======= SRPK1 ======= == Gene Information == * **Official Symbol**: SRPK1 * **Official Name**: SRSF protein kinase 1 * **Aliases and Previous Symbols**: N/A * **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=6732|6732]] * **UniProt**: [[https://www.uniprot.org/uniprot/Q96SB4|Q96SB4]] * **Interactions**: [[https://thebiogrid.org/search.php?search=SRPK1&organism=9606|BioGRID]] * **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SRPK1|Open PubMed]] * **OMIM**: [[https://omim.org/entry/601939|Open OMIM]] == Function Summary == * **Entrez Summary**: 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]. * **UniProt Summary**: 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. {ECO:0000269|PubMed:10049757, ECO:0000269|PubMed:10390541, ECO:0000269|PubMed:11509566, ECO:0000269|PubMed:12134018, ECO:0000269|PubMed:14555757, ECO:0000269|PubMed:15034300, ECO:0000269|PubMed:16122776, ECO:0000269|PubMed:16209947, ECO:0000269|PubMed:18155240, ECO:0000269|PubMed:18687337, ECO:0000269|PubMed:19240134, ECO:0000269|PubMed:19477182, ECO:0000269|PubMed:19886675, ECO:0000269|PubMed:20708644, ECO:0000269|PubMed:8208298, ECO:0000269|PubMed:9237760}. |Pkinase Tyr| |Pkinase| |sperm chromatin condensation| |spermatid nucleus differentiation| |positive regulation of viral genome replication| |spliceosomal complex assembly| |negative regulation of viral genome replication| |positive regulation of viral life cycle| |negative regulation of viral life cycle| |regulation of viral genome replication| |negative regulation of viral process| |regulation of mRNA splicing, via spliceosome| |positive regulation of viral process| |nuclear matrix| |nucleus organization| |regulation of RNA splicing| |regulation of mRNA processing| |regulation of viral life cycle| |spermatid development| |spermatid differentiation| |DNA packaging| |regulation of viral process| |negative regulation of multi-organism process| |magnesium ion binding| |regulation of symbiosis, encompassing mutualism through parasitism| |ribonucleoprotein complex assembly| |protein kinase activity| |ribonucleoprotein complex subunit organization| |germ cell development| |chromosome segregation| |mRNA splicing, via spliceosome| |DNA conformation change| |RNA splicing, via transesterification reactions with bulged adenosine as nucleophile| |RNA splicing, via transesterification reactions| |regulation of mRNA metabolic process| |cellular process involved in reproduction in multicellular organism| |protein serine/threonine kinase activity| |RNA splicing| |ribonucleoprotein complex biogenesis| |mRNA processing| |positive regulation of multi-organism process| |spermatogenesis| |male gamete generation| |developmental process involved in reproduction| |gamete generation| |mRNA metabolic process| |chromatin organization| |viral process| |innate immune response| |regulation of multi-organism process| |symbiotic process| |interspecies interaction between organisms| |multicellular organismal reproductive process| |sexual reproduction| |cellular protein-containing complex assembly| |multicellular organism reproduction| |RNA processing| |defense response to other organism| |protein phosphorylation| |multi-organism reproductive process| |endoplasmic reticulum| |chromosome organization| |phosphorylation| |response to other organism| |response to external biotic stimulus| |response to biotic stimulus| |defense response| |RNA binding| |reproductive process| |reproduction| |ATP binding| |protein-containing complex assembly| |cell development| |RNA metabolic process| |intracellular signal transduction| |protein-containing complex subunit organization| |immune response| |gene expression| \\ === CRISPR Data === ^Screen^Score^ |[[:results:exp485|GSK626616 14μM R08 exp485]]|-2.58| |[[:results:exp42|BI-6727 0.001μM R01 exp42]]|-2.29| |[[:results:exp430|Rifampicin 30μM R08 exp430]]|-2.15| |[[:results:exp354|Diepoxybutane 3μM R07 exp354]]|-2.07| |[[:results:exp226|Cerivastatin 0.15μM R05 exp226]]|-1.92| |[[:results:exp478|Doxorubicin 0.02μM R08 exp478]]|1.83| |[[:results:exp531|THZ1 0.06μM R08 exp531]]|1.85| |[[:results:exp134|MS023 2μM R03 exp134]]|2.01| |[[:results:exp489|Hippuristanol 0.12μM R08 exp489 no dilution day6]]|2.26| |[[:results:exp488|Hippuristanol 0.12μM R08 exp488]]|2.52| ^Gene^Correlation^ |[[:human genes:r:rpp21|RPP21]]|0.471| |[[:human genes:u:urm1|URM1]]|0.452| |[[:human genes:m:mcts1|MCTS1]]|0.442| |[[:human genes:k:kmt2d|KMT2D]]|0.431| |[[:human genes:s:sgol1|SGOL1]]|0.422| |[[:human genes:k:kdm8|KDM8]]|0.422| |[[:human genes:s:sugt1|SUGT1]]|0.413| |[[:human genes:e:elp3|ELP3]]|0.409| |[[:human genes:g:gmppb|GMPPB]]|0.406| |[[:human genes:a:alg1|ALG1]]|0.405| |[[:human genes:d:ddx55|DDX55]]|0.403| Global Fraction of Cell Lines Where Essential: 0/739 ^Tissue^Fraction Of Cell Lines Where Essential^ |1290807.0|0/1| |909776.0|0/1| |bile duct|0/28| |blood|0/28| |bone|0/26| |breast|0/33| |central nervous system|0/56| |cervix|0/4| |colorectal|0/17| |esophagus|0/13| |fibroblast|0/1| |gastric|0/16| |kidney|0/21| |liver|0/20| |lung|0/75| |lymphocyte|0/16| |ovary|0/26| |pancreas|0/24| |peripheral nervous system|0/16| |plasma cell|0/15| |prostate|0/1| |skin|0/24| |soft tissue|0/9| |thyroid|0/2| |upper aerodigestive|0/22| |urinary tract|0/29| |uterus|0/5| == Essentiality in NALM6 == * **Essentiality Rank**: 4304 * **Expression level (log2 read counts)**: 7.54 {{:chemogenomics:nalm6 dist.png?nolink |}}