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Description | The human nfkb2 gene encodes a protein composed 900 amino acids with an approximately molecular weight of 100 kDa, which was considered as a precursor of p52 subunit of NF-kB complexes. The structural characteristics of NF-kB2 are much similar with that of NF-kB1: A N-terminal RHD; two nuclear localization sequences within the C-terminus of RHD, a putative GRR region that possibly contributes to the generation of NF-kB p52 from the precursor, NF-kB2. The C-terminal region of NF-kB2 also contains multiple copies of the so-called ankyrin repeats and one proline, glutamic acid, serine, and threonine (PEST) domain. Studies demonstrated that NF-kB2 was posttranslationally cleaved to produce the p52 molecule through the ubiquitin-proteasome dependent degradation of the C-terminal 406-900 portion of NF-kB2. However, other studies revealed that the mechanism for the generation of NF-kB p52 is through cotranslational processing. Recent studies demonstrated that the processing of NF-kB p52 required IKKa- and/or NIK-dependent C-terminal phosphorylation of NF-kB2. |
Expression | nfkb2 is expressed mainly in lymphoid cells and mononuclear cells. |
Localisation | cytosol, nuclei after activation. |
Function | regulation of the genes involved in cell-to-cell interaction, intercellular communication, cell recruitment or transmigration, amplification or spreading of primary pathogenic signals, and initiation or acceleration of tumorigenesis. Similar with NF-kB1, the full length of NF-kB2 can serve as an endogenous inhibitor for the NF-kB p50/ p65(RelA) or NF-kB p52/p65 heterodimer. The homodimer of NF-kB p52 was transcriptionally inactive in the absence of Bcl3. Furthermore, the NF-kB p52 homodimer may function to competitively inhibit B binding by transactivating NF- B dimers. The Bcl3 protein can form a complex with this homodimer at B sites and act as a transactivator of NF-kB p52 homodimer. Interaction with : members of IkB family and Rel family, Bcl3. |
Note | |
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Entity | hematological malignancies (see below) and other diseases: autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, cancer, HTLV-1 infection, and AIDS. |
Disease | t(10;14)(q24;q11) or t(10;14)(q24;q32) in hematological malignancies |
Cytogenetics | poor. |
Oncogenesis | Unlike its relative nfkb1, rearrangement of nfkb2 gene locus has been found in many forms of lymophomas. The chromosomal translocations by t(10;14)(q24;q11) and t(10;14)(q24;q32) cause deletions of sequences encoding the ankyrin repeat motif of NF-kB2. Consequently, this carboxyl terminal truncated NF-kB2 is constitutively located in the nucleus of cells, which was found in small percentage of B-cell non-Hodgkin's lymphoma, cutaneous lymphomas, T-cell acute lymphoblastic leukemia, chronic lymphocytic leukemias, and multiple myelomas. Chromosomal translocation generated a fusion NF-kB2- IGHA1 or NF-kB2- TCRa or TCRd transcriptional unit. |
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The NF-kappa B and I kappa B proteins: new discoveries and insights. |
Baldwin AS Jr |
Annual review of immunology. 1996 ; 14 : 649-683. |
PMID 8717528 |
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New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases. |
Chen F, Castranova V, Shi X, Demers LM |
Clinical chemistry. 1999 ; 45 (1) : 7-17. |
PMID 9895331 |
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NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses. |
Ghosh S, May MJ, Kopp EB |
Annual review of immunology. 1998 ; 16 : 225-260. |
PMID 9597130 |
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The generation of nfkb2 p52: mechanism and efficiency. |
Heusch M, Lin L, Geleziunas R, Greene WC |
Oncogene. 1999 ; 18 (46) : 6201-6208. |
PMID 10597218 |
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Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2. |
Liptay S, Schmid RM, Perkins ND, Meltzer P, Altherr MR, McPherson JD, Wasmuth JJ, Nabel GJ |
Genomics. 1992 ; 13 (2) : 287-292. |
PMID 1612589 |
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B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50. |
Neri A, Chang CC, Lombardi L, Salina M, Corradini P, Maiolo AT, Chaganti RS, Dalla-Favera R |
Cell. 1991 ; 67 (6) : 1075-1087. |
PMID 1760839 |
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Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. |
Senftleben U, Cao Y, Xiao G, Greten FR, Krähn G, Bonizzi G, Chen Y, Hu Y, Fong A, Sun SC, Karin M |
Science (New York, N.Y.). 2001 ; 293 (5534) : 1495-1499. |
PMID 11520989 |
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Retroviral oncoprotein Tax induces processing of NF-kappaB2/p100 in T cells: evidence for the involvement of IKKalpha. |
Xiao G, Cvijic ME, Fong A, Harhaj EW, Uhlik MT, Waterfield M, Sun SC |
The EMBO journal. 2001 ; 20 (23) : 6805-6815. |
PMID 11726516 |
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| Nomenclature |
HGNC (Hugo) | NFKB2 7795 |
| Cards |
Atlas | NFKB2ID362 |
Entrez_Gene (NCBI) | NFKB2 nuclear factor kappa B subunit 2 |
Aliases | CVID10; H2TF1; LYT-10; LYT10; |
| NF-kB2; p100; p49/p100; p52 |
GeneCards (Weizmann) | NFKB2 |
Ensembl hg19 (Hinxton) | ENSG00000077150 [Gene_View] |
Ensembl hg38 (Hinxton) | ENSG00000077150 [Gene_View]  ENSG00000077150 [Sequence] chr10:102395705-102402524 [Contig_View] NFKB2 [Vega] |
ICGC DataPortal | ENSG00000077150 |
TCGA cBioPortal | NFKB2 |
AceView (NCBI) | NFKB2 |
Genatlas (Paris) | NFKB2 |
SOURCE (Princeton) | NFKB2 |
Genetics Home Reference (NIH) | NFKB2 |
| Genomic and cartography |
GoldenPath hg38 (UCSC) | NFKB2 - chr10:102395705-102402524 + 10q24.32 [Description] (hg38-Dec_2013) |
GoldenPath hg19 (UCSC) | NFKB2 - 10q24.32 [Description] (hg19-Feb_2009) |
GoldenPath | NFKB2 - 10q24.32 [CytoView hg19] NFKB2 - 10q24.32 [CytoView hg38] |
ImmunoBase | ENSG00000077150 |
genome Data Viewer NCBI | NFKB2 [Mapview hg19] |
OMIM | 164012 615577 |
| Gene and transcription |
Genbank (Entrez) | AK098415 AK292654 BC002844 BT009769 BY799958 |
RefSeq transcript (Entrez) | NM_001077494 NM_001261403 NM_001288724 NM_001322934 NM_001322935 NM_002502 |
RefSeq genomic (Entrez) | |
Consensus coding sequences : CCDS (NCBI) | NFKB2 |
Alternative Splicing Gallery | ENSG00000077150 |
Gene Expression | NFKB2 [ NCBI-GEO ] NFKB2 [ EBI - ARRAY_EXPRESS ]
NFKB2 [ SEEK ] NFKB2 [ MEM ] |
Gene Expression Viewer (FireBrowse) | NFKB2 [ Firebrowse - Broad ] |
Genevisible | Expression of NFKB2 in : [tissues]  [cell-lines]  [cancer]  [perturbations]   |
BioGPS (Tissue expression) | 4791 |
GTEX Portal (Tissue expression) | NFKB2 |
Human Protein Atlas | ENSG00000077150-NFKB2 [pathology] [cell] [tissue] |
| Protein : pattern, domain, 3D structure |
UniProt/SwissProt | Q00653 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
NextProt | Q00653 [Sequence] [Exons] [Medical] [Publications] |
With graphics : InterPro | Q00653 |
Splice isoforms : SwissVar | Q00653 |
PhosPhoSitePlus | Q00653 |
Domaine pattern : Prosite (Expaxy) | ANK_REP_REGION (PS50297) ANK_REPEAT (PS50088) REL_1 (PS01204) REL_2 (PS50254) |
Domains : Interpro (EBI) | Ankyrin_rpt Ankyrin_rpt-contain_dom Ankyrin_rpt-contain_sf DEATH-like_dom_sf Death_domain Ig-like_fold Ig_E-set IPT_dom IPT_NFkappaB NFkB/Dor p53-like_TF_DNA-bd RHD_CS RHD_dimer RHD_DNA_bind_dom RHD_DNA_bind_dom_sf |
Domain families : Pfam (Sanger) | Ank_2 (PF12796) Death (PF00531) RHD_dimer (PF16179) RHD_DNA_bind (PF00554) |
Domain families : Pfam (NCBI) | pfam12796 pfam00531 pfam16179 pfam00554 |
Domain families : Smart (EMBL) | ANK (SM00248) DEATH (SM00005) IPT (SM00429) |
Conserved Domain (NCBI) | NFKB2 |
Blocks (Seattle) | NFKB2 |
PDB (RSDB) | 1A3Q 2D96 3DO7 4OT9 5ZMC |
PDB Europe | 1A3Q 2D96 3DO7 4OT9 5ZMC |
PDB (PDBSum) | 1A3Q 2D96 3DO7 4OT9 5ZMC |
PDB (IMB) | 1A3Q 2D96 3DO7 4OT9 5ZMC |
Structural Biology KnowledgeBase | 1A3Q 2D96 3DO7 4OT9 5ZMC |
SCOP (Structural Classification of Proteins) | 1A3Q 2D96 3DO7 4OT9 5ZMC |
CATH (Classification of proteins structures) | 1A3Q 2D96 3DO7 4OT9 5ZMC |
Superfamily | Q00653 |
Human Protein Atlas [tissue] | ENSG00000077150-NFKB2 [tissue] |
Peptide Atlas | Q00653 |
HPRD | 01239 |
IPI | IPI00845373 IPI00973137 IPI00807463 |
| Protein Interaction databases |
DIP (DOE-UCLA) | Q00653 |
IntAct (EBI) | Q00653 |
BioGRID | NFKB2 |
STRING (EMBL) | NFKB2 |
ZODIAC | NFKB2 |
| Ontologies - Pathways |
QuickGO | Q00653 |
Ontology : AmiGO | "nuclear chromatin RNA polymerase II proximal promoter sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription activator activity, RNA polymerase II-specific follicular dendritic cell differentiation germinal center formation DNA-binding transcription factor activity transcription coactivator activity protein binding nucleus nucleoplasm cytoplasm cytosol cytosol regulation of transcription, DNA-templated aging extracellular matrix organization positive regulation of type I interferon production response to lipopolysaccharide Bcl3/NF-kappaB2 complex NIK/NF-kappaB signaling host cell nucleus positive regulation of transcription by RNA polymerase II rhythmic process spleen development positive regulation of NF-kappaB transcription factor activity" |
Ontology : EGO-EBI | "nuclear chromatin RNA polymerase II proximal promoter sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription factor activity, RNA polymerase II-specific DNA-binding transcription activator activity, RNA polymerase II-specific follicular dendritic cell differentiation germinal center formation DNA-binding transcription factor activity transcription coactivator activity protein binding nucleus nucleoplasm cytoplasm cytosol cytosol regulation of transcription, DNA-templated aging extracellular matrix organization positive regulation of type I interferon production response to lipopolysaccharide Bcl3/NF-kappaB2 complex NIK/NF-kappaB signaling host cell nucleus positive regulation of transcription by RNA polymerase II rhythmic process spleen development positive regulation of NF-kappaB transcription factor activity" |
Pathways : KEGG | MAPK signaling pathway NF-kappa B signaling pathway Osteoclast differentiation Legionellosis HTLV-I infection Epstein-Barr virus infection Pathways in cancer Viral carcinogenesis |
REACTOME | Q00653 [protein] |
REACTOME Pathways | R-HSA-933542 [pathway] |
NDEx Network | NFKB2 |
Atlas of Cancer Signalling Network | NFKB2 |
Wikipedia pathways | NFKB2 |
| Orthology - Evolution |
OrthoDB | 4791 |
GeneTree (enSembl) | ENSG00000077150 |
Phylogenetic Trees/Animal Genes : TreeFam | NFKB2 |
HOGENOM | Q00653 |
Homologs : HomoloGene | NFKB2 |
Homology/Alignments : Family Browser (UCSC) | NFKB2 |
| Gene fusions - Rearrangements |
Fusion : Mitelman | IGH/NFKB2 [14q32.33/10q24.32]   |
Fusion : Mitelman | NFKB2/GBF1 [10q24.32/10q24.32]   |
Fusion Portal | NFKB2 10q24.32 GBF1 10q24.32 BRCA |
Fusion : Fusion_Hub | BCL10--NFKB2 COL25A1--NFKB2 GPI--NFKB2 IGH@--NFKB2 IGHA1--NFKB2 JAK1--NFKB2 NFKB2--CORO7 NFKB2--GBF1 NFKB2--IGH NFKB2--IGHA1 NFKB2--INA NFKB2--SRRM2 NFKB2--TBXAS1 P100--NFKB2 P52--NFKB2 |
| PFKL--NFKB2 SNX17--NFKB2 TBXAS1--NFKB2 |
Fusion : Quiver | NFKB2 |
| Polymorphisms : SNP and Copy number variants |
NCBI Variation Viewer | NFKB2 [hg38] |
dbVar | NFKB2 |
ClinVar | NFKB2 |
Monarch | NFKB2 |
1000_Genomes | NFKB2 |
Exome Variant Server | NFKB2 |
GNOMAD Browser | ENSG00000077150 |
Varsome Browser | NFKB2 |
Genomic Variants (DGV) | NFKB2 [DGVbeta] |
DECIPHER | NFKB2 [patients] [syndromes] [variants] [genes] |
CONAN: Copy Number Analysis | NFKB2 |
| Mutations |
ICGC Data Portal | NFKB2 |
TCGA Data Portal | NFKB2 |
Broad Tumor Portal | NFKB2 |
OASIS Portal | NFKB2 [ Somatic mutations - Copy number] |
Cancer Gene: Census | NFKB2 |
Somatic Mutations in Cancer : COSMIC | NFKB2 [overview] [genome browser] [tissue] [distribution] |
Somatic Mutations in Cancer : COSMIC3D | NFKB2 |
Mutations and Diseases : HGMD | NFKB2 |
LOVD (Leiden Open Variation Database) | Whole genome datasets |
LOVD (Leiden Open Variation Database) | LOVD - Leiden Open Variation Database |
LOVD (Leiden Open Variation Database) | LOVD 3.0 shared installation |
BioMuta | search NFKB2 |
DgiDB (Drug Gene Interaction Database) | NFKB2 |
DoCM (Curated mutations) | NFKB2 (select the gene name) |
CIViC (Clinical Interpretations of Variants in Cancer) | NFKB2 (select a term) |
intoGen | NFKB2 |
OncoKB | NFKB2 |
NCG6 (London) | select NFKB2 |
Cancer3D | NFKB2(select the gene name) |
Impact of mutations | [PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
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OMIM | 164012 615577 |
Orphanet | 3469 20898 |
DisGeNET | NFKB2 |
Medgen | NFKB2 |
Genetic Testing Registry | NFKB2
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NextProt | Q00653 [Medical] |
GENETests | NFKB2 |
Target Validation | NFKB2 |
Huge Navigator |
NFKB2 [HugePedia] |
ClinGen | NFKB2 |
| Clinical trials, drugs, therapy |
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MyCancerGenome | NFKB2 |
Protein Interactions : CTD | |
Pharm GKB Gene | PA31600 |
Pharm GKB Pathways | PA162356267 PA165985892 |
Pharos | Q00653 |
Clinical trial | NFKB2 |
| Miscellaneous |
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canSAR (ICR) | NFKB2 (select the gene name) |
Harmonizome | NFKB2 |
DataMed Index | NFKB2 |
| Probes |
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| Litterature |
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PubMed | 313 Pubmed reference(s) in Entrez |
GeneRIFs | Gene References Into Functions (Entrez) |
EVEX | NFKB2 |