NFKB1_RAT
ID NFKB1_RAT Reviewed; 522 AA.
AC Q63369;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Nuclear factor NF-kappa-B p105 subunit;
DE AltName: Full=DNA-binding factor KBF1;
DE AltName: Full=EBP-1;
DE AltName: Full=Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1;
DE Contains:
DE RecName: Full=Nuclear factor NF-kappa-B p50 subunit;
DE Flags: Fragment;
GN Name=Nfkb1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=8161377; DOI=10.1210/endo.134.3.8161377;
RA Hamil K.G., Hall S.H.;
RT "Cloning of rat Sertoli cell follicle-stimulating hormone primary response
RT complementary deoxyribonucleic acid: regulation of TSC-22 gene
RT expression.";
RL Endocrinology 134:1205-1212(1994).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-306, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: NF-kappa-B is a pleiotropic transcription factor present in
CC almost all cell types and is the endpoint of a series of signal
CC transduction events that are initiated by a vast array of stimuli
CC related to many biological processes such as inflammation, immunity,
CC differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B
CC is a homo- or heterodimeric complex formed by the Rel-like domain-
CC containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and
CC NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most
CC abundant one. The dimers bind at kappa-B sites in the DNA of their
CC target genes and the individual dimers have distinct preferences for
CC different kappa-B sites that they can bind with distinguishable
CC affinity and specificity. Different dimer combinations act as
CC transcriptional activators or repressors, respectively. NF-kappa-B is
CC controlled by various mechanisms of post-translational modification and
CC subcellular compartmentalization as well as by interactions with other
CC cofactors or corepressors. NF-kappa-B complexes are held in the
CC cytoplasm in an inactive state complexed with members of the NF-kappa-B
CC inhibitor (I-kappa-B) family. In a conventional activation pathway, I-
CC kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to
CC different activators, subsequently degraded thus liberating the active
CC NF-kappa-B complex which translocates to the nucleus. NF-kappa-B
CC heterodimeric p65-p50 and RelB-p50 complexes are transcriptional
CC activators. The NF-kappa-B p50-p50 homodimer is a transcriptional
CC repressor, but can act as a transcriptional activator when associated
CC with BCL3. NFKB1 appears to have dual functions such as cytoplasmic
CC retention of attached NF-kappa-B proteins by p105 and generation of p50
CC by a cotranslational processing. The proteasome-mediated process
CC ensures the production of both p50 and p105 and preserves their
CC independent function, although processing of NFKB1/p105 also appears to
CC occur post-translationally. p50 binds to the kappa-B consensus sequence
CC 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in
CC immune response and acute phase reactions. Plays a role in the
CC regulation of apoptosis. Isoform 5, isoform 6 and isoform 7 act as
CC inhibitors of transactivation of p50 NF-kappa-B subunit, probably by
CC sequestering it in the cytoplasm. Isoform 3 (p98) (but not p84 or p105)
CC acts as a transactivator of NF-kappa-B-regulated gene expression. In a
CC complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK
CC signaling; active MAP3K8 is released by proteasome-dependent
CC degradation of NFKB1/p105 (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Component of the NF-kappa-B p65-p50 complex (By similarity).
CC Homodimer; component of the NF-kappa-B p50-p50 complex (By similarity).
CC Component of the NF-kappa-B p105-p50 complex (By similarity). Component
CC of the NF-kappa-B p50-c-Rel complex (By similarity). Component of a
CC complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3 (By
CC similarity). Also interacts with MAP3K8 (By similarity). NF-kappa-B p50
CC subunit interacts with NCOA3 coactivator, which may coactivate NF-
CC kappa-B dependent expression via its histone acetyltransferase activity
CC (By similarity). Interacts with DSIPI; this interaction prevents
CC nuclear translocation and DNA-binding (By similarity). Interacts with
CC SPAG9 and UNC5CL (By similarity). NFKB1/p105 interacts with CFLAR; the
CC interaction inhibits p105 processing into p50 (By similarity).
CC NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2 (By
CC similarity). Interacts with GSK3B; the interaction prevents processing
CC of p105 to p50 (By similarity). NFKB1/p50 interacts with NFKBIE (By
CC similarity). NFKB1/p50 interacts with NFKBIZ. Nuclear factor NF-kappa-B
CC p50 subunit interacts with NFKBID (By similarity). Directly interacts
CC with MEN1 (By similarity). Interacts with HIF1AN (By similarity).
CC Interacts with FEM1A; interaction is direct (By similarity).
CC {ECO:0000250|UniProtKB:P19838, ECO:0000250|UniProtKB:P25799}.
CC -!- INTERACTION:
CC Q63369; P47196: Akt1; NbExp=9; IntAct=EBI-8498561, EBI-7204362;
CC Q63369; Q99N34: Dffb; NbExp=2; IntAct=EBI-8498561, EBI-8498730;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Note=Nuclear, but also found in the cytoplasm in an inactive form
CC complexed to an inhibitor (I-kappa-B). {ECO:0000250}.
CC -!- DOMAIN: The C-terminus of p105 might be involved in cytoplasmic
CC retention, inhibition of DNA-binding by p50 homodimers, and/or
CC transcription activation.
CC -!- PTM: While translation occurs, the particular unfolded structure after
CC the GRR repeat promotes the generation of p50 making it an acceptable
CC substrate for the proteasome. This process is known as cotranslational
CC processing. The processed form is active and the unprocessed form acts
CC as an inhibitor (I kappa B-like), being able to form cytosolic
CC complexes with NF-kappa B, trapping it in the cytoplasm. Complete
CC folding of the region downstream of the GRR repeat precludes processing
CC (By similarity). {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L26267; AAA20684.1; -; mRNA.
DR PIR; I67414; I67414.
DR AlphaFoldDB; Q63369; -.
DR SMR; Q63369; -.
DR CORUM; Q63369; -.
DR IntAct; Q63369; 3.
DR MINT; Q63369; -.
DR STRING; 10116.ENSRNOP00000028944; -.
DR iPTMnet; Q63369; -.
DR PaxDb; Q63369; -.
DR PeptideAtlas; Q63369; -.
DR PRIDE; Q63369; -.
DR RGD; 70498; Nfkb1.
DR eggNOG; KOG0504; Eukaryota.
DR InParanoid; Q63369; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0042805; F:actinin binding; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:RGD.
DR GO; GO:0031072; F:heat shock protein binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IDA:RGD.
DR GO; GO:1904385; P:cellular response to angiotensin; ISO:RGD.
DR GO; GO:1990416; P:cellular response to brain-derived neurotrophic factor stimulus; IDA:RGD.
DR GO; GO:0071322; P:cellular response to carbohydrate stimulus; IDA:RGD.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:MGI.
DR GO; GO:1904630; P:cellular response to diterpene; IDA:RGD.
DR GO; GO:0071359; P:cellular response to dsRNA; ISO:RGD.
DR GO; GO:1904632; P:cellular response to glucoside; IDA:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:RGD.
DR GO; GO:0071354; P:cellular response to interleukin-6; ISO:RGD.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IDA:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR GO; GO:0071316; P:cellular response to nicotine; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:MGI.
DR GO; GO:1901653; P:cellular response to peptide; IDA:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IDA:RGD.
DR GO; GO:0098586; P:cellular response to virus; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0007254; P:JNK cascade; ISO:RGD.
DR GO; GO:0002523; P:leukocyte migration involved in inflammatory response; IEP:RGD.
DR GO; GO:0000165; P:MAPK cascade; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0010956; P:negative regulation of calcidiol 1-monooxygenase activity; ISO:RGD.
DR GO; GO:0001818; P:negative regulation of cytokine production; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR GO; GO:0032695; P:negative regulation of interleukin-12 production; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:RGD.
DR GO; GO:1900127; P:positive regulation of hyaluronan biosynthetic process; ISO:RGD.
DR GO; GO:2000630; P:positive regulation of miRNA metabolic process; ISO:RGD.
DR GO; GO:1902895; P:positive regulation of miRNA transcription; IMP:BHF-UCL.
DR GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0009617; P:response to bacterium; IEP:RGD.
DR GO; GO:0046688; P:response to copper ion; IEP:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0035994; P:response to muscle stretch; ISO:RGD.
DR GO; GO:0014070; P:response to organic cyclic compound; IDA:RGD.
DR GO; GO:0006979; P:response to oxidative stress; IDA:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR030503; NF-kB_p105.
DR InterPro; IPR000451; NFkB/Dor.
DR PANTHER; PTHR24169; PTHR24169; 1.
DR PANTHER; PTHR24169:SF9; PTHR24169:SF9; 1.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF00531; Death; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 6.
DR SMART; SM00005; DEATH; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
PE 1: Evidence at protein level;
KW Activator; ANK repeat; Cytoplasm; DNA-binding; Hydroxylation; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; Transcription;
KW Transcription regulation.
FT CHAIN <1..522
FT /note="Nuclear factor NF-kappa-B p105 subunit"
FT /id="PRO_0000030314"
FT CHAIN <1..32
FT /note="Nuclear factor NF-kappa-B p50 subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000030315"
FT REPEAT 89..119
FT /note="ANK 1"
FT REPEAT 128..157
FT /note="ANK 2"
FT REPEAT 161..190
FT /note="ANK 3"
FT REPEAT 197..226
FT /note="ANK 4"
FT REPEAT 231..260
FT /note="ANK 5"
FT REPEAT 265..294
FT /note="ANK 6"
FT REPEAT 318..348
FT /note="ANK 7"
FT DOMAIN 352..439
FT /note="Death"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 197..231
FT /note="Essential for interaction with HIF1AN"
FT /evidence="ECO:0000250"
FT MOD_RES 225
FT /note="(3S)-3-hydroxyasparagine; by HIF1AN"
FT /evidence="ECO:0000250"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19838"
FT MOD_RES 461
FT /note="Phosphoserine; by GSK3-beta; in vitro"
FT /evidence="ECO:0000250|UniProtKB:P19838"
FT MOD_RES 481
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000250|UniProtKB:P19838"
FT MOD_RES 486
FT /note="Phosphoserine; by IKKB"
FT /evidence="ECO:0000250|UniProtKB:P19838"
FT MOD_RES 491
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P19838"
FT MOD_RES 497
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P25799"
FT NON_TER 1
SQ SEQUENCE 522 AA; 56554 MW; 12D89EE61E3163E2 CRC64;
REILNPPEKE TQGEGPSLFM ASTKTEAIAP ASTMEDKEED VGFQDNLFLE KALQLAKRHA
NALFDYAVTG DVKMLLAVQR HLTAVQDENG DSVLHLAIIH LHAQLVRDLL EVTSGSISDD
IINMRNDLYQ TPLHLAVITK QEDVVEDLLR VGADLSLLDR WGNSVLHLAA KEGHDKILGV
LLKNSKAALL INHPNGEGLN AIHIAVMSNS LSCLQLLVAA GAEVNAQEQK SGRTALHLAV
EYDNISLAGC LLLEGDALVD STTYDGTTPL HIAAGRGSTR LAALLKAAGA DPLVENFEPL
YDLDDSWEKA GEDEGVVPGT TPLDMAANWQ VFDILNGKPY EPVFTSDDIL PQGDIKQLTE
DTRLQLCKLL EIPDPDKNWA TLAQKLGLGI LNNAFRLSPA PSKTLMDNYE VSGGTIKELV
EALRQMGYTE AIEVIQAAFR TPETTASSPV TTAQAHLLPL SSSSTRQHID ELRDNDSVCD
SGVETSFRKL SFSESLTGDG PLLSLNKMPH NYGQDGPIEG KI
