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C-terminal, kinase associated domain 1 (KA1), a phospholipid binding domain, of microtubule affinity-regulating kinase 4 Microtubule-associated protein/microtubule affinity regulating kinases (MARKs), also called partition-defective (Par-1) kinases, are serine/threonine protein kinases (STKs) that catalyze the transfer of the gamma-phosphoryl group from ATP to S/T residues on protein substrates. They phosphorylate the tau protein and related microtubule-associated proteins (MAPs) on tubulin binding sites to induce detachment from microtubules, and are involved in the regulation of cell shape and polarity, cell cycle control, transport, and the cytoskeleton. Mammals contain four proteins, MARK1-4, encoded by distinct genes belonging to this subfamily, with additional isoforms arising from alternative splicing. MARK4 has two splicing isoforms: MARK4S, predominantly expressed in the brain; and MARK4L, expressed in all tissues. Unlike MARK1-3 that show cytoplasmic localization, MARK4 colocalizes with the centrosome and with microtubules. Decreased MARK4 expression in the brain may be involved in the pathogenesis of Prion diseases and may be correlated to PrP(Sc) deposits. MARK4 is also a component of the ectoplasmic specialization, a testis-specific adherens junction. MARKs contain an N-terminal catalytic kinase domain, a ubiquitin-associated domain (UBA), and a C-terminal kinase associated domain (KA1). The KA1 domain binds anionic phospholipids and may be involved in membrane localization as well as in auto-inhibition of the kinase domain. |
Jiyao W et al.(2023). "The conserved domain database in 2023.",