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Q9WTK5

- NFKB2_MOUSE

UniProt

Q9WTK5 - NFKB2_MOUSE

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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

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.

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
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

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
Complete GO annotation...

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 – 7131Phosphoserine By similarity
Modified residuei715 – 7151Phosphoserine By similarity
Modified residuei717 – 7171Phosphoserine By similarity
Cross-linki855 – 855Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Modified residuei865 – 8651Phosphoserine; by MAP3K14 By similarity
Modified residuei869 – 8691Phosphoserine; by MAP3K14 By 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.
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.

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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini35 – 224190RHDAdd
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 signal Reviewed prediction

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.
Contains 1 death domain.

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

« Hide 'large scale' publications
  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].

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: September 3, 2014
This is version 121 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

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