Nuclear factor NF-kappa-B p105 subunit - Rattus norvegicus (Rat)

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Reviewed, UniProtKB/Swiss-Prot Q63369 (NFKB1_RAT)

Last modified October 13, 2009. Version 78. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Nuclear factor NF-kappa-B p105 subunit
Alternative name(s):
    DNA-binding factor KBF1
    EBP-1
Cleaved into the following chain:
    1- Recommended name:
            Nuclear factor NF-kappa-B p50 subunit

Gene names

Name:

Nfkb1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

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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.

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General annotation (Comments)

Function	NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed 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.
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.

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Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Domain	ANK repeat Repeat
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from mutant phenotype. Source: RGD positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: RGD response to copper ion Inferred from expression pattern. Source: RGD response to oxidative stress Inferred from direct assay. Source: RGD signal transduction Inferred from electronic annotation. Source: InterPro transcription Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from direct assay. Source: RGD nucleus Inferred from direct assay. Source: RGD protein complex Inferred from direct assay. Source: RGD
Molecular function	actin binding Inferred from physical interaction. Source: RGD double-stranded DNA binding Inferred from direct assay. Source: RGD heat shock protein binding Inferred from physical interaction. Source: RGD protein dimerization activity Inferred from direct assay. Source: RGD sequence-specific DNA binding Inferred from direct assay. Source: RGD transcription activator activity Inferred from direct assay. Source: RGD transcription factor activity Traceable author statement. Source: RGD
Complete GO annotation...

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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

ANK 1

Repeat

128 – 157

ANK 2

Repeat

161 – 190

ANK 3

Repeat

197 – 226

ANK 4

Repeat

231 – 260

ANK 5

Repeat

265 – 294

ANK 6

Repeat

318 – 348

ANK 7

Domain

352 – 439

Death

Sites

Site

32 – 33

Cleavage (when cotranslationally processed) By similarity

Amino acid modifications

Modified residue

461

Phosphoserine; by GSK3-beta; in vitro By similarity

Modified residue

481

Phosphoserine; by IKKB By similarity

Modified residue

486

Phosphoserine; by IKKB By similarity

Experimental info

Non-terminal residue

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Sequences

Sequence

Length

Mass (Da)

Tools

Q63369-1 [UniParc].

Last modified November 1, 1997. Version 1.
Checksum: 12D89EE61E3163E2
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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

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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: 8161377] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Testis.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	L26267 mRNA. Translation: AAA20684.1.
IPI	IPI00373434.
PIR	I67414.
UniGene	Rn.2411
3D structure databases
HSSP	HSSP built from PDB template 1NFI based on UniProtKB P25963.
SMR	Q63369. Positions 353-436.
ModBase	Search...
Protein-protein interaction databases
STRING	Q63369.
Genome annotation databases
Ensembl	ENSRNOT00000036838; ENSRNOP00000028944; ENSRNOG00000023258; Rattus norvegicus. [Genome view]
Organism-specific databases
RGD	70498. Nfkb1.
Phylogenomic databases
HOVERGEN	Q63369.
Gene expression databases
ArrayExpress	Q63369.
Genevestigator	Q63369.
GermOnline	ENSRNOG00000023258. Rattus norvegicus.
Family and domain databases
InterPro	IPR002110. ANK. IPR000488. Death. IPR011029. DEATH-like. IPR000451. NF_Rel_dor. [Graphical view]
Gene3D	G3DSA:1.25.40.20. ANK. 1 hit. G3DSA:1.10.533.10. DEATH_like. 1 hit.
Pfam	PF00023. Ank. 6 hits. PF00531. Death. 1 hit. [Graphical view]
SMART	SM00248. ANK. 6 hits. SM00005. DEATH. 1 hit. [Graphical view]
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...

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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:	October 13, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Entry information

Relevant documents