Protein:NFKB2 |
Protein Summary |
 Gene summary |
| Gene name: NFKB2 | ASpdb.0 ID: 4791 | Gene | Gene symbol | NFKB2 | Gene ID | 4791 |
| Gene name | nuclear factor kappa B subunit 2 |
| Synonyms | CVID10|H2TF1|LYT-10|LYT10|NF-kB2|p100|p49/p100|p52 |
| Cytomap | 10q24.32 |
| Type of gene | protein-coding |
| Description | nuclear factor NF-kappa-B p100 subunitDNA-binding factor KBF2NFKB, p52/p100 subunitlymphocyte translocation chromosome 10 proteinnuclear factor Kappa-B, subunit 2nuclear factor NF-kappa-B p52 subunitnuclear factor of Kappa light chain gene enhancer |
| Modification date | 20240411 |
| UniProtAcc | Q00653 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | NFKB2 | GO:0000978 | RNA polymerase II cis-regulatory region sequence-specific DNA binding | 12835724 |
| Gene | NFKB2 | GO:0001228 | DNA-binding transcription activator activity, RNA polymerase II-specific | 12835724 |
| Gene | NFKB2 | GO:0005634 | nucleus | 15677444 |
| Gene | NFKB2 | GO:0005654 | nucleoplasm | - |
| Gene | NFKB2 | GO:0005737 | cytoplasm | 15677444 |
| Gene | NFKB2 | GO:0005829 | cytosol | - |
| Gene | NFKB2 | GO:0006355 | regulation of DNA-templated transcription | 8360178 |
| Gene | NFKB2 | GO:0007249 | canonical NF-kappaB signal transduction | 37816088 |
| Gene | NFKB2 | GO:0033257 | Bcl3/NF-kappaB2 complex | 9407099 |
| Gene | NFKB2 | GO:0045944 | positive regulation of transcription by RNA polymerase II | 12835724 |
| Gene | NFKB2 | GO:1990837 | sequence-specific double-stranded DNA binding | 28473536 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| Q00653-1 | Q00653-1_4ot9_A.pdb | 4OT9 | X-ray | 3.35 | A | 435 | 756 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| Q00653 | NFKB2 | Q00653-1 | Q00653-3 | 900 | 428 | 374 | 428 | Substitution | GSLGFFPSSLAYSPYQSGAGPMGCYPGGGGGAQMAATVPSRDSGEEAAEPSAPSR | EGVLMEGGVKVREAVEEKNLGEAGRGLHACNPALWEAKAGRLPEIRSSRPAWPTA | 374 | 428 |
| Q00653 | NFKB2 | Q00653-1 | Q00653-3 | 900 | 428 | 429 | 900 | Deletion | none | none | 428 | 428 |
| Q00653 | NFKB2 | Q00653-1 | Q00653-4 | 900 | 899 | 860 | 860 | Deletion | none | none | 859 | 859 |
| Multiple sequence alignment of our canonical and alternatively spliced NFKB2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of NFKB2 |
| UniProt-id | ENSG | ENST | ENSP |
| Q00653-1 | ENSG00000077150.21 | ENST00000369966.8 | ENSP00000358983.3 |
| Q00653-1 | ENSG00000077150.21 | ENST00000661543.1 | ENSP00000499294.1 |
| Q00653-4 | ENSG00000077150.21 | ENST00000189444.11 | ENSP00000189444.6 |
| Q00653-4 | ENSG00000077150.21 | ENST00000428099.6 | ENSP00000410256.1 |
| Q00653-4 | ENSG00000077150.21 | ENST00000652277.1 | ENSP00000498308.1 |
| UniProt-id | NM ID | NP ID |
| Q00653-1 | NM_001077494.3 | NP_001070962.1 |
| Q00653-1 | NM_001322934.1 | NP_001309863.1 |
| Q00653-4 | NM_001261403.2 | NP_001248332.1 |
| Q00653-4 | NM_001288724.1 | NP_001275653.1 |
| Q00653-4 | NM_002502.5 | NP_002493.3 |
| Amino acid sequences of our canonical and alternatively spliced NFKB2 |
| accession_id | Protein sequence |
| Q00653-1 | MESCYNPGLDGIIEYDDFKLNSSIVEPKEPAPETADGPYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAK IEVDLVTHSDPPRAHAHSLVGKQCSELGICAVSVGPKDMTAQFNNLGVLHVTKKNMMGTMIQKLQRQRLRSRPQGLTEAEQRELEQEAKE LKKVMDLSIVRLRFSAFLRASDGSFSLPLKPVISQPIHDSKSPGASNLKISRMDKTAGSVRGGDEVYLLCDKVQKDDIEVRFYEDDENGW QAFGDFSPTDVHKQYAIVFRTPPYHKMKIERPVTVFLQLKRKRGGDVSDSKQFTYYPLVEDKEEVQRKRRKALPTFSQPFGGGSHMGGGS GGAAGGYGGAGGGGSLGFFPSSLAYSPYQSGAGPMGCYPGGGGGAQMAATVPSRDSGEEAAEPSAPSRTPQCEPQAPEMLQRAREYNARL FGLAQRSARALLDYGVTADARALLAGQRHLLTAQDENGDTPLHLAIIHGQTSVIEQIVYVIHHAQDLGVVNLTNHLHQTPLHLAVITGQT SVVSFLLRVGADPALLDRHGDSAMHLALRAGAGAPELLRALLQSGAPAVPQLLHMPDFEGLYPVHLAVRARSPECLDLLVDSGAEVEATE RQGGRTALHLATEMEELGLVTHLVTKLRANVNARTFAGNTPLHLAAGLGYPTLTRLLLKAGADIHAENEEPLCPLPSPPTSDSDSDSEGP EKDTRSSFRGHTPLDLTCSTKVKTLLLNAAQNTMEPPLTPPSPAGPGLSLGDTALQNLEQLLDGPEAQGSWAELAERLGLRSLVDTYRQT TSPSGSLLRSYELAGGDLAGLLEALSDMGLEEGVRLLRGPETRDKLPSTAEVKEDSAYGSQSVEQEAEKLGPPPEPPGGLCHGHPQPQVH |
| Q00653-3 | MESCYNPGLDGIIEYDDFKLNSSIVEPKEPAPETADGPYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAK IEVDLVTHSDPPRAHAHSLVGKQCSELGICAVSVGPKDMTAQFNNLGVLHVTKKNMMGTMIQKLQRQRLRSRPQGLTEAEQRELEQEAKE LKKVMDLSIVRLRFSAFLRASDGSFSLPLKPVISQPIHDSKSPGASNLKISRMDKTAGSVRGGDEVYLLCDKVQKDDIEVRFYEDDENGW QAFGDFSPTDVHKQYAIVFRTPPYHKMKIERPVTVFLQLKRKRGGDVSDSKQFTYYPLVEDKEEVQRKRRKALPTFSQPFGGGSHMGGGS |
| Q00653-4 | MESCYNPGLDGIIEYDDFKLNSSIVEPKEPAPETADGPYLVIVEQPKQRGFRFRYGCEGPSHGGLPGASSEKGRKTYPTVKICNYEGPAK IEVDLVTHSDPPRAHAHSLVGKQCSELGICAVSVGPKDMTAQFNNLGVLHVTKKNMMGTMIQKLQRQRLRSRPQGLTEAEQRELEQEAKE LKKVMDLSIVRLRFSAFLRASDGSFSLPLKPVISQPIHDSKSPGASNLKISRMDKTAGSVRGGDEVYLLCDKVQKDDIEVRFYEDDENGW QAFGDFSPTDVHKQYAIVFRTPPYHKMKIERPVTVFLQLKRKRGGDVSDSKQFTYYPLVEDKEEVQRKRRKALPTFSQPFGGGSHMGGGS GGAAGGYGGAGGGGSLGFFPSSLAYSPYQSGAGPMGCYPGGGGGAQMAATVPSRDSGEEAAEPSAPSRTPQCEPQAPEMLQRAREYNARL FGLAQRSARALLDYGVTADARALLAGQRHLLTAQDENGDTPLHLAIIHGQTSVIEQIVYVIHHAQDLGVVNLTNHLHQTPLHLAVITGQT SVVSFLLRVGADPALLDRHGDSAMHLALRAGAGAPELLRALLQSGAPAVPQLLHMPDFEGLYPVHLAVRARSPECLDLLVDSGAEVEATE RQGGRTALHLATEMEELGLVTHLVTKLRANVNARTFAGNTPLHLAAGLGYPTLTRLLLKAGADIHAENEEPLCPLPSPPTSDSDSDSEGP EKDTRSSFRGHTPLDLTCSTKVKTLLLNAAQNTMEPPLTPPSPAGPGLSLGDTALQNLEQLLDGPEAQGSWAELAERLGLRSLVDTYRQT |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| NFKB2 (go to UniProt):Q00653 |
| Retention 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 * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q00653 | Repeat | 487 | 519 | Note=ANK 1 | Type=Deletion;Start=429;End=900 |
| Q00653 | Repeat | 526 | 555 | Note=ANK 2 | Type=Deletion;Start=429;End=900 |
| Q00653 | Repeat | 559 | 591 | Note=ANK 3 | Type=Deletion;Start=429;End=900 |
| Q00653 | Repeat | 599 | 628 | Note=ANK 4 | Type=Deletion;Start=429;End=900 |
| Q00653 | Repeat | 633 | 663 | Note=ANK 5 | Type=Deletion;Start=429;End=900 |
| Q00653 | Repeat | 667 | 696 | Note=ANK 6 | Type=Deletion;Start=429;End=900 |
| Q00653 | Repeat | 729 | 758 | Note=ANK 7 | Type=Deletion;Start=429;End=900 |
| Q00653 | Domain | 764 | 851 | Note=Death | Type=Deletion;Start=429;End=900 |
| Q00653 | Region | 346 | 377 | Note=GRR | Type=Substitution;Start=374;End=428 |
| Q00653 | Region | 404 | 435 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Substitution;Start=374;End=428 |
| Q00653 | Region | 404 | 435 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=429;End=900 |
| Q00653 | Region | 698 | 734 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=429;End=900 |
| Q00653 | Region | 849 | 900 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=429;End=900 |
| Q00653 | Region | 849 | 900 | Note=Disordered;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=860;End=860 |
| Q00653 | Compositional bias | 715 | 729 | Note=Basic and acidic residues;Ontology_term=ECO:0000256;evidence=ECO:0000256|SAM:MobiDB-lite | Type=Deletion;Start=429;End=900 |
Gene Isoform Structures and Expression Levels for NFKB2 |
| Gene structures of our canonical and alternative spliced genes of NFKB2 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| 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 Q00653-1 |
| 3D view using mol* of Q00653-3 |
| 3D view using mol* of Q00653-4 |
pLDDT Score Distribution |
| 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 Q00653-1 |
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| pLDDT distribution across the protein length of Q00653-3 |
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| pLDDT distribution across the protein length of Q00653-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of Q00653-1 |
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| Ramachandran plot of Q00653-3 |
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| Ramachandran plot of Q00653-4 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| Q00653-1 | 1.121 | 111 | 1.16 | 226.38 | 0.422 | 0.816 | 1.108 | 1.388 | 0.826 | 1.68 | 0.767 | 92,93,94,95,96,103,104,105,107,108,109,116,117,118 ,119,149,152,153,154,156,157,160,193,195,197 |
| Q00653-3 | 1.084 | 180 | 1.12 | 673.309 | 0.532 | 0.775 | 0.999 | 0.97 | 0.875 | 1.108 | 1.058 | 22,23,24,25,26,27,28,30,40,90,92,93,94,95,104,105, 107,108,109,117,118,119,152,153,154,156,157,160,16 1,163,193,195,196,197,204,205,206,208,209,210,211 |
| Q00653-4 | 1.153 | 99 | 1.203 | 211.288 | 0.365 | 0.841 | 1.113 | 1.491 | 0.726 | 2.055 | 1.198 | 92,93,94,95,104,105,107,108,109,117,118,119,150,15 3,154,156,157,160,193,195,197,208 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of Q00653-1_Q00653-1_4ot9_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q00653-1_4ot9_A_Q00653-3.pdb |
| 3D view using mol* of Q00653-1_4ot9_A_Q00653-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q00653-1_Q00653-3.pdb |
| 3D view using mol* of Q00653-1_Q00653-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q00653-1_vs_Q00653-3.png |
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| ./stats/secondary_structure/figure/Q00653-1_vs_Q00653-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q00653-1_vs_Q00653-3.png |
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| ./stats/relative_asa/Q00653-1_vs_Q00653-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to NFKB2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| Q00653 | NFKB2 | DB05471 | SGN-30 | investigational | |
| Q00653 | NFKB2 | DB14059 | SC-236 | experimental, investigational | inhibitor |
| Q00653 | NFKB2 | DB01411 | Pranlukast | investigational | inhibitor |
| Q00653 | NFKB2 | DB05464 | NOX-700 | investigational | |
| Q00653 | NFKB2 | DB05451 | P54 | investigational | |
| Q00653 | NFKB2 | DB13751 | Glycyrrhizic acid | approved, experimental | translocation inhibitor |
| Q00653 | NFKB2 | DB13961 | Fish oil | approved, nutraceutical | regulator |
| Q00653 | NFKB2 | DB05559 | NF-kappaB Decoy | investigational | inhibitor |
| Q00653 | NFKB2 | DB05487 | Custirsen | investigational | |
| Q00653 | NFKB2 | DB00795 | Sulfasalazine | approved | inhibitor |
| Q00653 | NFKB2 | DB00843 | Donepezil | approved | inhibitor |
| Q00653 | NFKB2 | DB05767 | Andrographolide | investigational | |
| Q00653 | NFKB2 | DB05212 | HE3286 | investigational | |
| Q00653 | NFKB2 | DB12816 | Terpinen-4-ol | investigational | downregulator |
Related Diseases to NFKB2 |
| Previous studies relating to the alternative splicing of NFKB2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| NFKB2 | 8208540 | Rearranged NFKB2 gene in the HUT78 T-lymphoma cell line codes for a constitutively nuclear factor lacking transcriptional repressor functions. | Rearrangements of the NFKB2 gene are associated with lymphoid malignancies, but the functional significance of these alterations is not known. Here we characterize structurally and functionally a rearranged NFKB2 gene identified at the T cell lymphoma line, HUT78. The rearrangement has truncated NFKB2 sequences within the 3' ankyrin domain, leading to the production of truncated mRNA species and proteins as detected by Northern blot and immunoprecipitation analysis, respectively. Cloning and sequencing of the corresponding cDNAs indicates that, via alternative splicing, the rearranged gene codes for two proteins of 84 and 85 kD (p84/85) which retain the DNA-binding rel domain and the first five ankyrin repeats, but have lost their carboxy-terminus including the seventh ankyrin repeat. Immunofluorescence and immunoprecipitation analysis of HUT78 cells indicate that p84/85 are abnormally located in the nucleus in an unprocessed form, suggesting that these proteins can escape the cytoplasmic retention typical of the normal NFKB2 p100 protein before it is processed into p52. Electrophoretic mobility shift assays performed on HUT78 nuclear extracts indicate that the abnormal NFKB2 proteins bind kappa B sites specifically and alter the composition of NF-kappa B complexes in HUT78 cells. Transient co-transfection assays involving NFKB2 expression vectors and kappa B-driven reporter plasmids indicate that NFKB2 p85 has lost the transcriptional repressor functions typical of normal NFKB2 p52. These data indicate that the NFKB2 gene rearrangement detected in HUT78 cells leads to the production of abnormal NFKB2 proteins capable of altering the function of the NF-kappa B transcription system. Since analogous rearrangements are found in lymphoid malignancies, these findings further support a role of NFKB2 alterations in tumorigenesis. | D016399 | Lymphoma, T-Cell |
Clinically important variants in NFKB2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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