Vacuolar protein-sorting-associated protein 36 (VPS36)
The protein contains 386 amino acids for an estimated molecular weight of 43817 Da.
Component of the ESCRT-II complex (endosomal sorting complex required for transport II), which is required for multivesicular body (MVB) formation and sorting of endosomal cargo proteins into MVBs. The MVB pathway mediates delivery of transmembrane proteins into the lumen of the lysosome for degradation. The ESCRT-II complex is probably involved in the recruitment of the ESCRT-III complex. Its ability to bind ubiquitin probably plays a role in endosomal sorting of ubiquitinated cargo proteins by ESCRT complexes. The ESCRT-II complex may also play a role in transcription regulation, possibly via its interaction with ELL. Binds phosphoinosides such as PtdIns(3,4,5)P3. (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.
- 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.
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Biological Process
Endosomal transport
Macroautophagy
Membrane organization
Multivesicular body assembly
Protein transport
Protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
Regulation of transcription, DNA-templated
Transcription, DNA-templated
Cellular Component
Cytosol
Endosome
ESCRT II complex
Extracellular exosome
Late endosome
Late endosome membrane
Lysosome
Membrane
Nucleus
Molecular Function
Phosphatidylinositol-3-phosphate binding
Protein C-terminus binding
Ubiquitin binding
The reference OMIM entry for this protein is 610903
Vacuolar protein sorting 36, s. cerevisiae, homolog of; vps36
Ell-associated protein, 45-kd; eap45
DESCRIPTION
VPS36, VPS22 (SNF8; 610904), and VPS25 (610907) form ESCRT-II (endosomal sorting complex required for transport II), a complex involved in endocytosis of ubiquitinated membrane proteins. VPS36, VPS22, and VPS25 are also associated in a multiprotein complex with RNA polymerase II elongation factor (ELL; 600284) (Slagsvold et al., 2005; Kamura et al., 2001).CLONING
Kamura et al. (2001) purified an Ell-containing complex from rat liver extracts, and by peptide sequencing and database analysis, they identified mouse and human VPS36, which they called EAP45. The deduced 386-amino acid human protein shares 97% identity with mouse Eap45.GENE FUNCTION
Using mouse proteins expressed in mammalian and insect cells, Kamura et al. (2001) found that Eap30 (SNF8) and Eap20 (VPS25) could be coimmunoprecipitated in the absence of Eap45, and that Eap20 and Eap45 could be coimmunoprecipitated in the absence of Eap30. However, little Eap30 was coimmunoprecipitated with Eap45 in the absence of Eap20. Kamura et al. (2001) concluded that EAP20 bridges EAP30 and EAP45 and thereby nucleates assembly of the EAP complex. Slagsvold et al. (2005) found that mouse Eap45 contains a novel N-terminal ubiquitin-binding domain that they called the GLUE (GRAM-like ubiquitin binding in Eap45) domain. The Eap45 GLUE domain shares primary and secondary structures with those of the phosphoinositide-binding GRAM and pleckstrin (PLEK; 173570) homology (PH) domains. Slagsvold et al. (2005) showed that the GLUE domain of Eap45 bound ubiquitin with similar affinity and specificity as other ubiquitin-binding domains. The GLUE domain of Eap45 also bound specifically to phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and more weakly to PtdIns(3,4)P2 and PtdIns(3,5)P2. Eap45 colocalized with ubiquitinated proteins on late endosomes. Slagsvold et al. (2005) concluded that binding of phosphoinositides on endosomal membranes by EAP45 may control the localization and/or activity of EAP45.BIOCHEMICAL FEATURES
Alam et al. (2006) solved the crystal structure of the human EAP45 GLUE domain complexed with ubiquitin. The GLUE domain adopted a PH domain fold, with a 7-stranded beta sandwich capped by a C-terminal alpha helix. The PH domain fold was split by a 16-residue insertion that formed an exposed loop. Ubiquitin bound along one edge of the beta sandwich, and Alam et al. (2006) predicted that phosphoinositides would bind a noncanonical binding site on the other side at the apex of the beta sandwich.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the VPS36 gene to chromosome 13 (TMAP RH183). ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610903 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed