MAP3K14
Function
Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Phosphorylates CHUK/IKKA, thereby promoting proteolytic processing of NFKB2/P100, which leads to NF-kappa-B activation via the non-canonical pathway (PubMed:25406581, PubMed:29230214). Has an essential role in the non-canonical NF-kappa-B signaling that regulates genes encoding molecules involved in B-cell survival, lymphoid organogenesis, and immune response (PubMed:25406581). Could act in a receptor-selective manner.
Involvement in disease
Immunodeficiency 112
IMD112
An autosomal recessive, primary immunologic disorder characterized by variable abnormalities affecting lymphoid immunity, including hypogammaglobulinemia, lymphopenia or paradoxical lymphocytosis, and recurrent bacterial, viral, and fungal infections.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Autophosphorylated. Phosphorylation at Thr-559 is required to activate its kinase activity and 'Lys-63'-linked polyubiquitination. Phosphorylated by CHUK/IKKA leading to MAP3K14 destabilization.
Ubiquitinated. Undergoes both 'Lys-48'- and 'Lys-63'-linked polyubiquitination. 'Lys-48'-linked polyubiquitination leads to its degradation by the proteasome, while 'Lys-63'-linked polyubiquitination stabilizes and activates it.
Sequence Similarities
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Tissue Specificity
Weakly expressed in testis, small intestine, spleen, thymus, peripheral blood leukocytes, prostate, ovary and colon.
Cellular localization
- Cytoplasm
Alternative names
NIK, MAP3K14, Mitogen-activated protein kinase kinase kinase 14, NF-kappa-beta-inducing kinase, Serine/threonine-protein kinase NIK, HsNIK