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Protein

Nuclear factor NF-kappa-B p100 subunit

Gene

Nfkb2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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). In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Repressor
Biological processBiological rhythms, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-1810476 RIP-mediated NFkB activation via ZBP1
R-MMU-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-MMU-3214841 PKMTs methylate histone lysines
R-MMU-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-MMU-448706 Interleukin-1 processing
R-MMU-4755510 SUMOylation of immune response proteins
R-MMU-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-MMU-5676590 NIK-->noncanonical NF-kB signaling
R-MMU-933542 TRAF6 mediated NF-kB activation

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:1099800 Nfkb2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3879845

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000303231 – 899Nuclear factor NF-kappa-B p100 subunitAdd BLAST899
ChainiPRO_00000303241 – 454Nuclear factor NF-kappa-B p52 subunitAdd BLAST454

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei23PhosphoserineBy similarity1
Modified residuei161PhosphoserineBy similarity1
Modified residuei425PhosphothreonineCombined sources1
Modified residuei713PhosphoserineBy similarity1
Modified residuei715PhosphoserineBy similarity1
Modified residuei717PhosphoserineBy similarity1
Modified residuei812PhosphoserineBy similarity1
Cross-linki855Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei865Phosphoserine; by MAP3K14By similarity1
Modified residuei869Phosphoserine; by MAP3K14By similarity1

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei454 – 455Cleavage (when cotranslationally processed)2

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9WTK5
MaxQBiQ9WTK5
PaxDbiQ9WTK5
PRIDEiQ9WTK5

PTM databases

iPTMnetiQ9WTK5
PhosphoSitePlusiQ9WTK5
SwissPalmiQ9WTK5

Expressioni

Tissue specificityi

Highly expressed in lymph nodes and thymus.1 Publication

Gene expression databases

BgeeiENSMUSG00000025225 Expressed in 259 organ(s), highest expression level in spleen
ExpressionAtlasiQ9WTK5 baseline and differential
GenevisibleiQ9WTK5 MM

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, 7 interactors
IntActiQ9WTK5, 3 interactors
MINTiQ9WTK5
STRINGi10090.ENSMUSP00000072859

Structurei

Secondary structure

1899
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9WTK5
SMRiQ9WTK5
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 224RHDPROSITE-ProRule annotationAdd BLAST190
Repeati487 – 516ANK 1Add BLAST30
Repeati526 – 555ANK 2Add BLAST30
Repeati559 – 590ANK 3Add BLAST32
Repeati599 – 628ANK 4Add BLAST30
Repeati633 – 663ANK 5Add BLAST31
Repeati667 – 696ANK 6Add BLAST30
Repeati729 – 755ANK 7Add BLAST27
Domaini764 – 851DeathAdd BLAST88

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni346 – 377GRRAdd BLAST32

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi337 – 341Nuclear localization signalSequence analysis5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi351 – 404Gly-richAdd BLAST54

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.

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00500000044765
HOVERGENiHBG052613
InParanoidiQ9WTK5
KOiK04469
OMAiQKPLPHY
OrthoDBiEOG091G03PF
PhylomeDBiQ9WTK5
TreeFamiTF325632

Family and domain databases

CDDicd00204 ANK, 3 hits
cd01177 IPT_NFkappaB, 1 hit
Gene3Di1.25.40.20, 1 hit
2.60.40.10, 1 hit
2.60.40.340, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR002909 IPT_dom
IPR033926 IPT_NFkappaB
IPR000451 NFkB/Dor
IPR008967 p53-like_TF_DNA-bd
IPR030492 RHD_CS
IPR032397 RHD_dimer
IPR011539 RHD_DNA_bind_dom
IPR037059 RHD_DNA_bind_dom_sf
PANTHERiPTHR24169 PTHR24169, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PF00531 Death, 1 hit
PF16179 RHD_dimer, 1 hit
PF00554 RHD_DNA_bind, 1 hit
PRINTSiPR01415 ANKYRIN
PR00057 NFKBTNSCPFCT
SMARTiView protein in SMART
SM00248 ANK, 7 hits
SM00005 DEATH, 1 hit
SM00429 IPT, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48403 SSF48403, 1 hit
SSF49417 SSF49417, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 5 hits
PS01204 REL_1, 1 hit
PS50254 REL_2, 1 hit

Sequencei

Sequence statusi: Complete.

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

Q9WTK5-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MDNCYDPGLD GIPEYDDFEF SPSIVEPKDP APETADGPYL VIVEQPKQRG
60 70 80 90 100
FRFRYGCEGP SHGGLPGASS EKGRKTYPTV KICNYEGPAK IEVDLVTHSD
110 120 130 140 150
PPRAHAHSLV GKQCSELGVC AVSVGPKDMT AQFNNLGVLH VTKKNMMEIM
160 170 180 190 200
IQKLQRQRLR SKPQGLTEAE RRELEQEAKE LKKVMDLSIV RLRFSAFLRA
210 220 230 240 250
SDGSFSLPLK PVISQPIHDS KSPGASNLKI SRMDKTAGSV RGGDEVYLLC
260 270 280 290 300
DKVQKDDIEV RFYEDDENGW QAFGDFSPTD VHKQYAIVFR TPPYHKMKIE
310 320 330 340 350
RPVTVFLQLK RKRGGDVSDS KQFTYYPLVE DKEEVQRKRR KALPTFSQPF
360 370 380 390 400
GGGSHMGGGS GGSAGGYGGA GGGGSLGFFS SSLAYNPYQS GAAPMGCYPG
410 420 430 440 450
GGGGAQMAGS RRDTDAGEGA EEPRTPPEAP QGEPQALDTL QRAREYNARL
460 470 480 490 500
FGLAQRSARA LLDYGVTADA RALLAGQRHL LMAQDENGDT PLHLAIIHGQ
510 520 530 540 550
TGVIEQIAHV IYHAQYLGVI NLTNHLHQTP LHLAVITGQT RVVSFLLQVG
560 570 580 590 600
ADPTLLDRHG DSALHLALRA GAAAPELLQA LLRSGAHAVP QILHMPDFEG
610 620 630 640 650
LYPVHLAVHA RSPECLDLLV DCGAEVEAPE RQGGRTALHL ATEMEELGLV
660 670 680 690 700
THLVTKLHAN VNARTFAGNT PLHLAAGLGS PTLTRLLLKA GADIHAENEE
710 720 730 740 750
PLCPLPSPST SGSDSDSEGP ERDTQRNFRG HTPLDLTCST KVKTLLLNAA
760 770 780 790 800
QNTTEPPLAP PSPAGPGLSL GDAALQNLEQ LLDGPEAQGS WAELAERLGL
810 820 830 840 850
RSLVDTYRKT PSPSGSLLRS YKLAGGDLVG LLEALSDMGL HEGVRLLKGP
860 870 880 890
ETRDKLPSTE VKEDSAYGSQ SVEQEAEKLC PPPEPPGGLC HGHPQPQVH
Length:899
Mass (Da):96,832
Last modified:November 1, 1999 - v1
Checksum:i3E98619F7D1C8AC7
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3JV5X-ray2.65A/B/C/D225-328[»]
3JV6X-ray2.78B/D/F225-331[»]
ProteinModelPortaliQ9WTK5
SMRiQ9WTK5
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201752, 7 interactors
IntActiQ9WTK5, 3 interactors
MINTiQ9WTK5
STRINGi10090.ENSMUSP00000072859

Chemistry databases

ChEMBLiCHEMBL3879845

PTM databases

iPTMnetiQ9WTK5
PhosphoSitePlusiQ9WTK5
SwissPalmiQ9WTK5

Proteomic databases

EPDiQ9WTK5
MaxQBiQ9WTK5
PaxDbiQ9WTK5
PRIDEiQ9WTK5

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4791
MGIiMGI:1099800 Nfkb2

Phylogenomic databases

eggNOGiKOG0504 Eukaryota
COG0666 LUCA
GeneTreeiENSGT00500000044765
HOVERGENiHBG052613
InParanoidiQ9WTK5
KOiK04469
OMAiQKPLPHY
OrthoDBiEOG091G03PF
PhylomeDBiQ9WTK5
TreeFamiTF325632

Enzyme and pathway databases

ReactomeiR-MMU-1810476 RIP-mediated NFkB activation via ZBP1
R-MMU-3134963 DEx/H-box helicases activate type I IFN and inflammatory cytokines production
R-MMU-3214841 PKMTs methylate histone lysines
R-MMU-445989 TAK1 activates NFkB by phosphorylation and activation of IKKs complex
R-MMU-448706 Interleukin-1 processing
R-MMU-4755510 SUMOylation of immune response proteins
R-MMU-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-MMU-5676590 NIK-->noncanonical NF-kB signaling
R-MMU-933542 TRAF6 mediated NF-kB activation

Miscellaneous databases

ChiTaRSiNfkb2 mouse
PROiPR:Q9WTK5
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000025225 Expressed in 259 organ(s), highest expression level in spleen
ExpressionAtlasiQ9WTK5 baseline and differential
GenevisibleiQ9WTK5 MM

Family and domain databases

CDDicd00204 ANK, 3 hits
cd01177 IPT_NFkappaB, 1 hit
Gene3Di1.25.40.20, 1 hit
2.60.40.10, 1 hit
2.60.40.340, 1 hit
InterProiView protein in InterPro
IPR002110 Ankyrin_rpt
IPR020683 Ankyrin_rpt-contain_dom
IPR036770 Ankyrin_rpt-contain_sf
IPR011029 DEATH-like_dom_sf
IPR000488 Death_domain
IPR013783 Ig-like_fold
IPR014756 Ig_E-set
IPR002909 IPT_dom
IPR033926 IPT_NFkappaB
IPR000451 NFkB/Dor
IPR008967 p53-like_TF_DNA-bd
IPR030492 RHD_CS
IPR032397 RHD_dimer
IPR011539 RHD_DNA_bind_dom
IPR037059 RHD_DNA_bind_dom_sf
PANTHERiPTHR24169 PTHR24169, 1 hit
PfamiView protein in Pfam
PF12796 Ank_2, 2 hits
PF00531 Death, 1 hit
PF16179 RHD_dimer, 1 hit
PF00554 RHD_DNA_bind, 1 hit
PRINTSiPR01415 ANKYRIN
PR00057 NFKBTNSCPFCT
SMARTiView protein in SMART
SM00248 ANK, 7 hits
SM00005 DEATH, 1 hit
SM00429 IPT, 1 hit
SUPFAMiSSF47986 SSF47986, 1 hit
SSF48403 SSF48403, 1 hit
SSF49417 SSF49417, 1 hit
SSF81296 SSF81296, 1 hit
PROSITEiView protein in PROSITE
PS50297 ANK_REP_REGION, 1 hit
PS50088 ANK_REPEAT, 5 hits
PS01204 REL_1, 1 hit
PS50254 REL_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNFKB2_MOUSE
AccessioniPrimary (citable) accession number: Q9WTK5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: November 1, 1999
Last modified: November 7, 2018
This is version 160 of the entry and version 1 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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