Tchem RELA Transcription factor p65

Protein Summary

Description

NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The heterodimeric RELA-NFKB1 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. The NF-kappa-B heterodimeric RELA-NFKB1 and RELA-REL complexes, for instance, function as transcriptional activators. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF-kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. The inhibitory effect of I-kappa-B on NF-kappa-B through retention in the cytoplasm is exerted primarily through the interaction with RELA. RELA shows a weak DNA-binding site which could contribute directly to DNA binding in the NF-kappa-B complex. Beside its activity as a direct transcriptional activator, it is also able to modulate promoters accessibility to transcription factors and thereby indirectly regulate gene expression. Associates with chromatin at the NF-kappa-B promoter region via association with DDX1. Essential for cytokine gene expression in T-cells (PubMed:15790681). The NF-kappa-B homodimeric RELA-RELA complex appears to be involved in invasin-mediated activation of IL-8 expression. NF-kappa-B is a ubiquitous transcription factor involved in several biological processes. It is held in the cytoplasm in an inactive state by specific inhibitors. Upon degradation of the inhibitor, NF-kappa-B moves to the nucleus and activates transcription of specific genes. NF-kappa-B is composed of NFKB1 or NFKB2 bound to either REL, RELA, or RELB. The most abundant form of NF-kappa-B is NFKB1 complexed with the product of this gene, RELA. Four transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• Q04206
• Q6GTV1
• Q6SLK1

Gene Name

• RELA

Ensembl ID

• ENST00000308639
• ENSP00000311508
• ENSG00000173039
• ENST00000406246
• ENSP00000384273

Symbol

• NFKB3
• p65
• CMCU
• NFKB3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
biological term	1
chemical	1
hub protein	1
kinase	1

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Transcription Factor P65

Protein / ... / P53-like Transcription Factor / Transcription Factor P65

Protein / ... / Rel Homology Transcription Factor / Transcription Factor P65

DTO Classes

Protein / Transcription Factor / Immunoglobulin Fold Transcription Factor / Rel Homology Transcription Factor / Transcription Factor P65

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1509.21   (req: < 5)

Gene RIFs: 861   (req: <= 3)

Antibodies: 3431   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 1509.21   (req: >= 5)

Gene RIFs: 861   (req: > 3)

Antibodies: 3431   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 101

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 28

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 1

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (1)

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1 – 1 of 1

bortezomib

RELATchem TF

INHIBITOR pKi : 9.26

Active Ligands (28)

Explore Active Ligands

1 – 10 of 28

5Z-7-Oxozeaenol

RELATchem TF

pIC50 : 8.54

CHEMBL129857

RELATchem TF

pKi : 7.7

rocaglamide

RELATchem TF

pKd : 6.81

CHEMBL272552

RELATchem TF

pIC50 : 6.89

CHEMBL271669

RELATchem TF

pEC50 : 6.3

2-amino-N-(6-methoxyquinolin-8-yl)-4-methylbenzenesulfonamide

RELATchem TF

pIC50 : 6.23

Sphenostylisin A

RELATchem TF

pIC50 : 8.22

(+)-Ursolic acid

RELATchem TF

pIC50 : 7.51

US8980954, 4cc

RELATchem TF

pIC50 : 6.82

US8980954, 6p

RELATchem TF

pIC50 : 6.82

Protein-Protein Interactions (588)

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1 – 10 of 588

• See Interactions on String-DB

NFKBIA

Tchem

Novelty:  0.00022873

p_int:  0.999999997

p_ni:  3e-9

Score:  0.998

Data Source:  BioPlex,Reactome,STRINGDB

NFKBIB

Tbio

Novelty:  0.00517222

p_int:  0.999999997

p_ni:  3e-9

Score:  0.996

Data Source:  BioPlex,Reactome,STRINGDB

REL

Tbio

Family:  TF

Novelty:  0.00038265

p_int:  0.999999755

p_ni:  2.45e-7

p_wrong:  1e-9

Score:  0.988

Data Source:  BioPlex,STRINGDB

RELB

Tbio

Family:  TF

Novelty:  0.00216805

p_int:  0.999999545

p_ni:  4.55e-7

Score:  0.974

Data Source:  BioPlex,Reactome,STRINGDB

C2orf27A

Tdark

Novelty:  2.91059359

p_int:  0.999707622

p_ni:  0.000292375

p_wrong:  2e-9

Data Source:  BioPlex

FBXW11

Tbio

Novelty:  0.0715377

p_int:  0.99920131

p_ni:  0.00079869

Score:  0.916

Data Source:  BioPlex,Reactome,STRINGDB

BTRC

Tbio

Novelty:  0.00293475

p_int:  0.997572044

p_ni:  0.002427956

Score:  0.948

Data Source:  BioPlex,Reactome,STRINGDB

NUFIP2

Tbio

Novelty:  0.09366649

p_int:  0.948716992

p_ni:  0.051172321

p_wrong:  0.000110687

Score:  0.226

Data Source:  BioPlex,STRINGDB

LINC01587

Tdark

Novelty:  0.48128342

p_int:  0.940429022

p_ni:  0.059570971

p_wrong:  7e-9

Score:  0.181

Data Source:  BioPlex,STRINGDB

DAPP1

Tbio

Novelty:  0.05145215

p_int:  0.905464869

p_ni:  0.089771172

p_wrong:  0.004763959

Data Source:  BioPlex

Nearest Tclin Targets (13)

Explore Nearest Tclin Targets

Upstream (4)

Downstream (9)

1 – 4 of 4

RAF1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  28

1: PI3K-Akt signaling pathway

2: Chronic myeloid leukemia

3: Relaxin signaling pathway

4: T cell receptor signaling pathway

more:  24 more common pathways

ROCK2

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  8

1: Salmonella infection

2: Yersinia infection

3: Chemokine signaling pathway

4: cAMP signaling pathway

more:  4 more common pathways

ROCK1

Tclin

Family:  Kinase

KEGG Distance:  1

Common Pathways:  8

1: Salmonella infection

2: Yersinia infection

3: Chemokine signaling pathway

4: cAMP signaling pathway

more:  4 more common pathways

IL1R1

Tclin

Family:  Other

KEGG Distance:  1

Common Pathways:  8

1: Human T-cell leukemia virus 1 infection

2: Amoebiasis

3: Fluid shear stress and atherosclerosis

4: Th17 cell differentiation

more:  4 more common pathways

Pathways (239)

Reactome (70)

KEGG (66)

PathwayCommons (47)

WikiPathways (56)

Activation of NF-kappaB in B cells (R-HSA-1169091)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Activation of NF-kappaB in B cells	68 targets	R-HSA-1169091
Reactome	Adaptive Immune System	894 targets	R-HSA-1280218
Reactome	C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481
Reactome	CD209 (DC-SIGN) signaling	21 targets	R-HSA-5621575
Reactome	CLEC7A (Dectin-1) signaling	101 targets	R-HSA-5607764

Name	Explore in Pharos	Explore in Source
Activation of NF-kappaB in B cells	68 targets	R-HSA-1169091
Adaptive Immune System	894 targets	R-HSA-1280218
C-type lectin receptors (CLRs)	144 targets	R-HSA-5621481
CD209 (DC-SIGN) signaling	21 targets	R-HSA-5621575
CLEC7A (Dectin-1) signaling	101 targets	R-HSA-5607764

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (109)

Functions (29)

Components (8)

Processes (72)

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1 – 10 of 29

GO Term	Evidence	Assigned by
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
chromatin DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
distal enhancer DNA-binding transcription activator activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	NTNU_SB
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA-binding transcription factor activity	Inferred from Direct Assay (IDA)	UniProtKB
identical protein binding	Inferred from Direct Assay (IDA)	UniProtKB
phosphate ion binding	Inferred from Direct Assay (IDA)	UniProtKB
protein heterodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
protein homodimerization activity	Inferred from Direct Assay (IDA)	UniProtKB
proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific	Inferred from Direct Assay (IDA)	NTNU_SB

Disease Associations (null)

No disease associations found

GWAS Traits (46)

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1 – 5 of 46

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	4	4	5		97.8
glomerular filtration rate	EFO_0005208	4	5	5	9.3	95
heel bone mineral density	EFO_0009270	3	5	7		95
urate measurement	EFO_0004531	4	5	6		94.9
mean platelet volume	EFO_0004584	3	2	3		93.2

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 46

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
red blood cell distribution width	EFO_0005192	5		97.8
glomerular filtration rate	EFO_0005208	5	9.3	95
heel bone mineral density	EFO_0009270	7		95
urate measurement	EFO_0004531	6		94.9
mean platelet volume	EFO_0004584	3		93.2

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Activator
Alternative splicing
Chromosomal rearrangement
Complete proteome
Cytoplasm
DNA-binding
Host-virus interaction
Isopeptide bond

GWAS Trait Find Similar Targets

No Header	No Header
acne
age at onset
Agents acting on the renin-angiotensin system use measurement
albumin:globulin ratio measurement
alkaline phosphatase measurement
balding measurement
blood urea nitrogen measurement
BMI-adjusted hip circumference
BMI-adjusted waist circumference
BMI-adjusted waist-hip ratio

MGI Phenotype Find Similar Targets

No Header	No Header
cardiovascular system phenotype
cellular phenotype
digestive/alimentary phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype
limbs/digits/tail phenotype

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	RELA proto-oncogene, NF-kB subunit	VGNC:10283	466665
Macaque	RELA proto-oncogene, NF-kB subunit		715919
Mouse	v-rel reticuloendotheliosis viral oncogene homolog A (avian)	MGI:103290	19697
Rat	RELA proto-oncogene, NF-kB subunit	RGD:727889	309165
Dog	RELA proto-oncogene, NF-kB subunit	VGNC:45466	483729

Species	Name	OMA	EggNOG	Inparanoid
Chimp	RELA proto-oncogene, NF-kB subunit
Macaque	RELA proto-oncogene, NF-kB subunit
Mouse	v-rel reticuloendotheliosis viral oncogene homolog A (avian)
Rat	RELA proto-oncogene, NF-kB subunit
Dog	RELA proto-oncogene, NF-kB subunit

Publication Statistics

PubMed Score 1509.21

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PubTator Score 2856.78

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Related Publications

Text Mined References (1126)

GeneRif Annotations (861)

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PMID	Year	Title