AREL1 is a cytosolic HECT-domain E3 ubiquitin ligase that assembles K11- and K33-linked ubiquitin chains. It ubiquitinates substrates including the IAP antagonists SMAC/DIABLO, HTRA2, and ARTS, promoting their degradation and thereby limiting apoptosis; additional context-specific substrates include SOCS2. Its primary molecular role is substrate-selective protein ubiquitination.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Cytoplasm is a correct broad localization for the experimentally cytosolic AREL1 protein. Reason: Direct evidence places AREL1 in the cytosol, which is part of the cytoplasm; the broader IBA annotation remains biologically correct. Supporting Evidence: PMID:23479728 AREL1 was cytosolic and did not localize to nuclei or mitochondria. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: AREL1 promotes ubiquitination and degradation of IAP antagonists, consistent with ubiquitin-dependent protein catabolic process. Reason: AREL1 enhances degradation of SMAC, HtrA2, and ARTS following apoptotic stimulation. Supporting Evidence: PMID:23479728 the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells |
| GO:0061630 ubiquitin protein ligase activity | IBA GO_REF:0000033 | ACCEPT | Summary: AREL1 encodes a HECT family E3 ubiquitin ligase, which is its core molecular function. Reason: The study describes AREL1 as a HECT family E3 ubiquitin ligase. Supporting Evidence: PMID:23479728 AREL1, which encodes a HECT (homologous to E6-AP carboxyl terminus) family E3 ubiquitin ligase. |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: Cytosolic localization is supported by experimental evidence. Reason: AREL1 is reported to be cytosolic and not nuclear or mitochondrial. Supporting Evidence: PMID:23479728 AREL1 was cytosolic and did not localize to nuclei or mitochondria. |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | ACCEPT | Summary: AREL1 is anti-apoptotic via degradation of IAP antagonists. Reason: AREL1-mediated degradation of SMAC, HtrA2, and ARTS inhibits apoptosis. Supporting Evidence: PMID:23479728 the anti-apoptotic role of AREL1-mediated degradation of SMAC, HtrA2, and ARTS was shown |
| GO:0004842 ubiquitin-protein transferase activity | IEA GO_REF:0000002 | MODIFY | Summary: This generic ubiquitin-protein transferase term is less specific than the E3 ligase activity term. Reason: GO:0061630 captures the specific ubiquitin protein ligase activity of AREL1. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:23479728 AREL1, which encodes a HECT (homologous to E6-AP carboxyl terminus) family E3 ubiquitin ligase. |
| GO:0006915 apoptotic process | IEA GO_REF:0000043 | MARK AS OVER ANNOTATED | Summary: Evidence supports negative regulation of apoptosis rather than direct participation in apoptotic process. Reason: AREL1 is anti-apoptotic by degrading IAP antagonists; the specific regulation term is already present. Supporting Evidence: PMID:23479728 the anti-apoptotic role of AREL1-mediated degradation of SMAC, HtrA2, and ARTS was shown |
| GO:0016740 transferase activity | IEA GO_REF:0000043 | MODIFY | Summary: Transferase activity is too broad for an E3 ubiquitin ligase. Reason: GO:0061630 provides the specific molecular function for AREL1. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:23479728 AREL1, which encodes a HECT (homologous to E6-AP carboxyl terminus) family E3 ubiquitin ligase. |
| GO:0061630 ubiquitin protein ligase activity | IEA GO_REF:0000003 | ACCEPT | Summary: Ubiquitin protein ligase activity is consistent with AREL1 function. Reason: AREL1 is described as a HECT family E3 ubiquitin ligase. Supporting Evidence: PMID:23479728 AREL1, which encodes a HECT (homologous to E6-AP carboxyl terminus) family E3 ubiquitin ligase. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IEA GO_REF:0000120 | ACCEPT | Summary: AREL1-mediated degradation of IAP antagonists supports a role in ubiquitin-dependent protein catabolism. Reason: AREL1 enhances ubiquitination and degradation of SMAC, HtrA2, and ARTS. Supporting Evidence: PMID:23479728 the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000120 | ACCEPT | Summary: AREL1 ubiquitinates IAP antagonists, consistent with protein ubiquitination. Reason: Direct ubiquitination of SMAC, HtrA2, and ARTS is reported. Supporting Evidence: PMID:23479728 AREL1 interacted with and ubiquitinated IAP antagonists such as SMAC, HtrA2, and ARTS. |
| GO:0050727 regulation of inflammatory response | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: KIAA0317/AREL1 regulates pulmonary inflammation via SOCS2 degradation; this is a context-specific role. Reason: Evidence supports inflammatory regulation but this is secondary to the core E3 ligase function. Supporting Evidence: PMID:31578312 KIAA0317-mediated degradation of SOCS2 exacerbated inflammation in vitro, and depletion of KIAA0317 in vivo ameliorated pulmonary inflammation. |
| GO:0005515 protein binding | IPI PMID:23479728 Identification of a novel anti-apoptotic E3 ubiquitin ligase... | KEEP AS NON CORE | Summary: AREL1 binds IAP antagonists including SMAC, HtrA2, and ARTS. Reason: Specific interactions are documented but the generic protein binding term is non-core. Supporting Evidence: PMID:23479728 AREL1 interacted with and ubiquitinated IAP antagonists such as SMAC, HtrA2, and ARTS. |
| GO:0061630 ubiquitin protein ligase activity | IDA PMID:25752577 Assembly and specific recognition of k29- and k33-linked pol... | ACCEPT | Summary: AREL1 is a HECT E3 ligase that assembles atypical ubiquitin chains. Reason: AREL1 is explicitly identified as a HECT E3 ligase in the study. Supporting Evidence: PMID:25752577 We found that the human HECT E3 ligases UBE3C and AREL1 assemble K48/K29- and K11/K33-linked Ub chains, respectively |
| GO:0070979 protein K11-linked ubiquitination | IDA PMID:25752577 Assembly and specific recognition of k29- and k33-linked pol... | ACCEPT | Summary: AREL1 assembles K11-linked ubiquitin chains. Reason: The study reports AREL1 assembling K11-linked ubiquitin chains. Supporting Evidence: PMID:25752577 We found that the human HECT E3 ligases UBE3C and AREL1 assemble K48/K29- and K11/K33-linked Ub chains, respectively |
| GO:1990390 protein K33-linked ubiquitination | IDA PMID:25752577 Assembly and specific recognition of k29- and k33-linked pol... | ACCEPT | Summary: AREL1 assembles K33-linked ubiquitin chains. Reason: The study reports AREL1 assembling K33-linked ubiquitin chains. Supporting Evidence: PMID:25752577 We found that the human HECT E3 ligases UBE3C and AREL1 assemble K48/K29- and K11/K33-linked Ub chains, respectively |
| GO:0005515 protein binding | IPI PMID:31578312 KIAA0317 regulates pulmonary inflammation through SOCS2 degr... | UNDECIDED | Summary: SOCS2 interaction is not explicitly described in the accessible abstract. Reason: The abstract describes SOCS2 regulation but does not state physical binding; full text is not available here. Supporting Evidence: PMID:31578312 Here we describe a mechanism of SOCS2 regulation by the action of the ubiquitin E3 ligase KIAA0317. |
| GO:0016567 protein ubiquitination | IDA PMID:31578312 KIAA0317 regulates pulmonary inflammation through SOCS2 degr... | ACCEPT | Summary: KIAA0317 E3 ligase activity regulates SOCS2, consistent with protein ubiquitination. Reason: The study describes KIAA0317 as a ubiquitin E3 ligase acting on SOCS2. Supporting Evidence: PMID:31578312 Here we describe a mechanism of SOCS2 regulation by the action of the ubiquitin E3 ligase KIAA0317. |
| GO:0050727 regulation of inflammatory response | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Regulation of inflammatory response is supported by SOCS2 degradation phenotypes. Reason: The inflammatory phenotype is specific to pulmonary contexts and secondary to the E3 ligase core function. Supporting Evidence: PMID:31578312 KIAA0317-mediated degradation of SOCS2 exacerbated inflammation in vitro, and depletion of KIAA0317 in vivo ameliorated pulmonary inflammation. |
| GO:0004842 ubiquitin-protein transferase activity | IDA PMID:23479728 Identification of a novel anti-apoptotic E3 ubiquitin ligase... | MODIFY | Summary: E3 ubiquitin ligase activity is demonstrated; a more specific term should be used. Reason: GO:0061630 specifically captures ubiquitin protein ligase activity for AREL1. Proposed replacements: ubiquitin protein ligase activity Supporting Evidence: PMID:23479728 AREL1, which encodes a HECT (homologous to E6-AP carboxyl terminus) family E3 ubiquitin ligase. |
| GO:0005829 cytosol | IDA PMID:23479728 Identification of a novel anti-apoptotic E3 ubiquitin ligase... | ACCEPT | Summary: AREL1 localizes to the cytosol. Reason: The study reports cytosolic localization for AREL1. Supporting Evidence: PMID:23479728 AREL1 was cytosolic and did not localize to nuclei or mitochondria. |
| GO:0006511 ubiquitin-dependent protein catabolic process | IDA PMID:23479728 Identification of a novel anti-apoptotic E3 ubiquitin ligase... | ACCEPT | Summary: AREL1 promotes ubiquitination and degradation of IAP antagonists. Reason: Enhanced degradation of SMAC, HtrA2, and ARTS supports ubiquitin-dependent protein catabolism. Supporting Evidence: PMID:23479728 the ubiquitination and degradation of SMAC, HtrA2, and ARTS were significantly enhanced in AREL1-expressing cells |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:23479728 Identification of a novel anti-apoptotic E3 ubiquitin ligase... | ACCEPT | Summary: AREL1-mediated degradation of IAP antagonists inhibits apoptosis. Reason: AREL1 is explicitly described as anti-apoptotic through degradation of IAP antagonists. Supporting Evidence: PMID:23479728 the anti-apoptotic role of AREL1-mediated degradation of SMAC, HtrA2, and ARTS was shown |
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)