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Protein

Nuclear factor NF-kappa-B p100 subunit

Gene

NFKB2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-ARNTL/BMAL1 heterodimer.1 Publication

GO - Molecular functioni

  • chromatin binding Source: GO_Central
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcription coactivator activity Source: ProtInc
  • transcription factor activity, sequence-specific DNA binding Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator, Repressor

Keywords - Biological processi

Biological rhythms, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000077150-MONOMER.
ReactomeiR-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-3214841. PKMTs methylate histone lysines.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-448706. Interleukin-1 processing.
R-HSA-5603027. IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
R-HSA-5603029. IkBA variant leads to EDA-ID.
R-HSA-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-HSA-5676590. NIK-->noncanonical NF-kB signaling.
R-HSA-933542. TRAF6 mediated NF-kB activation.
SIGNORiQ00653.

Names & Taxonomyi

Protein namesi
Recommended 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:
Gene namesi
Name:NFKB2
Synonyms:LYT10
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:7795. NFKB2.

Subcellular locationi

  • Nucleus
  • Cytoplasm

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

GO - Cellular componenti

  • Bcl3/NF-kappaB2 complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: GO_Central
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:615577
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074035865D → G in CVID10; unknown pathological significance; de novo mutation. 1 PublicationCorresponds to variant rs727502787dbSNPEnsembl.1
Natural variantiVAR_074036867A → V in CVID10; unknown pathological significance; de novo mutation. 1 PublicationCorresponds to variant rs727502788dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi247 – 249YLL → AAA: Two-fold reduction in heterodimerization with RelA. 1 Publication3
Mutagenesisi399P → A: No change in cleavage rate or products. 1 Publication1
Mutagenesisi404G → A: No change in cleavage rate or products. 1 Publication1
Mutagenesisi405A → P: No change in cleavage rate or products. 1 Publication1
Mutagenesisi406Q → N: No change in cleavage rate or products. 1 Publication1
Mutagenesisi713S → G: Loss of phosphorylation; when associated with A-715 and A-717. 1 Publication1
Mutagenesisi715S → A: Loss of phosphorylation; when associated with G-713 and A-717. 1 Publication1
Mutagenesisi717S → A: Loss of phosphorylation; when associated with G-713 and A-715. 1 Publication1
Mutagenesisi866S → A: Decrease in MAP3K14-induced phosphorylation; no inducible processing occurs; when associated with A-869. 1 Publication1
Mutagenesisi870S → A: Decrease in MAP3K14-induced phosphorylation; no inducible processing occurs; when associated with A-865. 1 Publication1

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei490 – 491Breakpoint for translocation to form NFKB2-IGHA1 oncogene2

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

DisGeNETi4791.
MalaCardsiNFKB2.
MIMi615577. phenotype.
OpenTargetsiENSG00000077150.
Orphaneti1572. Common variable immunodeficiency.
PharmGKBiPA31600.

Chemistry databases

ChEMBLiCHEMBL3003.
DrugBankiDB00945. Acetylsalicylic acid.
DB01296. Glucosamine.

Polymorphism and mutation databases

DMDMi116242678.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000303211 – 900Nuclear factor NF-kappa-B p100 subunitAdd BLAST900
ChainiPRO_00000303221 – 454Nuclear factor NF-kappa-B p52 subunitAdd BLAST454

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei23PhosphoserineCombined sources1
Modified residuei161PhosphoserineCombined sources1
Modified residuei429PhosphothreonineCombined sources1
Modified residuei713Phosphoserine1 Publication1
Modified residuei715Phosphoserine1 Publication1
Modified residuei717Phosphoserine1 Publication1
Modified residuei812PhosphoserineCombined sources1
Cross-linki855Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei866Phosphoserine; by MAP3K141 Publication1
Modified residuei870Phosphoserine; by MAP3K141 Publication1

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.
Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing.3 Publications
Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain.

Sites

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

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ00653.
MaxQBiQ00653.
PaxDbiQ00653.
PeptideAtlasiQ00653.
PRIDEiQ00653.

PTM databases

iPTMnetiQ00653.
PhosphoSitePlusiQ00653.
SwissPalmiQ00653.

Miscellaneous databases

PMAP-CutDBQ00653.

Expressioni

Gene expression databases

BgeeiENSG00000077150.
CleanExiHS_NFKB2.
ExpressionAtlasiQ00653. baseline and differential.
GenevisibleiQ00653. HS.

Organism-specific databases

HPAiCAB022098.
HPA008422.
HPA023900.

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. Directly interacts with MEN1.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAP3K8P412792EBI-307326,EBI-354900
MEN1O00255-23EBI-9869360,EBI-9869387
NFKB1P198388EBI-307326,EBI-300010
RELQ048643EBI-307326,EBI-307352
RELBQ012013EBI-307326,EBI-357837
SUMO1P631652EBI-307326,EBI-80140

Protein-protein interaction databases

BioGridi110858. 52 interactors.
DIPiDIP-24239N.
DIP-27535N.
IntActiQ00653. 36 interactors.
MINTiMINT-7944680.
STRINGi9606.ENSP00000358983.

Structurei

Secondary structure

1900
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi39 – 44Combined sources6
Beta strandi48 – 51Combined sources4
Turni56 – 58Combined sources3
Beta strandi79 – 83Combined sources5
Beta strandi87 – 96Combined sources10
Beta strandi98 – 101Combined sources4
Beta strandi106 – 111Combined sources6
Beta strandi116 – 118Combined sources3
Beta strandi120 – 124Combined sources5
Beta strandi130 – 132Combined sources3
Beta strandi136 – 140Combined sources5
Turni143 – 145Combined sources3
Helixi146 – 158Combined sources13
Turni159 – 161Combined sources3
Helixi168 – 182Combined sources15
Beta strandi189 – 198Combined sources10
Beta strandi205 – 207Combined sources3
Beta strandi217 – 219Combined sources3
Beta strandi220 – 222Combined sources3
Turni223 – 225Combined sources3
Beta strandi230 – 234Combined sources5
Beta strandi236 – 239Combined sources4
Beta strandi240 – 242Combined sources3
Beta strandi245 – 252Combined sources8
Turni255 – 257Combined sources3
Beta strandi258 – 264Combined sources7
Beta strandi266 – 268Combined sources3
Beta strandi270 – 273Combined sources4
Helixi278 – 280Combined sources3
Turni283 – 285Combined sources3
Beta strandi286 – 290Combined sources5
Beta strandi303 – 311Combined sources9
Turni312 – 314Combined sources3
Beta strandi321 – 326Combined sources6
Helixi439 – 467Combined sources29
Helixi470 – 475Combined sources6
Helixi476 – 480Combined sources5
Helixi491 – 497Combined sources7
Helixi501 – 512Combined sources12
Turni513 – 515Combined sources3
Helixi519 – 521Combined sources3
Helixi530 – 536Combined sources7
Helixi540 – 548Combined sources9
Helixi563 – 567Combined sources5
Helixi575 – 582Combined sources8
Helixi586 – 588Combined sources3
Turni589 – 593Combined sources5
Turni597 – 599Combined sources3
Helixi603 – 609Combined sources7
Helixi613 – 621Combined sources9
Turni631 – 633Combined sources3
Helixi637 – 643Combined sources7
Helixi647 – 654Combined sources8
Turni655 – 657Combined sources3
Helixi671 – 678Combined sources8
Helixi681 – 689Combined sources9
Turni733 – 735Combined sources3
Helixi740 – 751Combined sources12
Beta strandi752 – 754Combined sources3
Helixi772 – 782Combined sources11
Beta strandi783 – 786Combined sources4
Helixi791 – 798Combined sources8
Helixi801 – 808Combined sources8
Helixi813 – 823Combined sources11
Helixi828 – 838Combined sources11
Helixi841 – 848Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A3QX-ray2.10A/B37-327[»]
2D96NMR-A766-859[»]
3DO7X-ray3.05B37-329[»]
4OT9X-ray3.35A407-765[»]
ProteinModelPortaliQ00653.
SMRiQ00653.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ00653.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini38 – 343RHDPROSITE-ProRule annotationAdd BLAST306
Repeati487 – 519ANK 1Add BLAST33
Repeati526 – 555ANK 2Add BLAST30
Repeati559 – 591ANK 3Add BLAST33
Repeati599 – 628ANK 4Add BLAST30
Repeati633 – 663ANK 5Add BLAST31
Repeati667 – 696ANK 6Add BLAST30
Repeati729 – 758ANK 7Add BLAST30
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 biasi350 – 400Gly-richAdd BLAST51

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.

Sequence similaritiesi

Contains 7 ANK repeats.PROSITE-ProRule annotation
Contains 1 death domain.Curated
Contains 1 RHD (Rel-like) domain.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00500000044765.
HOGENOMiHOG000004822.
HOVERGENiHBG052613.
InParanoidiQ00653.
KOiK04469.
OMAiFRGHTPL.
OrthoDBiEOG091G03PF.
PhylomeDBiQ00653.
TreeFamiTF325632.

Family and domain databases

CDDicd01177. IPT_NFkappaB. 1 hit.
Gene3Di1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR033926. IPT_NFkappaB.
IPR000451. NFkB/Dor.
IPR030497. NFkB_p100.
IPR008967. p53-like_TF_DNA-bd.
IPR030492. RHD_CS.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
[Graphical view]
PANTHERiPTHR24169. PTHR24169. 2 hits.
PTHR24169:SF21. PTHR24169:SF21. 2 hits.
PfamiPF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
PF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
PR00057. NFKBTNSCPFCT.
SMARTiSM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
SM00429. IPT. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q00653-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MESCYNPGLD GIIEYDDFKL NSSIVEPKEP APETADGPYL VIVEQPKQRG
60 70 80 90 100
FRFRYGCEGP SHGGLPGASS EKGRKTYPTV KICNYEGPAK IEVDLVTHSD
110 120 130 140 150
PPRAHAHSLV GKQCSELGIC AVSVGPKDMT AQFNNLGVLH VTKKNMMGTM
160 170 180 190 200
IQKLQRQRLR SRPQGLTEAE QRELEQEAKE 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 GGAAGGYGGA GGGGSLGFFP SSLAYSPYQS GAGPMGCYPG
410 420 430 440 450
GGGGAQMAAT VPSRDSGEEA AEPSAPSRTP QCEPQAPEML QRAREYNARL
460 470 480 490 500
FGLAQRSARA LLDYGVTADA RALLAGQRHL LTAQDENGDT PLHLAIIHGQ
510 520 530 540 550
TSVIEQIVYV IHHAQDLGVV NLTNHLHQTP LHLAVITGQT SVVSFLLRVG
560 570 580 590 600
ADPALLDRHG DSAMHLALRA GAGAPELLRA LLQSGAPAVP QLLHMPDFEG
610 620 630 640 650
LYPVHLAVRA RSPECLDLLV DSGAEVEATE RQGGRTALHL ATEMEELGLV
660 670 680 690 700
THLVTKLRAN VNARTFAGNT PLHLAAGLGY PTLTRLLLKA GADIHAENEE
710 720 730 740 750
PLCPLPSPPT SDSDSDSEGP EKDTRSSFRG HTPLDLTCST KVKTLLLNAA
760 770 780 790 800
QNTMEPPLTP PSPAGPGLSL GDTALQNLEQ LLDGPEAQGS WAELAERLGL
810 820 830 840 850
RSLVDTYRQT TSPSGSLLRS YELAGGDLAG LLEALSDMGL EEGVRLLRGP
860 870 880 890 900
ETRDKLPSTA EVKEDSAYGS QSVEQEAEKL GPPPEPPGGL CHGHPQPQVH
Length:900
Mass (Da):96,749
Last modified:October 17, 2006 - v4
Checksum:i6BAD7038834783CA
GO
Isoform 3 (identifier: Q00653-3) [UniParc]FASTAAdd to basket
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: PubMed:1876189 (CAA43716.1) sequence(s) differ(s) from that shown due to frameshifts in positions 407, 414.
Show »
Length:428
Mass (Da):47,021
Checksum:iE4D38A8635501807
GO
Isoform 4 (identifier: Q00653-4) [UniParc]FASTAAdd to basket

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

Show »
Length:899
Mass (Da):96,678
Checksum:iB3753FF15B7BDF57
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti144K → E in AAB21124 (PubMed:1531086).Curated1
Sequence conflicti213I → T in CAA43715 (PubMed:1876189).Curated1
Sequence conflicti213I → T in CAA43716 (PubMed:1876189).Curated1
Sequence conflicti213I → T in AAA68171 (PubMed:7969113).Curated1
Sequence conflicti396G → R in CAA43715 (PubMed:1876189).Curated1
Sequence conflicti433 – 434EP → DA in AAB21124 (PubMed:1531086).Curated2
Sequence conflicti459R → K AA sequence (PubMed:8360178).Curated1
Sequence conflicti465G → C in CAA43715 (PubMed:1876189).Curated1
Sequence conflicti470A → R in CAA43715 (PubMed:1876189).Curated1
Sequence conflicti470A → R in AAB21124 (PubMed:1531086).Curated1
Sequence conflicti741K → L in CAA43715 (PubMed:1876189).Curated1
Sequence conflicti860A → T in AAB21124 (PubMed:1531086).Curated1
Sequence conflicti876E → K in AAB21124 (PubMed:1531086).Curated1
Sequence conflicti891C → S in CAA43715 (PubMed:1876189).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02222314E → K.1 PublicationCorresponds to variant rs45581936dbSNPEnsembl.1
Natural variantiVAR_022224351G → R.1 PublicationCorresponds to variant rs45580031dbSNPEnsembl.1
Natural variantiVAR_051781392A → G.Corresponds to variant rs11574848dbSNPEnsembl.1
Natural variantiVAR_022225452G → R.1 PublicationCorresponds to variant rs45471103dbSNPEnsembl.1
Natural variantiVAR_018452618 – 900Missing in truncated form EB308. Add BLAST283
Natural variantiVAR_006909667 – 669AGN → SAS in truncated form p80HT. 3
Natural variantiVAR_006910670 – 900Missing in truncated form p80HT. Add BLAST231
Natural variantiVAR_018453703 – 900Missing in truncated form LB40. Add BLAST198
Natural variantiVAR_074035865D → G in CVID10; unknown pathological significance; de novo mutation. 1 PublicationCorresponds to variant rs727502787dbSNPEnsembl.1
Natural variantiVAR_074036867A → V in CVID10; unknown pathological significance; de novo mutation. 1 PublicationCorresponds to variant rs727502788dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_040082374 – 428GSLGF…SAPSR → EGVLMEGGVKVREAVEEKNL GEAGRGLHACNPALWEAKAG RLPEIRSSRPAWPTA in isoform 3. 1 PublicationAdd BLAST55
Alternative sequenceiVSP_040083429 – 900Missing in isoform 3. 1 PublicationAdd BLAST472
Alternative sequenceiVSP_040084860Missing in isoform 4. 4 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41564.1. [Q00653-1]
CCDS41565.1. [Q00653-4]
PIRiA42024.
A57034.
I38609.
S17233.
RefSeqiNP_001070962.1. NM_001077494.3. [Q00653-1]
NP_001248332.1. NM_001261403.2. [Q00653-4]
NP_001275653.1. NM_001288724.1. [Q00653-4]
NP_001309863.1. NM_001322934.1. [Q00653-1]
NP_001309864.1. NM_001322935.1.
NP_002493.3. NM_002502.5. [Q00653-4]
UniGeneiHs.73090.

Genome annotation databases

EnsembliENST00000189444; ENSP00000189444; ENSG00000077150. [Q00653-4]
ENST00000369966; ENSP00000358983; ENSG00000077150. [Q00653-1]
ENST00000428099; ENSP00000410256; ENSG00000077150. [Q00653-4]
GeneIDi4791.
KEGGihsa:4791.
UCSCiuc001kva.4. human. [Q00653-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41564.1. [Q00653-1]
CCDS41565.1. [Q00653-4]
PIRiA42024.
A57034.
I38609.
S17233.
RefSeqiNP_001070962.1. NM_001077494.3. [Q00653-1]
NP_001248332.1. NM_001261403.2. [Q00653-4]
NP_001275653.1. NM_001288724.1. [Q00653-4]
NP_001309863.1. NM_001322934.1. [Q00653-1]
NP_001309864.1. NM_001322935.1.
NP_002493.3. NM_002502.5. [Q00653-4]
UniGeneiHs.73090.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1A3QX-ray2.10A/B37-327[»]
2D96NMR-A766-859[»]
3DO7X-ray3.05B37-329[»]
4OT9X-ray3.35A407-765[»]
ProteinModelPortaliQ00653.
SMRiQ00653.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110858. 52 interactors.
DIPiDIP-24239N.
DIP-27535N.
IntActiQ00653. 36 interactors.
MINTiMINT-7944680.
STRINGi9606.ENSP00000358983.

Chemistry databases

ChEMBLiCHEMBL3003.
DrugBankiDB00945. Acetylsalicylic acid.
DB01296. Glucosamine.

PTM databases

iPTMnetiQ00653.
PhosphoSitePlusiQ00653.
SwissPalmiQ00653.

Polymorphism and mutation databases

DMDMi116242678.

Proteomic databases

EPDiQ00653.
MaxQBiQ00653.
PaxDbiQ00653.
PeptideAtlasiQ00653.
PRIDEiQ00653.

Protocols and materials databases

DNASUi4791.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000189444; ENSP00000189444; ENSG00000077150. [Q00653-4]
ENST00000369966; ENSP00000358983; ENSG00000077150. [Q00653-1]
ENST00000428099; ENSP00000410256; ENSG00000077150. [Q00653-4]
GeneIDi4791.
KEGGihsa:4791.
UCSCiuc001kva.4. human. [Q00653-1]

Organism-specific databases

CTDi4791.
DisGeNETi4791.
GeneCardsiNFKB2.
HGNCiHGNC:7795. NFKB2.
HPAiCAB022098.
HPA008422.
HPA023900.
MalaCardsiNFKB2.
MIMi164012. gene.
615577. phenotype.
neXtProtiNX_Q00653.
OpenTargetsiENSG00000077150.
Orphaneti1572. Common variable immunodeficiency.
PharmGKBiPA31600.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00500000044765.
HOGENOMiHOG000004822.
HOVERGENiHBG052613.
InParanoidiQ00653.
KOiK04469.
OMAiFRGHTPL.
OrthoDBiEOG091G03PF.
PhylomeDBiQ00653.
TreeFamiTF325632.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000077150-MONOMER.
ReactomeiR-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-3214841. PKMTs methylate histone lysines.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-448706. Interleukin-1 processing.
R-HSA-5603027. IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
R-HSA-5603029. IkBA variant leads to EDA-ID.
R-HSA-5607761. Dectin-1 mediated noncanonical NF-kB signaling.
R-HSA-5676590. NIK-->noncanonical NF-kB signaling.
R-HSA-933542. TRAF6 mediated NF-kB activation.
SIGNORiQ00653.

Miscellaneous databases

ChiTaRSiNFKB2. human.
EvolutionaryTraceiQ00653.
GeneWikiiNFKB2.
GenomeRNAii4791.
PMAP-CutDBQ00653.
PROiQ00653.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000077150.
CleanExiHS_NFKB2.
ExpressionAtlasiQ00653. baseline and differential.
GenevisibleiQ00653. HS.

Family and domain databases

CDDicd01177. IPT_NFkappaB. 1 hit.
Gene3Di1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR033926. IPT_NFkappaB.
IPR000451. NFkB/Dor.
IPR030497. NFkB_p100.
IPR008967. p53-like_TF_DNA-bd.
IPR030492. RHD_CS.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
[Graphical view]
PANTHERiPTHR24169. PTHR24169. 2 hits.
PTHR24169:SF21. PTHR24169:SF21. 2 hits.
PfamiPF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
PF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
PR00057. NFKBTNSCPFCT.
SMARTiSM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
SM00429. IPT. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNFKB2_HUMAN
AccessioniPrimary (citable) accession number: Q00653
Secondary accession number(s): A8K9D9
, D3DR83, Q04860, Q9BU75, Q9H471, Q9H472
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 17, 2006
Last modified: November 30, 2016
This is version 208 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.