Q63369 (NFKB1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
DNA-binding factor KBF1
EBP-1
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1

Cleaved into the following chain:

1. Nuclear factor NF-kappa-B p50 subunit

Gene names

Name:

Nfkb1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	522 AA.
Sequence status	Fragment.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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 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. Plays a role in the regulation of apoptosis. Isoform 5, isoform 6 and isoform 7 act as inhibitors of transactivation of p50 NF-kappa-B subunit, probably by sequestering it in the cytoplasm. Isoform 3 (p98) (but not p84 or p105) acts as a transactivator of NF-kappa-B-regulated gene expression. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105 By similarity.
Subunit structure	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 By similarity. Interacts with HIF1AN By similarity.
Subcellular location	Nucleus By similarity. Cytoplasm By similarity. Note: Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B) By similarity.
Domain	The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding by p50 homodimers, and/or transcription activation.
Post-translational modification	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 processing By similarity.
Sequence similarities	Contains 7 ANK repeats. Contains 1 death domain. Contains 1 RHD (Rel-like) domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	ANK repeat Repeat
Ligand	DNA-binding
Molecular function	Activator
PTM	Hydroxylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to interleukin-1 Inferred from electronic annotation. Source: Compara cellular response to mechanical stimulus Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from mutant phenotype PubMed 16354757. Source: RGD negative regulation of calcidiol 1-monooxygenase activity Inferred from electronic annotation. Source: Compara negative regulation of cytokine production Inferred from electronic annotation. Source: Compara negative regulation of interleukin-12 biosynthetic process Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara positive regulation of canonical Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of hyaluronan biosynthetic process Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from electronic annotation. Source: Compara response to bacterium Inferred from expression pattern PubMed 15777838. Source: RGD response to copper ion Inferred from expression pattern PubMed 17418555. Source: RGD response to oxidative stress Inferred from direct assay PubMed 12193536. Source: RGD signal transduction Inferred from electronic annotation. Source: InterPro transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Inferred from direct assay PubMed 16135962. Source: RGD mitochondrion Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay PubMed 16135962PubMed 9343439. Source: RGD protein complex Inferred from direct assay PubMed 10620707PubMed 16135962PubMed 9343439. Source: RGD
Molecular_function	double-stranded DNA binding Inferred from direct assay PubMed 14576180. Source: RGD sequence-specific DNA binding transcription factor activity Traceable author statement PubMed 12193536. Source: RGD transcription regulatory region sequence-specific DNA binding Inferred from direct assay PubMed 14576180. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	‹1 – 522	›522	Nuclear factor NF-kappa-B p105 subunit		PRO_0000030314
	Chain	‹1 – 32	›32	Nuclear factor NF-kappa-B p50 subunit By similarity		PRO_0000030315
Regions
	Repeat	89 – 119	31	ANK 1
	Repeat	128 – 157	30	ANK 2
	Repeat	161 – 190	30	ANK 3
	Repeat	197 – 226	30	ANK 4
	Repeat	231 – 260	30	ANK 5
	Repeat	265 – 294	30	ANK 6
	Repeat	318 – 348	31	ANK 7
	Domain	352 – 439	88	Death
	Region	197 – 231	35	Essential for interaction with HIF1AN By similarity
Amino acid modifications
	Modified residue	225	1	(3S)-3-hydroxyasparagine; by HIF1AN By similarity
	Modified residue	461	1	Phosphoserine; by GSK3-beta; in vitro By similarity
	Modified residue	481	1	Phosphoserine; by IKKB By similarity
	Modified residue	486	1	Phosphoserine; by IKKB By similarity
	Modified residue	491	1	Phosphoserine By similarity
Experimental info
	Non-terminal residue	1	1

Sequences

	Sequence		Length	Mass (Da)
	Q63369 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 12D89EE61E3163E2	FASTA	522	56,554
	10 20 30 40 50 60 REILNPPEKE TQGEGPSLFM ASTKTEAIAP ASTMEDKEED VGFQDNLFLE KALQLAKRHA 70 80 90 100 110 120 NALFDYAVTG DVKMLLAVQR HLTAVQDENG DSVLHLAIIH LHAQLVRDLL EVTSGSISDD 130 140 150 160 170 180 IINMRNDLYQ TPLHLAVITK QEDVVEDLLR VGADLSLLDR WGNSVLHLAA KEGHDKILGV 190 200 210 220 230 240 LLKNSKAALL INHPNGEGLN AIHIAVMSNS LSCLQLLVAA GAEVNAQEQK SGRTALHLAV 250 260 270 280 290 300 EYDNISLAGC LLLEGDALVD STTYDGTTPL HIAAGRGSTR LAALLKAAGA DPLVENFEPL 310 320 330 340 350 360 YDLDDSWEKA GEDEGVVPGT TPLDMAANWQ VFDILNGKPY EPVFTSDDIL PQGDIKQLTE 370 380 390 400 410 420 DTRLQLCKLL EIPDPDKNWA TLAQKLGLGI LNNAFRLSPA PSKTLMDNYE VSGGTIKELV 430 440 450 460 470 480 EALRQMGYTE AIEVIQAAFR TPETTASSPV TTAQAHLLPL SSSSTRQHID ELRDNDSVCD 490 500 510 520 SGVETSFRKL SFSESLTGDG PLLSLNKMPH NYGQDGPIEG KI

References

[1]	"Cloning of rat Sertoli cell follicle-stimulating hormone primary response complementary deoxyribonucleic acid: regulation of TSC-22 gene expression." Hamil K.G., Hall S.H. Endocrinology 134:1205-1212(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Testis.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L26267 mRNA. Translation: AAA20684.1.
IPI	IPI00373434.
PIR	I67414.
UniGene	Rn.2411.
3D structure databases
ProteinModelPortal	Q63369.
SMR	Q63369. Positions 353-436.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2739834.
STRING	10116.ENSRNOP00000028944.
PTM databases
PhosphoSite	Q63369.
Proteomic databases
PaxDb	Q63369.
PRIDE	Q63369.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Organism-specific databases
RGD	70498. Nfkb1.
Phylogenomic databases
eggNOG	COG0666.
HOGENOM	HOG000004822.
HOVERGEN	HBG052613.
InParanoid	Q63369.
OrthoDB	EOG4SN1MX.
Gene expression databases
ArrayExpress	Q63369.
Genevestigator	Q63369.
GermOnline	ENSRNOG00000023258. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.533.10. 1 hit. 1.25.40.20. 1 hit.
InterPro	IPR002110. Ankyrin_rpt. IPR020683. Ankyrin_rpt-contain_dom. IPR011029. DEATH-like_dom. IPR000488. Death_domain. [Graphical view]
Pfam	PF12796. Ank_2. 2 hits. PF00531. Death. 1 hit. [Graphical view]
PRINTS	PR01415. ANKYRIN.
SMART	SM00248. ANK. 6 hits. SM00005. DEATH. 1 hit. [Graphical view]
SUPFAM	SSF48403. ANK. 1 hit. SSF47986. DEATH_like. 1 hit.
PROSITE	PS50297. ANK_REP_REGION. 1 hit. PS50088. ANK_REPEAT. 4 hits. PS50017. DEATH_DOMAIN. False negative. PS01204. REL_1. Partial match. PS50254. REL_2. Partial match. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

NFKB1_RAT

Accession

Primary (citable) accession number: Q63369

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program