MARK4

This gene encodes a member of the microtubule affinity-regulating kinase family. These protein kinases phosphorylate microtubule-associated proteins and regulate the transition between stable and dynamic microtubules. The encoded protein is associated with the centrosome throughout mitosis and may be involved in cell cycle control. Expression of this gene is a potential marker for cancer, and the encoded protein may also play a role in Alzheimer's disease. Pseudogenes of this gene are located on both the short and long arm of chromosome 3. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene.

MICROTUBULE AFFINITY REGULATING KINASE 4

Serine/threonine-protein kinase (PubMed:15009667, PubMed:14594945, PubMed:23666762, PubMed:23184942).

Phosphorylates the microtubule-associated protein MAPT/TAU (PubMed:14594945, PubMed:23666762).

Also phosphorylates the microtubule-associated proteins MAP2 and MAP4 (PubMed:14594945).

Involved in regulation of the microtubule network, causing reorganization of microtubules into bundles (PubMed:14594945, PubMed:25123532).

Required for the initiation of axoneme extension during cilium assembly (PubMed:23400999).

Regulates the centrosomal location of ODF2 and phosphorylates ODF2 in vitro (PubMed:23400999).

Plays a role in cell cycle progression, specifically in the G1/S checkpoint (PubMed:25123532).

Reduces neuronal cell survival (PubMed:15009667).

Plays a role in energy homeostasis by regulating satiety and metabolic rate (By similarity).

Promotes adipogenesis by activating JNK1 and inhibiting the p38MAPK pathway, and triggers apoptosis by activating the JNK1 pathway (By similarity).

Phosphorylates mTORC1 complex member RPTOR and acts as a negative regulator of the mTORC1 complex, probably due to disruption of the interaction between phosphorylated RPTOR and the RRAGA/RRAGC heterodimer which is required for mTORC1 activation (PubMed:23184942).

Cell cycle Source: UniProtKB-KW
Cell division Source: UniProtKB-KW
Cilium organization Source: ARUK-UCL
Intracellular signal transduction Source: GO_Central
Microtubule bundle formation Source: UniProtKB
Microtubule cytoskeleton organization Source: UniProtKB
Nervous system development Source: UniProtKB
Positive regulation of cell cycle Source: ARUK-UCL
Positive regulation of cilium assembly Source: ARUK-UCL
Positive regulation of programmed cell death Source: UniProtKB
Positive regulation of protein localization to centrosome Source: ARUK-UCL
Protein phosphorylation Source: UniProtKB
Regulation of centrosome cycle Source: ARUK-UCL

Cytoskeleton
Centrosome
Microtubule organizing center
Cilium basal body
Cilium axoneme
Cytoplasm and Cytosol
Cytoplasm
Other locations
Dendrite
Note: Localized at the tips of neurite-like processes in differentiated neuroblast cells. Detected in the cytoplasm and neuropil of the hippocampus.

Ubiquitinated with 'Lys-29'- and 'Lys-33'-linked polyubiquitins which appear to impede LKB1-mediated phosphorylation. Deubiquitinated by USP9X.
Phosphorylated at Thr-214 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (PubMed:14976552). Phosphorylated throughout the cell cycle (PubMed:25123532).