IKBKE
entrez
9641
canonical
uniprot
Q14164
canonical
ensembl
ENSG00000263528
resolver
ensp
ENSP00000462396
resolver
ensp
ENSP00000464030
resolver
ensp
ENSP00000473833
resolver
ensp
ENSP00000570060
resolver
ensp
ENSP00000692212
resolver
enst
ENST00000578328
resolver
genesymbol
IKBKE
resolver
genesymbol_syn
IKKE
resolver
genesymbol_syn
IKKI
resolver
genesymbol_syn
KIAA0151
resolver
hgnc
HGNC:14552
resolver
uniprot
A0A075B7B4
resolver
uniprot
D3DT78
resolver
uniprot
Q3B754
resolver
uniprot
Q3KR43
resolver
uniprot
Q5JTS6
resolver
uniprot_entry
A0A075B7B4_HUMAN
resolver
uniprot_entry
IKKE_HUMAN
resolver
uniprot_sec
D3DT78
resolver
uniprot_sec
Q3B754
resolver
uniprot_sec
Q3KR43
resolver
uniprot_sec
Q5JTS6
resolver
amino_acid_sequence
MQSTANYLWHTDDLLGQGATASVYKARNKKSGELVAVKVFNTTSYLRPREVQVREFEVLRKLNHQNIVKLFAVEETGGSRQKVLVMEYCSSGSLLSVLESPENAFGLPEDEFLVVLRCVVAGMNHLRENGIVHRDIKPGNIMRLVGEEGQSIYKLTDFGAARELDDDEKFVSVYGTEEYLHPDMYERAVLRKPQQKAFGVTVDLWSIGVTLYHAATGSLPFIPFGGPRRNKEIMYRITTEKPAGAIAGAQRRENGPLEWSYTLPITCQLSLGLQSQLVPILANILEVEQAKCWGFDQFFAETSDILQRVVVHVFSLSQAVLHHIYIHAHNTIAIFQEAVHKQTSVAPRHQEYLFEGHLCVLEPSVSAQHIAHTTASSPLTLFSTAIPKGLAFRDPALDVPKFVPKVDLQADYNTAKGVLGAGYQALRLARALLDGQELMFRGLHWVMEVLQATCRRTLEVARTSLLYLSSSLGTERFSSVAGTPEIQELKAAAELRSRLRTLAEVLSRCSQNITETQESLSSLNRELVKSRDQVHEDRSIQQIQCCLDKMNFIYKQFKKSRMRPGLGYNEEQIHKLDKVNFSHLAKRLLQVFQEECVQKYQASLVTHGKRMRVVHETRNHLRLVGCSVAACNTEAQGVQESLSKLLEELSHQLLQDRAKGAQASPPPIAPYPSPTRKDLLLHMQELCEGMKLLASDLLDNNRIIERLNRVPAPPDV
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
ec_number
2.7.11.10
uniprot
proteins
function
FUNCTION: Serine/threonine kinase that plays an essential role in regulating inflammatory responses to viral infection, through the activation of the type I IFN, NF-kappa-B and STAT signaling (PubMed:16840782, PubMed:18583960, PubMed:19153231, PubMed:19481526, PubMed:21138416, PubMed:22532683, PubMed:23453969, PubMed:23478265, PubMed:24882218, PubMed:32268090). Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling (PubMed:18583960, PubMed:19153231, PubMed:22532683, PubMed:23478265). Following activation of viral RNA sensors, such as RIG-I-like receptors, associates with DDX3X and phosphorylates interferon regulatory factors (IRFs), IRF3 and IRF7, as well as DDX3X (PubMed:18583960, PubMed:19153231, PubMed:22532683, PubMed:23478265). This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB (PubMed:18583960, PubMed:19153231, PubMed:22532683, PubMed:23478265). In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli (PubMed:17568778). Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes (PubMed:17568778). In addition, is also required for the induction of a subset of ISGs which displays antiviral activity, may be through the phosphorylation of STAT1 at 'Ser-708' (By similarity). Phosphorylation of STAT1 at 'Ser-708' also seems to promote the assembly and DNA binding of ISGF3 (STAT1:STAT2:IRF9) complexes compared to GAF (STAT1:STAT1) complexes, in this way regulating the balance between type I and type II IFN responses (By similarity). Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway via the phosphorylation of CYLD, NFKBIA and p65/RELA (PubMed:16840782, PubMed:19481526, PubMed:21138416, PubMed:23453969). Activates NF-kappa-B by mediating phosphorylation and inactivation of CYLD (PubMed:19481526). Phosphorylates inhibitors of NF-kappa-B, such as NFKBIA, thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor (PubMed:10882136). Also activates NF-kappa-B signaling by mediating phosphorylation and activation of STING1 (PubMed:32268090, PubMed:39262777, PubMed:40973797). Protects cells against DNA damage-induced cell death (PubMed:20188669). Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, which leads to a negative impact on insulin sensitivity (By similarity). Phosphorylates AKT1 (PubMed:21464307). {ECO:0000250|UniProtKB:Q9R0T8, ECO:0000269|PubMed:10882136, ECO:0000269|PubMed:16840782, ECO:0000269|PubMed:17568778, ECO:0000269|PubMed:18583960, ECO:0000269|PubMed:19153231, ECO:0000269|PubMed:19481526, ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:21464307, ECO:0000269|PubMed:22532683, ECO:0000269|PubMed:23453969, ECO:0000269|PubMed:23478265, ECO:0000269|PubMed:24882218, ECO:0000269|PubMed:32268090, ECO:0000269|PubMed:39262777, ECO:0000269|PubMed:40973797}.
uniprot
proteins
mass_dalton
80462
uniprot
proteins
mutagenesis
MUTAGEN 30; /note="K->A: Loss of ubiquitination and decreased kinase activity. No effect on homodimerization."; /evidence="ECO:0000269|PubMed:23453969"; MUTAGEN 30; /note="K->R: Loss of ubiquitination and decreased kinase activity. Decreases interaction with IKBKB, IKBKG and MYD88. No effect on homodimerization."; /evidence="ECO:0000269|PubMed:23453969"; MUTAGEN 38; /note="K->A: Loss of kinase activity and loss of nuclear import."; /evidence="ECO:0000269|PubMed:10421793"; MUTAGEN 168; /note="E->A: Slight decrease of kinase activity."; /evidence="ECO:0000269|PubMed:10421793"; MUTAGEN 172; /note="S->A: Loss of autophosphorylation and of kinase activity."; /evidence="ECO:0000269|PubMed:10421793"; MUTAGEN 172; /note="S->E: Decrease in kinase activity."; /evidence="ECO:0000269|PubMed:10421793"; MUTAGEN 231; /note="K->R: Loss of sumoylation and loss of targeting to nuclear bodies."; /evidence="ECO:0000269|PubMed:20188669"; MUTAGEN 401; /note="K->A: Loss of ubiquitination and decreased kinase activity. No effect on homodimerization."; /evidence="ECO:0000269|PubMed:23453969"; MUTAGEN 401; /note="K->R: Loss of ubiquitination and decreased kinase activity. Decreases interaction with IKBKB, IKBKG and MYD88. No effect on homodimerization."; /evidence="ECO:0000269|PubMed:23453969"; MUTAGEN 416; /note="K->A: No effect on ubiquitination."; /evidence="ECO:0000269|PubMed:23453969"; MUTAGEN 416; /note="K->R: No effect on ubiquitination."; /evidence="ECO:0000269|PubMed:23453969"; MUTAGEN 568..572; /note="YNEEQ->ANEEA: Abolished association with STING1."; /evidence="ECO:0000269|PubMed:39262777
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated and phosphorylated by IKBKB/IKKB. Phosphorylation at Ser-172 is enhanced by the interaction with DDX3X. Phosphorylated at Thr-501 upon IFN activation. {ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:23478265}.; PTM: Sumoylation by TOPORS upon DNA damage is required for protection of cells against DNA damage-induced cell death. Desumoylated by SENP1. {ECO:0000269|PubMed:20188669}.; PTM: 'Lys-63'-linked polyubiquitinated at Lys-30 and Lys-401 by TRAF2:BIRC2 and TRAF2:BIRC3 complexes. Ubiquitination is induced by LPS, TNFA and interleukin-1 and required for full kinase activity and KF-kappa-B pathway activation. {ECO:0000269|PubMed:23453969}.
uniprot
proteins
protein_family
I-kappa-B kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Ser/Thr protein kinase family
uniprot
proteins
pubmed
10421793
uniprot
proteins
pubmed
10882136
uniprot
proteins
pubmed
14560022
uniprot
proteins
pubmed
14739303
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16177806
uniprot
proteins
pubmed
16281057
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16840782
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17568778
uniprot
proteins
pubmed
17600090
uniprot
proteins
pubmed
18583960
uniprot
proteins
pubmed
18636086
uniprot
proteins
pubmed
18636090
uniprot
proteins
pubmed
19153231
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19481526
uniprot
proteins
pubmed
20188669
uniprot
proteins
pubmed
20657822
uniprot
proteins
pubmed
21138416
uniprot
proteins
pubmed
21464307
uniprot
proteins
pubmed
22532683
uniprot
proteins
pubmed
23453969
uniprot
proteins
pubmed
23478265
uniprot
proteins
pubmed
24706939
uniprot
proteins
pubmed
24882218
uniprot
proteins
pubmed
26101251
uniprot
proteins
pubmed
27980081
uniprot
proteins
pubmed
28011935
uniprot
proteins
pubmed
28768861
uniprot
proteins
pubmed
29251827
uniprot
proteins
pubmed
31434731
uniprot
proteins
pubmed
32268090
uniprot
proteins
pubmed
33391252
uniprot
proteins
pubmed
39262777
uniprot
proteins
pubmed
40973797
uniprot
proteins
pubmed
8590280
uniprot
proteins
sequence_length
716
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24882218}. Nucleus. Nucleus, PML body {ECO:0000269|PubMed:20188669}. Note=Targeting to PML nuclear bodies upon DNA damage is TOPORS-dependent (PubMed:20188669). Located diffusely throughout the cytoplasm but locates to punctate cytoplasmic bodies when coexpressed with TRIM6 (PubMed:24882218). {ECO:0000269|PubMed:20188669, ECO:0000269|PubMed:24882218}.
uniprot
proteins