PIK3R1

Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.^[5]

PIK3R1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1A0N, 1AZG, 1H9O, 1PBW, 1PHT, 1PIC, 1PKS, 1PKT, 2IUG, 2IUH, 2IUI, 2RD0, 2V1Y, 3HHM, 3HIZ, 3I5R, 3I5S, 4A55, 4JPS, 4L1B, 4L23, 4L2Y, 4OVU, 4OVV, 4WAF, 5AUL
Identifiers
Aliases	PIK3R1, AGM7, GRB1, IMD36, p85, p85-ALPHA, phosphoinositide-3-kinase regulatory subunit 1, PI3KR1
External IDs	OMIM: 171833; MGI: 97583; HomoloGene: 7889; GeneCards: PIK3R1; OMA:PIK3R1 - orthologs
Gene location (Human) Chr. Chromosome 5 (human)^[1] Band 5q13.1 Start 68,215,756 bp^[1] End 68,301,821 bp^[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)^[2] Band 13 D1|13 53.92 cM Start 101,817,071 bp^[2] End 101,904,725 bp^[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon caput epididymis corpus epididymis postcentral gyrus lactiferous duct trigeminal ganglion middle temporal gyrus superior frontal gyrus external globus pallidus pericardium Top expressed in lacrimal gland molar parotid gland intercostal muscle cumulus cell aortic valve submandibular gland retinal pigment epithelium pineal gland seminal vesicula More reference expression data BioGPS More reference expression data
Gene ontology Molecular function ErbB-3 class receptor binding phosphatidylinositol 3-kinase regulator activity insulin-like growth factor receptor binding transmembrane receptor protein tyrosine kinase adaptor activity insulin receptor binding neurotrophin TRKA receptor binding phosphatidylinositol 3-kinase regulatory subunit binding transcription factor binding insulin binding phosphatidylinositol 3-kinase binding 1-phosphatidylinositol-3-kinase regulator activity protein binding protein heterodimerization activity insulin receptor substrate binding protein phosphatase binding 1-phosphatidylinositol-3-kinase activity phosphatidylinositol-4,5-bisphosphate 3-kinase activity phosphotyrosine residue binding Cellular component cytoplasm cytosol phosphatidylinositol 3-kinase complex phosphatidylinositol 3-kinase complex, class IA membrane cell-cell junction cis-Golgi network plasma membrane nucleus perinuclear endoplasmic reticulum membrane protein-containing complex Biological process positive regulation of glucose import insulin-like growth factor receptor signaling pathway negative regulation of cell adhesion positive regulation of endoplasmic reticulum unfolded protein response epidermal growth factor receptor signaling pathway Fc-gamma receptor signaling pathway involved in phagocytosis negative regulation of osteoclast differentiation positive regulation of cell migration cellular glucose homeostasis cellular response to UV T cell costimulation protein stabilization negative regulation of apoptotic process response to endoplasmic reticulum stress regulation of stress fiber assembly negative regulation of cell-matrix adhesion platelet activation Fc-epsilon receptor signaling pathway protein phosphorylation phosphatidylinositol phosphate biosynthetic process vascular endothelial growth factor receptor signaling pathway growth hormone receptor signaling pathway regulation of phosphatidylinositol 3-kinase activity intrinsic apoptotic signaling pathway in response to DNA damage cellular response to insulin stimulus positive regulation of tumor necrosis factor production positive regulation of RNA splicing phosphatidylinositol biosynthetic process protein transport B cell differentiation viral process T cell receptor signaling pathway extrinsic apoptotic signaling pathway via death domain receptors phosphatidylinositol-mediated signaling leukocyte migration positive regulation of transcription by RNA polymerase II signal transduction phosphatidylinositol 3-kinase signaling phosphatidylinositol-3-phosphate biosynthetic process ERBB2 signaling pathway insulin receptor signaling pathway axon guidance regulation of insulin receptor signaling pathway interleukin-7-mediated signaling pathway transport regulation of protein localization to plasma membrane positive regulation of protein localization to plasma membrane G protein-coupled receptor signaling pathway positive regulation of protein kinase B signaling protein import into nucleus positive regulation of phosphatidylinositol 3-kinase signaling cytokine-mediated signaling pathway positive regulation of protein import into nucleus Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5295 18708 Ensembl ENSG00000145675 ENSMUSG00000041417 UniProt P27986 P26450 RefSeq (mRNA) NM_001242466 NM_181504 NM_181523 NM_181524 NM_001024955 NM_001077495 RefSeq (protein) NP_001229395 NP_852556 NP_852664 NP_852665 NP_001020126 NP_001070963 Location (UCSC) Chr 5: 68.22 – 68.3 Mb Chr 13: 101.82 – 101.9 Mb PubMed search ^[3] ^[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. The Pik3r1 gene locus encodes the 85 kD regulatory subunit, as well as 55 and 50 kD regulatory subunits. It used to be thought that alternative splicing of this gene resulted in three transcript variants encoding different isoforms.^[6] In fact, it has since been shown that the 55 and 50kD subunits have their own promotors within the gene locus Pik3r1.^[7]

Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance.^[8] Suppression specifically of the 85kD subunit in early murine embryoid body development results in a transient cell-cell adhesion deficiency, mediated by transient downregulation of the adhesion molecule integrin-beta1 (ITGB1).^[7]

Clinical significance

Mutations in PIK3R1 are implicated in cases of breast cancer.^[9]

Mutations in PIK3R1 are associated to SHORT syndrome.^[10]

Interactions

PIK3R1 has been shown to interact with:

• ADAM12,^[11]
• BCAR1,^[12]
• CBLB,^[13][14]
• CD117,^[15][16][17]
• CD28,^[18]
• CD7,^[19][20]
• CENTG1,^[21]
• CBL,^[22][23][24]
• EPHA2,^[25]
• EPOR,^[26][27]
• ERBB3,^[28][29]
• EZR,^[30]
• FCGR2A,^[31][32]
• GAB1,^[33][34][35]
• GAB2,^[36][37]
• Grb2,^[38][39]
• HRAS,^[40][41]
• IRS1^{[42][43][44][45]}
• IRS2,^{[42][46][47][48]}
• IL1R1,^[49]
• JAK2,^[50]
• KHDRBS1,^[51][52]
• LTK,^[53][54]
• LAT,^[55]
• LCP2,^[56]
• PIK3CD,^[57]
• PTK2,^[58]
• SHB,^[59]
• TUBA1B,^[60]
• TYRO3,^[61]
• VAV1,^[26][33] and
• WAS.^[62]

References

1. GRCh38: Ensembl release 89: ENSG00000145675 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041417 – Ensembl, May 2017
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4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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Further reading

• Benito M, Valverde AM, Lorenzo M (1996). "IGF-I: a mitogen also involved in differentiation processes in mammalian cells". Int. J. Biochem. Cell Biol. 28 (5): 499–510. doi:10.1016/1357-2725(95)00168-9. PMID 8697095.
• Snapper SB, Rosen FS (1999). "The Wiskott-Aldrich syndrome protein (WASP): roles in signaling and cytoskeletal organization". Annu. Rev. Immunol. 17: 905–29. doi:10.1146/annurev.immunol.17.1.905. PMID 10358777.
• Katada T, Kurosu H, Okada T, Suzuki T, Tsujimoto N, Takasuga S, Kontani K, Hazeki O, Ui M (1999). "Synergistic activation of a family of phosphoinositide 3-kinase via G-protein coupled and tyrosine kinase-related receptors". Chem. Phys. Lipids. 98 (1–2): 79–86. doi:10.1016/S0009-3084(99)00020-1. PMID 10358930.
• Zhang W, Samelson LE (2000). "The role of membrane-associated adaptors in T cell receptor signalling". Semin. Immunol. 12 (1): 35–41. doi:10.1006/smim.2000.0205. PMID 10723796.
• Greenway AL, Holloway G, McPhee DA, Ellis P, Cornall A, Lidman M (2003). "HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication". J. Biosci. 28 (3): 323–35. doi:10.1007/BF02970151. PMID 12734410. S2CID 33749514.
• Leavitt SA, SchOn A, Klein JC, Manjappara U, Chaiken IM, Freire E (2004). "Interactions of HIV-1 proteins gp120 and Nef with cellular partners define a novel allosteric paradigm". Curr. Protein Pept. Sci. 5 (1): 1–8. doi:10.2174/1389203043486955. PMID 14965316.
• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726.