NFKB1

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NFKB1

Identity

Other names NF-kB p105

NF-kB p50

Hugo NFKB1

Location 4q23-q24

Note see also, in the Deep Insight section: Upstream Signal Transduction of NF-kB Activation

DNA/RNA

Description The gene encoding human nfkb1 has 24 exons spanning 156 kb. The expression of nfkb1 can be positively regulated by NF-kB itself and possibly Ets family transcription factors.

Protein

Description The nfkb1 gene encodes a protein composed 968 amino acids with an approximately molecular weight of 105 kDa, which was considered as a precursor of p50 subunit of NF-kB complexes. In the N-terminal region of NF-kB1, there is a Rel homology domain (RHD) composed of ~300 amino acids that are responsible for DNA binding, dimerization with other Rel family members, and interaction with IkB proteins. The C-terminal region of NF-kB1 contains multiple copies of the so-called ankyrin repeats which is found in IkB family members, including IkBa, IkBb, IkBe, Bcl3, and Drosophila cactus. The earlier studies by several groups demonstrated that NF-kB1 was posttranslationally cleaved to produce the p50 molecule through the ubiquitin-proteasome dependent degradation of the C-terminal portion of NF-kB1. Further studies by Lin and Ghosh suggested that a glycine-rich region (GRR) within the region of 375 to 400 of NF-kB1 is necessary and sufficient for directing the cleavage of NF-kB1. However, recent studies challenged this model and revealed a novel mechanism in which p50 is generated by a unique cotranslational processing event involving the 26S proteasome. In other words, NF-kB1 is not the precursor of p50.

Expression nfkb1 is widely expressed in virtually all type of cells in both adults and in the embryo.

Localisation cytosol, nuclei after activation.

Function regulation of the genes involved in cell-to-cell interaction, intercellular communication, cell recruitment or transmigration, amplification or spreading of primary pathogenic signals, and initiation or acceleration of tumorigenesis. The full length of NF-kB1 can serve as an endogenous inhibitor for the NF-kB p50/p65(RelA) heterodimer. It has been proposed that the homodimer of NF-kB p50 was transcriptionally inactive in the absence of Bcl3. Furthermore, the NF-kB p50 homodimer may function to competitively inhibit B binding by transactivating NF- B dimers. The Bcl3 protein can form a complex with this homodimer at B sites and act as a transactivator of NF-kB p50 homodimer. Interaction with : members of IkB family and Rel family, LYL1 , Bcl3, NCOA1a(V).

Implicated in

Entity cancer (see below), autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, HTLV-1 infection, and AIDS.

Oncogenesis overexpression of nfkb1 has been found in a number of human cancer including non-small cell lung carcinoma, colon cancer, prostate cancer, breast cancer, bone cancer and brain cancer. The rearrangement of nfkb1 gene, however, only has been identified in certain acute lymphoblastic leukemias.

External links

	Nomenclature
Hugo	NFKB1
GDB	NFKB1
Entrez_Gene	NFKB1 4790 nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (p105)
	Cards
Atlas	NFKB1ID323
GeneCards	NFKB1
Ensembl	NFKB1 [Search_View] ENSG00000109320 [Gene_View]
Genatlas	NFKB1
GeneLynx	NFKB1
eGenome	NFKB1
euGene	4790
	Genomic and cartography
GoldenPath	NFKB1 - chr4:103641518-103757506 + 4q24 (hg18-Mar_2006)
Ensembl	NFKB1 - 4q24 [CytoView]
NCBI	Mapview
OMIM	Disease map [OMIM]
HomoloGene	NFKB1
	Gene and transcription
Genbank	AK122850 [ ENTREZ ]
Genbank	AK291450 [ ENTREZ ]
Genbank	BC033210 [ ENTREZ ]
Genbank	BC051765 [ ENTREZ ]
Genbank	BQ023914 [ ENTREZ ]
RefSeq	NM_003998 [ SRS ] NM_003998 [ ENTREZ ]
RefSeq	AC_000047 [ SRS ] AC_000047 [ ENTREZ ]
RefSeq	NC_000004 [ SRS ] NC_000004 [ ENTREZ ]
RefSeq	NT_016354 [ SRS ] NT_016354 [ ENTREZ ]
RefSeq	NW_922162 [ SRS ] NW_922162 [ ENTREZ ]
AceView	NFKB1 AceView - NCBI
Unigene	Hs.654408 [ SRS ] Hs.654408 [ NCBI ] HS654408 [ spliceNest ]
Fast-db	7894 (alternative variants)
	Protein : pattern, domain, 3D structure
SwissProt	P19838 [ SRS] P19838 [ EXPASY ] P19838 [ INTERPRO ]
Prosite	PS50297 ANK_REP_REGION [ SRS ] PS50297 ANK_REP_REGION [ Expasy ]
Prosite	PS50088 ANK_REPEAT [ SRS ] PS50088 ANK_REPEAT [ Expasy ]
Prosite	PS50017 DEATH_DOMAIN [ SRS ] PS50017 DEATH_DOMAIN [ Expasy ]
Prosite	PS01204 REL_1 [ SRS ] PS01204 REL_1 [ Expasy ]
Prosite	PS50254 REL_2 [ SRS ] PS50254 REL_2 [ Expasy ]
Interpro	IPR002110 ANK [ SRS ] IPR002110 ANK [ EBI ]
Interpro	IPR000488 Death [ SRS ] IPR000488 Death [ EBI ]
Interpro	IPR011029 DEATH_like [ SRS ] IPR011029 DEATH_like [ EBI ]
Interpro	IPR013783 Ig-like_fold [ SRS ] IPR013783 Ig-like_fold [ EBI ]
Interpro	IPR002909 IPT_TIG_rcpt [ SRS ] IPR002909 IPT_TIG_rcpt [ EBI ]
Interpro	IPR000451 NF_Rel_dor [ SRS ] IPR000451 NF_Rel_dor [ EBI ]
Interpro	IPR011539 RHD [ SRS ] IPR011539 RHD [ EBI ]
CluSTr	P19838
Pfam	PF00023 Ank [ SRS ] PF00023 Ank [ Sanger ] pfam00023 [ NCBI-CDD ]
Pfam	PF00531 Death [ SRS ] PF00531 Death [ Sanger ] pfam00531 [ NCBI-CDD ]
Pfam	PF00554 RHD [ SRS ] PF00554 RHD [ Sanger ] pfam00554 [ NCBI-CDD ]
Pfam	PF01833 TIG [ SRS ] PF01833 TIG [ Sanger ] pfam01833 [ NCBI-CDD ]
Smart	SM00248 ANK [EMBL]
Smart	SM00005 DEATH [EMBL]
Smart	SM00429 IPT [EMBL]
Blocks	P19838
PDB	1MDI [ SRS ] 1MDI [ PdbSum ], 1MDI [ IMB ] 1MDI [ RSDB ]
PDB	1MDJ [ SRS ] 1MDJ [ PdbSum ], 1MDJ [ IMB ] 1MDJ [ RSDB ]
PDB	1MDK [ SRS ] 1MDK [ PdbSum ], 1MDK [ IMB ] 1MDK [ RSDB ]
PDB	1NFI [ SRS ] 1NFI [ PdbSum ], 1NFI [ IMB ] 1NFI [ RSDB ]
PDB	1SVC [ SRS ] 1SVC [ PdbSum ], 1SVC [ IMB ] 1SVC [ RSDB ]
PDB	2DBF [ SRS ] 2DBF [ PdbSum ], 2DBF [ IMB ] 2DBF [ RSDB ]
PDB	2O61 [ SRS ] 2O61 [ PdbSum ], 2O61 [ IMB ] 2O61 [ RSDB ]
HPRD	01238
	Protein Interaction databases
DIP	P19838
IntAct	P19838
	Polymorphism : SNP, mutations, diseases
OMIM	164011 [ map ]
GENECLINICS	164011
SNP	NFKB1 [dbSNP-NCBI]
SNP	NM_003998 [SNP-NCI]
SNP	NFKB1 [GeneSNPs - Utah] NFKB1] [HGBASE - SRS]
HAPMAP	NFKB1 [HAPMAP]
COSMIC	NFKB1 [Somatic mutation (COSMIC-CGP-Sanger)]
HGMD	NFKB1
	General knowledge
Family Browser	NFKB1 [UCSC Family Browser]
SOURCE	NM_003998
SMD	Hs.654408
SAGE	Hs.654408
GO	transcription factor activity [Amigo] transcription factor activity
GO	protein binding [Amigo] protein binding
GO	nucleus [Amigo] nucleus
GO	cytoplasm [Amigo] cytoplasm
GO	regulation of transcription, DNA-dependent [Amigo] regulation of transcription, DNA-dependent
GO	transcription from RNA polymerase II promoter [Amigo] transcription from RNA polymerase II promoter
GO	apoptosis [Amigo] apoptosis
GO	anti-apoptosis [Amigo] anti-apoptosis
GO	inflammatory response [Amigo] inflammatory response
GO	signal transduction [Amigo] signal transduction
GO	positive regulation of transcription [Amigo] positive regulation of transcription
BIOCARTA	The 4-1BB-dependent immune response [Genes]
BIOCARTA	HIV-I Nef: negative effector of Fas and TNF [Genes]
BIOCARTA	Acetylation and Deacetylation of RelA in The Nucleus [Genes]
BIOCARTA	Influence of Ras and Rho proteins on G1 to S Transition [Genes]
BIOCARTA	AKT Signaling Pathway [Genes]
BIOCARTA	ATM Signaling Pathway [Genes]
BIOCARTA	Role of EGF Receptor Transactivation by GPCRs in Cardiac Hypertrophy [Genes]
BIOCARTA	CD40L Signaling Pathway [Genes]
BIOCARTA	Cadmium induces DNA synthesis and proliferation in macrophages [Genes]
BIOCARTA	Ceramide Signaling Pathway [Genes]
BIOCARTA	CXCR4 Signaling Pathway [Genes]
BIOCARTA	Induction of apoptosis through DR3 and DR4/5 Death Receptors [Genes]
BIOCARTA	Erythropoietin mediated neuroprotection through NF-kB [Genes]
BIOCARTA	fMLP induced chemokine gene expression in HMC-1 cells [Genes]
BIOCARTA	Free Radical Induced Apoptosis [Genes]
BIOCARTA	Corticosteroids and cardioprotection [Genes]
BIOCARTA	Inactivation of Gsk3 by AKT causes accumulation of b-catenin in Alveolar Macrophages [Genes]
BIOCARTA	Human Cytomegalovirus and Map Kinase Pathways [Genes]
BIOCARTA	Signal transduction through IL1R [Genes]
BIOCARTA	Keratinocyte Differentiation [Genes]
BIOCARTA	MAPKinase Signaling Pathway [Genes]
BIOCARTA	NF-kB Signaling Pathway [Genes]
BIOCARTA	NFkB activation by Nontypeable Hemophilus influenzae [Genes]
BIOCARTA	The information-processing pathway at the IFN-beta enhancer [Genes]
BIOCARTA	Activation of PKC through G protein coupled receptor [Genes]
BIOCARTA	Bone Remodelling [Genes]
BIOCARTA	Ras Signaling Pathway [Genes]
BIOCARTA	Double Stranded RNA Induced Gene Expression [Genes]
BIOCARTA	TNF/Stress Related Signaling [Genes]
BIOCARTA	TACI and BCMA stimulation of B cell immune responses. [Genes]
BIOCARTA	T Cell Receptor Signaling Pathway [Genes]
BIOCARTA	Chaperones modulate interferon Signaling Pathway [Genes]
BIOCARTA	TNFR2 Signaling Pathway [Genes]
BIOCARTA	Toll-Like Receptor Pathway [Genes]
BIOCARTA	Neuropeptides VIP and PACAP inhibit the apoptosis of activated T cells [Genes]
KEGG	MAPK signaling pathway
KEGG	Apoptosis
KEGG	Toll-like receptor signaling pathway
KEGG	T cell receptor signaling pathway
KEGG	B cell receptor signaling pathway
KEGG	Adipocytokine signaling pathway
KEGG	Epithelial cell signaling in Helicobacter pylori infection
PubGene	NFKB1
TreeFam	NFKB1
	Other databases
	Probes
Probe	NFKB1 Related clones (RZPD - Berlin)
	PubMed
PubMed	499 Pubmed reference(s) in LocusLink

Bibliography

Related subunits of NF-kappa B map to two distinct loci associated with translocations in leukemia, NFKB1 and NFKB2.

Liptay S, Schmid RM, Perkins ND, Meltzer P, Altherr MR, McPherson JD, Wasmuth JJ, Nabel GJ

Genomics. 1992 ; 13 (2) : 287-292.

PMID 1612589

The NF-kappa B and I kappa B proteins: new discoveries and insights.

Baldwin AS Jr

Annual review of immunology. 1996 ; 14 : 649-683.

PMID 8717528

NF-kappa B and Rel proteins: evolutionarily conserved mediators of immune responses.

Ghosh S, May MJ, Kopp EB

Annual review of immunology. 1998 ; 16 : 225-260.

PMID 9597130

Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome.

Lin L, DeMartino GN, Greene WC

Cell. 1998 ; 92 (6) : 819-828.

PMID 9529257

New insights into the role of nuclear factor-kappaB, a ubiquitous transcription factor in the initiation of diseases.

Chen F, Castranova V, Shi X, Demers LM

Clinical chemistry. 1999 ; 45 (1) : 7-17.

PMID 9895331

REVIEW articles automatic search in PubMed

Last year publications automatic search in PubMed

Search in all EBI NCBI

Contributor(s)

Written 01-2002 Fei Chen

Citation

This paper should be referenced as such :
Chen F . NFKB1. Atlas Genet Cytogenet Oncol Haematol. January 2002 .
URL : http://AtlasGeneticsOncology.org/Genes/NFKB1ID323.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon May 12 18:06:47 2008

Home Genes Leukemias Solid Tumours Cancer-Prone Deep Insight Case Reports Journals Portal Teaching

For comments and suggestions or contributions, please contact us
j.l.huret@chu-poitiers.fr.

Other names	NF-kB p105
	NF-kB p50
Hugo	NFKB1
Location	4q23-q24

Description	The nfkb1 gene encodes a protein composed 968 amino acids with an approximately molecular weight of 105 kDa, which was considered as a precursor of p50 subunit of NF-kB complexes. In the N-terminal region of NF-kB1, there is a Rel homology domain (RHD) composed of ~300 amino acids that are responsible for DNA binding, dimerization with other Rel family members, and interaction with IkB proteins. The C-terminal region of NF-kB1 contains multiple copies of the so-called ankyrin repeats which is found in IkB family members, including IkBa, IkBb, IkBe, Bcl3, and Drosophila cactus. The earlier studies by several groups demonstrated that NF-kB1 was posttranslationally cleaved to produce the p50 molecule through the ubiquitin-proteasome dependent degradation of the C-terminal portion of NF-kB1. Further studies by Lin and Ghosh suggested that a glycine-rich region (GRR) within the region of 375 to 400 of NF-kB1 is necessary and sufficient for directing the cleavage of NF-kB1. However, recent studies challenged this model and revealed a novel mechanism in which p50 is generated by a unique cotranslational processing event involving the 26S proteasome. In other words, NF-kB1 is not the precursor of p50.
Expression	nfkb1 is widely expressed in virtually all type of cells in both adults and in the embryo.
Localisation	cytosol, nuclei after activation.
Function	regulation of the genes involved in cell-to-cell interaction, intercellular communication, cell recruitment or transmigration, amplification or spreading of primary pathogenic signals, and initiation or acceleration of tumorigenesis. The full length of NF-kB1 can serve as an endogenous inhibitor for the NF-kB p50/p65(RelA) heterodimer. It has been proposed that the homodimer of NF-kB p50 was transcriptionally inactive in the absence of Bcl3. Furthermore, the NF-kB p50 homodimer may function to competitively inhibit B binding by transactivating NF- B dimers. The Bcl3 protein can form a complex with this homodimer at B sites and act as a transactivator of NF-kB p50 homodimer. Interaction with : members of IkB family and Rel family, LYL1 , Bcl3, NCOA1a(V).

Entity	cancer (see below), autoimmune arthritis, glomerulonephritis, asthma, inflammatory bowel disease, septic shock, lung fibrosis, HTLV-1 infection, and AIDS.
Oncogenesis	overexpression of nfkb1 has been found in a number of human cancer including non-small cell lung carcinoma, colon cancer, prostate cancer, breast cancer, bone cancer and brain cancer. The rearrangement of nfkb1 gene, however, only has been identified in certain acute lymphoblastic leukemias.

REVIEW articles	automatic search in PubMed
Last year publications	automatic search in PubMed