Q63369 (NFKB1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified April 3, 2013. Version 109. History...
Names and origin
|Protein names||Recommended name:|
Nuclear factor NF-kappa-B p105 subunit
DNA-binding factor KBF1
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
Cleaved into the following chain:
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||522 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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 and the heterodimeric p65-p50 complex appears to be most abundant one. 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. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur post-translationally. p50 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. Plays a role in the regulation of apoptosis. Isoform 5, isoform 6 and isoform 7 act as inhibitors of transactivation of p50 NF-kappa-B subunit, probably by sequestering it in the cytoplasm. Isoform 3 (p98) (but not p84 or p105) acts as a transactivator of NF-kappa-B-regulated gene expression. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105 By similarity.
Component of the NF-kappa-B p65-p50 complex. Component of the NF-kappa-B p65-p50 complex. Homodimer; component of the NF-kappa-B p50-p50 complex. Component of the NF-kappa-B p105-p50 complex. Component of the NF-kappa-B p50-c-Rel complex. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Also interacts with MAP3K8. NF-kappa-B p50 subunit interacts with NCOA3 coactivator, which may coactivate NF-kappa-B dependent expression via its histone acetyltransferase activity. Interacts with DSIPI; this interaction prevents nuclear translocation and DNA-binding. Interacts with SPAG9 and UNC5CL. NFKB1/p105 interacts with CFLAR; the interaction inhibits p105 processing into p50. NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2. Interacts with GSK3B; the interaction prevents processing of p105 to p50. NFKB1/p50 interacts with NFKBIE. NFKB1/p50 interacts with NFKBIZ. Nuclear factor NF-kappa-B p50 subunit interacts with NFKBID By similarity. Directly interacts with MEN1 By similarity. Interacts with HIF1AN By similarity.
The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding by p50 homodimers, and/or transcription activation.
While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p50 making it an acceptable substrate for the proteasome. This process is known as cotranslational processing. The processed form is active and the unprocessed form acts as an inhibitor (I kappa B-like), being able to form cytosolic complexes with NF-kappa B, trapping it in the cytoplasm. Complete folding of the region downstream of the GRR repeat precludes processing By similarity.
Contains 7 ANK repeats.
Contains 1 death domain.
Contains 1 RHD (Rel-like) domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||‹1 – 522||›522||Nuclear factor NF-kappa-B p105 subunit||PRO_0000030314|
|Chain||‹1 – 32||›32||Nuclear factor NF-kappa-B p50 subunit By similarity||PRO_0000030315|
|Repeat||89 – 119||31||ANK 1|
|Repeat||128 – 157||30||ANK 2|
|Repeat||161 – 190||30||ANK 3|
|Repeat||197 – 226||30||ANK 4|
|Repeat||231 – 260||30||ANK 5|
|Repeat||265 – 294||30||ANK 6|
|Repeat||318 – 348||31||ANK 7|
|Domain||352 – 439||88||Death|
|Region||197 – 231||35||Essential for interaction with HIF1AN By similarity|
Amino acid modifications
|Modified residue||225||1||(3S)-3-hydroxyasparagine; by HIF1AN By similarity|
|Modified residue||461||1||Phosphoserine; by GSK3-beta; in vitro By similarity|
|Modified residue||481||1||Phosphoserine; by IKKB By similarity|
|Modified residue||486||1||Phosphoserine; by IKKB By similarity|
|Modified residue||491||1||Phosphoserine By similarity|
|||"Cloning of rat Sertoli cell follicle-stimulating hormone primary response complementary deoxyribonucleic acid: regulation of TSC-22 gene expression."|
Hamil K.G., Hall S.H.
Endocrinology 134:1205-1212(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|+||Additional computationally mapped references.|
|L26267 mRNA. Translation: AAA20684.1.|
3D structure databases
|SMR||Q63369. Positions 353-436. |
Protein-protein interaction databases
Protocols and materials databases
|RGD||70498. Nfkb1. |
Gene expression databases
|GermOnline||ENSRNOG00000023258. Rattus norvegicus. |
Family and domain databases
|Gene3D||1.10.533.10. 1 hit. |
184.108.40.206. 1 hit.
|InterPro||IPR002110. Ankyrin_rpt. |
|Pfam||PF12796. Ank_2. 2 hits. |
PF00531. Death. 1 hit.
|PRINTS||PR01415. ANKYRIN. |
|SMART||SM00248. ANK. 6 hits. |
SM00005. DEATH. 1 hit.
|SUPFAM||SSF48403. ANK. 1 hit. |
SSF47986. DEATH_like. 1 hit.
|PROSITE||PS50297. ANK_REP_REGION. 1 hit. |
PS50088. ANK_REPEAT. 4 hits.
PS50017. DEATH_DOMAIN. False negative.
PS01204. REL_1. Partial match.
PS50254. REL_2. Partial match.
|Accession||Primary (citable) accession number: Q63369|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families