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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SRPK1
SRSF protein kinase 1
Chromosome 6 · 6p21.31
NCBI Gene: 6732Ensembl: ENSG00000096063.17HGNC: HGNC:11305UniProt: Q96SB4
251PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
magnesium ion bindingRNA bindingpositive regulation of viral genome replicationnegative regulation of viral genome replicationneurodegenerative diseaseCOVID-19type 1 diabetes mellitusulcerative colitis
✦AI Summary

SRPK1 (serine/arginine-rich protein kinase 1) is a multifunctional protein kinase that phosphorylates SR splicing factors at serine residues within RS domains, serving as a central regulator of pre-mRNA splicing and nuclear organization [UniProt]. Beyond splicing, SRPK1 catalyzes phosphorylation of diverse substrates including protamines during parental genome reprogramming in fertilized oocytes, initiating protamine-to-histone exchange essential for early embryonic development 1. SRPK1 exhibits spatiotemporal expression patterns throughout brain development with coexpression linked to neurodevelopmental processes 2. In disease contexts, SRPK1 becomes pathologically upregulated: in lung adenocarcinoma, METTL3-mediated m6A methylation stabilizes SRPK1, which then promotes glycolysis through PKM2 splicing regulation 3. SRPK1 expression is elevated in intracranial aneurysms, where its silencing reduces VSMC apoptosis and promotes pathological vascular remodeling via PI3K/Akt inhibition 4. In hepatic steatosis, SRPK1 activity is inhibited by DRAK2 binding, reducing splicing factor SRSF6 phosphorylation and suppressing NAFLD progression 5. Additionally, SRPK1 undergoes S-palmitoylation and ubiquitin-dependent degradation in high-fat conditions, modulating p53-dependent ferroptosis in endothelial dysfunction 6. These findings position SRPK1 as both essential for normal cellular processes and a therapeutic target in multiple pathological conditions.

Sources cited
1
SRPK1 catalyzes protamine phosphorylation to initiate protamine-to-histone exchange in fertilized oocytes for parental genome reprogramming
PMID: 32169215
2
SRPK1 shows spatiotemporal expression patterns enriched in neurodevelopmental processes throughout brain development
PMID: 38376036
3
METTL3-mediated m6A methylation stabilizes SRPK1 in lung adenocarcinoma, promoting glycolysis and tumor progression through PKM2 splicing
PMID: 39095708
4
SRPK1 is upregulated in intracranial aneurysms; its silencing promotes VSMC proliferation and vascular remodeling via PI3K/Akt pathway inhibition
PMID: 30101479
5
DRAK2 binding inhibits SRPK1-mediated phosphorylation of SRSF6, regulating alternative splicing of mitochondrial genes and suppressing NAFLD/NASH progression
PMID: 34614409
6
SRPK1 undergoes S-palmitoylation and MIB1-mediated ubiquitination in high-fat conditions; modulates p53 activation to suppress endothelial ferroptosis
PMID: 41610308
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.46Moderate
COVID-19Open Targets
0.37Weak
type 1 diabetes mellitusOpen Targets
0.28Weak
ulcerative colitisOpen Targets
0.15Weak
celiac diseaseOpen Targets
0.15Weak
gliomaOpen Targets
0.10Suggestive
neoplasmOpen Targets
0.10Suggestive
colorectal carcinomaOpen Targets
0.09Suggestive
non-small cell lung carcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
acute myeloid leukemiaOpen Targets
0.08Suggestive
osteosarcomaOpen Targets
0.08Suggestive
lung adenocarcinomaOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.07Suggestive
breast cancerOpen Targets
0.07Suggestive
gastric cancerOpen Targets
0.07Suggestive
cervical squamous cell carcinomaOpen Targets
0.06Suggestive
posterior cortical atrophyOpen Targets
0.05Suggestive
skin basal cell carcinomaOpen Targets
0.05Suggestive
cancerOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SAFBProtein interaction100%SNRNP70Protein interaction100%SF3A3Protein interaction100%USP39Protein interaction100%SRSF1Protein interaction98%SRSF2Protein interaction98%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
67%
Lung
47%
Liver
41%
Heart
29%
Ovary
24%
Gene Interaction Network
Click a node to explore
SRPK1SAFBSNRNP70SF3A3USP39SRSF1SRSF2
PROTEIN STRUCTURE
Preparing viewer…
PDB5NNG · 1.20 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.76LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.43–0.76]
RankingsWhere SRPK1 stands among ~20K protein-coding genes
  • #1,533of 20,598
    Most Researched251 · top 10%
  • #6,125of 17,882
    Most Constrained (LOEUF)0.76
Genes detectedSRPK1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility.
PMID: 23177736
Mol Cell · 2013
1.00
2
DRAK2 aggravates nonalcoholic fatty liver disease progression through SRSF6-associated RNA alternative splicing.
PMID: 34614409
Cell Metab · 2021
0.90
3
Initiation of Parental Genome Reprogramming in Fertilized Oocyte by Splicing Kinase SRPK1-Catalyzed Protamine Phosphorylation.
PMID: 32169215
Cell · 2020
0.80
4
SRPK Inhibitors Reduce the Phosphorylation and Translocation of SR Protein Splicing Factors, thereby Correcting
PMID: 39344395
Front Biosci (Schol Ed) · 2024
0.76
5
Aberrant FAM135B attenuates the efficacy of chemotherapy in colorectal cancer by modulating SRSF1-mediated alternative splicing.
PMID: 39397154
Oncogene · 2024
0.72