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P19838 (NFKB1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 185. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length968 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein 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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. Ref.35

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. Interacts with HIF1AN. Ref.10 Ref.12 Ref.15 Ref.17 Ref.18 Ref.20 Ref.22 Ref.25 Ref.26 Ref.28 Ref.30 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.37

Subcellular location

Nucleus. Cytoplasm. Note: Nuclear, but also found in the cytoplasm in an inactive form complexed to an inhibitor (I-kappa-B).

Induction

By phorbol ester and TNF.

Domain

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

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

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.

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 proteolysis.

Polyubiquitination seems to allow p105 processing.

S-nitrosylation of Cys-61 affects DNA binding.

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-palmitoylation.

Sequence similarities

Contains 7 ANK repeats.

Contains 1 death domain.

Contains 1 RHD (Rel-like) domain.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainANK repeat
Repeat
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Hydroxylation
Lipoprotein
Phosphoprotein
S-nitrosylation
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

MyD88-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

T cell receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to interleukin-1

Inferred from expression pattern PubMed 12958148. Source: BHF-UCL

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 19593445. Source: UniProtKB

inflammatory response

Traceable author statement Ref.3. Source: UniProtKB

innate immune response

Traceable author statement. Source: Reactome

membrane protein intracellular domain proteolysis

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Traceable author statement PubMed 10811897. Source: UniProtKB

negative regulation of calcidiol 1-monooxygenase activity

Inferred from direct assay PubMed 15243130. Source: BHF-UCL

negative regulation of cellular protein metabolic process

Inferred by curator PubMed 16938301. Source: BHF-UCL

negative regulation of cholesterol transport

Inferred by curator PubMed 16938301. Source: BHF-UCL

negative regulation of cytokine production

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-12 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 19881551. Source: UniProtKB

negative regulation of vitamin D biosynthetic process

Inferred by curator PubMed 15243130. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of NF-kappaB transcription factor activity

Traceable author statement. Source: Reactome

positive regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 20018240. Source: UniProtKB

positive regulation of hyaluronan biosynthetic process

Inferred from direct assay PubMed 17324121. Source: UniProtKB

positive regulation of lipid storage

Inferred by curator PubMed 16938301. Source: BHF-UCL

positive regulation of macrophage derived foam cell differentiation

Inferred by curator PubMed 16938301. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 17426251. Source: UniProtKB

positive regulation of type I interferon production

Traceable author statement. Source: Reactome

response to bacterium

Inferred from electronic annotation. Source: Ensembl

response to copper ion

Inferred from electronic annotation. Source: Ensembl

response to oxidative stress

Inferred from electronic annotation. Source: Ensembl

toll-like receptor 10 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 5 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 9 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR1:TLR2 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor TLR6:TLR2 signaling pathway

Traceable author statement. Source: Reactome

transcription from RNA polymerase II promoter

Traceable author statement Ref.3. Source: UniProtKB

   Cellular_componentI-kappaB/NF-kappaB complex

Traceable author statement PubMed 16938301. Source: BHF-UCL

cytosol

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay. Source: HPA

nucleoplasm

Traceable author statement. Source: Reactome

   Molecular_functiondouble-stranded DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Traceable author statement PubMed 10928981. Source: ProtInc

transcription factor binding

Inferred from direct assay PubMed 18270204. Source: MGI

transcription regulatory region sequence-specific DNA binding

Inferred from direct assay PubMed 18718911. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P19838-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P19838-2)

The sequence of this isoform differs from the canonical sequence as follows:
     39-39: T → TA
Isoform 3 (identifier: P19838-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-180: Missing.
     181-189: EGGGDRQLG → MNGLCCMAL
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 968968Nuclear factor NF-kappa-B p105 subunit
PRO_0000030310
Chain1 – 433433Nuclear factor NF-kappa-B p50 subunit
PRO_0000030311

Regions

Domain42 – 367326RHD
Repeat542 – 57130ANK 1
Repeat581 – 61030ANK 2
Repeat614 – 64330ANK 3
Repeat650 – 67930ANK 4
Repeat684 – 71431ANK 5
Repeat718 – 74730ANK 6
Repeat771 – 80131ANK 7
Domain805 – 89288Death
Region372 – 39423GRR
Region435 – 968534Interaction with CFLAR
Region650 – 68435Essential for interaction with HIF1AN
Motif360 – 3656Nuclear localization signal Potential
Compositional bias375 – 43359Gly-rich

Sites

Site433 – 4342Cleavage (when cotranslationally processed)

Amino acid modifications

Modified residue611S-nitrosocysteine; alternate Ref.14
Modified residue3371Phosphoserine; by PKA Potential
Modified residue4311N6-acetyllysine; by EP300 Probable
Modified residue4401N6-acetyllysine; by EP300 Probable
Modified residue4411N6-acetyllysine; by EP300 Probable
Modified residue6781(3S)-3-hydroxyasparagine; by HIF1AN; partial
Modified residue9031Phosphoserine; by GSK3-beta; in vitro Ref.30
Modified residue9071Phosphoserine; by GSK3-beta; in vitro Ref.30
Modified residue9271Phosphoserine; by IKKB Ref.24 Ref.31
Modified residue9321Phosphoserine; by IKKB Ref.31
Modified residue9371Phosphoserine Ref.39
Lipidation611S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternate

Natural variations

Alternative sequence1 – 180180Missing in isoform 3.
VSP_042869
Alternative sequence391T → TA in isoform 2.
VSP_021025
Alternative sequence181 – 1899EGGGDRQLG → MNGLCCMAL in isoform 3.
VSP_042870
Natural variant4891T → I. Ref.8
Corresponds to variant rs4648065 [ dbSNP | Ensembl ].
VAR_016268
Natural variant5061M → V. Ref.8
Corresponds to variant rs4648072 [ dbSNP | Ensembl ].
VAR_016269
Natural variant5661T → I. Ref.8
Corresponds to variant rs4648085 [ dbSNP | Ensembl ].
VAR_016270
Natural variant5781R → K. Ref.8
Corresponds to variant rs4648086 [ dbSNP | Ensembl ].
VAR_016271
Natural variant7111H → Q. Ref.8
Corresponds to variant rs4648099 [ dbSNP | Ensembl ].
VAR_016272
Natural variant9011A → T. Ref.8
Corresponds to variant rs4648118 [ dbSNP | Ensembl ].
VAR_016273

Experimental info

Mutagenesis611C → S: Suppresses S-nitrosylation-induced inhibition of DNA-binding activity. Loss of S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine-induced inhibition of DNA-binding activity. Ref.14 Ref.23
Mutagenesis6781N → A: Fails to promote HIF1AN-dependent 2-oxoglutarate decarboxylation. Ref.37
Mutagenesis9031S → A: Prevents p105 proteolysis in response to TNF-alpha. Ref.30
Mutagenesis9071S → A: Prevents p105 proteolysis in response to TNF-alpha. Ref.30
Mutagenesis9211S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-923 and A-932. Ref.17
Mutagenesis9231S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-932. Ref.17
Mutagenesis9321S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-923. Ref.17
Sequence conflict2431K → SE in CAB94757. Ref.4
Sequence conflict3611R → G in CAH18336. Ref.7
Sequence conflict551 – 5522II → SS in CAB94757. Ref.4
Sequence conflict5731D → G in BAF84139. Ref.6
Sequence conflict7261A → V in CAB94757. Ref.4
Sequence conflict8251I → T in CAH18336. Ref.7
Sequence conflict8691V → I in CAB94757. Ref.4
Sequence conflict9271S → T in AAA36361. Ref.1
Sequence conflict9271S → T in AAA36360. Ref.3
Sequence conflict9271S → T in CAB94757. Ref.4

Secondary structure

.................................................................................. 968
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 20, 2002. Version 2.
Checksum: 2A7C8FF86A10D1A8

FASTA968105,356
        10         20         30         40         50         60 
MAEDDPYLGR PEQMFHLDPS LTHTIFNPEV FQPQMALPTD GPYLQILEQP KQRGFRFRYV 

        70         80         90        100        110        120 
CEGPSHGGLP GASSEKNKKS YPQVKICNYV GPAKVIVQLV TNGKNIHLHA HSLVGKHCED 

       130        140        150        160        170        180 
GICTVTAGPK DMVVGFANLG ILHVTKKKVF ETLEARMTEA CIRGYNPGLL VHPDLAYLQA 

       190        200        210        220        230        240 
EGGGDRQLGD REKELIRQAA LQQTKEMDLS VVRLMFTAFL PDSTGSFTRR LEPVVSDAIY 

       250        260        270        280        290        300 
DSKAPNASNL KIVRMDRTAG CVTGGEEIYL LCDKVQKDDI QIRFYEEEEN GGVWEGFGDF 

       310        320        330        340        350        360 
SPTDVHRQFA IVFKTPKYKD INITKPASVF VQLRRKSDLE TSEPKPFLYY PEIKDKEEVQ 

       370        380        390        400        410        420 
RKRQKLMPNF SDSFGGGSGA GAGGGGMFGS GGGGGGTGST GPGYSFPHYG FPTYGGITFH 

       430        440        450        460        470        480 
PGTTKSNAGM KHGTMDTESK KDPEGCDKSD DKNTVNLFGK VIETTEQDQE PSEATVGNGE 

       490        500        510        520        530        540 
VTLTYATGTK EESAGVQDNL FLEKAMQLAK RHANALFDYA VTGDVKMLLA VQRHLTAVQD 

       550        560        570        580        590        600 
ENGDSVLHLA IIHLHSQLVR DLLEVTSGLI SDDIINMRND LYQTPLHLAV ITKQEDVVED 

       610        620        630        640        650        660 
LLRAGADLSL LDRLGNSVLH LAAKEGHDKV LSILLKHKKA ALLLDHPNGD GLNAIHLAMM 

       670        680        690        700        710        720 
SNSLPCLLLL VAAGADVNAQ EQKSGRTALH LAVEHDNISL AGCLLLEGDA HVDSTTYDGT 

       730        740        750        760        770        780 
TPLHIAAGRG STRLAALLKA AGADPLVENF EPLYDLDDSW ENAGEDEGVV PGTTPLDMAT 

       790        800        810        820        830        840 
SWQVFDILNG KPYEPEFTSD DLLAQGDMKQ LAEDVKLQLY KLLEIPDPDK NWATLAQKLG 

       850        860        870        880        890        900 
LGILNNAFRL SPAPSKTLMD NYEVSGGTVR ELVEALRQMG YTEAIEVIQA ASSPVKTTSQ 

       910        920        930        940        950        960 
AHSLPLSPAS TRQQIDELRD SDSVCDSGVE TSFRKLSFTE SLTSGASLLT LNKMPHDYGQ 


EGPLEGKI 

« Hide

Isoform 2 [UniParc].

Checksum: B4D57AC8A410941D
Show »

FASTA969105,427
Isoform 3 [UniParc].

Checksum: 7B9913B97F25DD3F
Show »

FASTA78885,520

References

« Hide 'large scale' references
[1]"The DNA binding subunit of NF-kappa B is identical to factor KBF1 and homologous to the rel oncogene product."
Kieran M., Blank V., Logeat F., Vandekerckhove J., Lottspeich F., le Bail O., Urban M.B., Kourilsky P., Baeuerle P.A., Israel A.
Cell 62:1007-1018(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), PARTIAL PROTEIN SEQUENCE.
[2]"Cloning of a mitogen-inducible gene encoding a kappa B DNA-binding protein with homology to the rel oncogene and to cell-cycle motifs."
Bours V., Villalobos J., Burd P.R., Kelly K., Siebenlist U.
Nature 348:76-80(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Cloning of the DNA-binding subunit of human nuclear factor kappa B: the level of its mRNA is strongly regulated by phorbol ester or tumor necrosis factor alpha."
Meyer R., Hatada E.N., Hohmann H.-P., Haiker M., Bartsch C., Roethlisberger U., Lahm H.-W., Schlaeger E.J., van Loon A.P.G.M., Scheidereit C.
Proc. Natl. Acad. Sci. U.S.A. 88:966-970(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE.
[4]"The complete exon-intron structure of the 156-kb human gene NFKB1, which encodes the p105 and p50 proteins of transcription factors NF-kappa B and I kappa B-gamma: implications for NF-kappa B-mediated signal transduction."
Heron E., Deloukas P., van Loon A.P.G.M.
Genomics 30:493-505(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Genome sequencing of the chromosome 4q region implicated in human hepatocellular carcinoma pathogenesis."
Chang H.-M., Tsai S.-F.
Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
Tissue: Brain and Hippocampus.
[7]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Rectum tumor.
[8]NIEHS SNPs program
Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-489; VAL-506; ILE-566; LYS-578; GLN-711 AND THR-901.
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Muscle and Uterus.
[10]"A novel complex between the p65 subunit of NF-kappa B and c-Rel binds to a DNA element involved in the phorbol ester induction of the human urokinase gene."
Hansen S.K., Nerlov C., Zabel U., Verde P., Johnsen M., Baeuerle P.A., Blasi F.
EMBO J. 11:205-213(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE NF-KAPPA-B P65-P50 COMPLEX.
[11]"The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B."
Palombella V.J., Rando O.J., Goldberg A.L., Maniatis T.
Cell 78:773-785(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION.
[12]"Activation of multiple NF-kappa B/Rel DNA-binding complexes by tumor necrosis factor."
Beg A.A., Baldwin A.S. Jr.
Oncogene 9:1487-1492(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE NF-KAPPA-B P50-C-REL COMPLEX.
[13]"A glycine-rich region in NF-kappaB p105 functions as a processing signal for the generation of the p50 subunit."
Lin L., Ghosh S.
Mol. Cell. Biol. 16:2248-2254(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING OF P105, GENERATION OF P50 AND P105.
[14]"Inhibition of NF-kappaB DNA binding by nitric oxide."
Matthews J.R., Botting C.H., Panico M., Morris H.R., Hay R.T.
Nucleic Acids Res. 24:2236-2242(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: S-NITROSYLATION AT CYS-61, MUTAGENESIS OF CYS-61, MASS SPECTROMETRY.
[15]"A new member of the IkappaB protein family, IkappaB epsilon, inhibits RelA (p65)-mediated NF-kappaB transcription."
Li Z., Nabel G.J.
Mol. Cell. Biol. 17:6184-6190(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NFKBIE.
[16]"Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome."
Lin L., DeMartino G.N., Greene W.C.
Cell 92:819-828(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: COTRANSLATIONAL FOLDING/PROCESSING OF P105, GENERATION OF P50/P105.
[17]"NF-kappaB p105 is a target of IkappaB kinases and controls signal induction of Bcl-3-p50 complexes."
Heissmeyer V., Krappmann D., Wulczyn F.G., Scheidereit C.
EMBO J. 18:4766-4778(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH BCL3, MUTAGENESIS OF SER-921; SER-923 AND SER-932.
[18]"TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105."
Belich M.P., Salmeron A., Johnston L.H., Ley S.C.
Nature 397:363-368(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K8.
[19]"Cotranslational dimerization of the Rel homology domain of NF-kappaB1 generates p50-p105 heterodimers and is required for effective p50 production."
Lin L., DeMartino G.N., Greene W.C.
EMBO J. 19:4712-4722(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: COTRANSLATIONAL FOLDING/PROCESSING OF P105, GENERATION OF P50/P105, P50-P105 TRANSIENT HETERODIMER FORMATION.
[20]"RAC-3 is a NF-kappa B coactivator."
Werbajh S., Nojek I., Lanz R., Costas M.A.
FEBS Lett. 485:195-199(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NCOA3.
[21]"Inhibition of NF-kappaB by S-nitrosylation."
Marshall H.E., Stamler J.S.
Biochemistry 40:1688-1693(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: S-NITROSYLATION.
[22]"Modulation of T-cell activation by the glucocorticoid-induced leucine zipper factor via inhibition of nuclear factor kappa B."
Ayroldi E., Migliorati G., Bruscoli S., Marchetti C., Zollo O., Cannarile L., D'Adamio F., Riccardi C.
Blood 98:743-753(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DSIPI.
[23]"15-Deoxy-Delta 12,14-prostaglandin J2 inhibition of NF-kappaB-DNA binding through covalent modification of the p50 subunit."
Cernuda-Morollon E., Pineda-Molina E., Canada F.J., Perez-Sala D.
J. Biol. Chem. 276:35530-35536(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: LIPID MODIFICATION OF CYS-61, MUTAGENESIS OF CYS-61.
[24]"Direct phosphorylation of NF-kappa B1 p105 by the Ikappa B kinase complex on serine 927 is essential for signal-induced p105 proteolysis."
Salmeron A., Janzen J., Soneji Y., Bump N., Kamens J., Allen H., Ley S.C.
J. Biol. Chem. 276:22215-22222(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-927.
[25]"The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation."
Heppner C., Bilimoria K.Y., Agarwal S.K., Kester M., Whitty L.J., Guru S.C., Chandrasekharappa S.C., Collins F.S., Spiegel A.M., Marx S.J., Burns A.L.
Oncogene 20:4917-4925(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MEN1.
[26]"Casper/c-FLIP is physically and functionally associated with NF-kappaB1 p105."
Li Z., Zhang J., Chen D., Shu H.B.
Biochem. Biophys. Res. Commun. 309:980-985(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CFLAR.
[27]"Enhancement of nuclear factor-kappa B acetylation by coactivator p300 and HIV-1 Tat proteins."
Furia B., Deng L., Wu K., Baylor S., Kehn K., Li H., Donnelly R., Coleman T., Kashanchi F.
J. Biol. Chem. 277:4973-4980(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-431; LYS-440 AND LYS-441.
[28]"Synthesis of glucocorticoid-induced leucine zipper (GILZ) by macrophages: an anti-inflammatory and immunosuppressive mechanism shared by glucocorticoids and IL-10."
Berrebi D., Bruscoli S., Cohen N., Foussat A., Migliorati G., Bouchet-Delbos L., Maillot M.-C., Portier A., Couderc J., Galanaud P., Peuchmaur M., Riccardi C., Emilie D.
Blood 101:729-738(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DSIPI.
[29]"Up-regulation of p300 binding and p50 acetylation in tumor necrosis factor-alpha-induced cyclooxygenase-2 promoter activation."
Deng W.G., Zhu Y., Wu K.K.
J. Biol. Chem. 278:4770-4777(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION.
[30]"Glycogen synthase kinase-3 beta regulates NF-kappa B1/p105 stability."
Demarchi F., Bertoli C., Sandy P., Schneider C.
J. Biol. Chem. 278:39583-39590(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GSK3B, PHOSPHORYLATION AT SER-903 AND SER-907, MUTAGENESIS OF SER-903 AND SER-907.
[31]"betaTrCP-mediated proteolysis of NF-kappaB1 p105 requires phosphorylation of p105 serines 927 and 932."
Lang V., Janzen J., Fischer G.Z., Soneji Y., Beinke S., Salmeron A., Allen H., Hay R.T., Ben-Neriah Y., Ley S.C.
Mol. Cell. Biol. 23:402-413(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-927 AND SER-932.
[32]"Identification of a ZU5 and death domain-containing inhibitor of NF-kappaB."
Zhang J., Xu L.-G., Han K.-J., Shu H.-B.
J. Biol. Chem. 279:17819-17825(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH UNC5CL.
[33]"ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability."
Lang V., Symons A., Watton S.J., Janzen J., Soneji Y., Beinke S., Howell S., Ley S.C.
Mol. Cell. Biol. 24:5235-5248(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K8 AND TNIP2.
[34]"Leishmania major amastigotes induce p50/c-Rel NF-kappa B transcription factor in human macrophages: involvement in cytokine synthesis."
Guizani-Tabbane L., Ben-Aissa K., Belghith M., Sassi A., Dellagi K.
Infect. Immun. 72:2582-2589(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN THE NF-KAPPA-B P50-C-REL COMPLEX.
[35]"Lipopolysaccharide activation of the TPL-2/MEK/extracellular signal-regulated kinase mitogen-activated protein kinase cascade is regulated by IkappaB kinase-induced proteolysis of NF-kappaB1 p105."
Beinke S., Robinson M.J., Hugunin M., Ley S.C.
Mol. Cell. Biol. 24:9658-9667(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP3K8.
[36]"A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway."
Bouwmeester T., Bauch A., Ruffner H., Angrand P.-O., Bergamini G., Croughton K., Cruciat C., Eberhard D., Gagneur J., Ghidelli S., Hopf C., Huhse B., Mangano R., Michon A.-M., Schirle M., Schlegl J., Schwab M., Stein M.A. expand/collapse author list , Bauer A., Casari G., Drewes G., Gavin A.-C., Jackson D.B., Joberty G., Neubauer G., Rick J., Kuster B., Superti-Furga G.
Nat. Cell Biol. 6:97-105(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SPAG9.
[37]"Posttranslational hydroxylation of ankyrin repeats in IkappaB proteins by the hypoxia-inducible factor (HIF) asparaginyl hydroxylase, factor inhibiting HIF (FIH)."
Cockman M.E., Lancaster D.E., Stolze I.P., Hewitson K.S., McDonough M.A., Coleman M.L., Coles C.H., Yu X., Hay R.T., Ley S.C., Pugh C.W., Oldham N.J., Masson N., Schofield C.J., Ratcliffe P.J.
Proc. Natl. Acad. Sci. U.S.A. 103:14767-14772(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIF1AN, ASPARAGINYL HYDROXYLATION, MUTAGENESIS OF ASN-678.
[38]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[39]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-937, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[40]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[41]"Structure of the NF-kappa B p50 homodimer bound to DNA."
Mueller C.W., Rey F.A., Sodeoka M., Verdine G.L., Harrison S.C.
Nature 373:311-317(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-365.
[42]"Structure of an IkappaBalpha/NF-kappaB complex."
Jacobs M.D., Harrison S.C.
Cell 95:749-758(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 248-354.
[43]"Solution structure of the death domain in human nuclear factor NF-kappa-B p105 subunit."
RIKEN structural genomics initiative (RSGI)
Submitted (DEC-2006) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 804-893.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M55643 mRNA. Translation: AAA36361.1.
M58603 mRNA. Translation: AAA36360.1.
Z47748 expand/collapse EMBL AC list , Z47749, Z47750, Z47751, Z47752, Z47753, Z47754, Z47755, Z47734, Z47735, Z47736, Z47737, Z47738, Z47739, Z47740, Z47741, Z47742, Z47743, Z47744 Genomic DNA. Translation: CAB94757.1.
AF213884 Genomic DNA. Translation: AAF35232.1.
AK122850 mRNA. Translation: BAG53760.1.
AK291450 mRNA. Translation: BAF84139.1.
CR749522 mRNA. Translation: CAH18336.1.
AY223820 Genomic DNA. Translation: AAO30127.1.
BC033210 mRNA. Translation: AAH33210.1.
BC051765 mRNA. Translation: AAH51765.1.
PIRA37867.
RefSeqNP_001158884.1. NM_001165412.1.
NP_003989.2. NM_003998.3.
UniGeneHs.618430.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MDINMR-B55-67[»]
1MDJNMR-B55-67[»]
1MDKNMR-B55-67[»]
1NFIX-ray2.70B/D248-354[»]
1SVCX-ray2.60P2-365[»]
2DBFNMR-A806-893[»]
2O61X-ray2.80B40-352[»]
3GUTX-ray3.59B/D/F/H41-352[»]
ProteinModelPortalP19838.
SMRP19838. Positions 42-353, 494-790, 804-889.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110857. 127 interactions.
DIPDIP-106N.
IntActP19838. 238 interactions.
MINTMINT-85658.
STRING9606.ENSP00000226574.

Chemistry

BindingDBP19838.
ChEMBLCHEMBL3251.
DrugBankDB01234. Dexamethasone.
DB01411. Pranlukast.
DB01041. Thalidomide.

PTM databases

PhosphoSiteP19838.

Polymorphism databases

DMDM21542418.

Proteomic databases

PaxDbP19838.
PRIDEP19838.

Protocols and materials databases

DNASU4790.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000226574; ENSP00000226574; ENSG00000109320. [P19838-2]
ENST00000394820; ENSP00000378297; ENSG00000109320. [P19838-1]
ENST00000505458; ENSP00000424790; ENSG00000109320. [P19838-1]
ENST00000600343; ENSP00000469340; ENSG00000109320. [P19838-3]
GeneID4790.
KEGGhsa:4790.
UCSCuc011cep.2. human. [P19838-2]
uc011ceq.2. human. [P19838-1]
uc011cer.2. human. [P19838-3]

Organism-specific databases

CTD4790.
GeneCardsGC04P103422.
HGNCHGNC:7794. NFKB1.
HPACAB004031.
HPA027305.
MIM164011. gene.
neXtProtNX_P19838.
PharmGKBPA248.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0666.
HOGENOMHOG000004822.
HOVERGENHBG052613.
KOK02580.
OMAPGYGFPH.
OrthoDBEOG7W154S.
TreeFamTF325632.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_120956. Cellular responses to stress.
REACT_6782. TRAF6 Mediated Induction of proinflammatory cytokines.
REACT_6900. Immune System.
SignaLinkP19838.

Gene expression databases

ArrayExpressP19838.
BgeeP19838.
CleanExHS_NFKB1.
GenevestigatorP19838.

Family and domain databases

Gene3D1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR000451. NF_Rel_Dor.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]
PfamPF00023. Ank. 3 hits.
PF12796. Ank_2. 1 hit.
PF00531. Death. 1 hit.
PF00554. RHD. 1 hit.
[Graphical view]
PRINTSPR01415. ANKYRIN.
PR00057. NFKBTNSCPFCT.
SMARTSM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
SM00429. IPT. 1 hit.
[Graphical view]
SUPFAMSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSNFKB1. human.
EvolutionaryTraceP19838.
GeneWikiNFKB1.
GenomeRNAi4790.
NextBio18454.
PMAP-CutDBP19838.
PROP19838.
SOURCESearch...

Entry information

Entry nameNFKB1_HUMAN
AccessionPrimary (citable) accession number: P19838
Secondary accession number(s): A8K5Y5 expand/collapse secondary AC list , B3KVE8, Q68D84, Q86V43, Q8N4X7, Q9NZC0
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: June 20, 2002
Last modified: March 19, 2014
This is version 185 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM