Proteasomal ubiquitin receptor ADRM1 (ADRM1)
The protein contains 407 amino acids for an estimated molecular weight of 42153 Da.
Component of the 26S proteasome, a multiprotein complex involved in the ATP-dependent degradation of ubiquitinated proteins. This complex plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins, which could impair cellular functions, and by removing proteins whose functions are no longer required. Therefore, the proteasome participates in numerous cellular processes, including cell cycle progression, apoptosis, or DNA damage repair. Within the complex, functions as a proteasomal ubiquitin receptor. Engages and activates 19S-associated deubiquitinases UCHL5 and PSMD14 during protein degradation. UCHL5 reversibly associate with the 19S regulatory particle whereas PSMD14 is an intrinsic subunit of the proteasome lid subcomplex. (updated: Nov. 22, 2017)
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.
This protein is annotated as membranous in Gene Ontology.
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Biological Process
Positive regulation of endopeptidase activity
Proteasome assembly
Protein deubiquitination
Transcription elongation from RNA polymerase II promoter
Ubiquitin-dependent protein catabolic process
Cellular Component
Cytoplasm
Cytosol
Integral component of plasma membrane
Membrane
Nucleoplasm
Plasma membrane
Proteasome complex
Proteasome regulatory particle, lid subcomplex
Molecular Function
Endopeptidase activator activity
Protease binding
Proteasome binding
Ubiquitin binding
The reference OMIM entry for this protein is 610650
Adhesion-regulating molecule 1; adrm1
Arm1
Rpn13, s. cerevisiae, homolog of; rpn13
DESCRIPTION
Ubiquitination targets proteins for degradation by the 26S proteasome. The 26S proteasome contains a 20S catalytic core particle (see 602175) capped at either or both ends by 19S regulatory particles, which prepare substrates for hydrolysis in the core region. ADRM1 is a component of the regulatory particle that functions as a polyubiquitin receptor and captures substrates by recognizing their covalently attached ubiquitin chains (Zhang et al., 2009).CLONING
Shimada et al. (1994) identified ADRM1 as a 110-kD antigen that cross-reacted with 2 different anti-CEA (CEACAM5; 114890) monoclonal antibodies and was upregulated following gamma-interferon (IFNG; 147570) treatment in human gastric cancer cell lines. By immunoscreening IFNG-treated GaCa gastric cancer cells, Shimada et al. (1994) obtained a full-length cDNA encoding ADRM1. The 5-prime end of the cDNA is GC rich. The deduced 407-amino acid ADRM1 protein has a calculated molecular mass of 41.2 kD. It has a putative N-terminal signal sequence, a potential C-terminal transmembrane region, and numerous sites for O- and N-glycosylation. Northern blot analysis detected a 1.5-kb ADRM1 transcript in GaCa cells. Simins et al. (1999) cloned mouse Adrm1, which they called Arm1. The deduced 407-amino acid mouse protein shares 96% identity with the human protein. Northern blot analysis detected expression of Arm1 in all mouse tissues examined. Using semiquantitative RT-PCR, Lamerant and Kieda (2005) detected ARM1 expression in human and mouse endothelial cell lines from various tissues, but not in human skin microvascular endothelial cells. ARM1 expression was also detected in mouse and human lymphocyte cell lines. In transfected COS cells, ARM1 was expressed predominantly as a 50-kD protein and more weakly as a 42-kD protein. Epitope-tagged ARM1 was expressed in the cytoplasm and beneath the plasma membrane of human skin microvascular endothelial cells, but it was not expressed on the cell surface. ARM1 was also secreted into the culture medium. Deglycosylation experiments indicated that ARM1 is not a glycoprotein. By SDS-PAGE of HeLa cell extracts, Jorgensen et al. (2006) found that endogenous ADRM1 had an apparent molecular mass of 42 kD. Western blot analysis detected Adrm1 at a similar molecular mass in all mouse tissues examined.GENE FUNCTION
Using Northern and Western blot analyses, Shimada et al. (1994) showed that IFNG treatment increased both ADRM1 mRNA and protein expression in GaCa cells. Simins et al. (1999) found that expression of mouse Arm1 in transfected 293T cells substantially increased their adhesion to endothelial cells. Increased adhesion was not due to altered expression or activity of integrins in 293T cells. Lamerant and Kieda (2005) found that human T cells, natural killer lymphocytes, and primary peripheral leukocytes showed increased adhesion to human skin endothelial cells overexpressing ARM1. Since ARM1 is not expressed on the cell surface, they proposed that it has an indirect role in cell-cell adhesion. By immunoprecipitation and protein pull-down assays, Jorgensen et al. (2006) found that ADRM1 was present almost exclusively in soluble 26S proteasomes in HeLa cells, although a small fraction was membrane associated. HeLa cells did not contain a pool of free ADRM1, but recombinant ADRM1 could bind preexisting 26S proteasomes in cell extracts. Knockdown of ADRM1 in HeLa cells had no apparent effect on the amount of pro ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
Nov. 23, 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 610650 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed