Q6F3J0
SS
Gene name |
NFKB1 |
Protein name |
Nuclear factor NF-kappa-B p105 subunit |
Names |
Nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 [Cleaved into: Nuclear factor NF-kappa-B p50 subunit] |
Species |
Canis lupus familiaris (Dog) (Canis familiaris) |
KEGG Pathway |
cfa:442859 |
EC number |
|
Protein Class |
|
Descriptions
NFκB1 is a nuclear factor NFκB p105 subunit (p50 and its precursor p105), and plays pivotal role in the regulation of the inflammatory response to pathogens, autoimmune diseases, and cancerous cells. The five members of the NF-κB family are normally kept inactive in the cytoplasm by interaction with inhibitors called IκBs or the unprocessed forms of NF-κB1 and NF-κB2. The C-terminal ankyrin repeats of p105 allow it to serve as an IkappaB-like function. The ankyrin repeats interact with and shield the nuclear localization signal located at the end of Rel-homology domain (RHD) domain and DNA binding of Rel/NF-kappaB complexes. RHD domain mediates DNA binding.
Autoinhibitory domains (AIDs)
Target domain |
38-352 (Rel-homology domain) |
Relief mechanism |
Cleavage, PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Vallabhapurapu S et al. (2009) "Regulation and function of NF-kappaB transcription factors in the immune system", Annual review of immunology, 27, 693-733
- Perkins ND (2007) "Integrating cell-signalling pathways with NF-kappaB and IKK function", Nature reviews. Molecular cell biology, 8, 49-62
- Dorrington MG et al. (2019) "NF-κB Signaling in Macrophages: Dynamics, Crosstalk, and Signal Integration", Frontiers in immunology, 10, 705
- Heusch M et al. (1999) "The generation of nfkb2 p52: mechanism and efficiency", Oncogene, 18, 6201-8
- Savinova OV et al. (2009) "The Nfkb1 and Nfkb2 proteins p105 and p100 function as the core of high-molecular-weight heterogeneous complexes", Molecular cell, 34, 591-602
- Hatada EN et al. (1992) "The ankyrin repeat domains of the NF-kappa B precursor p105 and the protooncogene bcl-3 act as specific inhibitors of NF-kappa B DNA binding", Proceedings of the National Academy of Sciences of the United States of America, 89, 2489-93
Autoinhibited structure
Activated structure
1 structures for Q6F3J0
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q6F3J0-F1 | Predicted | AlphaFoldDB |
10 variants for Q6F3J0
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3353013735 | 27 | P>LLI* | No | EVA | |
| rs3352556087 | 466 | E>K | No | EVA | |
| rs3352419819 | 473 | M>I | No | EVA | |
| rs3349754721 | 473 | M>K | No | EVA | |
| rs3351151548 | 474 | G>E | No | EVA | |
| rs3352556311 | 475 | V>D | No | EVA | |
| rs3349754713 | 508 | R>W | No | EVA | |
| rs853089281 | 673 | D>N | No | EVA | |
| rs3351970080 | 863 | G>R | No | EVA | |
| rs851308415 | 914 | A>V | No | EVA |
No associated diseases with Q6F3J0
12 regional properties for Q6F3J0
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Death domain | 802 - 889 | IPR000488 |
| repeat | Ankyrin repeat | 539 - 569 | IPR002110-1 |
| repeat | Ankyrin repeat | 578 - 679 | IPR002110-2 |
| repeat | Ankyrin repeat | 681 - 714 | IPR002110-3 |
| repeat | Ankyrin repeat | 715 - 747 | IPR002110-4 |
| domain | IPT domain | 249 - 350 | IPR002909 |
| domain | Rel homology domain, DNA-binding domain | 39 - 246 | IPR011539 |
| conserved_site | Rel homology domain, conserved site | 57 - 63 | IPR030492 |
| domain | Nuclear factor NF-kappa-B, p105 subunit, Rel homology domain, N-terminal | 42 - 243 | IPR030503 |
| domain | Rel homology dimerisation domain | 251 - 352 | IPR032397 |
| domain | NFkappaB IPT domain | 250 - 351 | IPR033926 |
| domain | Nuclear factor NF-kappa-B p105 subunit, death domain | 813 - 887 | IPR047096 |
2 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
4 GO annotations of molecular function
| Name | Definition |
|---|---|
| DNA-binding transcription factor activity | A transcription regulator activity that modulates transcription of gene sets via selective and non-covalent binding to a specific double-stranded genomic DNA sequence (sometimes referred to as a motif) within a cis-regulatory region. Regulatory regions include promoters (proximal and distal) and enhancers. Genes are transcriptional units, and include bacterial operons. |
| DNA-binding transcription factor activity, RNA polymerase II-specific | A DNA-binding transcription factor activity that modulates the transcription of specific gene sets transcribed by RNA polymerase II. |
| RNA polymerase II cis-regulatory region sequence-specific DNA binding | Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II. |
| transcription cis-regulatory region binding | Binding to a specific sequence of DNA that is part of a regulatory region that controls transcription of that section of the DNA. The transcribed region might be described as a gene, cistron, or operon. |
8 GO annotations of biological process
| Name | Definition |
|---|---|
| canonical NF-kappaB signal transduction | The process in which a signal is passed on to downstream components within the cell through the I-kappaB-kinase (IKK)-dependent activation of NF-kappaB. The cascade begins with activation of a trimeric IKK complex (consisting of catalytic kinase subunits IKKalpha and/or IKKbeta, and the regulatory scaffold protein NEMO) and ends with the regulation of transcription of target genes by NF-kappaB. In a resting state, NF-kappaB dimers are bound to I-kappaB proteins, sequestering NF-kappaB in the cytoplasm. Phosphorylation of I-kappaB targets I-kappaB for ubiquitination and proteasomal degradation, thus releasing the NF-kappaB dimers, which can translocate to the nucleus to bind DNA and regulate transcription. |
| inflammatory response | The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. |
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| negative regulation of transcription by RNA polymerase II | Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| non-canonical NF-kappaB signal transduction | The process in which a signal is passed on to downstream components within the cell through the NIK-dependent processing and activation of NF-KappaB. Begins with activation of the NF-KappaB-inducing kinase (NIK), which in turn phosphorylates and activates IkappaB kinase alpha (IKKalpha). IKKalpha phosphorylates the NF-Kappa B2 protein (p100) leading to p100 processing and release of an active NF-KappaB (p52). |
| positive regulation of DNA-templated transcription | Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription. |
| positive regulation of transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| response to cytokine | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cytokine stimulus. |
4 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| Q04861 | NFKB1 | Nuclear factor NF-kappa-B p105 subunit | Gallus gallus (Chicken) | SS |
| Q94527 | Rel | Nuclear factor NF-kappa-B p110 subunit | Drosophila melanogaster (Fruit fly) | EV |
| P19838 | NFKB1 | Nuclear factor NF-kappa-B p105 subunit | Homo sapiens (Human) | SS |
| P25799 | Nfkb1 | Nuclear factor NF-kappa-B p105 subunit [Cleaved into: Nuclear factor NF-kappa-B p50 subunit] | Mus musculus (Mouse) | EV |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MAEDDTYLGA | HEQMFHLDPL | THTIFNPELF | QPEMPLPTAD | GPYLQILEQP | KQRGFRFRYV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| CEGPSHGGLP | GASSEKNKKS | YPQVKICNYV | GPAKVIVQLV | TNGKNIHLHA | HSLVGKHCED |
| 130 | 140 | 150 | 160 | 170 | 180 |
| GICTVTAGPK | DMVVGFANLG | ILHVTKKKVF | ETLEARMTEA | CTKGYNPGLL | VHPDLAYLQA |
| 190 | 200 | 210 | 220 | 230 | 240 |
| EGGGDRQLTD | REKEIIRQAA | LQQTKEMDLS | VVRLMFTAFL | PDSTGSFTRR | LEPVVSDAIY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| DSKAPNASNL | KIVRMDRTAG | CVTGGEEIYL | LCDKVQKDDI | QIRFYEEEEN | GGIWEGFGDF |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SPTDVHRQFA | IVFKTPKYKD | VNITKPASVF | VQLRRKSDLE | TSEPKPFLYY | PEIKDKEEVQ |
| 370 | 380 | 390 | 400 | 410 | 420 |
| RKRQKLMPNF | SDSFGGGSGA | GAGGGGMFGS | GGGGGGAGST | GPGYGFPHYG | FPTYGGITFH |
| 430 | 440 | 450 | 460 | 470 | 480 |
| PGTTKSNAGM | KHGTIDTPSK | NDSEGCGKNV | DREAVNLSGK | VTEPTEQDKE | SSMGVDEVTL |
| 490 | 500 | 510 | 520 | 530 | 540 |
| TYTVGIKEEN | SRFQDNLFLE | KAMQLAKRHA | NALFDYAVTG | DVKMLLAVQR | HLTAVQDENG |
| 550 | 560 | 570 | 580 | 590 | 600 |
| DSVLHLAIIH | LHAQLVRDLL | EVTSGLISDD | IINMRNDLYQ | TPLHLAVITK | QEAVVDDLLR |
| 610 | 620 | 630 | 640 | 650 | 660 |
| AGADLSLLDR | LGNSVLHLAA | KEGQDKILSI | LLKHKKAALL | MDHPNGEGLN | AIHIAVMSNS |
| 670 | 680 | 690 | 700 | 710 | 720 |
| MPCLLLLVAA | GADVNAQERK | SGRTALHLAV | EHDNISLAGC | LLLEGDAHVD | STTYDGTTPL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| HIAAGRGSTR | LAALLKAAGA | DPLVENFEPL | YDLDDSWEKD | GEDEGVVPGT | TPLDMATNWQ |
| 790 | 800 | 810 | 820 | 830 | 840 |
| VFDILNGKPY | EPEFTSDDLL | AQGDMKQLTE | DAKLQLYKLL | EIPDPDKNWA | TLAQKLGLGI |
| 850 | 860 | 870 | 880 | 890 | 900 |
| LNNAFRLSPA | PSKTLMDNYE | VSGGTIKELV | EALRQMGYTE | AIEVIQAAFC | APETAAPSPG |
| 910 | 920 | 930 | 940 | 950 | 960 |
| KGAPQTLSLP | LSSASTRSPV | DEVRDDSICD | SGVETSFRKL | SFTESLTSGS | SLLTLNKAPH |
| 970 | |||||
| EYGQEGPIEG | KI |