Proteasome adapter and scaffold protein ECM29 (ECM29)
The protein contains 1845 amino acids for an estimated molecular weight of 204291 Da.
Adapter/scaffolding protein that binds to the 26S proteasome, motor proteins and other compartment specific proteins. May couple the proteasome to different compartments including endosome, endoplasmic reticulum and centrosome. May play a role in ERAD and other enhanced proteolysis (PubMed:15496406). Promotes proteasome dissociation under oxidative stress (By similarity). (updated: Nov. 13, 2019)
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.
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:rs16916091 |
Cellular Component
Centrosome
COPII-coated ER to Golgi transport vesicle
Cytoplasmic vesicle
Cytoplasmic, membrane-bounded vesicle
Early endosome
Endocytic vesicle
Endoplasmic reticulum
Endoplasmic reticulum-Golgi intermediate compartment
Late endosome
Membrane
Multivesicular body
Nucleoplasm
Nucleus
Proteasome complex
The reference OMIM entry for this protein is 616694
Kiaa0368 gene; kiaa0368
Ecm29, yeast, homolog of; ecm29
DESCRIPTION
KIAA0368 encodes a 200-kD HEAT repeat adaptor protein that binds the 26S proteasome (see 602706) (Gorbea et al., 2010).CLONING
By screening for large proteins expressed in brain, Nagase et al. (1997) cloned KIAA0368, which encodes a predicted 1,441-amino acid protein. RT-PCR analysis detected expression in all human tissues examined, with highest levels in ovary and brain, followed by prostate, thymus, testis, skeletal muscle, and kidney. By database analysis, Gorbea et al. (2004) obtained full-length KIAA0368, which they named ECM29, after its yeast homolog. The predicted 1,839-amino acid protein contains an N-terminal bipartite nuclear targeting signal, at least 23 HEAT motifs throughout its sequence, a central Vps27/HGS (604375)/STAM (601899) (VHS)-like domain, and 2 potential helical regions with homology to beta-adaptin (see 600157) N termini that the authors called HANT domains. Gorbea et al. (2004) also identified 2 additional alternative sequences for the ECM29 N terminus. Western blot analysis detected a 205-kD ECM29 protein in HeLa cells. Ecm29 protein expression was high in mouse testis and brain, low in liver, and almost undetectable in heart and kidney. ECM29 associated with the 26S proteasome in HeLa cells. Immunofluorescence analysis, confocal microscopy, and computational analysis demonstrated that ECM29 localized to centrosomes, nuclei, endoplasmic reticulum (ER), and ER-Golgi intermediate compartments of HeLa cells.GENE FUNCTION
Using genomewide 2-hybrid screens and mass spectrometric analysis, Gorbea et al. (2010) showed that the C terminus of ECM29 bound myosins (see 160730) and kinesins (see 602809), whereas the N terminus bound the endocytic proteins VPS11 (608549), RAB11FIP4 (611999), and rabaptin (RABEP1; 603616). Full-length ECM29, the ECM29 C-terminal half, and a small central region of ECM29, but not the EMC29 N-terminal half, bound 26S proteasomes. Confocal microscopy showed that ECM29-26S proteasomes were present on flotillin (FLOT1; 606998)-positive endosomes, but not clathrin (see 118960)- or caveolin (CAV1; 601047)-decorated endosomes. Gorbea et al. (2010) proposed that ECM29 serves as an adaptor for coupling 26S proteasomes to specific cellular compartments. Using RNA interference, Gorbea et al. (2013) showed that depletion of ECM29 in human cells led to increased TLR3 (603029)-dependent signaling with increased abundance of TRAF3 (601896), increased nuclear localization of IRF3 (603734), and inhibition of autophagy. They proposed that ECM29-26S proteasomes play a role in mediating autophagy, trafficking of TLR3, and attenuation of TLR3-dependent signaling.MAPPING
By radiation hybrid analysis, Nagase et al. (1997) mapped the KIAA0368 gene to chromosome 9. Gross (2015) mapped the KIAA0368 gene to chromosome 9q31.3 based on an alignment of the KIAA0368 sequence (GenBank GENBANK BC021127) with the genomic sequence (GRCh38). ... More on the omim web site
Dec. 2, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
April 12, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616694 was added.
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 25, 2017: Additional information
No protein expression data in P. Mayeux work for ECM29