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Center for Computational Systems Medicine
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Protein Summary

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AS Summary

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Protein Functional Features

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Gene Isoform Structures and Expression Levels

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Protein Structures

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pLDDT Score Distribution

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Ramachandran Plot of Protein Structures

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Potential Active Site Information

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Protein Structure and Feature Comparision

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Protein-Protein Interaction

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Related Drugs

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Related Diseases

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Clinically Important Variants

Protein:RELA

Protein Summary

check button Gene summary
Gene name: RELA
ASpdb.0 ID: 5970
Gene
Gene symbol

RELA

Gene ID

5970

Gene nameRELA proto-oncogene, NF-kB subunit
SynonymsAIF3BL3|CMCU|NFKB3|p65
Cytomap

11q13.1

Type of geneprotein-coding
Descriptiontranscription factor p65NF-kappa-B p65delta3NF-kappa-B transcription factor p65nuclear factor NF-kappa-B p65 subunitnuclear factor of kappa light polypeptide gene enhancer in B-cells 3v-rel avian reticuloendotheliosis viral oncogene homolog A
Modification date20240416
UniProtAcc

Q04206


check button Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez
PartnerGeneGO IDGO termPubMed ID
GeneRELA

GO:0000122

negative regulation of transcription by RNA polymerase II

17350185

GeneRELA

GO:0000785

chromatin

1406630|8413223|21343296|26268439

GeneRELA

GO:0000976

transcription cis-regulatory region binding

17350185

GeneRELA

GO:0000977

RNA polymerase II transcription regulatory region sequence-specific DNA binding

7959007|24955228|25411248

GeneRELA

GO:0000978

RNA polymerase II cis-regulatory region sequence-specific DNA binding

1406630|17350185|23729669|23811396|23878390

GeneRELA

GO:0000979

RNA polymerase II core promoter sequence-specific DNA binding

21343296

GeneRELA

GO:0000981

DNA-binding transcription factor activity, RNA polymerase II-specific

3091258|21343177|23878390

GeneRELA

GO:0001227

DNA-binding transcription repressor activity, RNA polymerase II-specific

17350185

GeneRELA

GO:0001228

DNA-binding transcription activator activity, RNA polymerase II-specific

1406630|17350185|23811396|26435691

GeneRELA

GO:0002357

defense response to tumor cell

28362429

GeneRELA

GO:0003677

DNA binding

15790681|18073330|23091055

GeneRELA

GO:0003682

chromatin binding

19058135

GeneRELA

GO:0003700

DNA-binding transcription factor activity

8413223|12048232|19103749

GeneRELA

GO:0005634

nucleus

1493333

GeneRELA

GO:0005634

nucleus

3140380|15790681|17350185|18045535|18212740|19058135|21097510|21343177|21343296|21474709|21830064|22065573|25411248

GeneRELA

GO:0005667

transcription regulator complex

12048232

GeneRELA

GO:0005730

nucleolus

21343177

GeneRELA

GO:0005737

cytoplasm

3140380|15790681|21097510|21343177|21830064|25411248|27736973

GeneRELA

GO:0005829

cytosol

21474709|25327529

GeneRELA

GO:0006357

regulation of transcription by RNA polymerase II

1406630

GeneRELA

GO:0006954

inflammatory response

12924514

GeneRELA

GO:0007249

canonical NF-kappaB signal transduction

1406630|21343177|23811396|23878390

GeneRELA

GO:0008284

positive regulation of cell population proliferation

23091055

GeneRELA

GO:0010033

response to organic substance

10747850

GeneRELA

GO:0010224

response to UV-B

15616591

GeneRELA

GO:0019221

cytokine-mediated signaling pathway

15876188

GeneRELA

GO:0031490

chromatin DNA binding

25411248

GeneRELA

GO:0032731

positive regulation of interleukin-1 beta production

27203220

GeneRELA

GO:0032755

positive regulation of interleukin-6 production

27203220

GeneRELA

GO:0032757

positive regulation of interleukin-8 production

27203220

GeneRELA

GO:0033209

tumor necrosis factor-mediated signaling pathway

21343177|25411248

GeneRELA

GO:0034142

toll-like receptor 4 signaling pathway

25355951

GeneRELA

GO:0035525

NF-kappaB p50/p65 complex

18045535

GeneRELA

GO:0035556

intracellular signal transduction

27203220

GeneRELA

GO:0038061

non-canonical NF-kappaB signal transduction

8413223|12048232

GeneRELA

GO:0042301

phosphate ion binding

10521409

GeneRELA

GO:0042802

identical protein binding

9437432

GeneRELA

GO:0042803

protein homodimerization activity

18045535|18212740

GeneRELA

GO:0043066

negative regulation of apoptotic process

10747850|23091055

GeneRELA

GO:0045892

negative regulation of DNA-templated transcription

17350185

GeneRELA

GO:0045893

positive regulation of DNA-templated transcription

17350185|18073330

GeneRELA

GO:0045944

positive regulation of transcription by RNA polymerase II

1406630|8246997|17350185|23091055|23811396|26435691

GeneRELA

GO:0051092

positive regulation of NF-kappaB transcription factor activity

15790681

GeneRELA

GO:0070301

cellular response to hydrogen peroxide

21830064

GeneRELA

GO:0070431

nucleotide-binding oligomerization domain containing 2 signaling pathway

12527755

GeneRELA

GO:0071347

cellular response to interleukin-1

18073330

GeneRELA

GO:0071356

cellular response to tumor necrosis factor

18073330|23091055

GeneRELA

GO:0098978

glutamatergic synapse

12947408

GeneRELA

GO:0099527

postsynapse to nucleus signaling pathway

12947408



AS Summary

check button Information of the canonical protein with experimentally identified structure from PDB (2023).
UniProt AccFile namePDB IDMethodResolutionChainStartEnd
Q04206-1Q04206-1_1nfi_C.pdb1NFIX-ray2.7C20320

check button ASpdb's canonical and alternatively spliced isoform information.
accession_idgene_namecanonical_idalternative_idcanonical_lengthalternative_lengthcanonical_startcanonical_endtypeoriginalSEQvariationSEQalternative_startalternative_end
Q04206RELAQ04206-1Q04206-25515371325Deletionnonenone1212
Q04206RELAQ04206-1Q04206-2551537506506Deletionnonenone492492
Q04206RELAQ04206-1Q04206-3551541222231Deletionnonenone221221
Q04206RELAQ04206-1Q04206-4551548143145Deletionnonenone142142

check buttonMultiple sequence alignment of our canonical and alternatively spliced RELA

check button Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of RELA
UniProt-idENSGENSTENSP
Q04206-1ENSG00000173039.20ENST00000406246.8ENSP00000384273.3
Q04206-4ENSG00000173039.20ENST00000308639.13ENSP00000311508.9

UniProt-idNM IDNP ID
Q04206-1NM_021975.3NP_068810.3
Q04206-4NM_001145138.1NP_001138610.1

check buttonAmino acid sequences of our canonical and alternatively spliced RELA
accession_idProtein sequence
Q04206-1MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHEL
VGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLS
HPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSM
QLRRPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINY
DEFPTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDL
GALLGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADM
Q04206-2MDELFPLIFPAEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHELVGKDCRDGFYEAE
LCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPIFDNRAPNTAE
LKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDRELSEP
MEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPSGQI
SQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDPAVF
Q04206-3MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHEL
VGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQVPIEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLS
HPIFDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLRRPSDREL
SEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEFPTMVFPS
GQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGALLGNSTDP
AVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFSALLSQIS
Q04206-4MDELFPLIFPAEPAQASGPYVEIIEQPKQRGMRFRYKCEGRSAGSIPGERSTDTTKTHPTIKINGYTGPGTVRISLVTKDPPHRPHPHEL
VGKDCRDGFYEAELCPDRCIHSFQNLGIQCVKKRDLEQAISQRIQTNNNPFQEEQRGDYDLNAVRLCFQVTVRDPSGRPLRLPPVLSHPI
FDNRAPNTAELKICRVNRNSGSCLGGDEIFLLCDKVQKEDIEVYFTGPGWEARGSFSQADVHRQVAIVFRTPPYADPSLQAPVRVSMQLR
RPSDRELSEPMEFQYLPDTDDRHRIEEKRKRTYETFKSIMKKSPFSGPTDPRPPPRRIAVPSRSSASVPKPAPQPYPFTSSLSTINYDEF
PTMVFPSGQISQASALAPAPPQVLPQAPAPAPAPAMVSALAQAPAPVPVLAPGPPQAVAPPAPKPTQAGEGTLSEALLQLQFDDEDLGAL
LGNSTDPAVFTDLASVDNSEFQQLLNQGIPVAPHTTEPMLMEYPEAITRLVTGAQRPPDPAPAPLGAPGLPNGLLSGDEDFSSIADMDFS

Protein Functional Features

check buttonMain function of this protein. (from UniProt)
RELA (go to UniProt):Q04206

check buttonRetention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at

download page

* Minus value of BPloci means that the break pointn is located before the CDS.
- Retained protein feature among the 13 regional features.
Accession_idSubsectionStartEndFuncitonal featureSplicing information
Q04206Domain19306Note=RHD;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00265Type=Deletion;Start=13;End=25
Q04206Domain19306Note=RHD;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00265Type=Deletion;Start=222;End=231
Q04206Domain19306Note=RHD;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00265Type=Deletion;Start=143;End=145
Q04206Region506530Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-liteType=Deletion;Start=506;End=506


Gene Isoform Structures and Expression Levels for RELA

check buttonGene structures of our canonical and alternative spliced genes of RELA
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.
gene isoform structure of RELA

check button Expression levels of gene isoforms across GTEx.
gtex expression

check button Expression levels of gene isoforms across TCGA.
tcga expression


Protein Structures

check button PDB and CIF files of the predicted protein structures
* Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format.
3D view using mol* of Q04206-1
3D view using mol* of Q04206-2
3D view using mol* of Q04206-3
3D view using mol* of Q04206-4


pLDDT Score Distribution

check button pLDDT score distribution of the predicted protein structures from AlphaFold2
* AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100.
pLDDT distribution across the protein length of Q04206-1
all structure
pLDDT distribution across the protein length of Q04206-2
all structure
pLDDT distribution across the protein length of Q04206-3
all structure
pLDDT distribution across the protein length of Q04206-4
all structure


Ramachandran Plot of Protein Structures


check button Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide.
Ramachandran plot of Q04206-1
all structure
Ramachandran plot of Q04206-2
all structure
Ramachandran plot of Q04206-4
all structure

Potential Active Site Information


check button The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite.
UniProt-idSite scoreSizeD scoreVolumeExposureEnclosureContactPhobicPhilicBalanceDon/AccResidues
Q04206-10.91880.91221.2350.5670.6310.9250.3631.0770.3370.70369,70,71,72,73,101,137,138,139,140,142,162,163,164
,166,172,174,175,177
Q04206-20.884780.857171.50.4870.6530.9490.4631.1210.4130.82658,59,60,88,124,125,126,127,129,149,150,151,159,16
1,162,164
Q04206-31.0851391.105246.960.3380.8071.1281.4530.9791.4840.749196,212,214,223,224,225,226,227,229,240,242,244,24
5,247,258,259,260,261,262,263,270,276,278
Q04206-40.802600.759149.5480.5590.6490.9920.5171.0980.470.94921,71,72,73,101,138,139,140,142,158,159,160,161,17
1,172,173,174

Protein Structure and Feature Comparision


check button Protein Structure Comparision Using Template Modeling Scores (TM-score).
all structure

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green)
3D view using mol* of Q04206-1_Q04206-1_1nfi_C.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of Q04206-1_1nfi_C_Q04206-2.pdb
3D view using mol* of Q04206-1_1nfi_C_Q04206-3.pdb
3D view using mol* of Q04206-1_1nfi_C_Q04206-4.pdb

check button Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green)
3D view using mol* of Q04206-1_Q04206-2.pdb
3D view using mol* of Q04206-1_Q04206-3.pdb
3D view using mol* of Q04206-1_Q04206-4.pdb

check button Protein Feature Comparison of the protein sequendary structures among the protiens.
./stats/secondary_structure/figure/Q04206-1_vs_Q04206-2.png
all structure<
./stats/secondary_structure/figure/Q04206-1_vs_Q04206-3.png
all structure<
./stats/secondary_structure/figure/Q04206-1_vs_Q04206-4.png
all structure<

check button Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens.
./stats/relative_asa/Q04206-1_vs_Q04206-2.png
all structure<
./stats/relative_asa/Q04206-1_vs_Q04206-3.png
all structure<
./stats/relative_asa/Q04206-1_vs_Q04206-4.png
all structure<


Protein-Protein Interaction


check button Interactors from UniProt.
Accession_idSubsectionStartEndFuncitonal featureSplicing information


check button Interactors from STRING.
Gene nameInteractors


Related Drugs to RELA


check button Drugs targeting this gene/protein.
(DrugBank)
UniProt accessionGene nameDrugBank IDDrug nameDrug groupActions
Q04206RELADB08908Dimethyl fumarateapproved, investigationalinhibitor, binder
Q04206RELADB01296Glucosamineapproved, investigationalinhibitor

Related Diseases to RELA


check button Previous studies relating to the alternative splicing of RELA and disease information from the MeSH term (PubMed)
GenePMIDTitleAbstractMeSH IDMeSH term
RELA8281153Genomic organization of the gene encoding the p65 subunit of NF-kappa B: multiple variants of the p65 protein may be generated by alternative splicing.Transcription factor NF-kappa B represents a family of closely related homo- and heterodimeric factors. The most abundant form of NF-kappa B is the p50/p65 heterodimer. We determined the complete genomic structure of the human gene and a partial structure of the mouse gene encoding p65. The human gene consists of ten exons and spans about 8.1 kbp of DNA. The exon-intron organization in the rel homology domain (exons 2 to 7) is conserved when compared to human and turkey c-rel, strengthening the evolutionary relationship between p65 and c-rel. The lengths of the corresponding introns 5 and 6 in the human and mouse p65 genes are not conserved. However, a surprisingly high degree of conservation of intron sequences was observed between both species. We show that the naturally occurring shorter variant of p65 (p65 delta) can be generated by alternative splicing of intron 6, not only in humans but also in mouse. In addition, the existence of another, as yet unknown splice variant of p65 is predicted.D015473Leukemia, Promyelocytic, Acute
RELA8543190A novel NF-kappa B p65 spliced transcript lacking exons 6 and 7 in a non-small cell lung carcinoma cell line.Transcripts of the gene encoding the p65 subunit of the NF-kappa B/Rel transcription factor complex have been reported to undergo alternative splicing to generate one derivative lacking codons for amino acids (aa) 222 to 231 (p65 delta 1) and another that lacks codons for aa 13 to 25 (p65 delta 2) of the conserved Rel homology domain [Narayaran et al., Science 256 (1992) 317-320; Lyle et al., Gene 138 (1994) 265-266]. We have identified a third splicing event in a non-small-cell lung carcinoma cell line that potentially generates a novel p65 mRNA derivative lacking codons for aa 187 to 293 (p65 delta 3) of the Rel homology domain.D002277Carcinoma
RELA8543190A novel NF-kappa B p65 spliced transcript lacking exons 6 and 7 in a non-small cell lung carcinoma cell line.Transcripts of the gene encoding the p65 subunit of the NF-kappa B/Rel transcription factor complex have been reported to undergo alternative splicing to generate one derivative lacking codons for amino acids (aa) 222 to 231 (p65 delta 1) and another that lacks codons for aa 13 to 25 (p65 delta 2) of the conserved Rel homology domain [Narayaran et al., Science 256 (1992) 317-320; Lyle et al., Gene 138 (1994) 265-266]. We have identified a third splicing event in a non-small-cell lung carcinoma cell line that potentially generates a novel p65 mRNA derivative lacking codons for aa 187 to 293 (p65 delta 3) of the Rel homology domain.D002289Carcinoma, Non-Small-Cell Lung
RELA8543190A novel NF-kappa B p65 spliced transcript lacking exons 6 and 7 in a non-small cell lung carcinoma cell line.Transcripts of the gene encoding the p65 subunit of the NF-kappa B/Rel transcription factor complex have been reported to undergo alternative splicing to generate one derivative lacking codons for amino acids (aa) 222 to 231 (p65 delta 1) and another that lacks codons for aa 13 to 25 (p65 delta 2) of the conserved Rel homology domain [Narayaran et al., Science 256 (1992) 317-320; Lyle et al., Gene 138 (1994) 265-266]. We have identified a third splicing event in a non-small-cell lung carcinoma cell line that potentially generates a novel p65 mRNA derivative lacking codons for aa 187 to 293 (p65 delta 3) of the Rel homology domain.D008175Lung Neoplasms


Clinically important variants in RELA


check button (ClinVar, 04/20/2024)
accession_iduniprot_idgene_nameTypeVariantClinical_significance