Nfkb1
entrez
18033
canonical
uniprot
P25799
canonical
ensembl
ENSMUSG00000028163
resolver
ensp
ENSMUSP00000029812
resolver
genesymbol
Nfkb1
resolver
uniprot
B2RRQ6
resolver
uniprot
Q3TZE8
resolver
uniprot
Q3V2V6
resolver
uniprot
Q6TDG8
resolver
uniprot
Q75ZL1
resolver
uniprot
Q80Y21
resolver
uniprot
Q8C712
resolver
uniprot_entry
NFKB1_MOUSE
resolver
uniprot_sec
B2RRQ6
resolver
uniprot_sec
Q3TZE8
resolver
uniprot_sec
Q3V2V6
resolver
uniprot_sec
Q6TDG8
resolver
uniprot_sec
Q75ZL1
resolver
uniprot_sec
Q80Y21
resolver
uniprot_sec
Q8C712
resolver
amino_acid_sequence
MADDDPYGTGQMFHLNTALTHSIFNAELYSPEIPLSTDGPYLQILEQPKQRGFRFRYVCEGPSHGGLPGASSEKNKKSYPQVKICNYVGPAKVIVQLVTNGKNIHLHAHSLVGKHCEDGVCTVTAGPKDMVVGFANLGILHVTKKKVFETLEARMTEACIRGYNPGLLVHSDLAYLQAEGGGDRQLTDREKEIIRQAAVQQTKEMDLSVVRLMFTAFLPDSTGSFTRRLEPVVSDAIYDSKAPNASNLKIVRMDRTAGCVTGGEEIYLLCDKVQKDDIQIRFYEEEENGGVWEGFGDFSPTDVHRQFAIVFKTPKYKDVNITKPASVFVQLRRKSDLETSEPKPFLYYPEIKDKEEVQRKRQKLMPNFSDSFGGGSGAGAGGGGMFGSGGGGGSTGSPGPGYGYSNYGFPPYGGITFHPGVTKSNAGVTHGTINTKFKNGPKDCAKSDDEESLTLPEKETEGEGPSLPMACTKTEPIALASTMEDKEQDMGFQDNLFLEKALQLARRHANALFDYAVTGDVKMLLAVQRHLTAVQDENGDSVLHLAIIHLHAQLVRDLLEVTSGLISDDIINMRNDLYQTPLHLAVITKQEDVVEDLLRVGADLSLLDRWGNSVLHLAAKEGHDRILSILLKSRKAAPLIDHPNGEGLNAIHIAVMSNSLPCLLLLVAAGAEVNAQEQKSGRTALHLAVEYDNISLAGCLLLEGDAHVDSTTYDGTTPLHIAAGRGSTRLAALLKAAGADPLVENFEPLYDLDDSWEKAGEDEGVVPGTTPLDMAANWQVFDILNGKPYEPVFTSDDILPQGDMKQLTEDTRLQLCKLLEIPDPDKNWATLAQKLGLGILNNAFRLSPAPSKTLMDNYEVSGGTIKELMEALQQMGYTEAIEVIQAAFRTPATTASSPVTTAQVHCLPLSSSSTRQHIDELRDSDSVCDSGVETSFRKLSFTESLTGDSPLLSLNKMPHGYGQEGPIEGKI
uniprot
proteins
function
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 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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. {ECO:0000269|PubMed:11970948, ECO:0000269|PubMed:18270204, ECO:0000269|PubMed:2203532, ECO:0000269|PubMed:7530332, ECO:0000269|PubMed:9384558, ECO:0000269|PubMed:9450761}.; FUNCTION: [Nuclear factor NF-kappa-B p105 subunit]: P105 is the precursor of the active p50 subunit (Nuclear factor NF-kappa-B p50 subunit) of the nuclear factor NF-kappa-B. Acts as a cytoplasmic retention of attached NF-kappa-B proteins by p105. {ECO:0000250|UniProtKB:P19838}.; FUNCTION: [Nuclear factor NF-kappa-B p50 subunit]: Constitutes the active form, which associates with RELA/p65 to form the NF-kappa-B p65-p50 complex to form a transcription factor. Together with RELA/p65, 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. {ECO:0000250|UniProtKB:P19838}.; FUNCTION: [Isoform 3]: Isoform 3 (p98) (but not p84 or p105) acts as a transactivator of NF-kappa-B-regulated gene expression. {ECO:0000269|PubMed:7969179}.; FUNCTION: [Isoform 5]: Acts as an inhibitor of transactivation of p50 NF-kappa-B subunit, probably by sequestering it in the cytoplasm. {ECO:0000269|PubMed:1339305}.; FUNCTION: [Isoform 6]: Acts as an inhibitor of transactivation of p50 NF-kappa-B subunit, probably by sequestering it in the cytoplasm. {ECO:0000269|PubMed:8183915}.; FUNCTION: [Isoform 7]: Acts as an inhibitor of transactivation of p50 NF-kappa-B subunit, probably by sequestering it in the cytoplasm. {ECO:0000269|PubMed:8183915}.
uniprot
proteins
mass_dalton
105615
uniprot
proteins
post_translational_modification
PTM: Generation of the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) transcription factor takes place both cotranslationally and post-translationally via non-mutually exclusive mechanisms (By similarity). A cotranslational processing allows the production of both p50 and p105 (Nuclear factor NF-kappa-B p105 subunit) from a single NFKB1 mRNA (PubMed:9529257). While translation occurs, the particular unfolded structure after the GRR repeat region acts as a substrate for the proteasome, promoting degradation of the C-terminus (PubMed:9529257). The GRR acts as a proteasomal 'stop signal', protecting the region upstream of the GRR from degradation and promoting generation of p50 (PubMed:9529257). It is unclear if limited proteasome degradation during cotranslational processing depends on ubiquitination (PubMed:9529257). NF-kappa-B p50 is also generated post-translationally following ubiquitination by the KPC complex, leading to limited processing by the proteasome downstream of the GRR region, thereby generating p50 (By similarity). {ECO:0000250|UniProtKB:P19838, ECO:0000269|PubMed:9529257}.; PTM: [Nuclear factor NF-kappa-B p105 subunit]: Phosphorylation at the C-terminus by IKBKB/IKKB acts as a signal for ubiquitination and promotes either complete degradation or processing to generate the NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (By similarity). Phosphorylation at Ser-910 primes p105 for proteolytic processing in response to TNF stimulation (By similarity). Phosphorylation at Ser-926, Ser-930 and Ser-935 are required for BTRC/BTRCP-mediated ubiquitination and proteolysis (By similarity). Phosphorylation at Ser-930 is also required for ubiquitination by the KPC complex and limited processing to generate NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (By similarity). {ECO:0000250|UniProtKB:P19838}.; PTM: [Nuclear factor NF-kappa-B p105 subunit]: Polyubiquitinated at multiple Lys residues in the C-terminus (By similarity). Polyubiquitinated by the SCF(FBXW11) and SCF(BTRC) complexes following phosphorylation at Ser-926, Ser-930 and Ser-935, leading to its complete degradation (By similarity). In contrast, polyubiquitination by the KPC complex following phosphorylation at Ser-930 leads to limited proteosomal processing and generation of the active NF-kappa-B p50 (Nuclear factor NF-kappa-B p50 subunit) (By similarity). {ECO:0000250|UniProtKB:P19838}.; PTM: S-nitrosylation of Cys-59 affects DNA binding. {ECO:0000250|UniProtKB:P19838}.; PTM: The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation. {ECO:0000250|UniProtKB:P19838}.
uniprot
proteins
pubmed
11356851
uniprot
proteins
pubmed
11931770
uniprot
proteins
pubmed
11970948
uniprot
proteins
pubmed
11970949
uniprot
proteins
pubmed
12886018
uniprot
proteins
pubmed
1339305
uniprot
proteins
pubmed
15051764
uniprot
proteins
pubmed
15241416
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
17869269
uniprot
proteins
pubmed
18270204
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
2203532
uniprot
proteins
pubmed
7530332
uniprot
proteins
pubmed
7969179
uniprot
proteins
pubmed
8183915
uniprot
proteins
pubmed
8398903
uniprot
proteins
pubmed
9384558
uniprot
proteins
pubmed
9450761
uniprot
proteins
pubmed
9529257
uniprot
proteins
pubmed
9865694
uniprot
proteins
sequence_length
971
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: [Nuclear factor NF-kappa-B p105 subunit]: Cytoplasm {ECO:0000250|UniProtKB:P19838}.; SUBCELLULAR LOCATION: [Nuclear factor NF-kappa-B p50 subunit]: Nucleus {ECO:0000269|PubMed:9865694}. Cytoplasm {ECO:0000269|PubMed:9865694}. Note=Association with NFKBIA inhibitor (I-kappa-B), promotes its retention in the cytoplasm in an inactive form. Translocates into the nucleus following NFKBIA degradation. {ECO:0000269|PubMed:9865694}.; SUBCELLULAR LOCATION: [Isoform 5]: Cytoplasm {ECO:0000269|PubMed:1339305}.; SUBCELLULAR LOCATION: [Isoform 6]: Nucleus {ECO:0000269|PubMed:8183915}. Cytoplasm {ECO:0000269|PubMed:8183915}.; SUBCELLULAR LOCATION: [Isoform 7]: Nucleus {ECO:0000269|PubMed:8183915}.
uniprot
proteins