Function: Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression. This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression. Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation. Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28. Can mediate hepatitis B virus (HBV) core protein phosphorylation. Plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles. Ref.1 Ref.6 Ref.8 Ref.10 Ref.12 Ref.15 Ref.19 Ref.21
Catalytic activity: ATP + a protein = ADP + a phosphoprotein.
Cofactor: Magnesium.
Enzyme regulation: Activated by phosphorylation on Ser-52 and Ser-588
By similarity.
Subunit structure: Interacts with PKB/AKT1 in a phosphorylation-dependent manner. The phosphorylated form (by PKB/AKT1) interacts with YWHAB and YWHAE. Interaction with YWHAB suppresses its cleavage by caspases and inhibits the release of its N-terminal pro-apoptotic fragment. Interacts with SFN. Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins (U4/U6-U5 tri-snRNPs). Ref.10 Ref.15
Subcellular location: Cytoplasm. Nucleus. Note: Shuttles between the nucleus and the cytoplasm. KAT5/TIP60 inhibits its nuclear translocation. Phosphorylation at Thr-492 by PKB/AKT1 promotes nuclear translocation. Ref.1 Ref.19 Ref.21
Tissue specificity: Highly expressed in brain, moderately expressed in heart and skeletal muscle and at low levels in lung, liver, and kidney. Ref.1
Post-translational modification: Phosphorylation at Thr-492 by PKB/AKT1 enhances its stimulatory activity in triggering cyclin-D1 (CCND1) expression and promoting apoptosis in neurons, which can be blocked by YWHAB. It also enhances its protein kinase activity toward ACIN1 and SRSF2, promotes its nuclear translocation and prevents its proteolytic cleavage.Proteolytically cleaved at Asp-139 and Asp-403 by caspase-3 during apoptotic cell death. Cleavage at Asp-139 which is the major site of cleavage, produces a small N-terminal fragment that translocates into nucleus and promotes VP16-induced apoptosis. Ref.21
Sequence similarities: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.Contains 1 protein kinase domain.
Sequence caution: The sequence AAQ63886.1 differs from that shown. Reason: The cDNA appears to contain a duplicated region.
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