UniProt Accession

 NFKB1_HUMAN; P19838; A8K5Y5; B3KVE8; Q68D84; Q86V43; Q8N4X7; Q9NZC0 

Genbank Protein ID

 M55643; M58603; Z47748; Z47749; Z47750; Z47751; Z47752; Z47753; Z47754; Z47755; Z47734; Z47735; Z47736; Z47737; Z47738; Z47739; Z47740; Z47741; Z47742; Z47743; Z47744; AF213884; AK122850; AK291450; CR749522; AY223820; BC033210; BC051765 

Genbank Nucleotide ID

 AAA36361.1; AAA36360.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; CAB94757.1; AAF35232.1; BAG53760.1; BAF84139.1; CAH18336.1; AAO30127.1; AAH33210.1; AAH51765.1 

Protein Name

 Nuclear factor NF-kappa-B p105 subunit 

Protein Synonyms/Alias

 DNA-binding factor KBF1; EBP-1; Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1; Nuclear factor NF-kappa-B p50 subunit 

Gene Name

 NFKB1 

Gene Synonyms/Alias

  

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
431	TKSNAGMKHGTMDTE	acetylation	[1]
440	GTMDTESKKDPEGCD	acetylation	[1, 2]
441	TMDTESKKDPEGCDK	acetylation	[1]
504	QDNLFLEKAMQLAKR	ubiquitination	[3]
624	SVLHLAAKEGHDKVL	ubiquitination	[4]
816	KQLAEDVKLQLYKLL	ubiquitination	[4]
821	DVKLQLYKLLEIPDP	ubiquitination	[3, 4, 5]
830	LEIPDPDKNWATLAQ	ubiquitination	[4]
856	RLSPAPSKTLMDNYE	ubiquitination	[3, 4, 5, 6, 7]

Reference

 [1] 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. 2002 Feb 15;277(7):4973-80. [PMID: 11739381]
 [2] Regulation of cellular metabolism by protein lysine acetylation.
 Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL.
 Science. 2010 Feb 19;327(5968):1000-4. [PMID: 20167786]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [7] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302] 

Functional Description

 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. 

Sequence Annotation

 DOMAIN 42 367 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 Interaction with CFLAR.
 REGION 650 684 Essential for interaction with HIF1AN.
 MOTIF 360 365 Nuclear localization signal (Potential).
 MOD_RES 61 61 S-nitrosocysteine; alternate.
 MOD_RES 337 337 Phosphoserine; by PKA (Potential).
 MOD_RES 431 431 N6-acetyllysine; by EP300 (Probable).
 MOD_RES 440 440 N6-acetyllysine; by EP300 (Probable).
 MOD_RES 441 441 N6-acetyllysine; by EP300 (Probable).
 MOD_RES 449 449 Phosphoserine (By similarity).
 MOD_RES 678 678 (3S)-3-hydroxyasparagine; by HIF1AN;
 MOD_RES 903 903 Phosphoserine; by GSK3-beta; in vitro.
 MOD_RES 907 907 Phosphoserine; by GSK3-beta; in vitro.
 MOD_RES 927 927 Phosphoserine; by IKKB.
 MOD_RES 932 932 Phosphoserine; by IKKB.
 MOD_RES 937 937 Phosphoserine.
 LIPID 61 61 S-(15-deoxy-Delta12,14-prostaglandin J2-  

Keyword

 3D-structure; Acetylation; Activator; Alternative splicing; ANK repeat; Apoptosis; Complete proteome; Cytoplasm; Direct protein sequencing; DNA-binding; Hydroxylation; Lipoprotein; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; S-nitrosylation; Transcription; Transcription regulation; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 968 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0033256; C:I-kappaB/NF-kappaB complex; TAS:BHF-UCL.
 GO:0005739; C:mitochondrion; IDA:HPA.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0003690; F:double-stranded DNA binding; IEA:Compara.
 GO:0003700; F:sequence-specific DNA binding transcription factor activity; TAS:ProtInc.
 GO:0008134; F:transcription factor binding; IDA:MGI.
 GO:0000976; F:transcription regulatory region sequence-specific DNA binding; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0071347; P:cellular response to interleukin-1; IEP:BHF-UCL.
 GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
 GO:0006954; P:inflammatory response; TAS:UniProtKB.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0031293; P:membrane protein intracellular domain proteolysis; TAS:Reactome.
 GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome.
 GO:0043066; P:negative regulation of apoptotic process; TAS:UniProtKB.
 GO:0010956; P:negative regulation of calcidiol 1-monooxygenase activity; IDA:BHF-UCL.
 GO:0032269; P:negative regulation of cellular protein metabolic process; IC:BHF-UCL.
 GO:0032375; P:negative regulation of cholesterol transport; IC:BHF-UCL.
 GO:0001818; P:negative regulation of cytokine production; IEA:Compara.
 GO:0045083; P:negative regulation of interleukin-12 biosynthetic process; IEA:Compara.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:UniProtKB.
 GO:0010957; P:negative regulation of vitamin D biosynthetic process; IC:BHF-UCL.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0090263; P:positive regulation of canonical Wnt receptor signaling pathway; IMP:UniProtKB.
 GO:1900127; P:positive regulation of hyaluronan biosynthetic process; IDA:UniProtKB.
 GO:0010884; P:positive regulation of lipid storage; IC:BHF-UCL.
 GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IC:BHF-UCL.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; TAS:Reactome.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0032481; P:positive regulation of type I interferon production; TAS:Reactome.
 GO:0009617; P:response to bacterium; IEA:Compara.
 GO:0046688; P:response to copper ion; IEA:Compara.
 GO:0006979; P:response to oxidative stress; IEA:Compara.
 GO:0050852; P:T cell receptor signaling pathway; TAS:Reactome.
 GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome.
 GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome.
 GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome.
 GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome.
 GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome.
 GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome.
 GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome.
 GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome.
 GO:0006366; P:transcription from RNA polymerase II promoter; TAS:UniProtKB.
 GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. 

Interpro

 IPR002110; Ankyrin_rpt.
 IPR020683; Ankyrin_rpt-contain_dom.
 IPR011029; DEATH-like_dom.
 IPR000488; Death_domain.
 IPR013783; Ig-like_fold.
 IPR014756; Ig_E-set.
 IPR002909; IPT_TIG_rcpt.
 IPR000451; NF_Rel_Dor.
 IPR008967; p53-like_TF_DNA-bd.
 IPR011539; RHD. 

Pfam

 PF00023; Ank
 PF00531; Death
 PF00554; RHD 

SMART

 SM00248; ANK
 SM00005; DEATH
 SM00429; IPT 

PROSITE

 PS50297; ANK_REP_REGION
 PS50088; ANK_REPEAT
 PS50017; DEATH_DOMAIN
 PS01204; REL_1
 PS50254; REL_2 

PRINTS

 PR01415; ANKYRIN.
 PR00057; NFKBTNSCPFCT.