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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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UCK2
uridine-cytidine kinase 2
Chromosome 1 · 1q24.1
NCBI Gene: 7371Ensembl: ENSG00000143179.16HGNC: HGNC:12562UniProt: A0A2R8Y653
89PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cytidine kinase activityCTP salvageidentical protein bindingUMP salvageneurodegenerative diseaseTesticular Germ Cell Tumorpreeclampsiachondromalacia
✦AI Summary

UCK2 (uridine-cytidine kinase 2) is a pyrimidine salvage pathway enzyme that phosphorylates uridine and cytidine to their monophosphate forms, utilizing ATP or GTP as phosphate donors 12. The enzyme also phosphorylates various nucleoside analogs including 5-fluorouridine and 5-fluorocytidine 1, making it relevant for antiviral and anticancer therapy. UCK2 functions as a rate-limiting enzyme in pyrimidine salvage 3. mTORC1 regulates UCK2 protein stability through the CTLH-WDR26 E3 ligase complex 3, while GART protects UCK2 stability under glucose limitation via AMPK-mediated signaling 4. Notably, UCK2 exhibits non-canonical, metabolism-independent functions: it forms a complex with UCKL1 that acts as a molecular scaffold to regulate TGF-β signaling in cardiac fibrosis 5. Clinically, UCK2 is significantly upregulated in hepatocellular carcinoma (HCC) and bladder cancer, correlating with poor prognosis, advanced tumor stage, and immunotherapy response 67. UCK2 modulates immune microenvironments through M2-macrophage polarization in HCC 6 and regulates PI3K/AKT/mTOR signaling in bladder cancer 7. These findings position UCK2 as a potential therapeutic target for metabolic reprogramming in cancer.

Sources cited
1
UCK2 phosphorylates uridine and cytidine to monophosphate forms and phosphorylates various nucleoside analogs
PMID: 11306702
2
UCK2 phosphorylates uridine and cytidine to their monophosphate forms
PMID: 11494055
3
mTORC1 controls UCK2 protein stability through CTLH-WDR26 E3 ligase-mediated degradation
PMID: 39808525
4
GART protects UCK2 protein stability under glucose limitation via AMPK signaling and prevents Trim21-mediated degradation
PMID: 39865175
5
UCK2/UCKL1 complex acts as a molecular scaffold to regulate TGF-β signaling and cardiac fibrosis through TRIM21/Smurf2/Smad3 pathway
PMID: 41457201
6
UCK2 is upregulated in HCC, correlates with poor prognosis, and regulates M2-macrophage polarization in tumor microenvironment
PMID: 38896142
7
UCK2 is upregulated in bladder cancer, correlates with poor prognosis and immunotherapy response, and regulates PI3K/AKT/mTOR signaling
PMID: 40542213
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.44Moderate
Testicular Germ Cell TumorOpen Targets
0.37Weak
preeclampsiaOpen Targets
0.32Weak
chondromalaciaOpen Targets
0.31Weak
liver diseaseOpen Targets
0.29Weak
arterial disorderOpen Targets
0.29Weak
capillary disorderOpen Targets
0.29Weak
ArthropathyOpen Targets
0.27Weak
neuroinflammatory disorderOpen Targets
0.27Weak
brain compressionOpen Targets
0.25Weak
edemaOpen Targets
0.24Weak
hepatocellular carcinomaOpen Targets
0.11Weak
neoplasmOpen Targets
0.11Weak
cancerOpen Targets
0.09Suggestive
gastric cancerOpen Targets
0.09Suggestive
lung cancerOpen Targets
0.08Suggestive
glaucomaOpen Targets
0.08Suggestive
Abruptio PlacentaeOpen Targets
0.08Suggestive
breast cancerOpen Targets
0.08Suggestive
melanomaOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
UPP2Protein interaction98%UPP1Protein interaction98%ENTPD1Protein interaction98%ENTPD6Protein interaction98%ENTPD3Protein interaction98%ENTPD5Protein interaction98%
Tissue Expression6 tissues
Brain
100%
Lung
62%
Liver
56%
Bone Marrow
56%
Heart
50%
Ovary
45%
Gene Interaction Network
Click a node to explore
UCK2UPP2UPP1ENTPD1ENTPD6ENTPD3ENTPD5
PROTEIN STRUCTURE
Preparing viewer…
PDB1UJ2 · 1.80 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.42Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.21 [0.12–0.42]
RankingsWhere UCK2 stands among ~20K protein-coding genes
  • #5,391of 20,598
    Most Researched89
  • #2,224of 17,882
    Most Constrained (LOEUF)0.42 · top quartile
Genes detectedUCK2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Integrating machine learning and molecular docking to decipher the molecular network of aflatoxin B1-induced hepatocellular carcinoma.
PMID: 40392001
Int J Surg · 2025
1.00
2
PMID: 20641989
0.90
3
Immune- and metabolism-related gene signature analysis uncovers the prognostic and immune microenvironments of hepatocellular carcinoma.
PMID: 38896142
J Cancer Res Clin Oncol · 2024
0.80
4
mTORC1 regulates the pyrimidine salvage pathway by controlling UCK2 turnover via the CTLH-WDR26 E3 ligase.
PMID: 39808525
Cell Rep · 2025
0.70
5
The protection of UCK2 protein stability by GART maintains pyrimidine salvage synthesis for HCC growth under glucose limitation.
PMID: 39865175
Oncogene · 2025
0.60