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Q00653 (NFKB2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 181. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·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
H2TF1
Lymphocyte translocation chromosome 10 protein
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2
Oncogene Lyt-10
Short name=Lyt10

Cleaved into the following chain:

  1. Nuclear factor NF-kappa-B p52 subunit
Gene names
Name:NFKB2
Synonyms:LYT10
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length900 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. Ref.14

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. Directly interacts with MEN1. Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.23 Ref.25

Subcellular location

Nucleus. Cytoplasm. Note: Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B).

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.

Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing.

Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain.

Involvement in disease

A chromosomal aberration involving NFKB2 is found in a case of B-cell non Hodgkin lymphoma (B-NHL). Translocation t(10;14)(q24;q32) with IGHA1. The resulting oncogene is also called Lyt-10C alpha variant.

A chromosomal aberration involving NFKB2 is found in a cutaneous T-cell leukemia (C-TCL) cell line. This rearrangement produces the p80HT gene which codes for a truncated 80 kDa protein (p80HT).

In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.

Immunodeficiency, common variable, 10 (CVID10) [MIM:615577]: A primary immunodeficiency characterized by childhood-onset of recurrent infections, hypogammaglobulinemia, and decreased numbers of memory and marginal zone B-cells. Some patients may develop autoimmune features and have circulating autoantibodies. An unusual feature is central adrenal insufficiency.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.29

Sequence similarities

Contains 7 ANK repeats.

Contains 1 death domain.

Contains 1 RHD (Rel-like) domain.

Sequence caution

The sequence CAA43715.1 differs from that shown. Reason: Frameshift at positions 456, 458, 470 and 900.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Chromosomal rearrangement
Polymorphism
   DiseaseDisease mutation
Proto-oncogene
   DomainANK repeat
Repeat
   LigandDNA-binding
   Molecular functionActivator
   PTMIsopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

follicular dendritic cell differentiation

Inferred from electronic annotation. Source: Ensembl

germinal center formation

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Traceable author statement. Source: Reactome

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

regulation of transcription, DNA-templated

Inferred from direct assay Ref.12. Source: UniProtKB

spleen development

Inferred from electronic annotation. Source: Ensembl

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentBcl3/NF-kappaB2 complex

Inferred from direct assay PubMed 9407099. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 15677444. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay PubMed 15677444. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 14743216. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Traceable author statement Ref.20Ref.1. Source: ProtInc

transcription coactivator activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q00653-1)

Also known as: p100;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 3 (identifier: Q00653-3)

Also known as: p49;

The sequence of this isoform differs from the canonical sequence as follows:
     374-428: GSLGFFPSSL...EAAEPSAPSR → EGVLMEGGVK...RSSRPAWPTA
     429-900: Missing.
Note: Ref.1 (CAA43716.1) sequence(s) differ(s) from that shown due to frameshifts in positions 407, 414.
Isoform 4 (identifier: Q00653-4)

The sequence of this isoform differs from the canonical sequence as follows:
     860-860: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 900900Nuclear factor NF-kappa-B p100 subunit
PRO_0000030321
Chain1 – 454454Nuclear factor NF-kappa-B p52 subunit
PRO_0000030322

Regions

Domain38 – 343306RHD
Repeat487 – 51933ANK 1
Repeat526 – 55530ANK 2
Repeat559 – 59133ANK 3
Repeat599 – 62830ANK 4
Repeat633 – 66331ANK 5
Repeat667 – 69630ANK 6
Repeat729 – 75830ANK 7
Domain764 – 85188Death
Region346 – 37732GRR
Motif337 – 3415Nuclear localization signal Potential
Compositional bias350 – 40051Gly-rich

Sites

Site454 – 4552Cleavage (when cotranslationally processed)
Site490 – 4912Breakpoint for translocation to form NFKB2-IGHA1 oncogene

Amino acid modifications

Modified residue4291Phosphothreonine Ref.26
Modified residue7131Phosphoserine Ref.18
Modified residue7151Phosphoserine Ref.18
Modified residue7171Phosphoserine Ref.18
Modified residue8661Phosphoserine; by MAP3K14 Ref.19
Modified residue8701Phosphoserine; by MAP3K14 Ref.19
Cross-link855Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.24

Natural variations

Alternative sequence374 – 42855GSLGF…SAPSR → EGVLMEGGVKVREAVEEKNL GEAGRGLHACNPALWEAKAG RLPEIRSSRPAWPTA in isoform 3.
VSP_040082
Alternative sequence429 – 900472Missing in isoform 3.
VSP_040083
Alternative sequence8601Missing in isoform 4.
VSP_040084
Natural variant141E → K. Ref.7
Corresponds to variant rs45581936 [ dbSNP | Ensembl ].
VAR_022223
Natural variant3511G → R. Ref.7
Corresponds to variant rs45580031 [ dbSNP | Ensembl ].
VAR_022224
Natural variant3921A → G.
Corresponds to variant rs11574848 [ dbSNP | Ensembl ].
VAR_051781
Natural variant4521G → R. Ref.7
Corresponds to variant rs45471103 [ dbSNP | Ensembl ].
VAR_022225
Natural variant618 – 900283Missing in truncated form EB308.
VAR_018452
Natural variant667 – 6693AGN → SAS in truncated form p80HT.
VAR_006909
Natural variant670 – 900231Missing in truncated form p80HT.
VAR_006910
Natural variant703 – 900198Missing in truncated form LB40.
VAR_018453

Experimental info

Mutagenesis247 – 2493YLL → AAA: Two-fold reduction in heterodimerization with RelA.
Mutagenesis3991P → A: No change in cleavage rate or products.
Mutagenesis4041G → A: No change in cleavage rate or products.
Mutagenesis4051A → P: No change in cleavage rate or products.
Mutagenesis4061Q → N: No change in cleavage rate or products.
Mutagenesis7131S → G: Loss of phosphorylation; when associated with A-715 and A-717.
Mutagenesis7151S → A: Loss of phosphorylation; when associated with G-713 and A-717.
Mutagenesis7171S → A: Loss of phosphorylation; when associated with G-713 and A-715.
Mutagenesis8661S → A: Decrease in MAP3K14-induced phosphorylation; no inducible processing occurs; when associated with A-869. Ref.19
Mutagenesis8701S → A: Decrease in MAP3K14-induced phosphorylation; no inducible processing occurs; when associated with A-865. Ref.19
Sequence conflict1441K → E in AAB21124. Ref.2
Sequence conflict2131I → T in CAA43715. Ref.1
Sequence conflict2131I → T in CAA43716. Ref.1
Sequence conflict2131I → T in AAA68171. Ref.11
Sequence conflict3961G → R in CAA43715. Ref.1
Sequence conflict433 – 4342EP → DA in AAB21124. Ref.2
Sequence conflict4591R → K AA sequence Ref.12
Sequence conflict4651G → C in CAA43715. Ref.1
Sequence conflict4701A → R in CAA43715. Ref.1
Sequence conflict4701A → R in AAB21124. Ref.2
Sequence conflict7411K → L in CAA43715. Ref.1
Sequence conflict8601A → T in AAB21124. Ref.2
Sequence conflict8761E → K in AAB21124. Ref.2
Sequence conflict8911C → S in CAA43715. Ref.1

Secondary structure

.......................................................................... 900
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (p100) [UniParc].

Last modified October 17, 2006. Version 4.
Checksum: 6BAD7038834783CA

FASTA90096,749
        10         20         30         40         50         60 
MESCYNPGLD GIIEYDDFKL NSSIVEPKEP APETADGPYL VIVEQPKQRG FRFRYGCEGP 

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

       130        140        150        160        170        180 
AVSVGPKDMT AQFNNLGVLH VTKKNMMGTM IQKLQRQRLR SRPQGLTEAE QRELEQEAKE 

       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 
GGAAGGYGGA GGGGSLGFFP SSLAYSPYQS GAGPMGCYPG GGGGAQMAAT VPSRDSGEEA 

       430        440        450        460        470        480 
AEPSAPSRTP QCEPQAPEML QRAREYNARL FGLAQRSARA LLDYGVTADA RALLAGQRHL 

       490        500        510        520        530        540 
LTAQDENGDT PLHLAIIHGQ TSVIEQIVYV IHHAQDLGVV NLTNHLHQTP LHLAVITGQT 

       550        560        570        580        590        600 
SVVSFLLRVG ADPALLDRHG DSAMHLALRA GAGAPELLRA LLQSGAPAVP QLLHMPDFEG 

       610        620        630        640        650        660 
LYPVHLAVRA RSPECLDLLV DSGAEVEATE RQGGRTALHL ATEMEELGLV THLVTKLRAN 

       670        680        690        700        710        720 
VNARTFAGNT PLHLAAGLGY PTLTRLLLKA GADIHAENEE PLCPLPSPPT SDSDSDSEGP 

       730        740        750        760        770        780 
EKDTRSSFRG HTPLDLTCST KVKTLLLNAA QNTMEPPLTP PSPAGPGLSL GDTALQNLEQ 

       790        800        810        820        830        840 
LLDGPEAQGS WAELAERLGL RSLVDTYRQT TSPSGSLLRS YELAGGDLAG LLEALSDMGL 

       850        860        870        880        890        900 
EEGVRLLRGP ETRDKLPSTA EVKEDSAYGS QSVEQEAEKL GPPPEPPGGL CHGHPQPQVH 

« Hide

Isoform 3 (p49) [UniParc].

Checksum: E4D38A8635501807
Show »

FASTA42847,021
Isoform 4 [UniParc].

Checksum: B3753FF15B7BDF57
Show »

FASTA89996,678

References

« Hide 'large scale' references
[1]"Cloning of an NF-kappa B subunit which stimulates HIV transcription in synergy with p65."
Schmid R.M., Perkins N.D., Duckett C.S., Andrews P.C., Nabel G.J.
Nature 352:733-736(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4).
Tissue: Leukemia.
[2]"A novel mitogen-inducible gene product related to p50/p105-NF-kappa B participates in transactivation through a kappa B site."
Bours V., Burd P.R., Brown K., Villalobos J., Park S., Ryseck R.P., Bravo R., Kelly K., Siebenlist U.
Mol. Cell. Biol. 12:685-695(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]"Rearrangement and altered expression of the NFKB-2 gene in human cutaneous T-lymphoma cells."
Thakur S., Lin H.C., Tseng W.T., Kumar S., Bravo R., Foss F., Gelinas C., Rabson A.B.
Oncogene 9:2335-2344(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION, P80HT GENERATION.
[4]Rabson A.B.
Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[5]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Thymus.
[7]NIEHS SNPs program
Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LYS-14; ARG-351 AND ARG-452.
[8]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"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] (ISOFORM 4).
Tissue: Lymph.
[11]"Transcriptional regulation of NF-kappa B2: evidence for kappa B-mediated positive and negative autoregulation."
Liptay S., Schmid R.M., Nabel E.G., Nabel G.J.
Mol. Cell. Biol. 14:7695-7703(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-220.
[12]"Purification of the major histocompatibility complex class I transcription factor H2TF1. The full-length product of the nfkb2 gene."
Potter D.A., Larson C.J., Eckes P., Schmid R.M., Nabel G.J., Verdine G.L., Sharp P.A.
J. Biol. Chem. 268:18882-18890(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 459-470; 580-597 AND 636-647 (ISOFORM 1).
[13]"The oncoprotein Bcl-3 directly transactivates through kappa B motifs via association with DNA-binding p50B homodimers."
Bours V., Franzoso G., Azarenko V., Park S., Kanno T., Brown K., Siebenlist U.
Cell 72:729-739(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH BCL3.
[14]"Differential interactions of Rel-NF-kappa B complexes with I kappa B alpha determine pools of constitutive and inducible NF-kappa B activity."
Dobrzanski P., Ryseck R.P., Bravo R.
EMBO J. 13:4608-4616(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN THE NF-KAPPA-B RELB-P52 COMPLEX.
[15]"Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor necrosis factor."
Beg A.A., Baldwin A.S. Jr.
Oncogene 9:1487-1492(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE NF-KAPPA-B P52-C-REL COMPLEX, IDENTIFICATION IN THE NF-KAPPA-B P65-P52 COMPLEX.
[16]"A new member of the IkappaB protein family, IkappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription."
Li Z., Nabel G.J.
Mol. Cell. Biol. 17:6184-6190(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFKBIE.
[17]"The generation of nfkb2 p52: mechanism and efficiency."
Heusch M., Lin L., Geleziunas R., Greene W.C.
Oncogene 18:6201-6208(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: COTRANSLATIONAL FOLDING/PROCESSING OF P100, GENERATION OF P52/P100.
[18]"Differential regulation of NF-kappaB2(p100) processing and control by amino-terminal sequences."
Betts J.C., Nabel G.J.
Mol. Cell. Biol. 16:6363-6371(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-713; SER-715 AND SER-717, MUTAGENESIS, DIMERIZATION, PROTEOLYTIC PROCESSING OF P100.
[19]"NF-kappaB-inducing kinase regulates the processing of NF-kappaB2 p100."
Xiao G., Harhaj E.W., Sun S.-C.
Mol. Cell 7:401-409(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-866 AND SER-870, MUTAGENESIS OF SER-866 AND SER-870, PROTEOLYTIC PROCESSING OF P100.
[20]"B cell lymphoma-associated chromosomal translocation involves candidate oncogene lyt-10, homologous to NF-kappa B p50."
Neri A., Chang C.C., Lombardi L., Salina M., Corradini P., Maiolo A.T., Chaganti R.S., Dalla-Favera R.
Cell 67:1075-1087(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH IGHA1.
[21]"Heterogeneous chromosomal aberrations generate 3' truncations of the NFKB2/lyt-10 gene in lymphoid malignancies."
Migliazza A., Lombardi L., Rocchi M., Trecca D., Chang C.-C., Antonacci R., Fracchiolla N.S., Ciana P., Maiolo A.T., Neri A.
Blood 84:3850-3860(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL ABERRATIONS, GENERATION OF LB40 AND EB308.
[22]"Structural and functional characterization of the promoter regions of the NFKB2 gene."
Lombardi L., Ciana P., Cappellini C., Trecca D., Guerrini L., Migliazza A., Maiolo A.T., Neri A.
Nucleic Acids Res. 23:2328-2336(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF THE TWO PROMOTER REGIONS.
[23]"The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation."
Heppner C., Bilimoria K.Y., Agarwal S.K., Kester M., Whitty L.J., Guru S.C., Chandrasekharappa S.C., Collins F.S., Spiegel A.M., Marx S.J., Burns A.L.
Oncogene 20:4917-4925(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEN1.
[24]"Mechanism of processing of the NF-kappa B2 p100 precursor: identification of the specific polyubiquitin chain-anchoring lysine residue and analysis of the role of NEDD8-modification on the SCF(beta-TrCP) ubiquitin ligase."
Amir R.E., Haecker H., Karin M., Ciechanover A.
Oncogene 23:2540-2547(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION AT LYS-855.
[25]"IL-1 receptor-associated kinase 1 is critical for latent membrane protein 1-induced p65/RelA serine 536 phosphorylation and NF-kappaB activation."
Song Y.J., Jen K.Y., Soni V., Kieff E., Cahir-McFarland E.
Proc. Natl. Acad. Sci. U.S.A. 103:2689-2694(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE NF-KAPPA-B P65-P52 COMPLEX.
[26]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-429, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[27]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[28]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[29]"Germline mutations in NFKB2 implicate the noncanonical NF-kappaB pathway in the pathogenesis of common variable immunodeficiency."
Chen K., Coonrod E.M., Kumanovics A., Franks Z.F., Durtschi J.D., Margraf R.L., Wu W., Heikal N.M., Augustine N.H., Ridge P.G., Hill H.R., Jorde L.B., Weyrich A.S., Zimmerman G.A., Gundlapalli A.V., Bohnsack J.F., Voelkerding K.V.
Am. J. Hum. Genet. 93:812-824(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN CVID10.
[30]"Structure of the human NF-kappaB p52 homodimer-DNA complex at 2.1-A resolution."
Cramer P., Larson C.J., Verdine G.L., Mueller C.W.
EMBO J. 16:7078-7090(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 37-327.
[31]"Solution structure of the death domain of nuclear factor NF-kappa-B p100."
RIKEN structural genomics initiative (RSGI)
Submitted (DEC-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 764-859.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X61498 mRNA. Translation: CAA43715.1. Frameshift.
X61499 mRNA. Translation: CAA43716.1. Frameshift.
S76638 mRNA. Translation: AAB21124.1.
U09609 mRNA. Translation: AAA21462.2.
BT009769 mRNA. Translation: AAP88771.1.
AK292654 mRNA. Translation: BAF85343.1.
AY865619 Genomic DNA. Translation: AAW56071.1.
AL121928 Genomic DNA. Translation: CAC08399.1.
CH471066 Genomic DNA. Translation: EAW49700.1.
CH471066 Genomic DNA. Translation: EAW49701.1.
CH471066 Genomic DNA. Translation: EAW49702.1.
CH471066 Genomic DNA. Translation: EAW49704.1.
CH471066 Genomic DNA. Translation: EAW49706.1.
BC002844 mRNA. Translation: AAH02844.1.
U20816 Genomic DNA. Translation: AAA68171.1.
CCDSCCDS41564.1. [Q00653-1]
CCDS41565.1. [Q00653-4]
PIRA42024.
A57034.
I38609.
S17233.
RefSeqNP_001070962.1. NM_001077494.3. [Q00653-1]
NP_001248332.1. NM_001261403.2. [Q00653-4]
NP_001275653.1. NM_001288724.1. [Q00653-4]
NP_002493.3. NM_002502.5. [Q00653-4]
XP_005269917.1. XM_005269860.1. [Q00653-1]
XP_005269918.1. XM_005269861.2. [Q00653-1]
UniGeneHs.73090.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A3QX-ray2.10A/B37-327[»]
2D96NMR-A766-859[»]
3DO7X-ray3.05B37-329[»]
ProteinModelPortalQ00653.
SMRQ00653. Positions 37-329, 434-752, 772-859.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110858. 47 interactions.
DIPDIP-24239N.
DIP-27535N.
IntActQ00653. 30 interactions.
MINTMINT-7944680.
STRING9606.ENSP00000189444.

Chemistry

BindingDBQ00653.
ChEMBLCHEMBL2094258.

PTM databases

PhosphoSiteQ00653.

Polymorphism databases

DMDM116242678.

Proteomic databases

MaxQBQ00653.
PaxDbQ00653.
PRIDEQ00653.

Protocols and materials databases

DNASU4791.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000189444; ENSP00000189444; ENSG00000077150. [Q00653-4]
ENST00000369966; ENSP00000358983; ENSG00000077150. [Q00653-1]
ENST00000428099; ENSP00000410256; ENSG00000077150. [Q00653-4]
GeneID4791.
KEGGhsa:4791.
UCSCuc001kva.4. human. [Q00653-4]
uc001kvb.4. human. [Q00653-1]

Organism-specific databases

CTD4791.
GeneCardsGC10P104144.
HGNCHGNC:7795. NFKB2.
HPACAB022098.
HPA008422.
HPA023900.
MIM164012. gene.
615577. phenotype.
neXtProtNX_Q00653.
Orphanet1572. Common variable immunodeficiency.
PharmGKBPA31600.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000004822.
HOVERGENHBG052613.
InParanoidQ00653.
KOK04469.
OMAFRGHTPL.
OrthoDBEOG7W154S.
PhylomeDBQ00653.
TreeFamTF325632.

Enzyme and pathway databases

ReactomeREACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressQ00653.
BgeeQ00653.
CleanExHS_NFKB2.
GenevestigatorQ00653.

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. 5 hits.
PF00531. Death. 1 hit.
PF00554. RHD. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
PR00057. NFKBTNSCPFCT.
SMARTSM00248. ANK. 6 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. human.
EvolutionaryTraceQ00653.
GeneWikiNFKB2.
GenomeRNAi4791.
NextBio18458.
PMAP-CutDBQ00653.
PROQ00653.
SOURCESearch...

Entry information

Entry nameNFKB2_HUMAN
AccessionPrimary (citable) accession number: Q00653
Secondary accession number(s): A8K9D9 expand/collapse secondary AC list , D3DR83, Q04860, Q9BU75, Q9H471, Q9H472
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 17, 2006
Last modified: July 9, 2014
This is version 181 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM