PI3Kc Phosphoinositide 3-kinase, catalytic domain
SMART ACC:	SM000146
Description:	Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.
InterPro ACC:	IPR000403
InterPro abstract:	This entry represents the catalytic domain of PI3 and PI-4 kinases. This domain is also found in a number of pseudokinases, where a lack of typical motifs at the catalytic site suggest a lack of kinase activity. Phosphatidylinositol 3-kinase (PI3-kinase) ( EC:2.7.1.137 ) [ PUBMED:1322797 … expand This entry represents the catalytic domain of PI3 and PI-4 kinases. This domain is also found in a number of pseudokinases, where a lack of typical motifs at the catalytic site suggest a lack of kinase activity. Phosphatidylinositol 3-kinase (PI3-kinase) ( EC:2.7.1.137 ) [ PUBMED:1322797 ] is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. The three products of PI3-kinase - PI-3-P, PI-3,4-P(2) and PI-3,4,5-P(3) function as secondary messengers in cell signalling. Phosphatidylinositol 4-kinase (PI4-kinase) ( EC:2.7.1.67 ) [ PUBMED:8194527 ] is an enzyme that acts on phosphatidylinositol (PI) in the first committed step in the production of the secondary messenger inositol-1'4'5'-trisphosphate. This domain is also present in a wide range of protein kinases, involved in diverse cellular functions, such as control of cell growth, regulation of cell cycle progression, a DNA damage checkpoint, recombination, and maintenance of telomere length. Despite significant homology to lipid kinases, no lipid kinase activity has been demonstrated for any of the PIK-related kinases [ PUBMED:12456783 ]. The PI3- and PI4-kinases share a well conserved domain at their C-terminal section; this domain seems to be distantly related to the catalytic domain of protein kinases [ PUBMED:8387896 PUBMED:12151228 ]. The catalytic domain of PI3/PI4KK has the typical bilobal structure that is seen in other ATP-dependent kinases, divided into an N-lobe and a C-lobe [ PUBMED:24675427 ]. The core of this domain is the most conserved region of the PI3Ks. The N-lobe contains a five-stranded antiparallel β-sheet core flanked by a helical hairpin on one side and a helix on the other. The C-lobe contains helices, which form a helical bundle together with the N--obe helix. The helical bundle is flanked by three β-strands and a helix. Three loops are related to kinase activity, the glycine-rich G-loop, the catalytic loop and the activation loop. The G-loop has been reported to bind to the phosphate group of nucleotides [ PUBMED:24675427 ]. collapse
Family alignment:	View the Family alignment or the Alignment consensus sequence
There are 18 030 PI3Kc domains in 18 022 proteins in SMART's NRDB database.

Taxonomic distribution of proteins containing PI3Kc domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing PI3Kc domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Predicted cellular role

Binding / catalysis:	Phosphoinositide-phosphorylation

Relevant references for this domain

Primary literature for the PI3Kc domain is listed below. Automatically-derived, secondary literature is also available.

Disease genes where sequence variants are found in this domain

UniRef sequences and OMIM curated human diseases associated with missense mutations within the PI3Kc domain.

Protein	Description	Disease / phenotype
ATM_HUMAN		OMIM:208900 : Ataxia-telangiectasia ; T-cell prolymphocytic leukemia, sporadic ; Lymphoma, B-cell non-Hodgkin, somatic ; {Breast cancer, susceptibility to} ; Lymphoma, mantle cell

KEGG pathways involving proteins which contain this domain

This information is based on the mapping of SMART genomic protein database to KEGG orthologous groups. Percentages are related to the number of proteins containing a PI3Kc domain which could be assigned to a KEGG orthologous group, and not all proteins containing PI3Kc domains. Please note that proteins can be included in multiple pathways, ie. the numbers below will not add to 100%.

KEGG pathways

Some of these pathways are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

KEGG orthologous groups

Some of these KOs are included in the interactive Pathways Explorer overview maps. Select an overview map and click the button below to highlight them in iPath.

3D structures in PDB containing this domain

Links to other resources describing this domain

Pfam	PI3_PI4_kinase
InterPro	IPR000403