ARRDC3 is an alpha-arrestin (arrestin domain-containing) protein at the plasma membrane and mainly on early endosomes. Through two C-terminal PPxY motifs it binds NEDD4-family HECT ubiquitin ligases (NEDD4, WWP2, ITCH) and links them to cargo. It is required for WWP2-dependent ubiquitination of ALIX, which sorts the GPCR PAR1 at late endosomes for lysosomal degradation. It promotes ubiquitination and degradation of phosphorylated beta-4 integrin, and ITCH-mediated degradation of YAP. It sequesters TAZ through PPxY-WW contacts independently of trafficking. ARRDC3 binds beta2-adrenergic receptor directly and ligand-independently via a basic patch in its N-terminal lobe. Its role there is debated: early work saw NEDD4 recruitment for receptor degradation, while later studies place it as a secondary endosomal adaptor or as a brake on SNX27-mediated recycling. ARRDC3 is itself ubiquitinated through its PPxY motifs, and phosphorylation of Tyr394 switches its binding from WWP2 to c-Src. Arrdc3-deficient mice resist obesity with higher energy expenditure and adipocyte Ucp1, and ARRDC3 loss in invasive breast cancer causes persistent PAR1 signalling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:20603614 ARRDC3 suppresses breast cancer progression by negatively re... | MODIFY | Summary: Protein binding (IPI) with ITGB4. ARRDC3 binds phosphorylated beta-4 integrin and drives its internalization, ubiquitination and degradation. Modified to integrin binding. Reason: [PMID:20603614 "Our data indicates ARRDC3 directly binds to a phosphorylated form of ITGbeta4 leading to its internalization, ubiquitination and ultimate degradation."] Proposed replacements: integrin binding Supporting Evidence: PMID:20603614 Our data indicates ARRDC3 directly binds to a phosphorylated form of ITGbeta4 leading to its internalization, ubiquitination and ultimate degradation. |
| GO:0005515 protein binding | IPI PMID:23208550 Distinct roles for Ξ²-arrestin2 and arrestin-domain-containin... | MODIFY | Summary: Protein binding (IPI) with ADRB2, from the beta2AR trafficking study. ARRDC3 binds beta2-adrenergic receptor directly and ligand-independently, and basic-patch residues in its N-terminal arrestin lobe are needed for binding. Whether it acts as a primary or a secondary adaptor relative to beta-arrestin2 is debated. Modified to beta-2 adrenergic receptor binding. Reason: [PMID:25220262 "Residues within the basic patch were shown to be important for binding to Ξ²2AR, similar to the situation with Ξ²-arrestins."] [PMID:27226565 "We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner."] [PMID:23208550 "The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2."] Proposed replacements: beta-2 adrenergic receptor binding Supporting Evidence: PMID:25220262 Residues within the basic patch were shown to be important for binding to Ξ²2AR, similar to the situation with Ξ²-arrestins. PMID:27226565 We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner. PMID:20559325 The ARRDC3 protein also interacts and co-localizes with activated beta2AR. PMID:23208550 The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2. |
| GO:0005515 protein binding | IPI PMID:23208550 Distinct roles for Ξ²-arrestin2 and arrestin-domain-containin... | MODIFY | Summary: Protein binding (IPI) with NEDD4, from the beta2AR trafficking study. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | MODIFY | Summary: Protein binding (IPI) with WWP2, from the alpha-arrestin trafficking study. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | MODIFY | Summary: Protein binding (IPI) with ADRB2, from the alpha-arrestin trafficking study. ARRDC3 binds beta2-adrenergic receptor directly and ligand-independently, and basic-patch residues in its N-terminal arrestin lobe are needed for binding. Whether it acts as a primary or a secondary adaptor relative to beta-arrestin2 is debated. Modified to beta-2 adrenergic receptor binding. Reason: [PMID:25220262 "Residues within the basic patch were shown to be important for binding to Ξ²2AR, similar to the situation with Ξ²-arrestins."] [PMID:27226565 "We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner."] [PMID:23208550 "The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2."] Proposed replacements: beta-2 adrenergic receptor binding Supporting Evidence: PMID:25220262 Residues within the basic patch were shown to be important for binding to Ξ²2AR, similar to the situation with Ξ²-arrestins. PMID:27226565 We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner. PMID:20559325 The ARRDC3 protein also interacts and co-localizes with activated beta2AR. PMID:23208550 The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2. |
| GO:0005515 protein binding | IPI PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | MODIFY | Summary: Protein binding (IPI) with NEDD4, from the alpha-arrestin trafficking study. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | MODIFY | Summary: Protein binding (IPI) with ITCH, from the alpha-arrestin trafficking study. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | MODIFY | Summary: Protein binding (IPI) with NEDD4L, from the alpha-arrestin trafficking study. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:23886940 Ξ-arrestin 1 (ARRDC1) and Ξ²-arrestins cooperate to mediate N... | MODIFY | Summary: Protein binding (IPI) with ITCH, from an alpha-arrestin/Notch study. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with HPGDS, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with STAM2, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with BAG3, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with TNFAIP3, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with TRIM42, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with OTUB2, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with DCUN1D1, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with UBE2E2, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with MORF4L1, from the HI-II-14 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:25416956 A proteome-scale map of the human interactome network. | REMOVE | Summary: Protein binding (IPI) with MORF4L1, from the HI-II-14 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:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Protein binding (IPI) with ITCH, from the BioPlex affinity-purification network. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | MODIFY | Summary: Protein binding (IPI) with WWP2, from the HuRI binary yeast two-hybrid map. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with PHF1, 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 HPGDS, 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 STAM2, 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 EPN2, 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 BAG3, 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 EFEMP2, 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 TNFAIP3, 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 CDA, 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 BCL6, 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 UBE2D1, 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 PRKAA2, 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 UBASH3A, 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 UBE2D2, 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 UBA52, 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 RACK1, 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 FAM90A1, 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 CCDC50, 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 UBE2E3, 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 OPTN, 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 OTUB2, 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 DCUN1D1, 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 SMARCD1, 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 UBE2E2, 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. | MODIFY | Summary: Protein binding (IPI) with NEDD4L, from the HuRI binary yeast two-hybrid map. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with UBAC1, 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 TOLLIP, 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. | MODIFY | Summary: Protein binding (IPI) with WWP1, from the HuRI binary yeast two-hybrid map. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | REMOVE | Summary: Protein binding (IPI) with RAD18, 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 WWOX, 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 ZRANB1, 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 UBQLN2, 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 RABGEF1, 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... | MODIFY | Summary: Protein binding (IPI) with NEDD4, from the BioPlex dual proteome-scale network. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Protein binding (IPI) with ITCH, from the BioPlex dual proteome-scale network. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Protein binding (IPI) with NEDD4L, from the BioPlex dual proteome-scale network. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Protein binding (IPI) with WWP1, from the BioPlex dual proteome-scale network. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:38270169 Comparative interactome analysis of Ξ±-arrestin families in h... | MODIFY | Summary: Protein binding (IPI) with NEDD4, from a comparative alpha-arrestin interactome. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:38270169 Comparative interactome analysis of Ξ±-arrestin families in h... | MODIFY | Summary: Protein binding (IPI) with ITCH, from a comparative alpha-arrestin interactome. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:38270169 Comparative interactome analysis of Ξ±-arrestin families in h... | MODIFY | Summary: Protein binding (IPI) with NEDD4L, from a comparative alpha-arrestin interactome. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:38270169 Comparative interactome analysis of Ξ±-arrestin families in h... | MODIFY | Summary: Protein binding (IPI) with WWP1, from a comparative alpha-arrestin interactome. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Protein binding (IPI) with WWP2, from a multimodal cell map. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Protein binding (IPI) with NEDD4, from a multimodal cell map. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Protein binding (IPI) with ITCH, from a multimodal cell map. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Protein binding (IPI) with NEDD4L, from a multimodal cell map. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | REMOVE | Summary: Protein binding (IPI) with TOLLIP, from a multimodal cell 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:40205054 Multimodal cell maps as a foundation for structural and func... | MODIFY | Summary: Protein binding (IPI) with WWP1, from a multimodal cell map. ARRDC3 binds NEDD4-family HECT ubiquitin ligases through its two PPxY motifs and recruits them to activated receptors. Modified to ubiquitin protein ligase binding. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:24379409 "ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3."] [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] Proposed replacements: ubiquitin protein ligase binding Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:24379409 ARRDC3 PPXY-Nedd4 WW dissociation constants vary from unmeasurable to Kd = 3 ΞΌM for the third WW domain of Nedd4 binding to the first PPXY motif of ARRDC3. PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. |
| GO:0005737 cytoplasm | EXP PMID:16269462 Thioredoxin-binding protein-2-like inducible membrane protei... | KEEP AS NON CORE | Summary: Cytoplasm (EXP). Correct but broad; the plasma membrane and endosome rows give ARRDC3's sites of action. Kept as non-core. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. |
| GO:0005737 cytoplasm | EXP PMID:23208550 Distinct roles for Ξ²-arrestin2 and arrestin-domain-containin... | KEEP AS NON CORE | Summary: Cytoplasm (EXP). Correct but broad; the plasma membrane and endosome rows give ARRDC3's sites of action. Kept as non-core. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cytoplasm (IBA). Correct but broad; the plasma membrane and endosome rows give ARRDC3's sites of action. Kept as non-core. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN000127176 SUPPORTS TRANSFER Alpha-arrestin node, seeded by fungal, fly, Dictyostelium, mouse and human arrestin-domain proteins. Human ARRDC3 itself is among the seeds, with its own experimental annotation. Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Cytoplasm (IEA). Correct but broad; the plasma membrane and endosome rows give ARRDC3's sites of action. Kept as non-core. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. |
| GO:0005764 lysosome | EXP PMID:16269462 Thioredoxin-binding protein-2-like inducible membrane protei... | KEEP AS NON CORE | Summary: Lysosome (EXP). ARRDC3 (TLIMP) co-localizes with endocytosed cargo destined for endosomes and lysosomes. TLIMP co-localizes with endocytosed cargo in endosome- and lysosome-associated compartments, which supports the location. Its characterized work, sorting PAR1 at late endosomes through WWP2-dependent ALIX ubiquitination, delivers cargo to lysosomes, so lysosomes are a destination rather than its main site of action. Kept as non-core. Reason: [PMID:16269462 "TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions."] [PMID:26490116 "ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation."] Supporting Evidence: PMID:16269462 TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions. PMID:26490116 ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation. |
| GO:0005764 lysosome | EXP PMID:23208550 Distinct roles for Ξ²-arrestin2 and arrestin-domain-containin... | KEEP AS NON CORE | Summary: Lysosome (EXP). ARRDC3 (TLIMP) co-localizes with endocytosed cargo destined for endosomes and lysosomes. TLIMP co-localizes with endocytosed cargo in endosome- and lysosome-associated compartments, which supports the location. Its characterized work, sorting PAR1 at late endosomes through WWP2-dependent ALIX ubiquitination, delivers cargo to lysosomes, so lysosomes are a destination rather than its main site of action. Kept as non-core. Reason: [PMID:16269462 "TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions."] [PMID:26490116 "ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation."] Supporting Evidence: PMID:16269462 TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions. PMID:26490116 ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation. |
| GO:0005764 lysosome | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Lysosome (IEA). ARRDC3 (TLIMP) co-localizes with endocytosed cargo destined for endosomes and lysosomes. TLIMP co-localizes with endocytosed cargo in endosome- and lysosome-associated compartments, which supports the location. Its characterized work, sorting PAR1 at late endosomes through WWP2-dependent ALIX ubiquitination, delivers cargo to lysosomes, so lysosomes are a destination rather than its main site of action. Kept as non-core. Reason: [PMID:16269462 "TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions."] [PMID:26490116 "ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation."] Supporting Evidence: PMID:16269462 TLIMP exhibited an inner membrane-associated pattern of distribution and also colocalized with transferrin and low-density lipoprotein, indicating endosome- and lysosome-associated functions. PMID:26490116 ARRDC3 colocalizes with ALIX and is required for PAR1 sorting at late endosomes and degradation. |
| GO:0005768 endosome | EXP PMID:16269462 Thioredoxin-binding protein-2-like inducible membrane protei... | ACCEPT | Summary: Endosome (EXP). ARRDC3 localizes to cytoplasmic vesicles and endosomes, where it traffics NEDD4-receptor complexes. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:23208550 "The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:23208550 The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2. |
| GO:0005768 endosome | EXP PMID:23208550 Distinct roles for Ξ²-arrestin2 and arrestin-domain-containin... | ACCEPT | Summary: Endosome (EXP). ARRDC3 localizes to cytoplasmic vesicles and endosomes, where it traffics NEDD4-receptor complexes. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:23208550 "The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:23208550 The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2. |
| GO:0005768 endosome | IBA GO_REF:0000033 | ACCEPT | Summary: Endosome (IBA). ARRDC3 localizes to cytoplasmic vesicles and endosomes, where it traffics NEDD4-receptor complexes. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:23208550 "The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008513893 SUPPORTS TRANSFER ARRDC3 node; seeded only by human ARRDC3 itself (UniProtKB:Q96B67). Human ARRDC3 itself is among the seeds, with its own experimental annotation. Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:23208550 The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2. |
| GO:0005768 endosome | IDA PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | ACCEPT | Summary: Endosome (IDA). ARRDC3 localizes to cytoplasmic vesicles and endosomes, where it traffics NEDD4-receptor complexes. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:23208550 "The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:23208550 The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2. |
| GO:0005768 endosome | IEA GO_REF:0000044 | ACCEPT | Summary: Endosome (IEA). ARRDC3 localizes to cytoplasmic vesicles and endosomes, where it traffics NEDD4-receptor complexes. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:23208550 "The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:23208550 The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2. |
| GO:0005769 early endosome | EXP PMID:20559325 Arrestin domain-containing protein 3 recruits the NEDD4 E3 l... | ACCEPT | Summary: Early endosome (EXP). ARRDC3 localizes mainly to EEA1-positive early endosomes, where it restrains beta2AR entry into SNX27 recycling tubules; ARRDC proteins also traffic NEDD4-beta2AR complexes to early endosomes. Accepted. Reason: [PMID:27226565 "We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner."] [PMID:27226565 "Although ARRDC3 has no effect on Ξ²2AR endocytosis or degradation, it negatively regulates Ξ²2AR entry into SNX27-occupied endosomal tubules."] [PMID:23208550 "Rather, the role of ARRDC proteins is to traffic Nedd4-Ξ²(2)AR complexes to a subpopulation of early endosomes."] Supporting Evidence: PMID:27226565 We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner. PMID:27226565 Although ARRDC3 has no effect on Ξ²2AR endocytosis or degradation, it negatively regulates Ξ²2AR entry into SNX27-occupied endosomal tubules. PMID:23208550 Rather, the role of ARRDC proteins is to traffic Nedd4-Ξ²(2)AR complexes to a subpopulation of early endosomes. |
| GO:0005769 early endosome | EXP PMID:23208550 Distinct roles for Ξ²-arrestin2 and arrestin-domain-containin... | ACCEPT | Summary: Early endosome (EXP). ARRDC3 localizes mainly to EEA1-positive early endosomes, where it restrains beta2AR entry into SNX27 recycling tubules; ARRDC proteins also traffic NEDD4-beta2AR complexes to early endosomes. Accepted. Reason: [PMID:27226565 "We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner."] [PMID:27226565 "Although ARRDC3 has no effect on Ξ²2AR endocytosis or degradation, it negatively regulates Ξ²2AR entry into SNX27-occupied endosomal tubules."] [PMID:23208550 "Rather, the role of ARRDC proteins is to traffic Nedd4-Ξ²(2)AR complexes to a subpopulation of early endosomes."] Supporting Evidence: PMID:27226565 We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner. PMID:27226565 Although ARRDC3 has no effect on Ξ²2AR endocytosis or degradation, it negatively regulates Ξ²2AR entry into SNX27-occupied endosomal tubules. PMID:23208550 Rather, the role of ARRDC proteins is to traffic Nedd4-Ξ²(2)AR complexes to a subpopulation of early endosomes. |
| GO:0005769 early endosome | IEA GO_REF:0000044 | ACCEPT | Summary: Early endosome (IEA). ARRDC3 localizes mainly to EEA1-positive early endosomes, where it restrains beta2AR entry into SNX27 recycling tubules; ARRDC proteins also traffic NEDD4-beta2AR complexes to early endosomes. Accepted. Reason: [PMID:27226565 "We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner."] [PMID:27226565 "Although ARRDC3 has no effect on Ξ²2AR endocytosis or degradation, it negatively regulates Ξ²2AR entry into SNX27-occupied endosomal tubules."] [PMID:23208550 "Rather, the role of ARRDC proteins is to traffic Nedd4-Ξ²(2)AR complexes to a subpopulation of early endosomes."] Supporting Evidence: PMID:27226565 We find that ARRDC3 primarily localizes to EEA1-positive early endosomes and directly interacts with the Ξ²2AR in a ligand-independent manner. PMID:27226565 Although ARRDC3 has no effect on Ξ²2AR endocytosis or degradation, it negatively regulates Ξ²2AR entry into SNX27-occupied endosomal tubules. PMID:23208550 Rather, the role of ARRDC proteins is to traffic Nedd4-Ξ²(2)AR complexes to a subpopulation of early endosomes. |
| GO:0005886 plasma membrane | EXP PMID:16269462 Thioredoxin-binding protein-2-like inducible membrane protei... | ACCEPT | Summary: Plasma membrane (EXP). ARRDC3 localizes constitutively to the plasma membrane and binds beta2AR. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:20559325 "The ARRDC3 protein also interacts and co-localizes with activated beta2AR."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:20559325 The ARRDC3 protein also interacts and co-localizes with activated beta2AR. |
| GO:0005886 plasma membrane | EXP PMID:20559325 Arrestin domain-containing protein 3 recruits the NEDD4 E3 l... | ACCEPT | Summary: Plasma membrane (EXP). ARRDC3 localizes constitutively to the plasma membrane and binds beta2AR. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:20559325 "The ARRDC3 protein also interacts and co-localizes with activated beta2AR."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:20559325 The ARRDC3 protein also interacts and co-localizes with activated beta2AR. |
| GO:0005886 plasma membrane | EXP PMID:23208550 Distinct roles for Ξ²-arrestin2 and arrestin-domain-containin... | ACCEPT | Summary: Plasma membrane (EXP). ARRDC3 localizes constitutively to the plasma membrane and binds beta2AR. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:20559325 "The ARRDC3 protein also interacts and co-localizes with activated beta2AR."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:20559325 The ARRDC3 protein also interacts and co-localizes with activated beta2AR. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane (IBA). ARRDC3 localizes constitutively to the plasma membrane and binds beta2AR. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:20559325 "The ARRDC3 protein also interacts and co-localizes with activated beta2AR."] Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN008513893 SUPPORTS TRANSFER ARRDC3 node; seeded only by human ARRDC3 itself (UniProtKB:Q96B67). Human ARRDC3 itself is among the seeds, with its own experimental annotation. Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:20559325 The ARRDC3 protein also interacts and co-localizes with activated beta2AR. |
| GO:0005886 plasma membrane | IDA PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | ACCEPT | Summary: Plasma membrane (IDA). ARRDC3 localizes constitutively to the plasma membrane and binds beta2AR. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:20559325 "The ARRDC3 protein also interacts and co-localizes with activated beta2AR."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:20559325 The ARRDC3 protein also interacts and co-localizes with activated beta2AR. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane (IEA). ARRDC3 localizes constitutively to the plasma membrane and binds beta2AR. Core location. Reason: [PMID:23236378 "1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]."] [PMID:20559325 "The ARRDC3 protein also interacts and co-localizes with activated beta2AR."] Supporting Evidence: PMID:23236378 1) confirmed prior reports of constitutively nuclear localization of TXNIP [17], [57], and constitutive localization of ARRDC3 on the plasma membrane and in cytoplasmic vesicles or endosomes [17]. PMID:20559325 The ARRDC3 protein also interacts and co-localizes with activated beta2AR. |
| GO:0031699 beta-3 adrenergic receptor binding | IDA PMID:21982743 The arrestin domain-containing 3 protein regulates body mass... | ACCEPT | Summary: Beta-3 adrenergic receptor binding (IDA). ARRDC3 interacts directly with beta-adrenergic receptors. The same study's claim that ARRDC3 loss strengthens beta-adrenergic responses is disputed (PMID:28291835), but the binding itself is not and is all this term asserts. Accepted. Reason: [PMID:21982743 "ARRDC3 interacted directly with Ξ²-adrenergic receptors"] The functional claim is disputed: [PMID:28291835 "Additionally, canonical Ξ²-adrenergic receptor signaling was not different in Arrdc3-null adipocytes."] Supporting Evidence: PMID:21982743 ARRDC3 interacted directly with Ξ²-adrenergic receptors |
| GO:0035332 positive regulation of hippo signaling | IMP PMID:24114784 The Hippo signaling pathway interactome. | KEEP AS NON CORE | Summary: Positive regulation of hippo signaling (IMP). In the fly screen that identified Leash, an alpha-arrestin that binds Nedd4-family ligases and sends Yki to lysosomes, expression of mammalian Arrdc1 or Arrdc3 reduced Yki-reporter activity and Yki abundance. ARRDC3 limits the Hippo effector, reinforcing pathway output. A regulatory, tumour-suppressive role; kept as non-core. Reason: [PMID:24114784 "Expression of Arrdc1 or Arrdc3 reduced Yki-reporter activity"] [PMID:24114784 "4D), indicating that Leash decreases Yki abundance through the lysosomal degradation pathway."] [PMID:24114784 "We also identified additional Leash interactors by AP/MS (tables S8 and S9) and found that Leash strongly binds to Nedd4 and a few other HECT (homologous to E6-AP carboxyl terminus) ubiquitin ligases (Fig."] Supporting Evidence: PMID:24114784 Expression of Arrdc1 or Arrdc3 reduced Yki-reporter activity PMID:24114784 4D), indicating that Leash decreases Yki abundance through the lysosomal degradation pathway. PMID:24114784 We also identified additional Leash interactors by AP/MS (tables S8 and S9) and found that Leash strongly binds to Nedd4 and a few other HECT (homologous to E6-AP carboxyl terminus) ubiquitin ligases (Fig. |
| GO:0035332 positive regulation of hippo signaling | IMP PMID:29364502 ARRDC3 suppresses colorectal cancer progression through dest... | KEEP AS NON CORE | Summary: Positive regulation of hippo signaling (IMP). ARRDC3 binds YAP through its PPxY motifs and promotes ITCH-mediated YAP ubiquitination and degradation, reinforcing Hippo output. It also sequesters TAZ independently of its trafficking role. A regulatory, tumour-suppressive role; kept as non-core. Reason: [PMID:29364502 "Mechanistically, we reveal that ARRDC3 binds and decreases expression of the oncoprotein YAP, the cotranscription factor of the Hippo pathway."] [PMID:29416926 "Mechanically, ARRDC1/3 negatively regulates YAP1 protein stability by facilitating E3 ubiquitin ligase Itch-mediated ubiquitination and degradation of YAP1."] [PMID:33722977 "Additionally, ARRDC3 suppresses PAR1-induced Hippo signaling via sequestration of TAZ, which occurs independently of ARRDC3-regulated PAR1 trafficking."] Supporting Evidence: PMID:29364502 Mechanistically, we reveal that ARRDC3 binds and decreases expression of the oncoprotein YAP, the cotranscription factor of the Hippo pathway. PMID:29416926 Mechanically, ARRDC1/3 negatively regulates YAP1 protein stability by facilitating E3 ubiquitin ligase Itch-mediated ubiquitination and degradation of YAP1. PMID:33722977 Additionally, ARRDC3 suppresses PAR1-induced Hippo signaling via sequestration of TAZ, which occurs independently of ARRDC3-regulated PAR1 trafficking. |
| GO:0051443 positive regulation of ubiquitin-protein transferase activity | IPI PMID:23236378 Mammalian Ξ± arrestins link activated seven transmembrane rec... | MARK AS OVER ANNOTATED | Summary: Positive regulation of ubiquitin-protein transferase activity (IPI, with NEDD4L). Alpha-arrestins recruit NEDD4-family E3s to cargo, which increases cargo ubiquitination. No study shows ARRDC3 raising the ligase's catalytic activity, for example by relieving HECT autoinhibition. The adaptor role is captured by GO:1990756 and ligase binding; this regulatory term overshoots the evidence. Reason: [PMID:23236378 "[37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs."] [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] Supporting Evidence: PMID:23236378 [37] Here we report evidence supporting our previous proposal that aArrs 1) are involved in endocytic trafficking, 2) recruit WW proteins, including Nedd4 family E3s, to activated receptors and 3) heteroassociate with bArrs. PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. |
| GO:0060090 molecular adaptor activity | IBA GO_REF:0000033 | MODIFY | Summary: Molecular adaptor activity (IBA, alpha-arrestin node). ARRDC3 recruits NEDD4 through its PPxY motifs to activated beta2AR, the substrate, and is needed for receptor ubiquitination and degradation. A later study argues that beta-arrestin2 is the primary adaptor and ARRDC3 a secondary one acting on endosomes. ARRDC3 still links an E3 to a substrate; modified to ubiquitin-like ligase-substrate adaptor activity. Reason: [PMID:20559325 "The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor."] [PMID:20559325 "Using a genome-wide RNA interference screen, we identified arrestin domain-containing 3 (ARRDC3) as a gene required for beta2AR regulation."] [PMID:23208550 "The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2."] Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000127176 SUPPORTS TRANSFER Alpha-arrestin node, seeded by fungal, fly, Dictyostelium, mouse and human arrestin-domain proteins. ARRDC3 is not among the seeds for this row; the transfer is independently supported by ARRDC3's own adaptor literature (PMID:20559325, PMID:26490116). Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:20559325 The ARRDC3 protein interacts with ubiquitin ligase neural precursor development downregulated protein 4 (NEDD4) through two conserved PPXY motifs and recruits NEDD4 to the activated receptor. PMID:20559325 Using a genome-wide RNA interference screen, we identified arrestin domain-containing 3 (ARRDC3) as a gene required for beta2AR regulation. PMID:23208550 The arrestin-domain-containing (ARRDC) proteins 2, 3 and 4 are secondary adaptors recruited to internalized Ξ²(2)AR-Nedd4 complexes on endosomes and do not affect the adaptor roles of Ξ²-arrestin2. |
| GO:0120163 negative regulation of cold-induced thermogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of cold-induced thermogenesis (IEA, from mouse Arrdc3). Arrdc3-deficient mice resist obesity through increased energy expenditure, with greater thermogenesis of brown and white fat, and adipocyte-specific deletion raises Ucp1. The mechanism is disputed. An early study attributed the effect to stronger beta-adrenergic responses, but canonical beta-adrenergic signalling is unchanged in Arrdc3-null adipocytes. The phenotype stands; the mechanism does not. A physiological, non-core role. Reason: [PMID:21982743 "Mice with decreased ARRDC3 levels were protected from obesity due to increased energy expenditure through increased activity levels and increased thermogenesis of both brown and white adipose tissues."] [PMID:28291835 "We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue."] [PMID:28291835 "Additionally, canonical Ξ²-adrenergic receptor signaling was not different in Arrdc3-null adipocytes."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q7TPQ9 SUPPORTS TRANSFER Mouse Arrdc3; knockout phenotype of increased thermogenesis and energy expenditure (PMID:21982743). Supporting Evidence: PMID:21982743 Mice with decreased ARRDC3 levels were protected from obesity due to increased energy expenditure through increased activity levels and increased thermogenesis of both brown and white adipose tissues. PMID:28291835 We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue. PMID:28291835 Additionally, canonical Ξ²-adrenergic receptor signaling was not different in Arrdc3-null adipocytes. |
| GO:0120163 negative regulation of cold-induced thermogenesis | ISS PMID:21982743 The arrestin domain-containing 3 protein regulates body mass... | KEEP AS NON CORE | Summary: Negative regulation of cold-induced thermogenesis (ISS, from mouse Arrdc3). Arrdc3-deficient mice resist obesity through increased energy expenditure, with greater thermogenesis of brown and white fat, and adipocyte-specific deletion raises Ucp1. The mechanism is disputed. An early study attributed the effect to stronger beta-adrenergic responses, but canonical beta-adrenergic signalling is unchanged in Arrdc3-null adipocytes. The phenotype stands; the mechanism does not. A physiological, non-core role. Reason: [PMID:21982743 "Mice with decreased ARRDC3 levels were protected from obesity due to increased energy expenditure through increased activity levels and increased thermogenesis of both brown and white adipose tissues."] [PMID:28291835 "We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue."] [PMID:28291835 "Additionally, canonical Ξ²-adrenergic receptor signaling was not different in Arrdc3-null adipocytes."] Propagation Review Root cause: NO FAILURE NON CORE Sources checked: UniProtKB:Q7TPQ9 SUPPORTS TRANSFER Mouse Arrdc3; knockout phenotype of increased thermogenesis and energy expenditure (PMID:21982743). Supporting Evidence: PMID:21982743 Mice with decreased ARRDC3 levels were protected from obesity due to increased energy expenditure through increased activity levels and increased thermogenesis of both brown and white adipose tissues. PMID:28291835 We generated a mouse with conditional deletion of Arrdc3, and here we present evidence that genetic ablation of Arrdc3 specifically in adipocytes results in increased Ucp1 expression in subcutaneous and parametrial adipose tissue. PMID:28291835 Additionally, canonical Ξ²-adrenergic receptor signaling was not different in Arrdc3-null adipocytes. |
| GO:0016567 protein ubiquitination | IMP PMID:26490116 The Ξ±-arrestin ARRDC3 mediates ALIX ubiquitination and G pro... | NEW | Summary: Protein ubiquitination (NEW, IMP). ARRDC3 is required for WWP2-dependent ALIX ubiquitination after PAR1 activation, and its inactivation blocks beta2AR ubiquitination. As the ligase-substrate adaptor, ARRDC3 contributes to the ubiquitination step itself. Comparator check: the alpha-arrestins ARRDC1 and ARRDC4 and both beta-arrestins carry GO:0016567. Reason: [PMID:26490116 "We found that ARRDC3 is required for ALIX ubiquitination induced by activation of PAR1."] [PMID:26490116 "Moreover, activation of PAR1 increases ALIX ubiquitination that is dependent on ARRDC3 and WW domainβcontaining E3 ubiquitin protein ligase 2 (WWP2)."] [PMID:20559325 "Furthermore, functional inactivation of ARRDC3, either through small interfering RNA (siRNA)-mediated knockdown or overexpression of a mutant that does not interact with NEDD4, blocks receptor ubiquitination and degradation."] The beta2AR arm is contested ([PMID:27226565 "Although ARRDC3 has no effect on Ξ²2AR endocytosis or degradation, it negatively regulates Ξ²2AR entry into SNX27-occupied endosomal tubules."]); the term rests on the uncontested ALIX/WWP2 result. Supporting Evidence: PMID:26490116 We found that ARRDC3 is required for ALIX ubiquitination induced by activation of PAR1. PMID:26490116 Moreover, activation of PAR1 increases ALIX ubiquitination that is dependent on ARRDC3 and WW domainβcontaining E3 ubiquitin protein ligase 2 (WWP2). PMID:20559325 Furthermore, functional inactivation of ARRDC3, either through small interfering RNA (siRNA)-mediated knockdown or overexpression of a mutant that does not interact with NEDD4, blocks receptor ubiquitination and degradation. |
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Download this section (compressed HTML)Q: Is ARRDC3 a primary or a secondary adaptor for beta2AR ubiquitination, given the conflicting RNAi, beta-arrestin-knockout and SNX27-recycling results?
Q: How does ARRDC3 restrain thermogenesis and Ucp1 in adipocytes if canonical beta-adrenergic signalling is unchanged without it?
Q: Should ARRDC3's role in GPCR lysosomal sorting (PAR1 via ALIX) be captured as a process annotation, and which term fits an adaptor that ubiquitinates a sorting factor rather than the receptor?
Experiment: Compare beta2AR ubiquitination and degradation in beta-arrestin2-null versus ARRDC3-null cells, with PPxY-mutant rescue.
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