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Protein

Nuclear factor NF-kappa-B p105 subunit

Gene

Nfkb1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  1. chromatin binding Source: GO_Central
  2. double-stranded DNA binding Source: RGD
  3. heat shock protein binding Source: RGD
  4. RNA polymerase II regulatory region sequence-specific DNA binding Source: GO_Central
  5. sequence-specific DNA binding Source: RGD
  6. sequence-specific DNA binding RNA polymerase II transcription factor activity Source: GO_Central
  7. sequence-specific DNA binding transcription factor activity Source: RGD
  8. transcription regulatory region sequence-specific DNA binding Source: RGD

GO - Biological processi

  1. cellular response to interleukin-1 Source: Ensembl
  2. cellular response to interleukin-6 Source: Ensembl
  3. cellular response to lipopolysaccharide Source: Ensembl
  4. cellular response to mechanical stimulus Source: Ensembl
  5. cellular response to nicotine Source: Ensembl
  6. cellular response to peptide hormone stimulus Source: Ensembl
  7. I-kappaB kinase/NF-kappaB signaling Source: GO_Central
  8. inflammatory response Source: GO_Central
  9. innate immune response Source: GO_Central
  10. negative regulation of apoptotic process Source: RGD
  11. negative regulation of calcidiol 1-monooxygenase activity Source: Ensembl
  12. negative regulation of inflammatory response Source: Ensembl
  13. negative regulation of interleukin-12 biosynthetic process Source: Ensembl
  14. negative regulation of transcription from RNA polymerase II promoter Source: GO_Central
  15. NIK/NF-kappaB signaling Source: GO_Central
  16. positive regulation of canonical Wnt signaling pathway Source: Ensembl
  17. positive regulation of hyaluronan biosynthetic process Source: Ensembl
  18. positive regulation of miRNA metabolic process Source: Ensembl
  19. positive regulation of transcription from RNA polymerase II promoter Source: GO_Central
  20. response to bacterium Source: RGD
  21. response to copper ion Source: RGD
  22. response to cytokine Source: GO_Central
  23. response to oxidative stress Source: RGD
  24. transcription from RNA polymerase II promoter Source: GOC
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_194364. RIP-mediated NFkB activation via ZBP1.
REACT_194748. Senescence-Associated Secretory Phenotype (SASP).
REACT_196375. Interleukin-1 processing.
REACT_197513. FCERI mediated NF-kB activation.
REACT_199247. Activation of NF-kappaB in B cells.
REACT_230213. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_239306. Regulated proteolysis of p75NTR.
REACT_240855. NF-kB is activated and signals survival.
REACT_248474. TRAF6 mediated NF-kB activation.
REACT_249972. Interleukin-1 signaling.
REACT_254949. Downstream TCR signaling.
REACT_260360. Transcriptional regulation of white adipocyte differentiation.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Unplaced

Organism-specific databases

RGDi70498. Nfkb1.

Subcellular locationi

Nucleus By similarity. Cytoplasm By similarity
Note: Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B).By similarity

GO - Cellular componenti

  1. cytoplasm Source: RGD
  2. cytosol Source: RGD
  3. I-kappaB/NF-kappaB complex Source: GO_Central
  4. mitochondrion Source: Ensembl
  5. nucleoplasm Source: GO_Central
  6. nucleus Source: RGD
  7. protein complex Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – 522›522Nuclear factor NF-kappa-B p105 subunitPRO_0000030314Add
BLAST
Chaini‹1 – 32›32Nuclear factor NF-kappa-B p50 subunitBy similarityPRO_0000030315Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei225 – 2251(3S)-3-hydroxyasparagine; by HIF1ANBy similarity
Modified residuei447 – 4471PhosphoserineBy similarity
Modified residuei461 – 4611Phosphoserine; by GSK3-beta; in vitroBy similarity
Modified residuei481 – 4811Phosphoserine; by IKKBBy similarity
Modified residuei486 – 4861Phosphoserine; by IKKBBy similarity
Modified residuei491 – 4911PhosphoserineBy similarity

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.
PRIDEiQ63369.

PTM databases

PhosphoSiteiQ63369.

Expressioni

Gene expression databases

ExpressionAtlasiQ63369. baseline and differential.
GenevestigatoriQ63369.

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

WithEntry#Exp.IntActNotes
Akt1P471969EBI-8498561,EBI-7204362
DffbQ99N342EBI-8498561,EBI-8498730

Protein-protein interaction databases

IntActiQ63369. 3 interactions.
MINTiMINT-2739834.
STRINGi10116.ENSRNOP00000028944.

Structurei

3D structure databases

ProteinModelPortaliQ63369.
SMRiQ63369. Positions 353-436.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati89 – 11931ANK 1Add
BLAST
Repeati128 – 15730ANK 2Add
BLAST
Repeati161 – 19030ANK 3Add
BLAST
Repeati197 – 22630ANK 4Add
BLAST
Repeati231 – 26030ANK 5Add
BLAST
Repeati265 – 29430ANK 6Add
BLAST
Repeati318 – 34831ANK 7Add
BLAST
Domaini352 – 43988DeathAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni197 – 23135Essential for interaction with HIF1ANBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 7 ANK repeats.PROSITE-ProRule annotation
Contains 1 death domain.Curated
Contains 1 RHD (Rel-like) domain.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiCOG0666.
HOGENOMiHOG000004822.
HOVERGENiHBG052613.
InParanoidiQ63369.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 4 hits.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

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

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliQ63369.
SMRiQ63369. Positions 353-436.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ63369. 3 interactions.
MINTiMINT-2739834.
STRINGi10116.ENSRNOP00000028944.

PTM databases

PhosphoSiteiQ63369.

Proteomic databases

PaxDbiQ63369.
PRIDEiQ63369.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

RGDi70498. Nfkb1.

Phylogenomic databases

eggNOGiCOG0666.
HOGENOMiHOG000004822.
HOVERGENiHBG052613.
InParanoidiQ63369.

Enzyme and pathway databases

ReactomeiREACT_194364. RIP-mediated NFkB activation via ZBP1.
REACT_194748. Senescence-Associated Secretory Phenotype (SASP).
REACT_196375. Interleukin-1 processing.
REACT_197513. FCERI mediated NF-kB activation.
REACT_199247. Activation of NF-kappaB in B cells.
REACT_230213. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
REACT_239306. Regulated proteolysis of p75NTR.
REACT_240855. NF-kB is activated and signals survival.
REACT_248474. TRAF6 mediated NF-kB activation.
REACT_249972. Interleukin-1 signaling.
REACT_254949. Downstream TCR signaling.
REACT_260360. Transcriptional regulation of white adipocyte differentiation.

Gene expression databases

ExpressionAtlasiQ63369. baseline and differential.
GenevestigatoriQ63369.

Family and domain databases

Gene3Di1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
[Graphical view]
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
SMARTiSM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "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].
    Strain: Sprague-Dawley.
    Tissue: Testis.

Entry informationi

Entry nameiNFKB1_RAT
AccessioniPrimary (citable) accession number: Q63369
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: March 4, 2015
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.