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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NFKB1 Gene

protein-coding GIFtS: 73
GCID: GC04P103422

nuclear factor of kappa light polypeptide gene enhancer...

Explore 220 diseases affiliated with
NFKB1 via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Nuclear Factor Of Kappa Light Polypeptide Gene Enhancer In B-Cells 1¹ ² ³		DNA-Binding Factor KBF1² ³
KBF1¹ ²		NF-Kappa-B¹
NF-KB1¹		NF-Kappabeta¹
NF-KappaB¹		NFKB-P105¹
NFKB-P50¹		DNA Binding Factor KBF1²
NFkappaB¹ ²		Nuclear Factor Kappa-B DNA Binding Subunit²
P105¹		Nuclear Factor NF-Kappa-B P105 Subunit²
P50¹		Nuclear Factor NF-Kappa-B P50 Subunit²
EBP-1² ³

External Ids:	HGNC: 7794¹	Entrez Gene: 4790²	Ensembl: ENSG00000109320⁷	OMIM: 164011⁵	UniProtKB: P19838³

Export aliases for NFKB1 gene to outside databases

Previous GC identifers: GC04P103821 GC04P103880 GC04P103779 GC04P103641 GC04P099158

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NFKB1:

This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50

kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA

binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by

various intra- and extra-cellular stimuli such as cytokines, oxidant-free radicals, ultraviolet irradiation, and

bacterial or viral products. Activated NFKB translocates into the nucleus and stimulates the expression of genes

involved in a wide variety of biological functions. Inappropriate activation of NFKB has been associated with a number

of inflammatory diseases while persistent inhibition of NFKB leads to inappropriate immune cell development or delayed

cell growth. Two transcript variants encoding different isoforms have been found for this gene. (provided by RefSeq,

Sep 2009)

UniProtKB/Swiss-Prot: NFKB1_HUMAN, P19838

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 and the heterodimeric p65-p50 complex appears to be most abundant one. 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. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are

transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a

transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic

retention of attached NF-kappa-B proteins by p105 and generation of p50 by a cotranslational processing. The

proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function,

although processing of NFKB1/p105 also appears to occur post-translationally. p50 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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by

proteasome-dependent degradation of NFKB1/p105

summary for NFKB1:

NF-kappaB (nuclear factor-kappa B) is a rapidly acting primary transcription factor found in all cell types.

It is involved in cellular responses to stimuli such as cytokines and stress and plays a key role in

regulating the immune response to infection. In unstimulated cells NF-kappaB dimers are sequestered

inactively in the cytoplasm by a protein complex called inhibitor of kappa B (IkappaB). IkappaB inactivates

NF-kappaB by masking the nuclear localization signals (NLS). Activation of NF-kappaB occurs via degradation

of IkappaB, a process that is initiated by its phosphorylation by IkappaB kinase (IKK). Phosphorylated IvB

becomes dissociated from NF-kappaB, unmasking the NLS. Phosphorylation also results in IkappaB

ubiquitination and targeting to the proteasome. NF-kappaB can now enter the nucleus and regulate gene

expression. NF-kappaB turns on expression of IkappaB forming a negative feedback loop.

Gene Wiki entry for NFKB1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000004.11 NC_018915.1 NT_016354.19

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NFKB1 gene promoter:
Oct-B1 RORalpha1 Max1 TBP POU2F1 oct-B3 FOXC1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 3): NFKB1 promoter sequence

Search SABiosciences Chromatin IP Primers for NFKB1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NFKB1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 4q24 Ensembl cytogenetic band: 4q24 HGNC cytogenetic band: 4q24

NFKB1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NFKB1 gene location

GeneLoc information about chromosome 4 GeneLoc Exon Structure

GeneLoc location for GC04P103422: view genomic region (about GC identifiers)

Start:	103,422,486 bp from pter	End:	103,538,459 bp from pter
Size:	115,974 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: NFKB1_HUMAN, P19838 (See protein sequence)

Recommended Name: Nuclear factor NF-kappa-B p105 subunit

Size: 968 amino acids; 105356 Da

Subunit: Component of the NF-kappa-B p65-p50 complex. Component of the NF-kappa-B p65-p50 complex. Homodimer; component

of the NF-kappa-B p50-p50 complex. Component of the NF-kappa-B p105-p50 complex. Component of the NF-kappa-B p50-c-Rel

complex. Component of a complex consisting of the NF-kappa-B p50-p50 homodimer and BCL3. Also interacts with MAP3K8.

NF-kappa-B p50 subunit interacts with NCOA3 coactivator, which may coactivate NF-kappa-B dependent expression via its

histone acetyltransferase activity. Interacts with DSIPI; this interaction prevents nuclear translocation and

DNA-binding. Interacts with SPAG9 and UNC5CL. NFKB1/p105 interacts with CFLAR; the interaction inhibits p105

processing into p50. NFKB1/p105 forms a ternary complex with MAP3K8 and TNIP2. Interacts with GSK3B; the interaction

prevents processing of p105 to p50. NFKB1/p50 interacts with NFKBIE. NFKB1/p50 interacts with NFKBIZ. Nuclear factor

NF-kappa-B p50 subunit interacts with NFKBID (By similarity). Directly interacts with MEN1. Interacts with HIF1AN

Subcellular location: Nucleus. Cytoplasm. Note=Nuclear, but also found in the cytoplasm in an inactive form complexed

to an inhibitor (I-kappa-B)

6/8 PDB 3D structures from and Proteopedia for NFKB1 (see all 8):

1MDI (3D)

1MDJ (3D)

1MDK (3D)

1NFI (3D)

1SVC (3D)

2DBF (3D)

Secondary accessions: A8K5Y5 B3KVE8 Q68D84 Q86V43 Q8N4X7 Q9NZC0

Alternative splicing: 3 isoforms: P19838-1 P19838-2 P19838-3 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for NFKB1: NX_P19838

Post-translational modifications:

While translation occurs, the particular unfolded structure after the GRR repeat promotes the generation of p50 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

processing¹

Phosphorylation at 'Ser-903' and 'Ser-907' primes p105 for proteolytic processing in response to TNF-alpha stimulation.

Phosphorylation at 'Ser-927' and 'Ser-932' are required for BTRC/BTRCP-mediated proteolysis¹

Polyubiquitination seems to allow p105 processing¹

S-nitrosylation of Cys-61 affects DNA binding¹

The covalent modification of cysteine by 15-deoxy-Delta12,14-prostaglandin-J2 is autocatalytic and reversible. It may

occur as an alternative to other cysteine modifications, such as S-nitrosylation and S-palmitoylation¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P19838

NFKB1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001158884.1 NP_003989.2

ENSEMBL proteins:

ENSP00000226574 ENSP00000378297 ENSP00000420904 ENSP00000426147 ENSP00000424790

ENSP00000423877 ENSP00000424815

Reactome Protein details: P19838
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant NFKB1 Protein
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for NFKB1
	OriGene Purified Protein: NFKB1 OriGene Protein Over-expression Lysate: NFKB1 OriGene Custom Protein Services for NFKB1
	GenScript Custom Purified and Recombinant Proteins Services for NFKB1
	Novus Biologicals NFKB1 Proteins Novus Biologicals NFKB1 Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Uscn

Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	--
GO:0005654	nucleoplasm	TAS	--
GO:0005730	NOT nucleolus	IDA	--
GO:0005737	cytoplasm	IDA	--
GO:0005739	mitochondrion	IDA	--

NFKB1 for ontologies About GeneDecksing

NFKB1 Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of NFKB1
	R&D Systems Antibodies for NFKB1
	Cell Signaling Technology (CST) Antibodies for NFKB1 (NFkB-p105)
	OriGene Antibodies (see all 4): NFKB1 OriGene Custom Antibody Services for NFKB1
	GenScript Custom Superior Antibodies Services for NFKB1
	Novus Biologicals NFKB1 Antibodies
	Abcam antibodies for NFKB1
	Browse Antibodies at Uscn
	ThermoFisher Antibody for NFKB1

Assay Products for NFKB1:

	EMD Millipore Kits and Assays for the Analysis of NFKB1
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems Multiplex/Array Assay Kits & Reagents for NFKB1 (see all)
	GenScript Custom Assay Services for NFKB1
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NFKB1 for domains About GeneDecksing

5/10 InterPro domains/families (see all 10):

IPR014756 Ig_E-set

IPR008967 p53-like_TF_DNA-bd

IPR011029 DEATH-like_dom

IPR002909 IPT_TIG_rcpt

IPR000488 Death_domain

Graphical View of Domain Structure for InterPro Entry P19838

ProtoNet protein and cluster: P19838

4 Blocks protein families:

IPB000451 NF-kappa-B/Rel/dorsal family

IPB000488 Death domain

IPB002909 Cell surface receptor IPT/TIG

IPB011539 Rel homology

UniProtKB/Swiss-Prot: NFKB1_HUMAN, P19838

Domain: The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding, and transcription

activation

Domain: Glycine-rich region (GRR) appears to be a critical element in the generation of p50

Similarity: Contains 7 ANK repeats

Similarity: Contains 1 death domain

Similarity: Contains 1 RHD (Rel-like) domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: