Ubiquitin-like modifier-activating enzyme 1 (UBA1)
The protein contains 1058 amino acids for an estimated molecular weight of 117849 Da.
Catalyzes the first step in ubiquitin conjugation to mark cellular proteins for degradation through the ubiquitin-proteasome system (PubMed:1606621, PubMed:1447181). Activates ubiquitin 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 ubiquitin-E1 thioester and free AMP (PubMed:1447181). Essential for the formation of radiation-induced foci, timely DNA repair and for response to replication stress. Promotes the recruitment of TP53BP1 and BRCA1 at DNA damage sites (PubMed:22456334). (updated: Jan. 31, 2018)
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.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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 |
|---|---|
| dbSNP:rs2070169 | |
| SMAX2 | |
| SMAX2 | |
| SMAX2 |
The reference OMIM entry for this protein is 301830
Spinal muscular atrophy, x-linked 2; smax2
Spinal muscular atrophy, x-linked lethal infantile
Spinal muscular atrophy, infantile x-linked; xlsma
Arthrogryposis multiplex congenita, distal, x-linked
Amc, distal, x-linked
Arthrogryposis, x-li
A number sign (#) is used with this entry because of evidence that this X-linked form of infantile X-linked spinal muscular atrophy (SMAX2) is caused by mutations in the UBE1 gene (314370) at Xp11.
DESCRIPTION
X-linked infantile spinal muscular atrophy (XL-SMA) is characterized by neonatal onset of severe hypotonia, areflexia, and multiple congenital contractures, known as arthrogryposis, associated with loss of anterior horn cells and infantile death (summary by Ramser et al., 2008). Historically, Hall et al. (1982) distinguished at least 3 clinical varieties of X-linked arthrogryposis. (1) One family had a severe lethal form with severe contractures, scoliosis, chest deformities, hypotonia, micrognathia, and death from respiratory insufficiency by age 3 months. Apparently progressive loss of anterior horn cells was the cause. (2) Two families had moderately severe AMC associated with ptosis, microphallus, cryptorchidism, inguinal hernias, and normal intelligence. Nonprogressive intrauterine myopathy appeared to be the 'cause'. (3) In 2 families and a sporadic case, the disorder took the form of a resolving AMC, with mild to moderate contractures improving dramatically with time, normal intelligence, and no other anomalies; tight connective tissues on misplaced tendons was postulated.CLINICAL FEATURES
Greenberg et al. (1988) described under the label 'X-linked infantile spinal muscular atrophy' a disorder which appeared to be X-linked and was associated with contractures as in X-linked arthrogryposis. Kobayashi et al. (1995) studied the family originally reported by Greenberg et al. (1988). Affected individuals showed hypotonia, areflexia, chest deformities, facial dysmorphic features, and congenital joint contractures. The findings of electromyography and muscle biopsy were consistent with loss of anterior horn cells as in autosomal recessive infantile spinal muscular atrophy (253300). At the time of the linkage study by Kobayashi et al. (1995), 1 affected male was living at age 13 years, whereas the other affected males died within the first 2 years of life. Baumbach et al. (1994) described an X-linked form of proximal spinal muscular atrophy in 2 unrelated multigeneration families with similar clinical presentations of severe hypotonia, muscle weakness, and a disease course similar to that of Werdnig-Hoffmann disease (253300) except for the additional finding of congenital or early-onset contractures. Muscle biopsy and/or autopsy indicated anterior horn cell loss in affected males. The pedigree pattern in this and 2 additional families was that of an X-linked recessive disorder. Several sporadic male cases were also identified.MAPPING
By linkage studies in 2 families with an X-linked form of proximal spinal muscular atrophy, Baumbach et al. (1994) identified two 16-cM regions on Xp with complete concordance to the disease phenotype. One of these regions surrounded the Kallmann gene (KAL1; 300836). The remainder of the X chromosome was excluded, including the locus for the Kennedy type of spinal and bulbar muscular atrophy (SMAX1; 313200). Kobayashi et al. (1995) demonstrated linkage of the disorder in the family reported by Greenberg et al. (1988) to markers in the region of the centromere of the X chromosome: Xp11.3-q11.2. Dressman et al. (2007) studied 7 new families with new markers and narrowed the gene interval for the XLSMA locus on Xp11.3-q11.1.MOLECULAR GENETICS
To identify the ... More on the omim web site
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 301830 was added.