Vacuolar protein sorting-associated protein 29 (VPS29)
The protein contains 182 amino acids for an estimated molecular weight of 20506 Da.
Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA) (PubMed:15247922, PubMed:21725319, PubMed:23563491). Acts also as component of the retriever complex. The retriever complex is a heterotrimeric complex related to retromer cargo-selective complex (CSC) and essential for retromer-independent retrieval and recycling of numerous cargos such as integrin alpha-5/beta-1 (ITGA5:ITGB1) (PubMed:28892079). In the endosomes, retriever complex drives the retrieval and recycling of NxxY-motif-containing cargo proteins by coupling to SNX17, a cargo (updated: May 8, 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.
- 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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Biological Process
Endocytic recycling
Intracellular protein transport
Retrograde transport, endosome to Golgi
Retrograde transport, endosome to plasma membrane
Viral process
Wnt signaling pathway
The reference OMIM entry for this protein is 606932
Vacuolar protein sorting 29, yeast, homolog of; vps29
Retromer protein
Pep11
Dc7
Dc15
DESCRIPTION
The retromer is a membrane-associated coat complex that functions in the endosomal-to-Golgi retrieval of membrane proteins. The retromer consists of 2 distinct subcomplexes, a cargo-selective subcomplex containing VPS35 (601501), VPS29, and VPS26 (see 605506), and a subcomplex of sorting nexins, SNX1 (601272) and SNX2 (605929), that tubulates the endosomal membrane (summary by Seaman et al., 2009).CLONING
Edgar and Polak (2000) used sequences from S. cerevisiae to search an EST database for homologous human sequences. Sequences obtained from this search were used to develop primers to clone VPS29 by PCR from a human lung cDNA library. The deduced 20.5-kD VPS29 protein is hydrophilic and has a predicted mixed alpha-helix and beta-sheet structure. It has 2 polyadenylation signals and a charged C terminus containing the conserved NPGS amino acid motif. Northern blot analysis detected 2 transcripts of 0.8 and 2 kb corresponding to the 2 polyadenylation signals. The longer transcript was more abundant, showing highest expression in heart, skeletal muscle, and kidney, intermediate expression in brain, colon, and liver, and lowest expression in thymus, spleen, small intestine, placenta, lung, and leukocytes. Edgar and Polak (2000) also cloned mouse Vps29 by PCR from a mouse lung cDNA library. The mouse protein is identical to the human protein except for a C-terminal serine.GENE FUNCTION
Haft et al. (2000) used yeast 2-hybrid assays, mutation analysis, and expression in mammalian cells to define the binding interactions among VPS29 and other human orthologs of yeast vacuolar protein sorting proteins, VPS26, SNX1, and VPS35. Their results are consistent with a model in which VPS29 is bound to VPS35 in a multimeric complex. Haft et al. (2000) identified a discrete domain within VPS35 that interacts with VPS29. Gel filtration chromatography of COS-7 cells showed that both recombinant and endogenous VPS proteins coelute as a 220- to 240-kD complex, and in the absence of VPS35, neither VPS26 nor VPS29 is found in the complex. Seaman et al. (2009) found that the VPS35/VPS29/VPS26 retromer subcomplex interacted with the small GTPase RAB7 (602298) and required RAB7 for recruitment to endosomes. The subcomplex interacted with a GTP-locked RAB7 mutant, but a GDP-locked RAB7 mutant inhibited VPS26 recruitment to endosomal membranes. Knockdown of RAB7 in HeLa cells redistributed VPS26 and VPS35 from membranes to the cytoplasm and reduced the efficiency of endosome-to-Golgi retrieval of membrane proteins. Seaman et al. (2009) also found that the GTPase-activating protein TBC1D5 (615740) caused dissociation of RAB7 from endosomes and inhibited VPS26 recruitment to endosomal membranes.BIOCHEMICAL FEATURES
- Crystal Structure Hierro et al. (2007) reported the crystal structure of a VPS29-VPS35 subcomplex showing how the metallophosphoesterase-fold subunit VPS29 acts as a scaffold for the C-terminal half of VPS35. VPS35 forms a horseshoe-shaped, right-handed, alpha-helical solenoid, the concave face of which completely covers the metal-binding site of VPS29, whereas the convex face exposes a series of hydrophobic interhelical grooves. Electron microscopy showed that the intact VPS26-VPS29-VPS35 complex is a stick-shaped, flexible structure, approximately 21 nanometers long. A hybrid structural model derived from crystal structures, electron microscopy, interaction studies, and bioinformatics showed tha ... More on the omim web site
May 11, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.
Nov. 16, 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 606932 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed