PIK3C2B phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 beta [Homo sapiens (human)] - Gene

Summary

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Official Symbol: PIK3C2Bprovided by HGNC
Official Full Name: phosphatidylinositol-4-phosphate 3-kinase, catalytic subunit type 2 betaprovided by HGNC
Primary source: HGNC:8972
Locus tag: RP11-739N20.5
See related: Ensembl:ENSG00000133056; HPRD:04160; MIM:602838; Vega:OTTHUMG00000036101
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: C2-PI3K
Summary: The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmanin. The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 1q32

Sequence :: Chromosome: 1; NC_000001.10 (204391758..204459474, complement)

See PIK3C2B in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Data suggest a novel role for nucleotide-free Ras in cell signaling in which PI3KC2beta stabilizes nucleotide-free Ras and that interaction of Ras and PI3KC2beta mutually inhibit one another.
Title: A new dimension to Ras function: a novel role for nucleotide-free Ras in Class II phosphatidylinositol 3-kinase beta (PI3KC2β) regulation.
The results of this study showed that strong association between PIK3C2B gene alternation and high-grade oligodendroglial tumors.
Title: Identification of a novel population in high-grade oligodendroglial tumors not deleted on 1p/19q using array CGH.
These findings provide a unique mechanism for regulating class II PI3Ks, and identify TRIM27 as a previously undescribed negative regulator of CD4 T cells.
Title: Tripartite motif containing protein 27 negatively regulates CD4 T cells by ubiquitinating and inhibiting the class II PI3K-C2β.
Overexpression of PIK3C2B is associated with esophageal squamous cell carcinoma.
Title: Phosphatidylinositol 3-kinase-C2β inhibits cisplatin-mediated apoptosis via the Akt pathway in oesophageal squamous cell carcinoma.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Pooled analysis of phosphatidylinositol 3-kinase pathway variants and risk of prostate cancer.
Data show that the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta) is activated by the T-cell receptor (TCR) and functions upstream of NDPK-B to activate KCa3.1 channel activity.
Title: The class II phosphatidylinositol 3 kinase C2beta is required for the activation of the K+ channel KCa3.1 and CD4 T-cells.
Epidermal growth factor stimulates the appearance of PI3K-C2beta in nuclei.
Title: Epidermal growth factor stimulates translocation of the class II phosphoinositide 3-kinase PI3K-C2beta to the nucleus.
Observational study of gene-disease association. (HuGE Navigator)
Title: Physiogenomic analysis of statin-treated patients: domain-specific counter effects within the ACACB gene on low-density lipoprotein cholesterol?
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.

Submit: New GeneRIF Correction See all (16)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

HIV-1 protein interactions

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Protein	Gene	Interaction	Pubs
Env, gp160, envelope glycoprotein	env	HIV-1 gp160 disrupts the association between phospholipase C gamma-1 and phosphoinositide 3 kinase (PI3-kinase), and this effect is dependent on PI3-kinase activity	PubMed
	env	PI3-kinase activation induced by HIV-1 gp160 leads to downregulation of LFA-1-mediated T cell adhesion to B cells	PubMed
Envelope surface glycoprotein gp120	env	HIV-1 gp120-induced PI3-kinase activity and calcium mobilization are inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that this signaling is mediated through these chemokine receptors	PubMed
	env	CD45 modulates HIV-1 gp120-induced apoptosis by regulating Fas ligand induction and activation of the phosphoinositide 3-kinase/Akt pathway	PubMed
	env	HIV-1 gp120-induced TNF-alpha production by primary human macrophages is mediated by phosphatidylinositol-3 (PI-3) kinase and mitogen-activated protein (MAP) kinase pathways	PubMed
	env	CCR5 activation by gp120 triggers the assembly of endogenous Lyn, PI3K, and Pyk2 and is associated with PI3K and Pyk2 translocation from the cytoplasm to the membrane where they colocalized with Lyn	PubMed
	env	Concomitant activation of Lyn, Pyk2, and class IA PI3K are required for gp120-induced IL-1beta production	PubMed
	env	Insulin-like growth factor-I (IGF-I) and erythropoietin treatment protect against HIV/gp120-mediated neuronal damage in culture and in vivo, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling	PubMed
	env	Pre-treatment of endothelial cells with fibroblast growth factor 2 (FGF2) protects cells from HIV-1 gp120 angiotoxicity; this protection is regulated by crosstalk among the ERK, PI3K-AKT and PKC signaling pathways	PubMed
Nef, p27	nef	In the context of Nef-associated kinase complex (NAKC), hnRNP-K interacts with HIV-1 Nef and recruits LCK, PKCdelta, and PI-3 kinase	PubMed
	nef	The presence of HIV-1 Nef in Jurkat cells stimulated with a combination of PMA and anti-CD28 upregulates the levels of PI3K production	PubMed
	nef	Downregulation of cell surface major histocompatibility complex class I (MHC-I) protein expression by HIV-1 Nef depends on a phosphoinositide 3-kinase (PI3K)-regulated signaling pathway, suggesting an interaction between Nef and PI3K	PubMed
	nef	The association of phosphatidylinositol (PI) 3-kinase with platelet-derived growth factor (PDGF) activated receptor was downregulated by HIV-1 nef expression	PubMed
Tat, p14	tat	Pro-survival effects of intracellular HIV-1 Tat in a microglial cell line is attributed to activation of the PI-3-kinase (PI3K)/Akt pathway via decreasing expression of PTEN, a negative regulator of the PI-3-K pathway	PubMed
	tat	Phosphatidylinositol 3-kinase/Akt signaling pathway is involved in HIV-1 Tat-induced NADPH oxidase stimulation and LTR transactivation	PubMed
	tat	HIV-1 Tat in combination with KSHV kaposin A activates the MEK/ERK, STAT3, and PI3K/Akt signals in NIH3T3 cells	PubMed
	tat	The cysteine to serine mutation at position 31 in HIV-1 clade C Tat results in a marked decrease in IL-10 production in monocytes compared with clade B Tat. p38alpha/p38beta and phosphoinositide 3-kinase are crucial to Tat-induced IL-10 production	PubMed
	tat	HIV-1 Tat activates phosphatidylinositol 3-kinase (PI3K), leading to the activation of Akt/PKB, decreased levels of cAMP and CREB phosphorylation, and the protection of cells from apoptosis	PubMed
	tat	Phosphatidylinositol 3-kinase inhibits HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter by affecting the formation of the Tat-associated kinase transactivating complex	PubMed
	tat	HIV-1 Tat induced release of MCP-1 from human lung microvascular endothelial cells involves an interaction between Tat and PI3 kinase	PubMed
	tat	Activation of protein kinase C-epsilon by HIV-1 Tat involves an interaction with PI 3-kinase	PubMed
	tat	HIV-1 Tat-mediated cytopathic changes in human brain micro vascular endothelial cells involves its interaction with phosphatidylinositol 3-kinase (PI3K)	PubMed

Go to the HIV-1, Human Protein Interaction Database

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
O00750	P00533	EGFR	HPRD	PubMed
O00750	P04626	ERBB2	HPRD	PubMed
O00750	P62993	GRB2	HPRD	PubMed
O00750	P29376	LTK	HPRD	PubMed
O00750	P09619	PDGFRB	HPRD	PubMed
BioGRID:111305	BioGRID:107788	CRK	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111305	BioGRID:108276	EGFR	BioGRID	PubMed	Reconstituted Complex
BioGRID:111305	BioGRID:109142	GRB2	BioGRID	PubMed	Affinity Capture-MS; Reconstituted Complex
BioGRID:111305	BioGRID:112351	ITSN1	BioGRID	PubMed	Two-hybrid
BioGRID:111305	BioGRID:119098	ITSN2	BioGRID	PubMed	Two-hybrid
BioGRID:111305	BioGRID:109072	SFN	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111305	BioGRID:112361	SHC1	BioGRID	PubMed	Reconstituted Complex
BioGRID:111305	BioGRID:111919	TRIM27	BioGRID	PubMed	Affinity Capture-Western; Co-localization; Two-hybrid
BioGRID:111305	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:111305	BioGRID:113258	VCP	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111305	BioGRID:116168	YWHAQ	BioGRID	PubMed	Affinity Capture-MS

Pathways from BioSystems

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3-phosphoinositide biosynthesis, organism-specific biosystem (from BIOCYC)
3-phosphoinositide biosynthesis, organism-specific biosystem: Phosphoinositides "Phosphoinositides" play a key role in signal transduction, transmitting signals from the cell surface to modulate intracellular processes. One well known phosphoinositide pathway...
3-phosphoinositide biosynthesis, conserved biosystem (from BIOCYC)
3-phosphoinositide biosynthesis, conserved biosystem|FRAME: Phosphoinositides "Phosphoinositides"| play a key role in signal transduction in the eukaryotic cell, transmitting signals from the cell surface to modulate intracellular processes. One well ...
EGFR1 Signaling Pathway, organism-specific biosystem (from WikiPathways)
EGFR1 Signaling Pathway, organism-specific biosystemThe androgen receptor is a member of the nuclear receptor family of ligand activated transcription factors. These receptors bind to steroid hormones, thyroid hormone, retinoids and vitamin D among ot...
Inositol phosphate metabolism, organism-specific biosystem (from KEGG)
Inositol phosphate metabolism, organism-specific biosystem
Inositol phosphate metabolism
Inositol phosphate metabolism, conserved biosystem (from KEGG)
Inositol phosphate metabolism, conserved biosystem
Inositol phosphate metabolism
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of lipids and lipoproteins, organism-specific biosystem (from REACTOME)
Metabolism of lipids and lipoproteins, organism-specific biosystemLipids are hydrophobic but otherwise chemically diverse molecules that play a wide variety of roles in human biology. They include ketone bodies, fatty acids, triacylglycerols, phospholipids and sphi...
PI Metabolism, organism-specific biosystem (from REACTOME)
PI Metabolism, organism-specific biosystemPhosphatidylinositol (PI), a membrane phospholipid, can be reversibly phosphorylated at the 3, 4, and 5 positions of the inositol ring to generate seven phosphoinositides: phosphatidylinositol 3-phos...
Phosphatidylinositol signaling system, organism-specific biosystem (from KEGG)
Phosphatidylinositol signaling system, organism-specific biosystem
Phosphatidylinositol signaling system
Phosphatidylinositol signaling system, conserved biosystem (from KEGG)
Phosphatidylinositol signaling system, conserved biosystem
Phosphatidylinositol signaling system
Phospholipid metabolism, organism-specific biosystem (from REACTOME)
Phospholipid metabolism, organism-specific biosystemPhospholipids contain a polar head group and two long-chain fatty acyl moieties, one of which is generally unsaturated. The head group is a glycerol or serine phosphate attached to a polar group such...
Regulation of Actin Cytoskeleton, organism-specific biosystem (from WikiPathways)
Regulation of Actin Cytoskeleton, organism-specific biosystemhttp://www.genome.jp/kegg/pathway/hsa/hsa04810.html
Signal Transduction of S1P Receptor, organism-specific biosystem (from WikiPathways)
Signal Transduction of S1P Receptor, organism-specific biosystemMetabolism of sphingomyelin by the sphingomyelinase, ceramidase (Cer'ase) and the sphingosine kinase (SK) enzymes results in formation of S1P and receptor activation. Autocrine and paracrine modes of...
Signaling Pathways in Glioblastoma, organism-specific biosystem (from WikiPathways)
Signaling Pathways in Glioblastoma, organism-specific biosystemThe most frequently altered genes in glioblastoma. This pathway originally accompanied the 2008 Nature publication on the comprehensive genomic characterization of human glioblastoma genes and core p...
Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem (from Pathway Interaction Database)
Signaling events mediated by Stem cell factor receptor (c-Kit), organism-specific biosystem
Signaling events mediated by Stem cell factor receptor (c-Kit)
Synthesis of PIPs at the plasma membrane, organism-specific biosystem (from REACTOME)
Synthesis of PIPs at the plasma membrane, organism-specific biosystemAt the plasma membrane, subsequent phosphorylation of phosphatidylinositol 4-phosphate (PI4P) produces phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and phosphatidylinositol 3,4,5-trisphosphate (...
superpathway of inositol phosphate compounds, organism-specific biosystem (from BIOCYC)
superpathway of inositol phosphate compounds, organism-specific biosystem
superpathway of inositol phosphate compounds

General gene information

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Markers

AL009631 (e-PCR)
- UniSTS:64264

A006Z05 (e-PCR)
- UniSTS:15898

D8S2279 (e-PCR)
- UniSTS:473907

WI-11932 (e-PCR)
- UniSTS:41324

SHGC-76195 (e-PCR)
- UniSTS:75655

D11S3114 (e-PCR)
- UniSTS:152207

Homology

Homologs of the PIK3C2B gene: The PIK3C2B gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
1-phosphatidylinositol-3-kinase activity	IBA Inferred from Biological aspect of Ancestor more info
1-phosphatidylinositol-4-phosphate 3-kinase activity	NAS Non-traceable Author Statement more info	PubMed
ATP binding	IEA Inferred from Electronic Annotation more info
lipid kinase activity	IEA Inferred from Electronic Annotation more info
phosphatidylinositol binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
biological_process	ND No biological Data available more info
phosphatidylinositol biosynthetic process	TAS Traceable Author Statement more info
phosphatidylinositol-3-phosphate biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
phosphatidylinositol-mediated signaling	IEA Inferred from Electronic Annotation more info
phospholipid metabolic process	TAS Traceable Author Statement more info
protein kinase B signaling cascade	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytosol	NAS Non-traceable Author Statement more info
cytosol	TAS Traceable Author Statement more info
endocytic vesicle	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
intracellular membrane-bounded organelle	NAS Non-traceable Author Statement more info
nucleus	IEA Inferred from Electronic Annotation more info
phosphatidylinositol 3-kinase complex	IBA Inferred from Biological aspect of Ancestor more info
plasma membrane	NAS Non-traceable Author Statement more info

General protein information

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Preferred Names: phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta

Names: phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta; PI3K-C2beta; PI3K-C2-beta; PTDINS-3-kinase C2 beta; ptdIns-3-kinase C2 subunit beta; phosphoinositide 3-kinase-C2-beta; phosphoinositide-3-kinase, class 2, beta polypeptide; phosphatidylinositol 3-kinase C2 domain-containing beta polypeptide; phosphatidylinositol-4-phosphate 3-kinase C2 domain-containing subunit beta

NP_002637.3

EC 2.7.1.154

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_002646.3 → NP_002637.3 phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta

Status: REVIEWED

Source sequence(s)

AK308153, AL606489, BC132876, F17716, Y11312

Consensus CDS

CCDS1446.1

UniProtKB/TrEMBL

A2RUF7

UniProtKB/Swiss-Prot

O00750

Related

ENSP00000356155, OTTHUMP00000034333, ENST00000367187, OTTHUMT00000087965

Conserved Domains (7) summary

cd00869
Location:813 – 973
Blast Score: 606

PI3Ka_II; Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases ...

cd00895
Location:987 – 1340
Blast Score: 1980

PI3Kc_C2_beta; Phosphoinositide 3-kinase (PI3K), class II, beta isoform, catalytic domain; The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein ...

cd07290
Location:1369 – 1477
Blast Score: 399

PX_PI3K_C2_beta; The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases

cd04012
Location:622 – 794
Blast Score: 627

C2A_PI3K_class_II; C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

cd08381
Location:1505 – 1627
Blast Score: 498

C2B_PI3K_class_II; C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks)

smart00146
Location:1080 – 1291
Blast Score: 671

PI3Kc; Phosphoinositide 3-kinase, catalytic domain

pfam00794
Location:364 – 465
Blast Score: 318

PI3K_rbd; PI3-kinase family, ras-binding domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p10 Primary Assembly

Range

204391758..204459474, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

175556880..175624580, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018912.1 Alternate CHM1_1.0

Range

210929574..210997137, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01027443.1 (8881..13479)	None
genomic	ABBA01027444.1	None
genomic	ABBA01027445.1	None
genomic	ABBA01027446.1	None
genomic	AL606489.26 (74588..142304)	None
genomic	AMYH01001663.1 (10542..78105)	None
genomic	CH471067.1	EAW91513.1
		EAW91514.1
genomic	EU332863.1	ABY87552.1
genomic	JX512455.1	AGC09602.1
mRNA	AB210006.1	BAE06088.1
mRNA	AK308153.1	None
mRNA	BC094741.1	None
mRNA	BC132876.1	AAI32877.1
mRNA	BC136645.1	AAI36646.1
mRNA	BC144342.1	AAI44343.1
mRNA	CR749201.1	CAH18059.1
mRNA	F17716.1	None
mRNA	Y11312.1	CAA72168.1
mRNA	Y13892.1	CAA74194.1