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PIK3R1

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PIK3R1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPIK3R1, AGM7, GRB1, IMD36, p85, p85-ALPHA, phosphoinositide-3-kinase regulatory subunit 1, PI3KR1
External IDsOMIM: 171833; MGI: 97583; HomoloGene: 7889; GeneCards: PIK3R1; OMA:PIK3R1 - orthologs
Orthologs
SpeciesHumanMouse
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 MbChr 13: 101.82 – 101.9 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

Function

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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

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

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

Interactions

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PIK3R1 has been shown to interact with:

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000145675 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000041417 – 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.
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  6. ^ "Entrez Gene: PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (p85 alpha)".
  7. ^ a b Gurney SM, Forster P, Just U, Schwanbeck R (2011). "Suppression of the PI3K Subunit p85alpha Delays Embryoid Body Development and Inhibits Cell Adhesion". J. Cell. Biochem. 112 (12): 3573–81. doi:10.1002/jcb.23285. PMID 11313349. S2CID 206020214.
  8. ^ "Entrez Gene: PIK3R1 phosphoinositide-3-kinase, regulatory subunit 1 (p85 alpha)".
  9. ^ The Cancer Genome Atlas Network (October 2012). "Comprehensive molecular portraits of human breast tumours". Nature. 490 (7418): 61–70. Bibcode:2012Natur.490...61T. doi:10.1038/nature11412. PMC 3465532. PMID 23000897.
  10. ^ Bárcena C, Quesada V, De Sandre-Giovannoli A, Puente DA, Fernández-Toral J, Sigaudy S, Baban A, Lévy N, Velasco G, López-Otín C (2014). "Exome sequencing identifies a novel mutation in PIK3R1 as the cause of SHORT syndrome". BMC Med. Genet. 15 (1): 3573–3581. doi:10.1186/1471-2350-15-51. PMC 4022398. PMID 21780162.
  11. ^ Kang Q, Cao Y, Zolkiewska A (2001). "Direct interaction between the cytoplasmic tail of ADAM 12 and the Src homology 3 domain of p85alpha activates phosphatidylinositol 3-kinase in C2C12 cells". J. Biol. Chem. 276 (27): 24466–72. doi:10.1074/jbc.M101162200. PMID 11313349.
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Further reading

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