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
Gene location (Human) Chr. Chromosome 13 (human) [1] Band 13q13.3 Start 38,349,849 bp [1] End 38,363,619 bp [1]
Gene location (Mouse) Chr. Chromosome 3 (mouse) [2] Band 3|3 C Start 53,760,797 bp [2] End 53,771,251 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in corpus epididymis caput epididymis seminal vesicula internal globus pallidus body of pancreas Achilles tendon endometrium sperm synovial joint subthalamic nucleus Top expressed in yolk sac lip morula superior frontal gyrus proximal tubule neural tube cerebellar cortex thymus duodenum corneal stroma More reference expression data BioGPS 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 Species Human Mouse Entrez 51569 67890 Ensembl ENSG00000120686 ENSMUSG00000027746 UniProt P61960 P61961 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 Mb Chr 3: 53.76 – 53.77 Mb PubMed search [3] [4]
Wikidata
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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]

References

1. GRCh38: Ensembl release 89: ENSG00000120686 - Ensembl, May 2017
2. 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. 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. 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. 116 (4): 1299–1308. doi: 10.1073/pnas.1816202116 . ISSN   0027-8424. PMC   6347690 . PMID   30626644.
8. "Boston Biochem UFM1 overview". Archived from the original on October 15, 2007. Retrieved 2008-05-21.

Further reading

• Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and Functional Analysis of cDNAs with Open Reading Frames for 300 Previously Undefined Genes Expressed in CD34+ Hematopoietic Stem/Progenitor Cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC   310934 . PMID   11042152.
• Yu Y, Zhang C, Zhou G, et al. (2001). "Gene Expression Profiling in Human Fetal Liver and Identification of Tissue- and Developmental-Stage-Specific Genes through Compiled Expression Profiles and Efficient Cloning of Full-Length cDNAs". Genome Res. 11 (8): 1392–403. doi:10.1101/gr.175501. PMC   311073 . PMID   11483580.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Dunham A, Matthews LH, Burton J, et al. (2004). "The DNA sequence and analysis of human chromosome 13". Nature. 428 (6982): 522–8. Bibcode:2004Natur.428..522D. doi:10.1038/nature02379. PMC   2665288 . PMID   15057823.
• Komatsu M, Chiba T, Tatsumi K, et al. (2005). "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.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Sasakawa H, Sakata E, Yamaguchi Y, et al. (2006). "Solution structure and dynamics of Ufm1, a ubiquitin-fold modifier 1". Biochem. Biophys. Res. Commun. 343 (1): 21–6. doi:10.1016/j.bbrc.2006.02.107. PMID   16527251.
• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein–protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.

External links

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