Ubiquitin-fold modifier 1 (UFM1)
The protein contains 85 amino acids for an estimated molecular weight of 9118 Da.
Ubiquitin-like modifier which can be covalently attached via an isopeptide bond to lysine residues of substrate proteins as a monomer or a lysine-linked polymer (PubMed:15071506, PubMed:20018847, PubMed:29868776, PubMed:27653677). The so-called ufmylation, requires the UFM1-activating E1 enzyme UBA5, the UFM1-conjugating E2 enzyme UFC1, and the UFM1-ligase E3 enzyme UFL1 (PubMed:15071506, PubMed:20018847, PubMed:29868776, PubMed:27653677). Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress (PubMed:32160526). Ufmylation of TRIP4 regulates nuclear receptors-mediated transcription (PubMed:25219498). (updated: Aug. 12, 2020)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| HLD14 |
Biological Process
Brain development
Negative regulation of apoptotic process
Negative regulation of protein import into nucleus
Protein K69-linked ufmylation
Protein polyufmylation
Protein ufmylation
Regulation of intracellular estrogen receptor signaling pathway
Response to endoplasmic reticulum stress
Reticulophagy
Molecular Function
The reference OMIM entry for this protein is 610553
Ubiquitin-fold modifier 1; ufm1
DESCRIPTION
UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 (UBE1DC1; 610552) and E2-like conjugating enzyme UFC1 (610554) in a manner analogous to ubiquitylation (see UBE2M; 603173) (Komatsu et al., 2004).CLONING
Using coimmunoprecipitation with FLAG-tagged ubiquitin-like activating enzyme UBE1DC1 expressed in HEK293 cells, Komatsu et al. (2004) purified fragments of proteins physically associated with UBE1DC1. By database analysis with these fragments followed by PCR of human liver cDNA, they cloned UFM1 and UFC1. The deduced 85-amino acid UFM1 protein has a predicted molecular mass of 9.1 kD and shares no overall sequence identity to ubiquitin or other modifiers; however, UFM1 and ubiquitin (UBB; 191339) share highly similar predicted tertiary structures. Western blot analysis of mouse tissues with anti-UFM1 serum detected expression of mouse Ufm1 protein in all tissues examined, including brain, heart, lung, liver, and kidney. Immunocytochemistry of HeLa cells using anti-UFM1 serum showed predominant distribution of UFM1 in the nucleus, with diffuse staining in the cytoplasm. Immunoreactivity within the nucleus localized as dot-like structures that may represent UFM1 conjugates.GENE FUNCTION
Using Myc-tagged UFM1 coexpressed with FLAG-tagged UBE1DC1, FLAG-tagged UFC1, and mutant constructs, as well as in vitro UFM1 conjugation assays, Komatsu et al. (2004) showed that UFM1 is a ubiquitin-like protein that is activated by the E1-like enzyme UBE1DC1 by formation of a thioester bond and conjugated by the E2-like enzyme UFC1 with a similar thioester linkage. Using FLAG- and His-tagged UFM1 constructs in HEK293 followed by purification and analysis of protein complexes formed, Komatsu et al. (2004) showed that UFM1 is conjugated to target proteins in cells by a covalent linkage, possibly via an isopeptide bond between the C-terminal gly83 of UFM1 and a lysine residue in the target protein. ... More on the omim web site
Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 22, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 26, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610553 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed