Ubiquitin-like modifier-activating enzyme 5 (UBA5)
The protein contains 404 amino acids for an estimated molecular weight of 44863 Da.
E1-like enzyme which specifically catalyzes the first step in ufmylation (PubMed:15071506, PubMed:18442052, PubMed:25219498, PubMed:20368332, PubMed:27653677, PubMed:26929408, PubMed:27545674, PubMed:30412706, PubMed:27545681). Activates UFM1 by first adenylating its C-terminal glycine residue with ATP, and thereafter linking this residue to the side chain of a cysteine residue in E1, yielding a UFM1-E1 thioester and free AMP (PubMed:20368332, PubMed:27653677, PubMed:26929408, PubMed:30412706). Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts with distinct sites in both subunits of the UBA5 homodimer (PubMed:27653677). Trans-binding also promotes stabilization of the UBA5 homodimer, and enhances ATP-binding (PubMed:29295865). Transfer of UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a trans mechanism (PubMed:27653677). Ufmylation is involved in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress (PubMed:32160526). Ufmylation is essential for erythroid differentiation of both megakaryocytes and erythrocytes (By similarity). (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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
Biological Process
Erythrocyte differentiation
Megakaryocyte differentiation
Neuromuscular process
Protein K69-linked ufmylation
Protein modification by small protein conjugation
Protein polyufmylation
Protein ufmylation
Regulation of intracellular estrogen receptor signaling pathway
Response to endoplasmic reticulum stress
Reticulophagy
The reference OMIM entry for this protein is 610552
Ubiquitin-activating enzyme e1 domain-containing 1; ube1dc1
Uba5
DESCRIPTION
UBE1DC1 is an E1-like activating enzyme for ubiquitin-fold modifier-1 (UFM1; 610553) (Komatsu et al., 2004).CLONING
Using yeast 2-hybrid analysis with GATE16 (GABARAPL2; 607452), a human homolog of yeast Atg8p, as bait, followed by PCR of human liver cDNA, Komatsu et al. (2004) cloned UBE1DC1, which they called UBA5. The deduced 404-amino acid protein shares similarity with members of the E1-like enzyme family of ubiquitin-like posttranslational modifiers. Using large-scale cDNA sequencing of human fetal brain cDNAs, Dou et al. (2005) cloned UBE1DC1. The deduced protein has a predicted molecular mass of 43.9 kD and contains a conserved ThiF domain with a nearby cysteine residue similar to ubiquitin activating enzyme E1C (UBE1C; 603172). RT-PCR analysis detected highest UBE1DC1 expression in spleen, high expression in most other tissues examined, and low expression in colon, prostate, brain, and ovary.GENE FUNCTION
Using immunoprecipitation of intermediates formed from FLAG-tagged UBE1DC1 and mutant constructs coexpressed with Myc-tagged UFM1 in HEK293 cells as well as an in vitro UFM1 conjugation assay, Komatsu et al. (2004) showed that UBE1DC1 is a UFM1-activating enzyme with the active site at cys250.GENE STRUCTURE
Dou et al. (2005) determined that the UBE1DC1 gene contains 12 exons and spans 17.4 kb.MAPPING
By genomic sequence analysis, Dou et al. (2005) mapped the UBE1DC1 gene to chromosome 3q22. ... More on the omim web site
Aug. 24, 2020: 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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610552 was added.
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed