The DOI matches its Crossref record; 64 of the 65 references it cites were found in a registry or an index; 16 of the 20 sources its claims cite were checked for support.
Phosphorylation of SNX17 impedes activation of Retriever-mediated sorting
Open accessAbstract
Sorting nexin 17 (SNX17) functions as cargo receptor on endosomal membranes that enables the recycling of numerous membrane cargo proteins by binding to the Retriever complex. Yet, little is known how SNX17 activity or its membrane recruitment is regulated. Here, we report that phosphorylation of SNX17 at serine 38 (Ser38) within the phox domain serves as a critical regulatory switch governing its endosomal localization and function. A mutant form mimicking the phosphorylated state disrupts SNX17's ability to bind phosphatidylinositol-3-phosphate, which in turn impairs its association with early endosomal membranes and inactivates SNX17-dependent cargo-recycling in cells. Furthermore, our results demonstrate that Ser38 is part of an autoinhibitory mechanism to regulate SNX17 cargo binding. Collectively, these findings provide new insights into the dynamic regulation of SNX17 activity and Retriever-mediated sorting processes. It also highlights SNX17 Ser38 phosphorylation as a critical regulatory mechanism that controls SNX17's endosomal localization and cargo recycling function.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
Phosphorylation of SNX17 at Ser38 within its PX domain acts as a regulatory switch that blocks PI3P binding, reduces endosomal localization, impairs cargo binding, and inactivates Retriever-mediated recycling. The phosphomimetic S38D mutant fails to rescue β1-integrin recycling and cell migration, whereas S437 phosphorylation mimetics do not affect these SNX17-dependent functions.
Key findings
- SNX17 membrane association is limited despite increasing expression: cytoplasmic SNX17 increased proportionally, but membrane-associated SNX17 remained relatively constant; S38 and S437 phosphorylation occupancy increased with SNX17 expression, while S15 and S331/335/T334 remained stable.
- The phosphomimetic SNX17 S38D failed to restore α5β1-integrin surface levels and β1-integrin stability in SNX17 KO fibroblasts, whereas WT, S38A, S437A, and S437D rescued these readouts; S38D also caused β1-integrin accumulation in LAMP1-positive lysosomes and impaired random migration comparably to SNX17 KO cells.
- Live imaging showed SNX17-positive endosomes averaged 114 ± 24 in WT, 68 ± 13 in S38A, and 3 ± 1 in S38D cells, while SNX27-positive endosomes remained relatively constant (113 ± 33, 114 ± 15, and 92 ± 19, respectively).
- Mass spectrometry found S38 phosphorylation largely restricted to the cytoplasm, detected in only 2 of 13 membrane samples, and SNX17 was approximately 25-fold more abundant in cytoplasm than membrane; in vitro, WT SNX17 PX domain bound PI3P-containing liposomes, but S38A and S38D lost selective lipid binding.
- The chimeric SNX17 PXSNX27 maintained endosomal localization but failed to rescue β1-integrin and Itga5 surface levels, completely lost β1-integrin tail peptide binding, and showed enhanced VPS35L interaction, suggesting PX-domain roles beyond membrane targeting.
Methods
- CRISPR-Cas9 SNX17 knockout mouse fibroblasts and HeLa cells were used, with stable retroviral re-expression of moxGFP-tagged SNX17 WT, S38A, S38D, S437A, S437D, or chimeric PXSNX27 variants at matched expression levels.
- Analyses included flow cytometry for surface integrins, subcellular fractionation, LC-MS/MS for phosphorylation occupancy and fraction-specific phosphosites, live-cell and fixed imaging, capture ELISA for β1-integrin stability, peptide pull-downs, GFP immunoprecipitation, liposome pelleting with recombinant SNX17 PX domains, and random migration tracking.
- Statistical comparisons used one-way ANOVA with Dunnett, Tukey, or Šidak tests unless otherwise stated; data are reported as mean ± s.d. or median ± range, with n values typically 3–5 independent experiments.
Limitations
- The paper states no formal limitations section; it notes that the precise mechanism of PX–FERM interplay “remains unclear and warrants further investigation” and that the kinase(s) phosphorylating S38 remain unidentified, with candidate kinases including SNRK, DAPK2, DAPK1, and CAMK-class kinases.
- Evident from the text: key conclusions rely on phosphomimetic S38D/S38A mutants rather than direct phosphorylation, and several assays use overexpression or re-expression systems in immortalized cell lines.
- Evident from the text: the in vitro lipid-binding conclusion uses purified PX domain and synthetic LUVs, and some functional effects, such as reduced migration in S38A cells, were not statistically significant compared with WT.
Model-written summary. Check it against the paper before relying on it.
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Cites
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Verification
Claims the paper makes
16 of 20 cited sources checked · 4 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Spatial proteomics data from human and mouse cells reveal that SNX family members with a potential phosphorylation site in the conserved lipid-binding pocket are more abundant in the cytoplasm compared to those lacking this site.
“Spatial proteomics data from human and mouse cells further reinforce this trend, revealing that SNX family members with a potential phosphorylation site in the conserved lipid-binding pocket are more abundant in the cytoplasm compared to those lacking this site (43, 44).”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [43] Itzhak, 2016, Global, quantitative and dynamic mapping of protein subcellular localization, elife source
The Materials and methods (Bioinformatic analysis; page not provided) describe quantitative cytosolic and organellar distributions in human cells, so this paper is a source of spatial proteomics data. The Discussion (Accurate, quantitative and reproducible organellar maps; page not provided) compares its human-cell map with a separate mouse-cell study. Our copy does not report the claimed comparison between SNX family members with and without a potential phosphorylation site in the lipid-binding pocket. (LLM, conf=0.82)
Experimental — accuracy not yet measured - cites [44] Itzhak, 2017, A mass spectrometry-based approach for mapping protein subcellular localization reveals the spatial proteome of mouse primary neurons, Cell. Rep. source
The Results and Discussion section, “Application of LFQ Organellar Maps to Mouse Neurons” (page unavailable), reports spatial proteomics data for mouse neurons, including protein distributions across cytosolic and other fractions. Our copy does not report a comparison of SNX family members by phosphorylation-site status, so it does not establish the claimed cytoplasmic-abundance trend. Searches for SNX and the conserved lipid-binding pocket found no passage addressing that comparison. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Findingcitation
An in silico kinase library screen for SNX17 S38 phosphorylation expanded the list of candidates to include SNRK, DAPK2, DAPK1, and kinases of the CAMK class.
“Our comprehensive in silico kinase library screen for SNX17 S38 phosphorylation has expanded the list of candidates to include SNRK, DAPK2, DAPK1, and kinases of the CAMK class (45, 46).”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [45] Johnson, 2023, An atlas of substrate specificities for the human serine/threonine kinome, Nature source
The Profiling kinase substrate specificity and Annotation of the human phosphoproteome sections describe a kinome-wide motif library and its use to rank candidate kinases for phosphorylation sites. The cited paper therefore supports the basis for an in silico screen, but our copy does not report a screen of SNX17 S38 or identify SNRK, DAPK2, DAPK1, and CAMK-class kinases as its candidates. No page numbers are available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measured - cites [46] Yaron-Barir, 2024, The intrinsic substrate specificity of the human tyrosine kinome, Nature source
The Methods (PSPA experiments; page unavailable) describe a tyrosine-centered peptide substrate library, but do not address an SNX17 S38 screen. Searches for SNX17 S38 and the named candidates returned no passage reporting that screen or its results. The citing authors describe the screen as their own, so this verdict does not assess whether they performed it. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Premisecitation
Proteomic analyses have detected phosphorylated SNX3 S72 and SNX12 S73 only in cytosolic fractions, whereas their nonphosphorylated counterparts associate with membrane-bound organelles.
“proteomic analyses have detected phosphorylated SNX3 S72 and SNX12 S73 only in cytosolic fractions, whereas their nonphosphorylated counterparts associate with membrane-bound organelles (41).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [41] Martinez-Val, 2021, Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution, Nat. Commun. source
The Results section on subcellular phosphoproteomes distinguishes cytosolic fractions 1–2 from membrane and organelle fractions 3–4, and reports a phosphorylation-dependent difference for RPS6. Searches for SNX3, SNX12, S72 and S73 found no passage in our copy reporting the claimed distribution of those proteins or their nonphosphorylated counterparts. Page numbers were not available in the indexed passages. (LLM, conf=0.73)
Experimental — accuracy not yet measured
- Premisecitation
Of the 51 human PX domain-containing proteins, 26 possess a serine or threonine at positions corresponding to SNX17 S38 or SNX3 S72.
“of the 51 human PX domain-containing proteins, 26 possess a serine or threonine at positions corresponding to SNX17 S38 or SNX3 S72 (38, 42)”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [38] Kervin, 2021, Regulation of the phosphoinositide code by phosphorylation of membrane readers, Cells source
Materials and Methods describes aligning human PX-domain sequences, and the Discussion identifies a conserved serine-containing motif in the PX superfamily. But the cited paper does not report that 26 of 51 human PX-domain proteins have serine or threonine at positions corresponding to SNX17 S38 or SNX3 S72; Results §3.1 instead describes an analysis of 49 human PX domains. The specific count and positional comparison are therefore unsupported by this source. (LLM, conf=0.78)
Experimental — accuracy not yet measured - cites [42] Consortium, 2022, UniProt: the universal protein knowledgebase in 2023, Nucleic. Acids. Res. source
The Data integration section describes mapping protein-sequence features and future work on phosphorylation sites, but does not report a PX-domain analysis. Searches for SNX17, SNX3, and the 26-of-51 count found no passage in our copy addressing the claimed residues or counts. (LLM, conf=0.76)
Experimental — accuracy not yet measured
- Findingown data
Cytoplasmic SNX17 levels increased proportionally with total SNX17 expression.
“While cytoplasmic SNX17 levels increased proportionally with total SNX17 expression”
Quote in the paperNot a substantial claim
- Findingown data
The distribution of VPS35L did not change across cell lines with different SNX17 expression levels.
“The distribution of other endosomal proteins, such as VPS35L, did not change (Fig. 1G).”
Quote in the paperNot a substantial claim - Findingown data
SNX17 phosphorylation occupancy at S15 and S331/335/T334 remained stable with SNX17 expression.
“whereas it remained stable for S15 and S331/335/T334 (Fig. 1I).”
Quote in the paperNot a substantial claim - Findingown data
S446 phosphorylation occupancy increased only at high SNX17 expression levels.
“S446 phosphorylation occupancy increased only at high expression levels”
Quote in the paperSubstantial claim - Findingown data
A mutant form mimicking the phosphorylated state of SNX17 Ser38 disrupts SNX17's ability to bind phosphatidylinositol-3-phosphate.
“A mutant form mimicking the phosphorylated state disrupts SNX17’s ability to bind phosphatidylinositol-3-phosphate”
Quote in the paperSubstantial claim - Findingown data
Membrane-associated SNX17 remained relatively constant across cell lines expressing low, medium, and high levels of moxGFP-SNX17.
“membrane-associated SNX17 remained relatively constant across all cell lines”
Quote in the paperSubstantial claim - Findingown data
S409 was detected almost exclusively in its phosphorylated state.
“while S409 was detected almost exclusively in its phosphorylated state (data not shown)”
Quote in the paperNot a substantial claim - Findingown data
SNX17 phosphorylation occupancy at S38 and S437 increased proportionally with SNX17 expression.
“The proportion of phosphorylated to nonphosphorylated peptides for S38 and S437 increased proportionally with SNX17 expression”
Quote in the paperSubstantial claim - Findingreasoning
The S38 phosphomimetic mutant inactivates SNX17-dependent cargo recycling in cells.
“and inactivates SNX17-dependent cargo-recycling in cells.”
Quote in the paperSubstantial claim - Findingreasoning
The S38 phosphomimetic mutant impairs SNX17 association with early endosomal membranes.
“which in turn impairs its association with early endosomal membranes”
Quote in the paperSubstantial claim - Findingown data
SNX17 S38D expression failed to restore α5β1-integrin surface levels.
“SNX17 S38D expression failed to restore α5β1-integrin surface levels”
Quote in the paperSubstantial claim - Findingown data
SNX17 S38D was found exclusively in the cytoplasm.
“SNX17 S38D was found exclusively in the cytoplasm”
Quote in the paperSubstantial claim - Findingown data
The model predicts hydrogen bonding between the 3′-phosphate group of PI3P, the hydroxyl and amino groups of SNX17 S38, and other nearby amino acids.
“Our model predicts hydrogen bonding between the 3′-phosphate group of PI3P, the hydroxyl and amino groups of SNX17 S38, and other nearby amino acids.”
Quote in the paperSubstantial claim- Rests on an assumption: The modeled SNX17 PX domain structure based on SNX9 PX-BAR and p40phox structures accurately represents the SNX17–PI3P interaction.
- Findingown data
SNX17 S38A, S437A, and S437D expression rescued Itgb1 and Itgα5 surface levels comparably to SNX17 WT.
“While SNX17 S38A, S437A, and S437D expression rescued Itgb1 and Itgα5 surface levels comparable to SNX17 WT”
Quote in the paperSubstantial claim - Findingown data
The exchange of the PX domains between SNX17 and SNX27 enhanced the interaction of moxGFP-SNX17 PXSNX27 with the Retriever subunit VPS35L in HeLa cells.
“The exchange of the PX domains between SNX17 and SNX27 enhanced the interaction of moxGFP–SNX17 PXSNX27 with the Retriever subunit VPS35L in HeLa cells”
Quote in the paperSubstantial claim - Findingown data
WT SNX17 PX domain binding required PI3P.
“WT SNX17 PX domain binding required PI3P”
Quote in the paperSubstantial claim - Findingown data
S38 phosphorylation was largely restricted to the cytoplasm, appearing in only two of 13 membrane samples.
“S38 phosphorylation was largely restricted to the cytoplasm, appearing in only two of 13 membrane samples”
Quote in the paperSubstantial claim - Findingown data
The AMPK-activation-induced increase in β1 integrin stability was SNX17-independent.
“but this increase was SNX17-independent (Fig. S2E).”
Quote in the paperNot a substantial claim - Findingown data
Binding of moxGFP-SNX17 PXSNX27 to β1-integrin tail peptides was completely inhibited.
“In contrast, binding to β1-integrin tail peptides was completely inhibited”
Quote in the paperSubstantial claim - Findingown data
The number of SNX27-positive endosomes remained relatively constant across all cell lines.
“while the number of SNX27-positive endosomes remained relatively constant across all cell lines”
Quote in the paperSubstantial claim - Findingown data
Cells expressing SNX17 S38D exhibited impaired migration comparable to SNX17 KO cells.
“cells expressing SNX17 S38D exhibited impaired migration comparable to SNX17 KO cells”
Quote in the paperSubstantial claim - Findingown data
Our experiments did not detect increased SNX17 S38 phosphorylation upon AMPK or PKC activation.
“our experiments did not detect increased SNX17 S38 phosphorylation upon AMPK or PKC activation (Speidel & Böttcher, unpublished).”
Quote in the paperNot a substantial claim - Findingown data
The S38A mutation showed reduced, although not statistically significant, migration compared to SNX17 WT-expressing cells.
“The S38A mutation showed reduced, although not statistically significant, migration compared to SNX17 WT-expressing cells.”
Quote in the paperNot a substantial claim - Findingown data
S437 phosphorylation mimetics did not affect SNX17-mediated cargo recycling.
“Together, these data indicate that S437 phosphorylation mimetics did not affect SNX17-mediated cargo recycling.”
Quote in the paperSubstantial claim - Findingown data
SNX17 S38 phosphorylation increased concomitantly with SNX17 expression.
“our investigation revealed that SNX17 S38 phosphorylation increased concomitantly with SNX17 expression.”
Quote in the paperSubstantial claim - Findingown data
Immunoprecipitation of moxGFP-SNX17 WT detected VPS35L, a component of the Retriever complex.
“immunoprecipitation (IP) of moxGFP-SNX17 WT detected VPS35L, a component of the Retriever complex”
Quote in the paperSubstantial claim - Findingown data
SNX17 PX S38A and PX S38D mutants lost selective lipid-binding activity.
“while SNX17 PX S38A and PX S38D mutants lost selective lipid-binding activity”
Quote in the paperSubstantial claim - Findingown data
Surface levels of SNX17-independent cargo proteins Itgb3 and ItgαV remained unaffected across all SNX17 variants.
“Surface levels of SNX17-independent cargo proteins Itgb3 (Fig. S2G) and ItgαV (Fig. S2H) remained unaffected across all SNX17 variants.”
Quote in the paperSubstantial claim- Rests on an assumption: Itgb3, ItgaV, and TFR are SNX17-independent cargo proteins.
- Findingown data
Expression of SNX17 WT, S38A, S437A, or S437D rescued β1-integrin stability in SNX17 KO fibroblasts.
“Expression of SNX17 WT, S38A, S437A, or S437D rescued β1-integrin stability in SNX17 KO fibroblasts”
Quote in the paperSubstantial claim - Findingown data
S409 phosphorylation was enriched in the membrane extract.
“S409 phosphorylation was enriched in the membrane extract”
Quote in the paperSubstantial claim - Findingown data
Phosphorylated S437 was predominantly detected in the cytoplasm.
“while phosphorylated S437 was predominantly detected in the cytoplasm”
Quote in the paperSubstantial claim - Findingown data
Phosphorylation of SNX17 at S38 reduces its binding to β1 integrin.
“We demonstrated that phosphorylation of SNX17 at S38 reduces its binding to β1 integrin”
Quote in the paperSubstantial claim - Interpretationown data
Ser38 is part of an autoinhibitory mechanism that regulates SNX17 cargo binding.
“Furthermore, our results demonstrate that Ser38 is part of an autoinhibitory mechanism to regulate SNX17 cargo binding.”
Quote in the paperSubstantial claim - Interpretationown data
Phosphorylation of SNX17 at Ser38 within the PX domain serves as a critical regulatory switch governing its endosomal localization and function.
“Here, we report that phosphorylation of SNX17 at serine 38 (Ser38) within the phox domain serves as a critical regulatory switch governing its endosomal localization and function.”
Quote in the paperSubstantial claim - Interpretationown data
The dose-dependent increase in S38 and S437 phosphorylation occupancy suggests that phosphorylation is a regulatory mechanism controlling SNX17 function.
“The dose-dependent increase in S38 and S437 phosphorylation occupancy suggested that phosphorylation is a regulatory mechanism controlling SNX17 function.”
Quote in the paperSubstantial claim - Interpretationown data
Increased expression of SNX17 regulates its activity or subcellular localization to mitigate potential disruptions in endosomal cargo trafficking.
“These results suggest that increased expression of SNX17 regulates its activity or subcellular localization to mitigate potential disruptions in endosomal cargo trafficking.”
Quote in the paperSubstantial claim - Interpretationown data
The SNX17 PX domain plays a role in cargo binding that extends beyond simply facilitating membrane-targeting.
“This suggests that the SNX17 PX domain plays a role in cargo binding that extends beyond simply facilitating membrane-targeting.”
Quote in the paperSubstantial claim - Interpretationreasoning
Introducing a negative charge at S38 through phosphorylation might inhibit SNX17 binding to endosomal PI3P due to electrostatic repulsion between the negatively charged S38D and the phosphate group of PI3P.
“Introducing a negative charge at S38 through phosphorylation might inhibit SNX17 binding to endosomal PI3P due to electrostatic repulsion between the negatively charged S38D and the phosphate group of PI3P.”
Quote in the paperSubstantial claim - Interpretationown data
Modifications to the SNX17 PX domain, such as Ser38 phosphorylation, can impact its ability to recognize and bind cargo proteins.
“These findings suggest that modifications to the SNX17 PX domain, such as Ser38 phosphorylation, can impact its ability to recognize and bind cargo proteins.”
Quote in the paperSubstantial claim - Interpretationown data
S38 phosphorylation prevents SNX17 binding to early endosomes.
“S38 phosphorylation prevents SNX17 binding to early endosomes”
Quote in the paperSubstantial claim - Interpretationown data
SNX17 binding to endosomal PI3P requires hydrogen bonds between S38 and the phosphate group of PI3P.
“Our findings demonstrate that SNX17 binding to endosomal PI3P requires hydrogen bonds between S38 and the phosphate group of PI3P.”
Quote in the paperSubstantial claim - Interpretationown data
S38 phosphorylation plays a crucial role in regulating SNX17 recruitment to early endosomes.
“These findings support the crucial role of S38 phosphorylation in regulating SNX17 recruitment to early endosomes.”
Quote in the paperSubstantial claim - Interpretationown data
S38 phosphorylation plays a critical role in regulating SNX17's membrane association.
“This highlights the critical role of S38 phosphorylation in regulating SNX17's membrane association.”
Quote in the paperSubstantial claim - Interpretationreasoning
The S38 phosphorylation site within the PX domain acts as a molecular switch, regulating membrane association of SNX17 through a mechanism reminiscent of PIP-stop motifs.
“The S38 phosphorylation site within the PX domain acts as a molecular switch, regulating membrane association of SNX17 through a mechanism reminiscent of PIP-stop motifs.”
Quote in the paperSubstantial claim - Interpretationown data
Structural modeling predicted that S38 phosphorylation prevents recruitment to endosomes by blocking PI3P binding.
“Structural modeling predicted that S38 phosphorylation prevents recruitment to endosomes by blocking PI3P binding”
Quote in the paperSubstantial claim- Rests on an assumption: The modeled SNX17 PX domain structure based on SNX9 PX-BAR and p40phox structures accurately represents the SNX17–PI3P interaction.
- Interpretationown data
The PX domain exerts an inhibitory effect on FERM domain cargo binding.
“our data suggest the PX domain exerts an inhibitory effect on FERM domain cargo binding.”
Quote in the paperSubstantial claim
- It may state two separate claims as one. 30
- Probably not a substantial claim. 9
It may state two separate claims as one.
PremisecitationSNX17 functions as a cargo receptor on endosomal membranes that enables recycling of numerous membrane cargo proteins by binding to the Retriever complex.
“Cargo recognition and tethering to the Retriever complex is achieved by the cargo adaptor SNX17 (16, 17).”
Quote in the paperSubstantial claim2 of 2 sources checkedProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationPhosphorylation at corresponding sites in SNX1, SNX3, SNX12, and SNX17 has been reported in various cancer types.
“phosphorylation at corresponding sites in SNX1, SNX3, SNX12, and SNX17 has been reported in various cancer types (47, 48, 49, 50, 51, 52)”
Quote in the paperNot a substantial claim5 of 6 sources checked- cites [47] Mertins, 2014, Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels, Mol. Cell. Proteomics. source
The Results passages discuss phosphorylation in tumor samples, including EGFR and stress-kinase pathways, but do not identify phosphorylation sites in SNX1, SNX3, SNX12, or SNX17. Searches for those protein names and for sorting-neXIN phosphorylation found no passage in our copy establishing the claimed sites across cancer types. (LLM, conf=0.75)
Experimental — accuracy not yet measured - cites [48] Stuart, 2015, A phosphoproteomic comparison of B-RAFV600E and MKK1/2 inhibitors in melanoma cells∗[S], Mol. Cell Proteomics. source
The results section identifies SNX13 as a phosphosite-bearing target in melanoma cells, but it does not establish phosphorylation at corresponding sites in SNX1, SNX3, SNX12, or SNX17. Searches for those proteins and sorting-nexin phosphosites found no passage in our copy reporting the claimed sites across various cancer types. (LLM, conf=0.72)
Experimental — accuracy not yet measured - cites [49] Lundby, 2012, Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues, Nat. Commun. source
The Results section reports phosphorylation sites across rat tissues, and the Discussion mentions cancer only in general terms; neither identifies the corresponding sites in SNX1, SNX3, SNX12, or SNX17 in cancer types. Searches for those SNX proteins and for sorting-neXin phosphorylation in cancer found no passage addressing the claim. (LLM, conf=0.75)
Experimental — accuracy not yet measured - cites [50] Klammer, 2012, Phosphosignature predicts dasatinib response in non-small cell lung cancer, Mol. Cell Proteomics. source
The Dasatinib Sensitivity tables and Discussion report phosphorylation sites in other proteins, but do not address SNX1, SNX3, SNX12, or SNX17 at corresponding sites. Searches for those SNX names and for sorting-ne xin phosphorylation found no passage supporting the claim across cancer types. (LLM, conf=0.72)
Experimental — accuracy not yet measured - cites [51] Zhou, 2013, Toward a comprehensive characterization of a human cancer cell phosphoproteome, J. Proteome Res. source
- cites [52] Rolland, 2014, Global phosphoproteomic profiling reveals distinct signatures in B-cell non-Hodgkin lymphomas, Am. J. Pathol. source
The Identification and Quantification and Discussion passages report phosphorylation in B-cell non-Hodgkin lymphomas, but do not identify phosphorylation sites in SNX1, SNX3, SNX12, or SNX17. Searches for those proteins and for “sorting nexin” found no passage addressing the claimed sites or their occurrence across cancer types. (LLM, conf=0.74)
Experimental — accuracy not yet measured
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationSNX17 knockout mouse kidney fibroblasts were described previously.
“SNX17 KO mouse kidney fibroblasts were described before (57).”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [57] Yu, 2024, The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation, EMBO Rep. source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationA mutation in the SNX17 FERM-like domain (V380D) inhibits both cargo binding and endosomal recruitment.
“A mutation in the SNX17 FERM-like domain (V380D) inhibits both cargo binding and endosomal recruitment (16)”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [16] Butkovič, 2024, Mechanism and regulation of cargo entry into the Commander endosomal recycling pathway, Nat. Commun. source
It may state two separate claims as one.
Findingown dataThe amount of membrane-localized SNX17 remained constant despite increasing cytosolic levels, suggesting a regulatory mechanism to maintain homeostasis.
“we observed that the amount of membrane-localized SNX17 remained constant despite increasing cytosolic levels, suggesting a regulatory mechanism to maintain homeostasis.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataSNX17 S38A and S38D showed reduced levels in the membrane fraction compared to WT, while maintaining similar levels in the cytoplasm.
“SNX17 S38A and S38D showed reduced levels in the membrane fraction compared to WT, while maintaining similar levels in the cytoplasm”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataSNX17 S38A maintained cargo-binding interaction, whereas S38D exhibited significantly reduced binding.
“the SNX17 S38A mutant maintained this cargo-binding interaction, whereas S38D exhibited significantly reduced binding”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataβ1 integrin accumulated in SNX17 S38D-expressing cells and colocalized with LAMP1-positive lysosomes.
“β1 integrin accumulated in SNX17 S38D-expressing cells and colocalized with LAMP1-positive lysosomes”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataBoth SNX17 S38A and S38D mutants maintained VPS35L interaction, though at slightly reduced levels.
“Both SNX17 S38A and S38D mutants maintained VPS35L interaction, though at slightly reduced levels”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Findingown dataAMPK activation increased the stability of β1 integrin.
“We found increased stability of β1 integrin after AMPK activation with different concentrations of A-769662”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingnone givenAMPK activation decreases SNX17 protein stability over time but mimicking S437 phosphorylation has no effect on β1-integrin surface levels and stability.
“Conversely, AMPK activation decreases SNX17 protein stability over time but mimicking S437 phosphorylation has no effect on β1-integrin surface levels and stability.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataAMPK activation led to a weak reduction in SNX17 levels after more than 6 hours while the subcellular localization of SNX17 was not affected.
“AMPK activation led to a weak reduction in SNX17 levels after >6 h while the subcellular localization of SNX17 was not affected”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Findingown dataThe chimeric moxGFP-SNX17 PXSNX27 maintained endosomal localization and colocalized with mScarlet-SNX17 WT or mCherry-SNX27.
“The chimeric moxGFP-SNX17 PXSNX27 maintained endosomal localization and colocalized with mScarlet-SNX17 WT (Fig. S4D) or mCherry-SNX27 (Fig. S4E).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataWT SNX17 and Kindlin-2 specifically bound the β1-integrin tail peptide, but not the scrambled control.
“WT SNX17 and the known integrin interactor Kindlin-2 specifically bound the β1-integrin tail peptide, but not the scrambled control.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataThe chimeric moxGFP-SNX17 PXSNX27 failed to rescue cell surface levels of β1 integrin and Itga5, indicating that it was functionally inactive.
“the chimeric moxGFP-SNX17 PXSNX27 failed to rescue cell surface levels of β1 integrin (Fig. 5G) and Itga5 (Fig. 5H), indicating that it was functionally inactive.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataIncreased SNX17 expression did not significantly impact the endosomal trafficking of β1 integrins or SNX17-independent cargo proteins.
“Surprisingly, increased SNX17 expression did not significantly impact the endosomal trafficking of β1 integrins or SNX17-independent cargo proteins.”
Quote in the paperNot a substantial claim- Rests on an assumption: Itgb3, ItgaV, and TFR are SNX17-independent cargo proteins.
It may state two separate claims as one.
Findingown dataQuantitative analysis of 247 cells revealed an average of 114 ± 24 SNX17-positive endosomes in SNX17 WT cells, 68 ± 13 in S38A cells, and only 3 ± 1 in S38D-expressing cells.
“Quantitative analysis of 247 cells revealed an average of 114 ± 24 SNX17-positive endosomes in SNX17 WT cells, 68 ± 13 in S38A cells, and only 3 ± 1 in S38D-expressing cells”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataSNX17 S38D had no effect on β1-integrin stability, yielding degradation rates like SNX17 KO cells.
“In contrast, SNX17 S38D had no effect, yielding degradation rates like SNX17 KO cells (Fig. 2D).”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataSubcellular fractionation studies show that the phospho-mimicking SNX17 S38D mutant localizes exclusively to the cytosol, and mass spectrometry analysis demonstrates that S38 phosphorylation is barely detectable in membrane fractions while present in cytosolic extracts.
“the phospho-mimicking SNX17 S38D mutant localizes exclusively to the cytosol, and mass spectrometry analysis demonstrates that S38 phosphorylation is barely detectable in membrane fractions while present in cytosolic extracts.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown datamoxGFP-SNX17 S38A maintained punctate endosomal localization and colocalized with mCherry-SNX27, although less prominently than moxGFP-SNX17 WT.
“While moxGFP-SNX17 S38A maintained punctate endosomal localization and colocalized with mCherry-SNX27, although less prominent compared to moxGFP-SNX17 WT”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataA phospho-mimicking mutation abolished PI3P binding in vitro, dislodged SNX17 from endosomes, and inactivated SNX17 function in cells.
“a phospho-mimicking mutation abolished PI3P binding in vitro, dislodged SNX17 from endosomes, and inactivated SNX17 function in cells.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Interpretationown dataSNX17 membrane localization is tightly regulated even at increased levels and points to cellular mechanisms that maintain endosomal trafficking homeostasis.
“Taken together, these data indicate that SNX17 membrane localization is tightly regulated even at increased levels and point to cellular mechanisms that maintain endosomal trafficking homeostasis.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Interpretationown dataSNX17 S38 phosphorylation impairs β1-integrin stability and recycling, resulting in reduced surface levels and compromised cell migration.
“In summary, our findings reveal that SNX17 S38 phosphorylation impairs β1-integrin stability and recycling, resulting in reduced surface levels and compromised cell migration.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationIncreased phosphorylation of SNX3 and SNX17 PIP-stop motifs has been observed during cold ischemia, coinciding with MAPK stress-response pathway activation.
“increased phosphorylation of SNX3 and SNX17 PIP-stop motifs has been observed during cold ischemia, coinciding with MAPK stress-response pathway activation (47).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [47] Mertins, 2014, Ischemia in tumors induces early and sustained phosphorylation changes in stress kinase pathways but does not affect global protein levels, Mol. Cell. Proteomics. source
Checked before — its earlier verdict is held back until a new check runs.
It may state two separate claims as one.
InterpretationreasoningThe model indicates that S38 phosphorylation would prevent ligand binding by blocking inositol 3-phosphate entry and thereby fulfill the function of a PIP-stop motif similar to Ser72 of SNX3.
“the model indicates that S38 phosphorylation would prevent ligand binding by blocking inositol 3-phosphate entry and thereby fulfill the function of a PIP-stop motif similar to Ser72 of SNX3 (34).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [34] Lenoir, 2018, Phosphorylation of conserved phosphoinositide binding pocket regulates sorting nexin membrane targeting, Nat. Commun. source
Checked before — its earlier verdict is held back until a new check runs.
- Rests on an assumption: The modeled SNX17 PX domain structure based on SNX9 PX-BAR and p40phox structures accurately represents the SNX17–PI3P interaction.
It may state two separate claims as one.
InterpretationreasoningThere is a complex interplay between SNX17's endosomal localization, cargo recognition, and Retriever complex interaction, with the PX domain serving as a key modulator of these functions.
“This implies a complex interplay between SNX17's endosomal localization, cargo recognition, and Retriever complex interaction, with the PX domain serving as a key modulator of these functions.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Interpretationown dataThis phosphorylation not only affects PI3P binding but also influences cargo interaction, suggesting an expanded role for the SNX17 PX domain beyond mere lipid binding.
“This phosphorylation not only affects PI3P binding but also influences cargo interaction, suggesting an expanded role for the SNX17 PX domain beyond mere lipid binding.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
InterpretationreasoningPIP-stop phosphorylation maintains a dynamic equilibrium between membrane-bound and cytosolic SNX17, potentially preserving the homeostasis of cargo protein trafficking even under conditions of SNX17 overexpression.
“These observations lead us to propose that PIP-stop phosphorylation maintains a dynamic equilibrium between membrane-bound and cytosolic SNX17, potentially preserving the homeostasis of cargo protein trafficking even under conditions of SNX17 overexpression.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Interpretationown dataSNX17 S38D is nonfunctional and cannot prevent lysosomal targeting of β1 integrin.
“further supporting the observation that SNX17 S38D is nonfunctional and cannot prevent lysosomal targeting of β1 integrin.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenAll cell lines used were regularly checked for mycoplasma.
“All cell lines were regularly checked for mycoplasma.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Interpretationown dataThe chimeric SNX17 PXSNX27 construct maintained endosomal localization but failed to rescue β1-integrin surface levels, indicating that the PX domain's function in cargo recognition encompasses more than its known role in lipid binding.
“this construct maintained endosomal localization but failed to rescue β1-integrin surface levels indicating that the PX domain's function in cargo recognition encompasses more than its known role in lipid binding.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationSNX17 binding to PI3P facilitates its membrane attachment, which releases autoinhibition, exposes the Retriever-binding motif for interaction with the Retriever complex, and liberates the cargo recognition site.
“SNX17 binding to PI3P facilitates its membrane attachment, which releases this autoinhibition, exposes the Retriever-binding motif for interaction with the Retriever complex, and liberates the cargo recognition site (55).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [55] Martín-González, 2025, Selective cargo and membrane recognition by SNX17 regulates its interaction with Retriever, EMBO Rep. source
It may state two separate claims as one.
InterpretationreasoningThe phospho-mimicking SNX17 S38D mutant failed to bind PI3P, thereby remaining in its autoinhibited form characterized by reduced cargo and Retriever binding.
“the phospho-mimicking SNX17 S38D mutant failed to bind PI3P, thereby remaining in its autoinhibited form characterized by reduced cargo and Retriever binding.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductown dataThe correct sequences of all constructs were verified by Sanger sequencing.
“The correct sequences of all constructs were verified by Sanger sequencing (Microsynth Seqlab).”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
Interpretationown dataSNX17 exists in an autoinhibited form, with its activity finely regulated by phosphorylation and intramolecular interactions.
“our findings support a model in which SNX17 exists in an autoinhibited form, with its activity finely regulated by phosphorylation and intramolecular interactions.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductnone givenSamples in which the sequence coverage of SNX17 was below 16% were excluded from the calculation.
“Samples in which the sequence coverage of SNX17 was below 16% were excluded from the calculation.”
Quote in the paperNot a substantial claimProbably not a substantial claim.
Study design and conductown dataSNX17 knockout clones were confirmed by Western blot analysis.
“SNX17 KO clones were confirmed by WB analysis.”
Quote in the paperSubstantial claim
The paper relies on this without support.
The functional impact of AMPK-mediated SNX17 S437 phosphorylation on cargo recycling and Retriever binding has not been investigated, and no other signals are known that dynamically regulate SNX17 activity.
“However, the functional impact of this phosphorylation on SNX17 cargo recycling and Retriever binding has not yet been investigated nor are other signals known that dynamically regulate SNX17 activity.”
The paper relies on this without support.
Phosphomimetic S38D and nonphosphorylatable S38A mutations faithfully mimic the phosphorylated and unphosphorylated states of SNX17 Ser38, respectively.
“we generated phosphomimetic (S to D) and nonphosphorylatable (S to A) mutants of both phosphorylation sites.”
The authors state this as an assumption.
PI3P-containing large unilamellar vesicles accurately mimic early endosomal membranes for assessing SNX17 PX domain binding.
“To mimic early endosomes, we generated large LUVs containing PI3P”
The paper relies on this without support.
The modeled SNX17 PX domain structure based on SNX9 PX-BAR and p40phox structures accurately represents the SNX17–PI3P interaction.
“we modeled the SNX17 PX domain bound to PI3P based on the known structures of PI3P-bound SNX9 PX-BAR (PDB: 2RAK; Fig. 4A) and p40phox (PDB: 1H6H; Fig. S3A).”
The paper relies on this without support.
Itgb3, ItgaV, and TFR are SNX17-independent cargo proteins.
“had no effect on the surface levels of the SNX17-independent cargo proteins Itgb3, ItgaV, and TFR”
The paper relies on this without support.
The SNX27 PX domain lacks a phosphorylation site corresponding to S38 in SNX17.
“but lacks a phosphorylation site corresponding to S38 in SNX17.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
LUV lipid is labeled both PIP3 and PI3P
MinorThe preparation is introduced as producing PIP3-containing LUVs, but the lipid named in that sentence and specified in the LUV mixture is PI3P. These labels identify different phosphoinositides.
“To generate PIP3-containing LUVs, 18:1 1,2-dioleoyl-sn-glycero-3-phospho-(1′-myo-inositol-3′-phosphate) (PI3P; Avanti; 850150) was protonated as described before (20).”
“For PI3P+-LUVs, DOPC, DOPS, PI3P, and Atto655-DOPE were mixed at a molecular ratio of 80:10:10:1”
Citations
Cites
Fiji: an open-source platform for biological-image analysis
Schindelin, J., Arganda-Carreras, I., Frise, E., Kaynig, V., Longair, M., Pietzsch, T., Preibisch, S., Rueden, C., Saalfeld, S., Schmid, B., et al. (2012) · Nature Methods · doi:10.1038/nmeth.2019 · Cited by 66,890
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133
UniProt: the Universal Protein Knowledgebase in 2023
The UniProt Consortium, Bateman, A., Martin, M.-J., Orchard, S., Magrane, M., Ahmad, S., Alpi, E., Bowler-Barnett, E. H., Britto, R., Bye-A-Jee, H., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkac1052 · Cited by 7,210
The PRIDE database at 20 years: 2025 update
Pérez‐Riverol, Y., Bandla, C., Kundu, D. J., Kamatchinathan, S., Bai, J., Hewapathirana, S., John, N. S., Prakash, A., Walzer, M., Wang, S., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1011 · Cited by 2,140
Methods for Cell and Particle Tracking
Meijering, E. H. W., Dzyubachyk, O., & Smal, I. (2012) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-391857-4.00009-4 · Cited by 1,443
MorphoLibJ: integrated library and plugins for mathematical morphology with ImageJ
Legland, D., Arganda‐Carreras, I., & Andrey, P. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw413 · Cited by 1,415
An atlas of substrate specificities for the human serine/threonine kinome
Johnson, J. L., Yaron, T. M., Huntsman, E. M., Kerelsky, A., Song, J., Regev, A., Lin, T.-Y., Liberatore, K., Cizin, D. M., Cohen, B. M., et al. (2023) · Nature · doi:10.1038/s41586-022-05575-3 · Cited by 728
Global, quantitative and dynamic mapping of protein subcellular localization
Itzhak, D. N., Tyanova, S., Cox, J., & Borner, G. H. (2016) · eLife · doi:10.7554/elife.16950 · Cited by 649
Identification of Required Host Factors for SARS-CoV-2 Infection in Human Cells
Daniloski, Z., Jordan, T. X., Wessels, H., Hoagland, D. A., Kasela, S., Legut, M., Maniatis, S., Mimitou, E. P., Lu, L., Geller, E. T., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.030 · Cited by 561
Toward a comprehensive characterization of a human cancer cell phosphoproteome
Zhou, H., Di Palma, S., Preisinger, C., Peng, M., Polat, A. N., Heck, A. J. R., & Mohammed, S. (2013) · Journal of Proteome Research · doi:10.1021/pr300630k · Cited by 438
Endosomal sorting and signalling: an emerging role for sorting nexins
Cullen, P. J. (2008) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2427 · Cited by 404
Mertins, P., Yang, F., Liu, T., Mani, D. R., Petyuk, V. A., Gillette, M. A., Clauser, K. R., Qiao, J. W., Gritsenko, M. A., Moore, R. J., et al. (2014) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m113.036392 · Cited by 400
Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling
McNally, K. E., Faulkner, R., Steinberg, F., Gallon, M., Ghai, R., Pim, D., Langton, P., Pearson, N., Danson, C. M., Nägele, H., et al. (2017) · Nature Cell Biology · doi:10.1038/ncb3610 · Cited by 346
Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues
Lundby, A., Secher, A., Lage, K., Nordsborg, N. B., Dmytriyev, A., Lundby, C., & Olsen, J. V. (2012) · Nature Communications · doi:10.1038/ncomms1871 · Cited by 343
A genome-wide CRISPR screen identifies host factors that regulate SARS-CoV-2 entry
Zhu, Y., Feng, F., Hu, G., Wang, Y., Yin, Y., Zhu, Y., Xü, W., Cai, X., Sun, Z., Han, W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-21213-4 · Cited by 307
SNX17 protects integrins from degradation by sorting between lysosomal and recycling pathways
Steinberg, F., Heesom, K. J., Bass, M. D., & Cullen, P. J. (2012) · Journal of Cell Biology · doi:10.1083/jcb.201111121 · Cited by 206
CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL
Bartuzi, P., Billadeau, D. D., Favier, R., Rong, S., Dekker, D., Fedoseienko, A., Fieten, H., Wijers, M., Levels, J. H., Huijkman, N., et al. (2016) · Nature Communications · doi:10.1038/ncomms10961 · Cited by 205
Sorting nexin 17 prevents lysosomal degradation of β1 integrins by binding to the β1-integrin tail
Böttcher, R. T., Stremmel, C., Meves, A., Meyer, H., Widmaier, M., Tseng, H.-Y., & Fässler, R. (2012) · Nature Cell Biology · doi:10.1038/ncb2501 · Cited by 202
Self-citationThe intrinsic substrate specificity of the human tyrosine kinome
Yaron-Barir, T. M., Joughin, B. A., Huntsman, E. M., Kerelsky, A., Cizin, D. M., Cohen, B. M., Regev, A., Song, J., Vasan, N., Lin, T.-Y., et al. (2024) · Nature · doi:10.1038/s41586-024-07407-y · Cited by 189
Schaffer, B. E., Levin, R. S., Hertz, N. T., Maures, T. J., Schoof, M. L., Hollstein, P. E., Benayoun, B. A., Banko, M. R., Shaw, R. J., Shokat, K. M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.09.009 · Cited by 184
Gallon, M., Clairfeuille, T., Steinberg, F., Mas, C., Ghai, R., Sessions, R. B., Teasdale, R. D., Collins, B. M., & Cullen, P. J. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1410552111 · Cited by 182
A molecular code for endosomal recycling of phosphorylated cargos by the SNX27–retromer complex
Clairfeuille, T., Mas, C., Chan, A. S. M., Yang, Z., Tello-Lafoz, M., Chandra, M., Widagdo, J., Kerr, M. C., Paul, B., Mérida, I., et al. (2016) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.3290 · Cited by 164
Lee, J., Retamal, C., Cuitiño, L., Caruano-Yzermans, A., Shin, J.-E., van Kerkhof, P., Marzolo, M.-P., & Bu, G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800642200 · Cited by 162
A unique sorting nexin regulates trafficking of potassium channels via a PDZ domain interaction
Lunn, M.-L., Nassirpour, R., Arrabit, C., Tan, J., Mcleod, I., Arias, C. M., Sawchenko, P. E., Yates, J. R., & Slesinger, P. A. (2007) · Nature Neuroscience · doi:10.1038/nn1953 · Cited by 151
Sorting nexin 17 facilitates LRP recycling in the early endosome
van Kerkhof, P., Lee, J., McCormick, L., Tetrault, E., Lu, W., Schoenfish, M., Oorschot, V., Strous, G. J., Klumperman, J., & Bu, G. (2005) · The EMBO Journal · doi:10.1038/sj.emboj.7600756 · Cited by 148
Getting active: protein sorting in endocytic recycling
Hsu, V. W., Bai, M., & Li, J. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3332 · Cited by 139
Chandra, M., Chin, Y. K. ‐., Mas, C., Feathers, J. R., Paul, B., Datta, S., Chen, K., Jia, X., Yang, Z., Norwood, S. J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09355-y · Cited by 137
Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins
Ghai, R., Bugarcic, A., Liu, H., Norwood, S. J., Skeldal, S., Coulson, E. J., Li, S. S.-C., Teasdale, R. D., & Collins, B. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216229110 · Cited by 134
Fedoseienko, A., Wijers, M., Wolters, J. C., Dekker, D., Smit, M., Huijkman, N., Kloosterhuis, N., Klug, H., Schepers, A., Willems van Dijk, K., et al. (2018) · Circulation Research · doi:10.1161/circresaha.117.312004 · Cited by 126
Itzhak, D. N., Davies, C., Tyanova, S., Mishra, A., Williamson, J., Antrobus, R., Cox, J., Weekes, M. P., & Borner, G. H. H. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.08.063 · Cited by 124
Phosphosignature predicts dasatinib response in non-small cell lung cancer
Klammer, M., Kaminski, M., Zedler, A., Oppermann, F., Blencke, S., Marx, S., Müller, S., Tebbe, A., Godl, K., & Schaab, C. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.016410 · Cited by 118
A Phosphoproteomic Comparison of B-RAFV600E and MKK1/2 Inhibitors in Melanoma Cells*
Stuart, S. A., Houel, S., Lee, T., Wang, N., Old, W. M., & Ahn, N. G. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.047233 · Cited by 116
Ghai, R., Mobli, M., Norwood, S. J., Bugarcic, A., Teasdale, R. D., King, G. F., & Collins, B. M. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1017110108 · Cited by 114
Singla, A., Fedoseienko, A., Giridharan, S. S. P., Overlee, B. L., Lopez, A., Jia, D., Song, J., Huff-Hardy, K., Weisman, L., Burstein, E., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12221-6 · Cited by 113
Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution
Martinez-Val, A., Bekker-Jensen, D. B., Steigerwald, S., Koenig, C., Østergaard, O., Mehta, A., Tran, T., Sikorski, K., Torres-Vega, E., Kwasniewicz, E., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-27398-y · Cited by 111
Recycling of autophagosomal components from autolysosomes by the recycler complex
Zhou, C., Wu, Z., Du, W., Que, H., Wang, Y., Ouyang, Q., Jian, F., Yuan, W., Zhao, Y., Tian, R. L., et al. (2022) · Nature Cell Biology · doi:10.1038/s41556-022-00861-8 · Cited by 98
Systems-wide Studies Uncover Commander, a Multiprotein Complex Essential to Human Development
Mallam, A. L., & Marcotte, E. M. (2017) · Cell Systems · doi:10.1016/j.cels.2017.04.006 · Cited by 94
Sorting Nexins in Protein Homeostasis
Hanley, S. E., & Cooper, K. F. (2020) · Cells · doi:10.3390/cells10010017 · Cited by 87
Burden, J. J., Sun, X.-M., García, A. B. G., & Soutar, A. K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313689200 · Cited by 82
Cell Biology Of Intracellular Protein Trafficking
Schwartz, A. L. (1990) · Annual Review of Immunology · doi:10.1146/annurev.iy.08.040190.001211 · Cited by 64
Azimifar, S. B., Böttcher, R. T., Zanivan, S. R., Grashoff, C., Krüger, M., Legate, K. R., Mann, M., & Fässler, R. (2012) · Journal of Cell Science · doi:10.1242/jcs.091652 · Cited by 58
Self-citationJang, I. H., Lee, S., Park, J. B., Kim, J. H., Lee, C. S., Hur, E., Kim, I. S., Kim, K., Yagisawa, H., Suh, P., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m208438200 · Cited by 56
Functions of Sorting Nexin 17 Domains and Recognition Motif for P-selectin Trafficking
Knauth, P., Schlüter, T., Czubayko, M., Kirsch, C., Florian, V., Schreckenberger, S., Hahn, H., & Bohnensack, R. (2005) · Journal of Molecular Biology · doi:10.1016/j.jmb.2005.02.004 · Cited by 55
Kolanczyk, M., Krawitz, P., Hecht, J., Hupalowska, A., Miaczynska, M., Marschner, K., Schlack, C., Emmerich, D., Kobus, K., Kornak, U., et al. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.109 · Cited by 54
The Phox Homology (PX) Domain Protein Interaction Network in Yeast
Vollert, C. S., & Uetz, P. (2004) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400081-mcp200 · Cited by 53
Farfán, P., Lee, J., Larios, J., Sotelo, P., Bu, G., & Marzolo, M. (2013) · Traffic · doi:10.1111/tra.12076 · Cited by 51
Lenoir, M., Ustunel, C., Rajesh, S., Kaur, J., Moreau, D., Gruenberg, J., & Overduin, M. (2018) · Nature Communications · doi:10.1038/s41467-018-03370-1 · Cited by 49
Sorting nexin 17 regulates ApoER2 recycling and reelin signaling
Sotelo, P., Farfán, P., Benitez, M. L., Bu, G., & Marzolo, M.-P. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093672 · Cited by 47
A New Member of the Sorting Nexin Family Interacts with the C-Terminus of P-Selectin
Florian, V., Schlüter, T., & Bohnensack, R. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.4467 · Cited by 44
β1 integrin cytoplasmic tyrosines promote skin tumorigenesis independent of their phosphorylation
Meves, A., Geiger, T., Zanivan, S. R., DiGiovanni, J., Mann, M., & Fässler, R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1105689108 · Cited by 39
Tseng, H.-Y., Thorausch, N., Ziegler, T., Meves, A., Fässler, R., & Böttcher, R. T. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.07.003 · Cited by 34
Self-citationGlobal phosphoproteomic profiling reveals distinct signatures in B-cell non-Hodgkin lymphomas
Rolland, D., Basrur, V., Conlon, K., Wolfe, T., Fermin, D., Nesvizhskii, A. I., Lim, M. S., & Elenitoba-Johnson, K. S. J. (2014) · The American Journal of Pathology · doi:10.1016/j.ajpath.2014.01.036 · Cited by 31
Mechanism and regulation of cargo entry into the Commander endosomal recycling pathway
Butkovič, R., Walker, A. P., Healy, M. D., McNally, K. E., Liu, M., Veenendaal, T., Kato, K., Liv, N., Klumperman, J., Collins, B. M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-50971-0 · Cited by 26
Feng, Z., Kovalev, N., & Nagy, P. D. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1009120 · Cited by 24
Structural basis for Retriever-SNX17 assembly and endosomal sorting
Singla, A., Boesch, D. J., Fung, H. Y. J., Ngoka, C., Enriquez, A. S., Song, R., Kramer, D. A., Han, Y., Banarer, E., Lemoff, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54583-6 · Cited by 23
Pim, D., Broniarczyk, J. K., Siddiqa, A., Massimi, P., & Banks, L. (2020) · Journal of Virology · doi:10.1128/jvi.02068-20 · Cited by 21
Clinical diversity and molecular mechanism of VPS35L-associated Ritscher-Schinzel syndrome
Otsuji, S., Nishio, Y., Tsujita, M., Rio, M., Huber, C., Antón-Plágaro, C., Mizuno, S., Kawano, Y., Miyatake, S., Simon, M., et al. (2023) · Journal of Medical Genetics · doi:10.1136/jmg-2022-108602 · Cited by 19
The recognition of membrane-bound PtdIns3P by PX domains
Jia, Z., Ghai, R., Collins, B. M., & Mark, A. E. (2014) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24593 · Cited by 15
Selective cargo and membrane recognition by SNX17 regulates its interaction with Retriever
Martín-González, A., Méndez-Guzmán, I., Zabala-Zearreta, M., Quintanilla, A., García-López, A., Martínez-Lombardía, E., Albesa-Jové, D., Acosta, J. C., & Lucas, M. (2025) · EMBO Reports · doi:10.1038/s44319-024-00340-1 · Cited by 15
Pigino, G. F., Morfini, G. A., & Brady, S. T. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-374947-5.00007-9 · Cited by 14
Regulation of the phosphoinositide code by phosphorylation of membrane readers
Kervin, T. A., & Overduin, M. (2021) · Cells · doi:10.3390/cells10051205 · Cited by 13
Phosphoinositide Recognition Sites Are Blocked by Metabolite Attachment
Kervin, T. A., Wiseman, B., & Overduin, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.690461 · Cited by 11
The USP12/46 deubiquitinases protect integrins from ESCRT-mediated lysosomal degradation
Yu, K., Wang, G. M., Guo, S. S., Bassermann, F., & Fässler, R. (2024) · EMBO Reports · doi:10.1038/s44319-024-00300-9 · Cited by 10
Self-citation
Flagged first, then by citations
1 of the 65 references couldn’t be matched to a known paper.
Cited by
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Metadata
- Authors
- Speidel, J. D., Yu, K., & Böttcher, R. T.
- Affiliations
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Böttcher, Ralph Thomas
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2025-06
- Volume
- 301
- Issue
- 6
- Pages
- 110222
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC12182294
- OpenAlex
- W4410221777
- Cited by
- 0
- References
- 65
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Max Planck Society
- German Research Foundation (SFB914)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- SNX17, phosphorylation, sorting nexins, endosomal trafficking, phosphatidylinositol 3-phosphate, early endosomes, autoinhibition, cargo binding, protein regulation
- MeSH terms
- HeLa Cells, Humans, Phosphorylation, Endosomes, Phosphatidylinositol Phosphates, Protein Transport, HEK293 Cells, Sorting Nexins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-11-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-11-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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