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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SRPK2
SRSF protein kinase 2
Chromosome 7 · 7q22.3
NCBI Gene: 6733Ensembl: ENSG00000135250.17HGNC: HGNC:11306UniProt: A0A994J591
144PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedKinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
positive regulation of viral genome replicationnegative regulation of viral genome replicationnucleolusnucleoplasmschizophreniaCOVID-19autism spectrum disorderattention deficit hyperactivity disorder
✦AI Summary

SRPK2 is a serine/arginine-rich protein kinase that phosphorylates SR splicing factors at RS domains, regulating pre-mRNA splicing and spliceosomal B complex formation 1. Beyond splicing, SRPK2 functions as a metabolic regulator and oncogenic driver with diverse pathological implications. In lipid metabolism, SRPK2 operates downstream of mTORC1 to phosphorylate SRSF1, coupling transcription and splicing of lipogenic enzymes through the FAM120A-SREBP1 complex 2. This function is pathologically relevant in alcohol-associated liver disease, where SRPK2 activation promotes lipogenesis via altered splicing of lipin 1 and SREBP1, and inhibition by FGF21 ameliorates disease progression 3. Similarly, in osteosarcoma, SRPK2 regulates ACSL3 splicing to influence ferroptosis susceptibility through lipid metabolism 4. In cancer, SRPK2 promotes tumorigenesis across multiple malignancies. In colorectal cancer, SRPK2 drives migration, invasion, and chemoresistance via SRPK2-Numb-p53 signaling, negatively regulating wild-type p53 5. SRPK2 activates ERK signaling in colon cancer growth and migration 6. In hepatocellular carcinoma, LINC01446 activates SRPK2-SRSF1 axis to promote VEGFA165 splicing, enhancing angiogenesis and proliferation 7. In obesity-associated pancreatic cancer, SRPK2 drives stress granule formation downstream of mTOR/S6K1 hyperactivation 8. These findings establish SRPK2 as a therapeutic target in metabolic and malignant diseases.

Sources cited
1
SRPK2 phosphorylates SR splicing factors at RS domains and regulates spliceosomal complex formation
PMID: 18559500
2
SRPK2 operates downstream of mTORC1 to phosphorylate SRSF1 and couple transcription-splicing of lipogenic enzymes via FAM120A-SREBP1
PMID: 37595559
3
SRPK2 activation promotes lipogenesis in alcohol-associated liver disease by regulating alternative splicing of lipin 1 and SREBP1
PMID: 37129868
4
SRPK2 regulates splicing of ACSL3 to influence ferroptosis susceptibility in osteosarcoma cells
PMID: 37993451
5
SRPK2 promotes colorectal cancer cell migration, invasion, and chemoresistance through SRPK2-Numb-p53 signaling pathway
PMID: 31898732
6
SRPK2 promotes colon cancer growth and migration by activating ERK signaling
PMID: 27041240
7
SRPK2 activation of SRSF1 promotes HCC progression and angiogenesis via VEGFA165 splicing
PMID: 38945203
8
SRPK2 drives stress granule formation in obesity-associated pancreatic cancer downstream of mTOR/S6K1 pathway
PMID: 35674408
Disease Associationsⓘ20
schizophreniaOpen Targets
0.46Moderate
COVID-19Open Targets
0.41Moderate
autism spectrum disorderOpen Targets
0.39Weak
attention deficit hyperactivity disorderOpen Targets
0.39Weak
smoking cessationOpen Targets
0.38Weak
neurodegenerative diseaseOpen Targets
0.37Weak
skin agingOpen Targets
0.37Weak
bipolar disorderOpen Targets
0.37Weak
intelligenceOpen Targets
0.36Weak
anorexia nervosaOpen Targets
0.29Weak
Tourette syndromeOpen Targets
0.29Weak
StutteringOpen Targets
0.29Weak
major depressive disorderOpen Targets
0.29Weak
obsessive-compulsive disorderOpen Targets
0.29Weak
sunburnOpen Targets
0.28Weak
type 2 diabetes mellitusOpen Targets
0.28Weak
obesityOpen Targets
0.27Weak
poisoningOpen Targets
0.27Weak
tongue cancerOpen Targets
0.26Weak
bone remodeling diseaseOpen Targets
0.26Weak
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TRA2BProtein interaction100%CLK1Protein interaction97%CLK3Protein interaction97%SRSF3Protein interaction97%U2AF2Protein interaction97%LUC7L3Protein interaction96%
Tissue Expression6 tissues
Brain
100%
Heart
31%
Bone Marrow
26%
Ovary
19%
Lung
19%
Liver
16%
Gene Interaction Network
Click a node to explore
SRPK2TRA2BCLK1CLK3SRSF3U2AF2LUC7L3
PROTEIN STRUCTURE
Preparing viewer…
PDB7ZKX · 2.06 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.35Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.23 [0.16–0.35]
RankingsWhere SRPK2 stands among ~20K protein-coding genes
  • #3,181of 20,598
    Most Researched144 · top quartile
  • #1,518of 17,882
    Most Constrained (LOEUF)0.35 · top 10%
Genes detectedSRPK2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Stress Granules Determine the Development of Obesity-Associated Pancreatic Cancer.
PMID: 35674408
Cancer Discov · 2022
1.00
2
FAM120A couples SREBP-dependent transcription and splicing of lipogenesis enzymes downstream of mTORC1.
PMID: 37595559
Mol Cell · 2023
0.90
3
The BRD4-SRPK2-SRSF2 signal modulates the splicing efficiency of ACSL3 pre-mRNA and influences erastin-induced ferroptosis in osteosarcoma cells.
PMID: 37993451
Cell Death Dis · 2023
0.80
4
Targeting hepatic serine-arginine protein kinase 2 ameliorates alcohol-associated liver disease by alternative splicing control of lipogenesis.
PMID: 37129868
Hepatology · 2023
0.70
5
Cooperation of SRPK2, Numb and p53 in the malignant biology and chemosensitivity of colorectal cancer.
PMID: 31898732
Biosci Rep · 2020
0.60