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

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: 1604.89   (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: 1604.89   (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

Protein Data Bank (5)

1 – 5 of 5

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	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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Items per page:

5

1 – 5 of 36

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)

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: 0.0029743

Score: 0.999

Data Source: Reactome,STRINGDB

PTPN11

Tchem

Family: Enzyme

Novelty: 0.00086268

Score: 0.999

Data Source: STRINGDB

IGF1R

Tclin

Family: Kinase

Novelty: 0.00039695

Score: 0.997

Data Source: Reactome,STRINGDB

INS

Tbio

Novelty: 0.00000614

Score: 0.997

Data Source: Reactome,STRINGDB

RPS6KB1

Tchem

Family: Kinase

Novelty: 0.00059352

Score: 0.996

Data Source: STRINGDB

PIK3R1

Tchem

Family: Kinase

Novelty: 0.00286014

Score: 0.992

Data Source: Reactome,STRINGDB

IGF1

Tbio

Novelty: 0.00004544

Score: 0.992

Data Source: Reactome,STRINGDB

SH2B2

Tbio

Novelty: 0.326382

Score: 0.992

Data Source: STRINGDB

GRB2

Tchem

Novelty: 0.00060543

Score: 0.992

Data Source: Reactome,STRINGDB

MTOR

Tclin

Family: Kinase

Novelty: 0.00014431

Score: 0.99

Data Source: STRINGDB

Publication Statistics

PubMed Score  1604.89

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

Sequence

MASPPESDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCF

1-70

NINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKGHHDGAAALGAGGGGGSCSGSS

70-140

GLGEAGEDLSYGDVPPGPAFKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMN

140-210

IRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEFRPRSKSQSSSNCSNPI

210-280

SVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPS

280-350

TNRTHAHRHRGSARLHPPLNHSRSIPMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSP

350-420

SDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGPSTLTAPNGHYILSRGGN

420-490

GHRCTPGTGLGTSPALAGDEAASAADLDNRFRKRTHSAGTSPTITHQKTPSQSSVASIEEYTEMMPAYPP

490-560

GGGSGGRLPGHRHSAFVPTRSYPEEGLEMHPLERRGGHHRPDSSTLHTDDGYMPMSPGVAPVPSGRKGSG

560-630

DYMPMSPKSVSAPQQIINPIRRHPQRVDPNGYMMMSPSGGCSPDIGGGPSSSSSSSNAVPSGTSYGKLWT

630-700

NGVGGHHSHVLPHPKPPVESSGGKLLPCTGDYMNMSPVGDSNTSSPSDCYYGPEDPQHKPVLSYYSLPRS

700-770

FKHTQRPGEPEEGARHQHLRLSTSSGRLLYAATADDSSSSTSSDSLGGGYCGARLEPSLPHPHHQVLQPH

770-840

LPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRAREQQQQQQPLLHPPEPKSPGEYVNIEFGSDQSGYLS

840-910

GPVAFHSSPSVRCPSQLQPAPREEETGTEEYMKMDLGPGRRAAWQESTGVEMGRLGPAPPGAASICRPTR

910-980

AVPSSRGDYMTMQMSCPRQSYVDTSPAAPVSYADMRTGIAAEEVSLPRATMAAASSSSAASASPTGPQGA

980-1050

AELAAHSSLLGGPQGPGGMSAFTRVNLSPNRNQSAKVIRADPQGCRRRHSSETFSSTPSATRVGNTVPFG

1050-1120

AGAAVGGGGGSSSSSEDVKRHSSASFENVWLRPGELGGAPKEPAKLCGAAGGLENGLNYIDLDLVKDFKQ

1120-1190

CPQECTPEPQPPPPPPPHQPLGSGESSSTRRSSEDLSAYASISFQKQPEDRQ

1190-1242

MASPPESDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKGHHDGAAALGAGGGGGSCSGSSGLGEAGEDLSYGDVPPGPAFKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEFRPRSKSQSSSNCSNPISVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHRGSARLHPPLNHSRSIPMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGPSTLTAPNGHYILSRGGNGHRCTPGTGLGTSPALAGDEAASAADLDNRFRKRTHSAGTSPTITHQKTPSQSSVASIEEYTEMMPAYPPGGGSGGRLPGHRHSAFVPTRSYPEEGLEMHPLERRGGHHRPDSSTLHTDDGYMPMSPGVAPVPSGRKGSGDYMPMSPKSVSAPQQIINPIRRHPQRVDPNGYMMMSPSGGCSPDIGGGPSSSSSSSNAVPSGTSYGKLWTNGVGGHHSHVLPHPKPPVESSGGKLLPCTGDYMNMSPVGDSNTSSPSDCYYGPEDPQHKPVLSYYSLPRSFKHTQRPGEPEEGARHQHLRLSTSSGRLLYAATADDSSSSTSSDSLGGGYCGARLEPSLPHPHHQVLQPHLPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRAREQQQQQQPLLHPPEPKSPGEYVNIEFGSDQSGYLSGPVAFHSSPSVRCPSQLQPAPREEETGTEEYMKMDLGPGRRAAWQESTGVEMGRLGPAPPGAASICRPTRAVPSSRGDYMTMQMSCPRQSYVDTSPAAPVSYADMRTGIAAEEVSLPRATMAAASSSSAASASPTGPQGAAELAAHSSLLGGPQGPGGMSAFTRVNLSPNRNQSAKVIRADPQGCRRRHSSETFSSTPSATRVGNTVPFGAGAAVGGGGGSSSSSEDVKRHSSASFENVWLRPGELGGAPKEPAKLCGAAGGLENGLNYIDLDLVKDFKQCPQECTPEPQPPPPPPPHQPLGSGESSSTRRSSEDLSAYASISFQKQPEDRQ

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Uniprot Keyword

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