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Protein

Phosphatidylinositol 3-kinase catalytic subunit type 3

Gene

PIK3C3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Involved in regulation of degradative endocytic trafficking and required for the abcission step in cytokinesis, probably in the context of PI3KC3-C2 (PubMed:20643123, PubMed:20208530). Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for transport from early to late endosomes (By similarity).By similarityCurated4 Publications

Catalytic activityi

ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate.

Cofactori

Mn2+1 Publication

GO - Molecular functioni

  • 1-phosphatidylinositol-3-kinase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: MGI
  • protein kinase activity Source: Ensembl

GO - Biological processi

Keywordsi

Molecular functionKinase, Transferase
Biological processAutophagy, Cell cycle, Cell division
LigandATP-binding, Manganese, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS01275-MONOMER
BRENDAi2.7.1.137 2681
ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-1632852 Macroautophagy
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-5668599 RHO GTPases Activate NADPH Oxidases
SIGNORiQ8NEB9

Chemistry databases

SwissLipidsiSLP:000000904

Names & Taxonomyi

Protein namesi
Recommended name:
Phosphatidylinositol 3-kinase catalytic subunit type 3 (EC:2.7.1.137)
Short name:
PI3-kinase type 3
Short name:
PI3K type 3
Short name:
PtdIns-3-kinase type 3
Alternative name(s):
Phosphatidylinositol 3-kinase p100 subunit
Phosphoinositide-3-kinase class 3
hVps34
Gene namesi
Name:PIK3C3Imported
Synonyms:VPS34Curated
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000078142.11
HGNCiHGNC:8974 PIK3C3
MIMi602609 gene
neXtProtiNX_Q8NEB9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasmic vesicle, Endosome

Pathology & Biotechi

Organism-specific databases

DisGeNETi5289
OpenTargetsiENSG00000078142
PharmGKBiPA33307

Chemistry databases

ChEMBLiCHEMBL1075165
DrugBankiDB06836 N-(5-(4-CHLORO-3-(2-HYDROXY-ETHYLSULFAMOYL)- PHENYLTHIAZOLE-2-YL)-ACETAMIDE
GuidetoPHARMACOLOGYi2152

Polymorphism and mutation databases

BioMutaiPIK3C3
DMDMi74730233

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000888021 – 887Phosphatidylinositol 3-kinase catalytic subunit type 3Add BLAST887

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei163Phosphothreonine; by AMPKBy similarity1
Modified residuei165Phosphoserine; by AMPKBy similarity1
Modified residuei244PhosphoserineBy similarity1
Modified residuei261PhosphoserineCombined sources1
Modified residuei282PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8NEB9
MaxQBiQ8NEB9
PaxDbiQ8NEB9
PeptideAtlasiQ8NEB9
PRIDEiQ8NEB9
ProteomicsDBi73147

PTM databases

iPTMnetiQ8NEB9
PhosphoSitePlusiQ8NEB9

Expressioni

Tissue specificityi

Ubiquitously expressed, with a highest expression in skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000078142 Expressed in 230 organ(s), highest expression level in corpus callosum
CleanExiHS_PIK3C3
ExpressionAtlasiQ8NEB9 baseline and differential
GenevisibleiQ8NEB9 HS

Organism-specific databases

HPAiHPA040718

Interactioni

Subunit structurei

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/auxilliary subunits to form alternative complex forms. Alternative complex forms containing a forth 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:7628435, PubMed:19050071, PubMed:20643123, PubMed:19270696, PubMed:23878393, PubMed:25490155). 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).By similarityCurated10 Publications

Binary interactionsi

Protein-protein interaction databases

BioGridi111307, 36 interactors
ComplexPortaliCPX-73 Phosphatidylinositol 3-kinase complex, class III, ATG14 variant
CPX-74 Phosphatidylinositol 3-kinase complex, class III, UVRAG variant
CORUMiQ8NEB9
DIPiDIP-42272N
IntActiQ8NEB9, 22 interactors
MINTiQ8NEB9
STRINGi9606.ENSP00000262039

Chemistry databases

BindingDBiQ8NEB9

Structurei

Secondary structure

1887
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ8NEB9
SMRiQ8NEB9
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8NEB9

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 184C2 PI3K-typePROSITE-ProRule annotationAdd BLAST150
Domaini283 – 520PIK helicalPROSITE-ProRule annotationAdd BLAST238
Domaini631 – 885PI3K/PI4KPROSITE-ProRule annotationAdd BLAST255

Sequence similaritiesi

Belongs to the PI3/PI4-kinase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0906 Eukaryota
COG5032 LUCA
GeneTreeiENSGT00760000119110
HOGENOMiHOG000174003
HOVERGENiHBG082145
InParanoidiQ8NEB9
KOiK00914
OMAiFKKHEMG
OrthoDBiEOG091G036A
PhylomeDBiQ8NEB9
TreeFamiTF102032

Family and domain databases

Gene3Di1.10.1070.11, 1 hit
2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR035892 C2_domain_sf
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR002420 PI3K_C2_dom
IPR008290 PI3K_Vps34
IPR015433 PI_Kinase
IPR001263 PInositide-3_kin_accessory_dom
PANTHERiPTHR10048 PTHR10048, 1 hit
PfamiView protein in Pfam
PF00454 PI3_PI4_kinase, 1 hit
PF00792 PI3K_C2, 1 hit
PF00613 PI3Ka, 1 hit
PIRSFiPIRSF000587 PI3K_Vps34, 1 hit
SMARTiView protein in SMART
SM00142 PI3K_C2, 1 hit
SM00145 PI3Ka, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF48371 SSF48371, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00915 PI3_4_KINASE_1, 1 hit
PS00916 PI3_4_KINASE_2, 1 hit
PS50290 PI3_4_KINASE_3, 1 hit
PS51547 PI3K_C2, 1 hit
PS51545 PIK_HELICAL, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 8 potential isoforms that are computationally mapped.Show allAlign All

Q8NEB9-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGEAEKFHYI YSCDLDINVQ LKIGSLEGKR EQKSYKAVLE DPMLKFSGLY
60 70 80 90 100
QETCSDLYVT CQVFAEGKPL ALPVRTSYKA FSTRWNWNEW LKLPVKYPDL
110 120 130 140 150
PRNAQVALTI WDVYGPGKAV PVGGTTVSLF GKYGMFRQGM HDLKVWPNVE
160 170 180 190 200
ADGSEPTKTP GRTSSTLSED QMSRLAKLTK AHRQGHMVKV DWLDRLTFRE
210 220 230 240 250
IEMINESEKR SSNFMYLMVE FRCVKCDDKE YGIVYYEKDG DESSPILTSF
260 270 280 290 300
ELVKVPDPQM SMENLVESKH HKLARSLRSG PSDHDLKPNA ATRDQLNIIV
310 320 330 340 350
SYPPTKQLTY EEQDLVWKFR YYLTNQEKAL TKFLKCVNWD LPQEAKQALE
360 370 380 390 400
LLGKWKPMDV EDSLELLSSH YTNPTVRRYA VARLRQADDE DLLMYLLQLV
410 420 430 440 450
QALKYENFDD IKNGLEPTKK DSQSSVSENV SNSGINSAEI DSSQIITSPL
460 470 480 490 500
PSVSSPPPAS KTKEVPDGEN LEQDLCTFLI SRACKNSTLA NYLYWYVIVE
510 520 530 540 550
CEDQDTQQRD PKTHEMYLNV MRRFSQALLK GDKSVRVMRS LLAAQQTFVD
560 570 580 590 600
RLVHLMKAVQ RESGNRKKKN ERLQALLGDN EKMNLSDVEL IPLPLEPQVK
610 620 630 640 650
IRGIIPETAT LFKSALMPAQ LFFKTEDGGK YPVIFKHGDD LRQDQLILQI
660 670 680 690 700
ISLMDKLLRK ENLDLKLTPY KVLATSTKHG FMQFIQSVPV AEVLDTEGSI
710 720 730 740 750
QNFFRKYAPS ENGPNGISAE VMDTYVKSCA GYCVITYILG VGDRHLDNLL
760 770 780 790 800
LTKTGKLFHI DFGYILGRDP KPLPPPMKLN KEMVEGMGGT QSEQYQEFRK
810 820 830 840 850
QCYTAFLHLR RYSNLILNLF SLMVDANIPD IALEPDKTVK KVQDKFRLDL
860 870 880
SDEEAVHYMQ SLIDESVHAL FAAVVEQIHK FAQYWRK
Length:887
Mass (Da):101,549
Last modified:October 1, 2002 - v1
Checksum:i1C03D97338E44976
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A8MYT4A8MYT4_HUMAN
Phosphatidylinositol 3-kinase catal...
PIK3C3
824Annotation score:
A0A1W2PS05A0A1W2PS05_HUMAN
Phosphatidylinositol 3-kinase catal...
PIK3C3
888Annotation score:
M0R308M0R308_HUMAN
Phosphatidylinositol 3-kinase catal...
PIK3C3
183Annotation score:
M0R386M0R386_HUMAN
Phosphatidylinositol 3-kinase catal...
PIK3C3
103Annotation score:
A0A0B4J2B1A0A0B4J2B1_HUMAN
Phosphatidylinositol 3-kinase catal...
PIK3C3
104Annotation score:
K7ENH3K7ENH3_HUMAN
Phosphatidylinositol 3-kinase catal...
PIK3C3
134Annotation score:
K7EIV6K7EIV6_HUMAN
Phosphatidylinositol 3-kinase catal...
PIK3C3
178Annotation score:
K7EKH3K7EKH3_HUMAN
Phosphatidylinositol 3-kinase catal...
PIK3C3
201Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti36K → N in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti70L → S in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti136F → S in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti158K → N in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti208E → V in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti219 – 220VE → GG in CAA87094 (PubMed:7628435).Curated2
Sequence conflicti262M → L in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti272 – 274KLA → NLP in CAA87094 (PubMed:7628435).Curated3
Sequence conflicti289 – 292NAAT → YPSP in CAA87094 (PubMed:7628435).Curated4
Sequence conflicti297 – 298NI → KN in CAA87094 (PubMed:7628435).Curated2
Sequence conflicti305 – 308TKQL → SKPP in CAA87094 (PubMed:7628435).Curated4
Sequence conflicti318K → E in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti327E → D in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti333 – 338FLKCVN → ILTSVI in CAA87094 (PubMed:7628435).Curated6
Sequence conflicti344E → G in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti350E → A in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti356K → N in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti367L → I in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti397L → S in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti428E → G in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti484C → S in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti750L → V in CAA87094 (PubMed:7628435).Curated1
Sequence conflicti826A → P in CAA87094 (PubMed:7628435).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46973 mRNA Translation: CAA87094.1
BC033004 mRNA Translation: AAH33004.1
BC053651 mRNA Translation: AAH53651.1
CCDSiCCDS11920.1
PIRiS57219
RefSeqiNP_002638.2, NM_002647.3
UniGeneiHs.464971
Hs.656958

Genome annotation databases

EnsembliENST00000262039; ENSP00000262039; ENSG00000078142
GeneIDi5289
KEGGihsa:5289
UCSCiuc002lap.4 human

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z46973 mRNA Translation: CAA87094.1
BC033004 mRNA Translation: AAH33004.1
BC053651 mRNA Translation: AAH53651.1
CCDSiCCDS11920.1
PIRiS57219
RefSeqiNP_002638.2, NM_002647.3
UniGeneiHs.464971
Hs.656958

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3IHYX-ray2.80A/B/C/D/E282-879[»]
3LS8X-ray2.25A/B268-879[»]
4OYSX-ray2.90A282-879[»]
4PH4X-ray2.80B293-887[»]
4UWFX-ray2.99A282-879[»]
4UWGX-ray2.70A282-879[»]
4UWHX-ray1.93A282-879[»]
4UWKX-ray2.83A282-879[»]
4UWLX-ray2.80A282-879[»]
5ANLX-ray2.70A282-879[»]
5ENNX-ray2.70A/B293-887[»]
ProteinModelPortaliQ8NEB9
SMRiQ8NEB9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111307, 36 interactors
ComplexPortaliCPX-73 Phosphatidylinositol 3-kinase complex, class III, ATG14 variant
CPX-74 Phosphatidylinositol 3-kinase complex, class III, UVRAG variant
CORUMiQ8NEB9
DIPiDIP-42272N
IntActiQ8NEB9, 22 interactors
MINTiQ8NEB9
STRINGi9606.ENSP00000262039

Chemistry databases

BindingDBiQ8NEB9
ChEMBLiCHEMBL1075165
DrugBankiDB06836 N-(5-(4-CHLORO-3-(2-HYDROXY-ETHYLSULFAMOYL)- PHENYLTHIAZOLE-2-YL)-ACETAMIDE
GuidetoPHARMACOLOGYi2152
SwissLipidsiSLP:000000904

PTM databases

iPTMnetiQ8NEB9
PhosphoSitePlusiQ8NEB9

Polymorphism and mutation databases

BioMutaiPIK3C3
DMDMi74730233

Proteomic databases

EPDiQ8NEB9
MaxQBiQ8NEB9
PaxDbiQ8NEB9
PeptideAtlasiQ8NEB9
PRIDEiQ8NEB9
ProteomicsDBi73147

Protocols and materials databases

DNASUi5289
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000262039; ENSP00000262039; ENSG00000078142
GeneIDi5289
KEGGihsa:5289
UCSCiuc002lap.4 human

Organism-specific databases

CTDi5289
DisGeNETi5289
EuPathDBiHostDB:ENSG00000078142.11
GeneCardsiPIK3C3
HGNCiHGNC:8974 PIK3C3
HPAiHPA040718
MIMi602609 gene
neXtProtiNX_Q8NEB9
OpenTargetsiENSG00000078142
PharmGKBiPA33307
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0906 Eukaryota
COG5032 LUCA
GeneTreeiENSGT00760000119110
HOGENOMiHOG000174003
HOVERGENiHBG082145
InParanoidiQ8NEB9
KOiK00914
OMAiFKKHEMG
OrthoDBiEOG091G036A
PhylomeDBiQ8NEB9
TreeFamiTF102032

Enzyme and pathway databases

BioCyciMetaCyc:HS01275-MONOMER
BRENDAi2.7.1.137 2681
ReactomeiR-HSA-109704 PI3K Cascade
R-HSA-1632852 Macroautophagy
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-5668599 RHO GTPases Activate NADPH Oxidases
SIGNORiQ8NEB9

Miscellaneous databases

ChiTaRSiPIK3C3 human
EvolutionaryTraceiQ8NEB9
GeneWikiiPIK3C3
GenomeRNAii5289
PROiPR:Q8NEB9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000078142 Expressed in 230 organ(s), highest expression level in corpus callosum
CleanExiHS_PIK3C3
ExpressionAtlasiQ8NEB9 baseline and differential
GenevisibleiQ8NEB9 HS

Family and domain databases

Gene3Di1.10.1070.11, 1 hit
2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR016024 ARM-type_fold
IPR035892 C2_domain_sf
IPR011009 Kinase-like_dom_sf
IPR000403 PI3/4_kinase_cat_dom
IPR036940 PI3/4_kinase_cat_sf
IPR018936 PI3/4_kinase_CS
IPR002420 PI3K_C2_dom
IPR008290 PI3K_Vps34
IPR015433 PI_Kinase
IPR001263 PInositide-3_kin_accessory_dom
PANTHERiPTHR10048 PTHR10048, 1 hit
PfamiView protein in Pfam
PF00454 PI3_PI4_kinase, 1 hit
PF00792 PI3K_C2, 1 hit
PF00613 PI3Ka, 1 hit
PIRSFiPIRSF000587 PI3K_Vps34, 1 hit
SMARTiView protein in SMART
SM00142 PI3K_C2, 1 hit
SM00145 PI3Ka, 1 hit
SM00146 PI3Kc, 1 hit
SUPFAMiSSF48371 SSF48371, 2 hits
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00915 PI3_4_KINASE_1, 1 hit
PS00916 PI3_4_KINASE_2, 1 hit
PS50290 PI3_4_KINASE_3, 1 hit
PS51547 PI3K_C2, 1 hit
PS51545 PIK_HELICAL, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPK3C3_HUMAN
AccessioniPrimary (citable) accession number: Q8NEB9
Secondary accession number(s): Q15134
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: October 1, 2002
Last modified: September 12, 2018
This is version 160 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
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