Ubiquitin-fold modifier-conjugating enzyme 1

UFC1 (ubiquitin-fold modifier-conjugating enzyme 1) is an E2-like enzyme that catalyzes the conjugation of the ubiquitin-like modifier UFM1 to target proteins. The enzyme accepts UFM1 from the E1 enzyme UBA5 and forms a thioester intermediate, playing a central role in the ufmylation pathway, which regulates diverse cellular processes including ribosome recycling, DNA damage response, interferon signaling, and reticulophagy (UniProt: Q9Y3C8).

UFC1 is implicated in neurodevelopmental disease; biallelic UFC1 mutations cause neurodevelopmental disorder with spasticity and poor growth (NEDSG; MIM 618076), an autosomal recessive condition characterized by hypotonia, psychomotor delay, growth failure, and spasticity (UniProt: Q9Y3C8). The protein's role in cellular stress responses and protein quality control suggests broader relevance to neurological function.

In Alzheimer's disease, UFC1 is upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.55 across measured subcellular fractions in TMT-labeled proteomics (Chaparral AD proteomics). This increased expression may reflect enhanced ufmylation signaling as part of the AD pathological response.