MAP4K4
Description
The MAP4K4 (mitogen-activated protein kinase kinase kinase kinase 4) is a protein-coding gene located on chromosome 2.
Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) – also known as hepatocyte progenitor kinase-like/germinal center kinase-like kinase (HGK) and Nck-interacting kinase (NIK) – is an enzyme, specifically a serine/threonine (S/T) kinase encoded by the MAP4K4 gene in humans. MAP4K4 is involved in a wide array of physiological processes including cell migration, proliferation and adhesion; its activity has been implicated in systemic inflammation, metabolic disorders, cardiovascular disease and cancer. While MAP4K4 has been found to be upregulated in a wide array of cancers, there is currently limited information regarding its specific involvement. However, there is increasing evidence that suggests MAP4K4 has an important role in the development and progression of cancer, and may serve as a novel target for cancer therapeutics.
== Discovery and classification == MAP4K4 is categorized under the mammalian sterile 20 protein (Ste20p) kinase family due to its shared homology with the Ste20p kinase found in budding yeast and is a member of the GCK-IV subfamily. Mammalian MAP4K4 was initially identified in mice as a kinase activator for a protein called Nck followed shortly by identification and cloning of the human orthologue encoded by the MAP4K4 gene.
== Structure and expression == In humans, MAP4K4 is encoded by the MAP4K4 gene located on chromosome 2, position q11.2 and consists of 33 exons responsible for its synthesis. It contains approximately 1200 amino acids, has a molecular mass of ~140 KDa. and its orthologues across various species share molecular and structural similarities. Structurally MAP4K4 contains the following domains:
N-Terminal Kinase Domain Coiled-coil domain C-Terminal Hydrophobic Leucine-Rich Citron Homology Domain (CNH) Interdomain - Connects the kinase and CNH domains, facilitates protein-protein interactions.
MAP4K4 is a serine/threonine kinase that may be involved in responding to environmental stress and cytokines like TNF-alpha. It appears to function upstream of the JUN N-terminal pathway and phosphorylates SMAD1 at threonine 322.
MAP4K4 is also known as FLH21957, HEL-S-31, HGK, MEKKK4, NIK.
