ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKK-E); IKK-E (EC 2.7.11.10), also termed I-kappa-B kinase epsilon (IKKepsilon), or IKK-epsilon, or IkBKE, or inducible I kappa-B kinase (IKK-i), is an interferon regulatory factor-activating kinase that is a non-canonical member of IKK family. It is involved in the cellular innate immunity by inducing type I interferons. It is induced by the activation of nuclear factor-kappaB (NF-kappaB). IKK-E has also been implicated in antiviral immune response in higher vertebrates. It acts as a crucial pro-survival factor in human T cell leukemia virus type 1 (HTLV-1)-transformed T lymphocytes. Moreover, IKK-E plays an essential role in tumor initiation and progression. It inhibits protein kinase C (PKC) to promote Fascin-dependent actin bundling. IKK-E contains an N-terminal protein kinase domain followed a ubiquitin-like (Ubl) domain, and a C-terminal elongated helical domain. The Ubl domain acts as a protein-protein interaction domain, and has been implicated in regulating kinase activity, which modulates interactions in the interferon pathway.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119613954  71 RVVVHVFSLSQAVLHHIYIHAHNTIAIFQEAVHKQTSVAPRHQEYLFEGHLCVLEPSVSAQHIAHTTASSPLTLFSTA 148
Cdd:cd17128    1 RIVIHVFSLQQATMHHIYIHSYNTTTIFLEDVFKQTSIAPAHQEYLFEGHLYELEPNLQAQHFPKTTENKPLILISTE 78

C-terminal domain of non-canonical Inhibitor of kappa B kinases, IKK-E and TBK1, and similar proteins; Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKK-E or IKK-epsilon) and TANK-binding kinase 1 (TBK1) are non-canonical members of IKK family. They have been characterized as activators of nuclear factor-kappaB (NF-kappaB), but they are not essential for NF-kappaB activation. They play critical roles in antiviral response via phosphorylation and activation of transcription factors IRF3, IRF7, STAT1, and STAT3. They are also involved in the survival, tumorigenesis, and development of various cancers. Both IKK-epsilon and TBK1 contain an N-terminal protein kinase domain followed by a ubiquitin-like (Ubl) domain, a coiled-coil domain 1 (CCD1), and a C-terminal elongated alpha-helical domain. The model corresponds to the C-terminal elongated alpha-helical domain. It is responsible for the binding of adaptor proteins, optineurin (OPTN) and NAP1, to TBK1.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 119613954 438 TRKDLLLHMQELCEGMKLLASDLLDNNRIIERLNRVPAPPD 478
Cdd:cd21953    8 TPKELLLHMQELLEEMKLVARDLQQNNSIIERLDEVPPTPD 48

ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKK-E); IKK-E (EC 2.7.11.10), also termed I-kappa-B kinase epsilon (IKKepsilon), or IKK-epsilon, or IkBKE, or inducible I kappa-B kinase (IKK-i), is an interferon regulatory factor-activating kinase that is a non-canonical member of IKK family. It is involved in the cellular innate immunity by inducing type I interferons. It is induced by the activation of nuclear factor-kappaB (NF-kappaB). IKK-E has also been implicated in antiviral immune response in higher vertebrates. It acts as a crucial pro-survival factor in human T cell leukemia virus type 1 (HTLV-1)-transformed T lymphocytes. Moreover, IKK-E plays an essential role in tumor initiation and progression. It inhibits protein kinase C (PKC) to promote Fascin-dependent actin bundling. IKK-E contains an N-terminal protein kinase domain followed a ubiquitin-like (Ubl) domain, and a C-terminal elongated helical domain. The Ubl domain acts as a protein-protein interaction domain, and has been implicated in regulating kinase activity, which modulates interactions in the interferon pathway.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119613954  71 RVVVHVFSLSQAVLHHIYIHAHNTIAIFQEAVHKQTSVAPRHQEYLFEGHLCVLEPSVSAQHIAHTTASSPLTLFSTA 148
Cdd:cd17128    1 RIVIHVFSLQQATMHHIYIHSYNTTTIFLEDVFKQTSIAPAHQEYLFEGHLYELEPNLQAQHFPKTTENKPLILISTE 78

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119613954  22 WSYTLPITCQLSLGLQSQLVPILANILEVEQAKCWGFDQFFAETSDILQRVVVHVFSLSQAVLHHIYIHAHN 93
Cdd:cd13988  245 WSGELPVSCSLSQGLQTLLTPVLANILEADQEKCWGFDQFFAETSDILSRKVIHVFSVQQMTAHKIYIHSYE 316

ubiquitin-like (Ubl) domain found in inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKK-E); IKK-E (EC 2.7.11.10), also termed I-kappa-B kinase epsilon (IKKepsilon), or IKK-epsilon, or IkBKE, or inducible I kappa-B kinase (IKK-i), is an interferon regulatory factor-activating kinase that is a non-canonical member of IKK family. It is involved in the cellular innate immunity by inducing type I interferons. It is induced by the activation of nuclear factor-kappaB (NF-kappaB). IKK-E has also been implicated in antiviral immune response in higher vertebrates. It acts as a crucial pro-survival factor in human T cell leukemia virus type 1 (HTLV-1)-transformed T lymphocytes. Moreover, IKK-E plays an essential role in tumor initiation and progression. It inhibits protein kinase C (PKC) to promote Fascin-dependent actin bundling. IKK-E contains an N-terminal protein kinase domain followed a ubiquitin-like (Ubl) domain, and a C-terminal elongated helical domain. The Ubl domain acts as a protein-protein interaction domain, and has been implicated in regulating kinase activity, which modulates interactions in the interferon pathway.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 119613954  71 RVVVHVFSLSQAVLHHIYIHAHNTIAIFQEAVHKQTSVAPRHQEYLFEGHLCVLEPSVSAQHIAHTTASSPLTLFSTA 148
Cdd:cd17128    1 RIVIHVFSLQQATMHHIYIHSYNTTTIFLEDVFKQTSIAPAHQEYLFEGHLYELEPNLQAQHFPKTTENKPLILISTE 78

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 119613954  22 WSYTLPITCQLSLGLQSQLVPILANILEVEQAKCWGFDQFFAETSDILQRVVVHVFSLSQAVLHHIYIHAHN 93
Cdd:cd13988  245 WSGELPVSCSLSQGLQTLLTPVLANILEADQEKCWGFDQFFAETSDILSRKVIHVFSVQQMTAHKIYIHSYE 316

ubiquitin-like (Ubl) domain found in TRAF family member-associated NF-kappaB activator (TANK)-binding kinase 1 (TBK1); TBK1, also termed NF-kappa-B-activating kinase, or T2K, or TANK-binding kinase 1, is an interferon regulatory factor-activating kinase that is a non-canonical member of IKK family. It plays a role in regulating innate immunity, inflammation and oncogenic signaling. TBK1 is involved in the regulation of type I interferons and of nuclear factor-kappaB (NF-kappaB) signal transduction. It regulates factors such as IRF3 and IRF7, promoting antiviral activity in the interferon signaling pathways. It modulates inflammatory hyperalgesia by regulating MAP kinases and NF-kappaB dependent genes. Moreover, TBK1 acts as a central player in the intracellular nucleic acid-sensing pathways involved in antiviral signaling. Dysregulation of TBK1 activity is often associated with autoimmune diseases and cancer. TBK1 contains an N-terminal protein kinase domain followed a ubiquitin-like (Ubl) domain, and a C-terminal elongated helical domain. The Ubl domain acts as a protein-protein interaction domain, and has been implicated in regulating kinase activity, which modulates interactions in the interferon pathway.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 119613954  71 RVVVHVFSLSQAVLHHIYIHAHNTIAIFQEAVHKQTSVAPRHQEYLFEGHLCVLEPSVSAQHIAHTTASSPLTLFS 146
Cdd:cd17127    1 RMVIHVFSLQQMTAHKIYIHSYNTATIFHELVYKQTKIISSNQELIYEGRRLVLEPGRLAQHFPKTTEENPIFVVS 76

C-terminal domain of non-canonical Inhibitor of kappa B kinases, IKK-E and TBK1, and similar proteins; Inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKK-E or IKK-epsilon) and TANK-binding kinase 1 (TBK1) are non-canonical members of IKK family. They have been characterized as activators of nuclear factor-kappaB (NF-kappaB), but they are not essential for NF-kappaB activation. They play critical roles in antiviral response via phosphorylation and activation of transcription factors IRF3, IRF7, STAT1, and STAT3. They are also involved in the survival, tumorigenesis, and development of various cancers. Both IKK-epsilon and TBK1 contain an N-terminal protein kinase domain followed by a ubiquitin-like (Ubl) domain, a coiled-coil domain 1 (CCD1), and a C-terminal elongated alpha-helical domain. The model corresponds to the C-terminal elongated alpha-helical domain. It is responsible for the binding of adaptor proteins, optineurin (OPTN) and NAP1, to TBK1.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|.
gi 119613954 438 TRKDLLLHMQELCEGMKLLASDLLDNNRIIERLNRVPAPPD 478
Cdd:cd21933    3 TLDEMTLRMKKLKEEMEGVAKELQENNHIIERLGALTAPGG 43