ARV1 is a conserved multi-pass ER membrane protein. It is a component of the GPI N-acetylglucosaminyltransferase (GPI-GnT) complex that initiates glycosylphosphatidylinositol anchor biosynthesis: it binds PIGQ and helps the enzyme use phosphatidylinositol. Biallelic ARV1 variants reduce cell-surface GPI-anchored proteins and cause developmental and epileptic encephalopathy. ARV1 also takes part in cellular sterol homeostasis. Its ARV1 homology domain binds cholesterol and phospholipids, and loss of ARV1 retains cholesterol in the ER and suppresses SREBP signalling. In yeast, however, sterol transport between the ER and plasma membrane is intact without Arv1, and Arv1 instead maintains ER and plasma membrane structure. An alternative model holds that Arv1 helps deliver the GlcN-acyl-PI intermediate to the luminal face of the ER.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: Protein binding (IPI) with SCN3B, from the BioPlex affinity-purification network. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with MUC1, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with AQP6, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with EBP, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with SLC10A6, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with FAM209A, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with RNASEK, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with GPR152, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with CREB3L1, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with TLCD4, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with TMEM14B, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with SCN3B, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with TMX2, from the HuRI binary yeast two-hybrid map. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI) with SCN3B, from the BioPlex dual proteome-scale network. Generic protein binding carries no functional information and no specific term captures this interaction, so the row is removed. Removal does not mean the interaction is false. Reason: Removed under the generic protein-binding policy: GO:0005515 is uninformative on its own. |
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Endoplasmic reticulum (IBA). ARV1 is a resident ER membrane protein and a component of the ER-membrane GPI-GnT complex. Core location. Reason: [PMID:20663892 "Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein."] [PMID:40378954 "Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000375090 SUPPORTS TRANSFER Eukaryote-wide ARV1 node, seeded by yeast, Candida, Arabidopsis, mouse and human ARV1. ER residence is conserved. Supporting Evidence: PMID:20663892 Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein. PMID:40378954 Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000117 | ACCEPT | Summary: Endoplasmic reticulum (IEA). ARV1 is a resident ER membrane protein and a component of the ER-membrane GPI-GnT complex. Core location. Reason: [PMID:20663892 "Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein."] [PMID:40378954 "Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3."] Supporting Evidence: PMID:20663892 Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein. PMID:40378954 Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:20663892 Decreased expression of ARV1 results in cholesterol retentio... | ACCEPT | Summary: Endoplasmic reticulum membrane (IDA). ARV1 is a resident ER membrane protein and a component of the ER-membrane GPI-GnT complex. Core location. Reason: [PMID:20663892 "Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein."] [PMID:40378954 "Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3."] Supporting Evidence: PMID:20663892 Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein. PMID:40378954 Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Endoplasmic reticulum membrane (IEA). ARV1 is a resident ER membrane protein and a component of the ER-membrane GPI-GnT complex. Core location. Reason: [PMID:20663892 "Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein."] [PMID:40378954 "Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3."] Propagation Review Root cause: NO FAILURE CORE Sources checked: UniProtKB:Q9D0U9 SUPPORTS TRANSFER Mouse Arv1 (UniProtKB:Q9D0U9); ER membrane; human ARV1 has direct evidence (PMID:20663892). Supporting Evidence: PMID:20663892 Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein. PMID:40378954 Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. |
| GO:0005789 endoplasmic reticulum membrane | TAS Reactome:R-HSA-5250531 | ACCEPT | Summary: Endoplasmic reticulum membrane (TAS). ARV1 is a resident ER membrane protein and a component of the ER-membrane GPI-GnT complex. Core location. Reason: [PMID:20663892 "Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein."] [PMID:40378954 "Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3."] Supporting Evidence: PMID:20663892 Mammalian ARV1, which can fully complement the yeast lesion, encodes a ubiquitously expressed, resident ER protein. PMID:40378954 Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. |
| GO:0006506 GPI anchor biosynthetic process | IBA GO_REF:0000033 | ACCEPT | Summary: GPI anchor biosynthetic process (IBA). ARV1 is a component of the GPI-GnT complex that starts GPI biosynthesis and helps the enzyme use phosphatidylinositol. Biallelic ARV1 loss reduces surface GPI-anchored proteins, rescued by wild-type ARV1. Core process. Reason: [PMID:40378954 "Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3."] [PMID:40378954 "ARV1-containing GPI-GnT used PI more efficiently than ARV1-less GPI-GnT in an in vitro enzyme assay."] [PMID:34296759 "Flow cytometric analysis on patient fibroblasts showed a decrease in GPI-anchored proteins on the cell surface, supporting a lower residual activity of the mutant ARV1 as compared to the wildtype."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000375090 SUPPORTS TRANSFER Eukaryote-wide ARV1 node, seeded by budding yeast and Candida Arv1. Human ARV1 has its own GPI-GnT evidence (PMID:40378954). Supporting Evidence: PMID:40378954 Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. PMID:40378954 ARV1-containing GPI-GnT used PI more efficiently than ARV1-less GPI-GnT in an in vitro enzyme assay. PMID:34296759 Flow cytometric analysis on patient fibroblasts showed a decrease in GPI-anchored proteins on the cell surface, supporting a lower residual activity of the mutant ARV1 as compared to the wildtype. |
| GO:0006695 cholesterol biosynthetic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cholesterol biosynthetic process (IEA). ARV1 is not a sterol-biosynthetic enzyme. Its loss suppresses SREBP targets as an indirect consequence of ER cholesterol retention. The term overstates its role; marked as over-annotated. Reason: [PMID:20663892 "Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets."] [PMID:20663892 "Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets."] Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: ROLE CONFLATION Sources checked: UniProtKB:Q9D0U9 SOURCE WEAK OR INFERRED Mouse Arv1 (UniProtKB:Q9D0U9); donor IMP (PMID:20663892, PMID:26479315) reflects altered SREBP signalling, not participation in sterol synthesis. Supporting Evidence: PMID:20663892 Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. |
| GO:0006695 cholesterol biosynthetic process | TAS Reactome:R-HSA-191273 | MARK AS OVER ANNOTATED | Summary: Cholesterol biosynthetic process (TAS). ARV1 is not a sterol-biosynthetic enzyme. Its loss suppresses SREBP targets as an indirect consequence of ER cholesterol retention. The term overstates its role; marked as over-annotated. Reason: [file:reactome/R-HSA-191273.md "display_name: Cholesterol biosynthesis"] [PMID:20663892 "Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets."] Supporting Evidence: PMID:20663892 Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. |
| GO:0030301 cholesterol transport | IDA PMID:20663892 Decreased expression of ARV1 results in cholesterol retentio... | KEEP AS NON CORE | Summary: Cholesterol transport (IDA). The source reports ER cholesterol accumulation in ARV1-deficient HepG2 cells and mouse liver, an observation of altered sterol distribution. These are real phenotypes of a sterol-homeostasis role, but its mechanism is undefined. Direct yeast assays find sterol transport intact without Arv1. Kept as non-core. Reason: [PMID:20663892 "Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets."] [PMID:23668914 "We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency."] Supporting Evidence: PMID:20663892 Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. PMID:23668914 We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency. |
| GO:0032366 intracellular sterol transport | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Intracellular sterol transport (IEA, InterPro). ARV1 knockdown in mammalian cells retains cholesterol in the ER, but the transport step itself was tested directly in yeast: anterograde and retrograde sterol transport between ER and plasma membrane are unaffected by Arv1 loss. The term asserts the very activity that the direct assay rules out in yeast and that has not been assayed in mammals. Marked as over-annotated. Reason: [PMID:23668914 "We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency."] [PMID:20663892 "Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets."] Supporting Evidence: PMID:23668914 We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency. PMID:20663892 Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. |
| GO:0032383 regulation of intracellular cholesterol transport | IMP PMID:20663892 Decreased expression of ARV1 results in cholesterol retentio... | KEEP AS NON CORE | Summary: Regulation of intracellular cholesterol transport (IMP). ARV1 knockdown in HepG2 cells and mouse liver retains cholesterol in the ER and suppresses SREBP signalling. These are real phenotypes of a sterol-homeostasis role, but its mechanism is undefined. Direct yeast assays find sterol transport intact without Arv1. Kept as non-core. Reason: [PMID:20663892 "Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets."] [PMID:23668914 "We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency."] Supporting Evidence: PMID:20663892 Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. PMID:23668914 We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency. |
| GO:0090181 regulation of cholesterol metabolic process | IMP PMID:20663892 Decreased expression of ARV1 results in cholesterol retentio... | KEEP AS NON CORE | Summary: Regulation of cholesterol metabolic process (IMP). ARV1 knockdown in HepG2 cells and mouse liver retains cholesterol in the ER and suppresses SREBP signalling. These are real phenotypes of a sterol-homeostasis role, but its mechanism is undefined. Direct yeast assays find sterol transport intact without Arv1. Kept as non-core. Reason: [PMID:20663892 "Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets."] [PMID:23668914 "We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency."] Supporting Evidence: PMID:20663892 Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. PMID:23668914 We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency. |
| GO:0120015 sterol transfer activity | IEA GO_REF:0000107 | MODIFY | Summary: Sterol transfer activity (IEA). ARV1 knockdown retains cholesterol in the ER, and Reactome describes ARV1 as a likely candidate for ER-to-plasma-membrane cholesterol transport. Purified ARV1 binds cholesterol, but no sterol transfer between membranes has been shown, and direct transport assays in yeast find ER-plasma membrane sterol transport unaffected by Arv1 loss. Modified to cholesterol binding. Reason: [PMID:20663892 "Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets."] [PMID:39952408 "Both full-length ARV1 and the AHD bound cholesterol, several phospholipids, and phosphoinositides with high affinity."] [PMID:23668914 "We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency."] Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: SOURCE EVIDENCE WEAK Sources checked: UniProtKB:Q9D0U9 SOURCE WEAK OR INFERRED Mouse Arv1 (UniProtKB:Q9D0U9); donor IMP (PMID:20663892, PMID:26479315) shows a cholesterol-distribution phenotype, not a transfer activity. Proposed replacements: cholesterol binding Supporting Evidence: PMID:20663892 Knockdown of ARV1 in murine liver and HepG2 cells was associated with accumulation of cholesterol in the ER at the expense of the plasma membrane and suppression of sterol regulatory element-binding proteins and their targets. PMID:39952408 Both full-length ARV1 and the AHD bound cholesterol, several phospholipids, and phosphoinositides with high affinity. PMID:23668914 We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency. |
| GO:0120015 sterol transfer activity | TAS Reactome:R-HSA-5250531 | MODIFY | Summary: Sterol transfer activity (TAS). ARV1 knockdown retains cholesterol in the ER, and Reactome describes ARV1 as a likely candidate for ER-to-plasma-membrane cholesterol transport. Purified ARV1 binds cholesterol, but no sterol transfer between membranes has been shown, and direct transport assays in yeast find ER-plasma membrane sterol transport unaffected by Arv1 loss. Modified to cholesterol binding. Reason: [file:reactome/R-HSA-5250531.md "display_name: ARV1 transports CHOL from ER membrane to plasma membrane"] [file:reactome/R-HSA-5250531.md "but a likely candidate is protein ARV1 (ARV1). Studies with mutant yeast Arv1 indicate"] [PMID:39952408 "Both full-length ARV1 and the AHD bound cholesterol, several phospholipids, and phosphoinositides with high affinity."] [PMID:23668914 "We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency."] Proposed replacements: cholesterol binding Supporting Evidence: file:reactome/R-HSA-5250531.md display_name: ARV1 transports CHOL from ER membrane to plasma membrane PMID:39952408 Both full-length ARV1 and the AHD bound cholesterol, several phospholipids, and phosphoinositides with high affinity. PMID:23668914 We report that sterol transport between the ER and PM is unaffected by Arv1 deficiency. |
| GO:0000506 glycosylphosphatidylinositol-N-acetylglucosaminyltransferase (GPI-GnT) complex | IDA PMID:40378954 ARV1 is a component of the enzyme initiating glycosylphospha... | NEW | Summary: GPI-GnT complex (NEW, IDA). ARV1 is a component of the GPI N-acetylglucosaminyltransferase complex that initiates GPI biosynthesis. It associates with PIGQ, and mutants that cannot bind PIGQ no longer enhance GPI-GnT activity. Reason: [PMID:40378954 "Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3."] [PMID:40378954 "ARV1 associates with PIGQ, a GPI-GnT component, and ARV1 mutants defective in this association lose their ability to enhance GPI-GnT activity, showing that association with PIGQ is critical for ARV1's function."] Supporting Evidence: PMID:40378954 Here, we show that ARV1 acts as a component of the enzyme initiating GPI biosynthesis, GPI N-acetylglucosaminyltransferase (GPI-GnT) complex, which forms a ring structure as predicted by AlphaFold3. PMID:40378954 ARV1 associates with PIGQ, a GPI-GnT component, and ARV1 mutants defective in this association lose their ability to enhance GPI-GnT activity, showing that association with PIGQ is critical for ARV1's function. |
| GO:0017176 phosphatidylinositol N-acetylglucosaminyltransferase activity | IDA PMID:40378954 ARV1 is a component of the enzyme initiating glycosylphospha... | NEW | Summary: Phosphatidylinositol N-acetylglucosaminyltransferase activity (NEW, IDA, contributes_to). The catalytic subunit is PIGA. ARV1-containing GPI-GnT uses PI more efficiently in vitro, and ARV1 mutants that cannot bind PIGQ lose this enhancement. ARV1 therefore contributes to the complex's activity, as PIGP and PIGY do. Reason: [PMID:40378954 "ARV1-containing GPI-GnT used PI more efficiently than ARV1-less GPI-GnT in an in vitro enzyme assay."] [PMID:40378954 "ARV1 associates with PIGQ, a GPI-GnT component, and ARV1 mutants defective in this association lose their ability to enhance GPI-GnT activity, showing that association with PIGQ is critical for ARV1's function."] Supporting Evidence: PMID:40378954 ARV1-containing GPI-GnT used PI more efficiently than ARV1-less GPI-GnT in an in vitro enzyme assay. PMID:40378954 ARV1 associates with PIGQ, a GPI-GnT component, and ARV1 mutants defective in this association lose their ability to enhance GPI-GnT activity, showing that association with PIGQ is critical for ARV1's function. |
| GO:0005543 phospholipid binding | IDA PMID:39952408 The sterol-regulating human ARV1 binds cholesterol and phosp... | NEW | Summary: Phospholipid binding (NEW, IDA). Purified ARV1 and its ARV1 homology domain bind several phospholipids and phosphoinositides with high affinity, and conserved AHD residues are needed for phospholipid binding. Phosphatidylinositol binding is a candidate link between its GPI-GnT and sterol roles. Reason: [PMID:39952408 "Both full-length ARV1 and the AHD bound cholesterol, several phospholipids, and phosphoinositides with high affinity."] [PMID:39952408 "Several conserved amino acids within the AHD were necessary for phospholipid binding."] Supporting Evidence: PMID:39952408 Both full-length ARV1 and the AHD bound cholesterol, several phospholipids, and phosphoinositides with high affinity. PMID:39952408 Several conserved amino acids within the AHD were necessary for phospholipid binding. |
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Download this section (compressed HTML)Q: Are ARV1's GPI-GnT role and its sterol-homeostasis role linked, for example through phosphatidylinositol or sterol binding by its ARV1 homology domain?
Q: Does mammalian ARV1 affect ER-to-plasma membrane cholesterol transport when assayed directly, or, as in yeast, is the ER cholesterol accumulation a consequence of altered membrane homeostasis?
Q: Is ARV1 a GPI-GnT subunit that enhances PI use, a flippase-like factor delivering GlcN-acyl-PI to the ER lumen, or both?
Experiment: Test whether AHD lipid-binding mutants separate GPI-GnT enhancement from ER cholesterol export in ARV1-null cells.
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