Vacuolar protein sorting-associated protein 45 (VPS45)
The protein contains 570 amino acids for an estimated molecular weight of 65077 Da.
May play a role in vesicle-mediated protein trafficking from the Golgi stack through the trans-Golgi network. (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.
- 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.
- 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.
Biological Process
Blood coagulation
Intracellular protein transport
Vesicle docking involved in exocytosis
Vesicle-mediated transport
Cellular Component
Endosome membrane
Golgi apparatus
Golgi membrane
Integral component of membrane
Synaptic vesicle
Molecular Function
The reference OMIM entry for this protein is 610035
Vacuolar protein sorting 45, yeast, homolog of, a; vps45a
Vps45
DESCRIPTION
The VPS45 gene encodes a protein associated with cellular membranes that functions in protein trafficking and the release of inflammatory mediators, particularly in leukocytes (summary by Vilboux et al., 2013).CLONING
By PCR, Pevsner et al. (1996) cloned human VPS45A from a brain cDNA library. The deduced 570-amino acid protein has a calculated molecular mass of 65 kD and shares 38% identity with yeast Vps45. Northern blot analysis detected a 2.3-kb transcript in all tissues examined. Highest expression was in testis, with progressively lower levels in brain, kidney, lung, skeletal muscle, spleen, and liver. Rajasekariah et al. (1999) cloned VPS45A from a human leukocyte cDNA library. The deduced 570-amino acid protein has a calculated molecular mass of 67 kD. VPS45A contains a potential N-glycosylation site, an amidation site close to the C terminus, 2 potential N-myristoylation sites, and several consensus phosphorylation sites. Northern blot analysis detected abundant expression in heart, spleen, and testis. Expression was moderate to low in all other tissues examined except lung and liver, in which expression was very low. RT-PCR revealed high VPS45A expression in peripheral blood mononuclear cells and neutrophils, but no expression in human hepatoma and breast cancer cell lines.MAPPING
By FISH, Rajasekariah et al. (1999) mapped the VPS45A gene to chromosome 1q21-q22.MOLECULAR GENETICS
In affected children from 4 consanguineous Palestinian families with severe congenital neutropenia-5 (SCN5; 615285), Vilboux et al. (2013) identified a homozygous mutation in the VPS45 gene (T224N; 610035.0001). The mutation, which was found by homozygosity mapping and whole-exome sequencing, segregated with the disorder in the families and was not found in several exome databases or in 250 ethnically matched controls. Patient neutrophils showed impaired neutrophil chemotaxis, impaired superoxide production, impaired migration, decreased beta-1 integrin (ITGB1; 135630) expression, and decreased levels of the VPS45-interacting proteins rabenosyn-5 (ZFYVE20; 609511) and syntaxin-16 (STX16; 603666). Mutant fibroblasts and bone marrow cells also showed increased apoptosis compared to controls. Many of these defects were corrected by transfection of wildtype VPS45. Stepensky et al. (2013) identified a homozygous T224N mutation in 3 patients from 2 consanguineous Palestinian families with SCN5. The mutation was found by whole-exome sequencing and confirmed by Sanger sequencing. It segregated with the disorder in the family and was not found in 120 Palestinian control individuals or in the Exome Variant Server. Analysis of the mutation in the yeast ortholog showed that it caused a decrease in cellular levels of the protein (about 50% compared to control), suggesting that it destabilizes the protein and abrogates its function in the endosomal pathway. Patient cells showed severely decreased levels of mutant VPS45 protein, decreased numbers of lysosomes, and decreased alpha-granules in platelets. Patient neutrophils and bone marrow myeloid cells showed accelerated apoptosis.ANIMAL MODEL
Vilboux et al. (2013) found that morpholino knock-out of the Vps45 gene in zebrafish resulted in decreased numbers of neutrophils. ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610035 was added.