E3 ubiquitin-protein ligase UBR1 (UBR1)
The protein contains 1749 amino acids for an estimated molecular weight of 200211 Da.
E3 ubiquitin-protein ligase which is a component of the N-end rule pathway. Recognizes and binds to proteins bearing specific N-terminal residues that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation. May be involved in pancreatic homeostasis. Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth. (updated: April 1, 2015)
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.
- 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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The reference OMIM entry for this protein is 243800
Johanson-blizzard syndrome; jbs
Nasal alar hypoplasia, hypothyroidism, pancreatic achylia, and congenital deafness
A number sign (#) is used with this entry because the Johanson-Blizzard syndrome (JBS) is caused by homozygous or compound heterozygous mutation in the UBR1 gene (605981) on chromosome 15q.
DESCRIPTION
Johanson-Blizzard syndrome is an autosomal recessive disorder characterized by poor growth, mental retardation, and variable dysmorphic features, including aplasia or hypoplasia of the nasal alae, abnormal hair patterns or scalp defects, and oligodontia. Other features include hypothyroidism, sensorineural hearing loss, imperforate anus, and pancreatic exocrine insufficiency (summary by Al-Dosari et al., 2008).CLINICAL FEATURES
Johanson and Blizzard (1971) and Park et al. (1972) described this syndrome in 3 unrelated girls; features included aplasia or hypoplasia of the nasal alae, congenital deafness, hypothyroidism, postnatal growth retardation, malabsorption, mental retardation, midline ectodermal scalp defects, and absent permanent teeth. Park et al. (1972) described urogenital abnormalities, including double vagina and double uterus. The male proband of Mardini et al. (1978) had aplasia of the alae nasi, scalp defects over the anterior and posterior fontanels, and imperforate anus. Affected brothers were reported by Day and Israel (1978). Flatz et al. (1979) described this disorder in 2 sisters. Daentl et al. (1979) reported a case in a male who died at the age of 8 years from complications of pancreatic exocrine insufficiency. Autopsy showed a small thyroid filled with colloid, almost complete replacement of the pancreas with fat, and abnormal gyral formation and cortical neuronal organization in the brain. Motohashi et al. (1981) reported 2 families; in 1, 2 children (earlier reported by Day and Israel, 1978) were affected and in the second, in addition to the 13-month-old proband, 2 affected sibs had died perinatally. Moeschler and Lubinsky (1985) described affected brother and sister. Reichart et al. (1979) and Helin and Jodal (1981) also reported affected sibs. Normal or near-normal intelligence often seems the case. In a review of JBS by Hurst and Baraitser (1989), it was indicated that 11 of 22 reported children had anorectal abnormalities, most often imperforate anus. Gould et al. (1989) described a family with 2 affected sibs and possibly a third who had died shortly after birth. One of the 2 sibs reported in detail (surprisingly, the sex was not given) died 3 days after birth, colostomy having been performed at age 36 hours for imperforate anus. Autopsy showed, in addition to hypoplasia of alae nasi and frontal and occipital scalp defects, pancreatic ducts and islets surrounded by connective tissue and a total absence of acini. Morphologic changes suggested dysplasia leading to developmental failure, although early acinar destruction could not be ruled out. The second sib, a male born 3 years later, also had the same facies and imperforate anus which was successfully treated surgically. He was treated for pancreatic insufficiency and hypothyroidism, and at age of 10 years performed satisfactorily in a school for the hearing impaired. In the case of the autopsied sib, the thyroid was grossly and microscopically normal with abundant scalloping of colloid. Gershoni-Baruch et al. (1990) described 2 patients. They stated that the girls reported as cases of trypsinogen deficiency (see 276000) by Morris and Fisher (1967) and Townes (1969) had in fact this syndrome, as did a patient with the XXY Klinefelter s ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 243800 was added.