IKBKE (inhibitor of nuclear factor kappa B kinase subunit epsilon)

Gene

• Entrez ID: 9641
• Gene name: Inhibitor of nuclear factor kappa B kinase subunit epsilon
• Gene symbol: IKBKE
• Synonyms: IKK-E, IKK-i, IKKE, IKKI
• Chromosome: 1
• Chromosome location: 1q32.1
• Summary: IKBKE is a noncanonical I-kappa-B (see MIM 164008) kinase (IKK) that is essential for regulating antiviral signaling pathways. IKBKE has also been identified as a breast cancer (MIM 114480) oncogene and is amplified and overexpressed in over 30% of breast carcinomas and breast cancer cell lines (Hutti et al., 2009 [PubMed 19481526]).[supplied by OMIM, Oct 2009]

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003484	hsa-miR-155-5p	qRT-PCR, Western blot	18753206
MIRT003484	hsa-miR-155-5p	Luciferase reporter assay	19177201
MIRT003484	hsa-miR-155-5p	Proteomics	20584899
MIRT003484	hsa-miR-155-5p	Luciferase reporter assay, Western blot	24151514
MIRT003484	hsa-miR-155-5p	Immunofluorescence, Immunohistochemistry, Luciferase reporter assay, qRT-PCR, Western blot	26934326
MIRT006572	hsa-miR-296-5p	Luciferase reporter assay	22114321
MIRT022344	hsa-miR-124-3p	Microarray	18668037

Transcription factors

Transcription factor	Regulation	Reference
STAT3	Activation	22330135
ZNF382	Repression	20682794

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004672	Function	Protein kinase activity	TAS
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004704	Function	NF-kappaB-inducing kinase activity	IDA	10882136
GO:0005515	Function	Protein binding	IPI	14743216, 16177806, 16281057, 17568778, 17599067, 17600090, 18636086, 18636090, 19153231, 20188669, 20657822, 21212807, 21903422, 21931555, 22939624, 23096996, 24706939, 25036637, 25852190, 27980081, 28011935, 29251827, 32814053
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IDA	20188669
GO:0005654	Component	Nucleoplasm	TAS
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005737	Component	Cytoplasm	IDA	20188669, 24882218
GO:0005829	Component	Cytosol	TAS
GO:0006468	Process	Protein phosphorylation	IDA	10882136, 20188669, 24882218
GO:0006955	Process	Immune response	NAS	10421793
GO:0007252	Process	I-kappaB phosphorylation	IEA
GO:0008384	Function	IkappaB kinase activity	IEA
GO:0008630	Process	Intrinsic apoptotic signaling pathway in response to DNA damage	IMP	20188669
GO:0010008	Component	Endosome membrane	TAS
GO:0010884	Process	Positive regulation of lipid storage	ISS
GO:0016032	Process	Viral process	IEA
GO:0016605	Component	PML body	IDA	20188669
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0019903	Function	Protein phosphatase binding	ISS
GO:0031625	Function	Ubiquitin protein ligase binding	IPI	24882218
GO:0031966	Component	Mitochondrial membrane	IMP	16876765
GO:0032480	Process	Negative regulation of type I interferon production	TAS
GO:0034340	Process	Response to type I interferon	IEA
GO:0035456	Process	Response to interferon-beta	IMP	24882218
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	TAS
GO:0036435	Function	K48-linked polyubiquitin modification-dependent protein binding	IMP	24882218
GO:0038061	Process	NIK/NF-kappaB signaling	IEA
GO:0042802	Function	Identical protein binding	IPI	24882218
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IEP	12761501
GO:0060340	Process	Positive regulation of type I interferon-mediated signaling pathway	IEA
GO:0070530	Function	K63-linked polyubiquitin modification-dependent protein binding	IMP	24882218
GO:0098586	Process	Cellular response to virus	IEA

Other IDs

• MIM: 605048
• HGNC: 14552
• e!Ensembl: ENSG00000263528

Protein

• UniProt ID: Q14164
• Protein name: Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i)
• Protein 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. Also involved in TNFA and inflammatory cytokines, like Interleukin-1, signaling. 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. This activity allows subsequent homodimerization and nuclear translocation of the IRF3 leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNB. In order to establish such an antiviral state, IKBKE forms several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including IPS1/MAVS, TANK, AZI2/NAP1 or TBKBP1/SINTBAD can be recruited to the IKBKE-containing-complexes. Activated by polyubiquitination in response to TNFA and interleukin-1, regulates the NF-kappa-B signaling pathway through, at least, the phosphorylation of CYLD. Phosphorylates inhibitors of NF-kappa-B thus leading to the dissociation of the inhibitor/NF-kappa-B complex and ultimately the degradation of the inhibitor. 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'. Phosphorylation of STAT1 at 'Ser-708' seems also 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. Protects cells against DNA damage-induced cell death. Also plays an important role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Phosphorylates AKT1.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	9 → 301	Protein kinase domain	Domain
  PF18396	TBK1_ULD	308 → 393	TANK binding kinase 1 ubiquitin-like domain	Domain
  PF18394	TBK1_CCD1	400 → 646	TANK-binding kinase 1 coiled-coil domain 1	Coiled-coil

• Sequence:

  MQSTANYLWHTDDLLGQGATASVYKARNKKSGELVAVKVFNTTSYLRPREVQVREFEVLR
  KLNHQNIVKLFAVEETGGSRQKVLVMEYCSSGSLLSVLESPENAFGLPEDEFLVVLRCVV
  AGMNHLRENGIVHRDIKPGNIMRLVGEEGQSIYKLTDFGAARELDDDEKFVSVYGTEEYL
  HPDMYERAVLRKPQQKAFGVTVDLWSIGVTLYHAATGSLPFIPFGGPRRNKEIMYRITTE
  KPAGAIAGAQRRENGPLEWSYTLPITCQLSLGLQSQLVPILANILEVEQAKCWGFDQFFA
  ETSDILQRVVVHVFSLSQAVLHHIYIHAHNTIAIFQEAVHKQTSVAPRHQEYLFEGHLCV
  LEPSVSAQHIAHTTASSPLTLFSTAIPKGLAFRDPALDVPKFVPKVDLQADYNTAKGVLG
  AGYQALRLARALLDGQELMFRGLHWVMEVLQATCRRTLEVARTSLLYLSSSLGTERFSSV
  AGTPEIQELKAAAELRSRLRTLAEVLSRCSQNITETQESLSSLNRELVKSRDQVHEDRSI
  QQIQCCLDKMNFIYKQFKKSRMRPGLGYNEEQIHKLDKVNFSHLAKRLLQVFQEECVQKY
  QASLVTHGKRMRVVHETRNHLRLVGCSVAACNTEAQGVQESLSKLLEELSHQLLQDRAKG
  AQASPPPIAPYPSPTRKDLLLHMQELCEGMKLLASDLLDNNRIIERLNRVPAPPDV

• Sequence length: 716