Reactome | UniProt:Q8NEB9 PIK3C3

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UniProt:Q8NEB9 PIK3C3 Show undefined attributes

chain	chain:1-887
checksum	1C03D97338E44976
comment	FUNCTION Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate; different complex forms are believed to play a role in multiple membrane trafficking pathways: PI3KC3-C1 is involved in initiation of autophagosomes and PI3KC3-C2 in maturation of autophagosomes and endocytosis (PubMed:14617358, PubMed:33637724, PubMed:7628435). As part of PI3KC3-C1, promotes endoplasmic reticulum membrane curvature formation prior to vesicle budding (PubMed:32690950). Involved in regulation of degradative endocytic trafficking and required for the abscission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20208530, PubMed:20643123). Involved in the transport of lysosomal enzyme precursors to lysosomes (By similarity). Required for transport from early to late endosomes (By similarity).FUNCTION (Microbial infection) Kinase activity is required for SARS coronavirus-2/SARS-CoV-2 replication.CATALYTIC ACTIVITY a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+)COFACTOR Component of the PI3K (PI3KC3/PI3K-III/class III phosphatidylinositol 3-kinase) complex the core of which is composed of the catalytic subunit PIK3C3, the regulatory subunit PIK3R4 and BECN1 associating with additional regulatory/auxiliary subunits to form alternative complex forms. Alternative complex forms containing a fourth regulatory subunit in a mutually exclusive manner are: the PI3K complex I (PI3KC3-C1) containing ATG14, and the PI3K complex II (PI3KC3-C2) containing UVRAG. PI3KC3-C1 displays a V-shaped architecture with PIK3R4 serving as a bridge between PIK3C3 and the ATG14:BECN1 subcomplex. Both, PI3KC3-C1 and PI3KC3-C2, can associate with further regulatory subunits such as RUBCN, SH3GLB1/Bif-1 and AMBRA1 (PubMed:19050071, PubMed:19270696, PubMed:20643123, PubMed:23878393, PubMed:25490155, PubMed:7628435). PI3KC3-C1 probably associates with PIK3CB (By similarity). Interacts with RAB7A in the presence of PIK3R4 (PubMed:14617358). Interacts with AMBRA1 (By similarity). Interacts with BECN1P1/BECN2 (PubMed:23954414). Interacts with SLAMF1 (PubMed:22493499). May be a component of a complex composed of RAB5A (in GDP-bound form), DYN2 and PIK3C3 (By similarity). Interacts with NCKAP1L (PubMed:16417406). Interacts with ATG14; this interaction is increased in the absence of TMEM39A (PubMed:31806350). Interacts with STEEP1; the interaction is STING1-dependent and required for trafficking of STING1 from the endoplasmic reticulum (PubMed:32690950). Interacts with YWHAG (PubMed:33473107). Interacts with ARMC3 (By similarity).INTERACTION As component of the PI3K complex I localized to pre-autophagosome structures. As component of the PI3K complex II localized predominantly to endosomes (PubMed:14617358). Also localizes to discrete punctae along the ciliary axoneme and to the base of the ciliary axoneme (By similarity).TISSUE SPECIFICITY Ubiquitously expressed, with a highest expression in skeletal muscle.PTM Ubiquitinated via 'Lys-29'- and 'Lys-48'-linked ubiquitination by UBE3C, promoting its degradation (PubMed:33637724). Deubiquitination by ZRANB1/TRABID promotes its stabilization, leading to autophagosome maturation (PubMed:33637724).SIMILARITY Belongs to the PI3/PI4-kinase family.
created	[InstanceEdit:188005] de Bono, B, 2006-09-29 15:31:50
crossReference	[DatabaseIdentifier:12165279] PDB:9MHH [DatabaseIdentifier:12814514] ZINC target:Q8NEB9 [DatabaseIdentifier:12811202] ZINC - Substances:PK3C3_HUMAN [DatabaseIdentifier:12808632] ZINC - Predictions - Purchasable:PK3C3_HUMAN [DatabaseIdentifier:12806668] ZINC - Investigational:PK3C3_HUMAN [DatabaseIdentifier:12362134] RefSeq:NP_002638.2 [DatabaseIdentifier:12284260] Pharos - Targets:Q8NEB9 [DatabaseIdentifier:12262685] PRO:Q8NEB9 [DatabaseIdentifier:12170578] PDB:6HOG [DatabaseIdentifier:12170567] PDB:3LS8 [DatabaseIdentifier:12170576] PDB:6HOH [DatabaseIdentifier:11469907] ENSEMBL:ENSG00000078142 [DatabaseIdentifier:11566497] ENSEMBL:ENSP00000262039 [DatabaseIdentifier:11689196] ENSEMBL:ENST00000262039 [DatabaseIdentifier:11779157] Guide to Pharmacology - Targets:2152 [DatabaseIdentifier:11786343] GeneCards:PIK3C3 [DatabaseIdentifier:11829496] HMDB Protein:HMDBP03992 [DatabaseIdentifier:11839421] HPA:ENSG00000078142-PIK3C3 [DatabaseIdentifier:11850453] IntEnz:2.7.1.137 [DatabaseIdentifier:12123941] OpenTargets:ENSG00000078142 [DatabaseIdentifier:12170560] PDB:7RSJ [DatabaseIdentifier:12170563] PDB:8RXR [DatabaseIdentifier:12170559] PDB:7RSV [DatabaseIdentifier:12170561] PDB:7BL1 [DatabaseIdentifier:12170558] PDB:7RSP [DatabaseIdentifier:12170564] PDB:4PH4 [DatabaseIdentifier:12170566] PDB:3IHY [DatabaseIdentifier:12170562] PDB:6I3U [DatabaseIdentifier:12170565] PDB:9E4V [DatabaseIdentifier:12165274] PDB:8SOR [DatabaseIdentifier:12170568] PDB:6YKG [DatabaseIdentifier:12170574] PDB:4UWK [DatabaseIdentifier:12170572] PDB:4UWH [DatabaseIdentifier:12170570] PDB:4UWG [DatabaseIdentifier:12170577] PDB:5ANL [DatabaseIdentifier:12170575] PDB:4UWL [DatabaseIdentifier:12165278] PDB:9C82 [DatabaseIdentifier:12170569] PDB:4UWF [DatabaseIdentifier:12165276] PDB:9MHG [DatabaseIdentifier:12165277] PDB:9MHF [DatabaseIdentifier:12170571] PDB:5ENN [DatabaseIdentifier:12170573] PDB:4OYS
databaseName	UniProt
dbId	188006
description	recommendedName: Phosphatidylinositol 3-kinase catalytic subunit type 3 shortName: PI3-kinase type 3 shortName: PI3K type 3 shortName: PtdIns-3-kinase type 3 ecNumber evidence="23"2.7.1.137 alternativeName: Phosphatidylinositol 3-kinase p100 subunit alternativeName: Phosphoinositide-3-kinase class 3 alternativeName: hVps34
displayName	UniProt:Q8NEB9 PIK3C3
geneName	PIK3C3 VPS34
identifier	Q8NEB9
isSequenceChanged	false
keyword	3D-structure ATP-binding Autophagy Cell cycle Cell division Cytoplasmic vesicle Endosome Kinase Lipid metabolism Manganese Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Transferase Ubl conjugation
modified	[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
moleculeType	Protein
name	PIK3C3
otherIdentifier	11755049_a_at 1569272_PM_at 1569272_at 16852098 204297_PM_at 204297_at 215394_PM_at 215394_at 229705_PM_at 229705_at 232086_PM_at 232086_at 239300_PM_at 239300_at 35665_at 3786078 3786079 3786080 3786081 3786082 3786083 3786084 3786085 3786094 3786096 3786097 3786098 3786099 3786101 3786102 3786103 3786105 3786108 3786109 3786112 3786113 3786114 3786115 3786117 3786118 3786120 3786121 3786124 3786127 3786129 3786130 3786131 3786134 3786135 3786137 3786139 3786140 3786141 3786146 3786147 3786148 3786149 3786150 3786151 3786152 3786153 3786154 3786155 3786156 3786189 5289 61096_at 8021015 A_14_P111156 A_14_P117012 A_14_P123049 A_23_P164536 A_24_P288116 GE60410 GE665503 GE88078 GO:0000045 GO:0000166 GO:0000407 GO:0000425 GO:0003824 GO:0004672 GO:0005515 GO:0005524 GO:0005737 GO:0005764 GO:0005768 GO:0005770 GO:0005773 GO:0005776 GO:0005777 GO:0005829 GO:0005886 GO:0005930 GO:0006622 GO:0006629 GO:0006886 GO:0006897 GO:0006914 GO:0007032 GO:0009267 GO:0010506 GO:0016020 GO:0016192 GO:0016236 GO:0016241 GO:0016301 GO:0016303 GO:0016485 GO:0016740 GO:0016773 GO:0030496 GO:0030670 GO:0031410 GO:0032465 GO:0034271 GO:0034272 GO:0034497 GO:0035032 GO:0036092 GO:0042149 GO:0043201 GO:0043491 GO:0044754 GO:0044829 GO:0045022 GO:0045335 GO:0045954 GO:0046854 GO:0048015 GO:0048488 GO:0051301 GO:0052742 GO:0060333 GO:0070102 GO:0097352 GO:0098794 GO:0098830 GO:0098845 GO:0098978 GO:0098982 GO:0140096 GO:1903061 HMNXSV003018200 Hs.193041.0.A1_3p_at Hs.239340.0.S1_3p_at Hs.239340.0.S1_3p_x_at Hs.306638.0.S1_3p_at Hs.3734.0.A1_3p_at Hs2.407259.1.S1_3p_at ILMN_1687896 PH_hs_0012896 PH_hs_0025089 TC18000156.hg TC18000689.hg Z46973_at g4505800_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-188011] PIK3C3 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6798182] PIK3C3 [phagocytic vesicle membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000078142] ENSEMBL:ENSG00000078142 PIK3C3 [ReferenceDNASequence:12736979] UCSC:Q8NEB9 PIK3C3 [ReferenceDNASequence:11334855] BioGPS Gene:5289 PIK3C3 [ReferenceDNASequence:11399143] COSMIC - genes:PIK3C3 PIK3C3 [ReferenceDNASequence:11411330] CTD Gene:5289 PIK3C3 [ReferenceDNASequence:11436079] dbSNP Gene:5289 PIK3C3 [ReferenceDNASequence:11817975] HGNC:8974 PIK3C3 [ReferenceDNASequence:11876118] KEGG:hsa:5289 PIK3C3 [ReferenceDNASequence:11964644] Monarch:5289 PIK3C3 [ReferenceDNASequence:12048737] NCBI Gene:5289 PIK3C3 [ReferenceDNASequence:12109408] OMIM:602609 PIK3C3
referenceTranscript	[ReferenceRNASequence:12543963] RefSeq:NM_002647.3 PIK3C3
schemaClass	ReferenceGeneProduct
secondaryIdentifier	PK3C3_HUMAN Q15134
sequenceLength	887
species	[Species:48887] Homo sapiens
stId	uniprot:Q8NEB9
url	http://purl.uniprot.org/uniprot/Q8NEB9

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-188011] PIK3C3 [cytosol] [EntityWithAccessionedSequence:R-HSA-6798182] PIK3C3 [phagocytic vesicle membrane]
(interactor)	[UndirectedInteraction:11213541] UniProt:Q9P2Y5 <-> UniProt:Q8NEB9 (IntAct) [UndirectedInteraction:11243355] UniProt:P61981 <-> UniProt:Q8NEB9 (IntAct) [UndirectedInteraction:11284591] UniProt:Q14457 <-> UniProt:Q8NEB9 (IntAct)

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