Fusion genes
(updated 2016) | GPI (19q13.11) / NFKB2 (10q24.32) | IGH (14q32.33) / NFKB2 (10q24.32) | IGHA1 (14q32.33) / NFKB2 (10q24.32) |
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IGHG1 (14q32.33) / NFKB2 (10q24.32) | NFKB2 (10q24.32) / GBF1 (10q24.32) | NFKB2 (10q24.32) / IGH (14q32.33) |
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NFKB2 (10q24.32) / IGHA1 (14q32.33) | NFKB2 (10q24.32) / INA (10q24.33) | NFKB2 (10q24.32) / TBXAS1 (7q34) |
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PFKL (21q22.3) / NFKB2 (10q24.32) |
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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 | |
| 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 |
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| HGNC (Hugo) | NFKB2 7795 |
| Cards |
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| Atlas | NFKB2ID362 |
| Entrez_Gene (NCBI) | NFKB2 4791 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 |
| Aliases | CVID10; H2TF1; LYT-10; LYT10; |
| NF-kB2; p100; p49/p100; p52 |
| GeneCards (Weizmann) | NFKB2 |
| Ensembl hg19 (Hinxton) | ENSG00000077150 [Gene_View] chr10:104154335-104162286 [Contig_View] NFKB2 [Vega] |
| Ensembl hg38 (Hinxton) | ENSG00000077150 [Gene_View] chr10:104154335-104162286 [Contig_View] NFKB2 [Vega] |
| ICGC DataPortal | ENSG00000077150 |
| TCGA cBioPortal | NFKB2 |
| AceView (NCBI) | NFKB2 |
| Genatlas (Paris) | NFKB2 |
| WikiGenes | 4791 |
| SOURCE (Princeton) | NFKB2 |
| Genomic and cartography |
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| GoldenPath hg19 (UCSC) | NFKB2 - chr10:104154335-104162286 + 10q24 [Description] (hg19-Feb_2009) |
| GoldenPath hg38 (UCSC) | NFKB2 - 10q24 [Description] (hg38-Dec_2013) |
| Ensembl | NFKB2 - 10q24 [CytoView hg19] NFKB2 - 10q24 [CytoView hg38] |
| Mapping of homologs : NCBI | NFKB2 [Mapview hg19] NFKB2 [Mapview hg38] |
| OMIM | 164012 615577 |
| Gene and transcription |
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| Genbank (Entrez) | AK098415 AK292654 BC002844 BT009769 BY799958 |
| RefSeq transcript (Entrez) | NM_001077494 NM_001261403 NM_001288724 NM_001322934 NM_002502 |
| RefSeq genomic (Entrez) | NC_000010 NC_018921 NG_033874 NT_030059 NW_004929376 |
| Consensus coding sequences : CCDS (NCBI) | NFKB2 |
| Cluster EST : Unigene | Hs.73090 [ NCBI ] |
| CGAP (NCI) | Hs.73090 |
| Alternative Splicing Gallery | ENSG00000077150 |
| Gene Expression | NFKB2 [ NCBI-GEO ] NFKB2 [ EBI - ARRAY_EXPRESS ]
NFKB2 [ SEEK ] NFKB2 [ MEM ] |
| Gene Expression Viewer (FireBrowse) | NFKB2 [ Firebrowse - Broad ] |
| SOURCE (Princeton) | Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60] |
| Genevisible | Expression in : [tissues] [cell-lines] [cancer] [perturbations] |
| BioGPS (Tissue expression) | 4791 |
| GTEX Portal (Tissue expression) | NFKB2 |
| Protein : pattern, domain, 3D structure |
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| UniProt/SwissProt | Q00653 (Uniprot) |
| NextProt | Q00653 [Sequence] [Exons] [Medical] [Publications] |
| With graphics : InterPro | Q00653 |
| Splice isoforms : SwissVar | Q00653 (Swissvar) |
| 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 DEATH-like_dom Death_domain Ig-like_fold Ig_E-set IPT NFkB/Dor NFkB_p100 p53-like_TF_DNA-bd RHD_CS RHD_dimer RHD_DNA_bind_dom |
| 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) |
| DMDM Disease mutations | 4791 |
| Blocks (Seattle) | NFKB2 |
| PDB (SRS) | 1A3Q 2D96 3DO7 4OT9 |
| PDB (PDBSum) | 1A3Q 2D96 3DO7 4OT9 |
| PDB (IMB) | 1A3Q 2D96 3DO7 4OT9 |
| PDB (RSDB) | 1A3Q 2D96 3DO7 4OT9 |
| Structural Biology KnowledgeBase | 1A3Q 2D96 3DO7 4OT9 |
| SCOP (Structural Classification of Proteins) | 1A3Q 2D96 3DO7 4OT9 |
| CATH (Classification of proteins structures) | 1A3Q 2D96 3DO7 4OT9 |
| Superfamily | Q00653 |
| Human Protein Atlas | ENSG00000077150 |
| Peptide Atlas | Q00653 |
| HPRD | 01239 |
| IPI | IPI00845373 IPI00973137 IPI00807463 |
| Protein Interaction databases |
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| DIP (DOE-UCLA) | Q00653 |
| IntAct (EBI) | Q00653 |
| FunCoup | ENSG00000077150 |
| BioGRID | NFKB2 |
| STRING (EMBL) | NFKB2 |
| ZODIAC | NFKB2 |
| Ontologies - Pathways |
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| QuickGO | Q00653 |
| Ontology : AmiGO | negative regulation of transcription from RNA polymerase II promoter RNA polymerase II core promoter proximal region sequence-specific DNA binding transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding follicular dendritic cell differentiation germinal center formation chromatin binding transcription factor activity, sequence-specific DNA binding transcription coactivator activity protein binding nucleus nucleoplasm nucleoplasm cytoplasm cytosol cytosol regulation of transcription, DNA-templated transcription from RNA polymerase II promoter inflammatory response I-kappaB kinase/NF-kappaB signaling aging extracellular matrix organization positive regulation of type I interferon production response to lipopolysaccharide Bcl3/NF-kappaB2 complex response to cytokine NIK/NF-kappaB signaling NIK/NF-kappaB signaling innate immune response positive regulation of transcription from RNA polymerase II promoter rhythmic process spleen development positive regulation of NF-kappaB transcription factor activity |
| Ontology : EGO-EBI | negative regulation of transcription from RNA polymerase II promoter RNA polymerase II core promoter proximal region sequence-specific DNA binding transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding follicular dendritic cell differentiation germinal center formation chromatin binding transcription factor activity, sequence-specific DNA binding transcription coactivator activity protein binding nucleus nucleoplasm nucleoplasm cytoplasm cytosol cytosol regulation of transcription, DNA-templated transcription from RNA polymerase II promoter inflammatory response I-kappaB kinase/NF-kappaB signaling aging extracellular matrix organization positive regulation of type I interferon production response to lipopolysaccharide Bcl3/NF-kappaB2 complex response to cytokine NIK/NF-kappaB signaling NIK/NF-kappaB signaling innate immune response positive regulation of transcription from RNA polymerase II promoter 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-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production [pathway] |
| REACTOME Pathways | R-HSA-5603027 IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR) [pathway] |
| REACTOME Pathways | R-HSA-5603029 IkBA variant leads to EDA-ID [pathway] |
| REACTOME Pathways | R-HSA-448706 Interleukin-1 processing [pathway] |
| REACTOME Pathways | R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling [pathway] |
| REACTOME Pathways | R-HSA-933542 TRAF6 mediated NF-kB activation [pathway] |
| REACTOME Pathways | noncanonical NF-kB signaling TARGET=REACTOME>R-HSA-5676590 NIK-->noncanonical NF-kB signaling [pathway] |
| REACTOME Pathways | R-HSA-1810476 RIP-mediated NFkB activation via ZBP1 [pathway] |
| REACTOME Pathways | R-HSA-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex [pathway] |
| NDEx Network | NFKB2 |
| Atlas of Cancer Signalling Network | NFKB2 |
| Wikipedia pathways | NFKB2 |
| Orthology - Evolution |
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| OrthoDB | 4791 |
| GeneTree (enSembl) | ENSG00000077150 |
| Phylogenetic Trees/Animal Genes : TreeFam | NFKB2 |
| Homologs : HomoloGene | NFKB2 |
| Homology/Alignments : Family Browser (UCSC) | NFKB2 |
| Gene fusions - Rearrangements |
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| Fusion : Mitelman | IGH/NFKB2 [14q32.33/10q24.32] [t(10;14)(q24;q32)] |
| Fusion : Mitelman | NFKB2/GBF1 [10q24.32/10q24.32] [t(10;10)(q24;q24)] |
| Fusion: TCGA | NFKB2 10q24.32 GBF1 10q24.32 BRCA |
| Polymorphisms : SNP, variants |
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| NCBI Variation Viewer | NFKB2 [hg38] |
| dbSNP Single Nucleotide Polymorphism (NCBI) | NFKB2 |
| dbVar | NFKB2 |
| ClinVar | NFKB2 |
| 1000_Genomes | NFKB2 |
| Exome Variant Server | NFKB2 |
| ExAC (Exome Aggregation Consortium) | NFKB2 (select the gene name) |
| Genetic variants : HAPMAP | 4791 |
| Genomic Variants (DGV) | NFKB2 [DGVbeta] |
| Mutations |
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| 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 |
| 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 |
| Impact of mutations | [PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] |
| Diseases |
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| DECIPHER (Syndromes) | 10:104154335-104162286 ENSG00000077150 |
| CONAN: Copy Number Analysis | NFKB2 |
| Mutations and Diseases : HGMD | NFKB2 |
| OMIM | 164012 615577 |
| Medgen | NFKB2 |
| Genetic Testing Registry | NFKB2
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| NextProt | Q00653 [Medical] |
| TSGene | 4791 |
| GENETests | NFKB2 |
| Huge Navigator |
NFKB2 [HugePedia] |
| snp3D : Map Gene to Disease | 4791 |
| BioCentury BCIQ | NFKB2 |
| ClinGen | NFKB2 |
| Clinical trials, drugs, therapy |
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| Chemical/Protein Interactions : CTD | 4791 |
| Chemical/Pharm GKB Gene | PA31600 |
| Clinical trial | NFKB2 |
| Miscellaneous |
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| canSAR (ICR) | NFKB2 (select the gene name) |
| Probes |
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| Litterature |
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| PubMed | 258 Pubmed reference(s) in Entrez |
| GeneRIFs | Gene References Into Functions (Entrez) |
| CoreMine | NFKB2 |
| EVEX | NFKB2 |
| GoPubMed | NFKB2 |
| iHOP | NFKB2 |
