UFM1

UFM1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1WXS, 5HKH
Identifiers
Aliases	UFM1, BM-002, C13orf20, ubiquitin-fold modifier 1, ubiquitin fold modifier 1, HLD14
External IDs	OMIM: 610553; MGI: 1915140; HomoloGene: 9594; GeneCards: UFM1; OMA:UFM1 - orthologs
Gene location (Human)
Chr.	Chromosome 13 (human)
End	38,363,619 bp
Gene location (Mouse)
Chr.	Chromosome 3 (mouse)
End	53,771,251 bp
RNA expression pattern
	Top expressed in
	corpus epididymis; ; Epithelium of choroid plexus; ; caput epididymis; ; seminal vesicula; ; internal globus pallidus; ; tail of epididymis; ; body of pancreas; ; Achilles tendon; ; endometrium; ; sperm;
	Top expressed in
	right kidney; ; ventricular zone; ; embryo; ; embryo; ; yolk sac; ; lip; ; morula; ; muscle of thigh; ; superior frontal gyrus; ; cardiac muscle tissue of left ventricle;
	More reference expression data
	n/a
Gene ontology
Molecular function	protein binding;
Cellular component	cytoplasm; nucleus; endoplasmic reticulum;
Biological process	regulation of intracellular estrogen receptor signaling pathway; protein K69-linked ufmylation; response to endoplasmic reticulum stress; protein ufmylation; negative regulation of apoptotic process; brain development;
	Sources:Amigo / QuickGO
Orthologs
	51569
	67890
	ENSG00000120686
	ENSMUSG00000027746
	P61960
	P61961
	NM_001286703; NM_001286704; NM_001286705; NM_001286706; NM_016617
	NM_026435
	NP_001273632; NP_001273633; NP_001273634; NP_001273635; NP_057701
	NP_080711
	Wikidata
View/Edit Human	View/Edit Mouse

Ubiquitin-fold modifier 1, also known as UFM1, is a protein which in humans is encoded by the UFM1 gene.^[5]^[6]

UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 and E2-like conjugating enzyme UFC1.^[6] This process is often referred to as UFMylation.^[7]

Function

UFM1 shares several common properties with ubiquitin (Ub) and the other ubiquitin-like proteins (UBLs). Ufm1 has similar tertiary structure to Ub but lacks any obvious sequence similarity. It is synthesized as an inactive precursor form (pro-Ufm1) which has 2 additional amino acids beyond the conserved glycine. The mechanism of Ufm1 conjugation is similar to that of ubiquitin. Mature Ufm1 has an exposed C-terminal glycine which is essential for subsequent activation by its cognate E1 protein (Uba5). This activation step results in the formation of a high-energy thiolester bond in the presence of ATP. The Ufm1 is subsequently transferred to its cognate E2-like enzyme (Ufc1) via a similar thioester linkage with a cysteine at the E2 active site. Ufm1 is conjugated to a variety of target proteins and forms complexes with as yet unidentified proteins. Thus, presumably there exist E3 ligases (none have been identified to date) to perform the final step in Ufm1 conjugation to relevant targets. The modification of proteins with Ufm1 is also reversible. Two novel cysteine proteases have been identified to date (UFSP1 and UFSP2) which cleave Ufm1-peptide C-terminal fusions and also removes Ufm1 from native intracellular conjugates. These proteases have no obvious homology to ubiquitin deconjugating enzymes. The proteins for Ufm1 conjugation (Uba5, Ufc1 and Ufm1) are all conserved in animals and plants (but not yeast) suggesting important roles in multicellular organisms. The exact role of Ufm1 modification in vivo is not yet known,^[8] but the primary target appear to be uL24/RPL26 in human cells.^[7]