SRSF1
GeneName
SRSF1
Summary
SRSF1, also known as SF2, ASF, or Asf1, is a 28 kDa nuclear protein that plays a central role in pre-mRNA splicing and is involved in the regulation of gene expression. It is primarily localised in the nucleus, particularly in nuclear speckles, and is also found in the cytoplasm. SRSF1 binds to RNA and is essential for the recognition of splice sites during the splicing process, facilitating alternative mRNA splicing via the spliceosome. Additionally, it participates in various biological processes such as mRNA processing, stabilization, and transport, as well as influencing cardiac muscle contraction and liver regeneration.
Importance
SRSF1 is relevant to: - Understanding alternative splicing mechanisms and their implications in gene expression regulation - Investigating its role in cardiac muscle function and development - Exploring its involvement in liver regeneration and associated signalling pathways - Studying its contributions to mRNA metabolism and stability, which can impact various cellular processes - Examining its potential role in diseases associated with splicing dysregulation, including cancer and neurodegenerative disorders
Top Products
For researchers investigating SRSF1, we recommend two excellent primary antibodies. The first is the well-cited polyclonal antibody, Anti-SF2 antibody (ab38017), which has garnered 34 citations, highlighting its reliability in Western blotting (WB). Additionally, we offer the recombinant antibody, Anti-SF2 antibody [EPR8240] (ab133689), which is validated for multiple applications including WB, immunocytochemistry (ICC), immunohistochemistry (IHC), and flow cytometry (FC). With 10 citations, this recombinant product ensures batch-to-batch consistency, making it an ideal choice for those requiring dependable detection of SRSF1 across various experimental setups.
Abcam Product Citation Summary
The data indicates that SRSF1 has been studied in both rat and human models, primarily using Western Blotting as the application method. The research contexts include general detection in rat samples and a specific focus on exon activation in human cell lysates.
Abcam Product Citation Table
Domain
The RRM 2 domain plays an important role in governing both the binding mode and the phosphorylation mechanism of the RS domain by SRPK1. RS domain and RRM 2 are uniquely positioned to initiate a highly directional (C-terminus to N-terminus) phosphorylation reaction in which the RS domain slides through an extended electronegative channel separating the docking groove of SRPK1 and the active site. RRM 2 binds toward the periphery of the active site and guides the directional phosphorylation mechanism. Both the RS domain and an RRM domain are required for nucleocytoplasmic shuttling.
Function
Plays a role in preventing exon skipping, ensuring the accuracy of splicing and regulating alternative splicing. Interacts with other spliceosomal components, via the RS domains, to form a bridge between the 5'- and 3'-splice site binding components, U1 snRNP and U2AF. Can stimulate binding of U1 snRNP to a 5'-splice site-containing pre-mRNA. Binds to purine-rich RNA sequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or the decamers, AGGACAGAGC/AGGACGAAGC. Binds preferentially to the 5'-CGAGGCG-3' motif in vitro. Three copies of the octamer constitute a powerful splicing enhancer in vitro, the ASF/SF2 splicing enhancer (ASE) which can specifically activate ASE-dependent splicing. Isoform ASF-2 and isoform ASF-3 act as splicing repressors. May function as export adapter involved in mRNA nuclear export through the TAP/NXF1 pathway.
Involvement in disease
Neurodevelopmental disorder with dysmorphic facies and behavioral abnormalities
NEDFBA
An autosomal dominant disorder characterized by developmental delay, intellectual disability, speech delay, hypotonia, behavioral abnormalities, and non-specific dysmorphic facial features. Some patients have variable skeletal and cardiac anomalies.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Phosphorylated by CLK1, CLK2, CLK3 and CLK4. Phosphorylated by SRPK1 at multiple serines in its RS domain via 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 to a docking groove in the large lobe of the kinase domain of SRPK1 and this induces certain structural changes in SRPK1 and/or RRM 2 domain of SRSF1, allowing RRM 2 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 RRM 2, which then docks at the docking groove of SRPK1. This also signals RRM 2 to begin to dissociate, which facilitates SRSF1 dissociation after phosphorylation is completed.
Asymmetrically dimethylated at arginines, probably by PRMT1, methylation promotes localization to nuclear speckles.
Sequence Similarities
Belongs to the splicing factor SR family.
Cellular localization
- Cytoplasm
- Nucleus speckle
- In nuclear speckles. Shuttles between the nucleus and the cytoplasm (PubMed:12215544, PubMed:20308322, PubMed:24449914, PubMed:9420331). Nuclear import is mediated via interaction with TNPO3 (PubMed:24449914).
Alternative names
ASF, SF2, SF2P33, SFRS1, OK/SW-cl.3, SRSF1, Serine/arginine-rich splicing factor 1, Alternative-splicing factor 1, ASF-1