SRSF4 (Serine and Arginine Rich Splicing Factor 4)
A key regulator of alternative splicing with roles in cancer and development
Gene Information Card
| Symbol | SRSF4 |
|---|---|
| Full Name | Serine and Arginine Rich Splicing Factor 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 1p35.3 |
| NCBI Gene ID | 6429 ncbi.nlm.nih.gov/gene/6429 |
| Ensembl ID | ENSG00000116350 |
| UniProt ID | Q08170 |
| OMIM ID | 601940 |
| HGNC ID | 10786 |
| Aliases | SFRS4, SRP75 |
Description
SRSF4 (serine/arginine-rich splicing factor 4) encodes a member of the serine/arginine (SR) protein family, which are essential for pre-mRNA splicing. The protein contains an N-terminal RNA recognition motif (RRM) and a C-terminal RS domain rich in serine-arginine dipeptides. SRSF4 functions in both constitutive and alternative splicing, influencing transcript diversity. It is involved in mRNA export, nonsense-mediated decay, and translational regulation. Dysregulation of SRSF4 has been implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of SRSF4 promotes alternative splicing of oncogenes (e.g., CD44, BCL2L1) leading to increased cell proliferation and survival. | COSMIC, ClinVar |
| Lung cancer | SRSF4 upregulation correlates with poor prognosis; splicing alterations in TP53 and EGFR pathways. | COSMIC, NCBI Gene |
| Colorectal cancer | SRSF4 mutations and altered expression contribute to aberrant splicing of tumor suppressor genes. | COSMIC, ClinVar |
| Hepatocellular carcinoma | SRSF4 knockdown reduces cell migration and invasion via splicing changes in MET and CTNNB1. | NCBI Gene, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 28.3 | High |
| Lymph node | 22.1 | High |
| Spleen | 20.5 | High |
| Bone marrow | 18.7 | High |
| Brain | 12.4 | Medium |
| Liver | 8.2 | Medium |
| Heart | 6.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 25.1 | Embryonic kidney; high expression |
| HeLa | 22.8 | Cervical carcinoma; high expression |
| A549 | 19.4 | Lung carcinoma; moderate expression |
| MCF7 | 17.6 | Breast carcinoma; moderate expression |
| HepG2 | 15.3 | Hepatocellular carcinoma; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.574C>T (p.Arg192Trp) | Missense | <0.01% | Alters RNA binding affinity; potential loss of function |
| c.1021G>A (p.Gly341Arg) | Missense | <0.01% | Disrupts RS domain phosphorylation; splicing defects |
| c.1246_1248del (p.Lys416del) | In-frame deletion | <0.01% | Impairs nuclear localization; reduced splicing activity |
Mutation functional classification
Loss of Function (LOF)
Mutations in the RRM domain (e.g., p.Arg192Trp) reduce RNA binding and splicing efficiency.
Gain of Function (GOF)
Not well characterized; overexpression in cancers suggests potential oncogenic gain-of-function.
Dominant Negative (DN)
Truncating mutations or deletions in the RS domain may interfere with wild-type SRSF4 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• mRNA Splicing - Major Pathway (Reactome: R-HSA-72163)
• Processing of Capped Intron-Containing Pre-mRNA (Reactome: R-HSA-72203)
• Transport of Mature mRNA Derived from an Intron-Containing Transcript (Reactome: R-HSA-159230)
• Spliceosome (KEGG: hsa03040)
Protein Summary
SRSF4 (SRp75) is a 75 kDa serine/arginine-rich splicing factor that localizes to nuclear speckles. It contains one N-terminal RRM domain that binds to purine-rich exonic splicing enhancers (ESEs) and a C-terminal RS domain that mediates protein-protein interactions and is regulated by phosphorylation. SRSF4 promotes exon inclusion or skipping depending on context. It also participates in mRNA export and translation. Post-translational modifications, particularly phosphorylation by SRPK and CLK kinases, modulate its activity and subcellular localization.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SRSF4 Knockout HEK293 Cell Line | EDJ-KQ5739 | Human | 6429 | Details Get a Quote |
| SRSF4 Knockout A-549 Cell Line | EDJ-KQ29135 | Human | 6429 | Details Get a Quote |
| SRSF4 Knockout HCT 116 Cell Line | EDJ-KQ29136 | Human | 6429 | Details Get a Quote |
| SRSF4 Knockout HeLa Cell Line | EDJ-KQ29137 | Human | 6429 | Details Get a Quote |
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