PK3C3_RAT
ID PK3C3_RAT Reviewed; 887 AA.
AC O88763;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 165.
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:0000250|UniProtKB:Q8NEB9};
DE AltName: Full=Phosphoinositide-3-kinase class 3;
GN Name=Pik3c3 {ECO:0000312|RGD:620899}; Synonyms=Vps34;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RC TISSUE=Liver;
RX PubMed=11171063; DOI=10.1042/0264-6021:3530655;
RA Row P.E., Reaves B.J., Domin J., Luzio J.P., Davidson H.W.;
RT "Overexpression of a rat kinase-deficient phosphoinositide 3-kinase,
RT Vps34p, inhibits cathepsin D maturation.";
RL Biochem. J. 353:655-661(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-244, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. As part of PI3KC3-C1,
CC promotes endoplasmic reticulum membrane curvature formation prior to
CC vesicle budding. Involved in regulation of degradative endocytic
CC trafficking and required for the abcission step in cytokinesis,
CC probably in the context of PI3KC3-C2 (By similarity). Involved in the
CC transport of lysosomal enzyme precursors to lysosomes
CC (PubMed:11171063). Required for transport from early to late endosomes
CC (PubMed:11171063). {ECO:0000250|UniProtKB:Q8NEB9,
CC ECO:0000269|PubMed:11171063}.
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:0000250|UniProtKB:Q8NEB9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12710;
CC Evidence={ECO:0000250|UniProtKB:Q8NEB9};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q8NEB9};
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. PI3KC3-C1
CC probably associates with PIK3CB. Interacts with RAB7A in the presence
CC of PIK3R4. Interacts with AMBRA1. Interacts with BECN1P1/BECN2.
CC Interacts with SLAMF1. May interact with DYN2. May be a component of a
CC complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By
CC similarity). Interacts with NCKAP1L (By similarity). Interacts with
CC ATG14; this interaction is increased in the absence of TMEM39A (By
CC similarity). Interacts with STEEP1; the interaction is STING1-dependent
CC and required for trafficking of STING1 from the endoplasmic reticulum
CC (By similarity). Interacts with YWHAG (By similarity).
CC {ECO:0000250|UniProtKB:Q6PF93, ECO:0000250|UniProtKB:Q8NEB9,
CC ECO:0000250|UniProtKB:Q9TXI7}.
CC -!- SUBCELLULAR LOCATION: Midbody {ECO:0000250|UniProtKB:Q8NEB9}. Late
CC endosome {ECO:0000250|UniProtKB:Q8NEB9}. Cytoplasmic vesicle,
CC autophagosome {ECO:0000250|UniProtKB:Q8NEB9}. 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 (By
CC similarity). 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:0000250|UniProtKB:Q8NEB9}.
CC -!- PTM: Ubiquitinated via 'Lys-29'- and 'Lys-48'-linked ubiquitination by
CC UBE3C, promoting its degradation. Deubiquitination by ZRANB1/TRABID
CC promotes its stabilization, leading to autophagosome maturation.
CC {ECO:0000250|UniProtKB:Q8NEB9}.
CC -!- SIMILARITY: Belongs to the PI3/PI4-kinase family. {ECO:0000255|PROSITE-
CC ProRule:PRU00880}.
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DR EMBL; AJ006710; CAA07199.1; -; mRNA.
DR EMBL; BC061981; AAH61981.1; -; mRNA.
DR RefSeq; NP_075247.1; NM_022958.2.
DR AlphaFoldDB; O88763; -.
DR SMR; O88763; -.
DR DIP; DIP-60851N; -.
DR IntAct; O88763; 3.
DR STRING; 10116.ENSRNOP00000060791; -.
DR iPTMnet; O88763; -.
DR PhosphoSitePlus; O88763; -.
DR PaxDb; O88763; -.
DR GeneID; 65052; -.
DR KEGG; rno:65052; -.
DR UCSC; RGD:620899; rat.
DR CTD; 5289; -.
DR RGD; 620899; Pik3c3.
DR VEuPathDB; HostDB:ENSRNOG00000017840; -.
DR eggNOG; KOG0906; Eukaryota.
DR HOGENOM; CLU_004869_0_0_1; -.
DR InParanoid; O88763; -.
DR OMA; GRQKCKI; -.
DR OrthoDB; 204282at2759; -.
DR PhylomeDB; O88763; -.
DR Reactome; R-RNO-109704; PI3K Cascade.
DR Reactome; R-RNO-1632852; Macroautophagy.
DR Reactome; R-RNO-1660514; Synthesis of PIPs at the Golgi membrane.
DR Reactome; R-RNO-1660516; Synthesis of PIPs at the early endosome membrane.
DR Reactome; R-RNO-1660517; Synthesis of PIPs at the late endosome membrane.
DR Reactome; R-RNO-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR Reactome; R-RNO-5668599; RHO GTPases Activate NADPH Oxidases.
DR PRO; PR:O88763; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000017840; Expressed in liver and 19 other tissues.
DR Genevisible; O88763; RN.
DR GO; GO:0044754; C:autolysosome; ISO:RGD.
DR GO; GO:0005930; C:axoneme; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005768; C:endosome; IBA:GO_Central.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0005777; C:peroxisome; IBA:GO_Central.
DR GO; GO:0045335; C:phagocytic vesicle; ISO:RGD.
DR GO; GO:0000407; C:phagophore assembly site; IBA:GO_Central.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; ISS:UniProtKB.
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; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016301; F:kinase activity; ISO:RGD.
DR GO; GO:0035004; F:phosphatidylinositol 3-kinase activity; IMP:RGD.
DR GO; GO:0052742; F:phosphatidylinositol kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0000045; P:autophagosome assembly; IMP:RGD.
DR GO; GO:0097352; P:autophagosome maturation; ISO:RGD.
DR GO; GO:0006914; P:autophagy; ISO:RGD.
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:0009267; P:cellular response to starvation; ISO:RGD.
DR GO; GO:0045022; P:early endosome to late endosome transport; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IBA:GO_Central.
DR GO; GO:0007032; P:endosome organization; IMP:RGD.
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; ISO:RGD.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IDA:RGD.
DR GO; GO:0006497; P:protein lipidation; ISO:RGD.
DR GO; GO:0034497; P:protein localization to phagophore assembly site; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0016485; P:protein processing; IMP:RGD.
DR GO; GO:0010506; P:regulation of autophagy; ISO:RGD.
DR GO; GO:0032465; P:regulation of cytokinesis; ISS:UniProtKB.
DR GO; GO:0016241; P:regulation of macroautophagy; ISO:RGD.
DR GO; GO:0050708; P:regulation of protein secretion; IMP:RGD.
DR GO; GO:0043201; P:response to leucine; IEP:RGD.
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 ATP-binding; Autophagy; Cell cycle; Cell division; Cytoplasmic vesicle;
KW Endosome; Kinase; Lipid metabolism; Manganese; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..887
FT /note="Phosphatidylinositol 3-kinase catalytic subunit type
FT 3"
FT /id="PRO_0000088805"
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 416..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 COMPBIAS 418..449
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0007744|PubMed:22673903"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NEB9"
FT MOD_RES 282
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8NEB9"
SQ SEQUENCE 887 AA; 101534 MW; 73822786C889035A CRC64;
MGEAEKFHYI YSCDLDINVQ LKIGSLEGKR EQKSYKAVLE DPMLKFSGLY QETCSDLYVT
CQVFAEGKPL ALPVRTSYKP FSTRWNWNEW LKLPVKYPDL PRNAQVALTI WDVYGPGRAV
PVGGTTVSLF GKYGMFRQGM HDLKVWPNVE ADGSEPTRTP GRTSSTLSED QMSRLAKLTK
AHRQGHMVKV DWLDRLTFRE IEMINESEKR SSNFMYLMVE FRCVKCDDKE YGIVYYEKDG
DESSPILTSF ELVKVPDPQM SMENLVESKH HKLARSLRSG PSDHDLKPNA TTRDQLNIIV
SYPPTKQLTY EEQDLVWKFR YYLTNQEKAL TKFLKCVNWD LPQEAKQALE LLGKWKPMDV
EDSLELLSSH YTNPTVRRYA VARLRQADDE DLLMYLLQLV QALKYENFDD IKNGLEPTKK
DSQASVSESL SSSGVSSADI DSSQIITNPL PPVASPPPAS KSKEVSDGEN LEQDLCTFLI
SRACKNSTLA NYLYWYVIVE CEDQDTQQRD PKTHEMYLNV MRRFSQALLK GDKSVRVMRS
LLAAQQTFVD RLVHLMKAVQ RESGNRKKKN ERLQALLGDN EKMNLSDVEL IPLPLEPQVK
IRGIIPETAT LFKSALMPAQ LFFKTEDGGK YPVIFKHGDD LRQDQLILQI ISLMDKLLRK
ENLDLKLTPY KVLATSTKHG FMQFIQSVPV AEVLDTEGSI QNFFRKYAPS ETGPNGISAE
VMDTYVKSCA GYCVITYILG VGDRHLDNLL LTKTGKLFHI DFGYILGRDP KPLPPPMKLN
KEMVEGMGGT QSEQYQEFRK QCYTAFLHLR RYSNLILNLF SLMVDANIPD IALEPDKTVK
KVQDKFRLDL SDEEAVHYMQ SLIDESVHAL FAAVVEQIHK FAQYWRK
