PIK3R2

Phosphatidylinositol 3-kinase regulatory subunit beta is an enzyme that in humans is encoded by the PIK3R2 gene.[4][5]

PIK3R2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2KT1, 2XS6, 3MTT, 3O5Z
Identifiers
Aliases	PIK3R2, MPPH, MPPH1, P85B, p85, p85-BETA, phosphoinositide-3-kinase regulatory subunit 2
External IDs	OMIM: 603157 MGI: 1098772 HomoloGene: 3687 GeneCards: PIK3R2
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.11 Start 18,153,163 bp[1] End 18,170,532 bp[1]
RNA expression pattern More reference expression data
Gene ontology Molecular function • phosphatidylinositol 3-kinase regulator activity • receptor tyrosine kinase binding • 1-phosphatidylinositol-3-kinase regulator activity • GO:0001948 protein binding • protein heterodimerization activity • protein phosphatase binding • GO:0005097, GO:0005099, GO:0005100 GTPase activator activity • phosphatidylinositol-4,5-bisphosphate 3-kinase activity • phosphotyrosine residue binding • 1-phosphatidylinositol-3-kinase activity Cellular component • cytosol • phosphatidylinositol 3-kinase complex • cell nucleus Biological process • Fc-gamma receptor signaling pathway involved in phagocytosis • cellular glucose homeostasis • response to endoplasmic reticulum stress • Fc-epsilon receptor signaling pathway • phosphatidylinositol phosphorylation • vascular endothelial growth factor receptor signaling pathway • regulation of autophagy • regulation of phosphatidylinositol 3-kinase activity • cellular response to insulin stimulus • protein transport • phosphatidylinositol 3-kinase signaling • T cell receptor signaling pathway • regulation of small GTPase mediated signal transduction • phosphatidylinositol-mediated signaling • leukocyte migration • positive regulation of transcription from RNA polymerase II promoter • signal transduction • insulin receptor signaling pathway • GO:0032320, GO:0032321, GO:0032855, GO:0043089, GO:0032854 positive regulation of GTPase activity • phosphatidylinositol-3-phosphate biosynthetic process • negative regulation of MAPK cascade • positive regulation of protein kinase B signaling • positive regulation of protein import into nucleus • phosphatidylinositol biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5296	18709
Ensembl	ENSG00000105647	ENSMUSG00000031834
UniProt	O00459	O08908
RefSeq (mRNA)	NM_005027	NM_008841
RefSeq (protein)	NP_005018	NP_032867
Location (UCSC)	Chr 19: 18.15 – 18.17 Mb	n/a
PubMed search	[2]	[3]
Wikidata
View/Edit Human View/Edit Mouse

Interactions

PIK3R2 has been shown to interact with:

• CRKL[6]
• Cbl gene,[7][8]
• Epidermal growth factor,[9]
• FYN,[9]
• HER2/neu,[9]
• Macrophage colony-stimulating factor,[9] and
• PIK3CD.[10]

Clinical relevance

PIK3R2 mutations were recently shown to be associated with polymicrogyria.[11]

References

1. GRCh38: Ensembl release 89: ENSG00000105647 - Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Volinia S, Patracchini P, Otsu M, Hiles I, Gout I, Calzolari E, Bernardi F, Rooke L, Waterfield MD (Apr 1992). "Chromosomal localization of human p85 alpha, a subunit of phosphatidylinositol 3-kinase, and its homologue p85 beta". Oncogene. 7 (4): 789–93. PMID 1314371.
5. "Entrez Gene: PIK3R2 phosphoinositide-3-kinase, regulatory subunit 2 (p85 beta)".
6. Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD (Apr 1997). "Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL)". The Journal of Biological Chemistry. 272 (15): 10248–53. doi:10.1074/jbc.272.15.10248. PMID 9092574.
7. Lin H, Martelli MP, Bierer BE (Jan 2001). "The involvement of the proto-oncogene p120 c-Cbl and ZAP-70 in CD2-mediated T cell activation". International Immunology. 13 (1): 13–22. doi:10.1093/intimm/13.1.13. PMID 11133830.
8. Hartley D, Meisner H, Corvera S (Aug 1995). "Specific association of the beta isoform of the p85 subunit of phosphatidylinositol-3 kinase with the proto-oncogene c-cbl". The Journal of Biological Chemistry. 270 (31): 18260–3. doi:10.1074/jbc.270.31.18260. PMID 7629144.
9. Gout I, Dhand R, Panayotou G, Fry MJ, Hiles I, Otsu M, Waterfield MD (Dec 1992). "Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system". The Biochemical Journal. 288 (2): 395–405. doi:10.1042/bj2880395. PMC 1132024. PMID 1334406.
10. Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD (Apr 1997). "P110delta, a novel phosphoinositide 3-kinase in leukocytes". Proceedings of the National Academy of Sciences of the United States of America. 94 (9): 4330–5. doi:10.1073/pnas.94.9.4330. PMC 20722. PMID 9113989.
11. Mirzaa, G.; Conti, V.; Timms, A. E.; Smyser, C. D.; Ahmed, S.; Carter, M.; Barnett, S.; Hufnagel, R. B.; Goldstein, A.; Narumi-Kishimoto, Y.; Olds, C.; Collins, S.; Johnston, K.; Deleuze, J. F.; Nitschké, P.; Friend, K.; Harris, C.; Goetsch, A.; Martin, B.; Boyle, E. A.; Parrini, E.; Mei, D.; Tattini, L.; Slavotinek, A.; Blair, E.; Barnett, C.; Shendure, J.; Chelly, J.; Dobyns, W. B.; Guerrini, R. (2015). "Characterisation of mutations of the phosphoinositide-3-kinase regulatory subunit, PIK3R2, in perisylvian polymicrogyria: a next-generation sequencing study". The Lancet Neurology. 14 (12): 1182–1195. doi:10.1016/S1474-4422(15)00278-1. PMC 4672724. PMID 26520804.

Further reading

• Lee C, Liu QH, Tomkowicz B, Yi Y, Freedman BD, Collman RG (Nov 2003). "Macrophage activation through CCR5- and CXCR4-mediated gp120-elicited signaling pathways". Journal of Leukocyte Biology. 74 (5): 676–82. doi:10.1189/jlb.0503206. PMID 12960231.
• Gout I, Dhand R, Panayotou G, Fry MJ, Hiles I, Otsu M, Waterfield MD (Dec 1992). "Expression and characterization of the p85 subunit of the phosphatidylinositol 3-kinase complex and a related p85 beta protein by using the baculovirus expression system". The Biochemical Journal. 288 (2): 395–405. doi:10.1042/bj2880395. PMC 1132024. PMID 1334406.
• Carpenter CL, Duckworth BC, Auger KR, Cohen B, Schaffhausen BS, Cantley LC (Nov 1990). "Purification and characterization of phosphoinositide 3-kinase from rat liver". The Journal of Biological Chemistry. 265 (32): 19704–11. PMID 2174051.
• Truitt KE, Hicks CM, Imboden JB (Mar 1994). "Stimulation of CD28 triggers an association between CD28 and phosphatidylinositol 3-kinase in Jurkat T cells". The Journal of Experimental Medicine. 179 (3): 1071–6. doi:10.1084/jem.179.3.1071. PMC 2191424. PMID 7509360.
• Herbst R, Shearman MS, Jallal B, Schlessinger J, Ullrich A (May 1995). "Formation of signal transfer complexes between stem cell and platelet-derived growth factor receptors and SH2 domain proteins in vitro". Biochemistry. 34 (17): 5971–9. doi:10.1021/bi00017a026. PMID 7537096.
• Craparo A, O'Neill TJ, Gustafson TA (Jun 1995). "Non-SH2 domains within insulin receptor substrate-1 and SHC mediate their phosphotyrosine-dependent interaction with the NPEY motif of the insulin-like growth factor I receptor". The Journal of Biological Chemistry. 270 (26): 15639–43. doi:10.1074/jbc.270.26.15639. PMID 7541045.
• He W, O'Neill TJ, Gustafson TA (Oct 1995). "Distinct modes of interaction of SHC and insulin receptor substrate-1 with the insulin receptor NPEY region via non-SH2 domains". The Journal of Biological Chemistry. 270 (40): 23258–62. doi:10.1074/jbc.270.40.23258. PMID 7559478.
• Kapeller R, Toker A, Cantley LC, Carpenter CL (Oct 1995). "Phosphoinositide 3-kinase binds constitutively to alpha/beta-tubulin and binds to gamma-tubulin in response to insulin". The Journal of Biological Chemistry. 270 (43): 25985–91. doi:10.1074/jbc.270.43.25985. PMID 7592789.
• Hartley D, Meisner H, Corvera S (Aug 1995). "Specific association of the beta isoform of the p85 subunit of phosphatidylinositol-3 kinase with the proto-oncogene c-cbl". The Journal of Biological Chemistry. 270 (31): 18260–3. doi:10.1074/jbc.270.31.18260. PMID 7629144.
• Pandey A, Lazar DF, Saltiel AR, Dixit VM (Dec 1994). "Activation of the Eck receptor protein tyrosine kinase stimulates phosphatidylinositol 3-kinase activity". The Journal of Biological Chemistry. 269 (48): 30154–7. PMID 7982920.
• August A, Dupont B (May 1994). "CD28 of T lymphocytes associates with phosphatidylinositol 3-kinase". International Immunology. 6 (5): 769–74. doi:10.1093/intimm/6.5.769. PMID 8080844.
• Fukazawa T, Miyake S, Band V, Band H (Jun 1996). "Tyrosine phosphorylation of Cbl upon epidermal growth factor (EGF) stimulation and its association with EGF receptor and downstream signaling proteins". The Journal of Biological Chemistry. 271 (24): 14554–9. doi:10.1074/jbc.271.24.14554. PMID 8662998.
• Milani D, Mazzoni M, Borgatti P, Zauli G, Cantley L, Capitani S (Sep 1996). "Extracellular human immunodeficiency virus type-1 Tat protein activates phosphatidylinositol 3-kinase in PC12 neuronal cells". The Journal of Biological Chemistry. 271 (38): 22961–4. doi:10.1074/jbc.271.38.22961. PMID 8798481.
• Sattler M, Salgia R, Shrikhande G, Verma S, Pisick E, Prasad KV, Griffin JD (Apr 1997). "Steel factor induces tyrosine phosphorylation of CRKL and binding of CRKL to a complex containing c-kit, phosphatidylinositol 3-kinase, and p120(CBL)". The Journal of Biological Chemistry. 272 (15): 10248–53. doi:10.1074/jbc.272.15.10248. PMID 9092574.
• Vanhaesebroeck B, Welham MJ, Kotani K, Stein R, Warne PH, Zvelebil MJ, Higashi K, Volinia S, Downward J, Waterfield MD (Apr 1997). "P110delta, a novel phosphoinositide 3-kinase in leukocytes". Proceedings of the National Academy of Sciences of the United States of America. 94 (9): 4330–5. doi:10.1073/pnas.94.9.4330. PMC 20722. PMID 9113989.
• Briand G, Barbeau B, Tremblay M (Feb 1997). "Binding of HIV-1 to its receptor induces tyrosine phosphorylation of several CD4-associated proteins, including the phosphatidylinositol 3-kinase". Virology. 228 (2): 171–9. doi:10.1006/viro.1996.8399. PMID 9123823.
• Braunger J, Schleithoff L, Schulz AS, Kessler H, Lammers R, Ullrich A, Bartram CR, Janssen JW (Jun 1997). "Intracellular signaling of the Ufo/Axl receptor tyrosine kinase is mediated mainly by a multi-substrate docking-site". Oncogene. 14 (22): 2619–31. doi:10.1038/sj.onc.1201123. PMID 9178760.
• Shepherd PR, Navé BT, Rincon J, Nolte LA, Bevan AP, Siddle K, Zierath JR, Wallberg-Henriksson H (Jul 1997). "Differential regulation of phosphoinositide 3-kinase adapter subunit variants by insulin in human skeletal muscle". The Journal of Biological Chemistry. 272 (30): 19000–7. doi:10.1074/jbc.272.30.19000. PMID 9228082.
• Mazerolles F, Barbat C, Fischer A (Sep 1997). "Down-regulation of LFA-1-mediated T cell adhesion induced by the HIV envelope glycoprotein gp160 requires phosphatidylinositol-3-kinase activity". European Journal of Immunology. 27 (9): 2457–65. doi:10.1002/eji.1830270946. PMID 9341793.