Human Gene PIK3C3 (uc002lap.3) Description and Page Index
  Description: Homo sapiens phosphatidylinositol 3-kinase, catalytic subunit type 3 (PIK3C3), mRNA.
Transcript (Including UTRs)
   Position: hg19 chr18:39,535,199-39,661,446 Size: 126,248 Total Exon Count: 25 Strand: +
Coding Region
   Position: hg19 chr18:39,535,257-39,661,101 Size: 125,845 Coding Exon Count: 25 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr18:39,535,199-39,661,446)mRNA (may differ from genome)Protein (887 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Phosphatidylinositol 3-kinase catalytic subunit type 3; Short=PI3-kinase type 3; Short=PI3K type 3; Short=PtdIns-3-kinase type 3; EC=; AltName: Full=Phosphatidylinositol 3-kinase p100 subunit; AltName: Full=Phosphoinositide-3-kinase class 3; AltName: Full=hVps34;
FUNCTION: Catalytic subunit of the PI3K complex that mediates formation of phosphatidylinositol 3-phosphate which plays a key role in initiation and maturation of autophagosomes. Involved in the transport of lysosomal enzyme precursors to lysosomes. Required for the abcission step in cytokinesis. Required for transport from early to late endosomes.
CATALYTIC ACTIVITY: ATP + 1-phosphatidyl-1D-myo-inositol = ADP + 1-phosphatidyl-1D-myo-inositol 3-phosphate.
COFACTOR: Manganese.
SUBUNIT: Heterodimer. This subunit, part of a complex composed of regulatory and catalytic subunits, associates with regulatory subunit PIK3R4. Forms a complex with BECN1, PIK3R4 and either UVRAG and KIAA0226/Rubicon, or with ATG14. In this complex, presence of UVRAG and ATG14 are mutually exclusive. Part of a complex composed of PIK3R4 and PIK3CB (By similarity). Interacts with RAB7A in the presence of PIK3R4.
INTERACTION: Q14457:BECN1; NbExp=6; IntAct=EBI-1056470, EBI-949378;
SUBCELLULAR LOCATION: Midbody. Late endosome.
TISSUE SPECIFICITY: Ubiquitously expressed, with a highest expression in skeletal muscle.
SIMILARITY: Belongs to the PI3/PI4-kinase family.
SIMILARITY: Contains 1 C2 PI3K-type domain.
SIMILARITY: Contains 1 PI3K/PI4K domain.
SIMILARITY: Contains 1 PIK helical domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PIK3C3
CDC HuGE Published Literature: PIK3C3
Positive Disease Associations: Angiography , Apolipoproteins B , Blood Pressure , Body Height , Body Mass Index , Body Weight , Body Weights and Measures , Cholesterol , Cholesterol, HDL , Cholesterol, LDL , Diabetes Mellitus , Echocardiography , Exercise Test , gamma-Glutamylcyclotransferase , Gout , Hemoglobin A, Glycosylated , Myocardial Infarction , Occipital Lobe , Psychomotor Performance , schizophrenia; bipolar disorder
Related Studies:
  1. Angiography
    Ramachandran S Vasan et al. BMC medical genetics 2007, Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study., BMC medical genetics. [PubMed 17903301]
    In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community.
  2. Apolipoproteins B
    Sekar Kathiresan et al. BMC medical genetics 2007, A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study., BMC medical genetics. [PubMed 17903299]
    Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects (i.e., <1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids.
  3. Blood Pressure
    Daniel Levy et al. BMC medical genetics 2007, Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness., BMC medical genetics. [PubMed 17903302]
    These results of genome-wide association testing for blood pressure and arterial stiffness phenotypes in an unselected community-based sample of adults may aid in the identification of the genetic basis of hypertension and arterial disease, help identify high risk individuals, and guide novel therapies for hypertension. Additional studies are needed to replicate any associations identified in these analyses.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PIK3C3
Diseases sorted by gene-association score: amyotrophic lateral sclerosis 1 (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene
  • D013749 Tetrachlorodibenzodioxin
  • C025946 3-methyladenine
  • C049325 1,2-dithiol-3-thione
  • C569670 1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno(3,2-d)pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one
  • C029497 2,3-bis(3'-hydroxybenzyl)butyrolactone
  • C085911 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • D015123 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • C501332 ABT-737
  • D000643 Ammonium Chloride
  • D002330 Carmustine
          more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 6.22 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 152.35 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -11.8058-0.203 Picture PostScript Text
3' UTR -73.20345-0.212 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR016024 - ARM-type_fold
IPR000008 - C2_Ca-dep
IPR008973 - C2_Ca/lipid-bd_dom_CaLB
IPR011009 - Kinase-like_dom
IPR000403 - PI3/4_kinase_cat_dom
IPR018936 - PI3/4_kinase_CS
IPR002420 - PI3K_C2_dom
IPR008290 - PI3K_Vps34
IPR015433 - PI_Kinase
IPR001263 - PInositide-3_kin_accessory_dom

Pfam Domains:
PF00454 - Phosphatidylinositol 3- and 4-kinase
PF00613 - Phosphoinositide 3-kinase family, accessory domain (PIK domain)
PF00792 - Phosphoinositide 3-kinase C2

SCOP Domains:
48371 - ARM repeat
49562 - C2 domain (Calcium/lipid-binding domain, CaLB)
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q8NEB9
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologGenome BrowserGenome Browser
Gene DetailsGene Details  Gene DetailsGene Details
Gene SorterGene Sorter  Gene SorterGene Sorter
 RGDEnsembl WormBaseSGD
 Protein SequenceProtein Sequence Protein SequenceProtein Sequence
 AlignmentAlignment AlignmentAlignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016303 1-phosphatidylinositol-3-kinase activity
GO:0016740 transferase activity
GO:0035004 phosphatidylinositol 3-kinase activity

Biological Process:
GO:0000045 autophagosome assembly
GO:0006468 protein phosphorylation
GO:0006497 protein lipidation
GO:0006897 endocytosis
GO:0006914 autophagy
GO:0007032 endosome organization
GO:0007049 cell cycle
GO:0009267 cellular response to starvation
GO:0016236 macroautophagy
GO:0016310 phosphorylation
GO:0016485 protein processing
GO:0030242 pexophagy
GO:0032465 regulation of cytokinesis
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034497 protein localization to pre-autophagosomal structure
GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process
GO:0042149 cellular response to glucose starvation
GO:0043201 response to leucine
GO:0045022 early endosome to late endosome transport
GO:0046854 phosphatidylinositol phosphorylation
GO:0048015 phosphatidylinositol-mediated signaling
GO:0050708 regulation of protein secretion
GO:0051301 cell division

Cellular Component:
GO:0000407 pre-autophagosomal structure
GO:0005768 endosome
GO:0005770 late endosome
GO:0005776 autophagosome
GO:0005777 peroxisome
GO:0005829 cytosol
GO:0005930 axoneme
GO:0016020 membrane
GO:0030496 midbody
GO:0030670 phagocytic vesicle membrane
GO:0031410 cytoplasmic vesicle
GO:0034271 phosphatidylinositol 3-kinase complex, class III, type I
GO:0034272 phosphatidylinositol 3-kinase complex, class III, type II
GO:0035032 phosphatidylinositol 3-kinase complex, class III
GO:0044754 autolysosome
GO:0045335 phagocytic vesicle

-  Descriptions from all associated GenBank mRNAs
  LF385239 - JP 2014500723-A/192742: Polycomb-Associated Non-Coding RNAs.
Z46973 - H.sapiens mRNA for phosphatidylinositol 3-kinase.
BC033004 - Homo sapiens phosphoinositide-3-kinase, class 3, mRNA (cDNA clone MGC:26376 IMAGE:4823337), complete cds.
AK298517 - Homo sapiens cDNA FLJ55742 complete cds, highly similar to Phosphatidylinositol 3-kinase catalyticsubunit type 3 (EC
AK308364 - Homo sapiens cDNA, FLJ98312.
BC053651 - Homo sapiens phosphoinositide-3-kinase, class 3, mRNA (cDNA clone MGC:61518 IMAGE:5517878), complete cds.
AB463170 - Synthetic construct DNA, clone: pF1KB9779, Homo sapiens PIK3C3 gene for phosphoinositide-3-kinase, class 3, without stop codon, in Flexi system.
DQ890552 - Synthetic construct clone IMAGE:100003182; FLH167020.01X; RZPDo839G0388D phosphoinositide-3-kinase, class 3 (PIK3C3) gene, encodes complete protein.
DQ893712 - Synthetic construct Homo sapiens clone IMAGE:100008172; FLH167016.01L; RZPDo839G0387D phosphoinositide-3-kinase, class 3 (PIK3C3) gene, encodes complete protein.
MA620816 - JP 2018138019-A/192742: Polycomb-Associated Non-Coding RNAs.
BC010388 - Homo sapiens phosphoinositide-3-kinase, class 3, mRNA (cDNA clone IMAGE:4132704), with apparent retained intron.
JD537806 - Sequence 518830 from Patent EP1572962.
LF342874 - JP 2014500723-A/150377: Polycomb-Associated Non-Coding RNAs.
LF342877 - JP 2014500723-A/150380: Polycomb-Associated Non-Coding RNAs.
LF342882 - JP 2014500723-A/150385: Polycomb-Associated Non-Coding RNAs.
LF342883 - JP 2014500723-A/150386: Polycomb-Associated Non-Coding RNAs.
MA578451 - JP 2018138019-A/150377: Polycomb-Associated Non-Coding RNAs.
MA578454 - JP 2018138019-A/150380: Polycomb-Associated Non-Coding RNAs.
MA578459 - JP 2018138019-A/150385: Polycomb-Associated Non-Coding RNAs.
MA578460 - JP 2018138019-A/150386: Polycomb-Associated Non-Coding RNAs.
AK090567 - Homo sapiens cDNA FLJ33248 fis, clone ASTRO2005008, highly similar to Rattus norvegicus mRNA for phosphatidylinositol 3-kinase.
AK022653 - Homo sapiens cDNA FLJ12591 fis, clone NT2RM4001313, moderately similar to PHOSPHATIDYLINOSITOL 3-KINASE VPS34-LIKE (EC
LF342894 - JP 2014500723-A/150397: Polycomb-Associated Non-Coding RNAs.
JD067174 - Sequence 48198 from Patent EP1572962.
LF342897 - JP 2014500723-A/150400: Polycomb-Associated Non-Coding RNAs.
JD322490 - Sequence 303514 from Patent EP1572962.
JD134409 - Sequence 115433 from Patent EP1572962.
MA578471 - JP 2018138019-A/150397: Polycomb-Associated Non-Coding RNAs.
MA578474 - JP 2018138019-A/150400: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00562 - Inositol phosphate metabolism
hsa01100 - Metabolic pathways
hsa04070 - Phosphatidylinositol signaling system
hsa04140 - Regulation of autophagy

BioCyc Knowledge Library
PWY-6352 - 3-phosphoinositide biosynthesis
PWY3DJ-219 - PIP metabolism

Reactome (by CSHL, EBI, and GO)

Protein Q8NEB9 (Reactome details) participates in the following event(s):

R-HSA-188002 Rab5-mediated recruitment of class III PI3K to TLR9
R-HSA-5678313 AMBRA1:DYNLL1,DYNLL2 binds Beclin-1 complex
R-HSA-5679266 Beclin-1 complex translocates to the ER
R-HSA-5678315 Beclin-1 complex, p-AMBRA1 dissociate from DYNLL1,DYNLL2
R-HSA-5679205 ULK1 phosphorylates Beclin-1
R-HSA-1632857 ULK1 phosphorylates AMBRA1:Beclin-1 complex
R-HSA-5672012 Beclin-1 complex phosphorylates PtdIns
R-HSA-6798174 PIK3C3:PIK3R4 phosphorylates PI to PI3P
R-HSA-109699 PI3K-containing complexes phosphorylate PIP2 to PIP3
R-HSA-1675939 PI is phosphorylated to PI3P by PIK3C2A/3 at the early endosome membrane
R-HSA-1675961 PI is phosphorylated to PI3P by PIK3C2A/3 at the Golgi membrane
R-HSA-1676024 PI is phosphorylated to PI3P by PIK3C2A/3 at the late endosome membrane
R-HSA-168138 Toll Like Receptor 9 (TLR9) Cascade
R-HSA-1632852 Macroautophagy
R-HSA-168898 Toll-Like Receptors Cascades
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-5668599 RHO GTPases Activate NADPH Oxidases
R-HSA-168249 Innate Immune System
R-HSA-195258 RHO GTPase Effectors
R-HSA-109704 PI3K Cascade
R-HSA-168256 Immune System
R-HSA-1660516 Synthesis of PIPs at the early endosome membrane
R-HSA-1660514 Synthesis of PIPs at the Golgi membrane
R-HSA-1660517 Synthesis of PIPs at the late endosome membrane
R-HSA-194315 Signaling by Rho GTPases
R-HSA-112399 IRS-mediated signalling
R-HSA-1483255 PI Metabolism
R-HSA-162582 Signal Transduction
R-HSA-74751 Insulin receptor signalling cascade
R-HSA-2428928 IRS-related events triggered by IGF1R
R-HSA-1483257 Phospholipid metabolism
R-HSA-74752 Signaling by Insulin receptor
R-HSA-2428924 IGF1R signaling cascade
R-HSA-556833 Metabolism of lipids
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-2404192 Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: NM_002647, NP_002638, PK3C3_HUMAN, Q15134, Q8NEB9, VPS34
UCSC ID: uc002lap.3
RefSeq Accession: NM_002647
Protein: Q8NEB9 (aka PK3C3_HUMAN)
CCDS: CCDS11920.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_002647.2
exon count: 25CDS single in 3' UTR: no RNA size: 3083
ORF size: 2664CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 5499.00frame shift in genome: no % Coverage: 99.48
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.