PMADS

Id:	acc1413
Group:	2sens
Protein:	BCL2
Gene Symbol:	BCL2
Protein Id:	P10415
Protein Name:	BCL2_HUMAN
PTM:	phosphorylation
Site:	Ser70
Site Sequence:	ASRDPVARTSPLQTPAAPGAA
Disease Category:	Cancer
Disease:	Lung Cancer
Disease Subtype:	SCLC
Disease Cellline:	NCI-H82
Disease Info:
Drug:	PD98059
Drug Info:	PD98059 is a selective and cell-permeable inhibitor of MAP kinase kinase (MEK) that blocks the activation of mitogen-activated protein (MAP) kinase by inhibiting MEK1 and MEK2 phosphorylation.
Effect:	modulate
Effect Info:	"Staurosporine and PD98059 block NNK-induced phosphorylation of Bcl2 and c-Myc, which is associated with reduced cell proliferation."
Note:
Score:	4.0
Pubmed(PMID):	15210690
Sentence Index:	15210690_4-5
Sentence:	"We report here that NNK simultaneously stimulates Bcl2 phosphorylation exclusively at Ser(70) and c-Myc at Thr(58) and Ser(62) through activation of both ERK1/2 and PKCalpha, which is required for NNK-induced survival and proliferation of human lung cancer cells. Treatment of cells with staurosporine or PD98059 blocks both Bcl2 and c-Myc phosphorylation and results in suppression of NNK-induced proliferation."

Sequence & Structure:

MAHAGRTGYDNREIVMKYIHYKLSQRGYEWDAGDVGAAPPGAAPAPGIFSSQPGHTPHPAASRDPVARTSPLQTPAAPGAAAGPALSPVPPVVHLTLRQAGDDFSRRYRRDFAEMSSQLHLTPFTARGRFATVVEELFRDGVNWGRIVAFFEFGGVMCVESVNREMSPLVDNIALWMTEYLNRHLHTWIQDNGGWDAFVELYGPSMRPLFDFSWLSLKTLLSLALVGACITLGAYLGHK

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	4	-	chronic lymphocytic leukemia	EMA DailyMed FDA
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	4	Not yet recruiting	chronic lymphocytic leukemia	ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	4	-	neoplasm	ATC
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Completed	chronic lymphocytic leukemia	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Not yet recruiting	chronic lymphocytic leukemia	ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Recruiting	chronic lymphocytic leukemia	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Active, not recruiting	chronic lymphocytic leukemia	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Active, not recruiting	acute myeloid leukemia	ClinicalTrials ClinicalTrials ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Completed	acute myeloid leukemia	ClinicalTrials ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Not yet recruiting	acute myeloid leukemia	ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Active, not recruiting	myelodysplastic syndrome	ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Recruiting	acute myeloid leukemia	ClinicalTrials ClinicalTrials ClinicalTrials ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Terminated	acute myeloid leukemia	ClinicalTrials ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Active, not recruiting	childhood acute myeloid leukemia	ClinicalTrials
BCL2	OBLIMERSEN SODIUM	Bcl-2 mRNA antisense inhibitor	3	Completed	cutaneous melanoma	ClinicalTrials
BCL2	OBLIMERSEN SODIUM	Bcl-2 mRNA antisense inhibitor	3	Completed	leukemia	ClinicalTrials
BCL2	OBATOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Withdrawn	small cell lung carcinoma	ClinicalTrials
BCL2	OBATOCLAX MESYLATE	Apoptosis regulator Bcl-2 inhibitor	3	Withdrawn	small cell lung carcinoma	ClinicalTrials
BCL2	OBLIMERSEN SODIUM	Bcl-2 mRNA antisense inhibitor	3	Completed	multiple myeloma	ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Active, not recruiting	multiple myeloma	ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Completed	multiple myeloma	ClinicalTrials
BCL2	NAVITOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Active, not recruiting	primary myelofibrosis	ClinicalTrials ClinicalTrials
BCL2	OBLIMERSEN SODIUM	Bcl-2 mRNA antisense inhibitor	3	Withdrawn	lymphoid leukemia	ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Completed	Mantle cell lymphoma	ClinicalTrials
BCL2	VENETOCLAX	Apoptosis regulator Bcl-2 inhibitor	3	Recruiting	cancer	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!

BCL2L11-Ser104
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

BCL2L11-Ser118
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

BCL2L11-Ser77
Cancer	Intensity
BRCA	-1.869
COAD
HGSC	1.655
ccRCC	0.169
GBM
HNSC	0.422
LUAD	0.134
LUSC	-0.138
non_ccRCC	0.29
PDAC
UCEC	-0.663

BCL2L11-Ser92
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	-0.707
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC

BCL2L11-Ser93
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	-0.707
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC

BCL2L11-Ser94
Cancer	Intensity
BRCA	-1.664
COAD
HGSC	1.002
ccRCC	-0.246
GBM
HNSC	-0.477
LUAD	0.629
LUSC	-0.105
non_ccRCC	1.47
PDAC
UCEC	-0.61

BCL2L12-Ser113
Cancer	Intensity
BRCA	-0.987
COAD
HGSC
ccRCC	-0.026
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	1.013

BCL2L12-Ser121
Cancer	Intensity
BRCA	-1.134
COAD
HGSC	1.006
ccRCC	0.652
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.524

BCL2L12-Ser194
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC	0.153
LUAD	0.915
LUSC	-1.068
non_ccRCC
PDAC
UCEC

BCL2L12-Ser195
Cancer	Intensity
BRCA	0.374
COAD
HGSC
ccRCC	-1.133
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.759

BCL2L12-Ser241
Cancer	Intensity
BRCA
COAD	-0.993
HGSC
ccRCC
GBM	1.084
HNSC	-0.554
LUAD	1.075
LUSC	-0.613
non_ccRCC
PDAC
UCEC

BCL2L12-Ser242
Cancer	Intensity
BRCA
COAD	-0.42
HGSC	-1.185
ccRCC	-0.19
GBM
HNSC	0.276
LUAD
LUSC
non_ccRCC
PDAC
UCEC	1.519

BCL2L12-Ser272
Cancer	Intensity
BRCA
COAD	-0.088
HGSC
ccRCC
GBM
HNSC	0.237
LUAD	-1.365
LUSC	-0.208
non_ccRCC
PDAC	1.424
UCEC

BCL2L12-Ser273
Cancer	Intensity
BRCA	0.524
COAD
HGSC	0.391
ccRCC	-1.495
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.58

BCL2L12-Thr117
Cancer	Intensity
BRCA	0.35
COAD
HGSC	-1.485
ccRCC	0.687
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	0.449

BCL2L13-Ser288
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

BCL2L13-Ser291
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

BCL2L13-Ser312
Cancer	Intensity
BRCA	-1.693
COAD
HGSC
ccRCC	0.081
GBM
HNSC	-0.729
LUAD
LUSC	-0.194
non_ccRCC	1.241
PDAC	0.345
UCEC	0.948

BCL2L13-Ser315
Cancer	Intensity
BRCA	-1.352
COAD
HGSC	1.857
ccRCC	-0.415
GBM
HNSC	-0.336
LUAD
LUSC	-0.57
non_ccRCC	1.042
PDAC	-0.121
UCEC	-0.106

BCL2L13-Ser327
Cancer	Intensity
BRCA
COAD
HGSC	0.707
ccRCC
GBM
HNSC	-0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

BCL2L13-Ser329
Cancer	Intensity
BRCA
COAD
HGSC	0.787
ccRCC	-0.543
GBM
HNSC	-1.095
LUAD
LUSC	-0.447
non_ccRCC
PDAC
UCEC	1.298

BCL2L13-Ser395
Cancer	Intensity
BRCA
COAD	0.707
HGSC	-0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

BCL2L13-Ser420
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	0.707
HNSC
LUAD	-0.707
LUSC
non_ccRCC
PDAC
UCEC

BCL2L13-Ser426
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	-0.707
HNSC
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC

BCL2L13-Ser434
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.729
GBM
HNSC	-0.126
LUAD
LUSC	-0.605
non_ccRCC	-0.275
PDAC	1.735
UCEC

BCL2L13-Ser444
Cancer	Intensity
BRCA	-2.092
COAD	0.9
HGSC	-0.546
ccRCC	-0.271
GBM
HNSC	-0.516
LUAD
LUSC	0.329
non_ccRCC	0.352
PDAC	1.271
UCEC	0.573

BCL2L13-Ser450
Cancer	Intensity
BRCA	-0.476
COAD	1.017
HGSC	-1.857
ccRCC	-0.033
GBM
HNSC	-0.184
LUAD
LUSC	-0.52
non_ccRCC	1.554
PDAC	0.723
UCEC	-0.225

BCL2L13-Ser453
Cancer	Intensity
BRCA
COAD	0.479
HGSC	-1.471
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC	0.735
PDAC
UCEC	0.256

BCL2L13-Ser468
Cancer	Intensity
BRCA
COAD	-0.707
HGSC	0.707
ccRCC
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

BCL2L13-Thr429
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM
HNSC	0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

BCL2L13-Thr431
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	-0.707
GBM
HNSC	0.707
LUAD
LUSC
non_ccRCC
PDAC
UCEC

BCL2L14-Ser135
Cancer	Intensity
BRCA	-0.901
COAD	0.578
HGSC
ccRCC
GBM
HNSC
LUAD
LUSC	-1.232
non_ccRCC
PDAC	0.522
UCEC	1.032

BCL2L14-Ser44
Cancer	Intensity
BRCA
COAD	0.973
HGSC
ccRCC
GBM
HNSC	-1.491
LUAD
LUSC	-0.305
non_ccRCC
PDAC	0.857
UCEC	-0.034

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	70	A	Cancer	Phosphorylation	32188705
S	70	U	Lung cancer/carcinoma	Phosphorylation	23514933
S	70	U	Prostate cancer	Phosphorylation	35013120

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