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Protein

Nuclear factor NF-kappa-B p105 subunit

Gene

NFKB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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/p105.1 Publication

GO - Molecular functioni

  • actinin binding Source: UniProtKB
  • chromatin binding Source: GO_Central
  • identical protein binding Source: IntAct
  • protein heterodimerization activity Source: UniProtKB
  • regulatory region DNA binding Source: UniProtKB
  • RNA polymerase II distal enhancer sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: MGI
  • transcriptional activator activity, RNA polymerase II distal enhancer sequence-specific binding Source: NTNU_SB
  • transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: MGI
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: MGI
  • transcription regulatory region DNA binding Source: BHF-UCL
  • transcription regulatory region sequence-specific DNA binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cellular response to dsRNA Source: Ensembl
  • cellular response to interleukin-1 Source: BHF-UCL
  • cellular response to interleukin-6 Source: BHF-UCL
  • cellular response to lipopolysaccharide Source: MGI
  • cellular response to mechanical stimulus Source: UniProtKB
  • cellular response to nicotine Source: BHF-UCL
  • cellular response to peptide hormone stimulus Source: BHF-UCL
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • I-kappaB kinase/NF-kappaB signaling Source: GO_Central
  • inflammatory response Source: UniProtKB
  • innate immune response Source: GO_Central
  • membrane protein intracellular domain proteolysis Source: Reactome
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of calcidiol 1-monooxygenase activity Source: BHF-UCL
  • negative regulation of cellular protein metabolic process Source: BHF-UCL
  • negative regulation of cholesterol transport Source: BHF-UCL
  • negative regulation of gene expression Source: BHF-UCL
  • negative regulation of inflammatory response Source: Ensembl
  • negative regulation of interleukin-12 biosynthetic process Source: Ensembl
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • negative regulation of vitamin D biosynthetic process Source: BHF-UCL
  • NIK/NF-kappaB signaling Source: GO_Central
  • positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  • positive regulation of hyaluronan biosynthetic process Source: UniProtKB
  • positive regulation of lipid storage Source: BHF-UCL
  • positive regulation of macrophage derived foam cell differentiation Source: BHF-UCL
  • positive regulation of miRNA metabolic process Source: BHF-UCL
  • positive regulation of NF-kappaB transcription factor activity Source: Reactome
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: NTNU_SB
  • positive regulation of type I interferon production Source: Reactome
  • response to muscle stretch Source: Ensembl
  • stimulatory C-type lectin receptor signaling pathway Source: Reactome
  • stress-activated MAPK cascade Source: Reactome
  • T cell receptor signaling pathway Source: Reactome
  • transcription from RNA polymerase II promoter Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109320-MONOMER.
ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-202424. Downstream TCR signaling.
R-HSA-209560. NF-kB is activated and signals survival.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-3214841. PKMTs methylate histone lysines.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-448706. Interleukin-1 processing.
R-HSA-5603027. IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
R-HSA-5603029. IkBA variant leads to EDA-ID.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5621575. CD209 (DC-SIGN) signaling.
R-HSA-5660668. CLEC7A/inflammasome pathway.
R-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
SignaLinkiP19838.
SIGNORiP19838.

Names & Taxonomyi

Protein namesi
Recommended 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:
Gene namesi
Name:NFKB1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:7794. NFKB1.

Subcellular locationi

  • Nucleus
  • Cytoplasm

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

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: GO_Central
  • I-kappaB/NF-kappaB complex Source: BHF-UCL
  • mitochondrion Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency, common variable, 12 (CVID12)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency characterized by antibody deficiency, hypogammaglobulinemia, recurrent bacterial infections and an inability to mount an antibody response to antigen.
See also OMIM:616576

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi61C → 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. 2 Publications1
Mutagenesisi678N → A: Fails to promote HIF1AN-dependent 2-oxoglutarate decarboxylation. 1 Publication1
Mutagenesisi903S → A: Prevents p105 proteolysis in response to TNF-alpha. 1 Publication1
Mutagenesisi907S → A: Prevents p105 proteolysis in response to TNF-alpha. 1 Publication1
Mutagenesisi921S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-923 and A-932. 1 Publication1
Mutagenesisi923S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-932. 1 Publication1
Mutagenesisi932S → A: Decrease in stimuli-induced phosphorylation. Loss of phosphorylation; when associated with A-921 and A-923. 1 Publication1

Organism-specific databases

DisGeNETi4790.
MIMi616576. phenotype.
OpenTargetsiENSG00000109320.
PharmGKBiPA248.

Chemistry databases

ChEMBLiCHEMBL3251.
DrugBankiDB00945. Acetylsalicylic acid.
DB01411. Pranlukast.
DB01041. Thalidomide.
DB08814. Triflusal.

Polymorphism and mutation databases

BioMutaiNFKB1.
DMDMi21542418.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000303101 – 968Nuclear factor NF-kappa-B p105 subunitAdd BLAST968
ChainiPRO_00000303111 – 433Nuclear factor NF-kappa-B p50 subunitAdd BLAST433

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei61S-nitrosocysteine; alternate1 Publication1
Lipidationi61S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternate1 Publication1
Modified residuei337Phosphoserine; by PKASequence analysis1
Modified residuei431N6-acetyllysine; by EP3001 Publication1
Modified residuei440N6-acetyllysine; by EP3001 Publication1
Modified residuei441N6-acetyllysine; by EP3001 Publication1
Modified residuei449PhosphoserineBy similarity1
Modified residuei678(3S)-3-hydroxyasparagine; by HIF1AN; partial1 Publication1
Modified residuei759PhosphoserineBy similarity1
Modified residuei892PhosphoserineCombined sources1
Modified residuei903Phosphoserine; by GSK3-beta; in vitroCombined sources1 Publication1
Modified residuei907Phosphoserine; by GSK3-beta; in vitroCombined sources1 Publication1
Modified residuei927Phosphoserine; by IKKB2 Publications1
Modified residuei932Phosphoserine; by IKKB1 Publication1
Modified residuei937PhosphoserineCombined sources1
Modified residuei943PhosphothreonineBy similarity1

Post-translational modificationi

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.1 Publication
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.4 Publications
Polyubiquitination seems to allow p105 processing.2 Publications
S-nitrosylation of Cys-61 affects DNA binding.2 Publications
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.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei433 – 434Cleavage (when cotranslationally processed)2

Keywords - PTMi

Acetylation, Hydroxylation, Lipoprotein, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

EPDiP19838.
MaxQBiP19838.
PaxDbiP19838.
PeptideAtlasiP19838.
PRIDEiP19838.

PTM databases

iPTMnetiP19838.
PhosphoSitePlusiP19838.

Miscellaneous databases

PMAP-CutDBP19838.

Expressioni

Inductioni

By phorbol ester and TNF.

Gene expression databases

BgeeiENSG00000109320.
CleanExiHS_NFKB1.
ExpressionAtlasiP19838. baseline and differential.
GenevisibleiP19838. HS.

Organism-specific databases

HPAiCAB004031.
HPA027305.

Interactioni

Subunit structurei

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.By similarity17 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself7EBI-300010,EBI-300010
ABCC2Q928873EBI-300010,EBI-3916193
CHUKO151113EBI-300010,EBI-81249
COPB2P356063EBI-300010,EBI-1056534
CTNNB1P352223EBI-300010,EBI-491549
ESR1P033723EBI-697771,EBI-78473
HDAC1Q135475EBI-300010,EBI-301834
HSP90AB1P082383EBI-300010,EBI-352572
HSPA1LP349313EBI-300010,EBI-354912
IKBKBO149203EBI-300010,EBI-81266
MAP3K8P4127913EBI-300010,EBI-354900
MEN1O002552EBI-697771,EBI-592789
MEN1O00255-24EBI-697771,EBI-9869387
NFKB2Q006538EBI-300010,EBI-307326
NFKBIAP259634EBI-300010,EBI-307386
NOTCH1P465312EBI-300010,EBI-636374
PDCD11Q146902EBI-300010,EBI-300028
PELP1Q8IZL82EBI-300010,EBI-716449
PLD3Q8IV082EBI-300010,EBI-2689908
RELAQ0420613EBI-300010,EBI-73886
RELBQ012015EBI-300010,EBI-357837
RPS3P233964EBI-300010,EBI-351193
TNIP1Q150254EBI-300010,EBI-357849
TNIP2Q8NFZ58EBI-1452239,EBI-359372
UL42P102264EBI-300010,EBI-1029310From a different organism.

GO - Molecular functioni

  • actinin binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • protein heterodimerization activity Source: UniProtKB
  • transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi110857. 147 interactors.
DIPiDIP-106N.
IntActiP19838. 472 interactors.
MINTiMINT-85658.
STRINGi9606.ENSP00000226574.

Chemistry databases

BindingDBiP19838.

Structurei

Secondary structure

1968
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi43 – 48Combined sources6
Beta strandi52 – 54Combined sources3
Helixi60 – 62Combined sources3
Beta strandi83 – 88Combined sources6
Beta strandi94 – 100Combined sources7
Beta strandi103 – 105Combined sources3
Beta strandi110 – 115Combined sources6
Beta strandi122 – 126Combined sources5
Beta strandi133 – 135Combined sources3
Beta strandi138 – 143Combined sources6
Helixi146 – 148Combined sources3
Helixi149 – 163Combined sources15
Helixi167 – 170Combined sources4
Helixi173 – 178Combined sources6
Beta strandi180 – 182Combined sources3
Turni184 – 187Combined sources4
Helixi190 – 204Combined sources15
Beta strandi211 – 221Combined sources11
Beta strandi223 – 225Combined sources3
Beta strandi227 – 230Combined sources4
Beta strandi234 – 240Combined sources7
Helixi245 – 247Combined sources3
Beta strandi252 – 256Combined sources5
Beta strandi258 – 261Combined sources4
Beta strandi267 – 274Combined sources8
Helixi277 – 279Combined sources3
Beta strandi281 – 288Combined sources8
Turni289 – 291Combined sources3
Beta strandi292 – 297Combined sources6
Helixi302 – 304Combined sources3
Turni307 – 309Combined sources3
Beta strandi310 – 314Combined sources5
Beta strandi319 – 322Combined sources4
Beta strandi327 – 334Combined sources8
Turni336 – 338Combined sources3
Beta strandi345 – 350Combined sources6
Helixi813 – 823Combined sources11
Helixi832 – 839Combined sources8
Helixi842 – 844Combined sources3
Helixi845 – 850Combined sources6
Helixi854 – 864Combined sources11
Helixi869 – 879Combined sources11
Helixi883 – 892Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP19838.
SMRiP19838.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP19838.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini42 – 367RHDPROSITE-ProRule annotationAdd BLAST326
Repeati542 – 571ANK 1Add BLAST30
Repeati581 – 610ANK 2Add BLAST30
Repeati614 – 643ANK 3Add BLAST30
Repeati650 – 679ANK 4Add BLAST30
Repeati684 – 714ANK 5Add BLAST31
Repeati718 – 747ANK 6Add BLAST30
Repeati771 – 801ANK 7Add BLAST31
Domaini805 – 892DeathAdd BLAST88

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni372 – 394GRRAdd BLAST23
Regioni435 – 968Interaction with CFLAR1 PublicationAdd BLAST534
Regioni650 – 684Essential for interaction with HIF1AN1 PublicationAdd BLAST35

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi360 – 365Nuclear localization signalSequence analysis6

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi375 – 433Gly-richAdd BLAST59

Domaini

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.

Sequence similaritiesi

Contains 7 ANK repeats.PROSITE-ProRule annotation
Contains 1 death domain.Curated
Contains 1 RHD (Rel-like) domain.PROSITE-ProRule annotation

Keywords - Domaini

ANK repeat, Repeat

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00500000044765.
HOGENOMiHOG000004822.
HOVERGENiHBG052613.
InParanoidiP19838.
KOiK02580.
OMAiHEQMFHL.
OrthoDBiEOG091G03PF.
PhylomeDBiP19838.
TreeFamiTF325632.

Family and domain databases

CDDicd01177. IPT_NFkappaB. 1 hit.
Gene3Di1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR033926. IPT_NFkappaB.
IPR030503. NF-kB_p105.
IPR000451. NFkB/Dor.
IPR008967. p53-like_TF_DNA-bd.
IPR030492. RHD_CS.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
[Graphical view]
PANTHERiPTHR24169. PTHR24169. 2 hits.
PTHR24169:SF9. PTHR24169:SF9. 2 hits.
PfamiPF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
PF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
PR00057. NFKBTNSCPFCT.
SMARTiSM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
SM00429. IPT. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P19838-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MAEDDPYLGR PEQMFHLDPS LTHTIFNPEV FQPQMALPTD GPYLQILEQP
60 70 80 90 100
KQRGFRFRYV CEGPSHGGLP GASSEKNKKS YPQVKICNYV GPAKVIVQLV
110 120 130 140 150
TNGKNIHLHA HSLVGKHCED GICTVTAGPK DMVVGFANLG ILHVTKKKVF
160 170 180 190 200
ETLEARMTEA CIRGYNPGLL VHPDLAYLQA EGGGDRQLGD REKELIRQAA
210 220 230 240 250
LQQTKEMDLS VVRLMFTAFL PDSTGSFTRR LEPVVSDAIY DSKAPNASNL
260 270 280 290 300
KIVRMDRTAG CVTGGEEIYL LCDKVQKDDI QIRFYEEEEN GGVWEGFGDF
310 320 330 340 350
SPTDVHRQFA IVFKTPKYKD INITKPASVF VQLRRKSDLE TSEPKPFLYY
360 370 380 390 400
PEIKDKEEVQ RKRQKLMPNF SDSFGGGSGA GAGGGGMFGS GGGGGGTGST
410 420 430 440 450
GPGYSFPHYG FPTYGGITFH PGTTKSNAGM KHGTMDTESK KDPEGCDKSD
460 470 480 490 500
DKNTVNLFGK VIETTEQDQE PSEATVGNGE VTLTYATGTK EESAGVQDNL
510 520 530 540 550
FLEKAMQLAK RHANALFDYA VTGDVKMLLA VQRHLTAVQD ENGDSVLHLA
560 570 580 590 600
IIHLHSQLVR DLLEVTSGLI SDDIINMRND LYQTPLHLAV ITKQEDVVED
610 620 630 640 650
LLRAGADLSL LDRLGNSVLH LAAKEGHDKV LSILLKHKKA ALLLDHPNGD
660 670 680 690 700
GLNAIHLAMM SNSLPCLLLL VAAGADVNAQ EQKSGRTALH LAVEHDNISL
710 720 730 740 750
AGCLLLEGDA HVDSTTYDGT TPLHIAAGRG STRLAALLKA AGADPLVENF
760 770 780 790 800
EPLYDLDDSW ENAGEDEGVV PGTTPLDMAT SWQVFDILNG KPYEPEFTSD
810 820 830 840 850
DLLAQGDMKQ LAEDVKLQLY KLLEIPDPDK NWATLAQKLG LGILNNAFRL
860 870 880 890 900
SPAPSKTLMD NYEVSGGTVR ELVEALRQMG YTEAIEVIQA ASSPVKTTSQ
910 920 930 940 950
AHSLPLSPAS TRQQIDELRD SDSVCDSGVE TSFRKLSFTE SLTSGASLLT
960
LNKMPHDYGQ EGPLEGKI
Length:968
Mass (Da):105,356
Last modified:June 20, 2002 - v2
Checksum:i2A7C8FF86A10D1A8
GO
Isoform 2 (identifier: P19838-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     39-39: T → TA

Show »
Length:969
Mass (Da):105,427
Checksum:iB4D57AC8A410941D
GO
Isoform 3 (identifier: P19838-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-180: Missing.
     181-189: EGGGDRQLG → MNGLCCMAL

Note: No experimental confirmation available.
Show »
Length:788
Mass (Da):85,520
Checksum:i7B9913B97F25DD3F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti243K → SE in CAB94757 (PubMed:8825636).Curated1
Sequence conflicti361R → G in CAH18336 (PubMed:17974005).Curated1
Sequence conflicti551 – 552II → SS in CAB94757 (PubMed:8825636).Curated2
Sequence conflicti573D → G in BAF84139 (PubMed:14702039).Curated1
Sequence conflicti726A → V in CAB94757 (PubMed:8825636).Curated1
Sequence conflicti825I → T in CAH18336 (PubMed:17974005).Curated1
Sequence conflicti869V → I in CAB94757 (PubMed:8825636).Curated1
Sequence conflicti927S → T in AAA36361 (PubMed:2203531).Curated1
Sequence conflicti927S → T in AAA36360 (PubMed:1992489).Curated1
Sequence conflicti927S → T in CAB94757 (PubMed:8825636).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_016268489T → I.1 PublicationCorresponds to variant rs4648065dbSNPEnsembl.1
Natural variantiVAR_016269506M → V.1 PublicationCorresponds to variant rs4648072dbSNPEnsembl.1
Natural variantiVAR_016270566T → I.1 PublicationCorresponds to variant rs4648085dbSNPEnsembl.1
Natural variantiVAR_016271578R → K.1 PublicationCorresponds to variant rs4648086dbSNPEnsembl.1
Natural variantiVAR_016272711H → Q.1 PublicationCorresponds to variant rs4648099dbSNPEnsembl.1
Natural variantiVAR_016273901A → T.1 PublicationCorresponds to variant rs4648118dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0428691 – 180Missing in isoform 3. 1 PublicationAdd BLAST180
Alternative sequenceiVSP_02102539T → TA in isoform 2. 3 Publications1
Alternative sequenceiVSP_042870181 – 189EGGGDRQLG → MNGLCCMAL in isoform 3. 1 Publication9

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55643 mRNA. Translation: AAA36361.1.
M58603 mRNA. Translation: AAA36360.1.
Z47748
, 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.
CCDSiCCDS3657.1. [P19838-2]
CCDS54783.1. [P19838-1]
PIRiA37867.
RefSeqiNP_001158884.1. NM_001165412.1. [P19838-1]
NP_001306155.1. NM_001319226.1. [P19838-1]
NP_003989.2. NM_003998.3. [P19838-2]
UniGeneiHs.618430.

Genome annotation databases

EnsembliENST00000226574; ENSP00000226574; ENSG00000109320. [P19838-2]
ENST00000394820; ENSP00000378297; ENSG00000109320. [P19838-1]
ENST00000505458; ENSP00000424790; ENSG00000109320. [P19838-1]
ENST00000600343; ENSP00000469340; ENSG00000109320. [P19838-3]
GeneIDi4790.
KEGGihsa:4790.
UCSCiuc011cep.2. human. [P19838-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55643 mRNA. Translation: AAA36361.1.
M58603 mRNA. Translation: AAA36360.1.
Z47748
, 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.
CCDSiCCDS3657.1. [P19838-2]
CCDS54783.1. [P19838-1]
PIRiA37867.
RefSeqiNP_001158884.1. NM_001165412.1. [P19838-1]
NP_001306155.1. NM_001319226.1. [P19838-1]
NP_003989.2. NM_003998.3. [P19838-2]
UniGeneiHs.618430.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
ProteinModelPortaliP19838.
SMRiP19838.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110857. 147 interactors.
DIPiDIP-106N.
IntActiP19838. 472 interactors.
MINTiMINT-85658.
STRINGi9606.ENSP00000226574.

Chemistry databases

BindingDBiP19838.
ChEMBLiCHEMBL3251.
DrugBankiDB00945. Acetylsalicylic acid.
DB01411. Pranlukast.
DB01041. Thalidomide.
DB08814. Triflusal.

PTM databases

iPTMnetiP19838.
PhosphoSitePlusiP19838.

Polymorphism and mutation databases

BioMutaiNFKB1.
DMDMi21542418.

Proteomic databases

EPDiP19838.
MaxQBiP19838.
PaxDbiP19838.
PeptideAtlasiP19838.
PRIDEiP19838.

Protocols and materials databases

DNASUi4790.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000226574; ENSP00000226574; ENSG00000109320. [P19838-2]
ENST00000394820; ENSP00000378297; ENSG00000109320. [P19838-1]
ENST00000505458; ENSP00000424790; ENSG00000109320. [P19838-1]
ENST00000600343; ENSP00000469340; ENSG00000109320. [P19838-3]
GeneIDi4790.
KEGGihsa:4790.
UCSCiuc011cep.2. human. [P19838-1]

Organism-specific databases

CTDi4790.
DisGeNETi4790.
GeneCardsiNFKB1.
HGNCiHGNC:7794. NFKB1.
HPAiCAB004031.
HPA027305.
MIMi164011. gene.
616576. phenotype.
neXtProtiNX_P19838.
OpenTargetsiENSG00000109320.
PharmGKBiPA248.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
GeneTreeiENSGT00500000044765.
HOGENOMiHOG000004822.
HOVERGENiHBG052613.
InParanoidiP19838.
KOiK02580.
OMAiHEQMFHL.
OrthoDBiEOG091G03PF.
PhylomeDBiP19838.
TreeFamiTF325632.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000109320-MONOMER.
ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-193692. Regulated proteolysis of p75NTR.
R-HSA-202424. Downstream TCR signaling.
R-HSA-209560. NF-kB is activated and signals survival.
R-HSA-2559582. Senescence-Associated Secretory Phenotype (SASP).
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-3134963. DEx/H-box helicases activate type I IFN and inflammatory cytokines production.
R-HSA-3214841. PKMTs methylate histone lysines.
R-HSA-381340. Transcriptional regulation of white adipocyte differentiation.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-448706. Interleukin-1 processing.
R-HSA-5603027. IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
R-HSA-5603029. IkBA variant leads to EDA-ID.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5621575. CD209 (DC-SIGN) signaling.
R-HSA-5660668. CLEC7A/inflammasome pathway.
R-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-HSA-6798695. Neutrophil degranulation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
SignaLinkiP19838.
SIGNORiP19838.

Miscellaneous databases

ChiTaRSiNFKB1. human.
EvolutionaryTraceiP19838.
GeneWikiiNFKB1.
GenomeRNAii4790.
PMAP-CutDBP19838.
PROiP19838.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109320.
CleanExiHS_NFKB1.
ExpressionAtlasiP19838. baseline and differential.
GenevisibleiP19838. HS.

Family and domain databases

CDDicd01177. IPT_NFkappaB. 1 hit.
Gene3Di1.10.533.10. 1 hit.
1.25.40.20. 1 hit.
2.60.40.10. 1 hit.
2.60.40.340. 1 hit.
InterProiIPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR011029. DEATH-like_dom.
IPR000488. Death_domain.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002909. IPT.
IPR033926. IPT_NFkappaB.
IPR030503. NF-kB_p105.
IPR000451. NFkB/Dor.
IPR008967. p53-like_TF_DNA-bd.
IPR030492. RHD_CS.
IPR032397. RHD_dimer.
IPR011539. RHD_DNA_bind_dom.
[Graphical view]
PANTHERiPTHR24169. PTHR24169. 2 hits.
PTHR24169:SF9. PTHR24169:SF9. 2 hits.
PfamiPF12796. Ank_2. 2 hits.
PF00531. Death. 1 hit.
PF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
[Graphical view]
PRINTSiPR01415. ANKYRIN.
PR00057. NFKBTNSCPFCT.
SMARTiSM00248. ANK. 6 hits.
SM00005. DEATH. 1 hit.
SM00429. IPT. 1 hit.
[Graphical view]
SUPFAMiSSF47986. SSF47986. 1 hit.
SSF48403. SSF48403. 1 hit.
SSF49417. SSF49417. 1 hit.
SSF81296. SSF81296. 1 hit.
PROSITEiPS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 5 hits.
PS01204. REL_1. 1 hit.
PS50254. REL_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNFKB1_HUMAN
AccessioniPrimary (citable) accession number: P19838
Secondary accession number(s): A8K5Y5
, B3KVE8, Q68D84, Q86V43, Q8N4X7, Q9NZC0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: June 20, 2002
Last modified: November 30, 2016
This is version 216 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.