NFKB2_MOUSE
ID NFKB2_MOUSE Reviewed; 899 AA.
AC Q9WTK5;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Nuclear factor NF-kappa-B p100 subunit;
DE AltName: Full=DNA-binding factor KBF2;
DE AltName: Full=Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2;
DE Contains:
DE RecName: Full=Nuclear factor NF-kappa-B p52 subunit;
GN Name=Nfkb2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RC STRAIN=129/Sv;
RX PubMed=10398801; DOI=10.1007/s002510050548;
RA Paxian S., Liptay S., Adler G., Hameister H., Schmid R.M.;
RT "Genomic organization and chromosomal mapping of mouse nuclear factor kappa
RT B 2 (NFKB2).";
RL Immunogenetics 49:743-750(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-425, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-425, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-425, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION.
RX PubMed=22894897; DOI=10.4161/cc.21669;
RA Bellet M.M., Zocchi L., Sassone-Corsi P.;
RT "The RelB subunit of NFkappaB acts as a negative regulator of circadian
RT gene expression.";
RL Cell Cycle 11:3304-3311(2012).
CC -!- FUNCTION: NF-kappa-B is a pleiotropic transcription factor present in
CC almost all cell types and is the endpoint of a series of signal
CC transduction events that are initiated by a vast array of stimuli
CC related to many biological processes such as inflammation, immunity,
CC differentiation, cell growth, tumorigenesis and apoptosis. NF-kappa-B
CC is a homo- or heterodimeric complex formed by the Rel-like domain-
CC containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and
CC NFKB2/p52. The dimers bind at kappa-B sites in the DNA of their target
CC genes and the individual dimers have distinct preferences for different
CC kappa-B sites that they can bind with distinguishable affinity and
CC specificity. Different dimer combinations act as transcriptional
CC activators or repressors, respectively. NF-kappa-B is controlled by
CC various mechanisms of post-translational modification and subcellular
CC compartmentalization as well as by interactions with other cofactors or
CC corepressors. NF-kappa-B complexes are held in the cytoplasm in an
CC inactive state complexed with members of the NF-kappa-B inhibitor (I-
CC kappa-B) family. In a conventional activation pathway, I-kappa-B is
CC phosphorylated by I-kappa-B kinases (IKKs) in response to different
CC activators, subsequently degraded thus liberating the active NF-kappa-B
CC complex which translocates to the nucleus. In a non-canonical
CC activation pathway, the MAP3K14-activated CHUK/IKKA homodimer
CC phosphorylates NFKB2/p100 associated with RelB, inducing its
CC proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B
CC RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a
CC transcriptional activator. The NF-kappa-B p52-p52 homodimer is a
CC transcriptional repressor. NFKB2 appears to have dual functions such as
CC cytoplasmic retention of attached NF-kappa-B proteins by p100 and
CC generation of p52 by a cotranslational processing. The proteasome-
CC mediated process ensures the production of both p52 and p100 and
CC preserves their independent function. p52 binds to the kappa-B
CC consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of
CC genes involved in immune response and acute phase reactions. p52 and
CC p100 are respectively the minor and major form; the processing of p100
CC being relatively poor. Isoform p49 is a subunit of the NF-kappa-B
CC protein complex, which stimulates the HIV enhancer in synergy with p65
CC (By similarity). In concert with RELB, regulates the circadian clock by
CC repressing the transcriptional activator activity of the CLOCK-
CC ARNTL/BMAL1 heterodimer. {ECO:0000250, ECO:0000269|PubMed:22894897}.
CC -!- SUBUNIT: Component of the NF-kappa-B RelB-p52 complex. Homodimer;
CC component of the NF-kappa-B p52-p52 complex. Component of the NF-kappa-
CC B p65-p52 complex. Component of the NF-kappa-B p52-c-Rel complex.
CC NFKB2/p52 interacts with NFKBIE. Component of a complex consisting of
CC the NF-kappa-B p50-p50 homodimer and BCL3 (By similarity). Directly
CC interacts with MEN1 (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q9WTK5; Q04207: Rela; NbExp=3; IntAct=EBI-1209166, EBI-644400;
CC Q9WTK5; Q04863: Relb; NbExp=3; IntAct=EBI-1209166, EBI-1209145;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}. Cytoplasm {ECO:0000250}.
CC Note=Nuclear, but also found in the cytoplasm in an inactive form
CC complexed to an inhibitor (I-kappa-B). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in lymph nodes and thymus.
CC {ECO:0000269|PubMed:10398801}.
CC -!- DOMAIN: The C-terminus of p100 might be involved in cytoplasmic
CC retention, inhibition of DNA-binding by p52 homodimers, and/or
CC transcription activation. {ECO:0000250}.
CC -!- DOMAIN: The glycine-rich region (GRR) appears to be a critical element
CC in the generation of p52.
CC -!- PTM: While translation occurs, the particular unfolded structure after
CC the GRR repeat promotes the generation of p52 making it an acceptable
CC substrate for the proteasome. This process is known as cotranslational
CC processing. The processed form is active and the unprocessed form acts
CC as an inhibitor (I kappa B-like), being able to form cytosolic
CC complexes with NF-kappa B, trapping it in the cytoplasm. Complete
CC folding of the region downstream of the GRR repeat precludes processing
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Subsequent to MAP3K14-dependent serine phosphorylation, p100
CC polyubiquitination occurs then triggering its proteasome-dependent
CC processing. {ECO:0000250}.
CC -!- PTM: Constitutive processing is tightly suppressed by its C-terminal
CC processing inhibitory domain, named PID, which contains the death
CC domain. {ECO:0000250}.
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DR EMBL; AF155373; AAD39547.1; -; mRNA.
DR EMBL; AF135125; AAD39462.1; -; Genomic_DNA.
DR EMBL; AF155372; AAD39546.1; -; mRNA.
DR EMBL; BC027423; AAH27423.1; -; mRNA.
DR CCDS; CCDS29874.1; -.
DR RefSeq; NP_001170840.1; NM_001177369.1.
DR RefSeq; NP_062281.1; NM_019408.3.
DR PDB; 3JV5; X-ray; 2.65 A; A/B/C/D=225-328.
DR PDB; 3JV6; X-ray; 2.78 A; B/D/F=225-331.
DR PDBsum; 3JV5; -.
DR PDBsum; 3JV6; -.
DR AlphaFoldDB; Q9WTK5; -.
DR SMR; Q9WTK5; -.
DR BioGRID; 201752; 11.
DR IntAct; Q9WTK5; 4.
DR STRING; 10090.ENSMUSP00000107512; -.
DR ChEMBL; CHEMBL3879845; -.
DR iPTMnet; Q9WTK5; -.
DR PhosphoSitePlus; Q9WTK5; -.
DR SwissPalm; Q9WTK5; -.
DR EPD; Q9WTK5; -.
DR jPOST; Q9WTK5; -.
DR MaxQB; Q9WTK5; -.
DR PaxDb; Q9WTK5; -.
DR PRIDE; Q9WTK5; -.
DR ProteomicsDB; 293551; -.
DR Antibodypedia; 1322; 1027 antibodies from 47 providers.
DR DNASU; 18034; -.
DR Ensembl; ENSMUST00000073116; ENSMUSP00000072859; ENSMUSG00000025225.
DR Ensembl; ENSMUST00000111881; ENSMUSP00000107512; ENSMUSG00000025225.
DR Ensembl; ENSMUST00000236591; ENSMUSP00000157542; ENSMUSG00000025225.
DR GeneID; 18034; -.
DR KEGG; mmu:18034; -.
DR UCSC; uc008hst.2; mouse.
DR CTD; 4791; -.
DR MGI; MGI:1099800; Nfkb2.
DR VEuPathDB; HostDB:ENSMUSG00000025225; -.
DR eggNOG; KOG0504; Eukaryota.
DR GeneTree; ENSGT00940000160968; -.
DR HOGENOM; CLU_004343_1_1_1; -.
DR InParanoid; Q9WTK5; -.
DR OMA; EQMAHII; -.
DR OrthoDB; 916931at2759; -.
DR PhylomeDB; Q9WTK5; -.
DR TreeFam; TF325632; -.
DR Reactome; R-MMU-1810476; RIP-mediated NFkB activation via ZBP1.
DR Reactome; R-MMU-3134963; DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
DR Reactome; R-MMU-3214841; PKMTs methylate histone lysines.
DR Reactome; R-MMU-445989; TAK1-dependent IKK and NF-kappa-B activation.
DR Reactome; R-MMU-448706; Interleukin-1 processing.
DR Reactome; R-MMU-4755510; SUMOylation of immune response proteins.
DR Reactome; R-MMU-5607761; Dectin-1 mediated noncanonical NF-kB signaling.
DR Reactome; R-MMU-5676590; NIK-->noncanonical NF-kB signaling.
DR Reactome; R-MMU-933542; TRAF6 mediated NF-kB activation.
DR BioGRID-ORCS; 18034; 9 hits in 81 CRISPR screens.
DR ChiTaRS; Nfkb2; mouse.
DR PRO; PR:Q9WTK5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9WTK5; protein.
DR Bgee; ENSMUSG00000025225; Expressed in peripheral lymph node and 244 other tissues.
DR ExpressionAtlas; Q9WTK5; baseline and differential.
DR Genevisible; Q9WTK5; MM.
DR GO; GO:0033257; C:Bcl3/NF-kappaB2 complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0071159; C:NF-kappaB complex; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:0002268; P:follicular dendritic cell differentiation; IMP:MGI.
DR GO; GO:0002467; P:germinal center formation; IMP:MGI.
DR GO; GO:0048535; P:lymph node development; TAS:MGI.
DR GO; GO:0038061; P:NIK/NF-kappaB signaling; IDA:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR GO; GO:0048536; P:spleen development; IMP:MGI.
DR CDD; cd01177; IPT_NFkappaB; 1.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 1.25.40.20; -; 1.
DR Gene3D; 2.60.40.10; -; 1.
DR Gene3D; 2.60.40.340; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR002909; IPT_dom.
DR InterPro; IPR033926; IPT_NFkappaB.
DR InterPro; IPR000451; NFkB/Dor.
DR InterPro; IPR030497; NFkB_p100.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR030492; RHD_CS.
DR InterPro; IPR032397; RHD_dimer.
DR InterPro; IPR011539; RHD_DNA_bind_dom.
DR InterPro; IPR037059; RHD_DNA_bind_dom_sf.
DR PANTHER; PTHR24169; PTHR24169; 1.
DR PANTHER; PTHR24169:SF21; PTHR24169:SF21; 1.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF16179; RHD_dimer; 1.
DR Pfam; PF00554; RHD_DNA_bind; 1.
DR PRINTS; PR01415; ANKYRIN.
DR PRINTS; PR00057; NFKBTNSCPFCT.
DR SMART; SM00248; ANK; 7.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00429; IPT; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 5.
DR PROSITE; PS01204; REL_1; 1.
DR PROSITE; PS50254; REL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; ANK repeat; Biological rhythms; Cytoplasm;
KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Repressor; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..899
FT /note="Nuclear factor NF-kappa-B p100 subunit"
FT /id="PRO_0000030323"
FT CHAIN 1..454
FT /note="Nuclear factor NF-kappa-B p52 subunit"
FT /id="PRO_0000030324"
FT DOMAIN 35..224
FT /note="RHD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00265"
FT REPEAT 487..516
FT /note="ANK 1"
FT REPEAT 526..555
FT /note="ANK 2"
FT REPEAT 559..590
FT /note="ANK 3"
FT REPEAT 599..628
FT /note="ANK 4"
FT REPEAT 633..663
FT /note="ANK 5"
FT REPEAT 667..696
FT /note="ANK 6"
FT REPEAT 729..755
FT /note="ANK 7"
FT DOMAIN 764..851
FT /note="Death"
FT REGION 346..377
FT /note="GRR"
FT REGION 403..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 698..734
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 851..899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 337..341
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT SITE 454..455
FT /note="Cleavage (when cotranslationally processed)"
FT MOD_RES 23
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT MOD_RES 161
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT MOD_RES 425
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:19144319, ECO:0007744|PubMed:21183079"
FT MOD_RES 713
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT MOD_RES 715
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT MOD_RES 717
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT MOD_RES 812
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT MOD_RES 865
FT /note="Phosphoserine; by MAP3K14"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT MOD_RES 869
FT /note="Phosphoserine; by MAP3K14"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT CROSSLNK 855
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q00653"
FT STRAND 230..234
FT /evidence="ECO:0007829|PDB:3JV5"
FT STRAND 236..239
FT /evidence="ECO:0007829|PDB:3JV5"
FT STRAND 245..252
FT /evidence="ECO:0007829|PDB:3JV5"
FT HELIX 255..257
FT /evidence="ECO:0007829|PDB:3JV5"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:3JV5"
FT TURN 265..268
FT /evidence="ECO:0007829|PDB:3JV6"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:3JV5"
FT HELIX 278..280
FT /evidence="ECO:0007829|PDB:3JV5"
FT HELIX 282..284
FT /evidence="ECO:0007829|PDB:3JV5"
FT STRAND 286..290
FT /evidence="ECO:0007829|PDB:3JV5"
FT STRAND 303..314
FT /evidence="ECO:0007829|PDB:3JV5"
FT STRAND 321..326
FT /evidence="ECO:0007829|PDB:3JV5"
SQ SEQUENCE 899 AA; 96832 MW; 3E98619F7D1C8AC7 CRC64;
MDNCYDPGLD GIPEYDDFEF SPSIVEPKDP APETADGPYL VIVEQPKQRG FRFRYGCEGP
SHGGLPGASS EKGRKTYPTV KICNYEGPAK IEVDLVTHSD PPRAHAHSLV GKQCSELGVC
AVSVGPKDMT AQFNNLGVLH VTKKNMMEIM IQKLQRQRLR SKPQGLTEAE RRELEQEAKE
LKKVMDLSIV RLRFSAFLRA SDGSFSLPLK PVISQPIHDS KSPGASNLKI SRMDKTAGSV
RGGDEVYLLC DKVQKDDIEV RFYEDDENGW QAFGDFSPTD VHKQYAIVFR TPPYHKMKIE
RPVTVFLQLK RKRGGDVSDS KQFTYYPLVE DKEEVQRKRR KALPTFSQPF GGGSHMGGGS
GGSAGGYGGA GGGGSLGFFS SSLAYNPYQS GAAPMGCYPG GGGGAQMAGS RRDTDAGEGA
EEPRTPPEAP QGEPQALDTL QRAREYNARL FGLAQRSARA LLDYGVTADA RALLAGQRHL
LMAQDENGDT PLHLAIIHGQ TGVIEQIAHV IYHAQYLGVI NLTNHLHQTP LHLAVITGQT
RVVSFLLQVG ADPTLLDRHG DSALHLALRA GAAAPELLQA LLRSGAHAVP QILHMPDFEG
LYPVHLAVHA RSPECLDLLV DCGAEVEAPE RQGGRTALHL ATEMEELGLV THLVTKLHAN
VNARTFAGNT PLHLAAGLGS PTLTRLLLKA GADIHAENEE PLCPLPSPST SGSDSDSEGP
ERDTQRNFRG HTPLDLTCST KVKTLLLNAA QNTTEPPLAP PSPAGPGLSL GDAALQNLEQ
LLDGPEAQGS WAELAERLGL RSLVDTYRKT PSPSGSLLRS YKLAGGDLVG LLEALSDMGL
HEGVRLLKGP ETRDKLPSTE VKEDSAYGSQ SVEQEAEKLC PPPEPPGGLC HGHPQPQVH
