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Q63369

- NFKB1_RAT

UniProt

Q63369 - NFKB1_RAT

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Protein

Nuclear factor NF-kappa-B p105 subunit

Gene
Nfkb1
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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.

GO - Molecular functioni

  1. double-stranded DNA binding Source: RGD
  2. heat shock protein binding Source: RGD
  3. protein binding Source: IntAct
  4. sequence-specific DNA binding Source: RGD
  5. sequence-specific DNA binding transcription factor activity Source: RGD
  6. transcription regulatory region sequence-specific DNA binding Source: RGD

GO - Biological processi

  1. cellular response to interleukin-1 Source: Ensembl
  2. cellular response to mechanical stimulus Source: Ensembl
  3. negative regulation of apoptotic process Source: RGD
  4. negative regulation of calcidiol 1-monooxygenase activity Source: Ensembl
  5. negative regulation of cytokine production Source: Ensembl
  6. negative regulation of inflammatory response Source: Ensembl
  7. negative regulation of interleukin-12 biosynthetic process Source: Ensembl
  8. negative regulation of transcription, DNA-templated Source: Ensembl
  9. positive regulation of canonical Wnt signaling pathway Source: Ensembl
  10. positive regulation of hyaluronan biosynthetic process Source: Ensembl
  11. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  12. response to bacterium Source: RGD
  13. response to copper ion Source: RGD
  14. response to oxidative stress Source: RGD
  15. signal transduction Source: InterPro
  16. transcription, DNA-templated Source: UniProtKB-KW
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.

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. mitochondrion Source: Ensembl
  4. nucleus Source: RGD
  5. 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 subunit By similarityPRO_0000030315Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei225 – 2251(3S)-3-hydroxyasparagine; by HIF1AN By similarity
Modified residuei461 – 4611Phosphoserine; by GSK3-beta; in vitro By similarity
Modified residuei481 – 4811Phosphoserine; by IKKB By similarity
Modified residuei486 – 4861Phosphoserine; by IKKB By similarity
Modified residuei491 – 4911Phosphoserine By 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.

Keywords - PTMi

Hydroxylation, Phosphoprotein

Proteomic databases

PaxDbiQ63369.
PRIDEiQ63369.

PTM databases

PhosphoSiteiQ63369.

Expressioni

Gene expression databases

ArrayExpressiQ63369.
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.

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.

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 HIF1AN By 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.
Contains 1 death domain.

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

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REILNPPEKE TQGEGPSLFM ASTKTEAIAP ASTMEDKEED VGFQDNLFLE    50
KALQLAKRHA NALFDYAVTG DVKMLLAVQR HLTAVQDENG DSVLHLAIIH 100
LHAQLVRDLL EVTSGSISDD IINMRNDLYQ TPLHLAVITK QEDVVEDLLR 150
VGADLSLLDR WGNSVLHLAA KEGHDKILGV LLKNSKAALL INHPNGEGLN 200
AIHIAVMSNS LSCLQLLVAA GAEVNAQEQK SGRTALHLAV EYDNISLAGC 250
LLLEGDALVD STTYDGTTPL HIAAGRGSTR LAALLKAAGA DPLVENFEPL 300
YDLDDSWEKA GEDEGVVPGT TPLDMAANWQ VFDILNGKPY EPVFTSDDIL 350
PQGDIKQLTE DTRLQLCKLL EIPDPDKNWA TLAQKLGLGI LNNAFRLSPA 400
PSKTLMDNYE VSGGTIKELV EALRQMGYTE AIEVIQAAFR TPETTASSPV 450
TTAQAHLLPL SSSSTRQHID ELRDNDSVCD SGVETSFRKL SFSESLTGDG 500
PLLSLNKMPH NYGQDGPIEG KI 522
Length:522
Mass (Da):56,554
Last modified:November 1, 1997 - v1
Checksum:i12D89EE61E3163E2
GO

Non-terminal residue

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L26267 mRNA. Translation: AAA20684.1.
PIRiI67414.
UniGeneiRn.2411.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
L26267 mRNA. Translation: AAA20684.1 .
PIRi I67414.
UniGenei Rn.2411.

3D structure databases

ProteinModelPortali Q63369.
SMRi Q63369. Positions 353-436.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q63369. 3 interactions.
MINTi MINT-2739834.
STRINGi 10116.ENSRNOP00000028944.

PTM databases

PhosphoSitei Q63369.

Proteomic databases

PaxDbi Q63369.
PRIDEi Q63369.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Organism-specific databases

RGDi 70498. Nfkb1.

Phylogenomic databases

eggNOGi COG0666.
HOGENOMi HOG000004822.
HOVERGENi HBG052613.
InParanoidi Q63369.

Enzyme and pathway databases

Reactomei REACT_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.

Gene expression databases

ArrayExpressi Q63369.
Genevestigatori Q63369.

Family and domain databases

Gene3Di 1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
InterProi IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
[Graphical view ]
Pfami PF00023. Ank. 1 hit.
PF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
[Graphical view ]
PRINTSi PR01415. ANKYRIN.
SMARTi SM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
[Graphical view ]
SUPFAMi SSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
PROSITEi PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 4 hits.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 118 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

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