SRPK2

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 (PubMed:18559500, PubMed:21056976, PubMed:9472028). Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression (PubMed:19592491). 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 (PubMed:21205200). Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation (PubMed:18559500). Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28 (PubMed:18425142). Probably by phosphorylating DDX23, leads to the suppression of incorrect R-loops formed during transcription; R-loops are composed of a DNA:RNA hybrid and the associated non-template single-stranded DNA (PubMed:28076779). Can mediate hepatitis B virus (HBV) core protein phosphorylation (PubMed:12134018). 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 (PubMed:16122776).

Post-translational modifications

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.

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.

Tissue specificity

Highly expressed in brain, moderately expressed in heart and skeletal muscle and at low levels in lung, liver, and kidney.

Cellular localization

• Cytoplasm
• Nucleus
• Nucleoplasm
• Nucleus speckle
• Chromosome
• Shuttles between the nucleus and the cytoplasm (PubMed:19592491, PubMed:21056976, PubMed:21157427). KAT5/TIP60 inhibits its nuclear translocation (PubMed:21157427). Phosphorylation at Thr-492 by PKB/AKT1 promotes nuclear translocation (PubMed:19592491). Preferentially localizes across the entire gene coding region (PubMed:28076779). During transcription, accumulates at chromatin loci where unscheduled R-loops form and colocalizes with paused 'Ser-5'-phosphorylated POLR2A/RNA polymerase II and helicase DDX23 (PubMed:28076779).

Alternative names

• SRSF protein kinase 2
• SFRS protein kinase 2
• Serine/arginine-rich protein-specific kinase 2
• SR-protein-specific kinase 2
• SRPK2

Database links

• entrezGene:6733
• omim:602980
• swissprot:P78362

Target type

Proteins

Molecular weight

77527Da