Molecule Information

General Information of the Molecule (ID: Mol00546)

• Name: PI3-kinase regulatory subunit beta (PIK3R2) ,Homo sapiens
• Synonyms: PI3-kinase regulatory subunit beta; PI3K regulatory subunit beta; PtdIns-3-kinase regulatory subunit beta; Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta; PI3-kinase subunit p85-beta; PtdIns-3-kinase regulatory subunit p85-beta
• Molecule Type: Protein
• Gene Name: PIK3R2
• Gene ID: 5296
• Location: chr19:18153163-18170532[+]
• Sequence:
  MAGPEGFQYRALYPFRRERPEDLELLPGDVLVVSRAALQALGVAEGGERCPQSVGWMPGL
  NERTRQRGDFPGTYVEFLGPVALARPGPRPRGPRPLPARPRDGAPEPGLTLPDLPEQFSP
  PDVAPPLLVKLVEAIERTGLDSESHYRPELPAPRTDWSLSDVDQWDTAALADGIKSFLLA
  LPAPLVTPEASAEARRALREAAGPVGPALEPPTLPLHRALTLRFLLQHLGRVASRAPALG
  PAVRALGATFGPLLLRAPPPPSSPPPGGAPDGSEPSPDFPALLVEKLLQEHLEEQEVAPP
  ALPPKPPKAKPASTVLANGGSPPSLQDAEWYWGDISREEVNEKLRDTPDGTFLVRDASSK
  IQGEYTLTLRKGGNNKLIKVFHRDGHYGFSEPLTFCSVVDLINHYRHESLAQYNAKLDTR
  LLYPVSKYQQDQIVKEDSVEAVGAQLKVYHQQYQDKSREYDQLYEEYTRTSQELQMKRTA
  IEAFNETIKIFEEQGQTQEKCSKEYLERFRREGNEKEMQRILLNSERLKSRIAEIHESRT
  KLEQQLRAQASDNREIDKRMNSLKPDLMQLRKIRDQYLVWLTQKGARQKKINEWLGIKNE
  TEDQYALMEDEDDLPHHEERTWYVGKINRTQAEEMLSGKRDGTFLIRESSQRGCYACSVV
  VDGDTKHCVIYRTATGFGFAEPYNLYGSLKELVLHYQHASLVQHNDALTVTLAHPVRAPG
  PGPPPAAR
• Function: Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase 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. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy. Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement.
• Uniprot ID: P85B_HUMAN
• Ensembl ID: ENSG00000105647
• HGNC ID: HGNC:8980

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Cisplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Gastric cancer [1]

• Resistant Disease: Gastric cancer [ICD-11: 2B72.1]
• Resistant Drug: Cisplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: PI3K/AKT/MRP1 signaling pathway; Activation; hsa04151
• In Vitro Model: BGC-823 cells; Gastric; Homo sapiens (Human); CVCL_3360
• In Vitro Model: SGC7901 cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: SGC-7901/DDP cells; Gastric; Homo sapiens (Human); CVCL_0520
• In Vitro Model: BGC-823/DDP cells; Gastric; Homo sapiens (Human); CVCL_3360
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; Colony formation assay; Flow cytometric cell cycle assay; Annexin V-FITC Apoptosis assay
• Mechanism Description: HOTAIR was shown to directly bind to and inhibit miR126 expression and then to promote VEGFA and PIk3R2 expression and activate the PI3k/AkT/MRP1 pathway.

Clinical Trial Drug(s) 1 drug(s) in total

MTOR inhibitors

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Endometrial adenocarcinoma [2]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: MTOR inhibitors
• Molecule Alteration: Missense mutation; p.N561D (c.1681A>G)
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Ba/F3 cells; Colon; Homo sapiens (Human); CVCL_0161
• Experiment for Molecule Alteration: Whole-gene resequencing assay
• Mechanism Description: The missense mutation p.N561D (c.1681A>G) in gene PIK3R2 cause the sensitivity of MTOR inhibitors by unusual activation of pro-survival pathway

Disease Class: Endometrial adenocarcinoma [2]

• Sensitive Disease: Endometrial adenocarcinoma [ICD-11: 2C76.0]
• Sensitive Drug: MTOR inhibitors
• Molecule Alteration: Missense mutation; p.A171V (c.512C>T)
• Experimental Note: Identified from the Human Clinical Data

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Gastric cancer [ICD-11: 2B72]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Gastric tissue
• The Specified Disease: Gastric cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 7.15E-01; Fold-change: -1.82E-02; Z-score: -2.78E-01
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 3.78E-02; Fold-change: 2.27E-01; Z-score: 7.67E-01

References

• Ref 1: LncRNA HOTAIR promotes cisplatin resistance in gastric cancer by targeting miR-126 to activate the PI3K/AKT/MRP1 genes. Tumour Biol. 2016 Nov 30. doi: 10.1007/s13277-016-5448-5. Online ahead of print.
• Ref 2: High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stabilityCancer Discov. 2011 Jul;1(2):170-85. doi: 10.1158/2159-8290.CD-11-0039. Epub 2011 Jun 7.