Reactome | UniProt:Q00653 NFKB2

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UniProt:Q00653 NFKB2 Show undefined attributes

chain	chain:1-900 chain:1-454
checksum	6BAD7038834783CA
comment	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 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-BMAL1 heterodimer.SUBUNIT 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.INTERACTION Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B).ALTERNATIVE PRODUCTS The C-terminus of p100 might be involved in cytoplasmic retention, inhibition of DNA-binding by p52 homodimers, and/or transcription activation.DOMAIN The glycine-rich region (GRR) appears to be a critical element in the generation of p52.PTM 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.PTM Subsequent to MAP3K14-dependent serine phosphorylation, p100 polyubiquitination occurs then triggering its proteasome-dependent processing.PTM Constitutive processing is tightly suppressed by its C-terminal processing inhibitory domain, named PID, which contains the death domain.PTM Ubiquitinated by TRIM55; leading to processing by VCP and subsequent ubiquitin-dependent protein degradation by the proteasome.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.DISEASE 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).DISEASE In B-cell leukemia (B-CLL) cell line, LB40 and EB308, can be found after heterogeneous chromosomal aberrations, such as internal deletions.DISEASE The disease is caused by variants affecting the gene represented in this entry.
crossReference	[DatabaseIdentifier:11785161] GeneCards:NFKB2 [DatabaseIdentifier:12405259] RefSeq:NP_001309864.1 [DatabaseIdentifier:12405262] RefSeq:NP_001275653.1 [DatabaseIdentifier:12405261] RefSeq:NP_001309863.1 [DatabaseIdentifier:12405258] RefSeq:NP_001248332.1 [DatabaseIdentifier:12405257] RefSeq:NP_001070962.1 [DatabaseIdentifier:12405260] RefSeq:NP_002493.3 [DatabaseIdentifier:12283074] Pharos - Targets:Q00653 [DatabaseIdentifier:12241326] PRO:Q00653 [DatabaseIdentifier:12163796] PDB:7VUP [DatabaseIdentifier:12163797] PDB:3DO7 [DatabaseIdentifier:12163802] PDB:4OT9 [DatabaseIdentifier:12163803] PDB:1A3Q [DatabaseIdentifier:12163799] PDB:5ZMC [DatabaseIdentifier:12163804] PDB:7W7L [DatabaseIdentifier:12163798] PDB:7VUQ [DatabaseIdentifier:12163801] PDB:2D96 [DatabaseIdentifier:12147092] PDB:8G8S [DatabaseIdentifier:12163800] PDB:7CLI [DatabaseIdentifier:12147094] PDB:8G8Q [DatabaseIdentifier:12137457] Orphanet:NFKB2 [DatabaseIdentifier:12122753] OpenTargets:ENSG00000077150 [DatabaseIdentifier:11838249] HPA:ENSG00000077150-NFKB2 [DatabaseIdentifier:11800686] GlyGen:Q00653 [DatabaseIdentifier:11488641] ENSEMBL:ENSG00000077150 [DatabaseIdentifier:11594096] ENSEMBL:ENSP00000498308 [DatabaseIdentifier:11594097] ENSEMBL:ENSP00000499294 [DatabaseIdentifier:11594095] ENSEMBL:ENSP00000358983 [DatabaseIdentifier:11594098] ENSEMBL:ENSP00000189444 [DatabaseIdentifier:11594094] ENSEMBL:ENSP00000410256 [DatabaseIdentifier:11716797] ENSEMBL:ENST00000369966 [DatabaseIdentifier:11716794] ENSEMBL:ENST00000652277 [DatabaseIdentifier:11716793] ENSEMBL:ENST00000189444 [DatabaseIdentifier:11716795] ENSEMBL:ENST00000661543 [DatabaseIdentifier:11716796] ENSEMBL:ENST00000428099
databaseName	UniProt
dbId	57857
description	recommendedName: Nuclear factor NF-kappa-B p100 subunit alternativeName: DNA-binding factor KBF2 alternativeName: H2TF1 alternativeName: Lymphocyte translocation chromosome 10 protein alternativeName: Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 alternativeName: Oncogene Lyt-10 shortName: Lyt10 component recommendedName: Nuclear factor NF-kappa-B p52 subunit /component
displayName	UniProt:Q00653 NFKB2
geneName	NFKB2 LYT10
identifier	Q00653
isSequenceChanged	false
keyword	3D-structure Activator Alternative splicing ANK repeat Biological rhythms Chromosomal rearrangement Cytoplasm Direct protein sequencing Disease variant DNA-binding Isopeptide bond Nucleus Phosphoprotein Proteomics identification Proto-oncogene Reference proteome Repeat Repressor Transcription Transcription regulation Ubl conjugation
modified	[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	NFKB2
otherIdentifier	11725153_a_at 16708623 207535_3p_s_at 207535_PM_s_at 207535_s_at 209636_3p_at 209636_PM_at 209636_at 3261644 3261645 3261646 3261647 3261648 3261649 3261650 3261651 3261652 3261653 3261654 3261655 3261656 3261657 3261658 3261659 3261660 3261661 3261662 3261663 3261664 3261665 3261666 3261667 3261668 3261669 3261670 3261671 3261672 3261673 3261674 3261675 3261676 3261677 3261678 3261679 3261680 3261681 3261682 40362_at 4791 535_s_at 544_at 545_g_at 7930074 A_14_P114090 A_23_P202156 GE81163 GO:0000785 GO:0000978 GO:0000981 GO:0001228 GO:0002268 GO:0002467 GO:0003677 GO:0003700 GO:0005515 GO:0005634 GO:0005654 GO:0005737 GO:0005829 GO:0006355 GO:0007165 GO:0007249 GO:0030198 GO:0032496 GO:0033256 GO:0033257 GO:0034097 GO:0038061 GO:0045944 GO:0048511 GO:0048536 GO:0048856 GO:0141124 GO:1990837 HMNXSV003045072 ILMN_1799062 ILMN_2247868 ILMN_2390859 PH_hs_0027671 S76638_at TC10000753.hg U20816_s_at g12803988_3p_at g12803988_3p_x_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-177674] NFKB2(1-454) [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-168144] NFKB2(1-454) [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5607629] p-7S-p100 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5607636] K48-polyUb-p-7S-p100 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-2677931] NFKB2(1-900) [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-4755500] monoSUMO1-K90,K298,K689,K863-NFKB2(1-900) [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000077150] ENSEMBL:ENSG00000077150 NFKB2 [ReferenceDNASequence:12747463] UCSC:Q00653 NFKB2 [ReferenceDNASequence:12108341] OMIM:164012 NFKB2 [ReferenceDNASequence:12067805] NCBI Gene:4791 NFKB2 [ReferenceDNASequence:11983712] Monarch:4791 NFKB2 [ReferenceDNASequence:11893512] KEGG:hsa:4791 NFKB2 [ReferenceDNASequence:11816788] HGNC:7795 NFKB2 [ReferenceDNASequence:11353923] BioGPS Gene:4791 NFKB2 [ReferenceDNASequence:11401212] COSMIC - genes:NFKB2 NFKB2 [ReferenceDNASequence:11409500] CTD Gene:4791 NFKB2 [ReferenceDNASequence:11438491] dbSNP Gene:4791 NFKB2
referenceTranscript	[ReferenceRNASequence:12586962] RefSeq:NM_001322934.2 NFKB2 [ReferenceRNASequence:12586964] RefSeq:NM_001077494.3 NFKB2 [ReferenceRNASequence:12586963] RefSeq:NM_001322935.1 NFKB2 [ReferenceRNASequence:12586965] RefSeq:NM_002502.5 NFKB2 [ReferenceRNASequence:12586960] RefSeq:NM_001261403.3 NFKB2 [ReferenceRNASequence:12586961] RefSeq:NM_001288724.1 NFKB2
schemaClass	ReferenceGeneProduct
secondaryIdentifier	NFKB2_HUMAN A8K9D9 D3DR83 Q04860 Q9BU75 Q9H471 Q9H472
sequenceLength	900
species	[Species:48887] Homo sapiens
stId	uniprot:Q00653
url	http://purl.uniprot.org/uniprot/Q00653

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-177674] NFKB2(1-454) [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-168144] NFKB2(1-454) [cytosol] [EntityWithAccessionedSequence:R-HSA-5607629] p-7S-p100 [cytosol] [EntityWithAccessionedSequence:R-HSA-5607636] K48-polyUb-p-7S-p100 [cytosol] [EntityWithAccessionedSequence:R-HSA-2677931] NFKB2(1-900) [cytosol] [EntityWithAccessionedSequence:R-HSA-4755500] monoSUMO1-K90,K298,K689,K863-NFKB2(1-900) [cytosol]
(referenceSequence)	[ModifiedResidue:5607653] O-phospho-L-serine at 108 [ModifiedResidue:5607637] O-phospho-L-serine at 123 [ModifiedResidue:5607639] O-phospho-L-serine at 872 [ModifiedResidue:5607632] O-phospho-L-serine at 866 [ModifiedResidue:5607648] O-phospho-L-serine at 870 [ModifiedResidue:5607660] O-phospho-L-serine at 115 [ModifiedResidue:5607630] O-phospho-L-serine at 99 [GroupModifiedResidue:5607651] ubiquitinylated lysine (K48polyUb [cytosol]) at 855 [GroupModifiedResidue:4755481] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 90 [GroupModifiedResidue:4755529] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 689 [GroupModifiedResidue:4755427] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 863 [GroupModifiedResidue:4755431] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 298
(interactor)	[UndirectedInteraction:11170093] UniProt:P41279 <-> UniProt:Q00653 (IntAct) [UndirectedInteraction:11173531] UniProt:P09917 <-> UniProt:Q00653 (IntAct) [UndirectedInteraction:11184861] UniProt:Q15653 <-> UniProt:Q00653 (IntAct) [UndirectedInteraction:11214601] UniProt:Q00653 <-> UniProt:P19838 (IntAct) [UndirectedInteraction:11214603] UniProt:Q00653 <-> UniProt:P25963 (IntAct) [UndirectedInteraction:11214605] UniProt:Q00653 <-> UniProt:Q01201 (IntAct) [UndirectedInteraction:11214607] UniProt:Q00653 <-> UniProt:Q04864 (IntAct) [UndirectedInteraction:11214609] UniProt:Q00653 <-> UniProt:Q9NWT6 (IntAct) [UndirectedInteraction:11214611] UniProt:Q00653 <-> UniProt:Q99558 (IntAct) [UndirectedInteraction:11214613] UniProt:Q00653 <-> UniProt:Q9H4E7 (IntAct) [UndirectedInteraction:11214615] UniProt:Q00653 <-> UniProt:Q9ULW8 (IntAct) [UndirectedInteraction:11214617] UniProt:Q00653 <-> UniProt:P12273 (IntAct) [UndirectedInteraction:11214619] UniProt:Q00653 <-> UniProt:Q8NI38 (IntAct)