UFL1

Description

The UFL1 (UFM1 specific ligase 1) is a protein-coding gene located on chromosome 6.

UFL1, also known as E3 UFM1-protein ligase 1 or E3 UFM1-protein transferase 1, is a key regulator of various cellular processes, including ribosome recycling, DNA damage response, interferon signaling, and reticulophagy (ER-phagy). It acts as an E3 ligase, mediating the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins. UFL1 plays a critical role in reticulophagy, a selective degradation of the endoplasmic reticulum (ER) in response to ER stress. During ER stress, UFL1 is recruited to the ER membrane by DDRGK1, where it ufmylates proteins such as RPN1 and RPL26/uL24, promoting the lysosomal degradation of ER sheets. This ufmylation-dependent reticulophagy effectively inhibits the unfolded protein response (UPR) via ERN1/IRE1-alpha. UFL1's role in ER stress response is crucial for processes like hematopoiesis, blood vessel morphogenesis, and inflammatory responses. Additionally, UFL1 regulates inflammation by promoting reticulophagy, which inhibits the activity of the NF-kappa-B transcription factor. Furthermore, UFL1 mediates ufmylation of DDRGK1 and CDK5RAP3, though the precise function of these modifications is not fully understood. UFL1 also participates in the response to DNA damage by being recruited to double-strand break sites and mediating monoufmylation of histone H4. UFL1 catalyzes ufmylation of various ribosomal subunits and associated components, including RPS3/uS3, RPS20/uS10, RPL10/uL16, RPL26/uL24, and EIF6. Moreover, UFL1 anchors CDK5RAP3 in the cytoplasm, preventing its nuclear translocation and ensuring the expression of the CCND1 cyclin, thereby facilitating cell cycle progression through the G1/S transition. UFL1 is essential for hematopoietic stem cell function, hematopoiesis, and cardiac homeostasis.

UFL1 is also known as KIAA0776, Maxer, NLBP, RCAD.

Associated Diseases

WES Whole Exome Sequencing