PK3C3_PIG
ID PK3C3_PIG Reviewed; 887 AA.
AC Q5D891;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 116.
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:0000250|UniProtKB:Q8NEB9};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15628029; DOI=10.1159/000082898;
RA Kim J.H., Lee Y.S., Park E.W., Seo B.Y., Cho I.C., Lee J.G., Oh S.J.,
RA Lee J.H., Jeon J.T.;
RT "Assignment of the phosphoinositide-3-kinase, class 3 (PIK3C3) gene to
RT porcine chromosome 6q22-->q23 by somatic cell and radiation hybrid panel
RT mapping.";
RL Cytogenet. Genome Res. 108:362-362(2005).
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. Involved in the transport of
CC lysosomal enzyme precursors to lysosomes. Required for transport from
CC early to late endosomes (By similarity). {ECO:0000250|UniProtKB:O88763,
CC ECO:0000250|UniProtKB:Q8NEB9}.
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 be a component of a complex composed of
CC RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity). Interacts
CC with NCKAP1L (By similarity). Interacts with ATG14; this interaction is
CC increased in the absence of TMEM39A (By similarity). Interacts with
CC STEEP1; the interaction is STING1-dependent and required for
CC trafficking of STING1 from the endoplasmic reticulum (By similarity).
CC Interacts with YWHAG (By similarity). {ECO:0000250|UniProtKB:Q6PF93,
CC ECO:0000250|UniProtKB:Q8NEB9, 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; AY823302; AAX12416.1; -; mRNA.
DR RefSeq; NP_001012974.1; NM_001012956.2.
DR AlphaFoldDB; Q5D891; -.
DR SMR; Q5D891; -.
DR STRING; 9823.ENSSSCP00000004057; -.
DR PaxDb; Q5D891; -.
DR PeptideAtlas; Q5D891; -.
DR PRIDE; Q5D891; -.
DR GeneID; 503700; -.
DR KEGG; ssc:503700; -.
DR CTD; 5289; -.
DR eggNOG; KOG0906; Eukaryota.
DR InParanoid; Q5D891; -.
DR OrthoDB; 204282at2759; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:GOC.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0030496; C:midbody; ISS:UniProtKB.
DR GO; GO:0035032; C:phosphatidylinositol 3-kinase complex, class III; ISS:UniProtKB.
DR GO; GO:0016303; F:1-phosphatidylinositol-3-kinase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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; ISS:UniProtKB.
DR GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR GO; GO:0048015; P:phosphatidylinositol-mediated signaling; IEA:InterPro.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0032465; P:regulation of cytokinesis; ISS:UniProtKB.
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 2: Evidence at transcript 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_0000088804"
FT DOMAIN 35..184
FT /note="C2 PI3K-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00880"
FT DOMAIN 282..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 150..170
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 416..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..468
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..435
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:0000250|UniProtKB:O88763"
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; 101234 MW; 1D1D954B3A6BB433 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
DESSPILTGF EIVKVPDPQM SMENLVESKH HKLARSLRSG PSDHGLKPNA ATRDQLNIIV
SYPPTKQLTY EEQDLVWKFR YYLTNQEKAL TKFLKCVNWD LPQEAKQALE LLGKWKPMDV
EDSLELLSSH YANPTVRRYA VARLRQADDE DLLMYLLQLV QALKYENFDD IKNGLEPTKK
ESQGSVSESV SNSGIGSAEI DSSQIITSPL PPVSSPPPAS KTKESSDGES LEQDLCTFLI
SRACKNSTLA NYLYWYVIVE CEGQDTQQRD 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
