Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q63369

- NFKB1_RAT

UniProt

Q63369 - NFKB1_RAT

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Nov 1997)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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. 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

    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

    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 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

    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.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

    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

    Experimental Info

    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: October 1, 2014
    This is version 119 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