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NFKB2 nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)

Identity

Other namesNF-kB p100
NF-kB p52
Lyt10
HGNC (Hugo) NFKB2
LocusID (NCBI) 4791
Location 10q24.32
Location_base_pair Starts at 104154335 and ends at 104162286 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note see also, in the Deep Insight section: Upstream Signal Transduction of NF-kB Activation

DNA/RNA

Description The gene encoding human nfkb2 has 24 exons spanning 8 kb. The expression of nfkb2 can be regulated by two distinct promoters, P1 and P2, in which a number of consensus binding sites for transcription factors, including SP1, AP1 and putative NF-kappa B (kappa B sites), were identified.

Protein

 
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.

Implicated in

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.
  

External links

Nomenclature
HGNC (Hugo)NFKB2   7795
Cards
AtlasNFKB2ID362
Entrez_Gene (NCBI)NFKB2  4791  nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100)
GeneCards (Weizmann)NFKB2
Ensembl (Hinxton)ENSG00000077150 [Gene_View]  chr10:104154335-104162286 [Contig_View]  NFKB2 [Vega]
ICGC DataPortalENSG00000077150
cBioPortalNFKB2
AceView (NCBI)NFKB2
Genatlas (Paris)NFKB2
WikiGenes4791
SOURCE (Princeton)NM_001077494 NM_001261403 NM_001288724 NM_002502
Genomic and cartography
GoldenPath (UCSC)NFKB2  -  10q24.32   chr10:104154335-104162286 +  10q24   [Description]    (hg19-Feb_2009)
EnsemblNFKB2 - 10q24 [CytoView]
Mapping of homologs : NCBINFKB2 [Mapview]
OMIM164012   615577   
Gene and transcription
Genbank (Entrez)AK098415 AK292654 BC002844 BT009769 BY799958
RefSeq transcript (Entrez)NM_001077494 NM_001261403 NM_001288724 NM_002502
RefSeq genomic (Entrez)AC_000142 NC_000010 NC_018921 NG_033874 NT_030059 NW_001838006 NW_004929376
Consensus coding sequences : CCDS (NCBI)NFKB2
Cluster EST : UnigeneHs.73090 [ NCBI ]
CGAP (NCI)Hs.73090
Alternative Splicing : Fast-db (Paris)GSHG0003646
Alternative Splicing GalleryENSG00000077150
Gene ExpressionNFKB2 [ NCBI-GEO ]     NFKB2 [ SEEK ]   NFKB2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ00653 (Uniprot)
NextProtQ00653  [Medical]
With graphics : InterProQ00653
Splice isoforms : SwissVarQ00653 (Swissvar)
Domaine pattern : Prosite (Expaxy)ANK_REP_REGION (PS50297)    ANK_REPEAT (PS50088)    REL_1 (PS01204)    REL_2 (PS50254)   
Domains : Interpro (EBI)Ankyrin_rpt [organisation]   Ankyrin_rpt-contain_dom [organisation]   DEATH-like_dom [organisation]   Death_domain [organisation]   Ig-like_fold [organisation]   Ig_E-set [organisation]   IPT [organisation]   NF_Rel_Dor [organisation]   p53-like_TF_DNA-bd [organisation]   RHD [organisation]  
Related proteins : CluSTrQ00653
Domain families : Pfam (Sanger)Ank (PF00023)    Death (PF00531)    RHD (PF00554)   
Domain families : Pfam (NCBI)pfam00023    pfam00531    pfam00554   
Domain families : Smart (EMBL)ANK (SM00248)  DEATH (SM00005)  IPT (SM00429)  
DMDM Disease mutations4791
Blocks (Seattle)Q00653
PDB (SRS)1A3Q    2D96    3DO7   
PDB (PDBSum)1A3Q    2D96    3DO7   
PDB (IMB)1A3Q    2D96    3DO7   
PDB (RSDB)1A3Q    2D96    3DO7   
Human Protein AtlasENSG00000077150 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ00653
HPRD01239
IPIIPI00845373   IPI00973137   IPI00807463   
Protein Interaction databases
DIP (DOE-UCLA)Q00653
IntAct (EBI)Q00653
FunCoupENSG00000077150
BioGRIDNFKB2
InParanoidQ00653
Interologous Interaction database Q00653
IntegromeDBNFKB2
STRING (EMBL)NFKB2
Ontologies - Pathways
Ontology : AmiGOtoll-like receptor signaling pathway  follicular dendritic cell differentiation  germinal center formation  MyD88-dependent toll-like receptor signaling pathway  MyD88-independent toll-like receptor signaling pathway  DNA binding  sequence-specific DNA binding transcription factor activity  transcription coactivator activity  protein binding  nucleus  nucleoplasm  nucleolus  cytoplasm  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  extracellular matrix organization  positive regulation of type I interferon production  Bcl3/NF-kappaB2 complex  toll-like receptor 2 signaling pathway  toll-like receptor 3 signaling pathway  toll-like receptor 4 signaling pathway  toll-like receptor 5 signaling pathway  toll-like receptor 9 signaling pathway  toll-like receptor 10 signaling pathway  TRIF-dependent toll-like receptor signaling pathway  toll-like receptor TLR1:TLR2 signaling pathway  toll-like receptor TLR6:TLR2 signaling pathway  innate immune response  spleen development  positive regulation of NF-kappaB transcription factor activity  
Ontology : EGO-EBItoll-like receptor signaling pathway  follicular dendritic cell differentiation  germinal center formation  MyD88-dependent toll-like receptor signaling pathway  MyD88-independent toll-like receptor signaling pathway  DNA binding  sequence-specific DNA binding transcription factor activity  transcription coactivator activity  protein binding  nucleus  nucleoplasm  nucleolus  cytoplasm  cytosol  transcription, DNA-templated  regulation of transcription, DNA-templated  extracellular matrix organization  positive regulation of type I interferon production  Bcl3/NF-kappaB2 complex  toll-like receptor 2 signaling pathway  toll-like receptor 3 signaling pathway  toll-like receptor 4 signaling pathway  toll-like receptor 5 signaling pathway  toll-like receptor 9 signaling pathway  toll-like receptor 10 signaling pathway  TRIF-dependent toll-like receptor signaling pathway  toll-like receptor TLR1:TLR2 signaling pathway  toll-like receptor TLR6:TLR2 signaling pathway  innate immune response  spleen development  positive regulation of NF-kappaB transcription factor activity  
Pathways : KEGGMAPK signaling pathway    NF-kappa B signaling pathway    Osteoclast differentiation    Legionellosis    HTLV-I infection    Epstein-Barr virus infection    Pathways in cancer    Viral carcinogenesis   
Protein Interaction DatabaseNFKB2
Wikipedia pathwaysNFKB2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)NFKB2
snp3D : Map Gene to Disease4791
SNP (GeneSNP Utah)NFKB2
SNP : HGBaseNFKB2
Genetic variants : HAPMAPNFKB2
Exome VariantNFKB2
1000_GenomesNFKB2 
ICGC programENSG00000077150 
Cancer Gene: CensusNFKB2 
Somatic Mutations in Cancer : COSMICNFKB2 
CONAN: Copy Number AnalysisNFKB2 
Mutations and Diseases : HGMDNFKB2
Mutations and Diseases : intOGenNFKB2
Genomic VariantsNFKB2  NFKB2 [DGVbeta]
dbVarNFKB2
ClinVarNFKB2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM164012    615577   
MedgenNFKB2
GENETestsNFKB2
Disease Genetic AssociationNFKB2
Huge Navigator NFKB2 [HugePedia]  NFKB2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneNFKB2
Homology/Alignments : Family Browser (UCSC)NFKB2
Phylogenetic Trees/Animal Genes : TreeFamNFKB2
Chemical/Protein Interactions : CTD4791
Chemical/Pharm GKB GenePA31600
Clinical trialNFKB2
Cancer Resource (Charite)ENSG00000077150
Other databases
Probes
Litterature
PubMed251 Pubmed reference(s) in Entrez
CoreMineNFKB2
iHOPNFKB2
OncoSearchNFKB2

Bibliography

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Baldwin AS Jr
Annual review of immunology. 1996 ; 14 : 649-683.
PMID 8717528
 
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PMID 9597130
 
New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases.
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PMID 9895331
 
The generation of nfkb2 p52: mechanism and efficiency.
Heusch M, Lin L, Geleziunas R, Greene WC
Oncogene. 1999 ; 18 (46) : 6201-6208.
PMID 10597218
 
Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway.
Senftleben U, Cao Y, Xiao G, Greten FR, Krˆ§hn 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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written01-2002Fei Chen

Citation

This paper should be referenced as such :
Chen, F
NFKB2 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 2)
Atlas Genet Cytogenet Oncol Haematol. 2002;6(2):98-99.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/NFKB2ID362.html

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indexed on : Tue Aug 26 15:24:57 CEST 2014

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