Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Human orthologs of yeast vacuolar protein sorting proteins Vps26, 29, and 35: assembly into multimeric complexes.
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Human VPS35, VPS29, and VPS26 assemble into a cytosolic and membrane-associated multimeric retromer complex.
"We report the cloning and characterization of human orthologs of three additional components of the complex: Vps26p, Vps29p, and Vps35p. ... Furthermore, hVps35, hVps29, and hVps26 have been found in membrane-associated and cytosolic compartments."
Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor.
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Human VPS26, VPS29, and VPS35 localize to tubular domains of early endosomes where CI-MPR is concentrated prior to transport to the TGN.
"In particular, retromer is associated with tubular-vesicular profiles that emanate from early endosomes or from intermediates in the maturation from early to late endosomes."
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RNAi depletion of retromer subunits causes missorting and lysosomal turnover of CI-MPR.
"Depletion of retromer by RNA interference increases the lysosomal turnover of the CI-MPR, decreases cellular levels of lysosomal hydrolases, and causes swelling of lysosomes."
A novel mammalian retromer component, Vps26B.
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Mammalian retromer consists of VPS26A or VPS26B together with VPS29 and VPS35 on endosomal membranes.
"The mammalian retromer protein complex, which consists of three proteins--Vps26, Vps29, and Vps35--in association with members of the sorting nexin family of proteins, has been implicated in the trafficking of receptors and their ligands within the endosomal/lysosomal system of mammalian cells."
The retromer subunit Vps26 has an arrestin fold and binds Vps35 through its C-terminal domain.
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VPS26 adopts an arrestin-like two-lobed beta-sandwich fold and binds the N-terminus of VPS35.
"The structure of human Vps26A at 2.1-A resolution reveals two curved beta-sandwich domains connected by a polar core and a flexible linker. Vps26 has an unpredicted structural relationship to arrestins. The Vps35-binding site on Vps26 maps to a mobile loop spanning residues 235-246, near the tip of the C-terminal domain."
Functional architecture of the retromer cargo-recognition complex.
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The C-terminal alpha-helical solenoid of VPS35 wraps around the metallophosphoesterase fold of VPS29 to form the rigid scaffold of the retromer cargo-recognition complex.
"Here we report the crystal structure of a VPS29-VPS35 subcomplex showing how the metallophosphoesterase-fold subunit VPS29 (refs 14, 15) acts as a scaffold for the carboxy-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."
Wingless secretion requires endosome-to-Golgi retrieval of Wntless/Evi/Sprinter by the retromer complex.
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Loss of retromer causes lysosomal degradation of Wntless and impairs Wnt secretion.
"Following dissociation from Wingless, Wntless is internalized and returns to the Golgi apparatus in a retromer-dependent manner. Without the retromer-dependent recycling route, Wingless secretion is impaired and, as electron microscopy suggests, Wntless is diverted to a degradative compartment."
The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network.
A protein interaction network for Ecm29 links the 26 S proteasome to molecular motors and endosomal components.
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VPS26A localizes to endosomal vesicles.
"Another membrane-associated component identified in similar analyses was Vps26A, which IF images show is present on a subset of Ecm29-positive vesicles"
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VPS26A mediates retrograde transport from endosomes to the TGN.
"Vps26A is a component of the retromer complex that regulates retrograde protein transport from endosomes to the trans -Golgi network on specific clathrin-coated carriers linked to the adaptors AP1 and epsinR"
SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors.
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SNX27 serves as an essential adaptor protein linking beta2-adrenergic receptors to Rab4-positive retromer tubules for endosome-to-plasma-membrane recycling.
"Here we show that sequence-directed sorting occurs at the level of entry into retromer tubules and that retromer tubules are associated with Rab4. Furthermore, we show that sorting nexin 27 (SNX27) serves as an essential adaptor protein linking β2ARs to the retromer tubule."
A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion.
The role of ceroid lipofuscinosis neuronal protein 5 (CLN5) in endosomal sorting.
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Recruitment of the retromer complex to endosomal membranes prevents lysosomal degradation of sortilin and CI-MPR.
"We demonstrate that in CLN5-depleted HeLa cells, the lysosomal sorting receptors sortilin and cation-independent mannose 6-phosphate receptor (CI-MPR) are degraded in lysosomes due to a defect in recruitment of the retromer (an endosome-to-Golgi compartment trafficking component)."
A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport.
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Direct interaction of the SNX27 PDZ domain with the retromer subunit VPS26 is necessary and sufficient to prevent lysosomal degradation and maintain surface recycling of SNX27 cargo.
"Furthermore, we establish that direct interaction of the SNX27 PDZ domain with the retromer subunit VPS26 is necessary and sufficient to prevent lysosomal entry of SNX27 cargo."
The Vps35 D620N mutation linked to Parkinson's disease disrupts the cargo sorting function of retromer.
Pharmacological chaperones stabilize retromer to limit APP processing.
Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation.
A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer.
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An exposed beta-hairpin in the SNX27 PDZ domain binds a groove in the arrestin-like fold of VPS26A, increasing SNX27 affinity for PDZ-binding motifs by an order of magnitude.
"Crystal structures and NMR experiments reveal that an exposed β-hairpin in the SNX27 PDZ domain engages a groove in the arrestin-like structure of the vacuolar protein sorting 26A (VPS26A) retromer subunit. The structure establishes how the SNX27 PDZ domain simultaneously binds PDZ-binding motifs and retromer-associated VPS26. Importantly, VPS26A binding increases the affinity of the SNX27 PDZ domain for PDZ- binding motifs by an order of magnitude, revealing cooperativity in cargo selection."
Retromer Ensures the Degradation of Autophagic Cargo by Maintaining Lysosome Function in Drosophila.
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Loss of retromer function causes accumulation of undigested cargo and autophagic structures in enlarged lysosomes.
"Here we show that the late stages of autophagy and endocytosis are impaired in Vps26 and Vps35 deficient Drosophila larval fat body cells, but formation of autophagosomes and endosomes is not compromised."
Retromer: Structure, function, and roles in mammalian disease.
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Retromer mediates retrograde transport of transmembrane cargo from endosomes to the Golgi.
"Retrograde transport from the endosome to the Golgi is mediated by a 5 protein complex known as the retromer."
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
Parkinson Disease-linked Vps35 R524W Mutation Impairs the Endosomal Association of Retromer and Induces α-Synuclein Aggregation.
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Retromer is a heterotrimeric complex that associates with endosomal membranes and facilitates retrograde receptor sorting, and the Parkinson disease-associated VPS35 R524W variant impairs endosomal retromer association and induces alpha-synuclein aggregation.
"Retromer is a heterotrimeric complex that associates with endosomal membranes and facilitates the retrograde sorting of multiple receptors, including the cation-independent mannose 6-phosphate receptor for lysosomal enzymes."
Structural Mechanism for Cargo Recognition by the Retromer Complex.
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X-ray crystal structure of the VPS26-VPS35-SNX3-DMT1-II complex identifies the canonical recycling signal binding site at the interface between VPS26 and SNX3.
"Here, we present an X-ray crystallographic analysis of a four-component complex comprising the VPS26 and VPS35 subunits of retromer, the sorting nexin SNX3, and a recycling signal from the divalent cation transporter DMT1-II. This analysis identifies a binding site for canonical recycling signals at the interface between VPS26 and SNX3. In addition, the structure highlights a network of cooperative interactions among the VPS subunits, SNX3, and cargo that couple signal-recognition to membrane recruitment."
Architecture of the human interactome defines protein communities and disease networks.
Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling.
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VPS29 is shared between the retromer complex (VPS35-VPS26-VPS29) and the retriever complex (VPS35L-VPS26C-VPS29).
"We have called this complex 'retriever'; it is a heterotrimer composed of DSCR3, C16orf62 and VPS29, and bears striking similarity to retromer."
Endosomal Retrieval of Cargo: Retromer Is Not Alone.
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Retromer is an evolutionarily conserved endosomal coat-like complex essential for retrieval and recycling of hundreds of transmembrane proteins.
"Retromer, an ancient multi-protein complex, is essential for the retrieval and recycling of hundreds of transmembrane proteins."
A reference map of the human binary protein interactome.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
OpenCell: Endogenous tagging for the cartography of human cellular organization.
Structure of the endosomal Commander complex linked to Ritscher-Schinzel syndrome.
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Cryo-EM structure of the Commander complex reveals how VPS29 assembles with VPS35L and VPS26C in Retriever.
"It comprises two sub-assemblies: Retriever composed of VPS35L, VPS26C, and VPS29; and the CCC complex which contains twelve subunits: COMMD1-COMMD10 and the coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93."
Multimodal cell maps as a foundation for structural and functional genomics.
Retromer recycles WLS to the Golgi
Retromer associates with WLS
WLS dissociates from retromer
UniProtKB record for human VPS26A
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VPS26A is an essential component of the retromer cargo-selective complex required for endosome-to-TGN retrieval and SNX27-dependent endocytic recycling.
"Acts as a 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."