PMADS

Id:	acc1391
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:	Hepatocellular Carcinoma
Disease Subtype:
Disease Cellline:	Bel7404
Disease Info:
Drug:	oxaliplatin (OXA)
Drug Info:	"Oxaliplatin (OXA) is a third-generation platinum-based chemotherapeutic agent primarily used in the treatment of colorectal, gastric, pancreatic, and other cancers, which inhibits DNA synthesis by inducing cross-linking damage, thereby blocking replication and transcription and triggering apoptosis."
Effect:	inhibit
Effect Info:	"Overexpression of sCLU significantly increases phosphorylated Akt, thereby activating the Akt pathway in hepatocellular carcinoma and leading to oxaliplatin resistance."
Note:
Score:	5.0
Pubmed(PMID):	23279642
Sentence Index:	23279642_4-5
Sentence:	"The stable transfectants that are depleted of or overexpress sCLU and OXA-resistant cells were generated using human HCC cells. Overexpression of sCLU abrogated OXA-induced inhibition of cell growth and cell apoptosis, but depletion of sCLU synergized with OXA to inhibit cell growth and enhance cell apoptosis, by regulating proteins involved in mitochondrial apoptosis pathways, such as Bcl-2, Bax, Bcl-xL and caspase-9, and affecting phosphorylation of Akt and GSK-3beta."

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