UniProt Accession

 NFKB2_HUMAN; Q00653; A8K9D9; D3DR83; Q04860; Q9BU75; Q9H471; Q9H472 

Genbank Protein ID

 X61498; X61499; S76638; U09609; BT009769; AK292654; AY865619; AL121928; CH471066; CH471066; CH471066; CH471066; CH471066; BC002844; U20816 

Genbank Nucleotide ID

 CAA43715.1; CAA43716.1; AAB21124.1; AAA21462.2; AAP88771.1; BAF85343.1; AAW56071.1; CAC08399.1; EAW49700.1; EAW49701.1; EAW49702.1; EAW49704.1; EAW49706.1; AAH02844.1; AAA68171.1 

Protein Name

 Nuclear factor NF-kappa-B p100 subunit 

Protein Synonyms/Alias

 DNA-binding factor KBF2; H2TF1; Lymphocyte translocation chromosome 10 protein; Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2; Oncogene Lyt-10; Lyt10; Nuclear factor NF-kappa-B p52 subunit 

Gene Name

 NFKB2 

Gene Synonyms/Alias

 LYT10 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
72	LPGASSEKGRKTYPT	ubiquitination	[1]
90	CNYEGPAKIEVDLVT	sumoylation	[2]
144	GVLHVTKKNMMGTMI	ubiquitination	[3]
153	MMGTMIQKLQRQRLR	ubiquitination	[3]
229	SPGASNLKISRMDKT	ubiquitination	[3, 4]
283	FSPTDVHKQYAIVFR	ubiquitination	[1]
298	TPPYHKMKIERPVTV	sumoylation	[2]
321	GGDVSDSKQFTYYPL	ubiquitination	[1, 3, 5]
332	YYPLVEDKEEVQRKR	ubiquitination	[1, 3]
656	LVTHLVTKLRANVNA	ubiquitination	[1, 6]
689	TLTRLLLKAGADIHA	sumoylation	[2]
741	LDLTCSTKVKTLLLN	ubiquitination	[1, 3, 4, 5]
855	RGPETRDKLPSTAEV	ubiquitination	[3, 7]
863	LPSTAEVKEDSAYGS	sumoylation	[2]

Reference

 [1] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [2] SUMO1 modification of NF-kappaB2/p100 is essential for stimuli-induced p100 phosphorylation and processing.
 Vatsyayan J, Qing G, Xiao G, Hu J.
 EMBO Rep. 2008 Sep;9(9):885-90. [PMID: 18617892]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [4] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [5] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [6] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [7] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 38 343 RHD.
 REPEAT 487 519 ANK 1.
 REPEAT 526 555 ANK 2.
 REPEAT 559 591 ANK 3.
 REPEAT 599 628 ANK 4.
 REPEAT 633 663 ANK 5.
 REPEAT 667 696 ANK 6.
 REPEAT 729 758 ANK 7.
 DOMAIN 764 851 Death.
 REGION 346 377 GRR.
 MOTIF 337 341 Nuclear localization signal (Potential).
 MOD_RES 429 429 Phosphothreonine.
 MOD_RES 713 713 Phosphoserine.
 MOD_RES 715 715 Phosphoserine.
 MOD_RES 717 717 Phosphoserine.
 MOD_RES 866 866 Phosphoserine; by MAP3K14.
 MOD_RES 870 870 Phosphoserine; by MAP3K14.
 CROSSLNK 855 855 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Activator; Alternative splicing; ANK repeat; Chromosomal rearrangement; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Repeat; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 900 AA 

Protein Sequence

Gene Ontology

 GO:0033257; C:Bcl3/NF-kappaB2 complex; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
 GO:0003713; F:transcription coactivator activity; TAS:ProtInc.
 GO:0030198; P:extracellular matrix organization; IEA:Compara.
 GO:0002268; P:follicular dendritic cell differentiation; IEA:Compara.
 GO:0002467; P:germinal center formation; IEA:Compara.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
 GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
 GO:0048536; P:spleen development; IEA:Compara.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 

Interpro

 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_TIG_rcpt.
 IPR000451; NF_Rel_Dor.
 IPR008967; p53-like_TF_DNA-bd.
 IPR011539; RHD. 

Pfam

 PF00023; Ank
 PF00531; Death
 PF00554; RHD 

SMART

 SM00248; ANK
 SM00005; DEATH
 SM00429; IPT 

PROSITE

 PS50297; ANK_REP_REGION
 PS50088; ANK_REPEAT
 PS50017; DEATH_DOMAIN
 PS01204; REL_1
 PS50254; REL_2 

PRINTS

 PR01415; ANKYRIN.
 PR00057; NFKBTNSCPFCT.