PMADS

Id:	acc1859
Group:	2sens_supp
Protein:	AKT
Gene Symbol:	AKT1
Protein Id:	P31749
Protein Name:	AKT1_HUMAN
PTM:	phosphorylation
Site:	Tyr308
Site Sequence:	GIKDGATMKTFCGTPEYLAPE
Disease Category:	Cancer
Disease:	Colorectal Cancer
Disease Subtype:
Disease Cellline:	LoVo
Disease Info:
Drug:	cetuximab
Drug Info:	"Cetuximab is a recombinant human-mouse chimeric monoclonal antibody that specifically binds to the epidermal growth factor receptor (EGFR), competitively inhibiting ligand binding and blocking downstream signaling pathways, thereby inhibiting cancer cell proliferation, inducing apoptosis, and reducing the production of matrix metalloproteinases and vascular endothelial growth factor; it is used in combination with irinotecan for EGFR-positive, irinotecan-resistant metastatic colorectal cancer, as a monotherapy for patients intolerant to irinotecan, and in combination with radiotherapy for locally advanced head and neck squamous cell carcinoma. "
Effect:	inhibit
Effect Info:	"Mithramycin inhibits SETDB1, leading to a decrease in AKT phosphorylation and rendering CRC sensitive to cetuximab, regardless of the KRAS mutation status."
Note:
Score:	5.0
Pubmed(PMID):	32473242
Sentence Index:	32473242_0-1
Sentence:	"Blocking histone methyltransferase SETDB1 inhibits tumorigenesis and enhances cetuximab sensitivity in colorectal cancer. The histone methyltransferase SETDB1 catalyzes the addition of methyl groups to histone H3 at lysine 9, and upregulation of SETDB1 is associated with poor prognosis in cancer patients. To examine the significance of SETDB1 in CRC response to cetuximab, we assessed the in vitro anti-proliferation effects of cetuximab using KRAS-mutated CRC cells and found that the IC50 values for cetuximab were significantly decreased upon mithramycin addition or SETDB1 knockdown (Fig. 4E and F). "

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
T	308	D	Ovarian cancer/carcinoma	Phosphorylation	20153512
T	308	D	Type 2 diabetes	Phosphorylation	15919790 ; 15919790
T	308	D	Head and neck squamous cell carcinoma	Phosphorylation	21281788
T	308	D	Diabetes mellitus	Phosphorylation	17272402 ; 20938636 ; 15919790
T	308	P	Non-small cell lung cancer/carcinoma	Phosphorylation	23091605
T	308	U	Chronic lymphocytic leukemia	Phosphorylation	16940331
T	308	U	Melanoma	Phosphorylation	19996208
T	308	U	Multiple myeloma	Phosphorylation	37781194
T	308	U	Neuroblastoma	Phosphorylation	17234785
T	308	U	Pancreatic cancer/carcinoma/adenocarcinoma	Phosphorylation	26676747
T	308	U	Rhabdomyosarcoma	Phosphorylation	17848913
T	308	U	Breast cancer	Phosphorylation	33571243
T	308	U	Acute myeloid leukemia/acute myelogenous leukemia	Phosphorylation	12750723
T	308	U	Cholangiocarcinoma	Phosphorylation	37752233
T	308	U	Lymphocytic leukemia	Phosphorylation	20576813
T	308	U	Obesity	Phosphorylation	35413055
T	308	U	Sjogren's syndrome	Phosphorylation	34948236
T	308	U	Endometrial cancer	Phosphorylation	35253622
T	308	U	Esophageal squamous cell carcinoma	Phosphorylation	36995521

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