Affinage

SNX9

Sorting nexin-9 · UniProt Q9Y5X1

Length
595 aa
Mass
66.6 kDa
Annotated
2026-06-10
33 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SNX9 is a multidomain SH3-PX-BAR scaffold that couples membrane deformation to actin dynamics during the late stages of clathrin-mediated endocytosis (PMID:15703209, PMID:18388313). Through its PX and BAR domains it senses and tubulates phosphoinositide-rich membranes, while its SH3 domain recruits the actin machinery: SNX9 binds and stimulates dynamin GTPase activity to drive vesicle scission (PMID:15703209), recruits N-WASP and dynamin to membrane tubules, engages the Arp2/3 complex via its low-complexity domain, and binds and stimulates PtdIns(4)P-5-kinases to reinforce local phosphoinositide synthesis (PMID:18388313). On membranes bearing both PI(3)P and PI(4,5)P2, SNX9 acts as an adaptor that mobilizes N-WASP/Arp2/3 actin polymerization in a Cdc42-dependent manner (PMID:23589871), and its PX domain uses a non-canonical interface to selectively bind PI(3,4)P2 during macropinocytic ruffling [PMID:bio_10.1101_2025.03.26.645564]. C-terminal BAR/coiled-coil-mediated dimerization is required for its proper localization and regulation (PMID:16316319). SNX9 functions partially redundantly with its paralog SNX18, which also heterodimerizes with it and shares dynamin, N-WASP, and synaptojanin interactions (PMID:20427313, PMID:29622675). Beyond canonical endocytosis, SNX9 supports RhoA/Cdc42-dependent clathrin-independent endocytosis and cell motility (PMID:26960793), filopodium biogenesis (PMID:32328641), cytokinesis and mitotic progression (PMID:22718350), and acts as a cargo adaptor for beta-arrestin-independent GPCR internalization by binding the phosphorylated CXCR4 C-tail (PMID:39511325). In immune cells, SNX9 is recruited to CD28 clusters at the immunological synapse to generate membrane tubulation and regulate CD28 signaling and IL-2 production (PMID:35050850), and it modulates TCR/CD28-driven PLCγ1-Ca2+-NFATc2 signaling to promote CD8 T cell exhaustion, such that its deletion enhances memory differentiation and CAR-T anti-tumor efficacy (PMID:36732507). SNX9 also serves as a host factor exploited by pathogens and viruses, including the EPEC effector EspF and an unusual RxAPxxP SH3-binding motif present in EEEV nsP3 and HTLV-1 Gag (PMID:20088948, PMID:35390274).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 Medium

    The first identified SNX9 partners established it as an SH3-domain adaptor engaging the cytoplasmic tails of ADAM-family metalloprotease disintegrins, hinting at a role in membrane-protein trafficking.

    Evidence Yeast two-hybrid, GST pulldown, and co-IP from COS-7 cells showing SH3-mediated binding to MDC9/ADAM9 and MDC15 precursors

    PMID:10531379

    Open questions at the time
    • Functional consequence of the interaction was not defined
    • Did not address endocytic or membrane-remodeling activity
  2. 2002 Medium

    Linking SNX9 to ACK2 and clathrin revealed it as a tyrosine-phosphorylated component of receptor downregulation, connecting it to growth-factor receptor degradation.

    Evidence Co-IP, kinase-dead ACK2(K158R) mutant, and EGF receptor degradation assay

    PMID:11799118

    Open questions at the time
    • Functional role of SNX9 phosphorylation not resolved
    • Did not establish mechanism of EGFR degradation
  3. 2005 High

    Biochemical and live-cell work established the core endocytic function: SNX9 directly stimulates dynamin GTPase activity and is recruited to clathrin-coated pits at the scission stage, with knockdown blocking transferrin uptake.

    Evidence In vitro dynamin binding and GTPase assays on liposomes, TIRF microscopy, siRNA knockdown with transferrin readout; parallel SH3-domain mapping of synaptojanin-1 and ACK1 binding

    PMID:15703209 PMID:16137687

    Open questions at the time
    • Did not define how multiple SH3 ligands are coordinated
    • Structural basis of dynamin stimulation not resolved
  4. 2006 Medium

    Mapping the dimerization determinant explained how SNX9 architecture controls its regulation, showing C-terminal BAR/coiled-coil dimerization is required for ACK2 binding, phosphorylation, and localization.

    Evidence Truncation mutagenesis, co-IP, and localization assays

    PMID:16316319

    Open questions at the time
    • Did not connect dimerization to membrane tubulation directly
    • No structural model of the dimer
  5. 2008 High

    Reconstitution defined SNX9 as a membrane-deforming hub: its PX-BAR-LC module tubulates membranes and recruits N-WASP, dynamin, and Arp2/3, while PX-domain stimulation of PI(4)P-5-kinases creates a phosphoinositide feedback loop at endocytic sites.

    Evidence In vitro liposome tubulation, domain mutants, co-IP, and kinase activity assays

    PMID:18388313

    Open questions at the time
    • In vivo significance of the kinase feedback loop not tested
    • Coupling of tubulation to scission timing not defined
  6. 2010 Medium

    Two studies broadened SNX9's roles: a redundant partnership with SNX18 in clathrin-mediated endocytosis, and exploitation of its membrane-deforming activity by the bacterial effector EspF for pathogen invasion.

    Evidence Co-IP, GTPase assays, TIRF, and transferrin uptake for SNX18 redundancy; SNX9/EspF mutagenesis and bacterial invasion assays with CCP/dynamin inhibitors

    PMID:20088948 PMID:20427313

    Open questions at the time
    • Degree of SNX9/SNX18 functional overlap in vivo unclear
    • EspF-driven invasion shown to be dynamin-independent but scission mechanism unresolved
  7. 2012 Medium

    Identifying a mitotic requirement distinguished a non-endocytic SNX9 function, as depletion caused cytokinesis failure and chromosome segregation defects without blocking transferrin uptake.

    Evidence siRNA, time-lapse microscopy, localization of MRLC, Rab11 endosomes, and Golgi, with transferrin uptake control

    PMID:22718350

    Open questions at the time
    • Molecular partners at the cytokinetic bridge not identified
    • Whether mitotic role uses the same membrane-remodeling machinery unknown
  8. 2013 High

    Cell-free reconstitution showed SNX9 acts as a curvature- and lipid-specific actin adaptor, replacing toca-1 to drive Cdc42-dependent N-WASP/Arp2/3 polymerization on PI(3)P/PI(4,5)P2 membranes.

    Evidence Cell-free actin polymerization on defined-lipid liposomes with systematic component omission

    PMID:23589871

    Open questions at the time
    • Physiological context where SNX9 substitutes for toca-1 not defined
    • Did not address branched vs bundled network outcomes
  9. 2016 Medium

    SNX9 was established as a multifunctional scaffold for RhoGTPase-dependent clathrin-independent endocytosis and motility, capable of substituting for the RhoGAP GRAF1.

    Evidence Knockdown with RhoA/Cdc42 activation assays, invasion and CIE assays, GRAF1 rescue

    PMID:26960793

    Open questions at the time
    • Direct biochemical effect of SNX9 on RhoA/Cdc42 nucleotide state not shown
    • Mechanism of GRAF1 substitution unresolved
  10. 2018 Medium

    SNX9 was shown to non-redundantly control surface ADAM9 levels and substrate shedding, refining the redundancy boundary with SNX18, and an SH3-mediated interaction with a Nedd4-family ligase implicated it in synaptic regulation.

    Evidence Co-IP, single and double SNX9/SNX18 knockdown, surface ADAM9 quantification and EphB4 shedding; in vitro binding, co-IP, and NMJ electrophysiology in Drosophila

    PMID:29622675 PMID:30518551

    Open questions at the time
    • Whether ADAM9 regulation uses canonical endocytic machinery unclear
    • Functional consequence of Nedd4-mediated SNX9 turnover at synapses not fully defined
  11. 2019 Medium

    Drosophila genetics placed the SNX9 ortholog in an endocytosis-autophagy network controlling EGFR degradation versus recycling, with loss hyperactivating ERK/Ca2+/ER-stress signaling to drive stem cell proliferation.

    Evidence Genetic screen and epistasis with Dynamin, Rab5/7, Atg, and Rab11 pathway genes in intestinal stem cells

    PMID:31006650

    Open questions at the time
    • Direct biochemical role of SNX9 in autophagosome formation not isolated
    • Conservation of the recycling-versus-degradation switch in mammals untested here
  12. 2020 Medium

    SNX9 was found at endogenous filopodia and reported to modulate Hippo signaling, extending its functions to filopodium biogenesis and YAP regulation.

    Evidence Phage-display antibody screen, in vitro filopodia assay, and immunolocalization in Xenopus/Chlamydia; co-IP, YAP phosphorylation and reporter assays in ADPKD models

    PMID:32328641 PMID:32974348

    Open questions at the time
    • Mechanism linking SNX9 membrane/actin activity to filopodial elongation not defined
    • The direct SNX9-YAP interaction (Low confidence) lacks independent validation
  13. 2022 High

    Structural and immunological studies defined SNX9's SH3 specificity for an unusual RxAPxxP motif exploited by viruses and revealed a CD28-synapse function generating membrane tubulation that tunes T cell activation.

    Evidence Crystal structure of SH3-EEEV nsP3 peptide with mutagenesis and HTLV-1 infection assay; 3D-CLEM, super-resolution, CD28 phosphorylation and IL-2 assays

    PMID:35050850 PMID:35390274

    Open questions at the time
    • Endogenous host ligands of the RxAPxxP-binding mode not catalogued
    • How CD28-cluster tubulation mechanistically alters signaling unresolved
  14. 2023 High

    A CRISPR screen identified SNX9 as a driver of CD8 T cell exhaustion through PLCγ1-Ca2+-NFATc2 signaling, making its deletion a strategy to enhance CAR-T efficacy.

    Evidence Pooled CRISPR-Cas9 screen, individual knockout, calcium flux and NFATc2 readouts, and in vivo adoptive transfer tumor model

    PMID:36732507

    Open questions at the time
    • Direct molecular link between SNX9 and PLCγ1 not biochemically defined
    • Whether membrane-remodeling activity underlies the signaling effect unclear
  15. 2024 Medium

    SNX9 was established as a cargo adaptor for beta-arrestin-independent GPCR endocytosis, binding the phosphorylated CXCR4 C-tail to drive agonist-stimulated internalization.

    Evidence siRNA of SNX9/SNX18 and beta-arrestins with CXCR4 internalization assay and co-IP with the receptor C-tail

    PMID:39511325

    Open questions at the time
    • Generality across other GPCRs not established
    • Phosphosite dependence of binding not mapped
  16. 2025 Medium

    Biophysical and structural studies refined SNX9 lipid selectivity, defining a non-canonical PX interface that selectively binds and protects PI(3,4)P2 during macropinocytosis and showing actin assembly requires the integrated PX-BAR/SH3 network.

    Evidence Biolayer interferometry, cell-free reconstitution, cryo-ET, MD simulations, and 3D-dSTORM (one peer-reviewed, one preprint)

    PMID:40105919 PMID:bio_10.1101_2025.03.26.645564

    Open questions at the time
    • In vivo role of PI(3,4)P2 protection in macropinocytosis not fully established
    • Preprint findings not yet peer-reviewed
  17. 2026 Low

    Multiple reports placed SNX9 under ubiquitin-proteasome control, identifying ITCH (via ZG16) and RAB40C as drivers of its degradation, implicating turnover in disease-relevant signaling.

    Evidence IP-MS/co-IP, GST pulldown, and ubiquitination assays for ITCH/ZG16 and RAB40C-mediated degradation with knockdown functional readouts

    PMID:41781795 PMID:42245125

    Open questions at the time
    • Single-lab co-IP findings without independent validation
    • Physiological contexts triggering SNX9 degradation not defined
    • Direct ubiquitination sites on SNX9 not mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SNX9's conserved membrane-deforming and actin-nucleating biochemistry is selectively deployed across its many cellular roles — endocytosis, cytokinesis, filopodia, immune synapse signaling, and GPCR adaptation — and how its abundance is regulated to set these outcomes remains unresolved.
  • No unifying model linking domain activities to context-specific functions
  • Regulatory inputs (phosphorylation, degradation) not integrated into a quantitative model

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0008092 cytoskeletal protein binding 3 GO:0008289 lipid binding 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005856 cytoskeleton 4 GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-1640170 Cell Cycle 1
Partners
ADAM9CD28CXCR4DNM2SNX18SYNJ1TNK2WASL

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 SNX9 binds directly to dynamin-1 and dynamin-2, stimulates dynamin assembly, potentiates dynamin's basal GTPase activity, and stimulates assembly-stimulated GTPase activity on liposomes. SNX9 is transiently recruited to clathrin-coated pits during late stages of vesicle formation coinciding with dynamin recruitment, and siRNA-mediated knockdown of SNX9 inhibits transferrin internalization in HeLa cells. Direct binding assays, GTPase activity assays on liposomes, TIRF microscopy in live cells, siRNA knockdown with transferrin internalization readout Molecular biology of the cell High 15703209
1999 SNX9 (SH3PX1) interacts with the cytoplasmic domains of the metalloprotease disintegrins MDC9 (ADAM9) and MDC15 via its SH3 domain, as established by yeast two-hybrid, bacterial fusion protein pulldowns, and co-immunoprecipitation from eukaryotic cells. Both proteins preferentially bind the precursor but not the processed form of MDC9 and MDC15. Yeast two-hybrid, GST-fusion protein pulldowns, co-immunoprecipitation from COS-7 cells The Journal of biological chemistry Medium 10531379
2008 SNX9 deforms plasma membranes and liposomes into narrow tubules via its BAR and PX domains plus low-complexity (LC) domain; it recruits N-WASP and dynamin 2 to these tubules via its SH3 domain. The LC domain binds the Arp2/3 complex. SNX9 binds PtdIns(4)P-5-kinases via its PX domain and stimulates their kinase activity, suggesting a positive feedback loop regulating phosphoinositide levels at endocytic sites. In vitro liposome tubulation assays, domain truncation/mutation analysis, co-immunoprecipitation, kinase activity assays Journal of cell science High 18388313
2002 SNX9 (SH3PX1) interacts with ACK2 via the ACK2 proline-rich domain and SNX9 SH3 domain. ACK2, clathrin, and SNX9 form a complex in cells. ACK2 mediates EGF-stimulated tyrosine phosphorylation of SNX9, and co-expression of ACK2 with SNX9 leads to constitutive SNX9 phosphorylation. Together ACK2 and SNX9 promote EGF receptor degradation. Co-immunoprecipitation, kinase-dead mutant ACK2(K158R) to block phosphorylation, EGF receptor degradation assay The Journal of biological chemistry Medium 11799118
2005 SNX9 SH3 domain binds synaptojanin-1 at multiple sites within its proline-rich region, and binds ACK1 at a single dominant site (residues 920–955). In the presence of SNX9, synaptojanin colocalizes with ACK1-containing vesicles, indicating SNX9 acts as an adaptor linking synaptojanin-1 to ACK1. In vivo biotinylated GST-SH3 domain blot overlays, synthetic peptide arrays, co-immunofluorescence localization FEBS letters Medium 16137687
2006 Dimerization of SNX9 (SH3PX1) mediated by its BAR/coiled-coil domain at the C-terminus is required for ACK2-catalyzed and EGF-stimulated tyrosine phosphorylation of SNX9, interaction with ACK2, and proper intracellular localization. Truncation of as few as 13 C-terminal residues abolishes dimerization, phosphorylation, ACK2 binding, and normal localization. Domain truncation mutagenesis, co-immunoprecipitation, intracellular localization assays The Biochemical journal Medium 16316319
2010 SNX18 and SNX9 can form a heterodimer, colocalize in tubular membrane structures, and are functionally redundant in clathrin-mediated endocytosis. Both interact with dynamin and stimulate its basal GTPase activity, and both interact with N-WASP and synaptojanin. TIRF microscopy shows SNX18 is transiently recruited to clathrin-coated pits coinciding with dynamin and SNX9. Co-immunoprecipitation, GTPase activity assay, siRNA knockdown with transferrin uptake readout, TIRF microscopy Journal of cell science Medium 20427313
2013 On curved membranes containing both PI(3)P and PI(4,5)P2, SNX9 acts as a specific adaptor replacing toca-1 to mobilize N-WASP and the Arp2/3 complex for actin polymerization, bypassing the requirement for toca-1 in a Cdc42-dependent manner. Cell-free reconstitution of actin polymerization on liposomes with defined lipid compositions Proceedings of the National Academy of Sciences of the United States of America High 23589871
2012 SNX9 is required for progression through mitosis: siRNA depletion induces multinucleation (cytokinesis failure), disrupts MRLC(S19) localization during ingression, blocks recruitment of Rab11-positive recycling endosomes to the intracellular bridge, and disrupts Golgi localization during cytokinesis. SNX9 depletion also delays chromosome alignment and segregation during metaphase without blocking transferrin uptake, indicating a non-endocytic mitotic role. siRNA knockdown, time-lapse microscopy, immunofluorescence localization, transferrin uptake assay Journal of cell science Medium 22718350
2010 The bacterial effector EspF binds SNX9 and exploits SNX9's membrane-deforming activity to promote EPEC invasion of intestinal epithelial cells. Invasion requires the SNX9 lipid-binding domains and the EspF SNX9-binding domain, as well as clathrin-coated pit assembly, but is independent of dynamin activity. Point mutagenesis of SNX9 lipid-binding domains, EspF truncation analysis, pharmacological inhibition of CCP assembly and dynamin, bacterial invasion assay Cellular microbiology Medium 20088948
2016 SNX9 controls activation of RhoA and Cdc42 GTPases, regulates cell motility via RhoA-ROCK and N-WASP pathways, and is required for RhoGTPase-dependent clathrin-independent endocytosis. SNX9 can functionally substitute for GRAF1 (a RhoGAP) in this pathway, establishing SNX9 as a multifunctional scaffold coordinating endocytosis and invasion. SNX9 knockdown with RhoA/Cdc42 activation assays, cell invasion assay, clathrin-independent endocytosis assay, rescue with GRAF1 Molecular biology of the cell Medium 26960793
2018 SNX9 interacts with ADAM9 and regulates ADAM9 protein levels at the cell surface. Single SNX9 knockdown increased ADAM9 levels at the plasma membrane and enhanced shedding of EphB4 (an ADAM9 substrate). Double knockdown of SNX9 and SNX18 was required to significantly decrease ADAM9 internalization, demonstrating redundancy for internalization but a non-redundant SNX9 role in controlling total ADAM9 levels. Co-immunoprecipitation, siRNA knockdown (single and double), cell-surface ADAM9 quantification, EphB4 shedding assay The Journal of biological chemistry Medium 29622675
2019 In Drosophila, SH3PX1 (SNX9 ortholog) acts in an endocytosis-autophagy network including Dynamin, Rab5, Rab7, and Atg proteins to promote lysosomal degradation of ligand-activated EGFRs. Loss of SH3PX1 stabilizes EGFRs and routes them via Rab11-dependent recycling endosomes back to the plasma membrane, hyperactivating ERK, calcium signaling, and ER stress to stimulate intestinal stem cell proliferation. Genetic screen, epistasis with endocytic/autophagic pathway genes, Rab11-dependent recycling assay, ERK pathway readout in Drosophila ISCs Developmental cell Medium 31006650
2020 SNX9 is an endogenous component of filopodia. Antibodies targeting SNX9 caused shorter filopodia-like structures in vitro. SNX9 is found at specialized filopodia in Xenopus development and at filopodia hijacked during Chlamydia cell entry. Phage display phenotypic antibody screen, in vitro filopodia-like structure assay, immunolocalization in Xenopus and during Chlamydia infection The Journal of cell biology Medium 32328641
2022 Upon CD28 triggering, SNX9 is recruited to CD28 clusters at the immunological synapse and generates membrane tubulation from CD28 clusters (shown by 3D correlative light and electron microscopy). SNX9 regulates the stability of CD28 clusters, CD28 phosphorylation, and IL-2 cytokine production. 3D correlative light and electron microscopy (CLEM), super-resolution microscopy, CD28 phosphorylation assay, IL-2 production assay eLife Medium 35050850
2022 The crystal structure of SNX9 SH3 in complex with an eastern equine encephalitis virus (EEEV) nsP3 peptide reveals that the length and composition of the n-Src loop determines specificity for an unusual RxAPxxP class I SH3 binding motif (with Ala instead of Pro/Leu at the hydrophobic position). The HTLV-1 Gag polyprotein also contains this motif, and it is required for efficient HTLV-1 infection. X-ray crystal structure of SH3–peptide complex, mutagenesis of binding interface residues, affinity measurements, viral infection assay Structure High 35390274
2023 SNX9 deletion in CD8 T cells decreases PLCγ1, Ca2+, and NFATc2-mediated TCR signaling downstream of TCR/CD28 stimulation and reduces expression of exhaustion transcription factors NR4A1/3 and TOX, resulting in enhanced memory differentiation, IFNγ secretion, and improved CAR-T anti-tumor efficacy in vivo. Pooled CRISPR-Cas9 screen, individual gene knockout validation, calcium flux assay, NFATc2 signaling readout, adoptive transfer in vivo tumor model Nature communications High 36732507
2022 In Drosophila, Sh3px1 (SNX9 ortholog) facilitates selective autophagy of the TAK1/TAB2 (Tak1/Tab2) kinase complex by interacting with Tab2 and the autophagy protein Atg8a, thereby targeting the complex to the autophagy platform and preventing constitutive activation of the IMD innate immune pathway. Co-immunoprecipitation, genetic epistasis in Drosophila IMD pathway, autophagy flux assays Cell reports Medium 35081354
2018 Drosophila Nedd4-long (dNedd4Lo) directly binds SH3PX1 (SNX9 ortholog) via the SH3PX1 SH3 domain interacting with a proline-rich sequence in the dNedd4Lo Middle region. Postsynaptic overexpression of dNedd4Lo reduces SH3PX1 levels at the subsynaptic reticulum and impairs presynaptic neurotransmitter release at the neuromuscular junction. In vitro binding assay, co-immunoprecipitation in S2 cells, in vivo overexpression with immunofluorescence and electrophysiology The Journal of biological chemistry Medium 30518551
2020 SNX9 interacts directly with YAP and increases LATS1-mediated phosphorylation of YAP, resulting in cytoplasmic retention of YAP, decreased YAP/TEAD4 transcriptional activity, and suppression of Hippo target gene expression and cyst development in polycystic kidney disease cells. Co-immunoprecipitation, YAP phosphorylation assay, transcriptional reporter assay, gain- and loss-of-function in ADPKD cell lines and Pkd1-/- mice Frontiers in cell and developmental biology Low 32974348
2024 SNX9 (and SNX18) act as cargo adaptors for β-arrestin-independent GPCR endocytosis. SNX9 is recruited to CXCR4 at the plasma membrane and interacts directly with the receptor's carboxyl-terminal tail in a phosphorylation-dependent manner to promote agonist-stimulated CXCR4 endocytosis. siRNA knockdown of SNX9/SNX18 and β-arrestins with CXCR4 internalization assay, co-immunoprecipitation of SNX9 with CXCR4 C-tail Communications biology Medium 39511325
2025 SNX9 forms a complex with NUMB (Ex3-containing isoform) at the plasma membrane and recruits p53 in a SNX9-dependent manner. This complex is internalized and trafficked to multivesicular bodies for exosomal secretion of p53, requiring both SNX9 and NUMB. Co-immunoprecipitation, live-cell imaging, exosome isolation and p53 tracking, SNX9 knockdown with functional p53 trafficking readout bioRxivpreprint Low bio_10.1101_2025.08.16.670648
2025 The SNX9 PX domain uses a non-canonical interface to selectively bind and sequester PI(3,4)P2 over PI(4,5)P2 during macropinocytic membrane ruffling. Mutational disruption of this non-canonical interface abolishes PI(3,4)P2 protection, demonstrating that SNX9 protects PI(3,4)P2 from hydrolysis. Actin assembly by SNX9 requires the combined PX-BAR and SH3 domain network; SNX9 can build both branched and bundled actin networks. Biolayer interferometry, cell-free reconstitution, live-cell imaging, molecular dynamics simulations, cryo-electron tomography, mutagenesis of PX domain residues bioRxivpreprint Medium bio_10.1101_2025.03.26.645564
2025 In B cells, SNX9 promotes the association of PI3K with CD19 in an AIM2-dependent manner, facilitating downstream PI3K-AKT signaling, and is involved in BCR/CD19 endocytosis and antigen uptake via SNX9-WASP interaction. IP-MS to identify SNX9 as AIM2 interactor, co-immunoprecipitation, BCR endocytosis assay, AIM2 knockout mice Cell death and differentiation Low 41437148
2026 ZG16 physically interacts with SNX9 and recruits the E3 ubiquitin ligase ITCH to promote ubiquitin-proteasome-dependent degradation of SNX9. IP-LC/MS, co-immunoprecipitation, GST pulldown, ubiquitination assay Hepatology international Low 41781795
2026 RAB40C promotes SNX9 degradation via the ubiquitin-proteasome pathway; silencing RAB40C increases SNX9 expression and influences Hippo signaling pathway target proteins. Co-immunoprecipitation, ubiquitination assay, siRNA knockdown with proliferation/invasion readouts Central-European journal of immunology Low 42245125
2025 SNX9 PX-BAR domain binds more PI(4,5)P2 and PI(3)P-containing liposomes than PI(3,4)P2 liposomes in terms of total binding capacity despite similar affinities. Actin assembly by SNX9 on membranes requires both PX-BAR and SH3 domain interactions. Biolayer interferometry, cell-free actin reconstitution, superresolution microscopy (3D-dSTORM) Molecular biology of the cell Medium 40105919

Source papers

Stage 0 corpus · 33 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Molecular biology of the cell 172 15703209
1999 Interaction of the metalloprotease disintegrins MDC9 and MDC15 with two SH3 domain-containing proteins, endophilin I and SH3PX1. The Journal of biological chemistry 149 10531379
2008 SNX9 regulates tubular invagination of the plasma membrane through interaction with actin cytoskeleton and dynamin 2. Journal of cell science 87 18388313
2009 SNX9 - a prelude to vesicle release. Journal of cell science 83 19092055
2002 The Cdc42 target ACK2 interacts with sorting nexin 9 (SH3PX1) to regulate epidermal growth factor receptor degradation. The Journal of biological chemistry 74 11799118
2023 Deletion of SNX9 alleviates CD8 T cell exhaustion for effective cellular cancer immunotherapy. Nature communications 71 36732507
2019 An SH3PX1-Dependent Endocytosis-Autophagy Network Restrains Intestinal Stem Cell Proliferation by Counteracting EGFR-ERK Signaling. Developmental cell 64 31006650
2016 Endocytosis, Metastasis and Beyond: Multiple Facets of SNX9. Trends in cell biology 59 27989654
2010 SNX18 shares a redundant role with SNX9 and modulates endocytic trafficking at the plasma membrane. Journal of cell science 57 20427313
2013 Phosphoinositides and membrane curvature switch the mode of actin polymerization via selective recruitment of toca-1 and Snx9. Proceedings of the National Academy of Sciences of the United States of America 46 23589871
2005 SNX9 as an adaptor for linking synaptojanin-1 to the Cdc42 effector ACK1. FEBS letters 43 16137687
2016 SNX9 promotes metastasis by enhancing cancer cell invasion via differential regulation of RhoGTPases. Molecular biology of the cell 40 26960793
2012 SNX9, SNX18 and SNX33 are required for progression through and completion of mitosis. Journal of cell science 33 22718350
2010 E. coli secreted protein F promotes EPEC invasion of intestinal epithelial cells via an SNX9-dependent mechanism. Cellular microbiology 29 20088948
2017 Attaching-and-Effacing Pathogens Exploit Junction Regulatory Activities of N-WASP and SNX9 to Disrupt the Intestinal Barrier. Cellular and molecular gastroenterology and hepatology 26 29675452
2011 A conserved role for SNX9-family members in the regulation of phagosome maturation during engulfment of apoptotic cells. PloS one 26 21494661
2022 Selective autophagy controls innate immune response through a TAK1/TAB2/SH3PX1 axis. Cell reports 23 35081354
2018 Sorting nexin 9 (SNX9) regulates levels of the transmembrane ADAM9 at the cell surface. The Journal of biological chemistry 18 29622675
2006 Dimerization is required for SH3PX1 tyrosine phosphorylation in response to epidermal growth factor signalling and interaction with ACK2. The Biochemical journal 18 16316319
2022 SNX9-induced membrane tubulation regulates CD28 cluster stability and signalling. eLife 12 35050850
2020 A direct role for SNX9 in the biogenesis of filopodia. The Journal of cell biology 12 32328641
2015 Depletion or over-expression of Sh3px1 results in dramatic changes in cell morphology. Biology open 12 26459243
2020 SNX9 Inhibits Cell Proliferation and Cyst Development in Autosomal Dominant Polycystic Kidney Disease via Activation of the Hippo-YAP Signaling Pathway. Frontiers in cell and developmental biology 10 32974348
2018 Regulation of SH3PX1 by dNedd4-long at the Drosophila neuromuscular junction. The Journal of biological chemistry 8 30518551
2024 SNX9 family mediates βarrestin-independent GPCR endocytosis. Communications biology 6 39511325
2020 Tanshinone IIA down-regulated p-Smad3 signaling to inhibit TGF-β1-mediated fibroblast proliferation via lncRNA-HSRL/SNX9. The international journal of biochemistry & cell biology 4 33049375
2025 AIM2 positively regulates B cell activation and function through the SNX9-PI3K-WASP axis. Cell death and differentiation 3 41437148
2022 Structure of SNX9 SH3 in complex with a viral ligand reveals the molecular basis of its unique specificity for alanine-containing class I SH3 motifs. Structure (London, England : 1993) 3 35390274
2021 Therapy-related acute myeloid leukemia with KMT2A-SNX9 gene fusion associated with a hyperdiploid karyotype after hemophagocytic lymphohistiocytosis. Cancer genetics 3 34034210
2026 ZG16 represses tumor progression and M2 polarization of tumor-associated macrophages in hepatocellular carcinoma by promoting ubiquitination and degradation of SNX9 via binding to ITCH. Hepatology international 0 41781795
2026 RAB40C regulates SNX9 stability via the ubiquitin-proteasome system and modulates the Hippo signaling pathway of prostate adenocarcinoma. Central-European journal of immunology 0 42245125
2025 Membrane composition and curvature in SNX9-mediated actin polymerization. Molecular biology of the cell 0 40105919
2020 Adding SNX to the mix: SNX9 drives filopodia biogenesis. The Journal of cell biology 0 32328644

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