Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
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
Gene Ontology annotation based on curation of intracellular localizations of expressed fusion proteins in living cells
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."
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."
The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network.
The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics.
The Vps35 D620N mutation linked to Parkinson's disease disrupts the cargo sorting function of retromer.
A mechanism for retromer endosomal coat complex assembly with cargo.
TBC1D5 and the AP2 complex regulate ATG9 trafficking and initiation of autophagy.
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Although TBC1D5 binds the retromer subunit VPS29 on endosomes, TBC1D5 and the clathrin adaptor AP2 complex regulate the rerouting of ATG9-containing vesicular carriers toward sites of autophagosome formation via association with ATG9 and the active ULK1 complex.
"The RabGAP protein TBC1D5 controls cellular endomembrane trafficking processes and binds the retromer subunit VPS29 and the ubiquitin-like protein ATG8 (LC3). Here, we describe that TBC1D5 also associates with ATG9 and the active ULK1 complex during autophagy. Moreover, ATG9 and TBC1D5 interact with clathrin and the AP2 complex. ... Taken together, our data show that TBC1D5 and the AP2 complex are important novel regulators of the rerouting of ATG9-containing vesicular carriers toward sites of autophagosome formation."
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 proteome-scale map of the human interactome network.
A massively parallel pipeline to clone DNA variants and examine molecular phenotypes of human disease mutations.
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."
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."
Extensive disruption of protein interactions by genetic variants across the allele frequency spectrum in human populations.
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
Commander Complex-A Multifaceted Operator in Intracellular Signaling and Cargo.
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Retromer and retriever orchestrate endosomal retrieval and recycling of transmembrane cargoes away from lysosomal degradation.
"Commander complex is a 16-protein complex that plays multiple roles in various intracellular events in endosomal cargo and in the regulation of cell homeostasis, cell cycle and immune response. It consists of COMMD1-10, CCDC22, CCDC93, DENND10, VPS26C, VPS29, and VPS35L."
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
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."
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."
UniProtKB record for human VPS29
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VPS29 is a shared scaffolding subunit of both the retromer cargo-selective complex and the retriever complex.
"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."
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VPS29 localizes to the cytoplasm and endosome membrane as a peripheral membrane protein.
"SUBCELLULAR LOCATION: Cytoplasm. Membrane; Peripheral membrane protein. Endosome membrane {ECO:0000250|UniProtKB:Q9QZ88}; Peripheral membrane protein {ECO:0000250|UniProtKB:Q9QZ88}. Early endosome {ECO:0000305}. Late endosome {ECO:0000305}."
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VPS29 lacks metallophosphoesterase catalytic activity and binds metals with very low affinity that is not required for its scaffolding function.
"CAUTION: Was originally believed to be a metal-dependent phosphatase but shown to lack catalytic activity; can bind metals with very low affinity suggesting that metal binding is not required for its function."