Homo sapiens Protein: NFKB2 | |||||||||||||||||||||||||||||||||||||
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Summary | |||||||||||||||||||||||||||||||||||||
InnateDB Protein | IDBP-384889.5 | ||||||||||||||||||||||||||||||||||||
Last Modified | 2014-10-13 [Report errors or provide feedback] | ||||||||||||||||||||||||||||||||||||
Gene Symbol | NFKB2 | ||||||||||||||||||||||||||||||||||||
Protein Name | nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (p49/p100) | ||||||||||||||||||||||||||||||||||||
Synonyms | CVID10; H2TF1; LYT-10; LYT10; NF-kB2; p100; p52; | ||||||||||||||||||||||||||||||||||||
Species | Homo sapiens | ||||||||||||||||||||||||||||||||||||
Ensembl Protein | ENSP00000410256 | ||||||||||||||||||||||||||||||||||||
InnateDB Gene | IDBG-87893 (NFKB2) | ||||||||||||||||||||||||||||||||||||
Protein Structure | |||||||||||||||||||||||||||||||||||||
UniProt Annotation | |||||||||||||||||||||||||||||||||||||
Function | NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related to many biological processes such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF- kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. In a non-canonical activation pathway, the MAP3K14- activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK- ARNTL/BMAL1 heterodimer. {ECO:0000269PubMed:7925301}. | ||||||||||||||||||||||||||||||||||||
Subcellular Localization | Nucleus. Cytoplasm. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B). | ||||||||||||||||||||||||||||||||||||
Disease Associations | Note=A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant.Note=A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which codes for a truncated 80 kDa protein (p80HT).Note=In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.Immunodeficiency, common variable, 10 (CVID10) [MIM:615577]: A primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B-cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency. {ECO:0000269PubMed:24140114}. Note=The disease is caused by mutations affecting the gene represented in this entry. | ||||||||||||||||||||||||||||||||||||
Tissue Specificity | |||||||||||||||||||||||||||||||||||||
Comments | |||||||||||||||||||||||||||||||||||||
Interactions | |||||||||||||||||||||||||||||||||||||
Number of Interactions |
This gene and/or its encoded proteins are associated with 123 experimentally validated interaction(s) in this database.
They are also associated with 17 interaction(s) predicted by orthology.
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Gene Ontology | |||||||||||||||||||||||||||||||||||||
Molecular Function |
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Biological Process |
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Cellular Component |
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Protein Structure and Domains | |||||||||||||||||||||||||||||||||||||
PDB ID | |||||||||||||||||||||||||||||||||||||
InterPro |
IPR000451
NF-kappa-B/Rel/Dorsal IPR000488 Death domain IPR002110 Ankyrin repeat IPR002909 IPT domain IPR008967 p53-like transcription factor, DNA-binding IPR011029 Death-like domain IPR011539 Rel homology domain IPR014756 Immunoglobulin E-set IPR020683 Ankyrin repeat-containing domain |
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PFAM |
PF00531
PF00023 PF13606 PF01833 PF00554 PF11929 PF12796 |
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PRINTS |
PR00057
PR01415 |
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PIRSF | |||||||||||||||||||||||||||||||||||||
SMART |
SM00005
SM00248 SM00429 |
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TIGRFAMs | |||||||||||||||||||||||||||||||||||||
Post-translational Modifications | |||||||||||||||||||||||||||||||||||||
Modification | |||||||||||||||||||||||||||||||||||||
Cross-References | |||||||||||||||||||||||||||||||||||||
SwissProt | Q00653 | ||||||||||||||||||||||||||||||||||||
PhosphoSite | PhosphoSite-Q00653 | ||||||||||||||||||||||||||||||||||||
TrEMBL | M0R119 | ||||||||||||||||||||||||||||||||||||
UniProt Splice Variant | |||||||||||||||||||||||||||||||||||||
Entrez Gene | 4791 | ||||||||||||||||||||||||||||||||||||
UniGene | Hs.742532 | ||||||||||||||||||||||||||||||||||||
RefSeq | NP_001275653 | ||||||||||||||||||||||||||||||||||||
HUGO | HGNC:7795 | ||||||||||||||||||||||||||||||||||||
OMIM | 164012 | ||||||||||||||||||||||||||||||||||||
CCDS | CCDS41565 | ||||||||||||||||||||||||||||||||||||
HPRD | 01239 | ||||||||||||||||||||||||||||||||||||
IMGT | |||||||||||||||||||||||||||||||||||||
EMBL | AK292654 AL121928 AY865619 BC002844 BT009769 CH471066 S76638 U09609 U20816 X61498 X61499 | ||||||||||||||||||||||||||||||||||||
GenPept | AAA21462 AAA68171 AAB21124 AAH02844 AAP88771 AAW56071 BAF85343 CAA43715 CAA43716 CAC08399 EAW49700 EAW49701 EAW49702 EAW49704 EAW49706 | ||||||||||||||||||||||||||||||||||||