SRSF protein kinase 1

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 leukemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation. Phosphorylates the N-terminus of ERC130745339

Quoted from UniProt’s FUNCTION annotation for Q96SB4 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Nucleoplasm
• Cytosol
• Plasma membraneadditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cytoplasm · Nucleus · Nucleus matrix · Microsome · Nucleus, nucleoplasm · Nucleus speckle · Chromosome

Expression by cell type

Single cell type RNA, the 5 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Neutrophils2,212.5 nCPM
• Late spermatids890.5 nCPM
• Neutrophil progenitors707.8 nCPM
• Urothelial cells497.5 nCPM
• Late primary spermatocytes437.4 nCPM