PK3CG_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PK3CG_MOUSE
• UniProt AC: Q9JHG7
• Protein Name: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform
• Gene Name: Pik3cg
• Organism: Mus musculus (Mouse).
• Sequence Length: 1102
• Subcellular Localization: Cytoplasm. Cell membrane.
• Protein Description: Phosphoinositide-3-kinase (PI3K) that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Links G-protein coupled receptor activation to PIP3 production. Involved in immune, inflammatory and allergic responses. Modulates leukocyte chemotaxis to inflammatory sites and in response to chemoattractant agents. May control leukocyte polarization and migration by regulating the spatial accumulation of PIP3 and by regulating the organization of F-actin formation and integrin-based adhesion at the leading edge. Controls motility of dendritic cells. Together with PIK3CD is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in T-lymphocyte migration. Regulates T-lymphocyte proliferation and cytokine production. Together with PIK3CD participates in T-lymphocyte development. Required for B-lymphocyte development and signaling. Together with PIK3CD participates in neutrophil respiratory burst. Together with PIK3CD is involved in neutrophil chemotaxis and extravasation. Together with PIK3CB promotes platelet aggregation and thrombosis. Regulates alpha-IIb/beta-3 integrins (ITGA2B/ ITGB3) adhesive function in platelets downstream of P2Y12 through a lipid kinase activity-independent mechanism. May have also a lipid kinase activity-dependent function in platelet aggregation. Involved in endothelial progenitor cell migration. Negative regulator of cardiac contractility. Modulates cardiac contractility by anchoring protein kinase A (PKA) and PDE3B activation, reducing cAMP levels. Regulates cardiac contractility also by promoting beta-adrenergic receptor internalization by binding to GRK2 and by non-muscle tropomyosin phosphorylation. Also has serine/threonine protein kinase activity: both lipid and protein kinase activities are required for beta-adrenergic receptor endocytosis. May also have a scaffolding role in modulating cardiac contractility. Contribute to cardiac hypertrophy under pathological stress. Through simultaneous binding of PDE3B to RAPGEF3 and PIK3R6 is assembled in a signaling complex in which the PI3K gamma complex is activated by RAPGEF3 and which is involved in angiogenesis (By similarity)..
• Protein Sequence: MELENYEQPVVLREDNLRRRRRMKPRSAAGSLSSMELIPIEFVLPTSQRISKTPETALLHVAGHGNVEQMKAQVWLRALETSVAAEFYHRLGPDQFLLLYQKKGQWYEIYDRYQVVQTLDCLHYWKLMHKSPGQIHVVQRHVPSEETLAFQKQLTSLIGYDVTDISNVHDDELEFTRRRLVTPRMAEVAGRDAKLYAMHPWVTSKPLPDYLSKKIANNCIFIVIHRGTTSQTIKVSADDTPGTILQSFFTKMAKKKSLMNISESQSEQDFVLRVCGRDEYLVGETPLKNFQWVRQCLKNGDEIHLVLDTPPDPALDEVRKEEWPLVDDCTGVTGYHEQLTIHGKDHESVFTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFAEEVLWNVWLEFGIKIKDLPKGALLNLQIYCCKTPSLSSKASAETPGSESKGKAQLLYYVNLLLIDHRFLLRHGDYVLHMWQISGKAEEQGSFNADKLTSATNPDKENSMSISILLDNYCHPIALPKHRPTPDPEGDRVRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARREIWDQSALDVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRHYQQRFAVILEAYLRGCGTAMLQDFTQQVHVIEMLQKVTIDIKSLSAEKYDVSSQVISQLKQKLESLQNSNLPESFRVPYDPGLKAGTLVIEKCKVMASKKKPLWLEFKCADPTVLSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAQIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMISETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGSSGKKTSPHFQKFQDVCVRAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIKQGEKHSA

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
6	Phosphorylation	--MELENYEQPVVLR --CCCCCCCCCEECC	13.43	-
27	Phosphorylation	RRRMKPRSAAGSLSS HHCCCCCCCCCCCCC	30.88	25367039
31	Phosphorylation	KPRSAAGSLSSMELI CCCCCCCCCCCCEEE	21.98	24719451
33	Phosphorylation	RSAAGSLSSMELIPI CCCCCCCCCCEEEEE	29.36	25367039
34	Phosphorylation	SAAGSLSSMELIPIE CCCCCCCCCEEEEEE	22.90	25367039
46	Phosphorylation	PIEFVLPTSQRISKT EEEEEECCCCCCCCC	33.07	25367039
47	Phosphorylation	IEFVLPTSQRISKTP EEEEECCCCCCCCCC	18.60	25367039
51	Phosphorylation	LPTSQRISKTPETAL ECCCCCCCCCCCCCH	32.44	25367039
53	Phosphorylation	TSQRISKTPETALLH CCCCCCCCCCCCHHH	21.40	25367039
56	Phosphorylation	RISKTPETALLHVAG CCCCCCCCCHHHHHC	24.65	25367039
182	Phosphorylation	FTRRRLVTPRMAEVA HHHHHCCCHHHHHHH	15.12	24719451
236	Phosphorylation	TSQTIKVSADDTPGT CCCEEEEECCCCCHH	22.45	29895711
240	Phosphorylation	IKVSADDTPGTILQS EEEECCCCCHHHHHH	24.94	29895711
243	Phosphorylation	SADDTPGTILQSFFT ECCCCCHHHHHHHHH	21.51	29895711
247	Phosphorylation	TPGTILQSFFTKMAK CCHHHHHHHHHHHHH	20.91	29895711
582	Phosphorylation	LWHFRYESLKHPKAY HHHHHHHHCCCCCCC	33.51	29176673
760	Phosphorylation	SAEKYDVSSQVISQL CCCCCCHHHHHHHHH	16.50	29895711
777	Phosphorylation	KLESLQNSNLPESFR HHHHHHCCCCCHHHC	27.12	22871156
782	Phosphorylation	QNSNLPESFRVPYDP HCCCCCHHHCCCCCC	19.20	22871156
787	Phosphorylation	PESFRVPYDPGLKAG CHHHCCCCCCCCCCC	31.73	22871156
899	Phosphorylation	QQSTVGNTGAFKDEV HHCCCCCCCCHHHHH	24.77	15851034
974	Phosphorylation	HILGNYKSFLGINKE HHHCCCHHHHCCCCC	18.49	27180971
1024	Phosphorylation	YLALRHHTNLLIILF HHHHHHHHHHHHHHH	22.80	21474070
1101	Phosphorylation	IKQGEKHSA------ CCCCCCCCC------	46.90	-

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
1024	T	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
1024	T	Phosphorylation	Kinase	PKA	-	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
1024	T	Phosphorylation	Phosphorylated at Thr-1024 by PKA.	21474070

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of PK3CG_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PK3CD_MOUSE	Pik3cd	genetic	17723215

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Integrating cardiac PIP3 and cAMP signaling through a PKA anchoringfunction of p110gamma.";
Perino A., Ghigo A., Ferrero E., Morello F., Santulli G.,Baillie G.S., Damilano F., Dunlop A.J., Pawson C., Walser R., Levi R.,Altruda F., Silengo L., Langeberg L.K., Neubauer G., Heymans S.,Lembo G., Wymann M.P., Wetzker R., Houslay M.D., Iaccarino G.,Scott J.D., Hirsch E.;
Mol. Cell 42:84-95(2011).
Cited for: FUNCTION ON CARDIAC CONTRACTILITY, AND PHOSPHORYLATION AT THR-1024.
PubMed: 21474070