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Q9WTK5 (NFKB2_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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 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:

  1. Nuclear factor NF-kappa-B p52 subunit
Gene names
Name:Nfkb2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length899 AA.
Sequence statusComplete.
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. 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 p49is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65 By similarity.

Subunit structure

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.

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.

Tissue specificity

Highly expressed in lymph nodes and thymus. Ref.1

Domain

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.

Post-translational modification

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.

Sequence similarities

Contains 7 ANK repeats.

Contains 1 death domain.

Contains 1 RHD (Rel-like) domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RelbQ048632EBI-1209166,EBI-1209145

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 899899Nuclear factor NF-kappa-B p100 subunit
PRO_0000030323
Chain1 – 454454Nuclear factor NF-kappa-B p52 subunit
PRO_0000030324

Regions

Domain35 – 224190RHD
Repeat487 – 51630ANK 1
Repeat526 – 55530ANK 2
Repeat559 – 59032ANK 3
Repeat599 – 62830ANK 4
Repeat633 – 66331ANK 5
Repeat667 – 69630ANK 6
Repeat729 – 75527ANK 7
Domain764 – 85188Death
Region346 – 37732GRR
Motif337 – 3415Nuclear localization signal Potential
Compositional bias351 – 40454Gly-rich

Sites

Site454 – 4552Cleavage (when cotranslationally processed)

Amino acid modifications

Modified residue4251Phosphothreonine Ref.3 Ref.4
Modified residue7131Phosphoserine By similarity
Modified residue7151Phosphoserine By similarity
Modified residue7171Phosphoserine By similarity
Modified residue8651Phosphoserine; by MAP3K14 By similarity
Modified residue8691Phosphoserine; by MAP3K14 By similarity
Cross-link855Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Secondary structure

........................ 899
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9WTK5 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 3E98619F7D1C8AC7

FASTA89996,832
        10         20         30         40         50         60 
MDNCYDPGLD GIPEYDDFEF SPSIVEPKDP APETADGPYL VIVEQPKQRG FRFRYGCEGP 

        70         80         90        100        110        120 
SHGGLPGASS EKGRKTYPTV KICNYEGPAK IEVDLVTHSD PPRAHAHSLV GKQCSELGVC 

       130        140        150        160        170        180 
AVSVGPKDMT AQFNNLGVLH VTKKNMMEIM IQKLQRQRLR SKPQGLTEAE RRELEQEAKE 

       190        200        210        220        230        240 
LKKVMDLSIV RLRFSAFLRA SDGSFSLPLK PVISQPIHDS KSPGASNLKI SRMDKTAGSV 

       250        260        270        280        290        300 
RGGDEVYLLC DKVQKDDIEV RFYEDDENGW QAFGDFSPTD VHKQYAIVFR TPPYHKMKIE 

       310        320        330        340        350        360 
RPVTVFLQLK RKRGGDVSDS KQFTYYPLVE DKEEVQRKRR KALPTFSQPF GGGSHMGGGS 

       370        380        390        400        410        420 
GGSAGGYGGA GGGGSLGFFS SSLAYNPYQS GAAPMGCYPG GGGGAQMAGS RRDTDAGEGA 

       430        440        450        460        470        480 
EEPRTPPEAP QGEPQALDTL QRAREYNARL FGLAQRSARA LLDYGVTADA RALLAGQRHL 

       490        500        510        520        530        540 
LMAQDENGDT PLHLAIIHGQ TGVIEQIAHV IYHAQYLGVI NLTNHLHQTP LHLAVITGQT 

       550        560        570        580        590        600 
RVVSFLLQVG ADPTLLDRHG DSALHLALRA GAAAPELLQA LLRSGAHAVP QILHMPDFEG 

       610        620        630        640        650        660 
LYPVHLAVHA RSPECLDLLV DCGAEVEAPE RQGGRTALHL ATEMEELGLV THLVTKLHAN 

       670        680        690        700        710        720 
VNARTFAGNT PLHLAAGLGS PTLTRLLLKA GADIHAENEE PLCPLPSPST SGSDSDSEGP 

       730        740        750        760        770        780 
ERDTQRNFRG HTPLDLTCST KVKTLLLNAA QNTTEPPLAP PSPAGPGLSL GDAALQNLEQ 

       790        800        810        820        830        840 
LLDGPEAQGS WAELAERLGL RSLVDTYRKT PSPSGSLLRS YKLAGGDLVG LLEALSDMGL 

       850        860        870        880        890 
HEGVRLLKGP ETRDKLPSTE VKEDSAYGSQ SVEQEAEKLC PPPEPPGGLC HGHPQPQVH 

« Hide

References

« Hide 'large scale' references
[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]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
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].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF155373 mRNA. Translation: AAD39547.1.
AF135125 Genomic DNA. Translation: AAD39462.1.
AF155372 mRNA. Translation: AAD39546.1.
BC027423 mRNA. Translation: AAH27423.1.
CCDSCCDS29874.1.
RefSeqNP_001170840.1. NM_001177369.1.
NP_062281.1. NM_019408.3.
UniGeneMm.102365.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3JV5X-ray2.65A/B/C/D225-328[»]
3JV6X-ray2.78B/D/F225-331[»]
ProteinModelPortalQ9WTK5.
SMRQ9WTK5. Positions 37-329, 459-866.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201752. 11 interactions.
IntActQ9WTK5. 3 interactions.
MINTMINT-4099482.

PTM databases

PhosphoSiteQ9WTK5.

Proteomic databases

MaxQBQ9WTK5.
PaxDbQ9WTK5.
PRIDEQ9WTK5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000073116; ENSMUSP00000072859; ENSMUSG00000025225.
ENSMUST00000111881; ENSMUSP00000107512; ENSMUSG00000025225.
GeneID18034.
KEGGmmu:18034.
UCSCuc008hst.2. mouse.

Organism-specific databases

CTD4791.
MGIMGI:1099800. Nfkb2.

Phylogenomic databases

eggNOGCOG0666.
GeneTreeENSGT00500000044765.
HOVERGENHBG052613.
InParanoidQ9WTK5.
KOK04469.
OMAFRGHTPL.
OrthoDBEOG7W154S.
PhylomeDBQ9WTK5.
TreeFamTF325632.

Gene expression databases

ArrayExpressQ9WTK5.
BgeeQ9WTK5.
GenevestigatorQ9WTK5.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProIPR002110. 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]
PfamPF00023. Ank. 1 hit.
PF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
PF00554. RHD. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
PR00057. NFKBTNSCPFCT.
SMARTSM00248. ANK. 7 hits.
SM00005. DEATH. 1 hit.
SM00429. IPT. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNFKB2. mouse.
NextBio293125.
PROQ9WTK5.
SOURCESearch...

Entry information

Entry nameNFKB2_MOUSE
AccessionPrimary (citable) accession number: Q9WTK5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 120 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot