CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-004810
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
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
252APNASNLKIVRMDRTubiquitination[1]
625SVLHLAAKEGHDKVLubiquitination[1]
817KQLAEDVKLQLYKLLubiquitination[1]
822DVKLQLYKLLEIPDPubiquitination[1, 2]
831LEIPDPDKNWATLAQubiquitination[1]
857RLSPAPSKTLMDNYEubiquitination[1, 2]
Reference
 [1] 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]
 [2] 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] 
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
MAEDDPYLGR PEQMFHLDPS LTHTIFNPEV FQPQMALPTA DGPYLQILEQ PKQRGFRFRY 60
VCEGPSHGGL PGASSEKNKK SYPQVKICNY VGPAKVIVQL VTNGKNIHLH AHSLVGKHCE 120
DGICTVTAGP KDMVVGFANL GILHVTKKKV FETLEARMTE ACIRGYNPGL LVHPDLAYLQ 180
AEGGGDRQLG DREKELIRQA ALQQTKEMDL SVVRLMFTAF LPDSTGSFTR RLEPVVSDAI 240
YDSKAPNASN LKIVRMDRTA GCVTGGEEIY LLCDKVQKDD IQIRFYEEEE NGGVWEGFGD 300
FSPTDVHRQF AIVFKTPKYK DINITKPASV FVQLRRKSDL ETSEPKPFLY YPEIKDKEEV 360
QRKRQKLMPN FSDSFGGGSG AGAGGGGMFG SGGGGGGTGS TGPGYSFPHY GFPTYGGITF 420
HPGTTKSNAG MKHGTMDTES KKDPEGCDKS DDKNTVNLFG KVIETTEQDQ EPSEATVGNG 480
EVTLTYATGT KEESAGVQDN LFLEKAMQLA KRHANALFDY AVTGDVKMLL AVQRHLTAVQ 540
DENGDSVLHL AIIHLHSQLV RDLLEVTSGL ISDDIINMRN DLYQTPLHLA VITKQEDVVE 600
DLLRAGADLS LLDRLGNSVL HLAAKEGHDK VLSILLKHKK AALLLDHPNG DGLNAIHLAM 660
MSNSLPCLLL LVAAGADVNA QEQKSGRTAL HLAVEHDNIS LAGCLLLEGD AHVDSTTYDG 720
TTPLHIAAGR GSTRLAALLK AAGADPLVEN FEPLYDLDDS WENAGEDEGV VPGTTPLDMA 780
TSWQVFDILN GKPYEPEFTS DDLLAQGDMK QLAEDVKLQL YKLLEIPDPD KNWATLAQKL 840
GLGILNNAFR LSPAPSKTLM DNYEVSGGTV RELVEALRQM GYTEAIEVIQ AASSPVKTTS 900
QAHSLPLSPA STRQQIDELR DSDSVCDSGV ETSFRKLSFT ESLTSGASLL TLNKMPHDYG 960
QEGPLEGKI 969 
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.