TISIDB

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cell membrane Golgi apparatus Cytoplasmic vesicle, clathrin-coated vesicle Nucleus Cytoplasm Note=Inserts preferentially into membranes containing PtdIns(4,5)P2 (PubMed:17038310). Associated with RNA-containing structures (PubMed:11606566).
Domain	PF00168 C2 domain PF00454 Phosphatidylinositol 3- and 4-kinase PF00792 Phosphoinositide 3-kinase C2 PF00794 PI3-kinase family PF00613 Phosphoinositide 3-kinase family PF00787 PX domain
Function	Generates phosphatidylinositol 3-phosphate (PtdIns3P) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) 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.

> Gene Ontology [ TOP ]
Biological Process	GO:0003012 muscle system process GO:0003013 circulatory system process GO:0003018 vascular process in circulatory system GO:0006644 phospholipid metabolic process GO:0006650 glycerophospholipid metabolic process GO:0006661 phosphatidylinositol biosynthetic process GO:0006887 exocytosis GO:0006936 muscle contraction GO:0006939 smooth muscle contraction GO:0007173 epidermal growth factor receptor signaling pathway GO:0008015 blood circulation GO:0008286 insulin receptor signaling pathway GO:0008654 phospholipid biosynthetic process GO:0014829 vascular smooth muscle contraction GO:0030258 lipid modification GO:0032868 response to insulin GO:0032869 cellular response to insulin stimulus GO:0035150 regulation of tube size GO:0036092 phosphatidylinositol-3-phosphate biosynthetic process GO:0038127 ERBB signaling pathway GO:0042310 vasoconstriction GO:0043434 response to peptide hormone GO:0045017 glycerolipid biosynthetic process GO:0046474 glycerophospholipid biosynthetic process GO:0046486 glycerolipid metabolic process GO:0046488 phosphatidylinositol metabolic process GO:0046834 lipid phosphorylation GO:0046854 phosphatidylinositol phosphorylation GO:0048008 platelet-derived growth factor receptor signaling pathway GO:0048015 phosphatidylinositol-mediated signaling GO:0048017 inositol lipid-mediated signaling GO:0048268 clathrin coat assembly GO:0050880 regulation of blood vessel size GO:0071375 cellular response to peptide hormone stimulus GO:0071417 cellular response to organonitrogen compound GO:0090066 regulation of anatomical structure size GO:1901652 response to peptide GO:1901653 cellular response to peptide
Molecular Function	GO:0005543 phospholipid binding GO:0016303 1-phosphatidylinositol-3-kinase activity GO:0016307 phosphatidylinositol phosphate kinase activity GO:0035004 phosphatidylinositol 3-kinase activity GO:0035005 1-phosphatidylinositol-4-phosphate 3-kinase activity GO:0035091 phosphatidylinositol binding GO:0052742 phosphatidylinositol kinase activity
Cellular Component	GO:0005942 phosphatidylinositol 3-kinase complex GO:0019898 extrinsic component of membrane GO:0030135 coated vesicle GO:0030136 clathrin-coated vesicle GO:0061695 transferase complex, transferring phosphorus-containing groups

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04070 Phosphatidylinositol signaling system hsa00562 Inositol phosphate metabolism hsa01100 Metabolic pathways
Reactome	R-HSA-421837: Clathrin derived vesicle budding R-HSA-8856828: Clathrin-mediated endocytosis R-HSA-432722: Golgi Associated Vesicle Biogenesis R-HSA-199991: Membrane Trafficking R-HSA-1430728: Metabolism R-HSA-556833: Metabolism of lipids and lipoproteins R-HSA-1483255: PI Metabolism R-HSA-1483257: Phospholipid metabolism 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-1660499: Synthesis of PIPs at the plasma membrane R-HSA-5653656: Vesicle-mediated transport R-HSA-199992: trans-Golgi Network Vesicle Budding

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04070 Phosphatidylinositol signaling system
hsa00562 Inositol phosphate metabolism
hsa01100 Metabolic pathways

Reactome

R-HSA-421837: Clathrin derived vesicle budding
R-HSA-8856828: Clathrin-mediated endocytosis
R-HSA-432722: Golgi Associated Vesicle Biogenesis
R-HSA-199991: Membrane Trafficking
R-HSA-1430728: Metabolism
R-HSA-556833: Metabolism of lipids and lipoproteins
R-HSA-1483255: PI Metabolism
R-HSA-1483257: Phospholipid metabolism
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-1660499: Synthesis of PIPs at the plasma membrane
R-HSA-5653656: Vesicle-mediated transport
R-HSA-199992: trans-Golgi Network Vesicle Budding

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PIK3C2A and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of PIK3C2A in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of PIK3C2A in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.068	0.832
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.271	0.849
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.077	0.939
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.068	0.865
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.485	0.83
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.455	0.872
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.118	0.766
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.068	0.971
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.166	0.935
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.121	0.911
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	1.072	0.468
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.055	0.292

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PIK3C2A in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	25.9	8.2	17.7	0.0389
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	25.9	8.5	17.4	0.0441
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	14.3	-14.3	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PIK3C2A. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PIK3C2A. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PIK3C2A. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PIK3C2A. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PIK3C2A expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PIK3C2A and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PIK3C2A
Name	phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 alpha
Aliases	PI3K-C2alpha; phosphoinositide-3-kinase, class 2, alpha polypeptide; CPK; PI3-K-C2(ALPHA); PI3-K-C2A; C2-con ......
Chromosomal Location	11p15.5-p14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PIK3C2A collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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