SRPK1

This gene encodes a serine/arginine protein kinase specific for the SR (serine/arginine-rich domain) family of splicing factors. The protein localizes to the nucleus and the cytoplasm. It is thought to play a role in regulation of both constitutive and alternative splicing by regulating intracellular localization of splicing factors. Alternative splicing of this gene results in multiple transcript variants. Additional alternatively spliced transcript variants have been described for this gene, but their full length nature have not been determined.[provided by RefSeq, Jul 2010]

SRSF Protein Kinase 1

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. Plays a central role in the regulatory network for splicing, controlling the intranuclear distribution of splicing factors in interphase cells and the reorganization of nuclear speckles during mitosis. Can influence additional steps of mRNA maturation, as well as other cellular activities, such as chromatin reorganization in somatic and sperm cells and cell cycle progression. Isoform 2 phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylates SRSF1 using a directional (C-terminal to N-terminal) and a dual-track mechanism incorporating both processive phosphorylation (in which the kinase stays attached to the substrate after each round of phosphorylation) and distributive phosphorylation steps (in which the kinase and substrate dissociate after each phosphorylation event). The RS domain of SRSF1 binds first to a docking groove in the large lobe of the kinase domain of SRPK1. This induces certain structural changes in SRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase and initiate phosphorylation. The cycles continue for several phosphorylation steps in a processive manner (steps 1-8) until the last few phosphorylation steps (approximately steps 9-12). During that time, a mechanical stress induces the unfolding of the beta-4 motif in RRM2, which then docks at the docking groove of SRPK1. This also signals RRM2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It 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. Isoform 1 and isoform 2 can induce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform 2 plays a decisive role in determining cell fate in K-562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation.

Biological Process chromosome segregationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process innate immune response1 PublicationIC:BHF-UCL
Biological Process intracellular signal transductionManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process negative regulation of viral genome replicationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process positive regulation of viral genome replicationManual Assertion Based On ExperimentIDA:BHF-UCL
Biological Process protein phosphorylationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of mRNA processingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of mRNA splicing, via spliceosomeManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process RNA splicingManual Assertion Based On ExperimentTAS:ProtInc
Biological Process sperm DNA condensationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process spliceosomal complex assemblyManual Assertion Based On ExperimentIBA:GO_Central

Isoform 2
Cytoplasm
Nucleus
Nucleus matrix
Microsome
Shuttles between the nucleus and the cytoplasm. Inhibition of the Hsp90 ATPase activity, osmotic stress and interaction with HHV-1 ICP27 protein can induce its translocation to the nucleus. KAT5/TIP60 inhibits its nuclear translocation.
Isoform 1
Cytoplasm
Nucleus matrix
Microsome
Mainly localized in the microsomal fraction and the cytoplasm, and to a lesser extent in the nuclear matrix.
Cytoplasm
Nucleus, nucleoplasm
Nucleus speckle
Chromosome
Preferentially localizes to the promoter of gene coding regions.