PMADS

Id:	acc3674
Group:	1sens
Protein:	IRS1
Gene Symbol:	IRS1
Protein Id:	P35568
Protein Name:	IRS1_HUMAN
PTM:	phosphorylation
Site:	Tyr612
Site Sequence:	SSTLHTDDGYMPMSPGVAPVP
Disease Category:	Endocrine and metabolic diseases
Disease:	Diabetes Mellitus
Disease Subtype:	type 2 diabetes
Disease Cellline:
Disease Info:
Drug:	Weight loss
Drug Info:	This drug is used for weight loss. It helps people reduce their body weight.
Effect:	modulate
Effect Info:	Weight loss in obese subjects normalizes PKCλ/ζ activation and increases IRS-1 phosphorylation and PI3K activity.
Note:	Non-conventional drugs
Score:	3.0
Pubmed(PMID):	12882908
Sentence Index:	12882908_9
Sentence:	Insulin-stimulated insulin receptor substrate (IRS)-1 tyrosine phosphorylation and PI3K activity are impaired 40-50% in diabetic subjects compared with lean or obese subjects.

Sequence & Structure:

MASPPESDGFSDVRKVGYLRKPKSMHKRFFVLRAASEAGGPARLEYYENEKKWRHKSSAPKRSIPLESCFNINKRADSKNKHLVALYTRDEHFAIAADSEAEQDSWYQALLQLHNRAKGHHDGAAALGAGGGGGSCSGSSGLGEAGEDLSYGDVPPGPAFKEVWQVILKPKGLGQTKNLIGIYRLCLTSKTISFVKLNSEAAAVVLQLMNIRRCGHSENFFFIEVGRSAVTGPGEFWMQVDDSVVAQNMHETILEAMRAMSDEFRPRSKSQSSSNCSNPISVPLRRHHLNNPPPSQVGLTRRSRTESITATSPASMVGGKPGSFRVRASSDGEGTMSRPASVDGSPVSPSTNRTHAHRHRGSARLHPPLNHSRSIPMPASRCSPSATSPVSLSSSSTSGHGSTSDCLFPRRSSASVSGSPSDGGFISSDEYGSSPCDFRSSFRSVTPDSLGHTPPARGEEELSNYICMGGKGPSTLTAPNGHYILSRGGNGHRCTPGTGLGTSPALAGDEAASAADLDNRFRKRTHSAGTSPTITHQKTPSQSSVASIEEYTEMMPAYPPGGGSGGRLPGHRHSAFVPTRSYPEEGLEMHPLERRGGHHRPDSSTLHTDDGYMPMSPGVAPVPSGRKGSGDYMPMSPKSVSAPQQIINPIRRHPQRVDPNGYMMMSPSGGCSPDIGGGPSSSSSSSNAVPSGTSYGKLWTNGVGGHHSHVLPHPKPPVESSGGKLLPCTGDYMNMSPVGDSNTSSPSDCYYGPEDPQHKPVLSYYSLPRSFKHTQRPGEPEEGARHQHLRLSTSSGRLLYAATADDSSSSTSSDSLGGGYCGARLEPSLPHPHHQVLQPHLPRKVDTAAQTNSRLARPTRLSLGDPKASTLPRAREQQQQQQPLLHPPEPKSPGEYVNIEFGSDQSGYLSGPVAFHSSPSVRCPSQLQPAPREEETGTEEYMKMDLGPGRRAAWQESTGVEMGRLGPAPPGAASICRPTRAVPSSRGDYMTMQMSCPRQSYVDTSPAAPVSYADMRTGIAAEEVSLPRATMAAASSSSAASASPTGPQGAAELAAHSSLLGGPQGPGGMSAFTRVNLSPNRNQSAKVIRADPQGCRRRHSSETFSSTPSATRVGNTVPFGAGAAVGGGGGSSSSSEDVKRHSSASFENVWLRPGELGGAPKEPAKLCGAAGGLENGLNYIDLDLVKDFKQCPQECTPEPQPPPPPPPHQPLGSGESSSTRRSSEDLSAYASISFQKQPEDRQ

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

No data.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

IRS1-Ser1078
Cancer	Intensity
BRCA	0.802
COAD	-0.081
HGSC
ccRCC	1.069
GBM
HNSC	-0.588
LUAD	-0.718
LUSC	-1.527
non_ccRCC	-0.92
PDAC	0.633
UCEC	1.329

IRS1-Ser1100
Cancer	Intensity
BRCA	-1.198
COAD	0.679
HGSC	-1.036
ccRCC
GBM
HNSC	1.268
LUAD	0.556
LUSC	1.082
non_ccRCC
PDAC	-0.795
UCEC	-0.556

IRS1-Ser1101
Cancer	Intensity
BRCA	-1.279
COAD	0.625
HGSC	1.291
ccRCC
GBM
HNSC	0.786
LUAD	0.106
LUSC	0.608
non_ccRCC
PDAC	-1.182
UCEC	-0.955

IRS1-Ser1109
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser1135
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser1142
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	-0.707
non_ccRCC
PDAC	0.707
UCEC

IRS1-Ser270
Cancer	Intensity
BRCA	1.766
COAD	-0.143
HGSC	1.365
ccRCC	-0.451
GBM	-0.761
HNSC	-0.219
LUAD	0.149
LUSC	0.407
non_ccRCC	0.42
PDAC	-1.81
UCEC	-0.724

IRS1-Ser272
Cancer	Intensity
BRCA
COAD	-1.052
HGSC	0.938
ccRCC
GBM
HNSC
LUAD	0.114
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser273
Cancer	Intensity
BRCA
COAD
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser277
Cancer	Intensity
BRCA	-0.707
COAD
HGSC
ccRCC
GBM
HNSC	0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser307
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	1.155
LUAD	-0.57
LUSC
non_ccRCC
PDAC
UCEC	-0.585

IRS1-Ser315
Cancer	Intensity
BRCA
COAD	0.703
HGSC	1.578
ccRCC	-0.025
GBM
HNSC	-1.037
LUAD	-0.298
LUSC
non_ccRCC
PDAC
UCEC	-0.922

IRS1-Ser323
Cancer	Intensity
BRCA	-1.325
COAD	-0.062
HGSC	1.91
ccRCC	-0.063
GBM	-0.274
HNSC	-0.33
LUAD	-0.103
LUSC	0.454
non_ccRCC	1.383
PDAC	-0.084
UCEC	-1.506

IRS1-Ser330
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser337
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser341
Cancer	Intensity
BRCA	-0.79
COAD	-0.134
HGSC	1.37
ccRCC
GBM
HNSC	0.694
LUAD	0.729
LUSC	-0.335
non_ccRCC
PDAC
UCEC	-1.535

IRS1-Ser345
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

IRS1-Ser348
Cancer	Intensity
BRCA
COAD	0.8
HGSC	-1.121
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.321

IRS1-Ser350
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser374
Cancer	Intensity
BRCA
COAD	0.565
HGSC	1.187
ccRCC	-0.149
GBM	-0.371
HNSC	-1.268
LUAD	-0.049
LUSC
non_ccRCC
PDAC	1.365
UCEC	-1.279

IRS1-Ser415
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC	-0.707

IRS1-Ser419
Cancer	Intensity
BRCA
COAD
HGSC	-1.115
ccRCC
GBM
HNSC
LUAD	0.818
LUSC
non_ccRCC
PDAC
UCEC	0.296

IRS1-Ser421
Cancer	Intensity
BRCA
COAD	0.524
HGSC	-1.494
ccRCC
GBM
HNSC
LUAD	0.589
LUSC
non_ccRCC
PDAC
UCEC	0.382

IRS1-Ser444
Cancer	Intensity
BRCA
COAD
HGSC	-0.707
ccRCC
GBM	0.707
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser449
Cancer	Intensity
BRCA
COAD
HGSC	1.255
ccRCC
GBM
HNSC	-0.142
LUAD	0.07
LUSC
non_ccRCC
PDAC
UCEC	-1.183

IRS1-Ser463
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.707
HNSC	0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Ser527
Cancer	Intensity
BRCA	-0.349
COAD	0.195
HGSC	1.597
ccRCC	-0.896
GBM	-0.176
HNSC	-1.431
LUAD	-0.424
LUSC	1.766
non_ccRCC
PDAC	0.043
UCEC	-0.324

IRS1-Ser531
Cancer	Intensity
BRCA	-2.281
COAD	0.378
HGSC	1.07
ccRCC	-0.307
GBM	0.901
HNSC	-0.537
LUAD	0.451
LUSC	-0.647
non_ccRCC
PDAC	0.154
UCEC	0.819

IRS1-Ser574
Cancer	Intensity
BRCA
COAD
HGSC	1.312
ccRCC
GBM
HNSC	-1.122
LUAD	-0.06
LUSC
non_ccRCC
PDAC
UCEC	-0.13

IRS1-Ser629
Cancer	Intensity
BRCA
COAD	-0.049
HGSC	1.819
ccRCC	-0.257
GBM	-0.559
HNSC	-0.813
LUAD	-0.141
LUSC	-0.142
non_ccRCC	1.506
PDAC	0.158
UCEC	-1.522

IRS1-Ser636
Cancer	Intensity
BRCA	0.864
COAD	-0.478
HGSC	-1.149
ccRCC
GBM	1.248
HNSC
LUAD
LUSC	0.421
non_ccRCC	0.982
PDAC	-1.278
UCEC	-0.61

IRS1-Ser862
Cancer	Intensity
BRCA	1.113
COAD	-0.289
HGSC
ccRCC
GBM
HNSC	-0.824
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Thr446
Cancer	Intensity
BRCA
COAD
HGSC	1.105
ccRCC
GBM	-0.921
HNSC	0.584
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.768

IRS1-Thr453
Cancer	Intensity
BRCA
COAD	0.424
HGSC	-0.776
ccRCC
GBM	1.145
HNSC	-1.021
LUAD	-1.197
LUSC	1.167
non_ccRCC
PDAC
UCEC	0.258

IRS1-Thr525
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.92
GBM	1.423
HNSC	-0.223
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.28

IRS1-Thr530
Cancer	Intensity
BRCA	-1.934
COAD	0.689
HGSC	1.779
ccRCC	0.009
GBM
HNSC	-0.527
LUAD	0.268
LUSC	-0.232
non_ccRCC
PDAC	0.301
UCEC	-0.353

IRS1-Thr533
Cancer	Intensity
BRCA	0.707
COAD	-0.707
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

IRS1-Tyr632
Cancer	Intensity
BRCA	-0.573
COAD	0.295
HGSC	1.706
ccRCC	0.013
GBM	-0.016
HNSC	-0.073
LUAD	0.15
LUSC	0.575
non_ccRCC
PDAC
UCEC	-2.077

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	616	D	Non-small cell lung cancer/carcinoma	Phosphorylation	18687633
-	-	D	Polycystic ovary syndrome	Phosphorylation	15130378
-	-	D	Primitive neuroectodermal tumor	Phosphorylation	8746448
S	307	P	Lung cancer/carcinoma	Phosphorylation	22348039
S	616	U	Head and neck squamous cell carcinoma	Phosphorylation	21281788
S	636	U	Diabetes mellitus	Phosphorylation	12765939
S	636	U	Pancreatic ductal adenocarcinoma	Phosphorylation	27014871
-	-	U	Ductal carcinoma in situ	Phosphorylation	23562473
-	-	U	Hepatocellular carcinoma/hepatocarcinoma/hepatoma	Phosphorylation	7542850
S	1101	U	Diabetes mellitus	Phosphorylation	17709744

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb