Stomatin (STOM/EPB72/Band 7.2b) is a 31-kDa integral membrane-associated scaffolding protein of the SPFH (stomatin-prohibitin-flotillin-HflK/C) superfamily. The protein contains a characteristic Band-7/SPFH domain and forms homo-oligomeric complexes (9-12 monomers) that organize cholesterol-rich, detergent-resistant membrane microdomains (lipid rafts). Stomatin is palmitoylated at Cys-30 and Cys-87, anchoring it to the cytoplasmic leaflet of the plasma membrane via an intramembrane hydrophobic segment (residues 26-54). The protein is abundantly expressed in erythrocyte membranes and platelets, where it associates with transporters and ion channels including GLUT1 (SLC2A1), anion exchanger 1 (AE1/SLC4A1), and aquaporin-1. Stomatin positively regulates AE1-mediated Cl-/HCO3- exchange activity through direct protein-protein interaction, and modulates GLUT1 substrate preference toward L-dehydroascorbic acid (DHA) during erythroid maturation. Loss of stomatin in hereditary stomatocytosis (stomatin-deficient cryohydrocytosis) is associated with RBC cation leak and hemolytic anemia. Stomatin also modulates acid-sensing ion channel (ASIC) activity, functioning as an ion channel inhibitor in the broader context of mechanosensation and chemosensation.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0008200 ion channel inhibitor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Stomatin regulates ASIC2 and ASIC3 channel activity according to UniProt functional annotation. The IBA annotation is consistent with the SPFH family paradigm where stomatin-domain proteins modulate acid-sensing ion channels in sensory signaling contexts [PMID:31949695, Carattino & Montalbetti 2020]. This represents a core function of the stomatin family. Reason: The IBA annotation correctly captures stomatin's role as an ion channel modulator. UniProt states "Regulates ion channel activity and transmembrane ion transport. Regulates ASIC2 and ASIC3 channel activity" with evidence from similarity to mouse stomatin (UniProtKB:P54116). This function is phylogenetically conserved across the SPFH family. Supporting Evidence: UniProt:P27105 Regulates ion channel activity and transmembrane ion transport. Regulates ASIC2 and ASIC3 channel activity. file:human/STOM/STOM-deep-research-falcon.md model: Edison Scientific Literature |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane localization is a core characteristic of stomatin, extensively documented in erythrocytes, platelets, and epithelial cells [PMID:1547348, PMID:12130500, PMID:9243190]. Reason: Stomatin localizes to the plasma membrane as a lipid-anchored peripheral membrane protein on the cytoplasmic side. This is a fundamental aspect of its function as a membrane microdomain scaffold. Supporting Evidence: PMID:1547348 Human red blood cells (RBCs) that are deficient in an integral membrane-associated protein ("stomatin") of apparent molecular mass 31 Kd show a catastrophic increase in passive membrane permeability to the univalent cations Na+ and K+ and are stomatocytic in shape. PMID:12130500 Stomatin, a major lipid-raft component of erythrocytes and epithelial cells, is also an abundant platelet protein. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Stomatin associates with the cortical actin cytoskeleton according to multiple studies [PMID:1547348, PMID:9243190, PMID:9642292]. This is supported by experimental evidence. Reason: Stomatin colocalizes with cortical actin microfilaments at small plasma membrane protrusions and the protein binds to the cytoskeleton according to detergent solubilization studies. UniProt notes "Colocalizes with cortical actin microfilaments at small plasma membrane protrusions" based on PMID:9243190. Supporting Evidence: PMID:1547348 Selective solubilization studies using detergents show that while the protein is strongly associated with the phospholipid bilayer, it also binds to the cytoskeleton. PMID:9642292 There is also evidence that stomatin is linked to the cortical actin cytoskeleton, suggesting a role in cortical morphogenesis of the cell. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Duplicate plasma membrane annotation via automated IEA. The annotation is correct but redundant with other plasma membrane annotations. Reason: Plasma membrane localization is well-established for stomatin. Duplicate annotations with different evidence codes are acceptable. |
| GO:0016020 membrane | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Generic membrane annotation inferred from InterPro domains. This is too broad given the well-characterized plasma membrane localization. Reason: While correct (stomatin is a membrane protein), this generic term is subsumed by the more specific plasma membrane annotations. It provides minimal additional information. |
| GO:0031410 cytoplasmic vesicle | IEA GO_REF:0000120 | ACCEPT | Summary: Stomatin localizes to cytoplasmic vesicles including alpha granules in platelets and is released in microvesicles upon platelet activation [PMID:12130500]. Reason: UniProt notes "Translocates from the alpha-granular lipid rafts to the cell membrane on thrombin activation and selectively enriched in released microvesicles." Supporting Evidence: PMID:12130500 Activation of platelets by calcium ionophore A23187 or thrombin led to translocation of stomatin to the plasma membrane, cleavage by calpain, and specific sorting into released microvesicles. |
| GO:0042470 melanosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Stomatin was identified by mass spectrometry in melanosome fractions (stages I-IV) according to UniProt (PMID:12643545, PMID:17081065). Reason: Melanosome localization is documented from proteomic studies but represents a cell-type specific observation rather than a core function. UniProt states "Identified by mass spectrometry in melanosome fractions from stage I to stage IV." |
| GO:0045121 membrane raft | IEA GO_REF:0000044 | ACCEPT | Summary: Lipid raft/membrane raft localization is a fundamental characteristic of stomatin as an SPFH family member. This is strongly supported by experimental evidence [PMID:12130500, PMID:23219802]. Reason: Stomatin is a major lipid raft component and organizes detergent-resistant membrane microdomains. This is central to its function as a membrane scaffold. Supporting Evidence: PMID:12130500 Lipid rafts are detergent-resistant, cholesterol- and sphingolipid-rich membrane domains that are involved in important cellular processes such as signal transduction and intracellular trafficking. |
| GO:0005515 protein binding | IPI PMID:19696025 Stomatin-like protein-1 interacts with stomatin and is targe... | MARK AS OVER ANNOTATED | Summary: This annotation refers to stomatin interaction with STOML1 (stomatin-like protein 1). However, protein binding is an uninformative term that should be replaced with more specific molecular function terms. Reason: Generic protein binding annotations provide no functional insight. The specific interaction with STOML1 is better captured through interaction databases. UniProt notes "Interacts with STOML1; may redistribute STOM from the plasma membrane to late endosomes." Proposed replacements: identical protein binding Supporting Evidence: PMID:19696025 2009 Aug 20. Stomatin-like protein-1 interacts with stomatin and is targeted to late endosomes. |
| GO:0005515 protein binding | IPI PMID:23219802 Stomatin interacts with GLUT1/SLC2A1, band 3/SLC4A1, and aqu... | MARK AS OVER ANNOTATED | Summary: This publication demonstrates stomatin interaction with GLUT1/SLC2A1, band 3/SLC4A1, and aquaporin-1 in human erythrocyte membrane domains. These are functionally meaningful interactions. Reason: The generic protein binding term does not capture the specific scaffold/adaptor function of stomatin. The interactions with GLUT1, AE1, and AQP1 are better described through other annotations. Supporting Evidence: PMID:28387307 The identification, as stomatin partners, of the glucose transporter (GLUT1), as well as of anion exchanger 1 (AE1) and water channel aquaporin-1 (AQP1) suggests that stomatin within cholesterol-rich membrane domains plays a role as a membrane-bound scaffolding protein modulating transport proteins. PMID:23219802 Stomatin interacts with GLUT1/SLC2A1, band 3/SLC4A1, and aquaporin-1 in human erythrocyte membrane domains. |
| GO:0005515 protein binding | IPI PMID:25262680 Interaction of stomatin with hepatitis C virus RNA polymeras... | KEEP AS NON CORE | Summary: This publication identifies stomatin interaction with HCV NS5B RNA polymerase. This represents a host-pathogen interaction rather than a core molecular function. Reason: The interaction with viral RNA polymerase is a pathogen exploitation of stomatin's membrane scaffolding function, not a core physiological role. Supporting Evidence: PMID:25262680 In this study, we took a proteomic approach to identify stomatin, a member of the integral proteins of lipid rafts, as a cellular protein interacting with HCV NS5B. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | MARK AS OVER ANNOTATED | Summary: High-throughput interactome mapping study. Generic protein binding from HTP data. Reason: Large-scale proteomics studies generate many protein binding annotations that lack functional context. The generic term does not inform on stomatin's actual molecular function. Supporting Evidence: PMID:25416956 A proteome-scale map of the human interactome network. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MARK AS OVER ANNOTATED | Summary: Reference map of human binary protein interactome. Generic protein binding from systematic interactome mapping. Reason: High-throughput protein interaction data leading to generic protein binding annotation. The identical protein binding annotation from the same PMID is more specific and informative. Supporting Evidence: PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Dual proteome-scale networks study. Generic protein binding from HTP interactome data. Reason: Large-scale interactome study generating uninformative generic protein binding annotations. Supporting Evidence: PMID:33961781 2021 May 6. Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. |
| GO:0042802 identical protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | ACCEPT | Summary: Stomatin forms homo-oligomeric complexes comprising 9-12 monomers as demonstrated by density gradient centrifugation and co-immunoprecipitation [PMID:9642292]. This self-interaction is essential for its scaffolding function. Reason: Homo-oligomerization is a fundamental property of stomatin required for membrane microdomain organization. The C-terminus is required for homo-oligomeric interaction. Supporting Evidence: PMID:9642292 In this study, we demonstrate that the fundamental structure of stomatin is oligomeric. PMID:32296183 Apr 8. A reference map of the human binary protein interactome. |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stomatin has cytoplasmic domains (both N- and C-termini are cytoplasmic) but primarily functions at the plasma membrane. The cytoplasmic localization is not well characterized beyond the membrane-associated pool. Reason: While stomatin has cytoplasmic exposure, the primary functional localization is at membrane microdomains. The IEA annotation from Ensembl Compara ortholog transfer is acceptable but represents a peripheral aspect of localization. |
| GO:0005739 mitochondrion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Mitochondrial localization is reported in PMID:25262680 (IDA evidence from AgBase) but represents a minor pool. The primary localization is plasma membrane/lipid rafts. Reason: Mitochondrial localization has experimental support from mass spectrometry (N-terminome analysis, PMID:25944712) but does not represent the core functional localization of stomatin. |
| GO:0008200 ion channel inhibitor activity | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate of the IBA annotation for ion channel inhibitor activity. Both are valid and supported by evidence for ASIC modulation. Reason: Ion channel inhibitor activity is a core molecular function of stomatin. Multiple evidence codes support this annotation. |
| GO:0034765 regulation of monoatomic ion transmembrane transport | IEA GO_REF:0000107 | ACCEPT | Summary: Stomatin regulates ion transmembrane transport through modulation of ASIC channels and effects on the anion exchanger AE1. This process annotation is consistent with the molecular function annotations. Reason: Regulation of ion transport is a core biological process for stomatin, supported by evidence showing stomatin modulates AE1 Cl-/HCO3- exchange activity and ASIC channel activity. Supporting Evidence: PMID:28387307 Here we show that stomatin modulates the transport activity of AE1 through a direct protein-protein interaction. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: Duplicate annotation for identical protein binding (homo-oligomerization). Well-supported by experimental evidence. Reason: Homo-oligomerization is essential for stomatin function and this annotation is well-supported regardless of evidence code. |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: Stomatin forms banana-shaped homodimers that further assemble into higher-order oligomers (9-12 mers) [PMID:9642292]. Crystal structures of mouse stomatin SPFH domain reveal typical banana-shaped dimers [PMID:28387307]. Reason: Homodimerization is the fundamental structural unit of stomatin oligomers. This is well-documented and represents a core molecular function. Supporting Evidence: PMID:28387307 Crystal structures of a SFPH-domain of mouse stomatin revealed typical banana-shaped dimers which can further assemble via two conserved surfaces into a cylindrical oligomer |
| GO:0044829 host-mediated activation of viral genome replication | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Stomatin interaction with HCV NS5B stabilizes viral replicase complexes on detergent-resistant membranes [PMID:25262680]. This is a pathogen exploitation of stomatin's scaffolding function. Reason: While experimentally supported, viral genome replication support represents pathogen exploitation rather than a core physiological function of stomatin. Supporting Evidence: PMID:25262680 Our results identify stomatin as a cellular protein that plays a role in the formation of an enzymatically active HCV RC on a detergent-resistant membrane structure. |
| GO:0048471 perinuclear region of cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: UniProt notes stomatin localizes to a "juxtanuclear structure probably derived from the Golgi apparatus" [PMID:9243190]. This perinuclear localization is consistent with trafficking through the secretory pathway. Reason: Perinuclear localization is observed but represents trafficking/biosynthetic intermediates rather than the primary functional localization at plasma membrane. |
| GO:0048524 positive regulation of viral process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Related to HCV replication support. Stomatin silencing inhibits HCV replication by releasing NS5B from detergent-resistant membranes [PMID:25262680]. Reason: Viral process regulation is a consequence of stomatin's membrane scaffolding being exploited by HCV, not a core physiological function. |
| GO:0090314 positive regulation of protein targeting to membrane | IEA GO_REF:0000107 | UNDECIDED | Summary: This annotation may relate to stomatin's role in organizing membrane protein complexes and its effects on transporter localization and activity. Reason: The evidence for stomatin specifically regulating protein targeting to membrane is unclear. Stomatin affects transporter activity but the mechanism may not involve targeting per se. More evidence needed. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Plasma membrane localization from immunofluorescence data curation. Well-supported. Reason: Plasma membrane is the primary functional localization of stomatin. |
| GO:0005515 protein binding | IPI PMID:28387307 Stomatin modulates the activity of the Anion Exchanger 1 (AE... | MARK AS OVER ANNOTATED | Summary: This publication demonstrates stomatin interaction with AE1 (SLC4A1) using proximity ligation assay and shows stomatin positively regulates AE1 activity. Reason: The specific interaction is with SLC4A1/AE1 and the functional outcome is modulation of anion exchanger activity. The generic protein binding term is uninformative for describing this specific functional relationship. Supporting Evidence: PMID:28387307 In situ Proximity Ligation Assays confirmed an interaction of AE1 with stomatin, in both HEK recombinant cells and RBCs. |
| GO:0005886 plasma membrane | IDA PMID:9642292 Oligomeric nature of the integral membrane protein stomatin. | ACCEPT | Summary: Stomatin plasma membrane localization demonstrated through immunofluorescence and biochemical fractionation studies. Reason: Primary localization of stomatin at plasma membrane is well-established. Supporting Evidence: PMID:9642292 We have previously shown in the human cell line UAC that stomatin concentrates preferentially in plasma membrane folds and protrusions. |
| GO:0042802 identical protein binding | IPI PMID:9642292 Oligomeric nature of the integral membrane protein stomatin. | ACCEPT | Summary: This study directly demonstrates stomatin homo-oligomerization using co-immunoprecipitation and density gradient centrifugation. Reason: Key experimental evidence for stomatin homo-oligomerization. The fundamental structure of stomatin is oligomeric (9-12 monomers). Supporting Evidence: PMID:9642292 We also show the existence of these oligomers by co-immunoprecipitation of the endogenous stomatin and a recombinantly expressed myc-tagged stomatin, using an anti-myc antibody. |
| GO:0035577 azurophil granule membrane | TAS Reactome:R-HSA-6798739 | KEEP AS NON CORE | Summary: Stomatin localizes to neutrophil azurophil granule membranes according to Reactome annotation for neutrophil degranulation pathway. Reason: Azurophil granule membrane localization in neutrophils is cell-type specific and represents a peripheral aspect of stomatin localization, not its core erythrocyte/platelet function. |
| GO:0035579 specific granule membrane | TAS Reactome:R-HSA-6799350 | KEEP AS NON CORE | Summary: Stomatin localizes to neutrophil specific granule membranes according to Reactome. Reason: Neutrophil granule localization is cell-type specific, not core function. |
| GO:0070821 tertiary granule membrane | TAS Reactome:R-HSA-6798747 | KEEP AS NON CORE | Summary: Stomatin localizes to neutrophil tertiary granule membranes according to Reactome. Reason: Neutrophil granule localization is cell-type specific, not core function. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798739 | ACCEPT | Summary: Plasma membrane localization from Reactome. Redundant with other PM annotations. Reason: Plasma membrane is the primary functional localization of stomatin. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798747 | ACCEPT | Summary: Plasma membrane localization from Reactome. Redundant with other PM annotations. Reason: Plasma membrane is well-established localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6799350 | ACCEPT | Summary: Plasma membrane localization from Reactome. Redundant with other PM annotations. Reason: Plasma membrane is well-established localization. |
| GO:0005739 mitochondrion | IDA PMID:25262680 Interaction of stomatin with hepatitis C virus RNA polymeras... | KEEP AS NON CORE | Summary: Mitochondrial localization detected in the context of HCV infection study. This may represent a minor pool or context-specific localization. Reason: Mitochondrial localization is not the primary functional location of stomatin. The plasma membrane/lipid raft localization is the core functional site. Supporting Evidence: PMID:25262680 Interaction of stomatin with hepatitis C virus RNA polymerase stabilizes the viral RNA replicase complexes on detergent-resistant membranes. |
| GO:0005783 endoplasmic reticulum | IDA PMID:25262680 Interaction of stomatin with hepatitis C virus RNA polymeras... | KEEP AS NON CORE | Summary: ER localization detected in HCV infection study, likely related to the association with viral replication complexes on modified ER membranes. Reason: ER localization may represent biosynthetic trafficking or context-specific localization during viral infection, not core functional localization. Supporting Evidence: PMID:25262680 Interaction of stomatin with hepatitis C virus RNA polymerase stabilizes the viral RNA replicase complexes on detergent-resistant membranes. |
| GO:0070063 RNA polymerase binding | IPI PMID:25262680 Interaction of stomatin with hepatitis C virus RNA polymeras... | KEEP AS NON CORE | Summary: Stomatin binds HCV NS5B RNA-dependent RNA polymerase. This is a host-pathogen interaction, not a normal physiological function. Reason: RNA polymerase binding specifically refers to interaction with viral RdRp (HCV NS5B). This represents pathogen exploitation of stomatin's scaffolding function, not a core cellular function. Supporting Evidence: PMID:25262680 In this study, we took a proteomic approach to identify stomatin, a member of the integral proteins of lipid rafts, as a cellular protein interacting with HCV NS5B. |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | ACCEPT | Summary: Stomatin is detected in extracellular exosomes by proteomics. This is consistent with its release in platelet microvesicles upon activation. Reason: Stomatin is released in microvesicles/exosomes upon cell activation, documented in platelets [PMID:12130500] and various proteomics studies. Supporting Evidence: PMID:12130500 Activation of platelets by calcium ionophore A23187 or thrombin led to translocation of stomatin to the plasma membrane, cleavage by calpain, and specific sorting into released microvesicles. PMID:23533145 2013 Apr 23. In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. |
| GO:0031982 vesicle | HDA PMID:19190083 Characterization of exosome-like vesicles released from huma... | ACCEPT | Summary: Stomatin detected in vesicle fractions from tracheobronchial epithelium proteomics. Reason: Vesicle localization is consistent with stomatin's presence in cytoplasmic vesicles, granules, and released microvesicles. Supporting Evidence: PMID:19190083 Characterization of exosome-like vesicles released from human tracheobronchial ciliated epithelium: a possible role in innate defense. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | KEEP AS NON CORE | Summary: Generic membrane annotation from NK cell membrane proteome study. Reason: Generic membrane term is subsumed by more specific localizations. Acceptable but not informative. Supporting Evidence: PMID:19946888 Defining the membrane proteome of NK cells. |
| GO:0005615 extracellular space | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | KEEP AS NON CORE | Summary: Stomatin detected in human colostrum proteomics. May represent secreted/shed protein in body fluids. Reason: Extracellular space detection in proteomics studies reflects release via microvesicles/exosomes rather than a primary secreted function. Supporting Evidence: PMID:16502470 Human colostrum: identification of minor proteins in the aqueous phase by proteomics. |
| GO:0072562 blood microparticle | HDA PMID:22516433 Proteomic analysis of microvesicles from plasma of healthy d... | ACCEPT | Summary: Stomatin detected in blood microparticles, consistent with platelet-derived microvesicle release. Reason: Blood microparticle localization is consistent with documented stomatin release in platelet microvesicles upon activation. Supporting Evidence: PMID:12130500 Activation of platelets by calcium ionophore A23187 or thrombin led to translocation of stomatin to the plasma membrane, cleavage by calpain, and specific sorting into released microvesicles. PMID:22516433 Epub 2012 Apr 10. Proteomic analysis of microvesicles from plasma of healthy donors reveals high individual variability. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | ACCEPT | Summary: Stomatin detected in urinary exosomes by proteomics. Reason: Exosome localization is consistent with stomatin's membrane association and release in extracellular vesicles. Supporting Evidence: PMID:19056867 2008 Dec 3. Large-scale proteomics and phosphoproteomics of urinary exosomes. |
| GO:0070062 extracellular exosome | HDA PMID:21362503 Protein profile of exosomes from trabecular meshwork cells. | ACCEPT | Summary: Stomatin detected in trabecular meshwork cell exosomes by proteomics. Reason: Multiple proteomics studies confirm stomatin presence in exosomes from various cell types. Supporting Evidence: PMID:21362503 Epub 2011 Mar 8. Protein profile of exosomes from trabecular meshwork cells. |
| GO:0005856 cytoskeleton | IDA PMID:1547348 Isolation of cDNA coding for an ubiquitous membrane protein ... | ACCEPT | Summary: This seminal paper establishing stomatin biochemistry shows stomatin binds to the cytoskeleton based on detergent solubilization studies. Reason: Cytoskeletal association is a core feature of stomatin, linking it to cortical actin and providing structural basis for membrane organization. Supporting Evidence: PMID:1547348 Selective solubilization studies using detergents show that while the protein is strongly associated with the phospholipid bilayer, it also binds to the cytoskeleton. |
| GO:0005886 plasma membrane | IDA PMID:1547348 Isolation of cDNA coding for an ubiquitous membrane protein ... | ACCEPT | Summary: Plasma membrane localization established in this foundational paper on stomatin. Reason: Primary reference establishing stomatin as a plasma membrane-associated protein in erythrocytes. Supporting Evidence: PMID:1547348 Human red blood cells (RBCs) that are deficient in an integral membrane-associated protein ("stomatin") of apparent molecular mass 31 Kd show a catastrophic increase in passive membrane permeability to the univalent cations Na+ and K+ and are stomatocytic in shape. |
| GO:0045121 membrane raft | IDA PMID:12130500 Stomatin is a major lipid-raft component of platelet alpha g... | ACCEPT | Summary: This key paper establishes stomatin as a major lipid raft component, demonstrating its association with detergent-resistant membranes in platelets. Reason: Lipid raft localization is central to stomatin function as a membrane microdomain scaffold. This is a core localization. Supporting Evidence: PMID:12130500 Stomatin and the flotillins were associated with Triton X-100-insoluble lipid rafts. |
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Download this section (compressed HTML)Q: What is the precise mechanism by which stomatin modulates ASIC channel gating? Is there direct structural interaction or is the effect mediated through membrane microdomain organization?
Q: Does stomatin interact with and modulate Piezo mechanosensitive channels, given the role of stomatin-like proteins in mechanosensation?
Q: What determines whether stomatin activates (AE1) versus inhibits (ASICs) different transport proteins?
Experiment: Cryo-EM structural analysis of full-length human stomatin oligomers in nanodiscs or reconstituted lipid bilayers to determine the precise architecture of membrane-associated complexes.
Experiment: Electrophysiological studies of ASIC channels in stomatin-knockout cells versus wild-type to quantify the magnitude of stomatin-mediated inhibition and determine mechanism (gating, trafficking, or surface expression).
Experiment: Proximity-dependent biotinylation (BioID/TurboID) in erythroid cells to comprehensively map the stomatin interactome and identify additional transporter/channel partners.
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