PIK3CG

PIK3CG
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1E8Y, 1E8Z, 1HE8, 2A4Z, 2A5U, 2CHW, 2CHX, 2CHZ, 2V4L, 3APC, 3APD, 3APF, 3CSF, 3CST, 3DBS, 3ENE, 3IBE, 3L08, 3L13, 3L16, 3L17, 3L54, 3LJ3, 3MJW, 3ML8, 3ML9, 3NZS, 3NZU, 3OAW, 3P2B, 3PRE, 3PRZ, 3PS6, 3QAQ, 3QAR, 3QJZ, 3QK0, 3R7Q, 3R7R, 3S2A, 3SD5, 3T8M, 3TJP, 3TL5, 3ZVV, 3ZW3, 4ANU, 4ANV, 4ANW, 4ANX, 4AOF, 4DK5, 4EZJ, 4EZK, 4EZL, 4F1S, 4FA6, 4FAD, 4FHJ, 4FHK, 4FJY, 4FJZ, 4FLH, 4FUL, 4G11, 4GB9, 4HLE, 4HVB, 4J6I, 4KZ0, 4KZC, 4PS3, 4PS7, 4PS8, 4URK, 4WWN, 4WWO, 4WWP, 4XX5, 4XZ4, 5EDS, 5G2N
Identifiers
Aliases	PIK3CG , PI3CG, PI3K, PI3Kgamma, PIK3, p110gamma, p120-PI3K, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma, IMD97
External IDs	OMIM: 601232; MGI: 1353576; HomoloGene: 68269; GeneCards: PIK3CG; OMA:PIK3CG - orthologs
EC number	2.7.11.1
Gene location (Human) Chr. Chromosome 7 (human) [1] Band 7q22.3 Start 106,865,278 bp [1] End 106,908,980 bp [1]
Gene location (Mouse) Chr. Chromosome 12 (mouse) [2] Band 12|12 A3 Start 32,223,472 bp [2] End 32,258,658 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in bone marrow trabecular bone bone marrow cells blood monocyte epithelium of nasopharynx granulocyte lymph node testicle visceral pleura Top expressed in granulocyte tibiofemoral joint blood thymus lumbar subsegment of spinal cord bone marrow spleen stroma of bone marrow lymph node mesenteric lymph nodes More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity protein kinase activity nucleotide binding ephrin receptor binding 1-phosphatidylinositol-4-phosphate 3-kinase activity protein serine/threonine kinase activity protein binding phosphatidylinositol 3-kinase activity ATP binding phosphatidylinositol-4,5-bisphosphate 3-kinase activity kinase activity 1-phosphatidylinositol-3-kinase activity identical protein binding phosphatidylinositol-3,4-bisphosphate 5-kinase activity Cellular component cytoplasm phosphatidylinositol 3-kinase complex membrane phosphatidylinositol 3-kinase complex, class IB cytosol mast cell granule plasma membrane Biological process regulation of protein phosphorylation G protein-coupled receptor signaling pathway positive regulation of protein kinase B signaling regulation of cell adhesion mediated by integrin endocytosis adaptive immune response respiratory burst involved in defense response positive regulation of MAP kinase activity immune system process positive regulation of cytosolic calcium ion concentration T cell chemotaxis cytokine production positive regulation of catalytic activity secretory granule localization dendritic cell chemotaxis neutrophil chemotaxis platelet activation T cell proliferation chemotaxis protein phosphorylation phosphatidylinositol-3-phosphate biosynthetic process phosphatidylinositol phosphate biosynthetic process natural killer cell chemotaxis angiogenesis positive regulation of acute inflammatory response phosphatidylinositol biosynthetic process negative regulation of fibroblast apoptotic process phosphatidylinositol 3-kinase signaling negative regulation of triglyceride catabolic process mast cell degranulation inflammatory response innate immune response platelet aggregation neutrophil extravasation T cell activation regulation of calcium ion transmembrane transport cellular response to cAMP hepatocyte apoptotic process phosphatidylinositol-mediated signaling negative regulation of cardiac muscle contraction phosphorylation positive regulation of phosphatidylinositol 3-kinase signaling cell migration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5294 30955 Ensembl ENSG00000105851 ENSMUSG00000020573 UniProt P48736 Q9JHG7 RefSeq (mRNA) NM_001282426 NM_001282427 NM_002649 NM_001146200 NM_001146201 NM_020272 RefSeq (protein) NP_001269355 NP_001269356 NP_002640 NP_001139672 NP_001139673 NP_064668 Location (UCSC) Chr 7: 106.87 – 106.91 Mb Chr 12: 32.22 – 32.26 Mb PubMed search [3] [4]
Wikidata
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Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform is an enzyme that in humans is encoded by the PIK3CG gene.

Function

This gene encodes a protein that belongs to the pi3/pi4-kinase family of proteins. The gene product is an enzyme that phosphorylates phosphoinositides on the 3-hydroxyl group of the inositol ring. It is an important modulator of extracellular signals, including those elicited by E-cadherin-mediated cell-cell adhesion, which plays an important role in maintenance of the structural and functional integrity of epithelia. In addition to its role in promoting assembly of adherens junctions, the protein is thought to play a pivotal role in the regulation of cytotoxicity in NK cells. The gene is located in a commonly deleted segment of chromosome 7 previously identified in myeloid leukemias. ^[5] . More recently, this gene has been shown to be a critical myeloid-restricted vulnerability in Acute Myeloid Leukemia (AML). Its targeting, either by the small-molecule inhibitor IPI-549 or by a first-in-class proteolysis-targeting chimera (PROTAC) named ARM165, has been shown to reduce AML cell progression both in vitro and in vivo. ^{[6] [7]}

Interactions

PIK3CG has been shown to interact with:

• BCR gene, ^{[8] [9] [10]}
• KRAS, ^[11]
• PIK3CD, ^[12] and
• PIK3R5. ^[13]

See also

• Class I PI 3-kinases
• p87PIKAP

References

1. GRCh38: Ensembl release 89: ENSG00000105851 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020573 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: PIK3CG phosphoinositide-3-kinase, catalytic, gamma polypeptide".
6. https://pubmed.ncbi.nlm.nih.gov/38720074/
7. https://pubmed.ncbi.nlm.nih.gov/38816660/
8. Bai RY, Jahn T, Schrem S, Munzert G, Weidner KM, Wang JY, Duyster J (August 1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene. 17 (8): 941–8. doi:10.1038/sj.onc.1202024. PMID   9747873. S2CID   20866214.
9. Salgia R, Sattler M, Pisick E, Li JL, Griffin JD (February 1996). "p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl". Exp. Hematol. 24 (2): 310–3. PMID   8641358.
10. Skorski T, Kanakaraj P, Nieborowska-Skorska M, Ratajczak MZ, Wen SC, Zon G, Gewirtz AM, Perussia B, Calabretta B (July 1995). "Phosphatidylinositol-3 kinase activity is regulated by BCR/ABL and is required for the growth of Philadelphia chromosome-positive cells". Blood. 86 (2): 726–36. doi: 10.1182/blood.V86.2.726.bloodjournal862726 . PMID   7606002.
11. Rubio I, Wittig U, Meyer C, Heinze R, Kadereit D, Waldmann H, Downward J, Wetzker R (November 1999). "Farnesylation of Ras is important for the interaction with phosphoinositide 3-kinase gamma". Eur. J. Biochem. 266 (1): 70–82. doi: 10.1046/j.1432-1327.1999.00815.x . PMID   10542052.
12. Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD (April 1997). "P110delta, a novel phosphoinositide 3-kinase in leukocytes". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4330–5. Bibcode:1997PNAS...94.4330V. doi: 10.1073/pnas.94.9.4330 . PMC   20722 . PMID   9113989.
13. Brock C, Schaefer M, Reusch HP, Czupalla C, Michalke M, Spicher K, Schultz G, Nürnberg B (January 2003). "Roles of G beta gamma in membrane recruitment and activation of p110 gamma/p101 phosphoinositide 3-kinase gamma". J. Cell Biol. 160 (1): 89–99. doi:10.1083/jcb.200210115. PMC   2172741 . PMID   12507995.

Further reading

• Alloatti G, Montrucchio G, Lembo G, Hirsch E (2004). "Phosphoinositide 3-kinase gamma: kinase-dependent and -independent activities in cardiovascular function and disease". Biochem. Soc. Trans. 32 (Pt 2): 383–6. doi:10.1042/BST0320383. PMID   15046613.
• Rommel C, Camps M, Ji H (2007). "PI3K delta and PI3K gamma: partners in crime in inflammation in rheumatoid arthritis and beyond?". Nat. Rev. Immunol. 7 (3): 191–201. doi:10.1038/nri2036. PMID   17290298. S2CID   43376714.