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Q9WTK5

- NFKB2_MOUSE

UniProt

Q9WTK5 - NFKB2_MOUSE

Protein

Nuclear factor NF-kappa-B p100 subunit

Gene

Nfkb2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    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. 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. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 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. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65 By similarity. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei454 – 4552Cleavage (when cotranslationally processed)

    GO - Molecular functioni

    1. DNA binding Source: UniProtKB-KW
    2. protein binding Source: IntAct
    3. sequence-specific DNA binding transcription factor activity Source: InterPro

    GO - Biological processi

    1. extracellular matrix organization Source: MGI
    2. follicular dendritic cell differentiation Source: MGI
    3. germinal center formation Source: MGI
    4. lymph node development Source: MGI
    5. NIK/NF-kappaB signaling Source: MGI
    6. spleen development Source: MGI
    7. transcription, DNA-templated Source: UniProtKB-KW

    Keywords - Molecular functioni

    Activator, Repressor

    Keywords - Biological processi

    Biological rhythms, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_198700. Interleukin-1 processing.
    REACT_202898. TRAF6 mediated NF-kB activation.
    REACT_219800. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
    REACT_222971. RIP-mediated NFkB activation via ZBP1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Nuclear factor NF-kappa-B p100 subunit
    Alternative name(s):
    DNA-binding factor KBF2
    Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
    Cleaved into the following chain:
    Gene namesi
    Name:Nfkb2
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 19

    Organism-specific databases

    MGIiMGI:1099800. Nfkb2.

    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. Bcl3/NF-kappaB2 complex Source: Ensembl
    2. cytoplasm Source: UniProtKB-SubCell
    3. nucleus Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 899899Nuclear factor NF-kappa-B p100 subunitPRO_0000030323Add
    BLAST
    Chaini1 – 454454Nuclear factor NF-kappa-B p52 subunitPRO_0000030324Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei425 – 4251Phosphothreonine2 Publications
    Modified residuei713 – 7131PhosphoserineBy similarity
    Modified residuei715 – 7151PhosphoserineBy similarity
    Modified residuei717 – 7171PhosphoserineBy similarity
    Cross-linki855 – 855Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei865 – 8651Phosphoserine; by MAP3K14By similarity
    Modified residuei869 – 8691Phosphoserine; by MAP3K14By similarity

    Post-translational modificationi

    While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p52 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
    Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing.By similarity
    Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain.By similarity

    Keywords - PTMi

    Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9WTK5.
    PaxDbiQ9WTK5.
    PRIDEiQ9WTK5.

    PTM databases

    PhosphoSiteiQ9WTK5.

    Expressioni

    Tissue specificityi

    Highly expressed in lymph nodes and thymus.1 Publication

    Gene expression databases

    ArrayExpressiQ9WTK5.
    BgeeiQ9WTK5.
    GenevestigatoriQ9WTK5.

    Interactioni

    Subunit structurei

    Component of the NF-kappa-B RelB-p52 complex. Homodimer; component of the NF-kappa-B p52-p52 complex. Component of the NF-kappa-B p65-p52 complex. Component of the NF-kappa-B p52-c-Rel complex. NFKB2/p52 interacts with NFKBIE. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3 By similarity. Directly interacts with MEN1 By similarity.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    RelbQ048632EBI-1209166,EBI-1209145

    Protein-protein interaction databases

    BioGridi201752. 11 interactions.
    IntActiQ9WTK5. 3 interactions.
    MINTiMINT-4099482.

    Structurei

    Secondary structure

    1
    899
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi230 – 2345
    Beta strandi236 – 2394
    Beta strandi245 – 2528
    Helixi255 – 2573
    Beta strandi258 – 2636
    Turni265 – 2684
    Beta strandi271 – 2733
    Helixi278 – 2803
    Helixi282 – 2843
    Beta strandi286 – 2905
    Beta strandi303 – 31412
    Beta strandi321 – 3266

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3JV5X-ray2.65A/B/C/D225-328[»]
    3JV6X-ray2.78B/D/F225-331[»]
    ProteinModelPortaliQ9WTK5.
    SMRiQ9WTK5. Positions 37-329, 459-866.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini35 – 224190RHDPROSITE-ProRule annotationAdd
    BLAST
    Repeati487 – 51630ANK 1Add
    BLAST
    Repeati526 – 55530ANK 2Add
    BLAST
    Repeati559 – 59032ANK 3Add
    BLAST
    Repeati599 – 62830ANK 4Add
    BLAST
    Repeati633 – 66331ANK 5Add
    BLAST
    Repeati667 – 69630ANK 6Add
    BLAST
    Repeati729 – 75527ANK 7Add
    BLAST
    Domaini764 – 85188DeathAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni346 – 37732GRRAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi337 – 3415Nuclear localization signalSequence Analysis

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi351 – 40454Gly-richAdd
    BLAST

    Domaini

    The C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, and/or transcription activation.By similarity
    The glycine-rich region (GRR) appears to be a critical element in the generation of p52.

    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.
    GeneTreeiENSGT00500000044765.
    HOVERGENiHBG052613.
    InParanoidiQ9WTK5.
    KOiK04469.
    OMAiFRGHTPL.
    OrthoDBiEOG7W154S.
    PhylomeDBiQ9WTK5.
    TreeFamiTF325632.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    1.25.40.20. 1 hit.
    2.60.40.10. 1 hit.
    2.60.40.340. 1 hit.
    InterProiIPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    IPR011029. DEATH-like_dom.
    IPR000488. Death_domain.
    IPR013783. Ig-like_fold.
    IPR014756. Ig_E-set.
    IPR002909. IPT.
    IPR000451. NF_Rel_Dor.
    IPR008967. p53-like_TF_DNA-bd.
    IPR011539. RHD.
    [Graphical view]
    PfamiPF00023. Ank. 1 hit.
    PF12796. Ank_2. 2 hits.
    PF00531. Death. 1 hit.
    PF00554. RHD. 1 hit.
    [Graphical view]
    PRINTSiPR01415. ANKYRIN.
    PR00057. NFKBTNSCPFCT.
    SMARTiSM00248. ANK. 7 hits.
    SM00005. DEATH. 1 hit.
    SM00429. IPT. 1 hit.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 1 hit.
    SSF48403. SSF48403. 1 hit.
    SSF49417. SSF49417. 1 hit.
    SSF81296. SSF81296. 1 hit.
    PROSITEiPS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 5 hits.
    PS01204. REL_1. 1 hit.
    PS50254. REL_2. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    Q9WTK5-1 [UniParc]FASTAAdd to Basket

    « Hide

    MDNCYDPGLD GIPEYDDFEF SPSIVEPKDP APETADGPYL VIVEQPKQRG    50
    FRFRYGCEGP SHGGLPGASS EKGRKTYPTV KICNYEGPAK IEVDLVTHSD 100
    PPRAHAHSLV GKQCSELGVC AVSVGPKDMT AQFNNLGVLH VTKKNMMEIM 150
    IQKLQRQRLR SKPQGLTEAE RRELEQEAKE LKKVMDLSIV RLRFSAFLRA 200
    SDGSFSLPLK PVISQPIHDS KSPGASNLKI SRMDKTAGSV RGGDEVYLLC 250
    DKVQKDDIEV RFYEDDENGW QAFGDFSPTD VHKQYAIVFR TPPYHKMKIE 300
    RPVTVFLQLK RKRGGDVSDS KQFTYYPLVE DKEEVQRKRR KALPTFSQPF 350
    GGGSHMGGGS GGSAGGYGGA GGGGSLGFFS SSLAYNPYQS GAAPMGCYPG 400
    GGGGAQMAGS RRDTDAGEGA EEPRTPPEAP QGEPQALDTL QRAREYNARL 450
    FGLAQRSARA LLDYGVTADA RALLAGQRHL LMAQDENGDT PLHLAIIHGQ 500
    TGVIEQIAHV IYHAQYLGVI NLTNHLHQTP LHLAVITGQT RVVSFLLQVG 550
    ADPTLLDRHG DSALHLALRA GAAAPELLQA LLRSGAHAVP QILHMPDFEG 600
    LYPVHLAVHA RSPECLDLLV DCGAEVEAPE RQGGRTALHL ATEMEELGLV 650
    THLVTKLHAN VNARTFAGNT PLHLAAGLGS PTLTRLLLKA GADIHAENEE 700
    PLCPLPSPST SGSDSDSEGP ERDTQRNFRG HTPLDLTCST KVKTLLLNAA 750
    QNTTEPPLAP PSPAGPGLSL GDAALQNLEQ LLDGPEAQGS WAELAERLGL 800
    RSLVDTYRKT PSPSGSLLRS YKLAGGDLVG LLEALSDMGL HEGVRLLKGP 850
    ETRDKLPSTE VKEDSAYGSQ SVEQEAEKLC PPPEPPGGLC HGHPQPQVH 899
    Length:899
    Mass (Da):96,832
    Last modified:November 1, 1999 - v1
    Checksum:i3E98619F7D1C8AC7
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF155373 mRNA. Translation: AAD39547.1.
    AF135125 Genomic DNA. Translation: AAD39462.1.
    AF155372 mRNA. Translation: AAD39546.1.
    BC027423 mRNA. Translation: AAH27423.1.
    CCDSiCCDS29874.1.
    RefSeqiNP_001170840.1. NM_001177369.1.
    NP_062281.1. NM_019408.3.
    UniGeneiMm.102365.

    Genome annotation databases

    EnsembliENSMUST00000073116; ENSMUSP00000072859; ENSMUSG00000025225.
    ENSMUST00000111881; ENSMUSP00000107512; ENSMUSG00000025225.
    GeneIDi18034.
    KEGGimmu:18034.
    UCSCiuc008hst.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF155373 mRNA. Translation: AAD39547.1 .
    AF135125 Genomic DNA. Translation: AAD39462.1 .
    AF155372 mRNA. Translation: AAD39546.1 .
    BC027423 mRNA. Translation: AAH27423.1 .
    CCDSi CCDS29874.1.
    RefSeqi NP_001170840.1. NM_001177369.1.
    NP_062281.1. NM_019408.3.
    UniGenei Mm.102365.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3JV5 X-ray 2.65 A/B/C/D 225-328 [» ]
    3JV6 X-ray 2.78 B/D/F 225-331 [» ]
    ProteinModelPortali Q9WTK5.
    SMRi Q9WTK5. Positions 37-329, 459-866.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201752. 11 interactions.
    IntActi Q9WTK5. 3 interactions.
    MINTi MINT-4099482.

    PTM databases

    PhosphoSitei Q9WTK5.

    Proteomic databases

    MaxQBi Q9WTK5.
    PaxDbi Q9WTK5.
    PRIDEi Q9WTK5.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000073116 ; ENSMUSP00000072859 ; ENSMUSG00000025225 .
    ENSMUST00000111881 ; ENSMUSP00000107512 ; ENSMUSG00000025225 .
    GeneIDi 18034.
    KEGGi mmu:18034.
    UCSCi uc008hst.2. mouse.

    Organism-specific databases

    CTDi 4791.
    MGIi MGI:1099800. Nfkb2.

    Phylogenomic databases

    eggNOGi COG0666.
    GeneTreei ENSGT00500000044765.
    HOVERGENi HBG052613.
    InParanoidi Q9WTK5.
    KOi K04469.
    OMAi FRGHTPL.
    OrthoDBi EOG7W154S.
    PhylomeDBi Q9WTK5.
    TreeFami TF325632.

    Enzyme and pathway databases

    Reactomei REACT_198700. Interleukin-1 processing.
    REACT_202898. TRAF6 mediated NF-kB activation.
    REACT_219800. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
    REACT_222971. RIP-mediated NFkB activation via ZBP1.

    Miscellaneous databases

    ChiTaRSi NFKB2. mouse.
    NextBioi 293125.
    PROi Q9WTK5.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9WTK5.
    Bgeei Q9WTK5.
    Genevestigatori Q9WTK5.

    Family and domain databases

    Gene3Di 1.10.533.10. 1 hit.
    1.25.40.20. 1 hit.
    2.60.40.10. 1 hit.
    2.60.40.340. 1 hit.
    InterProi IPR002110. Ankyrin_rpt.
    IPR020683. Ankyrin_rpt-contain_dom.
    IPR011029. DEATH-like_dom.
    IPR000488. Death_domain.
    IPR013783. Ig-like_fold.
    IPR014756. Ig_E-set.
    IPR002909. IPT.
    IPR000451. NF_Rel_Dor.
    IPR008967. p53-like_TF_DNA-bd.
    IPR011539. RHD.
    [Graphical view ]
    Pfami PF00023. Ank. 1 hit.
    PF12796. Ank_2. 2 hits.
    PF00531. Death. 1 hit.
    PF00554. RHD. 1 hit.
    [Graphical view ]
    PRINTSi PR01415. ANKYRIN.
    PR00057. NFKBTNSCPFCT.
    SMARTi SM00248. ANK. 7 hits.
    SM00005. DEATH. 1 hit.
    SM00429. IPT. 1 hit.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 1 hit.
    SSF48403. SSF48403. 1 hit.
    SSF49417. SSF49417. 1 hit.
    SSF81296. SSF81296. 1 hit.
    PROSITEi PS50297. ANK_REP_REGION. 1 hit.
    PS50088. ANK_REPEAT. 5 hits.
    PS01204. REL_1. 1 hit.
    PS50254. REL_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Genomic organization and chromosomal mapping of mouse nuclear factor kappa B 2 (NFKB2)."
      Paxian S., Liptay S., Adler G., Hameister H., Schmid R.M.
      Immunogenetics 49:743-750(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
      Strain: 129/Sv.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    3. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-425, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    4. "The phagosomal proteome in interferon-gamma-activated macrophages."
      Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
      Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-425, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    5. "The RelB subunit of NFkappaB acts as a negative regulator of circadian gene expression."
      Bellet M.M., Zocchi L., Sassone-Corsi P.
      Cell Cycle 11:3304-3311(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.

    Entry informationi

    Entry nameiNFKB2_MOUSE
    AccessioniPrimary (citable) accession number: Q9WTK5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 10, 2004
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 122 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3