Serine/arginine-rich protein-specific kinase whichspecifically phosphorylates its substrates at serine residues locatedin regions rich in arginine/serine dipeptides, known as RS domains andis involved in the phosphorylation of SR splicing factors and theregulation of splicing. Plays a central role in the regulatory networkfor splicing, controlling the intranuclear distribution of splicingfactors in interphase cells and the reorganization of nuclear specklesduring mitosis. Can influence additional steps of mRNA maturation, aswell as other cellular activities, such as chromatin reorganization insomatic and sperm cells and cell cycle progression. Isoform 2phosphorylates SFRS2, ZRSR2, LBR and PRM1. Isoform 2 phosphorylatesSRSF1 using a directional (C-terminal to N-terminal) and a dual-trackmechanism incorporating both processive phosphorylation (in which thekinase stays attached to the substrate after each round ofphosphorylation) and distributive phosphorylation steps (in which thekinase and substrate dissociate after each phosphorylation event). TheRS domain of SRSF1 binds first to a docking groove in the large lobe ofthe kinase domain of SRPK1. This induces certain structural changes inSRPK1 and/or RRM2 domain of SRSF1, allowing RRM2 to bind the kinase andinitiate phosphorylation. The cycles continue for severalphosphorylation steps in a processive manner (steps 1-8) until the lastfew 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 RRM2to begin to dissociate, which facilitates SRSF1 dissociation afterphosphorylation is completed. Isoform 2 can mediate hepatitis B virus (HBV) core protein phosphorylation. It plays a negative role in theregulation of HBV replication through a mechanism not involving thephosphorylation of the core protein but by reducing the packagingefficiency of the pregenomic RNA (pgRNA) without affecting theformation of the viral core particles. Isoform 1 and isoform 2 caninduce splicing of exon 10 in MAPT/TAU. The ratio of isoform 1/isoform2 plays a decisive role in determining cell fate in K-562 leukaemiccell line: isoform 2 favors proliferation where as isoform 1 favorsdifferentiation. [1-16]

MERKVLALQARKKRTKAKKDKAQRKSETQHRGSAPHSESDLPEQEEEILGSDDDEQEDPNDYCKGGYHLVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPNREMVVQLLDDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYIRRLAAEATEWQRSGAPPPSGSAVSTAPQPKPADKMSKNKKKKLKKKQKRQAELLEKRMQEIEEMEKESGPGQKRPNKQEESESPVERPLKENPPNKMTQEKLEESSTIGQDQTLMERDTEGGAAEINCNGVIEVINYTQNSNNETLRHKEDLHNANDCDVQNLNQESSFLSSQNGDSSTSQETDSCTPITSEVSDTMVCQSSSTVGQSFSEQHISQLQESIRAEIPCEDEQEQEHNGPLDNKGKSTAGNFLVNPLEPKNAEKLKVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATGDYLFEPHSGEEYTRDEDHIALIIELLGKVPRKLIVAGKYSKEFFTKKGDLKHITKLKPWGLFEVLVEKYEWSQEEAAGFTDFLLPMLELIPEKRATAAECLRHPWLNS