Q04861
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 |
Rattus norvegicus (Rat) |
KEGG Pathway |
gga:396033 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
SAD-B is a serine/threonine kinase involved in neuronal development, cell cycle, and energy metabolism. It is highly expressed in the brain and plays a role in axonal arborization, nerve terminal maturation, and neurotransmitter release. SAD-B contains an AIS near the KA1 domain that regulates its activity. This sequence is flexible and solvent-accessible, allowing it to interact with the kinase domain (KD) and ubiquitin-associated (UBA) domain to inhibit SAD-B activity. The crystal structure of the mouse SAD-B AIS-KA1 fragment reveals that the AIS is highly flexible in its isolated state, suggesting its readiness to bind to the KD-UBA junction for autoinhibition. Furthermore, the biochemical experiments demonstrate that the AIS of SAD-B non-competitively inhibits the kinase activity of SAD-B, similar to the autoinhibition observed in SAD-A, indicating a conserved mechanism between these kinases.
Autoinhibitory domains (AIDs)
Target domain |
44-357 (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 Q04861
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q04861-F1 | Predicted | AlphaFoldDB |
No variants for Q04861
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q04861 | |||||
No associated diseases with Q04861
1 regional properties for Q04861
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Chemokine interleukin-8-like domain | 28 - 90 | IPR001811 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.1 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
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. |
3 GO annotations of molecular function
| Name | Definition |
|---|---|
| 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. |
| NF-kappaB binding | Binding to NF-kappaB, a transcription factor for eukaryotic RNA polymerase II promoters. |
| 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. |
6 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. |
| 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 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. |
16 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P98150 | NFKB2 | Nuclear factor NF-kappa-B p100 subunit | Gallus gallus (Chicken) | SS |
| P51509 | RELB | Transcription factor RelB homolog | Gallus gallus (Chicken) | PR |
| Q6F3J0 | NFKB1 | Nuclear factor NF-kappa-B p105 subunit | Canis lupus familiaris (Dog) (Canis familiaris) | 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 |
| Q00653 | NFKB2 | Nuclear factor NF-kappa-B p100 subunit | Homo sapiens (Human) | SS |
| 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 |
| 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 |
| Q9WTK5 | Nfkb2 | Nuclear factor NF-kappa-B p100 subunit [Cleaved into: Nuclear factor NF-kappa-B p52 subunit] | Mus musculus (Mouse) | EV |
| 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 |
| MSSGSKEGGG | GSPAYHLPHP | HPHPPQHAQY | VGPYRLEKTL | GKGQTGLVKL | GVHCITGQKV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| AVKIVNREKL | SESVLMKVER | EIAILKLIEH | PHVLKLHDVY | ENKKYLYLVL | EHVSGGELFD |
| 130 | 140 | 150 | 160 | 170 | 180 |
| YLVKKGRLTP | KEARKFFRQI | VSALDFCHSY | SICHRDLKPE | NLLLDEKNNI | RIADFGMASL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| QVGDSLLETS | CGSPHYACPE | VIKGEKYDGR | RADMWSCGVI | LFALLVGALP | FDDDNLRQLL |
| 250 | 260 | 270 | 280 | 290 | 300 |
| EKVKRGVFHM | PHFIPPDCQS | LLRGMIEVEP | EKRLSLEQIQ | KHPWYLGGKH | EPDPCLEPAP |
| 310 | 320 | 330 | 340 | 350 | 360 |
| GRRVAMRSLP | SNGELDPDVL | ESMASLGCFR | DRERLHRELR | SEEENQEKMI | YYLLLDRKER |
| 370 | 380 | 390 | 400 | 410 | 420 |
| YPSCEDQDLP | PRNDVDPPRK | RVDSPMLSRH | GKRRPERKSM | EVLSITDAGS | GGSPVPTRRA |
| 430 | 440 | 450 | 460 | 470 | 480 |
| LEMAQHSQRS | RSVSGASTGL | SSSPLSSPRS | PVFSFSPEPG | VGDEARGGGS | PTSKTQTLPS |
| 490 | 500 | 510 | 520 | 530 | 540 |
| RGPRGGGAGE | QPPPPSARST | PLPGPPGSPR | SSGGTPLHSP | LHTPRASPTG | TPGTTPPPSP |
| 550 | 560 | 570 | 580 | 590 | 600 |
| GGGVGGAAWR | SRLNSIRNSF | LGSPRFHRRK | MQVPTAEEMS | SLTPESSPEL | AKRSWFGNFI |
| 610 | 620 | 630 | 640 | 650 | 660 |
| SLDKEEQIFL | VLKDKPLSSI | KADIVHAFLS | IPSLSHSVLS | QTSFRAEYKA | SGGPSVFQKP |
| 670 | 680 | 690 | 700 | 710 | 720 |
| VRFQVDISSS | EGPEPSPRRD | GSSGGGIYSV | TFTLISGPSR | RFKRVVETIQ | AQLLSTHDQP |
| 730 | 740 | 750 | 760 | 770 | |
| SVQALADEKN | GAQTRPAGTP | PRSLQPPPGR | PDPDLSSSPR | RGPSKDKKLL | ATNGTPLP |