PMADS

Id:	acc0197
Group:	1sens
Protein:	AKT
Gene Symbol:	AKT1
Protein Id:	P31749
Protein Name:	AKT1_HUMAN
PTM:	phosphorylation
Site:	unclear
Site Sequence:
Disease Category:	Cancer
Disease:	Ovarian Cancer
Disease Subtype:
Disease Cellline:	A2780
Disease Info:
Drug:	tamoxifen
Drug Info:	"Tamoxifen is a selective estrogen receptor modulator (SERM) used primarily for the treatment of estrogen receptor-positive breast cancer in women, including adjuvant therapy, advanced cases, and recurrent disease, by competitively inhibiting estrogen binding to its receptor and suppressing cancer cell proliferation."
Effect:	modulate
Effect Info:	"The autocrine of IL - 6 and IL - 8 in ovarian cancer cell lines is inversely proportional to the cells' response to TAM and directly proportional to phosphorylated MAPK, Akt, and ER."
Note:
Score:	4.0
Pubmed(PMID):	20056081
Sentence Index:	20056081_1
Sentence:	"AIM: To investigate the relationship of IL-6 and IL-8 secretion in four epithelial ovarian cancer cell lines (A2780, CAOV-3, SKOV-3 and ES-2) with their sensitivity to tamoxifen (TAM) as well as MAPK, Akt and estrogen receptor (ER) phosphorylation, and to explore the mechanism of endocrine therapy resistance caused by IL-6 and IL-8 in ovarian cancer cells."

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
-	-	D	Laryngeal cancer	Phosphorylation	23886414
-	-	D	Sepsis	Acetylation	37211747
-	-	D	Oral squamous cell carcinoma	Phosphorylation	23723304
-	-	D	Myelodysplasia	Phosphorylation	12529294
-	-	D	Glioma/adult gliomas	Phosphorylation	12839945
-	-	P	Cancer	SUMOylation	23884910
-	-	P	Acute monocytic leukemia	Phosphorylation	24422998
S	-	P	Colon cancer/carcinoma	Phosphorylation	24464560
-	-	P	Glioblastoma	Phosphorylation	23262078
-	-	P	Embryonal central nervous system tumor	Phosphorylation	16230398
-	-	P	Brain cancer	Phosphorylation	12388552
-	-	U	Endometrial cancer	Phosphorylation	12888921
-	-	U	Thyroid cancer	Phosphorylation	12788904
-	-	U	Cervical cancer/carcinoma	Phosphorylation	10853013
-	-	U	Prostate cancer/carcinoma/adenocarcinoma	Phosphorylation	10853013
-	-	U	Marek's disease	Phosphorylation	35795905
-	-	U	Prostate cancer/carcinoma/adenocarcinoma	Phosphorylation	23785446
-	-	U	Gastric cancer	Phosphorylation	23898095
-	-	U	Renal cell carcinoma	Phosphorylation	34257606
-	-	U	Hepatocellular carcinoma	Acetylation	31842909
-	-	U	Pancreatic cancer	Phosphorylation	31765735
-	-	U	Colorectal cancer	Phosphorylation	35110545
-	-	U	Gastric cancer	Phosphorylation	36604355
-	-	U	Urothelial bladder cancer	Phosphorylation	35691981
-	-	U	Epithelial ovarian cancer	Phosphorylation	35105347
-	-	U	Tongue cancer	Phosphorylation	37132640
-	-	U	Papillary thyroid cancer	Acetylation	37696385

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