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Protein

Nuclear factor NF-kappa-B p105 subunit

Gene

NFKB1

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 (By similarity).By similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Nuclear factor NF-kappa-B p105 subunit
Alternative name(s):
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1
Cleaved into the following chain:
Gene namesi
Name:NFKB1
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Unplaced

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity

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

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 972972Nuclear factor NF-kappa-B p105 subunitPRO_0000223240Add
BLAST
Chaini1 – 433433Nuclear factor NF-kappa-B p50 subunitBy similarityPRO_0000223241Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei61 – 611S-nitrosocysteineBy similarity
Lipidationi61 – 611S-(15-deoxy-Delta12,14-prostaglandin J2-9-yl)cysteine; alternateBy similarity
Modified residuei337 – 3371Phosphoserine; by PKASequence analysis
Modified residuei431 – 4311N6-acetyllysine; by EP300By similarity
Modified residuei440 – 4401N6-acetyllysine; by EP300By similarity
Modified residuei675 – 6751(3S)-3-hydroxyasparagine; by HIF1ANBy similarity
Modified residuei756 – 7561PhosphoserineBy similarity
Modified residuei908 – 9081Phosphoserine; by GSK3-beta; in vitroBy similarity
Modified residuei912 – 9121Phosphoserine; by GSK3-beta; in vitroBy similarity
Modified residuei931 – 9311Phosphoserine; by IKKBBy similarity
Modified residuei936 – 9361Phosphoserine; by IKKBBy similarity
Modified residuei941 – 9411PhosphoserineBy similarity
Modified residuei947 – 9471PhosphothreonineBy similarity

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 (By similarity).By similarity
Phosphorylation at 'Ser-931' and 'Ser-936' are required for BTRC/BTRCP-mediated proteolysis.By similarity
S-nitrosylation of Cys-61 affects DNA binding.By similarity
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 (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei433 – 4342Cleavage (when cotranslationally processed)By similarity

Keywords - PTMi

Acetylation, Hydroxylation, Lipoprotein, Phosphoprotein, S-nitrosylation

Proteomic databases

PaxDbiQ6F3J0.

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 (By similarity). Interacts with HIF1AN (By similarity).By similarity

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000015815.

Structurei

3D structure databases

ProteinModelPortaliQ6F3J0.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini39 – 246208RHDPROSITE-ProRule annotationAdd
BLAST
Repeati539 – 56830ANK 1Add
BLAST
Repeati578 – 60730ANK 2Add
BLAST
Repeati611 – 64030ANK 3Add
BLAST
Repeati647 – 67630ANK 4Add
BLAST
Repeati681 – 71131ANK 5Add
BLAST
Repeati715 – 74430ANK 6Add
BLAST
Repeati768 – 79831ANK 7Add
BLAST
Domaini814 – 88976DeathAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni372 – 39423GRRBy similarityAdd
BLAST
Regioni435 – 972538Interaction with CFLARBy similarityAdd
BLAST
Regioni647 – 68135Essential for interaction with HIF1ANBy similarityAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi360 – 3656Nuclear localization signalSequence analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi375 – 43359Gly-richAdd
BLAST

Domaini

The C-terminus of p105 might be involved in cytoplasmic retention, inhibition of DNA-binding by p50 homodimers, and/or transcription activation.

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.
HOGENOMiHOG000004822.
HOVERGENiHBG052613.
InParanoidiQ6F3J0.
KOiK02580.

Family and domain databases

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.
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.
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF00531. Death. 1 hit.
PF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
[Graphical view]
PRINTSiPR00057. 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]

Sequencei

Sequence statusi: Complete.

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

Q6F3J0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEDDTYLGA HEQMFHLDPL THTIFNPELF QPEMPLPTAD 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 CTKGYNPGLL VHPDLAYLQA EGGGDRQLTD REKEIIRQAA
210 220 230 240 250
LQQTKEMDLS VVRLMFTAFL PDSTGSFTRR LEPVVSDAIY DSKAPNASNL
260 270 280 290 300
KIVRMDRTAG CVTGGEEIYL LCDKVQKDDI QIRFYEEEEN GGIWEGFGDF
310 320 330 340 350
SPTDVHRQFA IVFKTPKYKD VNITKPASVF VQLRRKSDLE TSEPKPFLYY
360 370 380 390 400
PEIKDKEEVQ RKRQKLMPNF SDSFGGGSGA GAGGGGMFGS GGGGGGAGST
410 420 430 440 450
GPGYGFPHYG FPTYGGITFH PGTTKSNAGM KHGTIDTPSK NDSEGCGKNV
460 470 480 490 500
DREAVNLSGK VTEPTEQDKE SSMGVDEVTL TYTVGIKEEN SRFQDNLFLE
510 520 530 540 550
KAMQLAKRHA NALFDYAVTG DVKMLLAVQR HLTAVQDENG DSVLHLAIIH
560 570 580 590 600
LHAQLVRDLL EVTSGLISDD IINMRNDLYQ TPLHLAVITK QEAVVDDLLR
610 620 630 640 650
AGADLSLLDR LGNSVLHLAA KEGQDKILSI LLKHKKAALL MDHPNGEGLN
660 670 680 690 700
AIHIAVMSNS MPCLLLLVAA GADVNAQERK SGRTALHLAV EHDNISLAGC
710 720 730 740 750
LLLEGDAHVD STTYDGTTPL HIAAGRGSTR LAALLKAAGA DPLVENFEPL
760 770 780 790 800
YDLDDSWEKD GEDEGVVPGT TPLDMATNWQ VFDILNGKPY EPEFTSDDLL
810 820 830 840 850
AQGDMKQLTE DAKLQLYKLL EIPDPDKNWA TLAQKLGLGI LNNAFRLSPA
860 870 880 890 900
PSKTLMDNYE VSGGTIKELV EALRQMGYTE AIEVIQAAFC APETAAPSPG
910 920 930 940 950
KGAPQTLSLP LSSASTRSPV DEVRDDSICD SGVETSFRKL SFTESLTSGS
960 970
SLLTLNKAPH EYGQEGPIEG KI
Length:972
Mass (Da):105,631
Last modified:April 18, 2012 - v2
Checksum:i189557C55699014F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti289 – 2891E → G in BAD27479 (Ref. 1) Curated
Sequence conflicti295 – 2951E → G in BAD27479 (Ref. 1) Curated
Sequence conflicti327 – 3271A → T in BAD27479 (Ref. 1) Curated
Sequence conflicti432 – 4321H → N in BAD27479 (Ref. 1) Curated
Sequence conflicti538 – 5381E → G in BAD27479 (Ref. 1) Curated
Sequence conflicti822 – 8221I → T in BAD27479 (Ref. 1) Curated
Sequence conflicti838 – 8381L → Q in BAD27479 (Ref. 1) Curated
Sequence conflicti939 – 9391K → R in BAD27479 (Ref. 1) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB183419 mRNA. Translation: BAD27479.1.
RefSeqiNP_001003344.1. NM_001003344.1.
UniGeneiCfa.10766.

Genome annotation databases

GeneIDi442859.
KEGGicfa:442859.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB183419 mRNA. Translation: BAD27479.1.
RefSeqiNP_001003344.1. NM_001003344.1.
UniGeneiCfa.10766.

3D structure databases

ProteinModelPortaliQ6F3J0.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000015815.

Proteomic databases

PaxDbiQ6F3J0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi442859.
KEGGicfa:442859.

Organism-specific databases

CTDi4790.

Phylogenomic databases

eggNOGiKOG0504. Eukaryota.
COG0666. LUCA.
HOGENOMiHOG000004822.
HOVERGENiHBG052613.
InParanoidiQ6F3J0.
KOiK02580.

Family and domain databases

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.
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.
PfamiPF00023. Ank. 1 hit.
PF12796. Ank_2. 1 hit.
PF00531. Death. 1 hit.
PF16179. RHD_dimer. 1 hit.
PF00554. RHD_DNA_bind. 1 hit.
[Graphical view]
PRINTSiPR00057. 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_CANLF
AccessioniPrimary (citable) accession number: Q6F3J0
Secondary accession number(s): F1PM82
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: April 18, 2012
Last modified: June 8, 2016
This is version 95 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.