Tbio IRS1 Insulin receptor substrate 1

Protein Summary

Description

May mediate the control of various cellular processes by insulin. When phosphorylated by the insulin receptor binds specifically to various cellular proteins containing SH2 domains such as phosphatidylinositol 3-kinase p85 subunit or GRB2. Activates phosphatidylinositol 3-kinase when bound to the regulatory p85 subunit (By similarity). This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]

Uniprot Accession IDs

• P35568
• IRS-1

Gene Name

• IRS1

Ensembl ID

• ENST00000305123
• ENSP00000304895
• ENSG00000169047

Symbol

• HIRS-1

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological term	1
hub protein	1
kinase	1
biological process	0.99
gene perturbation	0.98

Related Tools

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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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: 1977.03   (req: < 5)

Gene RIFs: 304   (req: <= 3)

Antibodies: 2359   (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: 1977.03   (req: >= 5)

Gene RIFs: 304   (req: > 3)

Antibodies: 2359   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 32

Tchem

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

Active Ligand: 0

Tclin

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

Active Drug: 0

GWAS Traits (5)

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 5

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
sex hormone-binding globulin measurement	EFO_0004696	1	1	1		67.7
appendicular lean mass	EFO_0004980	2	1	2		66.3
heel bone mineral density	EFO_0009270	2	1	2		55.8
reticulocyte measurement	EFO_0010700	2	1	2		35.2
reticulocyte count	EFO_0007986	1	1	1		29

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 5

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
sex hormone-binding globulin measurement	EFO_0004696	1		67.7
appendicular lean mass	EFO_0004980	2		66.3
heel bone mineral density	EFO_0009270	2		55.8
reticulocyte measurement	EFO_0010700	2		35.2
reticulocyte count	EFO_0007986	1		29

Reset Zoom  Beta Count   Odds Ratio

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	insulin receptor substrate 1	VGNC:1981	459985
Macaque	insulin receptor substrate 1		707870
Mouse	insulin receptor substrate 1	MGI:99454	16367
Rat	insulin receptor substrate 1	RGD:2922	25467
Dog	insulin receptor substrate 1	VGNC:54317	486148

Species	Name	OMA	EggNOG	Inparanoid
Chimp	insulin receptor substrate 1
Macaque	insulin receptor substrate 1
Mouse	insulin receptor substrate 1
Rat	insulin receptor substrate 1
Dog	insulin receptor substrate 1

Protein Structure (5 Structures, 1 AlphaFold Model)

Representation

  axes   backbone   ball+stick   cartoon   rocket   rope   spacefill

Color Scheme

  target   atomindex   bfactor   chainname   electrostatic   element   hydrophobicity   resname   sstruc

Click on a row in the table to change the structure displayed.
More information can be found at RCSB PDB

AF-P35568-F1-model_v1

AlphaFold Structures Developed by DeepMind and EMBL-EBI

1 – 5 of 5

PDB Structure Id	Ligand	Method	Resolution (Å)	Residues	Fraction of Total Protein	Pub Year	Title

PDB Structure Id	Fraction of Total Protein	Resolution	Pub Year

Pathways (105)

Reactome (36)

KEGG (17)

PathwayCommons (28)

WikiPathways (24)

Activated NTRK3 signals through PI3K (R-HSA-9603381)

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Find Similar Targets

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5

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activated NTRK3 signals through PI3K	6 targets	R-HSA-9603381
Reactome	Constitutive Signaling by Aberrant PI3K in Cancer	75 targets	R-HSA-2219530
Reactome	Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Reactome	Disease	1105 targets	R-HSA-1643685
Reactome	Diseases of signal transduction	387 targets	R-HSA-5663202

Name	Explore in Pharos	Explore in Source
Activated NTRK3 signals through PI3K	6 targets	R-HSA-9603381
Constitutive Signaling by Aberrant PI3K in Cancer	75 targets	R-HSA-2219530
Cytokine Signaling in Immune system	922 targets	R-HSA-1280215
Disease	1105 targets	R-HSA-1643685
Diseases of signal transduction	387 targets	R-HSA-5663202

Gene Ontology Terms (39)

Functions (11)

Components (7)

Processes (21)

Find Similar Targets

Items per page:

10

1 – 10 of 11

GO Term	Evidence	Assigned by
SH3/SH2 adaptor activity	Inferred from Direct Assay (IDA)	BHF-UCL
insulin receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
insulin-like growth factor receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
phosphatidylinositol 3-kinase binding	Inferred from Physical Interaction (IPI)	UniProtKB
phosphotyrosine residue binding	Inferred from Physical Interaction (IPI)	CAFA
protein kinase C binding	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
SH2 domain binding	Inferred from Sequence or structural Similarity (ISS)	UniProtKB
transmembrane receptor protein tyrosine kinase adaptor activity	Inferred from Sequence or structural Similarity (ISS)	BHF-UCL
1-phosphatidylinositol-3-kinase activity	Traceable Author Statement (TAS)	Reactome
phosphatidylinositol-4,5-bisphosphate 3-kinase activity	Traceable Author Statement (TAS)	Reactome

Protein-Protein Interactions (363)

Explore Interacting Targets

1 – 10 of 363

• See Interactions on String-DB

INSR

Tclin

Family: Kinase

Novelty: 0.00230617

Score: 0.999

Data Source: Reactome,STRINGDB

PTPN11

Tchem

Family: Enzyme

Novelty: 0.00073124

Score: 0.999

Data Source: STRINGDB

IGF1R

Tclin

Family: Kinase

Novelty: 0.00034532

Score: 0.997

Data Source: Reactome,STRINGDB

INS

Tbio

Novelty: 0.00000499

Score: 0.997

Data Source: Reactome,STRINGDB

RPS6KB1

Tchem

Family: Kinase

Novelty: 0.00044681

Score: 0.996

Data Source: STRINGDB

PIK3R1

Tchem

Family: Kinase

Novelty: 0.00179772

Score: 0.992

Data Source: Reactome,STRINGDB

IGF1

Tbio

Novelty: 0.00003878

Score: 0.992

Data Source: Reactome,STRINGDB

SH2B2

Tbio

Novelty: 0.20893668

Score: 0.992

Data Source: STRINGDB

GRB2

Tchem

Novelty: 0.00091605

Score: 0.992

Data Source: Reactome,STRINGDB

MTOR

Tclin

Family: Kinase

Novelty: 0.00012333

Score: 0.99

Data Source: STRINGDB

Publication Statistics

PubMed Score  1977.03

PubMed score by year

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PubTator Score  1162.82

PubTator score by year

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Amino Acid Sequence

Residue Counts

Protein Sequence

Show Full Sequence

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UniProt Keyword Find Similar Targets

3D-structure
Complete proteome
Diabetes mellitus
Disease mutation
Phosphoprotein
Polymorphism
Reference proteome
Repeat
Transducer
Ubl conjugation

GWAS Trait Find Similar Targets

appendicular lean mass
heel bone mineral density
reticulocyte count
reticulocyte measurement
sex hormone-binding globulin measurement

MGI Phenotype Find Similar Targets

adipose tissue phenotype
cardiovascular system phenotype
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
limbs/digits/tail phenotype