MARK4
Developmental stage
Expressed at all stages of the mitotic cell cycle.
Function
Serine/threonine-protein kinase (PubMed:14594945, PubMed:15009667, PubMed:23184942, PubMed:23666762). 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). Involved in NLRP3 positioning along microtubules by mediating NLRP3 recruitment to microtubule organizing center (MTOC) upon inflammasome activation (PubMed:28656979).
Post-translational modifications
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).
Sequence Similarities
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.
Tissue Specificity
Ubiquitous. Isoform 2 is brain-specific (PubMed:11326310). Expressed at highest levels in brain and testis. Also expressed in heart, lung, liver, muscle, kidney and spleen (PubMed:14594945).
Cellular localization
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Centrosome
- Cytoplasm
- Cytoskeleton
- Microtubule organizing center
- Cytoplasm
- Cytoskeleton
- Cilium basal body
- Cytoplasm
- Cytoskeleton
- Cilium axoneme
- Cytoplasm
- Cell projection
- Dendrite
- Localized at the tips of neurite-like processes in differentiated neuroblast cells. Detected in the cytoplasm and neuropil of the hippocampus.
Alternative names
KIAA1860, MARKL1, MARK4, MAP/microtubule affinity-regulating kinase 4, MAP/microtubule affinity-regulating kinase-like 1