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Protein

Nuclear factor NF-kappa-B p105 subunit

Gene

Nfkb1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  • chromatin binding Source: GO_Central
  • DNA binding Source: MGI
  • DNA binding transcription factor activity Source: RGD
  • double-stranded DNA binding Source: RGD
  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: GO_Central
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: GO_Central
  • sequence-specific DNA binding Source: RGD
  • transcription regulatory region sequence-specific DNA binding Source: RGD

GO - Biological processi

  • cellular response to brain-derived neurotrophic factor stimulus Source: RGD
  • cellular response to carbohydrate stimulus Source: RGD
  • cellular response to cytokine stimulus Source: MGI
  • cellular response to diterpene Source: RGD
  • cellular response to glucoside Source: RGD
  • cellular response to interleukin-1 Source: RGD
  • cellular response to lipopolysaccharide Source: RGD
  • cellular response to organic cyclic compound Source: MGI
  • cellular response to peptide Source: RGD
  • cellular response to tumor necrosis factor Source: RGD
  • I-kappaB kinase/NF-kappaB signaling Source: GO_Central
  • inflammatory response Source: GO_Central
  • innate immune response Source: GO_Central
  • negative regulation of apoptotic process Source: RGD
  • negative regulation of transcription by RNA polymerase II Source: GO_Central
  • NIK/NF-kappaB signaling Source: GO_Central
  • positive regulation of gene expression Source: RGD
  • positive regulation of gene silencing by miRNA Source: BHF-UCL
  • positive regulation of pri-miRNA transcription by RNA polymerase II Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • response to bacterium Source: RGD
  • response to copper ion Source: RGD
  • response to organic cyclic compound Source: RGD
  • response to oxidative stress Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear factor NF-kappa-B p105 subunit
Alternative name(s):
DNA-binding factor KBF1
EBP-1
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
Cleaved into the following chain:
Gene namesi
Name:Nfkb1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi70498 Nfkb1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000030314‹1 – 522Nuclear factor NF-kappa-B p105 subunitAdd BLAST›522
ChainiPRO_0000030315‹1 – 32Nuclear factor NF-kappa-B p50 subunitBy similarityAdd BLAST›32

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei225(3S)-3-hydroxyasparagine; by HIF1ANBy similarity1
Modified residuei306PhosphoserineCombined sources1
Modified residuei447PhosphoserineBy similarity1
Modified residuei461Phosphoserine; by GSK3-beta; in vitroBy similarity1
Modified residuei481Phosphoserine; by IKKBBy similarity1
Modified residuei486Phosphoserine; by IKKBBy similarity1
Modified residuei491PhosphoserineBy similarity1
Modified residuei497PhosphothreonineBy similarity1

Post-translational modificationi

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).By similarity

Keywords - PTMi

Hydroxylation, Phosphoprotein

Proteomic databases

PaxDbiQ63369
PeptideAtlasiQ63369
PRIDEiQ63369

PTM databases

iPTMnetiQ63369

Interactioni

Subunit structurei

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).By similarity

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein heterodimerization activity Source: RGD
  • protein homodimerization activity Source: RGD

Protein-protein interaction databases

CORUMiQ63369
IntActiQ63369, 3 interactors
MINTiQ63369
STRINGi10116.ENSRNOP00000028944

Structurei

3D structure databases

ProteinModelPortaliQ63369
SMRiQ63369
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati89 – 119ANK 1Add BLAST31
Repeati128 – 157ANK 2Add BLAST30
Repeati161 – 190ANK 3Add BLAST30
Repeati197 – 226ANK 4Add BLAST30
Repeati231 – 260ANK 5Add BLAST30
Repeati265 – 294ANK 6Add BLAST30
Repeati318 – 348ANK 7Add BLAST31
Domaini352 – 439DeathAdd BLAST88

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni197 – 231Essential for interaction with HIF1ANBy similarityAdd BLAST35

Domaini

The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding by p50 homodimers, and/or transcription activation.

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
HOGENOMiHOG000004822
HOVERGENiHBG052613
InParanoidiQ63369

Family and domain databases

CDDicd00204 ANK, 2 hits
Gene3Di1.25.40.20, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR030503 NF-kB_p105
IPR000451 NFkB/Dor
PANTHERiPTHR24169 PTHR24169, 1 hit
PTHR24169:SF9 PTHR24169:SF9, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PF00531 Death, 1 hit
PRINTSiPR01415 ANKYRIN
SMARTiView protein in SMART
SM00248 ANK, 6 hits
SM00005 DEATH, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48403 SSF48403, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 4 hits

Sequencei

Sequence statusi: Fragment.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q63369-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
REILNPPEKE TQGEGPSLFM ASTKTEAIAP ASTMEDKEED VGFQDNLFLE
60 70 80 90 100
KALQLAKRHA NALFDYAVTG DVKMLLAVQR HLTAVQDENG DSVLHLAIIH
110 120 130 140 150
LHAQLVRDLL EVTSGSISDD IINMRNDLYQ TPLHLAVITK QEDVVEDLLR
160 170 180 190 200
VGADLSLLDR WGNSVLHLAA KEGHDKILGV LLKNSKAALL INHPNGEGLN
210 220 230 240 250
AIHIAVMSNS LSCLQLLVAA GAEVNAQEQK SGRTALHLAV EYDNISLAGC
260 270 280 290 300
LLLEGDALVD STTYDGTTPL HIAAGRGSTR LAALLKAAGA DPLVENFEPL
310 320 330 340 350
YDLDDSWEKA GEDEGVVPGT TPLDMAANWQ VFDILNGKPY EPVFTSDDIL
360 370 380 390 400
PQGDIKQLTE DTRLQLCKLL EIPDPDKNWA TLAQKLGLGI LNNAFRLSPA
410 420 430 440 450
PSKTLMDNYE VSGGTIKELV EALRQMGYTE AIEVIQAAFR TPETTASSPV
460 470 480 490 500
TTAQAHLLPL SSSSTRQHID ELRDNDSVCD SGVETSFRKL SFSESLTGDG
510 520
PLLSLNKMPH NYGQDGPIEG KI
Length:522
Mass (Da):56,554
Last modified:November 1, 1997 - v1
Checksum:i12D89EE61E3163E2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L26267 mRNA Translation: AAA20684.1
PIRiI67414
UniGeneiRn.2411

Similar proteinsi

Entry informationi

Entry nameiNFKB1_RAT
AccessioniPrimary (citable) accession number: Q63369
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: May 23, 2018
This is version 152 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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