Nuclear factor NF-kappa-B p105 subunit

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Reviewed, UniProtKB/Swiss-Prot P19838 (NFKB1_HUMAN)

Last modified January 19, 2010. Version 139. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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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

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Sequence length	968 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105. Ref.32
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. Ref.32 Ref.14 Ref.17 Ref.19 Ref.21 Ref.23 Ref.25 Ref.27 Ref.29 Ref.30 Ref.33
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-alpha.
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.
Sequence similarities	Contains 7 ANK repeats. Contains 1 death domain. Contains 1 RHD (Rel-like) domain.

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Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	ANK repeat Repeat
Ligand	DNA-binding
Molecular function	Activator
PTM	Acetylation Phosphoprotein S-nitrosylation Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anti-apoptosis Traceable author statement. Source: UniProtKB apoptosis Inferred from electronic annotation. Source: UniProtKB-KW inflammatory response Ref.3 Traceable author statement. Source: UniProtKB membrane protein intracellular domain proteolysis Inferred from Experiment. Source: Reactome negative regulation of calcidiol 1-monooxygenase activity Inferred from direct assay. Source: UniProtKB negative regulation of cellular protein metabolic process Inferred by curator. Source: UniProtKB negative regulation of cholesterol transport Inferred by curator. Source: UniProtKB negative regulation of gene-specific transcription from RNA polymerase II promoter Inferred by curator. Source: UniProtKB negative regulation of vitamin D biosynthetic process Inferred by curator. Source: UniProtKB positive regulation of lipid storage Inferred by curator. Source: UniProtKB positive regulation of macrophage derived foam cell differentiation Inferred by curator. Source: UniProtKB positive regulation of transcription Non-traceable author statement. Source: UniProtKB signal transduction Inferred from electronic annotation. Source: InterPro transcription from RNA polymerase II promoter Ref.3 Traceable author statement. Source: UniProtKB
Cellular component	I-kappaB/NF-kappaB complex Traceable author statement. Source: UniProtKB cytosol Inferred from Experiment. Source: Reactome nucleoplasm Inferred from Experiment. Source: Reactome
Molecular function	promoter binding Inferred from direct assay. Source: UniProtKB protein binding Ref.30 Ref.33 Inferred from physical interaction. Source: UniProtKB transcription factor activity Traceable author statement. Source: ProtInc
Complete GO annotation...

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With	Entry	#Exp.	IntAct
COMMD1	Q8N668	1	EBI-1452242,EBI-1550112
HDAC1	Q13547	2	EBI-300010,EBI-301834
PDCD11	Q14690	1	EBI-300010,EBI-300028
RELA	Q04206	2	EBI-300010,EBI-73886
RPS3	P23396	1	EBI-300010,EBI-351193
SPAG9	O60271	1	EBI-300010,EBI-1023301
TNIP2	Q8NFZ5	4	EBI-1452239,EBI-359372

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Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Chain

1 – 968

968

Nuclear factor NF-kappa-B p105 subunit

PRO_0000030310

Chain

1 – 433

433

Nuclear factor NF-kappa-B p50 subunit

PRO_0000030311

Domain

42 – 367

326

RHD

Repeat

542 – 571

ANK 1

Repeat

581 – 610

ANK 2

Repeat

614 – 643

ANK 3

Repeat

650 – 679

ANK 4

Repeat

684 – 714

ANK 5

Repeat

718 – 747

ANK 6

Repeat

771 – 801

ANK 7

Domain

805 – 892

Death

Region

372 – 394

GRR

Region

435 – 968

534

Interaction with CFLAR

Motif

360 – 365

Nuclear localization signal Potential

Compositional bias

375 – 433

Gly-rich

Site

433 – 434

Cleavage (when cotranslationally processed)

Modified residue

S-nitrosocysteine Ref.13

Modified residue

337

Phosphoserine; by PKA Potential

Modified residue

431

N6-acetyllysine; by EP300 Probable

Modified residue

440

N6-acetyllysine; by EP300 Probable

Modified residue

441

N6-acetyllysine; by EP300 Probable

Modified residue

449

Phosphoserine By similarity

Modified residue

893

Phosphoserine Ref.36

Modified residue

903

Phosphoserine; by GSK3-beta; in vitro Ref.27 Ref.36

Modified residue

907

Phosphoserine; by GSK3-beta; in vitro Ref.27 Ref.36 Ref.34

Modified residue

927

Phosphoserine; by IKKB Ref.22 Ref.28

Modified residue

932

Phosphoserine; by IKKB Ref.28

Modified residue

937

Phosphoserine Ref.36

Alternative sequence

T → TA in isoform 2.

VSP_021025

Natural variant

489

T → I

VAR_016268

Natural variant

506

M → V

VAR_016269

Natural variant

566

T → I

VAR_016270

Natural variant

578

R → K

VAR_016271

Natural variant

711

H → Q

VAR_016272

Natural variant

901

A → T

VAR_016273

Mutagenesis

C → S: Suppresses S-nitrosylation-induced inhibition of DNA-binding activity. Ref.13

Mutagenesis

903

S → A: Prevents p105 proteolysis in response to TNF-alpha. Ref.27

Mutagenesis

907

S → A: Prevents p105 proteolysis in response to TNF-alpha. Ref.27

Mutagenesis

921

S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-923 and A-932. Ref.16

Mutagenesis

923

S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-932. Ref.16

Mutagenesis

932

S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-923. Ref.16

Sequence conflict

243

K → SE Ref.4

Sequence conflict

361

R → G in CAH18336. Ref.6

Sequence conflict

551 – 552

II → SS in CAB94757. Ref.4

Sequence conflict

726

A → V in CAB94757. Ref.4

Sequence conflict

825

I → T in CAH18336. Ref.6

Sequence conflict

869

V → I in CAB94757. Ref.4

Sequence conflict

927

S → T in AAA36361. Ref.1

Sequence conflict

927

S → T in AAA36360. Ref.3

Sequence conflict

927

S → T in CAB94757. Ref.4

968

Helix Strand Turn

Details...

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Sequence		Length	Mass (Da)
Isoform 1 [UniParc]. Last modified June 20, 2002. Version 2. Checksum: 2A7C8FF86A10D1A8 Show »	FASTA	968	105,356
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. Checksum: B4D57AC8A410941D Show »	FASTA	969	105,427
10 20 30 40 50 60 MAEDDPYLGR PEQMFHLDPS LTHTIFNPEV FQPQMALPTA DGPYLQILEQ PKQRGFRFRY 70 80 90 100 110 120 VCEGPSHGGL PGASSEKNKK SYPQVKICNY VGPAKVIVQL VTNGKNIHLH AHSLVGKHCE 130 140 150 160 170 180 DGICTVTAGP KDMVVGFANL GILHVTKKKV FETLEARMTE ACIRGYNPGL LVHPDLAYLQ 190 200 210 220 230 240 AEGGGDRQLG DREKELIRQA ALQQTKEMDL SVVRLMFTAF LPDSTGSFTR RLEPVVSDAI 250 260 270 280 290 300 YDSKAPNASN LKIVRMDRTA GCVTGGEEIY LLCDKVQKDD IQIRFYEEEE NGGVWEGFGD 310 320 330 340 350 360 FSPTDVHRQF AIVFKTPKYK DINITKPASV FVQLRRKSDL ETSEPKPFLY YPEIKDKEEV 370 380 390 400 410 420 QRKRQKLMPN FSDSFGGGSG AGAGGGGMFG SGGGGGGTGS TGPGYSFPHY GFPTYGGITF 430 440 450 460 470 480 HPGTTKSNAG MKHGTMDTES KKDPEGCDKS DDKNTVNLFG KVIETTEQDQ EPSEATVGNG 490 500 510 520 530 540 EVTLTYATGT KEESAGVQDN LFLEKAMQLA KRHANALFDY AVTGDVKMLL AVQRHLTAVQ 550 560 570 580 590 600 DENGDSVLHL AIIHLHSQLV RDLLEVTSGL ISDDIINMRN DLYQTPLHLA VITKQEDVVE 610 620 630 640 650 660 DLLRAGADLS LLDRLGNSVL HLAAKEGHDK VLSILLKHKK AALLLDHPNG DGLNAIHLAM 670 680 690 700 710 720 MSNSLPCLLL LVAAGADVNA QEQKSGRTAL HLAVEHDNIS LAGCLLLEGD AHVDSTTYDG 730 740 750 760 770 780 TTPLHIAAGR GSTRLAALLK AAGADPLVEN FEPLYDLDDS WENAGEDEGV VPGTTPLDMA 790 800 810 820 830 840 TSWQVFDILN GKPYEPEFTS DDLLAQGDMK QLAEDVKLQL YKLLEIPDPD KNWATLAQKL 850 860 870 880 890 900 GLGILNNAFR LSPAPSKTLM DNYEVSGGTV RELVEALRQM GYTEAIEVIQ AASSPVKTTS 910 920 930 940 950 960 QAHSLPLSPA STRQQIDELR DSDSVCDSGV ETSFRKLSFT ESLTSGASLL TLNKMPHDYG QEGPLEGKI « Hide

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	« Hide 'large scale' referencesShow '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: 2203531] [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: 2234062] [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: 1992489] [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: 8825636] [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]	"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: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Rectum tumor.
[7]	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.
[8]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Muscle and Uterus.
[9]	"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: 1740106] [Abstract] Cited for: IDENTIFICATION IN THE NF-KAPPA-B P65-P50 COMPLEX.
[10]	"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: 8087845] [Abstract] Cited for: UBIQUITINATION.
[11]	"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: 8152812] [Abstract] Cited for: IDENTIFICATION IN THE NF-KAPPA-B P50-C-REL COMPLEX.
[12]	"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: 8628291] [Abstract] Cited for: PROTEOLYTIC PROCESSING OF P105, GENERATION OF P50 AND P105.
[13]	"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: 8710491] [Abstract] Cited for: S-NITROSYLATION AT CYS-61, MUTAGENESIS OF CYS-61, MASS SPECTROMETRY.
[14]	"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: 9315679] [Abstract] Cited for: INTERACTION WITH NFKBIE.
[15]	"Cotranslational biogenesis of NF-kappaB p50 by the 26S proteasome." Lin L., DeMartino G.N., Greene W.C. Cell 92:819-828(1998) [PubMed: 9529257] [Abstract] Cited for: COTRANSLATIONAL FOLDING/PROCESSING OF P105, GENERATION OF P50/P105.
[16]	"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: 10469655] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH BCL3, MUTAGENESIS OF SER-921; SER-923 AND SER-932.
[17]	"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: 9950430] [Abstract] Cited for: INTERACTION WITH MAP3K8.
[18]	"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: 10970863] [Abstract] Cited for: COTRANSLATIONAL FOLDING/PROCESSING OF P105, GENERATION OF P50/P105, P50-P105 TRANSIENT HETERODIMER FORMATION.
[19]	"RAC-3 is a NF-kappa B coactivator." Werbajh S., Nojek I., Lanz R., Costas M.A. FEBS Lett. 485:195-199(2000) [PubMed: 11094166] [Abstract] Cited for: INTERACTION WITH NCOA3.
[20]	"Inhibition of NF-kappaB by S-nitrosylation." Marshall H.E., Stamler J.S. Biochemistry 40:1688-1693(2001) [PubMed: 11327828] [Abstract] Cited for: S-NITROSYLATION.
[21]	"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: 11468175] [Abstract] Cited for: INTERACTION WITH DSIPI.
[22]	"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: 11297557] [Abstract] Cited for: PHOSPHORYLATION AT SER-927.
[23]	"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: 13679070] [Abstract] Cited for: INTERACTION WITH CFLAR.
[24]	"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: 11739381] [Abstract] Cited for: ACETYLATION AT LYS-431; LYS-440 AND LYS-441.
[25]	"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: 12393603] [Abstract] Cited for: INTERACTION WITH DSIPI.
[26]	"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: 12471036] [Abstract] Cited for: ACETYLATION.
[27]	"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: 12871932] [Abstract] Cited for: INTERACTION WITH GSK3B, PHOSPHORYLATION AT SER-903 AND SER-907, MUTAGENESIS OF SER-903 AND SER-907.
[28]	"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: 12482991] [Abstract] Cited for: PHOSPHORYLATION AT SER-927 AND SER-932.
[29]	"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: 14769797] [Abstract] Cited for: INTERACTION WITH UNC5CL.
[30]	"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: 15169888] [Abstract] Cited for: INTERACTION WITH MAP3K8 AND TNIP2.
[31]	"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: 15102766] [Abstract] Cited for: IDENTIFICATION IN THE NF-KAPPA-B P50-C-REL COMPLEX.
[32]	"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: 15485931] [Abstract] Cited for: FUNCTION, INTERACTION WITH MAP3K8.
[33]	"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. Superti-Furga G. Nat. Cell Biol. 6:97-105(2004) [PubMed: 14743216] [Abstract] Cited for: INTERACTION WITH SPAG9.
[34]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-907, MASS SPECTROMETRY.
[35]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[36]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-893; SER-903; SER-907 AND SER-937, MASS SPECTROMETRY. Tissue: T-cell.
[37]	"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: 7830764] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 1-365.
[38]	"Structure of an IkappaBalpha/NF-kappaB complex." Jacobs M.D., Harrison S.C. Cell 95:749-758(1998) [PubMed: 9865693] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 248-354.
[39]	"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.

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Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

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EMBL
GenBank
DDBJ

M55643 mRNA. Translation: AAA36361.1.
M58603 mRNA. Translation: AAA36360.1.
Z47748

Z47744 Genomic DNA. Translation: CAB94757.1.
AF213884 Genomic DNA. Translation: AAF35232.1.
CR749522 mRNA. Translation: CAH18336.1.
AY223820 Genomic DNA. Translation: AAO30127.1.
BC033210 mRNA. Translation: AAH33210.1.
BC051765 mRNA. Translation: AAH51765.1.

IPI

IPI00292537.
IPI00788987.

PIR

A37867.

RefSeq

NP_001158884.1.
NP_003989.2.

UniGene

Hs.654408

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MDI	NMR	-	B	55-67	[»]
1MDJ	NMR	-	B	55-67	[»]
1MDK	NMR	-	B	55-67	[»]
1NFI	X-ray	2.70	B/D	248-354	[»]
1SVC	X-ray	2.60	P	2-365	[»]
2DBF	NMR	-	A	806-893	[»]
2O61	X-ray	2.80	B	40-352	[»]
3GUT	X-ray	3.59	B/D/F/H	41-352	[»]

SMR

P19838. Positions 514-743, 541-790.

ModBase

Search...

DIP

DIP-106N.

IntAct

P19838. 30 interactions.

STRING

P19838.

PhosphoSite

P19838.

PRIDE

P19838.

Ensembl

ENST00000394820; ENSP00000378297; ENSG00000109320; Homo sapiens. [Genome view]

GeneID

4790.

KEGG

hsa:4790.

UCSC

uc003hwd.1. human.
uc003hwe.1. human.

CTD

4790.

GeneCards

GC04P103641.

HGNC

HGNC:7794. NFKB1.

HPA

CAB004031.
HPA027305.

MIM

164011. gene.

PharmGKB

PA248.

GenAtlas

Search...

eggNOG

prNOG10605.

HOVERGEN

P19838.

OMA

EGHDKIL.

PhylomeDB

P19838.

Pathway_Interaction_DB

nfkappabalternativepathway. Alternative NF-kappaB pathway.
amb2_neutrophils_pathway. amb2 Integrin signaling.
nfkappabatypicalpathway. Atypical NF-kappaB pathway.
bcr_5pathway. BCR signaling pathway.
nfkappabcanonicalpathway. Canonical NF-kappaB pathway.
ceramidepathway. Ceramide signaling pathway.
epopathway. EPO signaling pathway.
faspathway. FAS signaling pathway (CD95).
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
hivnefpathway. HIV-1 Nef: Negative effector of Fas and TNF-alpha.
il1pathway. IL1-mediated signaling events.
il12_2pathway. IL12-mediated signaling events.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
il23pathway. IL23-mediated signaling events.
lysophospholipid_pathway. LPA receptor mediated events.
avb3_opn_pathway. Osteopontin-mediated events.
telomerasepathway. Regulation of Telomerase.
hdac_classi_pathway. Signaling events mediated by HDAC Class I.
tnfpathway. TNF receptor signaling pathway.

Reactome

REACT_11061. Signalling by NGF.
REACT_6900. Signaling in Immune system.

ArrayExpress

P19838.

Bgee

P19838.

CleanEx

HS_NFKB1.

Genevestigator

P19838.

GermOnline

ENSG00000109320. Homo sapiens.

InterPro

IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR000488. Death.
IPR011029. DEATH-like.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT_TIG_rcpt.
IPR000451. NF_Rel_dor.
IPR008967. p53-like_TF_DNA-bd.
IPR011539. RHD.
[Graphical view]

Gene3D

G3DSA:1.25.40.20. ANK. 1 hit.
G3DSA:1.10.533.10. DEATH_like. 1 hit.
G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
G3DSA:2.60.40.340. RHD. 1 hit.

Pfam

PF00023. Ank. 3 hits.
PF00531. Death. 1 hit.
PF00554. RHD. 1 hit.
[Graphical view]

PRINTS

PR00057. NFKBTNSCPFCT.

SMART

SM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
SM00429. IPT. 1 hit.
[Graphical view]

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS50017. DEATH_DOMAIN. False negative.
PS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]

ProtoNet

Search...

DrugBank

DB01234. Dexamethasone.
DB01411. Pranlukast.
DB01041. Thalidomide.

NextBio

18454.

PMAP-CutDB

P19838.

SOURCE

Search...

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Entry name

NFKB1_HUMAN

Accession

Primary (citable) accession number: P19838
Secondary accession number(s): Q68D84

Q9NZC0

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	June 20, 2002
Last modified:	January 19, 2010
This is version 139 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.

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Human chromosome 4

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

This entry describes 2 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