PMADS

Id:	acc1024
Group:	2sens
Protein:	AKT
Gene Symbol:	AKT1
Protein Id:	P31749
Protein Name:	AKT1_HUMAN
PTM:	phosphorylation
Site:	Ser473
Site Sequence:	ERRPHFPQFSYSASGTA----
Disease Category:	Cancer
Disease:	Lung Cancer
Disease Subtype:
Disease Cellline:	PC9
Disease Info:
Drug:	erlotinib
Drug Info:	"Erlotinib is a medication used in the treatment of certain types of lung cancer, particularly non-small cell lung cancer (NSCLC), and pancreatic cancer, often as a maintenance therapy or after chemotherapy failure."
Effect:	inhibit
Effect Info:	RNA interference of integrin beta1 can restore the sensitivity to erlotinib and reduce the activation of Src and Akt.
Note:
Score:	5.0
Pubmed(PMID):	23872583
Sentence Index:	23872583_7-8
Sentence:	"Akt phosphorylation and cell growth, with this inhibitory effect further augmented by erlotinib treatment. Increased expression of integrin beta1, alpha5, and/or alpha2 was also observed in refractory tumor samples from patients with lung cancer treated with erlotinib and/or gefitinib."

Sequence & Structure:

MSDVAIVKEGWLHKRGEYIKTWRPRYFLLKNDGTFIGYKERPQDVDQREAPLNNFSVAQCQLMKTERPRPNTFIIRCLQWTTVIERTFHVETPEEREEWTTAIQTVADGLKKQEEEEMDFRSGSPSDNSGAEEMEVSLAKPKHRVTMNEFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEVIVAKDEVAHTLTENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKNVVYRDLKLENLMLDKDGHIKITDFGLCKEGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPRTLGPEAKSLLSGLLKKDPKQRLGGGSEDAKEIMQHRFFAGIVWQHVYEKKLSPPFKPQVTSETDTRYFDEEFTAQMITITPPDQDDSMECVDSERRPHFPQFSYSASGTA

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Completed	metastatic prostate cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Active, not recruiting	breast neoplasm	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Completed	triple-negative breast cancer	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Recruiting	cancer	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Active, not recruiting	breast cancer	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Completed	breast cancer	ClinicalTrials
AKT1	IPATASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Terminated	breast cancer	ClinicalTrials
AKT1	AFURESERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Recruiting	breast cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Active, not recruiting	breast cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Recruiting	breast cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Recruiting	prostate cancer	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	3	Active, not recruiting	prostate cancer	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	hepatocellular carcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	head and neck squamous cell carcinoma	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Active, not recruiting	neoplasm of mature B-cells	ClinicalTrials
AKT1	UPROSERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Terminated	acute myeloid leukemia	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Active, not recruiting	adenocarcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	breast carcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Terminated	breast carcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	adenosquamous lung carcinoma	ClinicalTrials
AKT1	UPROSERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Completed	breast carcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	bronchoalveolar adenocarcinoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Completed	diffuse large B-cell lymphoma	ClinicalTrials
AKT1	MK-2206	Serine/threonine-protein kinase AKT inhibitor	2	Terminated	diffuse large B-cell lymphoma	ClinicalTrials
AKT1	CAPIVASERTIB	Serine/threonine-protein kinase AKT inhibitor	2	Terminated	gastric adenocarcinoma	ClinicalTrials

Note: Only show clinically investigational or approved drugs with protein targets.

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!

AKT1-Ser124
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

AKT1-Ser126
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

AKT1-Ser129
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

AKT1-Thr448
Cancer	Intensity
BRCA
COAD
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.707

AKT1-Thr450
Cancer	Intensity
BRCA
COAD	-0.936
HGSC	-1.526
ccRCC	0.252
GBM	0.594
HNSC
LUAD	0.617
LUSC
non_ccRCC
PDAC
UCEC	0.999

AKT1-Tyr315
Cancer	Intensity
BRCA	0.788
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	-1.125
LUSC	0.336
non_ccRCC
PDAC
UCEC

AKT1S1-Ser183
Cancer	Intensity
BRCA	1.667
COAD	0.891
HGSC	0.725
ccRCC	-1.189
GBM	0.792
HNSC	0.064
LUAD	-0.194
LUSC	-0.266
non_ccRCC	-1.722
PDAC	-0.879
UCEC	0.11

AKT1S1-Ser202
Cancer	Intensity
BRCA	-0.344
COAD	-0.013
HGSC	-2.725
ccRCC	-0.093
GBM	-0.249
HNSC	0.707
LUAD	0.324
LUSC	0.615
non_ccRCC	0.322
PDAC	0.379
UCEC	1.076

AKT1S1-Ser203
Cancer	Intensity
BRCA	-0.189
COAD	0.095
HGSC	-2.902
ccRCC	0.277
GBM	0.142
HNSC	0.479
LUAD	0.265
LUSC	0.603
non_ccRCC	0.04
PDAC	0.419
UCEC	0.771

AKT1S1-Ser211
Cancer	Intensity
BRCA	-1.13
COAD	0.333
HGSC	-2.178
ccRCC	0.627
GBM	0.09
HNSC	1.177
LUAD	-0.47
LUSC	0.383
non_ccRCC
PDAC	0.715
UCEC	0.451

AKT1S1-Ser212
Cancer	Intensity
BRCA	-1.05
COAD	0.546
HGSC	-2.08
ccRCC	-0.197
GBM	0.641
HNSC	1.003
LUAD	-0.628
LUSC	0.311
non_ccRCC
PDAC	0.36
UCEC	1.094

AKT1S1-Ser247
Cancer	Intensity
BRCA
COAD	-1.124
HGSC
ccRCC
GBM	0.791
HNSC	0.334
LUAD
LUSC
non_ccRCC
PDAC
UCEC

AKT1S1-Ser88
Cancer	Intensity
BRCA	-1.265
COAD	-0.583
HGSC
ccRCC	-0.267
GBM	0.344
HNSC	2.36
LUAD	-0.052
LUSC	0.649
non_ccRCC	-0.088
PDAC	-0.187
UCEC	-0.912

AKT1S1-Ser92
Cancer	Intensity
BRCA	-1.122
COAD	-0.689
HGSC
ccRCC	0.068
GBM	-0.037
HNSC	2.235
LUAD	0.28
LUSC	0.221
non_ccRCC	-0.997
PDAC	0.777
UCEC	-0.735

AKT1S1-Thr198
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.647
GBM
HNSC
LUAD	-0.505
LUSC
non_ccRCC
PDAC
UCEC	1.152

AKT1S1-Thr246
Cancer	Intensity
BRCA
COAD	-0.468
HGSC	0.953
ccRCC
GBM	-1.179
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.694

AKT1S1-Thr90
Cancer	Intensity
BRCA
COAD	0.347
HGSC	-1.784
ccRCC	0.431
GBM
HNSC	0.542
LUAD	0.465
LUSC
non_ccRCC
PDAC
UCEC

AKT1S1-Thr97
Cancer	Intensity
BRCA	1.061
COAD	-1.872
HGSC
ccRCC	0.814
GBM	-0.592
HNSC	0.541
LUAD	0.201
LUSC
non_ccRCC
PDAC
UCEC	-0.152

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	473	D	Oral squamous cell carcinoma	Phosphorylation	31889370
S	473	D	Triple-negative breast cancer	Phosphorylation	34077419
S	473	D	Bladder cancer	Phosphorylation	23799035
S	473	D	Pancreatic cancer	Phosphorylation	28363942 ; 15467756
S	473	D	Colon cancer	Phosphorylation	35190555
S	473	D	Head and neck squamous cell carcinoma	Phosphorylation	21281788
S	473	P	Acute myeloid leukemia/acute myelogenous leukemia	Phosphorylation	18056483
S	473	P	Gastric cancer	Phosphorylation	23969493 ; 23440515
S	473	P	Ovarian cancer/carcinoma	Phosphorylation	23877012
S	473	P	Breast cancer	Phosphorylation	36632451
S	473	P	Anaplastic astrocytoma	Phosphorylation	23596468
S	473	P	Esophageal squamous cell carcinoma	Phosphorylation	23510069
S	473	P	Non-small cell lung cancer/carcinoma	Phosphorylation	23091605
S	473	P	Prostate cancer/carcinoma/adenocarcinoma	Phosphorylation	23732709
S	473	U	Pancreatic cancer	Phosphorylation	15467756 ; 28363942
S	473	U	Uveal melanoma	Phosphorylation	34918581
S	473	U	Osteosarcoma	Phosphorylation	34476004
S	473	U	Cancer	Phosphorylation	34767444
S	473	U	Cervical cancer	Phosphorylation	32047568
S	473	U	Acute myeloid leukemia/acute myelogenous leukemia	Phosphorylation	15289327
S	473	U	Breast cancer	Phosphorylation	17545609 ; 12244301 ; 12244301 ; 17545609 ; 21743495 ; 30413706
S	473	U	Chronic lymphocytic leukemia	Phosphorylation	16940331
S	473	U	Esophageal squamous cell carcinoma	Phosphorylation	31897228
S	473	U	Gallbladder cancer	Phosphorylation	33407730
S	473	U	Hepatocellular carcinoma	Phosphorylation	37573318 ; 36348350
S	473	U	Multiple myeloma	Phosphorylation	37781194
S	473	U	Pancreatic cancer/carcinoma/adenocarcinoma	Phosphorylation	15467756 ; 21474066 ; 28363942
S	473	U	Rhabdomyosarcoma	Phosphorylation	17848913
S	473	U	Synovial sarcoma	Phosphorylation	35556229
S	473	U	HER2-positive breast cancer	Phosphorylation	36314765
S	473	U	Thymic carcinoma	Phosphorylation	20597130
S	473	U	Systemic lupus erythematosus	Phosphorylation	23735868 ; 34522717 ; 23735868
S	473	U	Squamous cell carcinoma	Phosphorylation	21795477 ; 37109043
S	473	U	Sjogren's syndrome	Phosphorylation	34948236
S	473	U	Breast cancer/tumor/carcinoma	Phosphorylation	17545609 ; 12244301 ; 22476852
S	473	U	Cancer	Phosphorylation	21795477
S	473	U	Cholangiocarcinoma	Phosphorylation	37752233
S	473	U	Colon cancer/carcinoma	Phosphorylation	22975685
S	473	U	Colorectal cancer	Phosphorylation	37430297
S	473	U	Diabetes mellitus	Phosphorylation	35835217
S	473	U	Glioma	Phosphorylation	33820494
S	473	U	Renal cancer/carcinoma	Phosphorylation	19118035 ; 16247451 ; 12649200
S	473	U	Kidney cancer	Phosphorylation	12649200 ; 12649200 ; 22580611
S	473	U	Liver cancer	Phosphorylation	15684384
S	473	U	Lymphocytic leukemia	Phosphorylation	20576813
S	473	U	Melanoma	Phosphorylation	19996208 ; 12499277 ; 12499277 ; 19996208 ; 12499277
S	473	U	Neuroblastoma	Phosphorylation	17234785
S	473	U	Non-small cell squamous cell lung carcinoma	Phosphorylation	20008839
S	473	U	Obesity	Phosphorylation	35413055
S	473	U	Ovarian cancer	Phosphorylation	15208673
S	473	U	Ovarian epithelial carcinoma	Phosphorylation	32194423
S	473	U	Urethral cancer	Phosphorylation	22975685
S	473	U	Parkinson's disease	Phosphorylation	19800394 ; 19800394 ; 21658387

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