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Q63369 (NFKB1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Nuclear factor NF-kappa-B p50 subunit
Gene names
Name:Nfkb1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length522 AA.
Sequence statusFragment.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Isoform 5 isoform 6and isoform 7act 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.

Subunit structure

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.

Subcellular location

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.

Domain

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

Post-translational modification

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.

Sequence similarities

Contains 7 ANK repeats.

Contains 1 death domain.

Contains 1 RHD (Rel-like) domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DomainANK repeat
Repeat
   LigandDNA-binding
   Molecular functionActivator
   PTMHydroxylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

cellular response to mechanical stimulus

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 16354757. Source: RGD

negative regulation of calcidiol 1-monooxygenase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of cytokine production

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-12 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of hyaluronan biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

response to bacterium

Inferred from expression pattern PubMed 15777838. Source: RGD

response to copper ion

Inferred from expression pattern PubMed 17418555. Source: RGD

response to oxidative stress

Inferred from direct assay PubMed 12193536. Source: RGD

signal transduction

Inferred from electronic annotation. Source: InterPro

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 12193536. Source: RGD

cytosol

Inferred from direct assay PubMed 16135962. Source: RGD

mitochondrion

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 16135962PubMed 9343439. Source: RGD

protein complex

Inferred from direct assay PubMed 10620707PubMed 16135962PubMed 9343439. Source: RGD

   Molecular_functiondouble-stranded DNA binding

Inferred from direct assay PubMed 14576180. Source: RGD

heat shock protein binding

Inferred from physical interaction PubMed 16135962. Source: RGD

protein binding

Inferred from physical interaction PubMed 16642037. Source: IntAct

sequence-specific DNA binding

Inferred from direct assay PubMed 16135962. Source: RGD

sequence-specific DNA binding transcription factor activity

Traceable author statement PubMed 12193536. Source: RGD

transcription regulatory region sequence-specific DNA binding

Inferred from direct assay PubMed 14576180. Source: RGD

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain‹1 – 522›522Nuclear factor NF-kappa-B p105 subunit
PRO_0000030314
Chain‹1 – 32›32Nuclear factor NF-kappa-B p50 subunit By similarity
PRO_0000030315

Regions

Repeat89 – 11931ANK 1
Repeat128 – 15730ANK 2
Repeat161 – 19030ANK 3
Repeat197 – 22630ANK 4
Repeat231 – 26030ANK 5
Repeat265 – 29430ANK 6
Repeat318 – 34831ANK 7
Domain352 – 43988Death
Region197 – 23135Essential for interaction with HIF1AN By similarity

Amino acid modifications

Modified residue2251(3S)-3-hydroxyasparagine; by HIF1AN By similarity
Modified residue4611Phosphoserine; by GSK3-beta; in vitro By similarity
Modified residue4811Phosphoserine; by IKKB By similarity
Modified residue4861Phosphoserine; by IKKB By similarity
Modified residue4911Phosphoserine By similarity

Experimental info

Non-terminal residue11

Sequences

Sequence LengthMass (Da)Tools
Q63369 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 12D89EE61E3163E2

FASTA52256,554
        10         20         30         40         50         60 
REILNPPEKE TQGEGPSLFM ASTKTEAIAP ASTMEDKEED VGFQDNLFLE KALQLAKRHA 

        70         80         90        100        110        120 
NALFDYAVTG DVKMLLAVQR HLTAVQDENG DSVLHLAIIH LHAQLVRDLL EVTSGSISDD 

       130        140        150        160        170        180 
IINMRNDLYQ TPLHLAVITK QEDVVEDLLR VGADLSLLDR WGNSVLHLAA KEGHDKILGV 

       190        200        210        220        230        240 
LLKNSKAALL INHPNGEGLN AIHIAVMSNS LSCLQLLVAA GAEVNAQEQK SGRTALHLAV 

       250        260        270        280        290        300 
EYDNISLAGC LLLEGDALVD STTYDGTTPL HIAAGRGSTR LAALLKAAGA DPLVENFEPL 

       310        320        330        340        350        360 
YDLDDSWEKA GEDEGVVPGT TPLDMAANWQ VFDILNGKPY EPVFTSDDIL PQGDIKQLTE 

       370        380        390        400        410        420 
DTRLQLCKLL EIPDPDKNWA TLAQKLGLGI LNNAFRLSPA PSKTLMDNYE VSGGTIKELV 

       430        440        450        460        470        480 
EALRQMGYTE AIEVIQAAFR TPETTASSPV TTAQAHLLPL SSSSTRQHID ELRDNDSVCD 

       490        500        510        520 
SGVETSFRKL SFSESLTGDG PLLSLNKMPH NYGQDGPIEG KI 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L26267 mRNA. Translation: AAA20684.1.
PIRI67414.
UniGeneRn.2411.

3D structure databases

ProteinModelPortalQ63369.
SMRQ63369. Positions 353-436.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ63369. 3 interactions.
MINTMINT-2739834.
STRING10116.ENSRNOP00000028944.

PTM databases

PhosphoSiteQ63369.

Proteomic databases

PaxDbQ63369.
PRIDEQ63369.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

RGD70498. Nfkb1.

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000004822.
HOVERGENHBG052613.
InParanoidQ63369.

Gene expression databases

ArrayExpressQ63369.
GenevestigatorQ63369.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
[Graphical view]
PfamPF00023. Ank. 1 hit.
PF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
SMARTSM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 4 hits.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameNFKB1_RAT
AccessionPrimary (citable) accession number: Q63369
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1997
Last modified: June 11, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families