PMADS

Id:	acc2255
Group:	2sens
Protein:	RelA
Gene Symbol:	RELA
Protein Id:	Q04206
Protein Name:	TF65_HUMAN
PTM:	phosphorylation
Site:	Ser468
Site Sequence:	DPAVFTDLASVDNSEFQQLLN
Disease Category:	Cancer
Disease:	Colorectal Cancer
Disease Subtype:
Disease Cellline:	HCT116?
Disease Info:
Drug:	RITA
Drug Info:	"RITA (NSC 652287): A small molecule p53 activator that induces DNA-protein and DNA-DNA cross-links, inhibits MDM2-p53 interaction, and is used in experimental cancer therapy, such as glioblastoma research. Temozolomide (TMZ): A chemotherapeutic alkylating agent used primarily in the treatment of glioblastoma multiforme and other malignant gliomas."
Effect:	resist
Effect Info:	"In the naive MCF7 and HCT116 cells where RITA induces a large amount of cell apoptosis, the phosphorylation of RelA/p65 at Ser536 increases, but the phosphorylation at Ser276 and Ser468 decreases."
Note:
Score:	5.0
Pubmed(PMID):	27721021
Sentence Index:	27721021_4-5
Sentence:	"This study found that the site-differential phosphorylation of nuclear factor-kappaB (NF-kappaB) RelA/p65 creates a barcode for RITA chemosensitivity in cancer cells. In naive MCF7 and HCT116 cells where RITA triggered vast apoptosis, phosphorylation of RelA/p65 increased at Ser536, but decreased at Ser276 and Ser468; oppositely, in RITA-resistant cells, RelA/p65 phosphorylation decreased at Ser536, but increased at Ser276 and Ser468."

Sequence & Structure:

MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQISS

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

Target	Drug name	MOA	Phase	Status	Disease	Source
RELA	EDASALONEXENT	Nuclear factor NF-kappa-B complex inhibitor	3	Terminated	Duchenne muscular dystrophy	ClinicalTrials
RELA	EDASALONEXENT	Nuclear factor NF-kappa-B complex inhibitor	3	Completed	Duchenne muscular dystrophy	ClinicalTrials
RELA	EDASALONEXENT	Nuclear factor NF-kappa-B complex inhibitor	1	Completed	type 2 diabetes mellitus	ClinicalTrials
RELA	EDASALONEXENT	Nuclear factor NF-kappa-B complex inhibitor	1	Completed	Duchenne muscular dystrophy	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!

RELA-Ser112
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.367
GBM
HNSC
LUAD
LUSC	0.765
non_ccRCC
PDAC
UCEC	-1.132

RELA-Ser177
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.675
GBM	-0.474
HNSC
LUAD	-0.6
LUSC	-0.083
non_ccRCC	1.626
PDAC
UCEC	-1.143

RELA-Ser200
Cancer	Intensity
BRCA
COAD	0.131
HGSC	-2.56
ccRCC	0.526
GBM	0.516
HNSC	0.416
LUAD
LUSC	0.737
non_ccRCC	-0.008
PDAC	0.386
UCEC	-0.143

RELA-Ser202
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM	1.142
HNSC	-0.719
LUAD	-0.423
LUSC
non_ccRCC
PDAC
UCEC

RELA-Ser235
Cancer	Intensity
BRCA	-0.452
COAD	-0.397
HGSC	2.387
ccRCC	-0.206
GBM	-0.643
HNSC	0.08
LUAD	-0.689
LUSC	0.666
non_ccRCC
PDAC
UCEC	-0.747

RELA-Ser42
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.381
GBM	-1.76
HNSC	0.615
LUAD	0.173
LUSC
non_ccRCC
PDAC
UCEC	0.591

RELA-Ser45
Cancer	Intensity
BRCA
COAD
HGSC	-0.868
ccRCC	-0.94
GBM
HNSC	1.524
LUAD
LUSC
non_ccRCC
PDAC	0.148
UCEC	0.137

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	468	U	Colon cancer	Phosphorylation	30980866

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