Tchem PIK3R1 Phosphatidylinositol 3-kinase regulatory subunit alpha

Protein Summary

Description

Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Necessary for the insulin-stimulated increase in glucose uptake and glycogen synthesis in insulin-sensitive tissues. Plays an important role in signaling in response to FGFR1, FGFR2, FGFR3, FGFR4, KITLG/SCF, KIT, PDGFRA and PDGFRB. Likewise, plays a role in ITGB2 signaling (PubMed:17626883, PubMed:19805105, PubMed:7518429). Modulates the cellular response to ER stress by promoting 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 (PubMed:20348923). 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. This gene encodes the 85 kD regulatory subunit. 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. Alternative splicing of this gene results in four transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

Uniprot Accession IDs

• P27986
• B3KT19
• D3DWA0
• E7EX19
• Q15747
• Q4VBZ7
• Q53EM6
• Q8IXA2
• Q8N1C5
• PI3-kinase regulatory subunit alpha

Gene Name

• PIK3R1

Ensembl ID

• ENST00000320694
• ENSP00000323512
• ENSG00000145675
• ENST00000336483
• ENSP00000338554
• ENST00000521381
• ENSP00000428056
• ENST00000521657
• ENSP00000429277
• ENST00000523872
• ENSP00000430098

Symbol

• GRB1
• p85
• AGM7
• GRB1
• IMD36
• p85-ALPHA

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
interacting protein	1
transcription factor perturbation	1
kinase	0.99

Protein Classes

PANTHER Classes

Protein / Enzyme Modulator / Kinase Modulator / Phosphatidylinositol 3-kinase Regulatory Subunit Alpha

DTO Classes

Protein / Kinase / Non-protein Kinase / Lipid Kinase / Pi3k P85 Subunit Family / Phosphatidylinositol 3-kinase Regulatory Subunit Alpha

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 561.52   (req: < 5)

Gene RIFs: 178   (req: <= 3)

Antibodies: 994   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 561.52   (req: >= 5)

Gene RIFs: 178   (req: > 3)

Antibodies: 994   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 62

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 4

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (4)

Explore Active Ligands

1 – 4 of 4

US9321773, 4

PIK3R1Tchem Kinase

pIC50 : 7.92

US9321773, 5

PIK3R1Tchem Kinase

pIC50 : 7.8

3-(6,7-dimethoxyquinazolin-4-ylamino)phenol

PIK3R1Tchem Kinase

pIC50 : 8.7

US9321773, 86

PIK3R1Tchem Kinase

pIC50 : 7.66

Protein-Protein Interactions (676)

Explore Interacting Targets

1 – 10 of 676

• See Interactions on String-DB

PIK3R2

Tbio

Family:  Enzyme

Novelty:  0.00829659

p_int:  0.965590096

p_ni:  0.034409904

Score:  0.983

Data Source:  BioPlex,STRINGDB

FLRT1

Tdark

Novelty:  0.23047852

p_int:  0.959155169

p_ni:  0.040844831

Score:  0.55

Data Source:  BioPlex,STRINGDB

PCBP1

Tbio

Novelty:  0.00906713

p_int:  0.959080933

p_ni:  0.040919067

Score:  0.238

Data Source:  BioPlex,STRINGDB

TGFBR2

Tchem

Family:  Kinase

Novelty:  0.00085381

p_int:  0.944480495

p_ni:  0.055519505

Score:  0.676

Data Source:  BioPlex,STRINGDB

PIK3R3

Tbio

Family:  Enzyme

Novelty:  0.0136069

p_int:  0.94430652

p_ni:  0.05569348

Score:  0.982

Data Source:  BioPlex,STRINGDB

DEFA5

Tbio

Novelty:  0.00863727

p_int:  0.884561221

p_ni:  0.115438779

Data Source:  BioPlex

RNF19B

Tbio

Family:  Enzyme

Novelty:  0.20054824

p_int:  0.827620269

p_ni:  0.172379731

Data Source:  BioPlex

SNX32

Tdark

Novelty:  0.66136036

p_int:  0.827464286

p_ni:  0.172535714

Score:  0.161

Data Source:  BioPlex,STRINGDB

KIR2DL1

Tbio

Novelty:  0.00523657

p_int:  0.808972554

p_ni:  0.191027446

Score:  0.379

Data Source:  BioPlex,STRINGDB

NLGN3

Tbio

Family:  Enzyme

Novelty:  0.00819625

p_int:  0.799261238

p_ni:  0.200738762

Score:  0.512

Data Source:  BioPlex,STRINGDB

Nearest Tclin Targets (57)

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Upstream (42)

Downstream (15)

1 – 5 of 42

PDGFRA

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  16

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: EGFR tyrosine kinase inhibitor resistance

4: Focal adhesion

more:  12 more common pathways

IL2RG

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  5

1: PI3K-Akt signaling pathway

2: JAK-STAT signaling pathway

3: Human T-cell leukemia virus 1 infection

4: Measles

5: Pathways in cancer

IL2RA

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  5

1: PI3K-Akt signaling pathway

2: JAK-STAT signaling pathway

3: Human T-cell leukemia virus 1 infection

4: Measles

5: Pathways in cancer

MET

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  15

1: PI3K-Akt signaling pathway

2: Central carbon metabolism in cancer

3: Axon guidance

4: EGFR tyrosine kinase inhibitor resistance

more:  11 more common pathways

FLT4

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  6

1: PI3K-Akt signaling pathway

2: Focal adhesion

3: Breast cancer

4: Rap1 signaling pathway

more:  2 more common pathways

Pathways (376)

Reactome (114)

KEGG (92)

PathwayCommons (108)

WikiPathways (62)

Activated NTRK2 signals through PI3K (R-HSA-9028335)

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5

1 – 5 of 114

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activated NTRK2 signals through PI3K	7 targets	R-HSA-9028335
Reactome	Activated NTRK3 signals through PI3K	6 targets	R-HSA-9603381
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	92 targets	R-HSA-983695
Reactome	Axon guidance	533 targets	R-HSA-422475

Name	Explore in Pharos	Explore in Source
Activated NTRK2 signals through PI3K	7 targets	R-HSA-9028335
Activated NTRK3 signals through PI3K	6 targets	R-HSA-9603381
Adaptive Immune System	894 targets	R-HSA-1280218
Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	92 targets	R-HSA-983695
Axon guidance	533 targets	R-HSA-422475

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (72)

Functions (17)

Components (10)

Processes (45)

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1 – 10 of 17

GO Term	Evidence	Assigned by
ErbB-3 class receptor binding	Inferred from Direct Assay (IDA)	UniProtKB
insulin binding	Inferred from Direct Assay (IDA)	UniProtKB
insulin receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
insulin-like growth factor receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
neurotrophin TRKA receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
phosphotyrosine residue binding	Inferred from Physical Interaction (IPI)	CAFA
protein phosphatase binding	Inferred from Physical Interaction (IPI)	UniProtKB
transcription factor binding	Inferred from Physical Interaction (IPI)	UniProtKB
1-phosphatidylinositol-3-kinase regulator activity	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
phosphatidylinositol 3-kinase binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL

Disease Associations (null)

No disease associations found

GWAS Traits (12)

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5

1 – 5 of 12

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	3	3	4		92.1
mean corpuscular hemoglobin concentration	EFO_0004528	1	1	1		81.5
mean reticulocyte volume	EFO_0010701	1	1	1		77.1
lymphocyte count	EFO_0004587	2	2	2		73.2
body height	EFO_0004339	1	1	1		69.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 12

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	4		92.1
mean corpuscular hemoglobin concentration	EFO_0004528	1		81.5
mean reticulocyte volume	EFO_0010701	1		77.1
lymphocyte count	EFO_0004587	2		73.2
body height	EFO_0004339	1		69.2

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UniProt Keyword Find Similar Targets

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3D-structure
Acetylation
Alternative splicing
Complete proteome
Disease mutation
Dwarfism
Host-virus interaction
Phosphoprotein
Polymorphism
Protein transport

GWAS Trait Find Similar Targets

No Header	No Header
birth weight
BMI-adjusted waist circumference
body height
insomnia measurement
intelligence
lymphocyte count
mean corpuscular hemoglobin concentration
mean corpuscular volume
mean reticulocyte volume
red blood cell density measurement

MGI Phenotype Find Similar Targets

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adipose tissue phenotype
cardiovascular system phenotype
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
liver/biliary system phenotype

IDG Resources

No IDG generated resources found

Orthologs (11)

1 – 5 of 11

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Macaque	phosphoinositide-3-kinase regulatory subunit 1		698996
Mouse	phosphoinositide-3-kinase regulatory subunit 1	MGI:97583	18708
Rat	phosphoinositide-3-kinase regulatory subunit 1	RGD:3329	25513
Dog	phosphoinositide-3-kinase regulatory subunit 1	VGNC:44560	487235
Horse	phosphoinositide-3-kinase regulatory subunit 1	VGNC:21451	100050227

Species	Name	OMA	EggNOG	Inparanoid
Macaque	phosphoinositide-3-kinase regulatory subunit 1
Mouse	phosphoinositide-3-kinase regulatory subunit 1
Rat	phosphoinositide-3-kinase regulatory subunit 1
Dog	phosphoinositide-3-kinase regulatory subunit 1
Horse	phosphoinositide-3-kinase regulatory subunit 1

Publication Statistics

PubMed Score 561.52

PubMed score by year

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PubTator Score 415.38

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Related Publications

Text Mined References (506)

GeneRif Annotations (178)

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PMID	Year	Title