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

UFM1
Protein UFM1 PDB 1j0g.png
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesUFM1, BM-002, C13orf20, ubiquitin-fold modifier 1, ubiquitin fold modifier 1, HLD14
External IDsOMIM: 610553 MGI: 1915140 HomoloGene: 9594 GeneCards: UFM1
Gene location (Human)
Chromosome 13 (human)
Chr.Chromosome 13 (human)[1]
Chromosome 13 (human)
Genomic location for UFM1
Genomic location for UFM1
Band13q13.3Start38,349,849 bp[1]
End38,363,619 bp[1]
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001286703
NM_001286704
NM_001286705
NM_001286706
NM_016617

NM_026435

RefSeq (protein)

NP_001273632
NP_001273633
NP_001273634
NP_001273635
NP_057701

NP_080711

Location (UCSC)Chr 13: 38.35 – 38.36 MbChr 3: 53.85 – 53.86 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

FunctionEdit

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]

ReferencesEdit

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000120686 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000027746 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: UFM1 ubiquitin-fold modifier 1".
  6. ^ a b Komatsu M, Chiba T, Tatsumi K, Iemura S, Tanida I, Okazaki N, Ueno T, Kominami E, Natsume T, Tanaka K (May 2004). "A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier". EMBO J. 23 (9): 1977–86. doi:10.1038/sj.emboj.7600205. PMC 404325. PMID 15071506.
  7. ^ a b Walczak, Christopher P.; Leto, Dara E.; Zhang, Lichao; Riepe, Celeste; Muller, Ryan Y.; DaRosa, Paul A.; Ingolia, Nicholas T.; Elias, Joshua E.; Kopito, Ron R. (2019-01-09). "Ribosomal protein RPL26 is the principal target of UFMylation". Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. 116 (4): 1299–1308. doi:10.1073/pnas.1816202116. ISSN 0027-8424.
  8. ^ "Boston Biochem UFM1 overview". Archived from the original on October 15, 2007. Retrieved 2008-05-21.

Further readingEdit

External linksEdit

  • Overview of all the structural information available in the PDB for UniProt: P61960 (Human Ubiquitin-fold modifier 1) at the PDBe-KB.