UFM1
Encyclopedia
Ubiquitin-fold modifier 1, also known as UFM1, is a protein
which in humans is encoded by the UFM1 gene
.
UFM1 is a ubiquitin
-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 (UBE1DC1
) and E2-like conjugating enzyme UFC1 (see UBE2M
).
(Ub) and other ubiquitin-like molecules (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 protease
s 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.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
which in humans is encoded by the UFM1 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
UFM1 is a ubiquitin
Ubiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 (UBE1DC1
UBE1DC1
Ubiquitin-like modifier-activating enzyme 5 is a protein that in humans is encoded by the UBA5 gene.-Further reading:...
) and E2-like conjugating enzyme UFC1 (see UBE2M
UBE2M
NEDD8-conjugating enzyme Ubc12 is a protein that in humans is encoded by the UBE2M gene.-Interactions:UBE2M has been shown to interact with NEDD8, PRKAR1A and UBA3.-Further reading:...
).
Function
UFM1 shares several common properties with ubiquitinUbiquitin
Ubiquitin is a small regulatory protein that has been found in almost all tissues of eukaryotic organisms. Among other functions, it directs protein recycling.Ubiquitin can be attached to proteins and label them for destruction...
(Ub) and other ubiquitin-like molecules (UBLs). Ufm1 has similar tertiary structure
Tertiary structure
In biochemistry and molecular biology, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates.-Relationship to primary structure:...
to Ub but lacks any obvious sequence similarity
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...
. 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
Bioconjugation
Bioconjugation is the process of coupling two biomolecules together in a covalent linkage. Common types of bioconjugation chemistry are amine coupling of lysine amino acid residues , sulfhydryl coupling of cysteine residues , and photochemically initiated free radical reactions, which have broader...
is similar to that of ubiquitin. Mature Ufm1 has an exposed C-terminal glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
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
Thioester
Thioesters are compounds with the functional group C-S-CO-C. They are the product of esterification between a carboxylic acid and a thiol. Thioesters are widespread in biochemistry, the best-known derivative being acetyl-CoA.-Synthesis:...
linkage with a cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
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 protease
Cysteine protease
Proteases are enzymes that degrade polypeptides. Cysteine proteases have a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic dyad. The first step is deprotonation of a thiol in the enzyme's active site by an adjacent amino acid with a basic side chain, usually a...
s 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.