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FLASH GENE

Symbol

PIK3CG

contributors: mct - updated : 10-02-2014

HGNC name	phosphoinositide-3-kinase, catalytic, gamma polypeptide
HGNC id	8978

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	43.70 kb     11 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002649 11 - 5379 - 1102 - Stoyanov (1995) NM_001282426 11 - 7069 NP_001269355 - 1102 - - NM_001282427 11 - 6993 NP_001269356 - 1102 - -

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Digestive liver         Endocrine pancreas         Lymphoid/Immune lymph node       highly   spleen       moderately Reproductive female system ovary     moderately   male system testis     highly Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Epithelial secretory glandular endocrine   Epithelial secretory glandular exocrine   Muscular striatum skeletal

cell lineage
cell lines
fluid/secretion	blood

at STAGE

IMPRINTING

maternally

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	C2 domain
	PIK domain
	PH domain at the N terminus

HOMOLOGY

interspecies	ortholog to rattus Pik3cg_predicted
	ortholog to murine Pik3cg

Homologene

FAMILY

PI3/PI4-kinase family

CATEGORY

enzyme , tumor suppressor , signaling , receptor membrane G

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic,granule

basic FUNCTION	controlling with PTEN heart muscle contractility and cell size and modulating the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects
	playing a role in control of tissue growth
	having critical roles within the gradient-sensing machinery of a variety of highly motile cells
	acting as a critical determinant of the proportion of cells that can move
	plays an essential role in a number of physiological responses, including neutrophil chemotaxis, mast cell degranulation, and cardiac function
	has two potential regulatory subunits PIK3R5, PIK3R6
	implicated in a vast array of physiological settings including the activation of different leukocyte species and the regulation of myocardial contractility
	playing roles in the regulation of some aspects of neutrophil polarization that are relevant to movement, such as integrin-based adhesion and the accumulation of polymerized (F)-actin at the leading-edge
	having nonredundant function as an important regulator of fibroblast-induced cartilage destruction during chronic destructive arthritis (Hayer 2009)
	activation by CXCL12 regulates tumor cell adhesion through mechanisms different from those involved in cell invasion (Monte)
	essential for CCL2-stimulated aortic SMC migration and amplifies cell migration induced by PDGF by an autocrine/paracrine loop involving CCL2 secretion and CCR2 activation
	PI3KC2B and PIK3CG control distinct steps involved in cell migration supporting the hypothesis that different PI3Ks regulate distinct cellular processes
	its activity is important for its signaling functions in T cell development, activation, differentiation, and trafficking

CELLULAR PROCESS	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

critical roles for a PI3K3CG-RAP1A-dependent pathway in integrin activation during tumor inflammation

a component

INTERACTION

DNA

RNA

small molecule

protein	PTEN
	PDE3B(inducing cAMP level reduction and negatively modulating cardiac contractility)
	PIK3R5 is required for G protein-mediated activation of PIK3CG in living cells
	binding of PIK3R6 to PIK3CG substantially increases the ability of Gbetagamma to stimulate phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P(3)) production
	like PIK3R5, PIK3R6 binds to both PIK3CG and Gbetagamma and mediates activation of PIK3CG downstream of G protein-coupled receptors
	a kinase-independent function of PIK3CG could directly inhibit GSK3 function by preventing the PP2A-PPMT-1 interaction
	PIK3CG regulates the activity of RALA, which is one of the molecular mechanisms inducing NMDAR dependent long-term depression

cell & other

REGULATION

activated by

both the alpha and the beta gamma G proteins

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   underexpressed in primary colorectal adenocarcinomas constitutional imprinting       overgrowth syndrome (Cowden, tuberous sclerosis, Proteus)

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS