UCKL1

UCKL1 Full Name

uridine-cytidine kinase 1-like 1

UCKL1 Introduction

UCKL1 is a ~30 kDa enzyme related to the uridine-cytidine kinases (UCKs) that catalyze the first phosphorylation step of the pyrimidine salvage pathway, converting uridine and cytidine to UMP and CMP using ATP. Although long considered only a predicted kinase, recombinant UCKL1 was shown to phosphorylate both uridine and cytidine, with catalytic efficiencies of ~1.2 × 10^4 and ~0.7 × 10^4 M^-1 s^-1, respectively, confirming it as a bona fide nucleoside kinase. Its high sequence similarity to UCK1 and UCK2 places UCKL1 within the pyrimidine nucleotide–salvage network that sustains the nucleotide pools needed for proliferation, yet its activity is more modest than that of the canonical UCKs. UCKL1 also interacts with other proteins, including Epstein–Barr virus nuclear antigen 3, linking it to viral biology.

Figure 1. Salvage pathway for pyrimidine synthesis. (Source: Walter M, et al. 2022)

UCKL1 has attracted interest for its role in tumor cell survival and immune evasion. It is upregulated in tumor cells, where it protects them from natural killer (NK) cell–mediated lysis and from apoptosis. Downregulation of UCKL1 in lymphoma and leukemia models reduces proliferation, increases apoptosis, and diminishes tumor growth and metastasis in vivo, indicating that the protein actively promotes tumor fitness. The immune-evasion function is tied to the E3 ubiquitin ligase NKLAM, which ubiquitinates UCKL1 and lowers its levels, sensitizing tumor cells to killing. Elevated UCKL1 expression has also been noted in hepatocellular carcinoma arising in cirrhotic hepatitis C patients, suggesting a disease association. More recently, UCKL1 has been implicated in ferroptosis defense in colorectal cancer, pointing to non-canonical roles beyond nucleotide salvage. Because UCKL1 simultaneously supports nucleotide supply and blunts immune killing, it represents an attractive yet challenging therapeutic node where inhibition could compromise both tumor metabolism and immune evasion. These findings position UCKL1 as both a metabolic enzyme and a candidate target for weakening tumor resistance.

Alternate Names for UCKL1

UCKL1; uridine-cytidine kinase 1-like 1; uridine kinase like 1; URKL1; uridine-cytidine kinase-like 1; FLJ20517; uridine kinase-like 1; UCK1L; URKL1; UCK1-LIKE;

• 1. Walter M, et al. Re-Discovery of Pyrimidine Salvage as Target in Cancer Therapy. Cells. 2022 Feb 20;11(4):739.
  2. Matchett EC, et al. Characterization of uridine-cytidine kinase like-1 nucleoside kinase activity and its role in tumor growth. Biochem J. 2022 Jun 17;479(11):1149-1164.