Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002182
UniProt IDO00443
Primary gene name(s)PIK3C2A
Synonym gene name(s)unknown
Protein namePhosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha
Protein functionGenerates phosphatidylinositol 3-phosphate, PtdIns3P and phosphatidylinositol 3,4-bisphosphate, PtdIns(3,4P2 that act as second messengers. Has a role in several intracellular trafficking events. Functions in insulin signaling and secretion. Required for translocation of the glucose transporter SLC2A4/GLUT4 to the plasma membrane and glucose uptake in response to insulin-mediated RHOQ activation. Regulates insulin secretion through two different mechanisms: involved in glucose-induced insulin secretion downstream of insulin receptor in a pathway that involves AKT1 activation and TBC1D4/AS160 phosphorylation, and participates in the late step of insulin granule exocytosis probably in insulin granule fusion. Synthesizes PtdIns3P in response to insulin signaling. Functions in clathrin-coated endocytic vesicle formation and distribution. Regulates dynamin-independent endocytosis, probably by recruiting EEA1 to internalizing vesicles. In neurosecretory cells synthesizes PtdIns3P on large dense core vesicles. Participates in calcium induced contraction of vascular smooth muscle by regulating myosin light chain, MLC phosphorylation through a mechanism involving Rho kinase-dependent phosphorylation of the MLCP-regulatory subunit MYPT1. May play a role in the EGF signaling cascade. May be involved in mitosis and UV-induced damage response. Required for maintenance of normal renal structure and function by supporting normal podocyte function. {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:10805725, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:12719431, ECO:0000269|PubMed:16215232, ECO:0000269|PubMed:21081650, ECO:0000269|PubMed:9337861}.
Subcellular locationCell membrane {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:11239472, ECO:0000269|PubMed:17038310}. Golgi apparatus {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:11239472}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000269|PubMed:10766823, ECO:0000269|PubMed:11239472}. Nucleus {ECO:0000269|PubMed:11606566}. Cytoplasm {ECO:0000269|PubMed:11606566, ECO:0000269|PubMed:14563213}. Note=Inserts preferentially into membranes containing PtdIns(4,5P2, PubMed:17038310. Associated with RNA-containing structures, PubMed:11606566. {ECO:0000269|PubMed:11606566, ECO:0000269|PubMed:17038310}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: O00443
Gene Ontology
(Biological Process)
Complete annatation
clathrin coat assembly [GO:0048268];
endocytosis [GO:0006897];
epidermal growth factor receptor signaling pathway [GO:0007173];
exocytosis [GO:0006887];
insulin receptor signaling pathway [GO:0008286];
phosphatidylinositol biosynthetic process [GO:0006661];
phosphatidylinositol-mediated signaling [GO:0048015];
platelet-derived growth factor receptor signaling pathway [GO:0048008];
vascular smooth muscle contraction [GO:0014829]
Gene Ontology
(Molecular Function)
Complete annatation
1-phosphatidylinositol-3-kinase activity [GO:0016303];
1-phosphatidylinositol-4-phosphate 3-kinase activity [GO:0035005];
ATP binding [GO:0005524];
phosphatidylinositol 3-kinase activity [GO:0035004];
phosphatidylinositol binding [GO:0035091]
Gene Ontology
(Cellular Component)
Complete annatation
clathrin-coated vesicle [GO:0030136];
cytoplasm [GO:0005737];
cytosol [GO:0005829];
extracellular exosome [GO:0070062];
Golgi apparatus [GO:0005794];
membrane [GO:0016020];
nucleus [GO:0005634];
phosphatidylinositol 3-kinase complex [GO:0005942];
plasma membrane [GO:0005886];
vesicle [GO:0031982]
Protein-protein interaction111304
Phylogenetic treeO00443
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD30.5240398826086580.1126652469641120.193669092409113
AZA vs. DISU0.2455348324242320.3841859856612680.900307314749944
AZA vs. IL70.005479667191854680.9773668960957810.999311006273513
AZA vs. SAHA0.1262663766070370.6063095950651680.870346713266579
DISU vs. CD3-0.2914455623432160.4361280066417630.567618488411987
DISU vs. IL7-0.2482392550315940.3927391288505610.75826618435223
DISU vs. SAHA-0.1191204898450.7056718254879170.91288546904155
DMSO vs. AZA-0.0835574989677210.6204337491996851
DMSO vs. CD3-0.6197963632370690.05459224278261370.103803122241585
DMSO vs. DISU-0.3312051853110950.2020025602215680.717776976395015
DMSO vs. IL70.09645614713735050.59358532589340.910768324462392
DMSO vs. SAHA0.2020534238105910.393206401614160.738076183675053
HIV vs. Mock in Activation0.02760483192990890.9651013295691830.999983755607037
HIV vs. Mock in Latency-0.007850765257596820.9622477399203090.999834320637052
IL7 vs. CD3-0.5093598055158540.1159070456407580.212385087168444
SAHA vs. CD3-0.4243146816910170.2308549700341520.337568833535287
SAHA vs. IL70.1158907591415130.6354541658715910.819969273585197
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.272844 0.0549192
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
2AR5 X-ray 1.8Å A=1421-1532.
2IWL X-ray 2.6Å X=1405-1544.
2REA X-ray 2.5Å A=1421-1532.
2RED X-ray 2.1Å A=1421-1532.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Nef interacts with 11289809
Tat activates 17157319
Envelope surface glycoprotein gp120 modulated by 16524887
Envelope surface glycoprotein gp160; precursor inhibits 9808187
Envelope surface glycoprotein gp160; precursor activates 9341793
Envelope surface glycoprotein gp120 mediated by 16081599
Tat interacts with 11154208
Nef complexes with 18854243
Tat inhibited by 12077252
Envelope surface glycoprotein gp120 inhibited by 20818790
Envelope surface glycoprotein gp120 relocalizes 18453587
reverse transcriptase phosphorylated by 10641798
Tat induces phosphorylation of 23301033
Nef downregulates 8636073
Tat regulated by 24073214
Envelope surface glycoprotein gp120 activates 12551992
Envelope surface glycoprotein gp120 regulated by 15689238
Nef upregulates 10985305

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00562 Inositol phosphate metabolism - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)
hsa04070 Phosphatidylinositol signaling system - Homo sapiens (human)