VPS26A

VPS26A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2FAU
Identifiers
Aliases	VPS26A , HB58, Hbeta58, PEP8A, VPS26, VPS26 retromer complex component A, VPS26, retromer complex component A
External IDs	OMIM: 605506 MGI: 1353654 HomoloGene: 68420 GeneCards: VPS26A
Gene location (Human) Chr. Chromosome 10 (human) [1] Band 10q22.1 Start 69,123,512 bp [1] End 69,174,412 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10|10 B4 Start 62,291,014 bp [2] End 62,322,584 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in parietal pleura parotid gland visceral pleura germinal epithelium endothelial cell cavity of mouth palpebral conjunctiva lower lobe of lung glomerulus gums Top expressed in spermatocyte spermatid seminiferous tubule cumulus cell yolk sac secondary oocyte superior cervical ganglion ileum pyloric antrum hair follicle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Cellular component cytoplasm tubular endosome retromer complex vesicle endosome early endosome membrane lysosome endosome membrane retromer, cargo-selective complex cytosol Biological process protein transport retrograde transport, endosome to Golgi regulation of macroautophagy intracellular protein transport Wnt signaling pathway signal transduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9559 30930 Ensembl ENSG00000122958 ENSMUSG00000020078 UniProt O75436 P40336 RefSeq (mRNA) NM_001035260 NM_004896 NM_001318944 NM_001318945 NM_001318946 NM_001113355 NM_133672 NM_001358543 RefSeq (protein) NP_001030337 NP_001305873 NP_001305874 NP_001305875 NP_004887 NP_001106826 NP_598433 NP_001345472 Location (UCSC) Chr 10: 69.12 – 69.17 Mb Chr 10: 62.29 – 62.32 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Vacuolar protein sorting-associated protein 26A is a protein that in humans is encoded by the VPS26A gene. ^{[5] [6] [7]}

This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. Alternative splicing results in multiple transcript variants encoding different isoforms. ^[7]

Structure

Structural comparison of Vps26 with arrestins

Vps26 is a 38-kDa subunit that has a two-lobed structure with a polar core that resembles the arrestin family of trafficking adaptor. ^{[8] [9]} This fold consist of two related β-sandwich subdomains with a fibronectin type III domain topology. The two domains are joined together by a flexible linker and are closely associated by an unusual polar core. Arrestins are regulatory proteins known for connecting G-protein coupled receptors (GPCRs) to clathrin during endocytosis. They play many critical roles in cell signalling and membrane trafficking. ^[10] Both Vps26 and arrestins are composed of two structurally related β-sheet domains forming extensive interfaces with each other, using polar and electrostatic contacts to create interdomain interactions for ligand binding. However, there are significant structural differences between both Vps26 and arrestins. Vps26 protein has extended C-terminal tails that do not contain identifiable clathrin- or AP2-binding sequences, and therefore cannot form stable intramolecular contacts with clathrin and AP2, which has been observed for arrestins. Moreover, Vps26 does not have similar sequences as arrestins for GPCR and phospholipid interactions. ^[11]

Vps26B paralogue

Structural differences between Vps26A and Vps26B

In yeast, there is only one Vps26 species, whereas there are two Vps26 paralogues (Vps26A and Vps26B) in mammals. ^[12]

X-ray crystallography revealed that the structures of both Vps26A and Vps26B share a similar bilobal β-sandwich structure and possess 70% sequence homology. ^[8] However, these two paralogues distinctly differ on the surface patch within the N-terminal domain, the apex region where the N-terminal and C-terminal domains meet and the disordered C-terminal tail. Vps26B contains several putative serine phosphorylation residues within this disordered tail, which may represent a potential mechanism to modulate the difference between Vps26A and Vps26B. A recent study conducted by Bugarcic et al. pinpointed that this disordered tail on C-terminal region of Vps26B is one of the underlying factors that contributes to the failure for Vps26B-containing Retromer to associate with CI-M6PR, ultimately leading to CI-M6PR degradation, accompanied with increased cathepsin D secretion. ^[13]

References

1. GRCh38: Ensembl release 89: ENSG00000122958 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000020078 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Lee JJ, Radice G, Perkins CP, Costantini F (Aug 1992). "Identification and characterization of a novel, evolutionarily conserved gene disrupted by the murine H beta 58 embryonic lethal transgene insertion". Development. 115 (1): 277–88. doi:10.1242/dev.115.1.277. PMID   1638986.
6. Mao M, Fu G, Wu JS, Zhang QH, Zhou J, Kan LX, Huang QH, He KL, Gu BW, Han ZG, Shen Y, Gu J, Yu YP, Xu SH, Wang YX, Chen SJ, Chen Z (Aug 1998). "Identification of genes expressed in human CD34+ hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning". Proc Natl Acad Sci U S A. 95 (14): 8175–80. Bibcode:1998PNAS...95.8175M. doi: 10.1073/pnas.95.14.8175 . PMC   20949 . PMID   9653160.
7. "Entrez Gene: VPS26A vacuolar protein sorting 26 homolog A (S. pombe)".
8. Collins BM, Norwood SJ, Kerr MC, Mahony D, Seaman MN, Teasdale RD, Owen DJ (March 2008). "Structure of Vps26B and mapping of its interaction with the retromer protein complex". Traffic. 9 (3): 366–79. doi:10.1111/j.1600-0854.2007.00688.x. PMID   18088321. S2CID   37113942.
9. Shi H, Rojas R, Bonifacino JS, Hurley JH (June 2006). "The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain". Nat. Struct. Mol. Biol. 13 (6): 540–8. doi:10.1038/nsmb1103. PMC   1584284 . PMID   16732284.
10. Gurevich VV, Gurevich EV (June 2006). "The structural basis of arrestin-mediated regulation of G-protein-coupled receptors". Pharmacol. Ther. 110 (3): 465–502. doi:10.1016/j.pharmthera.2005.09.008. PMC   2562282 . PMID   16460808.
11. Collins BM (November 2008). "The structure and function of the retromer protein complex". Traffic. 9 (11): 1811–22. doi:10.1111/j.1600-0854.2008.00777.x. PMID   18541005. S2CID   28028098.
12. Kerr MC, Bennetts JS, Simpson F, Thomas EC, Flegg C, Gleeson PA, Wicking C, Teasdale RD (November 2005). "A novel mammalian retromer component, Vps26B". Traffic. 6 (11): 991–1001. doi:10.1111/j.1600-0854.2005.00328.x. PMID   16190980. S2CID   31954489.
13. Bugarcic A, Zhe Y, Kerr MC, Griffin J, Collins BM, Teasdale RD (December 2011). "Vps26A and Vps26B subunits define distinct retromer complexes". Traffic. 12 (12): 1759–73. doi: 10.1111/j.1600-0854.2011.01284.x . PMID   21920005. S2CID   24548200.

Further reading

• Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and Functional Analysis of cDNAs with Open Reading Frames for 300 Previously Undefined Genes Expressed in CD34+ Hematopoietic Stem/Progenitor Cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC   310934 . PMID   11042152.
• Haft CR, de la Luz Sierra M, Bafford R, et al. (2001). "Human Orthologs of Yeast Vacuolar Protein Sorting Proteins Vps26, 29, and 35: Assembly into Multimeric Complexes". Mol. Biol. Cell. 11 (12): 4105–16. doi:10.1091/mbc.11.12.4105. PMC   15060 . PMID   11102511.
• Reddy JV, Seaman MN (2002). "Vps26p, a Component of Retromer, Directs the Interactions of Vps35p in Endosome-to-Golgi Retrieval". Mol. Biol. Cell. 12 (10): 3242–56. doi:10.1091/mbc.12.10.3242. PMC   60170 . PMID   11598206.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
• Deloukas P, Earthrowl ME, Grafham DV, et al. (2004). "The DNA sequence and comparative analysis of human chromosome 10". Nature. 429 (6990): 375–81. Bibcode:2004Natur.429..375D. doi: 10.1038/nature02462 . PMID   15164054.
• Vergés M, Luton F, Gruber C, et al. (2004). "The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor". Nat. Cell Biol. 6 (8): 763–9. doi:10.1038/ncb1153. PMID   15247922. S2CID   22296469.
• Mingot JM, Bohnsack MT, Jäkle U, Görlich D (2005). "Exportin 7 defines a novel general nuclear export pathway". EMBO J. 23 (16): 3227–36. doi:10.1038/sj.emboj.7600338. PMC   514512 . PMID   15282546.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Kerr MC, Bennetts JS, Simpson F, et al. (2006). "A novel mammalian retromer component, Vps26B". Traffic. 6 (11): 991–1001. doi:10.1111/j.1600-0854.2005.00328.x. PMID   16190980. S2CID   31954489.
• Small SA, Kent K, Pierce A, et al. (2006). "Model-guided microarray implicates the retromer complex in Alzheimer's disease". Ann. Neurol. 58 (6): 909–19. doi:10.1002/ana.20667. PMID   16315276. S2CID   34144181.
• Gullapalli A, Wolfe BL, Griffin CT, et al. (2006). "An Essential Role for SNX1 in Lysosomal Sorting of Protease-activated Receptor-1: Evidence for Retromer-, Hrs-, and Tsg101-independent Functions of Sorting Nexins". Mol. Biol. Cell. 17 (3): 1228–38. doi:10.1091/mbc.E05-09-0899. PMC   1382312 . PMID   16407403.
• Shi H, Rojas R, Bonifacino JS, Hurley JH (2006). "The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain". Nat. Struct. Mol. Biol. 13 (6): 540–8. doi:10.1038/nsmb1103. PMC   1584284 . PMID   16732284.
• Riemenschneider M, Schoepfer-Wendels A, Friedrich P, et al. (2007). "No association of vacuolar protein sorting 26 polymorphisms with Alzheimer's disease". Neurobiol. Aging. 28 (6): 883–4. doi:10.1016/j.neurobiolaging.2006.05.009. PMID   16784798. S2CID   20057417.
• Rojas R, Kametaka S, Haft CR, Bonifacino JS (2007). "Interchangeable but Essential Functions of SNX1 and SNX2 in the Association of Retromer with Endosomes and the Trafficking of Mannose 6-Phosphate Receptors". Mol. Cell. Biol. 27 (3): 1112–24. doi:10.1128/MCB.00156-06. PMC   1800681 . PMID   17101778.