Affinage

SNX27

Sorting nexin-27 · UniProt Q96L92

Length
541 aa
Mass
61.3 kDa
Annotated
2026-06-10
56 papers in source corpus 41 papers cited in narrative 42 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNX27 is an endosomal sorting nexin that functions as a cargo-selective adaptor coupling PDZ-binding-motif (PBM)-containing transmembrane proteins to the retromer complex for endosome-to-plasma-membrane recycling, preventing their default lysosomal degradation (PMID:20733053, PMID:23563491). Its modular architecture integrates three activities: a PX domain that binds PtdIns(3)P to target early endosomes (PMID:21300787), a PDZ domain that recognizes C-terminal PBMs on cargo, and a FERM domain that engages the retromer and downstream coat machinery (PMID:34866035, PMID:35417450). The PDZ domain directly binds the retromer subunit VPS26A through an exposed β-hairpin, and this interaction reciprocally enhances PDZ affinity for cargo PBMs by an order of magnitude, embedding cooperativity into cargo selection (PMID:25136126); engagement is further tuned by acidic residues upstream of the PBM whose function can be substituted by regulated phosphorylation, creating a phospho-switch for cargo capture (PMID:27595347). Through these interactions SNX27 recycles over 100 surface proteins, including nutrient and ion transporters (GLUT1, ASCT2/SLC1A5, DRA/SLC26A3), signaling receptors (β2-adrenoreceptor, NMDA receptor, GPR17), and adhesion/junction proteins (PMID:23563491, PMID:29563155, PMID:32116023). The SNX27 FERM domain organizes a hierarchical endosomal coat by binding aDLF/DxF motifs in the SNX1/SNX2 subunits of ESCPE-1 — handing cargo into tubular transport carriers — and analogous aDLF motifs in FAM21 of the WASH complex, with VARP bridging the SNX27–Retromer–ESCPE-1 assembly into a reconstitutable supercomplex that remodels PI(3)P membranes into cargo-laden tubules (PMID:34866035, PMID:35417450, PMID:39116126, PMID:39937906). Recycling output is controlled by post-translational and competitive regulation: stress-activated MAPK11/14 (p38) directly phosphorylate SNX27 at Ser51 to reshape the cargo-binding pocket and redirect cargo to lysosomes (PMID:33605979), while PTEN and OTULIN competitively bind the SNX27 PDZ/FERM surfaces to block VPS26A association and cargo loading (PMID:29117568, PMID:31541095). Beyond housekeeping recycling, SNX27 shapes physiology in neurons, where PI(3)P-driven recruitment supports synaptic cargo recycling during LTP (PMID:40920104), and is exploited by viruses including SARS-CoV-2, whose spike and ACE2 engage the SNX27 PDZ domain to influence endocytic entry and surface expression (PMID:35022217, PMID:34909756).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2004 Medium

    Established SNX27 as a PDZ-domain protein capable of binding a specific GPCR splice variant and directing it to endosomes, the first hint of an endosomal sorting role.

    Evidence Peptide-affinity chromatography, mass spectrometry and localization imaging of the 5-HT4(a) receptor

    PMID:15466885

    Open questions at the time
    • No retromer link or recycling function defined
    • Mechanism of endosomal targeting unaddressed
  2. 2011 High

    Defined the two-domain logic of SNX27 sorting — PX-domain PtdIns(3)P binding for endosome targeting and PDZ-domain recognition of cargo PBMs — and showed it is required for recycling of β2AR and NMDA receptor cargo to the surface.

    Evidence Knockdown/knockout, subcellular fractionation, domain mutagenesis and endocytosis/recycling assays for β2AR and NR2C

    PMID:20733053 PMID:21300787 PMID:21602791

    Open questions at the time
    • Molecular basis of retromer coupling not yet resolved
    • Cargo repertoire unknown
  3. 2013 High

    Generalized SNX27 from a few-receptor adaptor to a master recycling hub for >100 cargo and showed that direct PDZ–VPS26 binding is necessary and sufficient to divert cargo away from lysosomes.

    Evidence Quantitative interactome and surface proteomics with domain-mutant rescue in SNX27/retromer-depleted cells

    PMID:23563491

    Open questions at the time
    • Structural basis of PDZ–VPS26 cooperativity not yet defined
    • How tubular carriers form downstream unresolved
  4. 2014 High

    Provided the structural mechanism by which retromer enhances cargo capture: VPS26A binds an exposed PDZ β-hairpin and allosterically increases PDZ affinity for cargo PBMs, establishing cooperative cargo selection.

    Evidence X-ray crystallography, NMR, ITC/SPR and cell-based sorting assays of the SNX27 PDZ–VPS26A complex

    PMID:25136126

    Open questions at the time
    • Did not address FERM-domain partner interactions
    • Regulation of the allosteric switch not examined
  5. 2016 High

    Identified an acidic/phosphorylation code upstream of the PBM that controls high-affinity PDZ engagement, defining a phospho-regulated switch for cargo selection.

    Evidence Crystallography, NMR, ITC and phosphopeptide binding with cell-based trafficking assays

    PMID:27595347

    Open questions at the time
    • Kinases generating the relevant phosphorylations on cargo not all identified
    • In vivo prevalence of the switch unquantified
  6. 2016 High

    Linked SNX27 to actin-based endosomal sorting machinery by showing direct PDZ-domain binding to FAM21 of the WASH complex controls SNX27 subdomain localization and PI4P levels to prevent Golgi mis-sorting.

    Evidence Co-IP, siRNA knockdown, localization imaging and lipid measurement

    PMID:26956659

    Open questions at the time
    • Structural basis of FAM21 binding not resolved at this stage
    • PDZ vs FERM contribution to FAM21 binding not disentangled
  7. 2018 High

    Demonstrated that SNX27 loss redirects nutrient transporter cargo to lysosomes with downstream metabolic consequences, connecting recycling to mTORC1 signaling and autophagy.

    Evidence CRISPR KO with surface biotinylation, glutamine uptake, mTORC1 and autophagy readouts for ASCT2/SLC1A5

    PMID:29563155

    Open questions at the time
    • Whether other transporters share this metabolic coupling not established
    • Tissue-level metabolic phenotype not addressed
  8. 2018 Medium

    Established post-translational and competitive regulation of SNX27: PKA-driven PDZ phosphorylation (cholera toxin) and phosphatase-independent PTEN binding both block VPS26 association and cargo recycling.

    Evidence Phospho-mutagenesis, Co-IP, surface biotinylation and trafficking/uptake assays (NHE3, GLUT1)

    PMID:29117568 PMID:30030371

    Open questions at the time
    • Physiological signals controlling PTEN–SNX27 competition unclear
    • Phospho-site identity in cholera-toxin model not crystallographically resolved
  9. 2019 High

    Revealed dual-mode competitive inhibition by OTULIN, which uses both its PBM and a second OTU–PDZ interface to occupy the cargo-binding site and antagonize cargo loading without affecting catalysis.

    Evidence X-ray crystallography, Co-IP, mass spectrometry and surface trafficking assays

    PMID:31541095

    Open questions at the time
    • Cellular trigger that shifts OTULIN between competitor and cargo not defined here
  10. 2021 High

    Identified the master stress switch on SNX27 itself: p38 MAPK (MAPK11/14) directly phosphorylates Ser51 to reshape the cargo-binding pocket, globally suppressing recycling and promoting lysosomal degradation under stress.

    Evidence In vitro kinase assay, phospho-site mutagenesis, Co-IP and cargo recycling/conformational analysis

    PMID:33605979

    Open questions at the time
    • Which cargo subsets are most sensitive to Ser51 phosphorylation not resolved
    • Phosphatase reversing Ser51 unidentified
  11. 2021 Medium

    Expanded the coat to include VARP as a retromer-interacting partner with cargo-specific roles, foreshadowing a higher-order assembly.

    Evidence Quantitative proteomics, Co-IP and siRNA knockdown with trafficking assays

    PMID:25278552

    Open questions at the time
    • Direct SNX27–VARP contact not yet defined at this stage
  12. 2022 High

    Resolved the FERM-domain handover mechanism: SNX27 directly binds aDLF/DxF motifs in SNX1/SNX2 of ESCPE-1, transferring captured cargo into tubular carriers, an assembly tracing to early metazoan evolution.

    Evidence Biochemical reconstitution, structural analysis, mutagenesis, ITC and cellular trafficking with evolutionary analysis

    PMID:34866035 PMID:35417450

    Open questions at the time
    • Stoichiometry of the cargo handover in carriers not fully defined
  13. 2024 High

    Showed FAM21 uses aDLF motifs analogous to ESCPE-1 to bind the SNX27 FERM domain and contacts Retromer at three sites, molecularly unifying WASH–SNX27–Retromer coupling.

    Evidence Crystallography, AlphaFold modeling, mutagenesis, Co-IP and cellular trafficking

    PMID:39116126

    Open questions at the time
    • Why VPS35-site mutation only partially reduces WASH association unresolved
  14. 2025 High

    Reconstituted the full endosomal coat in vitro, demonstrating VARP directly binds SNX27 and is required to assemble the SNX27–Retromer–ESCPE-1 supercomplex, with SNX27/Retromer alone remodeling PI(3)P membranes carrying PBM cargo into tubules.

    Evidence Reconstitution with purified proteins, liposome tubulation, AlphaFold modeling, Co-IP and ITC

    PMID:39937906

    Open questions at the time
    • Native regulation and disassembly of the supercomplex in cells not addressed
    • Cryo-EM structure of the assembled coat absent
  15. 2025 High

    Placed SNX27 recycling in neuronal plasticity, showing PI(3)P synthesis during LTP recruits SNX27-Retromer to synapses to drive cargo recycling and spine enlargement in parallel with SNX17-Retriever.

    Evidence Live imaging with PI(3)P biosensor, knockdown, spine morphometry and LTP recordings in hippocampal neurons/slices

    PMID:40920104

    Open questions at the time
    • Identity of the LTP-relevant SNX27 cargo set not fully enumerated
    • PI 3-kinase driving synaptic PI(3)P synthesis not pinned down

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs (Ser51 phosphorylation, PTEN and OTULIN competition, cargo-PBM phosphorylation, PI(3)P dynamics) are integrated in real time to set cargo-specific recycling versus degradation outcomes remains unresolved.
  • No unified model coupling stress kinase signaling to coat assembly state
  • In vivo phenotypic dissection of individual regulatory arms incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3 GO:0060090 molecular adaptor activity 3 GO:0008289 lipid binding 2
Localization
GO:0005768 endosome 3 GO:0005886 plasma membrane 2 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-9609507 Protein localization 3 R-HSA-162582 Signal Transduction 2
Partners
FAM21MAPK14OTULINPTENSNX1SNX2VARPVPS26A
Complex memberships
Retromer (VPS26-VPS35-VPS29)SNX27-Retromer-ESCPE-1 supercomplexWASH complex (via FAM21)

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2010 SNX27 is required for efficient PDZ-directed recycling of the β2-adrenoreceptor (β2AR) from early endosomes to the plasma membrane. This recycling activity requires both PDZ domain-dependent recognition of the β2AR cytoplasmic tail and PX domain-dependent association with the endosome membrane. Endogenous expression knockdown, domain mutagenesis, subcellular fractionation, live-cell imaging The Journal of cell biology High 20733053
2011 SNX27 serves as an essential adaptor protein linking β2ARs to the retromer tubule, enabling endosome-to-plasma membrane trafficking. SNX27 interacts with the retromer-associated WASH complex and mediates entry of β2ARs into Rab4-associated retromer tubules. shRNA knockdown, Co-IP, fluorescence microscopy, receptor recycling assays Nature cell biology High 21602791
2011 SNX27 is primarily targeted to the early endosome by interaction of its PX domain with PtdIns(3)P. SNX27 interacts with NMDA receptor 2C (NR2C) via its PDZ domain and the C-terminal PDZ-binding motif of NR2C, and its absence impairs NR2C endocytosis/endosomal sorting. Knockout mouse, subcellular fractionation, Co-IP, endocytosis assay Molecular and cellular biology High 21300787
2013 SNX27 promotes recycling of over 100 cell-surface transmembrane proteins (including GLUT1, ATP7A, zinc/amino acid transporters, and signaling receptors) from endosomes to the plasma membrane by linking PDZ-dependent cargo recognition to the retromer complex. Direct interaction of the SNX27 PDZ domain with the retromer subunit VPS26 is necessary and sufficient to prevent lysosomal entry of SNX27 cargo. Quantitative proteomics of SNX27 interactome, quantitative surface proteomics of SNX27/retromer-depleted cells, domain mutant rescue experiments Nature cell biology High 23563491
2013 SNX27 PDZ domain interacts with the C-terminal PDZ-binding motif of ZO-2. Upon tight junction disruption, ZO-2 transiently localizes to SNX27-positive early endosomes. SNX27 depletion reduces ZO-2 mobility at cell-cell contacts and increases junctional permeability to large solutes. Proteomic pulldown, Co-IP, live FRAP imaging, epithelial permeability assay, siRNA knockdown The Biochemical journal Medium 23826934
2014 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 VPS26A. VPS26A binding increases the affinity of the SNX27 PDZ domain for PDZ-binding motifs by an order of magnitude, demonstrating cooperativity in cargo selection. X-ray crystallography, NMR, biophysical binding assays (ITC/SPR), functional cell-based cargo sorting assays Proceedings of the National Academy of Sciences of the United States of America High 25136126
2014 Quantitative proteomics of the VPS35 retromer interactome confirmed functional heterogeneity in SNX27-retromer-mediated endosome-to-plasma membrane sorting; suppression of the retromer-associated WASH complex did not uniformly affect retromer/SNX27 cargo, indicating cargo-specific functions for retromer-interacting proteins. Quantitative proteomics (SILAC), siRNA knockdown, trafficking assays Journal of cell science Medium 25278552
2015 SNX27 directly interacts with FAM21, a subunit of the WASH complex, via its PDZ domain. This interaction is required for precise localization of SNX27 at an endosomal subdomain and for efficient recycling of SNX27-retromer cargoes to the plasma membrane. FAM21 prevents cargo transport to the Golgi by controlling phosphatidylinositol 4-phosphate levels. Co-IP, siRNA knockdown, subcellular localization imaging, lipid measurement Nature communications High 26956659
2015 The SNX27 FERM domain contains a phosphoinositide-binding site preferring bi- and tri-phosphorylated phosphoinositides. Perturbing this site alters SNX27 distribution between endosomal recycling compartments and PtdIns(3,4,5)P3-enriched plasma membrane domains during immunological synapse formation in activated T-cells. Biophysical binding assays, mutagenesis, live-cell fluorescence imaging, phosphoinositide pulldown Journal of cell science High 25472716
2015 VPS26A-SNX27 interaction mediates mGluR5 recycling in dorsal horn neurons. Spinal nerve ligation enhanced VPS26A-SNX27 coprecipitation and increased mGluR5 membrane abundance; focal knockdown of VPS26A or SNX27 attenuated mGluR5 membrane insertion and behavioral allodynia. Co-IP, siRNA knockdown in vivo, immunofluorescence, behavioral pain assay The Journal of neuroscience Medium 26538661
2016 Specific acidic amino acid sequences upstream of the PDZ-binding motif are required for high-affinity engagement of the SNX27 PDZ domain. A subset of SNX27 ligands (β2AR, NMDA receptor) use conserved phosphorylation sites that substitute for acidic residues to enhance SNX27 binding, suggesting a phosphorylation-regulated switch for PDZ interaction and protein transport. Crystal structure, NMR, ITC binding assays, phosphopeptide binding studies, mutagenesis, cell-based trafficking assays Nature structural & molecular biology High 27595347
2016 SNX27 interacts with SORLA via the SORLA cytosolic tail to form a ternary complex with APP. SNX27 enhances cell-surface SORLA and APP levels, and depletion of SNX27 or SORLA reduces APP endosome-to-cell surface recycling kinetics. SNX27 overexpression enhances non-amyloidogenic APP surface cleavage products in a SORLA-dependent manner. Co-IP, siRNA knockdown, surface biotinylation, recycling kinetics assay, APP cleavage product quantification The Journal of neuroscience Medium 27466343
2016 SNX27 binds parathyroid hormone receptor (PTHR) via a PDZ domain-PDZ-binding motif interaction at endosomes. Mass spectrometry identified SNX27 in isolated endosomes as a PTHR binding partner. Depletion of SNX27 or VPS35 or actin depolymerization decreased the rate of PTHR recycling. PTHR can also engage retromer directly through VPS26, forming a ternary PTHR/SNX27/retromer complex. Mass spectrometry, Co-IP, molecular dynamics, protein binding assays, siRNA knockdown, receptor recycling assay The Journal of biological chemistry Medium 27008860
2016 SNX27 deficiency in mice results in reductions in ependymal cells and cilia density and severe postnatal hydrocephalus. SNX27 knockout leads to Notch hyperactivation, and inhibition of Notch intracellular domain signaling with γ-secretase inhibitors reversed ependymal cell/cilia loss and ventricular dilation, indicating SNX27 promotes ependymal cell differentiation and ciliogenesis by suppressing γ-secretase-dependent Notch signaling. SNX27 knockout mouse, γ-secretase inhibitor rescue, immunohistochemistry, cilia density quantification The Journal of neuroscience Medium 27974614
2017 PTEN physically interacts with SNX27, and this interaction (phosphatase-independent) blocks the association of SNX27 with VPS26, thereby preventing SNX27-retromer assembly and impairing GLUT1 recycling from endosomes to the plasma membrane. Co-IP, siRNA knockdown, glucose uptake assay, surface biotinylation, somatic mutant analysis Cell reports Medium 29117568
2017 SNX27 limits TCR-stimulated DAG-based signals in T lymphocytes by recycling DGKζ (diacylglycerol kinase ζ) via a PDZ-domain interaction. SNX27 silencing enhanced AP-1 and NF-κB transcription, while DGKζ silencing did not increase transcription, suggesting DGKζ function is SNX27-dependent. siRNA silencing, transcription reporter assays, Co-IP, Snx27-/- mouse analysis Scientific reports Medium 29180720
2018 SNX27 directly interacts with the PDZ-binding motif of ASCT2 (glutamine transporter SLC1A5) via its PDZ domain. CRISPR-mediated SNX27 KO causes ASCT2 missorting to lysosomes, reducing surface ASCT2, glutamine uptake, and mTORC1 activation, while enhancing autophagy. CRISPR KO, subcellular fractionation, surface biotinylation, glutamine uptake assay, mTORC1 signaling assay The Journal of biological chemistry High 29563155
2018 Cholera toxin causes PKA-dependent phosphorylation of an amino acid in the SNX27 PDZ domain, inhibiting SNX27-mediated trafficking of NHE3 from early endosomes to the plasma membrane. Mutagenesis (Ser to Asp) phenocopied loss of SNX27 function. Cholera toxin also destabilizes retromer. These effects can be partially rescued by pharmacological chaperones that enhance retromer stability. Phospho-mutagenesis, siRNA knockdown, surface biotinylation, NHE3 activity assay, pharmacological rescue Journal of cell science Medium 30030371
2019 OTULIN's C-terminal PDZ-binding motif (PDZbm) binds the cargo-binding site in the SNX27 PDZ domain. A second interface between the OTULIN OTU domain and SNX27 PDZ domain contributes to high-affinity interaction (revealed by crystal structure). OTULIN does not affect SNX27's catalytic function but antagonizes SNX27-dependent cargo loading, VPS26A binding, and endosome-to-plasma membrane trafficking. X-ray crystallography, Co-IP, mass spectrometry, siRNA knockdown, surface trafficking assay Nature communications High 31541095
2019 SNX27-mediated recycling of neuroligin-2 requires direct interaction between the SNX27 PDZ domain and the PDZ-binding motif in neuroligin-2. SNX27 knockdown reduces surface neuroligin-2, decreasing inhibitory synapse clustering and signaling strength; overexpression has the opposite effect. Co-IP, siRNA knockdown, live-cell imaging, electrophysiology, immunofluorescence Cell reports Medium 31775031
2020 SNX27 and retromer directly interact with MT1-MMP (ITC-based binding studies) and selectively recycle MT1-MMP (but not MT2-MMP) to invadopodia in metastatic breast cancer cells. SNX27 depletion reduces matrix degradation activity. ITC binding assay, siRNA knockdown, matrix degradation assay, Co-IP, colocalization imaging The Journal of cell biology Medium 31820782
2020 SNX27 regulates DRA (SLC26A3) activity and recycling via a direct PDZ domain-PDZ-binding motif interaction. SNX27 knockdown reduced DRA activity by 50% without decreasing DRA surface expression, indicating SNX27 directs DRA to active lipid raft domains. SNX27 and DRA colocalize in Rab5-positive early endosomes at the apical pole of intestinal cells. siRNA knockdown, PDZ domain interaction assay, DRA activity assay (chloride flux), superresolution microscopy, subcellular colocalization American journal of physiology. Gastrointestinal and liver physiology Medium 32116023
2021 MAPK11/14 (p38 kinases), activated by multiple extracellular stressors (starvation, LPS, IL-6, EGF), directly phosphorylate SNX27 at serine 51. This phosphorylation alters the conformation of the SNX27 cargo-binding pocket and decreases SNX27-cargo interactions, thereby inhibiting endocytic recycling and promoting lysosomal degradation of cargo. In vitro kinase assay, phospho-site mutagenesis, Co-IP, cargo recycling assay, structural/conformational analysis The Journal of cell biology High 33605979
2021 SNX27 interacts with VARP (VPS9-ankyrin repeat protein/ANKRD27) as a new retromer-interacting protein. VARP depletion causes differential trafficking defects of retromer cargo, suggesting cargo-specific roles within the SNX27-retromer pathway. Quantitative proteomics, Co-IP, siRNA knockdown, trafficking assays Journal of cell science Medium 25278552
2021 SNX27 inhibits TNFα-induced NF-κB signaling activation by facilitating OTULIN localization to the TNF receptor complex at the membrane. SNX27-retromer translocation is required for this membrane targeting; chemical inhibition of SNX27-retromer (by cholera toxin) blocks OTULIN membrane localization. Co-IP, siRNA knockdown, NF-κB reporter assay, fractionation, cholera toxin inhibition Cell & bioscience Medium 34315543
2021 AQP4 is a cargo of the SNX27-retromer complex. Kidins220 deficiency causes downregulation of SNX27-retromer, resulting in AQP4 lysosomal degradation. SNX27 silencing decreases AQP4 levels; SNX27 overexpression restores AQP4 content in Kidins220-deficient astrocytes. siRNA knockdown, SNX27 overexpression, lysosomal degradation assay, Co-IP, immunofluorescence, conditional KO mouse Molecular psychiatry Medium 34002021
2021 The SNX27 FERM domain directly binds the flexible SNX1/SNX2 N-terminus through acidic-DxF motifs. Forty residues containing two DxF motifs in the SNX1 N-terminus are sufficient for SNX27 binding (KD ~10 µM by ITC). Mutation of either DxF sequence abrogates binding. Pulldown with purified proteins, ITC calorimetry, mutagenesis, sequence alignment Advances in biological regulation High 34866035
2022 SNX27 directly interacts with ACE2 via the ACE2 PDZ-binding motif and the SNX27 PDZ domain (complex structure determined). SNX27-retromer prevents ACE2/SARS-CoV-2 virus complex from entering lysosomes/late endosomes, thereby decreasing viral endocytic entry in cells where the endocytic pathway dominates. Crystal structure, functional viral infection assay, siRNA knockdown, surface trafficking assay Proceedings of the National Academy of Sciences of the United States of America High 35022217
2022 The SNX27 FERM domain directly binds acidic-Asp-Leu-Phe (aDLF) motifs in the SNX1/SNX2 subunits of ESCPE-1, establishing a 'handover' model where SNX27-Retromer-captured cargo proteins are transferred into ESCPE-1 transport carriers for endosome-to-plasma membrane recycling. This assembly of SNX27:Retromer:ESCPE-1 evolved in a stepwise manner during early metazoan evolution. Biochemical reconstitution, structural analysis, mutagenesis, cellular trafficking assays, evolutionary analysis PLoS biology High 35417450
2022 SNX27 interacts with TANC2 via its PDZ domain; in the absence of HPV-18 E6, SNX27 directs TANC2 toward lysosomal degradation. HPV-18 E6 inhibits SNX27-TANC2 interaction in a PBM-dependent manner, increasing TANC2 levels and enhancing cell proliferation. Co-immunoprecipitation, mass spectrometry, siRNA knockdown, cell proliferation assay Journal of virology Medium 36326272
2023 SNX27 regulates apical targeting and turnover of membrane mucin MUC17 in enterocytes. SNX27 controls MUC17 turnover at the brush border in concert with the motor protein MYO1B. siRNA knockdown, surface biotinylation, pulse-chase turnover assay, immunofluorescence The Biochemical journal Medium 39661054
2024 Crystal structures reveal that FAM21 (WASH complex subunit) binds the SNX27 FERM domain using aDLF motifs similar to those found in SNX1/SNX2. Overlapping FAM21 repeats and a Pro-Leu-containing motif bind three distinct sites on Retromer (VPS35 and VPS29). Mutation of the major VPS35-binding site partially reduces endosomal WASH association without fully preventing cargo recycling. X-ray crystallography, AlphaFold modeling, biochemical mutagenesis, Co-IP, cellular trafficking assay Proceedings of the National Academy of Sciences of the United States of America High 39116126
2025 VARP directly interacts with SNX27 (new interaction identified by biochemical/biophysical approaches and AlphaFold modeling). VARP co-immunoprecipitates all coat components (SNX27, ESCPE-1, Retromer) in cells and is required to reconstitute a proposed endosomal 'supercomplex' in vitro. SNX27 alone and with Retromer remodels PI(3)P-containing membranes carrying PDZbm cargo into tubules in a reconstituted system. Biochemical reconstitution with purified proteins, liposome tubulation assay, AlphaFold modeling, Co-IP, ITC/biophysical binding measurements Science advances High 39937906
2025 PI(3)P synthesis during chemical LTP induction drives coordinate recruitment of SNX27-Retromer to endosomes and synaptic sites in hippocampal neurons. Both SNX27-Retromer and SNX17-Retriever pathways are necessary for cLTP-dependent dendritic spine structural enlargement, acting in parallel by recycling distinct cargo sets. Preventing PI(3)P synthesis blocks synaptic recruitment of SNX27, decreases cargo recycling, and blocks LTP. Live-cell imaging in primary hippocampal neurons, PI(3)P biosensor, siRNA/shRNA knockdown, dendritic spine morphometry, LTP recording in hippocampal slices The Journal of cell biology High 40920104
2004 SNX27 (identified as a new PDZ-containing protein) interacts specifically with the 5-HT4(a) receptor splice variant via a PDZ-domain interaction. SNX27a redirects part of the 5-HT4(a)R to early endosomes. Peptide-affinity chromatography, 2D electrophoresis, mass spectrometry, subcellular localization imaging Journal of cell science Medium 15466885
2007 Endosomal SNX27 polarizes to the immunological synapse (IS) in a distinct compartment adjacent to cytotoxic granules during NK cell tumor engagement, and polarizes to the apical membrane during NK cell migration. In vitro NK-tumor conjugation assay, fluorescence microscopy Biochemical and biophysical research communications Low 17644068
2016 SNX27 interacts with GPR17 via a PDZ-binding motif at the GPR17 C-terminus and mediates GPR17 plasma membrane recycling in oligodendrocytes. SNX27 knockdown reduces GPR17 plasma membrane recycling and accelerates oligodendrocyte terminal maturation. Co-IP, siRNA knockdown, surface trafficking assay, cell differentiation assay Glia Medium 27270750
2019 HTLV-1 Tax-1 interacts with SNX27 via its PDZ-binding motif and the SNX27 PDZ domain. Tax-1 overexpression causes reduction of GLUT1 on the plasma membrane. SNX27 knockdown increases virion release and decreases HTLV-1 infectivity, revealing a mechanism by which HTLV-1 regulates a receptor post-infection. Mass spectrometry, Co-IP, flow cytometry (surface GLUT1), siRNA knockdown, viral infectivity assay PloS one Medium 30897179
2021 SARS-CoV-2 spike (S) protein binds to the PDZ domain of SNX27 through an 'MTSC' motif (not a canonical PDZbm). Abrogation of either the SNX27 PDZ domain or the S protein MTSC motif decreases surface S protein expression and viral production. Co-IP, mutagenesis, surface expression assay, viral production assay MedComm Medium 34909756
2026 VPS26A-retromer, together with SNX27, mediates unconventional protein secretion (Golgi-bypass) of transmembrane proteins including trafficking-deficient ΔF508-CFTR and SARS-CoV-2 spike protein under cellular stress. SNX27 recruits ΔF508-CFTR to the VPS26A-VPS35-VPS29 retromer complex for transport to the cell surface under UPS-inducing conditions. CRISPR KO screen, molecular interaction analysis, surface expression assay, viral particle assay Nature communications Medium 41942457
2024 SNX27 interacts with EMILIN2 via its PDZ domain; HPV-18 E6 enhances (rather than disrupts) this SNX27-EMILIN2 interaction in a PBM-dependent manner, blocking EMILIN2 secretion and its inhibition of WNT1 signaling. Co-IP, mass spectrometry proteomics, siRNA knockdown, WNT signaling assay Journal of virology Low 38874360
2022 Tex264 interacts with SNX27 (confirmed by Co-IP and immunofluorescence). siRNA-mediated TEX264 knockdown inhibits cell migration potentially through reduced SNX27-mediated Itgα5 receptor membrane recycling. Co-IP, immunofluorescence, siRNA knockdown, cell migration assay BioMed research international Low 35837377

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport. Nature cell biology 444 23563491
2011 SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors. Nature cell biology 393 21602791
2010 SNX27 mediates PDZ-directed sorting from endosomes to the plasma membrane. The Journal of cell biology 227 20733053
2014 A unique PDZ domain and arrestin-like fold interaction reveals mechanistic details of endocytic recycling by SNX27-retromer. Proceedings of the National Academy of Sciences of the United States of America 156 25136126
2016 A molecular code for endosomal recycling of phosphorylated cargos by the SNX27-retromer complex. Nature structural & molecular biology 134 27595347
2004 New sorting nexin (SNX27) and NHERF specifically interact with the 5-HT4a receptor splice variant: roles in receptor targeting. Journal of cell science 120 15466885
2014 Identification of molecular heterogeneity in SNX27-retromer-mediated endosome-to-plasma-membrane recycling. Journal of cell science 90 25278552
2011 Deficiency of sorting nexin 27 (SNX27) leads to growth retardation and elevated levels of N-methyl-D-aspartate receptor 2C (NR2C). Molecular and cellular biology 87 21300787
2016 FAM21 directs SNX27-retromer cargoes to the plasma membrane by preventing transport to the Golgi apparatus. Nature communications 62 26956659
2016 Actin-Sorting Nexin 27 (SNX27)-Retromer Complex Mediates Rapid Parathyroid Hormone Receptor Recycling. The Journal of biological chemistry 58 27008860
2016 SNX27 and SORLA Interact to Reduce Amyloidogenic Subcellular Distribution and Processing of Amyloid Precursor Protein. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 27466343
2017 PTEN Regulates Glucose Transporter Recycling by Impairing SNX27 Retromer Assembly. Cell reports 52 29117568
2019 Regulation of the endosomal SNX27-retromer by OTULIN. Nature communications 43 31541095
2021 Toward Understanding the Molecular Role of SNX27/Retromer in Human Health and Disease. Frontiers in cell and developmental biology 41 33937239
2015 A defect in the retromer accessory protein, SNX27, manifests by infantile myoclonic epilepsy and neurodegeneration. Neurogenetics 41 25894286
2020 SNX27-retromer assembly recycles MT1-MMP to invadopodia and promotes breast cancer metastasis. The Journal of cell biology 40 31820782
2022 SNX27 suppresses SARS-CoV-2 infection by inhibiting viral lysosome/late endosome entry. Proceedings of the National Academy of Sciences of the United States of America 39 35022217
2022 SNX27-Retromer directly binds ESCPE-1 to transfer cargo proteins during endosomal recycling. PLoS biology 36 35417450
2021 Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling. The Journal of cell biology 36 33605979
2016 SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 27974614
2018 Sorting nexin 27 (SNX27) regulates the trafficking and activity of the glutamine transporter ASCT2. The Journal of biological chemistry 34 29563155
2015 VPS26A-SNX27 Interaction-Dependent mGluR5 Recycling in Dorsal Horn Neurons Mediates Neuropathic Pain in Rats. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 26538661
2015 Phosphoinositide binding by the SNX27 FERM domain regulates its localization at the immune synapse of activated T-cells. Journal of cell science 29 25472716
2021 Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation. Molecular psychiatry 24 34002021
2013 Sorting nexin 27 (SNX27) associates with zonula occludens-2 (ZO-2) and modulates the epithelial tight junction. The Biochemical journal 24 23826934
2019 SNX27-Mediated Recycling of Neuroligin-2 Regulates Inhibitory Signaling. Cell reports 23 31775031
2019 HTLV-1 Tax-1 interacts with SNX27 to regulate cellular localization of the HTLV-1 receptor molecule, GLUT1. PloS one 19 30897179
2018 Cholera toxin inhibits SNX27-retromer-mediated delivery of cargo proteins to the plasma membrane. Journal of cell science 19 30030371
2016 SNX27, a protein involved in down syndrome, regulates GPR17 trafficking and oligodendrocyte differentiation. Glia 19 27270750
2021 SARS-CoV-2 spike protein harnesses SNX27-mediated endocytic recycling pathway. MedComm 17 34909756
2017 SNX27 links DGKζ to the control of transcriptional and metabolic programs in T lymphocytes. Scientific reports 17 29180720
2021 Biochemical basis for an interaction between SNX27 and the flexible SNX1 N-terminus. Advances in biological regulation 14 34866035
2021 SNX27-driven membrane localisation of OTULIN antagonises linear ubiquitination and NF-κB signalling activation. Cell & bioscience 12 34315543
2020 SNX27 regulates DRA activity and mediates its direct recycling by PDZ-interaction in early endosomes at the apical pole of Caco2 cells. American journal of physiology. Gastrointestinal and liver physiology 12 32116023
2019 Sorting nexin 27 (SNX27) variants associated with seizures, developmental delay, behavioral disturbance, and subcortical brain abnormalities. Clinical genetics 11 31721175
2023 Circ-SNX27 sponging miR-375/RPN1 axis contributes to hepatocellular carcinoma progression. The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology 10 37386831
2024 Structural basis for coupling of the WASH subunit FAM21 with the endosomal SNX27-Retromer complex. Proceedings of the National Academy of Sciences of the United States of America 8 39116126
2022 Circ_SNX27 regulates hepatocellular carcinoma development via miR-637/FGFR1 axis. Environmental toxicology 8 36029209
2007 Polarization of endosomal SNX27 in migrating and tumor-engaged natural killer cells. Biochemical and biophysical research communications 7 17644068
2022 Endosomal Sorting Protein SNX27 and Its Emerging Roles in Human Cancers. Cancers 6 36612066
2020 Interplay Between SNX27 and DAG Metabolism in the Control of Trafficking and Signaling at the IS. International journal of molecular sciences 6 32549284
2020 Overexpression of Human SNX27 Enhances Learning and Memory Through Modulating Synaptic Plasticity in Mice. Frontiers in cell and developmental biology 6 33330482
2015 A role for novel lipid interactions in the dynamic recruitment of SNX27 to the T-cell immune synapse. Bioarchitecture 6 25996807
2024 SNX27:Retromer:ESCPE-1-mediated early endosomal tubulation impacts cytomegalovirus replication. Frontiers in cellular and infection microbiology 5 39359939
2025 VARP binds SNX27 to promote endosomal supercomplex formation on membranes. Science advances 4 39937906
2019 Downregulation of SNX27 expression does not exacerbate amyloidogenesis in the APP/PS1 Alzheimer's disease mouse model. Neurobiology of aging 4 30797171
2024 Fish Snx27 promotes viral products by modulating the innate immune response and exosomal machinery. Journal of virology 2 39494909
2023 The MYO1B and MYO5B motor proteins and the SNX27 sorting nexin regulate membrane mucin MUC17 trafficking in enterocytes. bioRxiv : the preprint server for biology 2 36945389
2022 HPV-18E6 Inhibits Interactions between TANC2 and SNX27 in a PBM-Dependent Manner and Promotes Increased Cell Proliferation. Journal of virology 2 36326272
2025 The MYO1B and MYO5B motor proteins and the sorting nexin SNX27 regulate apical targeting of membrane mucin MUC17 in enterocytes. The Biochemical journal 1 39661054
2024 HPV-18 E6 enhances the interaction between EMILIN2 and SNX27 to promote WNT signaling. Journal of virology 1 38874360
2022 Tex264 Binding to SNX27 Regulates Itgα5 Receptor Membrane Recycling and Affects Cell Migration. BioMed research international 1 35837377
2026 Novel Variants Identified in Families With SNX27 -Related Neurodevelopmental Disorder, Aiding in Characterizing Its Genotypic and Phenotypic Spectrum. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 0 41609011
2026 VPS26A retromer complex and SNX27 mediate stress-induced Golgi bypass of membrane proteins. Nature communications 0 41942457
2025 PI(3)P coordinates SNX17- and SNX27-dependent protein recycling for long-term synaptic plasticity. The Journal of cell biology 0 40920104
2024 Circular RNA SNX27 Facilitates Gastric Cancer Progression By Sponging miR-638. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 0 39128090

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