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

44-357 (Rel-homology domain)

Relief mechanism

Cleavage, PTM

Assay

Accessory elements

No accessory elements

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

13 regional properties for Q04861

Type Name Position InterPro Accession
domain C2 domain 158 - 277 IPR000008
domain Protein kinase domain 339 - 597 IPR000719
domain AGC-kinase, C-terminal 598 - 668 IPR000961
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 36 - 87 IPR002219-1
domain Protein kinase C-like, phorbol ester/diacylglycerol-binding domain 101 - 153 IPR002219-2
active_site Serine/threonine-protein kinase, active site 459 - 471 IPR008271
binding_site Protein kinase, ATP binding site 345 - 368 IPR017441
domain Protein kinase, C-terminal 624 - 658 IPR017892
domain Diacylglycerol/phorbol-ester binding 34 - 48 IPR020454-1
domain Diacylglycerol/phorbol-ester binding 50 - 59 IPR020454-2
domain Diacylglycerol/phorbol-ester binding 63 - 74 IPR020454-3
domain Diacylglycerol/phorbol-ester binding 140 - 152 IPR020454-4
domain Classical Protein Kinase C alpha, catalytic domain 328 - 668 IPR034663

Functions

Description
EC Number
Subcellular Localization
  • [Nuclear factor NF-kappa-B p105 subunit]: Cytoplasm
  • ;
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
MAGEDPYIMG VSDPQMFAMD QLMGMSTIFN NTGYITSDLP LRTADGPYLQ IIEQPKQRGF
70 80 90 100 110 120
RFRYVCEGPS HGGLPGASSE KNKKSYPQVK ICNYVGPAKV IVQLVTNGKY VHLHAHSLVG
130 140 150 160 170 180
KFCEDGVCTV NAGPKDMVVG FANLGILHVT KKKVFETLET RMIDACKKGY NPGLLVHPEL
190 200 210 220 230 240
GYLQAEGCGD RQLTEREREI IRQAAVQQTK EMDLSVVRLM FTAFLPDSNG GFTRRLDPVI
250 260 270 280 290 300
SDAIYDSKAP NASNLKIVRM DRTAGCVTGG EEIYLLCDKV QKDDIQIRFY EEDENGGMWE
310 320 330 340 350 360
GFGDFSPTDV HRQFAIVFKT PKYRDVNITK PASVFVQLRR KSDLETSEPK PFLYYPEIKD
370 380 390 400 410 420
KEEVQRKRQK LMPNFSDGYG GGSGAGGGGM FGGGGGGAGS GFSYPSYGYS AFGGMHFHPG
430 440 450 460 470 480
TTKSNAGMKH ELSNSTVKKD EESSDKQSDK WDTKHDVKVE TVEKNECRTS GHNEEKEDAS
490 500 510 520 530 540
LCCKDEGNKP KCGCQDGLFL EKAMQLAKRH CNALFDYAVT GDVRMLLAVQ RHLTAVQDDN
550 560 570 580 590 600
GDNVLHLSII HLHRELVKNL LEVMPDMNYN NIINMRNDLY QTPLHLAVIT KQAEVVEDLL
610 620 630 640 650 660
KAGANVNLLD RHGNSVLHLA AAEGDDKILS LLLKHQKASS MIDLSNGEGL SAIHMVVTAN
670 680 690 700 710 720
SLSCLKLLIA AGVDVNAQEQ KSGRTALHLA VEQENVPLAG CLLLEGDADV DSTTYDGTTP
730 740 750 760 770 780
LHIAAGRGFT KLAAVLKAAG ADPHVENFEP LFDVEEDVKD DDDDEGIVPG TTPLDMAANW
790 800 810 820 830 840
EVYDILNGKP YIAAAAVSED LLSQGPLREL NESSKQQLYK LLETPDPSKN WSTLAEKLGL
850 860 870 880 890 900
GILNNAFRLS PSPSKTLLDN YKISGGTVQE LIAALTQMDH TEAIEVIQKA LSSSQRQSHQ
910 920 930 940 950 960
EDNTIEAFPS LSPTSFAKEE TGELYNHKFQ DPESTCDSGV ETSFRKLSFT YSDSLNSKSS
970 980
ITLSKMTLGY RKAQCKAVIY LTR