)
CC containing UVRAG. PI3KC3-C1 displays a V-shaped architecture with
CC PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1
CC subcomplex. Both, PI3KC3-C1 and PI3KC3-C2, can associate with further
CC regulatory subunits such as RUBCN, SH3GLB1/Bif-1 and AMBRA1
CC (PubMed:7628435, PubMed:19050071, PubMed:20643123, PubMed:19270696,
CC PubMed:23878393, PubMed:25490155). PI3KC3-C1 probably associates with
CC PIK3CB (By similarity). Interacts with RAB7A in the presence of PIK3R4
CC (PubMed:14617358). Interacts with AMBRA1 (By similarity). Interacts
CC with BECN1P1/BECN2 (PubMed:23954414). Interacts with
CC SLAMF1(PubMed:22493499). May be a component of a complex composed of
CC RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity). Interacts
CC with NCKAP1L (PubMed:16417406). Interacts with ATG14; this interaction
CC is increased in the absence of TMEM39A (PubMed:31806350). Interacts
CC with STEEP1; the interaction is STING1-dependent and required for
CC trafficking of STING1 from the endoplasmic reticulum (PubMed:32690950).
CC Interacts with YWHAG (PubMed:33473107). {ECO:0000250|UniProtKB:Q6PF93,
CC ECO:0000250|UniProtKB:Q9TXI7, ECO:0000269|PubMed:14617358,
CC ECO:0000269|PubMed:16417406, ECO:0000269|PubMed:19050071,
CC ECO:0000269|PubMed:19270696, ECO:0000269|PubMed:20643123,
CC ECO:0000269|PubMed:22493499, ECO:0000269|PubMed:23878393,
CC ECO:0000269|PubMed:23954414, ECO:0000269|PubMed:25490155,
CC ECO:0000269|PubMed:31806350, ECO:0000269|PubMed:32690950,
CC ECO:0000269|PubMed:33473107, ECO:0000269|PubMed:7628435, ECO:0000305}.
CC -!- INTERACTION:
CC Q8NEB9; Q6ZNE5: ATG14; NbExp=27; IntAct=EBI-1056470, EBI-2690371;
CC Q8NEB9; Q14457: BECN1; NbExp=39; IntAct=EBI-1056470, EBI-949378;
CC Q8NEB9; Q96F24: NRBF2; NbExp=12; IntAct=EBI-1056470, EBI-2362014;
CC Q8NEB9; Q92622: RUBCN; NbExp=7; IntAct=EBI-1056470, EBI-2952709;
CC Q8NEB9; Q9P2Y5: UVRAG; NbExp=23; IntAct=EBI-1056470, EBI-2952704;
CC Q8NEB9; Q17UT5: X; Xeno; NbExp=2; IntAct=EBI-1056470, EBI-15834514;
CC -!- SUBCELLULAR LOCATION: Midbody {ECO:0000269|PubMed:20208530}. Late
CC endosome {ECO:0000269|PubMed:14617358}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000305|PubMed:14617358}. Note=As component of the
CC PI3K complex I localized to pre-autophagosome structures. As component
CC of the PI3K complex II localized predominantly to endosomes
CC (PubMed:14617358). Localizes also to discrete punctae along the ciliary
CC axoneme and to the base of the ciliary axoneme (By similarity).
CC {ECO:0000250|UniProtKB:Q6PF93, ECO:0000305|PubMed:14617358}.
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with a highest expression
CC in skeletal muscle. {ECO:0000269|PubMed:7628435}.
CC -!- PTM: Ubiquitinated via 'Lys-29'- and 'Lys-48'-linked ubiquitination by
CC UBE3C, promoting its degradation (PubMed:33637724). Deubiquitination by
CC ZRANB1/TRABID promotes its stabilization, leading to autophagosome
CC maturation (PubMed:33637724). {ECO:0000269|PubMed:33637724}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00880}.
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DR EMBL; Z46973; CAA87094.1; -; mRNA.
DR EMBL; BC033004; AAH33004.1; -; mRNA.
DR EMBL; BC053651; AAH53651.1; -; mRNA.
DR CCDS; CCDS11920.1; -.
DR PIR; S57219; S57219.
DR RefSeq; NP_002638.2; NM_002647.3.
DR PDB; 3IHY; X-ray; 2.80 A; A/B/C/D/E=282-879.
DR PDB; 3LS8; X-ray; 2.25 A; A/B=268-879.
DR PDB; 4OYS; X-ray; 2.90 A; A=282-879.
DR PDB; 4PH4; X-ray; 2.80 A; B=293-887.
DR PDB; 4UWF; X-ray; 2.99 A; A=282-879.
DR PDB; 4UWG; X-ray; 2.70 A; A=282-879.
DR PDB; 4UWH; X-ray; 1.93 A; A=282-879.
DR PDB; 4UWK; X-ray; 2.83 A; A=282-879.
DR PDB; 4UWL; X-ray; 2.80 A; A=282-879.
DR PDB; 5ANL; X-ray; 2.70 A; A=282-879.
DR PDB; 5ENN; X-ray; 2.70 A; A/B=293-887.
DR PDB; 6HOH; X-ray; 2.25 A; A/B/C/D=244-258.
DR PDB; 6I3U; X-ray; 2.09 A; A=268-879.
DR PDB; 6YKG; X-ray; 3.12 A; AAA=268-879.
DR PDB; 7BL1; EM; 9.80 A; BBB=1-887.
DR PDB; 7RSJ; X-ray; 1.88 A; A=282-879.
DR PDB; 7RSP; X-ray; 1.67 A; A/B=282-879.
DR PDB; 7RSV; X-ray; 1.78 A; A/B=282-879.
DR PDBsum; 3IHY; -.
DR PDBsum; 3LS8; -.
DR PDBsum; 4OYS; -.
DR PDBsum; 4PH4; -.
DR PDBsum; 4UWF; -.
DR PDBsum; 4UWG; -.
DR PDBsum; 4UWH; -.
DR PDBsum; 4UWK; -.
DR PDBsum; 4UWL; -.
DR PDBsum; 5ANL; -.
DR PDBsum; 5ENN; -.
DR PDBsum; 6HOH; -.
DR PDBsum; 6I3U; -.
DR PDBsum; 6YKG; -.
DR PDBsum; 7BL1; -.
DR PDBsum; 7RSJ; -.
DR PDBsum; 7RSP; -.
DR PDBsum; 7RSV; -.
DR AlphaFoldDB; Q8NEB9; -.
DR SMR; Q8NEB9; -.
DR BioGRID; 111307; 92.
DR ComplexPortal; CPX-73; Phosphatidylinositol 3-kinase complex, class III, ATG14 variant.
DR ComplexPortal; CPX-74; Phosphatidylinositol 3-kinase complex, class III, UVRAG variant.
DR CORUM; Q8NEB9; -.
DR DIP; DIP-42272N; -.
DR IntAct; Q8NEB9; 29.
DR MINT; Q8NEB9; -.
DR STRING; 9606.ENSP00000262039; -.
DR BindingDB; Q8NEB9; -.
DR ChEMBL; CHEMBL1075165; -.
DR DrugBank; DB06836; N-(5-{4-Chloro-3-[(2-hydroxyethyl)sulfamoyl]phenyl}-4-methyl-1,3-thiazol-2-yl)acetamide.
DR GuidetoPHARMACOLOGY; 2152; -.
DR SwissLipids; SLP:000000904; -.
DR iPTMnet; Q8NEB9; -.
DR MetOSite; Q8NEB9; -.
DR PhosphoSitePlus; Q8NEB9; -.
DR BioMuta; PIK3C3; -.
DR DMDM; 74730233; -.
DR EPD; Q8NEB9; -.
DR jPOST; Q8NEB9; -.
DR MassIVE; Q8NEB9; -.
DR MaxQB; Q8NEB9; -.
DR PaxDb; Q8NEB9; -.
DR PeptideAtlas; Q8NEB9; -.
DR PRIDE; Q8NEB9; -.
DR ProteomicsDB; 73147; -.
DR Antibodypedia; 22392; 952 antibodies from 39 providers.
DR DNASU; 5289; -.
DR Ensembl; ENST00000262039.9; ENSP00000262039.3; ENSG00000078142.14.
DR GeneID; 5289; -.
DR KEGG; hsa:5289; -.
DR MANE-Select; ENST00000262039.9; ENSP00000262039.3; NM_002647.4; NP_002638.2.
DR UCSC; uc002lap.4; human.
DR CTD; 5289; -.
DR DisGeNET; 5289; -.
DR GeneCards; PIK3C3; -.
DR HGNC; HGNC:8974; PIK3C3.
DR HPA; ENSG00000078142; Low tissue specificity.
DR MIM; 602609; gene.
DR neXtProt; NX_Q8NEB9; -.
DR OpenTargets; ENSG00000078142; -.
DR PharmGKB; PA33307; -.
DR VEuPathDB; HostDB:ENSG00000078142; -.
DR eggNOG; KOG0906; Eukaryota.
DR GeneTree; ENSGT00940000156943; -.
DR InParanoid; Q8NEB9; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; Q8NEB9; -.
DR TreeFam; TF102032; -.
DR BioCyc; MetaCyc:HS01275-MON; -.
DR BRENDA; 2.7.1.137; 2681.
DR PathwayCommons; Q8NEB9; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1632852; Macroautophagy.
DR Reactome; R-HSA-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-HSA-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-HSA-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-HSA-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-9679504; Translation of Replicase and Assembly of the Replication Transcription Complex.
DR Reactome; R-HSA-9694676; Translation of Replicase and Assembly of the Replication Transcription Complex.
DR Reactome; R-HSA-9705671; SARS-CoV-2 activates/modulates innate and adaptive immune responses.
DR Reactome; R-HSA-983170; Antigen Presentation: Folding, assembly and peptide loading of class I MHC.
DR SignaLink; Q8NEB9; -.
DR SIGNOR; Q8NEB9; -.
DR BioGRID-ORCS; 5289; 557 hits in 1101 CRISPR screens.
DR ChiTaRS; PIK3C3; human.
DR EvolutionaryTrace; Q8NEB9; -.
DR GeneWiki; PIK3C3; -.
DR GenomeRNAi; 5289; -.
DR Pharos; Q8NEB9; Tchem.
DR PRO; PR:Q8NEB9; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q8NEB9; protein.
DR Bgee; ENSG00000078142; Expressed in calcaneal tendon and 200 other tissues.
DR ExpressionAtlas; Q8NEB9; baseline and differential.
DR Genevisible; Q8NEB9; HS.
DR GO; GO:0044754; C:autolysosome; IDA:MGI.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IBA:GO_Central.
DR GO; GO:0030670; C:phagocytic vesicle membrane; TAS:Reactome.
DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; IPI:ComplexPortal.
DR GO; GO:0034271; C:phosphatidylinositol 3-kinase complex, class III, type I; IBA:GO_Central.
DR GO; GO:0034272; C:phosphatidylinositol 3-kinase complex, class III, type II; IBA:GO_Central.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; IMP:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:Ensembl.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0097352; P:autophagosome maturation; IDA:ComplexPortal.
DR GO; GO:0006914; P:autophagy; IMP:MGI.
DR GO; GO:0030242; P:autophagy of peroxisome; IBA:GO_Central.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0042149; P:cellular response to glucose starvation; ISS:UniProtKB.
DR GO; GO:0045022; P:early endosome to late endosome transport; IDA:ComplexPortal.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0007032; P:endosome organization; IEA:Ensembl.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:0046854; P:phosphatidylinositol phosphate biosynthetic process; IBA:GO_Central.
DR GO; GO:0036092; P:phosphatidylinositol-3-phosphate biosynthetic process; IDA:ComplexPortal.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IBA:GO_Central.
DR GO; GO:0006497; P:protein lipidation; IMP:MGI.
DR GO; GO:0034497; P:protein localization to phagophore assembly site; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:ComplexPortal.
DR GO; GO:0016485; P:protein processing; IEA:Ensembl.
DR GO; GO:0006622; P:protein targeting to lysosome; IC:ComplexPortal.
DR GO; GO:0010506; P:regulation of autophagy; IDA:ComplexPortal.
DR GO; GO:0032465; P:regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; IDA:ComplexPortal.
DR GO; GO:0050708; P:regulation of protein secretion; IEA:Ensembl.
DR GO; GO:0043201; P:response to leucine; IEA:Ensembl.
DR Gene3D; 1.10.1070.11; -; 1.
DR Gene3D; 1.25.40.70; -; 1.
DR Gene3D; 2.60.40.150; -; 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; PTHR10048; 1.
DR Pfam; PF00454; PI3_PI4_kinase; 1.
DR Pfam; PF00792; PI3K_C2; 1.
DR Pfam; PF00613; PI3Ka; 1.
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; SSF48371; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 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 3D-structure; ATP-binding; Autophagy; Cell cycle; Cell division;
KW Cytoplasmic vesicle; Endosome; Kinase; Lipid metabolism; Manganese;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Transferase;
KW Ubl conjugation.
FT CHAIN 1..887
FT /note="Phosphatidylinositol 3-kinase catalytic subunit type
FT 3"
FT /id="PRO_0000088802"
FT DOMAIN 35..184
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 283..520
FT /note="PIK helical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00878"
FT DOMAIN 605..871
FT /note="PI3K/PI4K catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 149..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 447..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 611..617
FT /note="G-loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 740..748
FT /note="Catalytic loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT REGION 759..780
FT /note="Activation loop"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00269"
FT MOD_RES 163
FT /note="Phosphothreonine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:Q6PF93"
FT MOD_RES 165
FT /note="Phosphoserine; by AMPK"
FT /evidence="ECO:0000250|UniProtKB:Q6PF93"
FT MOD_RES 244
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88763"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CONFLICT 36
FT /note="K -> N (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 70
FT /note="L -> S (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="F -> S (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 158
FT /note="K -> N (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 208
FT /note="E -> V (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 219..220
FT /note="VE -> GG (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 262
FT /note="M -> L (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 272..274
FT /note="KLA -> NLP (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 289..292
FT /note="NAAT -> YPSP (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 297..298
FT /note="NI -> KN (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 305..308
FT /note="TKQL -> SKPP (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 318
FT /note="K -> E (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="E -> D (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 333..338
FT /note="FLKCVN -> ILTSVI (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="E -> G (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 350
FT /note="E -> A (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 356
FT /note="K -> N (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 367
FT /note="L -> I (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 397
FT /note="L -> S (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 428
FT /note="E -> G (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 484
FT /note="C -> S (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 750
FT /note="L -> V (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT CONFLICT 826
FT /note="A -> P (in Ref. 1; CAA87094)"
FT /evidence="ECO:0000305"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:6I3U"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:6I3U"
FT HELIX 290..301
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:4UWG"
FT HELIX 310..318
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 320..323
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 330..336
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 342..354
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 360..367
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 374..384
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 389..402
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 403..405
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 408..413
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 437..439
FT /evidence="ECO:0007829|PDB:4UWH"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:7RSJ"
FT TURN 445..447
FT /evidence="ECO:0007829|PDB:7RSJ"
FT HELIX 475..484
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 487..501
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 504..509
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 511..530
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 533..561
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 566..578
FT /evidence="ECO:0007829|PDB:7RSP"
FT TURN 580..583
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 591..593
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 596..604
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 606..608
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 613..616
FT /evidence="ECO:0007829|PDB:6I3U"
FT STRAND 619..625
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 630..638
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 642..660
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 672..676
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 679..683
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 690..697
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 700..707
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 711..713
FT /evidence="ECO:0007829|PDB:4UWH"
FT HELIX 714..716
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 719..738
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 748..751
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 757..759
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 770..773
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 781..786
FT /evidence="ECO:0007829|PDB:7RSP"
FT STRAND 790..792
FT /evidence="ECO:0007829|PDB:4UWF"
FT HELIX 793..811
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 813..821
FT /evidence="ECO:0007829|PDB:7RSP"
FT TURN 822..825
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 829..832
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 835..837
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 838..845
FT /evidence="ECO:0007829|PDB:7RSP"
FT TURN 846..849
FT /evidence="ECO:0007829|PDB:7RSP"
FT HELIX 852..868
FT /evidence="ECO:0007829|PDB:7RSP"
SQ SEQUENCE 887 AA; 101549 MW; 1C03D97338E44976 CRC64;
MGEAEKFHYI YSCDLDINVQ LKIGSLEGKR EQKSYKAVLE DPMLKFSGLY QETCSDLYVT
CQVFAEGKPL ALPVRTSYKA FSTRWNWNEW LKLPVKYPDL PRNAQVALTI WDVYGPGKAV
PVGGTTVSLF GKYGMFRQGM HDLKVWPNVE ADGSEPTKTP GRTSSTLSED QMSRLAKLTK
AHRQGHMVKV DWLDRLTFRE IEMINESEKR SSNFMYLMVE FRCVKCDDKE YGIVYYEKDG
DESSPILTSF ELVKVPDPQM SMENLVESKH HKLARSLRSG PSDHDLKPNA ATRDQLNIIV
SYPPTKQLTY EEQDLVWKFR YYLTNQEKAL TKFLKCVNWD LPQEAKQALE LLGKWKPMDV
EDSLELLSSH YTNPTVRRYA VARLRQADDE DLLMYLLQLV QALKYENFDD IKNGLEPTKK
DSQSSVSENV SNSGINSAEI DSSQIITSPL PSVSSPPPAS KTKEVPDGEN LEQDLCTFLI
SRACKNSTLA NYLYWYVIVE CEDQDTQQRD PKTHEMYLNV MRRFSQALLK GDKSVRVMRS
LLAAQQTFVD RLVHLMKAVQ RESGNRKKKN ERLQALLGDN EKMNLSDVEL IPLPLEPQVK
IRGIIPETAT LFKSALMPAQ LFFKTEDGGK YPVIFKHGDD LRQDQLILQI ISLMDKLLRK
ENLDLKLTPY KVLATSTKHG FMQFIQSVPV AEVLDTEGSI QNFFRKYAPS ENGPNGISAE
VMDTYVKSCA GYCVITYILG VGDRHLDNLL LTKTGKLFHI DFGYILGRDP KPLPPPMKLN
KEMVEGMGGT QSEQYQEFRK QCYTAFLHLR RYSNLILNLF SLMVDANIPD IALEPDKTVK
KVQDKFRLDL SDEEAVHYMQ SLIDESVHAL FAAVVEQIHK FAQYWRK
