Q9WTK5
EV
Gene name |
Nfkb2 |
Protein name |
Nuclear factor NF-kappa-B p100 subunit [Cleaved into: Nuclear factor NF-kappa-B p52 subunit] |
Names |
DNA-binding factor KBF2, Nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:18034 |
EC number |
|
Protein Class |
NUCLEAR FACTOR NF-KAPPA-B PROTEIN (PTHR24169) |
Descriptions
NFκB2 is a nuclear factor NFκB p100 subunit (p52 and its precursor p100), 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 p100 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 |
35-327 (Rel-homology domain) |
Relief mechanism |
Cleavage, PTM |
Assay |
Deletion 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
3 structures for Q9WTK5
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 3JV5 | X-ray | 265 A | A/B/C/D | 225-328 | PDB |
| 3JV6 | X-ray | 278 A | B/D/F | 225-331 | PDB |
| AF-Q9WTK5-F1 | Predicted | AlphaFoldDB |
57 variants for Q9WTK5
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs245938882 | 31 | A>T | No | EVA | |
| rs3389558948 | 51 | F>I | No | EVA | |
| rs3389555881 | 67 | G>R | No | EVA | |
| rs3389545195 | 81 | K>T | No | EVA | |
| rs3389545210 | 86 | E>K | No | EVA | |
| rs3389491660 | 87 | G>* | No | EVA | |
| rs3389543754 | 111 | G>R | No | EVA | |
| rs3389543736 | 122 | V>L | No | EVA | |
| rs3389539592 | 162 | K>T | No | EVA | |
| rs3389548828 | 180 | E>K | No | EVA | |
| rs252198909 | 201 | S>R | No | EVA | |
| rs3409205599 | 213 | I>N | No | EVA | |
| rs3389546198 | 218 | H>L | No | EVA | |
| rs3389510100 | 219 | D>E | No | EVA | |
| rs3389539597 | 269 | G>E | No | EVA | |
| rs3389538435 | 288 | V>A | No | EVA | |
| rs3389510059 | 328 | L>P | No | EVA | |
| rs3389523808 | 339 | R>Q | No | EVA | |
| rs3554144091 | 364 | A>T | No | EVA | |
| rs259204478 | 370 | A>S | No | EVA | |
| rs224310280 | 374 | G>S | No | EVA | |
| rs3389500038 | 400 | G>C | No | EVA | |
| rs3389558946 | 402 | G>E | No | EVA | |
| rs13460843 | 408 | A>S | No | EVA | |
| rs3389538360 | 411 | R>I | No | EVA | |
| rs3389537807 | 423 | P>S | No | EVA | |
| rs3389493177 | 429 | A>P | No | EVA | |
| rs219421272 | 430 | P>R | No | EVA | |
| rs3389545171 | 432 | G>D | No | EVA | |
| rs239905812 | 436 | A>T | No | EVA | |
| rs3389558894 | 447 | N>K | No | EVA | |
| rs3554350346 | 448 | A>T | No | EVA | |
| rs3389553664 | 479 | H>R | No | EVA | |
| rs3389510104 | 497 | I>T | No | EVA | |
| rs247258004 | 520 | I>F | No | EVA | |
| rs247258004 | 520 | I>V | No | EVA | |
| rs3389555873 | 522 | L>P | No | EVA | |
| rs1132935504 | 538 | G>R | No | EVA | |
| rs3389523755 | 584 | S>R | No | EVA | |
| rs3389543698 | 625 | E>D | No | EVA | |
| rs212463939 | 628 | A>T | No | EVA | |
| rs3409365600 | 631 | R>M | No | EVA | |
| rs3389548794 | 635 | R>Q | No | EVA | |
| rs3389546185 | 683 | L>F | No | EVA | |
| rs3389523833 | 685 | R>H | No | EVA | |
| rs224230368 | 701 | P>A | No | EVA | |
| rs3413090639 | 732 | T>N | No | EVA | |
| rs3389545188 | 738 | C>S | No | EVA | |
| rs3389553665 | 739 | S>C | No | EVA | |
| rs3389545184 | 744 | T>I | No | EVA | |
| rs3389493181 | 751 | Q>H | No | EVA | |
| rs3409297093 | 770 | L>P | No | EVA | |
| rs3389537823 | 780 | Q>E | No | EVA | |
| rs3389537850 | 833 | E>G | No | EVA | |
| rs3389452670 | 880 | C>F | No | EVA | |
| rs3389553659 | 882 | P>S | No | EVA | |
| rs3409123856 | 891 | H>N | No | EVA |
No associated diseases with Q9WTK5
Functions
| Description | ||
|---|---|---|
| EC Number | ||
| Subcellular Localization |
|
|
| PANTHER Family | PTHR24169 | NUCLEAR FACTOR NF-KAPPA-B PROTEIN |
| PANTHER Subfamily | PTHR24169:SF21 | NUCLEAR FACTOR NF-KAPPA-B P100 SUBUNIT |
| PANTHER Protein Class |
DNA-binding transcription factor
Rel homology transcription factor immunoglobulin fold transcription factor |
|
| PANTHER Pathway Category |
Inflammation mediated by chemokine and cytokine signaling pathway NFkappaB B cell activation NFkappaB T cell activation NFkappaB Toll receptor signaling pathway NFkappaB Apoptosis signaling pathway NFkappaB |
|
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| Bcl3/NF-kappaB2 complex | A protein complex containing one Bcl protein and one or more copies of NF-kappaB2; formation of complexes of different stoichiometry depends on the Bcl3:NF-kappaB2 ratio, and allow Bcl3 to exert different regulatory effects on NF-kappaB2-dependent transcription. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| NF-kappaB complex | A protein complex that consists of a homo- or heterodimer of members of a family of structurally related proteins that contain a conserved N-terminal region called the Rel homology domain (RHD). In the nucleus, NF-kappaB complexes act as transcription factors. In unstimulated cells, NF-kappaB dimers are sequestered in the cytoplasm by IkappaB monomers; signals that induce NF-kappaB activity cause degradation of IkappaB, allowing NF-kappaB dimers to translocate to the nucleus and induce gene expression. |
| nucleoplasm | That part of the nuclear content other than the chromosomes or the nucleolus. |
| 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 activator activity, RNA polymerase II-specific | A DNA-binding transcription factor activity that activates or increases transcription of specific gene sets transcribed by RNA polymerase II. |
| 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. |
| sequence-specific double-stranded DNA binding | Binding to double-stranded DNA of a specific nucleotide composition, e.g. GC-rich DNA binding, or with a specific sequence motif or type of DNA, e.g. promotor binding or rDNA binding. |
15 GO annotations of biological process
| Name | Definition |
|---|---|
| extracellular matrix organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of an extracellular matrix. |
| follicular dendritic cell differentiation | The process in which a relatively unspecialized precursor cell acquires the specialized features of a follicular dendritic cell. |
| germinal center formation | The process in which germinal centers form. A germinal center is a specialized microenvironment formed when activated B cells enter lymphoid follicles. Germinal centers are the foci for B cell proliferation and somatic hypermutation. |
| I-kappaB kinase/NF-kappaB signaling | 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. |
| lymph node development | The process whose specific outcome is the progression of lymph nodes over time, from their formation to the mature structure. A lymph node is a round, oval, or bean shaped structure localized in clusters along the lymphatic vessels, with a distinct internal structure including specialized vasculature and B- and T-zones for the activation of lymphocytes. |
| NIK/NF-kappaB signaling | 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 transcription by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter. |
| regulation of DNA-templated transcription | Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription. |
| regulation of transcription by RNA polymerase II | Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II. |
| 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. |
| response to lipopolysaccharide | Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. |
| rhythmic process | Any process pertinent to the generation and maintenance of rhythms in the physiology of an organism. |
| spleen development | The process whose specific outcome is the progression of the spleen over time, from its formation to the mature structure. The spleen is a large vascular lymphatic organ composed of white and red pulp, involved both in hemopoietic and immune system functions. |
16 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 |
| P98150 | NFKB2 | Nuclear factor NF-kappa-B p100 subunit | Gallus gallus (Chicken) | SS |
| Q94527 | Rel | Nuclear factor NF-kappa-B p110 subunit | Drosophila melanogaster (Fruit fly) | EV |
| Q99549 | MPHOSPH8 | M-phase phosphoprotein 8 | Homo sapiens (Human) | PR |
| Q8N9B4 | ANKRD42 | Ankyrin repeat domain-containing protein 42 | Homo sapiens (Human) | PR |
| Q6ZVZ8 | ASB18 | Ankyrin repeat and SOCS box protein 18 | Homo sapiens (Human) | PR |
| P19838 | NFKB1 | Nuclear factor NF-kappa-B p105 subunit | Homo sapiens (Human) | SS |
| Q00653 | NFKB2 | Nuclear factor NF-kappa-B p100 subunit | Homo sapiens (Human) | SS |
| Q04206 | RELA | Transcription factor p65 | Homo sapiens (Human) | EV |
| Q9CZK6 | Anks3 | Ankyrin repeat and SAM domain-containing protein 3 | Mus musculus (Mouse) | PR |
| Q8VHA6 | Asb18 | Ankyrin repeat and SOCS box protein 18 | Mus musculus (Mouse) | PR |
| Q04207 | Rela | Transcription factor p65 | Mus musculus (Mouse) | SS |
| P25799 | Nfkb1 | Nuclear factor NF-kappa-B p105 subunit [Cleaved into: Nuclear factor NF-kappa-B p50 subunit] | Mus musculus (Mouse) | EV |
| Q9TZM3 | lrk-1 | Leucine-rich repeat serine/threonine-protein kinase 1 | Caenorhabditis elegans | SS |
| O22265 | CAO | Signal recognition particle 43 kDa protein, chloroplastic | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9SZI3 | NPR2 | Regulatory protein NPR2 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MDNCYDPGLD | GIPEYDDFEF | SPSIVEPKDP | APETADGPYL | VIVEQPKQRG | FRFRYGCEGP |
| 70 | 80 | 90 | 100 | 110 | 120 |
| SHGGLPGASS | EKGRKTYPTV | KICNYEGPAK | IEVDLVTHSD | PPRAHAHSLV | GKQCSELGVC |
| 130 | 140 | 150 | 160 | 170 | 180 |
| AVSVGPKDMT | AQFNNLGVLH | VTKKNMMEIM | IQKLQRQRLR | SKPQGLTEAE | RRELEQEAKE |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LKKVMDLSIV | RLRFSAFLRA | SDGSFSLPLK | PVISQPIHDS | KSPGASNLKI | SRMDKTAGSV |
| 250 | 260 | 270 | 280 | 290 | 300 |
| RGGDEVYLLC | DKVQKDDIEV | RFYEDDENGW | QAFGDFSPTD | VHKQYAIVFR | TPPYHKMKIE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| RPVTVFLQLK | RKRGGDVSDS | KQFTYYPLVE | DKEEVQRKRR | KALPTFSQPF | GGGSHMGGGS |
| 370 | 380 | 390 | 400 | 410 | 420 |
| GGSAGGYGGA | GGGGSLGFFS | SSLAYNPYQS | GAAPMGCYPG | GGGGAQMAGS | RRDTDAGEGA |
| 430 | 440 | 450 | 460 | 470 | 480 |
| EEPRTPPEAP | QGEPQALDTL | QRAREYNARL | FGLAQRSARA | LLDYGVTADA | RALLAGQRHL |
| 490 | 500 | 510 | 520 | 530 | 540 |
| LMAQDENGDT | PLHLAIIHGQ | TGVIEQIAHV | IYHAQYLGVI | NLTNHLHQTP | LHLAVITGQT |
| 550 | 560 | 570 | 580 | 590 | 600 |
| RVVSFLLQVG | ADPTLLDRHG | DSALHLALRA | GAAAPELLQA | LLRSGAHAVP | QILHMPDFEG |
| 610 | 620 | 630 | 640 | 650 | 660 |
| LYPVHLAVHA | RSPECLDLLV | DCGAEVEAPE | RQGGRTALHL | ATEMEELGLV | THLVTKLHAN |
| 670 | 680 | 690 | 700 | 710 | 720 |
| VNARTFAGNT | PLHLAAGLGS | PTLTRLLLKA | GADIHAENEE | PLCPLPSPST | SGSDSDSEGP |
| 730 | 740 | 750 | 760 | 770 | 780 |
| ERDTQRNFRG | HTPLDLTCST | KVKTLLLNAA | QNTTEPPLAP | PSPAGPGLSL | GDAALQNLEQ |
| 790 | 800 | 810 | 820 | 830 | 840 |
| LLDGPEAQGS | WAELAERLGL | RSLVDTYRKT | PSPSGSLLRS | YKLAGGDLVG | LLEALSDMGL |
| 850 | 860 | 870 | 880 | 890 | |
| HEGVRLLKGP | ETRDKLPSTE | VKEDSAYGSQ | SVEQEAEKLC | PPPEPPGGLC | HGHPQPQVH |