Linked Life Data

Q96SB4

Source:http://identifiers.org/uniprot/Q96SB4

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
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. 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 K562 leukaemic cell line: isoform 2 favors proliferation where as isoform 1 favors differentiation. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. ENZYME REGULATION: Activated by phosphorylation on Ser-51 and Ser- 555. SUBUNIT: Monomer. Isoform 2 is found in a multisubunit complex containing seven proteins, named toposome, which separates entangled circular chromatin DNA during chromosome segregation. Isoform 2 interacts with HHV-1 ICP27 protein. Isoform 2 interacts with DNAJB1/HSP40 and AHSA1/AHA1 and this mediates formation of a complex with the Hsp70 /Hsp90 machinery. Isoform 1 is found in a complex with: DHX9, MOV10, MATR3, HNRNPU, NCL, DDX21, HSD17B4, PABPC1, HNRNPM, IGF2BP1, SYNCRIP, RPL3, VIM, YBX1, NPM1, HNRNPA2B1, HNRNPC, RPLP0, RPL7A and RALY. Isoform 2 binds to IGF2BP1, SYNCRIP, HNRNPA2B1 and HNRNPC. Isoform 1 and isoform 2 interact with SAFB which inhibits its activity. Isoform 2 interacts with SAFB2 which inhibits its activity. SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Nucleus. Nucleus matrix. Microsome. Note=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. SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Nucleus matrix. Microsome. Note=Mainly localized in the microsomal fraction and the cytoplasm, and to a lesser extent in the nuclear matrix. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=2; Name=2; IsoId=Q96SB4-2; Sequence=Displayed; Name=1; Synonyms=1a; IsoId=Q96SB4-3; Sequence=VSP_042130; Note=Due to intron retention; TISSUE SPECIFICITY: Isoform 2 is predominantly expressed in the testis but is also present at lower levels in heart, ovary, small intestine, liver, kidney, pancreas and skeletal muscle. Isoform 1 is only seen in the testis, at lower levels than isoform 2. Highly expressed in different erythroid and lymphoid cell lines, with isoform 2 being far more abundant than isoform 1. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=CAI20544.1; Type=Erroneous gene model prediction; Sequence=CAI20545.1; Type=Erroneous gene model prediction; GENE SYNONYMS:SRPK1. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 655 AA; 74325 MW; 900E980FE1C16B9A CRC64;
biopax3:xref
biopax3:displayName
SRPK1_HUMAN
biopax3:name
2.7.11.1, SFRS protein kinase 1, SR-protein-specific kinase 1, SRPK1, Serine/arginine-rich protein-specific kinase 1
biopax3:entityFeature
biopax3:organism
biopax3:sequence
MERKVLALQARKKRTKAKKDKAQRKSETQHRGSAPHSESDLPEQEEEILGSDDDEQEDPNDYCKGGYHLVKIGDLFNGRYHVIRKLGWGHFSTVWLSWDIQGKKFVAMKVVKSAEHYTETALDEIRLLKSVRNSDPNDPNREMVVQLLDDFKISGVNGTHICMVFEVLGHHLLKWIIKSNYQGLPLPCVKKIIQQVLQGLDYLHTKCRIIHTDIKPENILLSVNEQYIRRLAAEATEWQRSGAPPPSGSAVSTAPQPKPADKMSKNKKKKLKKKQKRQAELLEKRMQEIEEMEKESGPGQKRPNKQEESESPVERPLKENPPNKMTQEKLEESSTIGQDQTLMERDTEGGAAEINCNGVIEVINYTQNSNNETLRHKEDLHNANDCDVQNLNQESSFLSSQNGDSSTSQETDSCTPITSEVSDTMVCQSSSTVGQSFSEQHISQLQESIRAEIPCEDEQEQEHNGPLDNKGKSTAGNFLVNPLEPKNAEKLKVKIADLGNACWVHKHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATGDYLFEPHSGEEYTRDEDHIALIIELLGKVPRKLIVAGKYSKEFFTKKGDLKHITKLKPWGLFEVLVEKYEWSQEEAAGFTDFLLPMLELIPEKRATAAECLRHPWLNS
biopax3:standardName
SRSF protein kinase 1