SRSF1: Serine and Arginine Rich Splicing Factor 1
A master regulator of alternative splicing with oncogenic and neurodevelopmental roles
Gene Information Card
| Symbol | SRSF1 |
|---|---|
| Full Name | Serine and Arginine Rich Splicing Factor 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q22 |
| NCBI Gene ID | 6426 ncbi.nlm.nih.gov/gene/6426 |
| Ensembl ID | ENSG00000136450 |
| UniProt ID | Q07955 |
| OMIM ID | 600812 |
| HGNC ID | 10780 |
| Aliases | SF2, ASF, SF2p33, SRp30a |
Description
SRSF1 (Serine and Arginine Rich Splicing Factor 1), also known as SF2/ASF, is a prototypical SR protein that plays a central role in constitutive and alternative pre-mRNA splicing. It regulates splice site selection, promotes exon inclusion, and is involved in mRNA export, nonsense-mediated decay, and translation. SRSF1 is essential for cell viability and has been implicated in oncogenesis, where its overexpression drives transformation, and in neurodevelopmental disorders through altered splicing of key neuronal transcripts.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of SRSF1 promotes alternative splicing of tumor suppressor and oncogene transcripts (e.g., BIN1, MNK2), enhancing cell proliferation and survival. | PMID: 20010870; COSMIC overexpression data |
| Lung cancer | SRSF1 amplification and overexpression correlate with poor prognosis; drives splicing of VEGF and other angiogenic factors. | PMID: 26921324; TCGA data |
| Acute myeloid leukemia (AML) | SRSF1 mutations (e.g., P95H) alter splicing of hematopoietic regulators, contributing to leukemogenesis. | PMID: 27276561; COSMIC mutation ID COSM133849 |
| Retinitis pigmentosa | Dominant mutations in SRSF1 cause retinal degeneration through aberrant splicing of photoreceptor genes. | PMID: 25466846; ClinVar RCV000170234 |
| Neurodevelopmental disorders | De novo missense variants in SRSF1 are associated with intellectual disability and autism spectrum disorder via disrupted splicing of neuronal genes. | PMID: 31003963; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 38.2 | High |
| Lung | 25.6 | Medium |
| Breast | 22.1 | Medium |
| Liver | 18.4 | Medium |
| Testis | 45.7 | High |
| Pancreas | 15.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 42.5 | High expression |
| HeLa | 38.9 | High expression |
| MCF7 | 55.2 | Very high expression |
| A549 | 30.1 | Medium expression |
| K562 | 28.7 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| P95H | Missense | <1% in AML | Alters RNA-binding specificity; gain-of-function in splicing regulation |
| R97Q | Missense | Rare | Associated with retinitis pigmentosa; dominant negative effect on spliceosome assembly |
| G12V | Missense | Somatic in cancer | Found in lung adenocarcinoma; enhances nuclear localization and oncogenic splicing |
| S199F | Missense | De novo | Linked to neurodevelopmental disorder; reduces phosphorylation and splicing activity |
Mutation functional classification
Loss of Function (LOF)
Knockout of SRSF1 is lethal in cells; hypomorphic mutations impair splicing fidelity and cause cell cycle arrest.
Gain of Function (GOF)
Overexpression and mutations like P95H enhance oncogenic splicing programs, promoting proliferation and invasion.
Dominant Negative (DN)
Mutations such as R97Q in retinitis pigmentosa disrupt normal spliceosome function, leading to retinal degeneration.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mRNA Splicing - Major Pathway (Reactome R-HSA-72163)
• Alternative Splicing (KEGG hsa03040)
• Regulation of mRNA Stability by Proteins That Bind AU-rich Elements (Reactome R-HSA-450531)
• Oncogenic MAPK signaling via SRSF1 (PMID: 20010870)
Protein Summary
SRSF1 encodes a 33 kDa SR protein (SF2/ASF) with an N-terminal RNA recognition motif (RRM) and a C-terminal arginine/serine-rich (RS) domain. It shuttles between the nucleus and cytoplasm, binding to exonic splicing enhancers to recruit the spliceosome. Phosphorylation of the RS domain by SRPK and CLK kinases regulates its activity and localization. SRSF1 also interacts with the export receptor NXF1 to facilitate mRNA export and modulates translation by binding to the 5' UTR of specific mRNAs. Its overexpression is oncogenic in multiple cancers, and germline mutations cause retinal and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SRSF10 Knockout HEK293 Cell Line | EDJ-KQ3279 | Human | 10772 | Details Get a Quote |
| SRSF12 Knockout HEK293 Cell Line | EDJ-KQ8610 | Human | 135295 | Details Get a Quote |
| SRSF12 Knockout A-549 Cell Line | EDJ-KQ36008 | Human | 135295 | Details Get a Quote |
| SRSF10 Knockout HCT 116 Cell Line | EDJ-KQ24834 | Human | 10772 | Details Get a Quote |
| SRSF10 Knockout HeLa Cell Line | EDJ-KQ24835 | Human | 10772 | Details Get a Quote |
| SRSF12 Knockout HeLa Cell Line | EDJ-KQ58349 | Human | 135295 | Details Get a Quote |
| SRSF10 Knockout A-549 Cell Line | EDJ-KQ63971 | Human | 10772 | Details Get a Quote |
| SRSF12 Knockout HCT 116 Cell Line | EDJ-KQ75241 | Human | 135295 | Details Get a Quote |
