SMART: PI3K_C2 domain annotation

PI3K_C2 Phosphoinositide 3-kinase, region postulated to contain C2 domain

SMART accession number:	SM00142
Description:	Outlier of C2 family.
Interpro abstract (IPR002420):	Phosphatidylinositol 3-kinase (PI3-kinase) (EC 2.7.1.137) is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The usually N-terminal C2 domain interacts mainly with the scaffolding helical domain of the enzyme, and exhibits only minor interactions with the catalytic domain (PUBMED:12151228). The domain consists of two four-stranded antiparallel beta-sheets that form a beta-sandwich. Isolated C2 domain binds multilamellar phospholipid vesicles which suggests that this domain could play a role in membrane association. Membrane attachment by C2 domains is typically mediated by the loops connecting beta-strand regions that in other C2 domain-containing proteins are calcium-binding region
GO process:	phosphoinositide phosphorylation (GO:0046854), phosphoinositide-mediated signaling (GO:0048015)
GO component:	phosphoinositide 3-kinase complex (GO:0005942)
GO function:	1-phosphatidylinositol-3-kinase activity (GO:0016303)
Family alignment:	View or

There are 324 PI3K_C2 domains in 324 proteins in SMART's nrdb database.

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Evolution (species in which this domain is found)
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This tree shows only several representative species. The complete taxonomic breakdown of all proteins with PI3K_C2 domain is also avaliable.

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Go to specific node: Anopheles gambiae, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens, Mus musculus, Rattus norvegicus, Saccharomyces cerevisiae, Takifugu rubripes
Cellular role (predicted cellular role)
Binding / catalysis: Ca2+-binding (putative)
Literature (relevant references for this domain)
Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.
- Walker EH, Perisic O, Ried C, Stephens L, Williams RL
- Structural insights into phosphoinositide 3-kinase catalysis and signalling.
- Nature. 1999; 402: 313-20
- Display abstract
- Phosphoinositide 3-kinases (PI3Ks) are ubiquitous lipid kinases that function both as signal transducers downstream of cell-surface receptors and in constitutive intracellular membrane and protein trafficking pathways. All PI3Ks are dual-specificity enzymes with a lipid kinase activity which phosphorylates phosphoinositides at the 3-hydroxyl, and a protein kinase activity. The products of PI3K-catalysed reactions, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), PtdIns(3,4)P2 and PtdIns(3)P, are second messengers in a variety of signal transduction pathways, including those essential to cell proliferation, adhesion, survival, cytoskeletal rearrangement and vesicle trafficking. Here we report the 2.2 A X-ray crystallographic structure of the catalytic subunit of PI3Kgamma, the class I enzyme that is activated by heterotrimeric G-protein betagamma subunits and Ras. PI3Kgamma has a modular organization centred around a helical-domain spine, with C2 and catalytic domains positioned to interact with phospholipid membranes, and a Ras-binding domain placed against the catalytic domain where it could drive allosteric activation of the enzyme.
- Domin J, Waterfield MD
- Using structure to define the function of phosphoinositide 3-kinase family members.
- FEBS Lett. 1997; 410: 91-5
- Vanhaesebroeck B, Leevers SJ, Panayotou G, Waterfield MD
- Phosphoinositide 3-kinases: a conserved family of signal transducers.
- Trends Biochem Sci. 1997; 22: 267-72
- Display abstract
- Phosphoinositide 3-kinases (PI3Ks) generate lipids that are implicated in receptor-stimulated signalling and in the regulation of membrane traffic. Several distinct classes of PI3Ks have now been identified that have been conserved throughout eukaryotic evolution. Potential signalling pathways downstream of PI3Ks have been elucidated and PI3K function is now being characterised in several model organisms.
Metabolism (metabolic pathways involving proteins which contain this domain)

Structure (3D structures containing this domain)

3D Structures of PI3K_C2 domains in PDB

PDB code	Main view	Title
1e7u		Structure determinants of phosphoinositide 3-kinase inhibition by wortmannin, ly294002, quercetin, myricetin and staurosporine
1e7v		Structure determinants of phosphoinositide 3-kinase inhibition by wortmannin, ly294002, quercetin, myricetin and staurosporine
1e8w		Structure determinants of phosphoinositide 3-kinase inhibition by wortmannin, ly294002, quercetin, myricetin and staurosporine
1e8x		Structural insights into phoshoinositide 3-kinase enzymatic mechanism and signalling
1e8y		Structure determinants of phosphoinositide 3-kinase inhibition by wortmannin, ly294002, quercetin, myricetin and staurosporine
1e8z		Structure determinants of phosphoinositide 3-kinase inhibition by wortmannin, ly294002, quercetin, myricetin and staurosporine
1e90		Structure determinants of phosphoinositide 3-kinase inhibition by wortmannin, ly294002, quercetin, myricetin and staurosporine
1he8		Ras g12v-pi 3-kinase gamma complex
2a4z		Crystal structure of human pi3kgamma complexed with as604850
2a5u		Crystal structure of human pi3kgamma complexed with as605240
2chw		A pharmacological map of the pi3-k family defines a role for p110 alpha in signaling: the structure of complex of phosphoinositide 3-kinase gamma with inhibitor pik-39
2chx		A pharmacological map of the pi3-k family defines a role for p110alpha in signaling: the structure of complex of phosphoinositide 3-kinase gamma with inhibitor pik-90
2chz		A pharmacological map of the pi3-k family defines a role for p110alpha in signaling: the structure of complex of phosphoinositide 3-kinase gamma with inhibitor pik-93
2enq		Solution structure of the c2 domain from human pi3-kinase p110 subunit alpha
2rd0		Structure of a human p110alpha/p85alpha complex
2v4l
3csf		Crystal structure of pi3k p110gamma catalytical domain in complex with organoruthenium inhibitor dw2
3cst		Crystal structure of pi3k p110gamma catalytical domain in complex with organoruthenium inhibitor e5e2
3dbs		Structure of pi3k gamma in complex with gdc0941
3dpd
3ene
3hhm
3hiz
3ibe

Links (links to other resources describing this domain)
INTERPRO IPR002420