UBA5
Description
The UBA5 (ubiquitin like modifier activating enzyme 5) is a protein-coding gene located on chromosome 3.
UBA5 is a human gene that encodes a protein belonging to the E1-like activating enzyme family. This protein is involved in the process of ufmylation. Two different isoforms of this protein are generated through alternative splicing.
UBA5 is an E1-like enzyme that catalyzes the first step in ufmylation, a process involved in various cellular functions, including ribosome recycling, response to DNA damage, interferon response, and reticulophagy. It activates UFM1 by adenylating its C-terminal glycine residue with ATP and then linking this residue to the side chain of a cysteine residue in UBA5, forming a UFM1-UBA5 thioester and free AMP. This activation occurs via a trans-binding mechanism, where UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer. This trans-binding also promotes stabilization of the UBA5 homodimer and enhances ATP-binding. The transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also occurs through a trans mechanism. Ufmylation plays a role in reticulophagy induced by endoplasmic reticulum stress and is essential for erythroid differentiation of megakaryocytes and erythrocytes.
UBA5 is also known as DEE44, EIEE44, SCAR24, THIFP1, UBE1DC1.
Associated Diseases
- Developmental and epileptic encephalopathy 44
- Non-specific early-onset epileptic encephalopathy
- Spinocerebellar ataxia, autosomal recessive 24
