AHR encodes the aryl hydrocarbon receptor, a ligand-activated bHLH-PAS transcription factor that senses xenobiotic, dietary, microbiome-derived, and endogenous metabolites. In unstimulated cells AHR is mainly cytoplasmic in a chaperone-associated receptor complex; ligand binding promotes nuclear accumulation, heterodimerization with ARNT, binding to AHR/xenobiotic response elements, and regulation of RNA polymerase II target genes. AHR controls detoxification and xenobiotic-response programs such as CYP1A1 induction and also has context-dependent roles in immune regulation, intestinal epithelial responses, tumor immune escape, circadian cross-talk, development, and retinal biology.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0004879 nuclear receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: regulation of transcription by RNA polymerase II is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0000976 transcription cis-regulatory region binding | IBA GO_REF:0000033 | ACCEPT | Summary: transcription cis-regulatory region binding is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0034751 aryl hydrocarbon receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: aryl hydrocarbon receptor complex is an appropriate AHR complex annotation. AHR forms cytosolic chaperone-associated complexes before activation and nuclear AHR:ARNT complexes after ligand-induced activation. Reason: AHR complex membership is central to the receptor activation cycle. The receptor is maintained in a cytosolic HSP90/XAP2/p23 complex before activation and forms an AHR:ARNT DNA-bound complex in the nucleus after ligand activation. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:11259606 The molecular chaperone complex hsp90-p23 interacts with the dioxin receptor PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0004879 nuclear receptor activity | IEA GO_REF:0000117 | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | ACCEPT | Summary: cytoplasm localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: regulation of DNA-templated transcription is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0006805 xenobiotic metabolic process | IEA GO_REF:0000002 | ACCEPT | Summary: xenobiotic metabolic process is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:0009410 response to xenobiotic stimulus | IEA GO_REF:0000120 | ACCEPT | Summary: response to xenobiotic stimulus is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:0030522 intracellular receptor signaling pathway | IEA GO_REF:0000108 | ACCEPT | Summary: AHR signaling is an intracellular ligand-receptor pathway that couples xenobiotic, dietary, microbiome-derived, and endogenous metabolites to transcriptional responses. Reason: The term is broad but correct for AHR. AHR activation by ligand causes nuclear translocation and transcriptional regulation of target genes including xenobiotic-response genes and immunometabolic targets. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:32818467 IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000117 | ACCEPT | Summary: positive regulation of DNA-templated transcription is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000002 | MODIFY | Summary: AHR dimerization is real, but the generic protein dimerization activity term should be replaced by the more informative heterodimerization term. Reason: The biologically relevant dimer for activated AHR is AHR:ARNT. Existing human evidence specifically supports heterodimerization, so the generic dimerization annotation should be refined. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0051239 regulation of multicellular organismal process | IEA GO_REF:0000117 | MARK AS OVER ANNOTATED | Summary: regulation of multicellular organismal process is biologically connected to AHR pleiotropy but is too broad or indirect for a core AHR annotation. Reason: AHR affects development, cell cycle, apoptosis, and organism-level phenotypes through transcriptional programs, but these high-level process annotations risk implying a direct pathway role that is not supported by the specific evidence used here. Supporting Evidence: PMID:12213388 This review addresses novel findings relating to AHR functions that have resulted from experimental approaches markedly outside traditional receptor analyses. |
| GO:1904613 cellular response to 2,3,7,8-tetrachlorodibenzodioxine | IEA GO_REF:0000117 | ACCEPT | Summary: cellular response to 2,3,7,8-tetrachlorodibenzodioxine is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:1990837 sequence-specific double-stranded DNA binding | IEA GO_REF:0000117 | ACCEPT | Summary: sequence-specific double-stranded DNA binding is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0005515 protein binding | IPI PMID:10395741 Interactions of nuclear receptor coactivator/corepressor pro... | MODIFY | Summary: The original IPI evidence documents AHR/ARNT and coactivator/corepressor interactions, but protein binding is uninformative. Reason: Replace the generic term with specific AHR heterodimerization and transcription cofactor-binding activities, which capture the relevant molecular interactions. Proposed replacements: protein heterodimerization activity TFIID-class transcription factor complex binding transcription coactivator binding Supporting Evidence: PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. |
| GO:0005515 protein binding | IPI PMID:16257957 Regulation of transactivation function of the aryl hydrocarb... | MARK AS OVER ANNOTATED | Summary: This generic protein binding annotation reflects a viral EBNA3 interaction that modulates AHR transactivation, but it is not informative for the normal AHR core function. Reason: The interaction may be experimentally real, but generic protein binding from a virus-specific perturbation should not be used as a functional summary of AHR. Supporting Evidence: PMID:16257957 Regulation of transactivation function of the aryl hydrocarbon receptor by the Epstein-Barr virus-encoded EBNA-3 protein. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: The protein binding annotation reflects AHR interactions with ARNT/related bHLH-PAS partners, but the generic term should be refined. Reason: AHR:ARNT or related heterodimerization is the informative activity supported by the interaction evidence. The review therefore proposes protein heterodimerization activity rather than generic protein binding. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: The protein binding annotation reflects AHR interactions with ARNT/related bHLH-PAS partners, but the generic term should be refined. Reason: AHR:ARNT or related heterodimerization is the informative activity supported by the interaction evidence. The review therefore proposes protein heterodimerization activity rather than generic protein binding. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005515 protein binding | IPI PMID:9704006 Transcriptionally active heterodimer formation of an Arnt-li... | MODIFY | Summary: The protein binding annotation reflects AHR interactions with ARNT/related bHLH-PAS partners, but the generic term should be refined. Reason: AHR:ARNT or related heterodimerization is the informative activity supported by the interaction evidence. The review therefore proposes protein heterodimerization activity rather than generic protein binding. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: nucleoplasm localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: cytosol localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0006805 xenobiotic metabolic process | TAS Reactome:R-HSA-8937144 | ACCEPT | Summary: xenobiotic metabolic process is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:0004879 nuclear receptor activity | EXP PMID:11259606 The hsp90 chaperone complex regulates intracellular localiza... | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0004879 nuclear receptor activity | TAS Reactome:R-HSA-8936849 | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0004879 nuclear receptor activity | TAS Reactome:R-HSA-8937191 | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005737 cytoplasm | EXP PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: cytoplasm localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0050728 negative regulation of inflammatory response | IDA PMID:29454749 Microbiota-Derived Indole Metabolites Promote Human and Muri... | KEEP AS NON CORE | Summary: negative regulation of inflammatory response is supported as a downstream immunological context of AHR activation, especially through microbial or tryptophan-derived ligands. Reason: AHR has substantial immune biology, but these process terms are cell-type- and disease-context-dependent outputs of AHR signaling rather than the core molecular function of the gene product. Supporting Evidence: PMID:32818467 IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. PMID:29454749 Administration of indole metabolites showed prominent induction of IL-10R1 on cultured intestinal epithelia that was explained by activation of the aryl hydrocarbon receptor. PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0004879 nuclear receptor activity | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005515 protein binding | IPI PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | MODIFY | Summary: The protein binding annotation reflects AHR interactions with ARNT/related bHLH-PAS partners, but the generic term should be refined. Reason: AHR:ARNT or related heterodimerization is the informative activity supported by the interaction evidence. The review therefore proposes protein heterodimerization activity rather than generic protein binding. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005634 nucleus | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0009410 response to xenobiotic stimulus | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: response to xenobiotic stimulus is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:0034753 nuclear aryl hydrocarbon receptor complex | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: nuclear aryl hydrocarbon receptor complex is an appropriate AHR complex annotation. AHR forms cytosolic chaperone-associated complexes before activation and nuclear AHR:ARNT complexes after ligand-induced activation. Reason: AHR complex membership is central to the receptor activation cycle. The receptor is maintained in a cytosolic HSP90/XAP2/p23 complex before activation and forms an AHR:ARNT DNA-bound complex in the nucleus after ligand activation. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:11259606 The molecular chaperone complex hsp90-p23 interacts with the dioxin receptor PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: positive regulation of transcription by RNA polymerase II is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0046982 protein heterodimerization activity | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: AHR heterodimerization, especially with ARNT, is essential for DNA binding and transcriptional activation. Reason: The AHR:ARNT heterodimer is a core mechanistic state of activated AHR. Structural and mutational evidence supports this term directly. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: sequence-specific double-stranded DNA binding is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0001094 TFIID-class transcription factor complex binding | IPI PMID:15641800 Induced alpha-helix structure in the aryl hydrocarbon recept... | ACCEPT | Summary: TFIID-class transcription factor complex binding is supported by AHR transactivation-domain interactions with general transcription machinery and coactivators/coregulators. Reason: These binding annotations are more informative than generic protein binding and connect directly to AHR transcriptional regulation. They should be retained as molecular-function annotations supporting the core transactivation mechanism. Supporting Evidence: PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. |
| GO:0071219 cellular response to molecule of bacterial origin | IDA PMID:29454749 Microbiota-Derived Indole Metabolites Promote Human and Muri... | KEEP AS NON CORE | Summary: AHR responds to microbiota-derived indole metabolites and bacterial-origin molecules in intestinal epithelial/immune contexts. Reason: This is a well supported physiological context for AHR signaling, but it is ligand/source-specific and should not displace the core receptor/transcription-factor function. Supporting Evidence: PMID:29454749 Administration of indole metabolites showed prominent induction of IL-10R1 on cultured intestinal epithelia that was explained by activation of the aryl hydrocarbon receptor. |
| GO:0004879 nuclear receptor activity | IDA PMID:28602820 Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene... | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005634 nucleus | IDA PMID:28602820 Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene... | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005634 nucleus | IDA PMID:32866000 Endogenous Indole Pyruvate Pathway for Tryptophan Metabolism... | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:9079689 Characterization of a subset of the basic-helix-loop-helix-P... | ACCEPT | Summary: RNA polymerase II-specific DNA-binding transcription factor binding is supported by AHR transactivation-domain interactions with general transcription machinery and coactivators/coregulators. Reason: These binding annotations are more informative than generic protein binding and connect directly to AHR transcriptional regulation. They should be retained as molecular-function annotations supporting the core transactivation mechanism. Supporting Evidence: PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. |
| GO:0004879 nuclear receptor activity | IDA PMID:32866000 Endogenous Indole Pyruvate Pathway for Tryptophan Metabolism... | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:32818467 IL4I1 Is a Metabolic Immune Checkpoint that Activates the AH... | ACCEPT | Summary: regulation of transcription by RNA polymerase II is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0002819 regulation of adaptive immune response | IDA PMID:32818467 IL4I1 Is a Metabolic Immune Checkpoint that Activates the AH... | KEEP AS NON CORE | Summary: regulation of adaptive immune response is supported as a downstream immunological context of AHR activation, especially through microbial or tryptophan-derived ligands. Reason: AHR has substantial immune biology, but these process terms are cell-type- and disease-context-dependent outputs of AHR signaling rather than the core molecular function of the gene product. Supporting Evidence: PMID:32818467 IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. PMID:29454749 Administration of indole metabolites showed prominent induction of IL-10R1 on cultured intestinal epithelia that was explained by activation of the aryl hydrocarbon receptor. PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0002841 negative regulation of T cell mediated immune response to tumor cell | IDA PMID:32818467 IL4I1 Is a Metabolic Immune Checkpoint that Activates the AH... | KEEP AS NON CORE | Summary: negative regulation of T cell mediated immune response to tumor cell is supported as a downstream immunological context of AHR activation, especially through microbial or tryptophan-derived ligands. Reason: AHR has substantial immune biology, but these process terms are cell-type- and disease-context-dependent outputs of AHR signaling rather than the core molecular function of the gene product. Supporting Evidence: PMID:32818467 IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. PMID:29454749 Administration of indole metabolites showed prominent induction of IL-10R1 on cultured intestinal epithelia that was explained by activation of the aryl hydrocarbon receptor. PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0004879 nuclear receptor activity | IDA PMID:32818467 IL4I1 Is a Metabolic Immune Checkpoint that Activates the AH... | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005634 nucleus | IDA PMID:32818467 IL4I1 Is a Metabolic Immune Checkpoint that Activates the AH... | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005737 cytoplasm | IDA PMID:32818467 IL4I1 Is a Metabolic Immune Checkpoint that Activates the AH... | ACCEPT | Summary: cytoplasm localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:32818467 IL4I1 Is a Metabolic Immune Checkpoint that Activates the AH... | ACCEPT | Summary: positive regulation of transcription by RNA polymerase II is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IDA PMID:23275542 2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymer... | ACCEPT | Summary: cis-regulatory region sequence-specific DNA binding is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: chromatin localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0042803 protein homodimerization activity | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Homodimerization is transferred by similarity and may occur, but it is not the core activated AHR mechanism in human cells. Reason: The main supported functional complex is the AHR:ARNT heterodimer. Homodimerization should not be treated as the central AHR molecular function. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:28602820 Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene... | ACCEPT | Summary: DNA-binding transcription factor activity is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0005515 protein binding | IPI PMID:28602820 Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene... | MODIFY | Summary: The protein binding annotation reflects AHR interactions with ARNT/related bHLH-PAS partners, but the generic term should be refined. Reason: AHR:ARNT or related heterodimerization is the informative activity supported by the interaction evidence. The review therefore proposes protein heterodimerization activity rather than generic protein binding. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0046982 protein heterodimerization activity | IDA PMID:28602820 Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene... | ACCEPT | Summary: AHR heterodimerization, especially with ARNT, is essential for DNA binding and transcriptional activation. Reason: The AHR:ARNT heterodimer is a core mechanistic state of activated AHR. Structural and mutational evidence supports this term directly. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28602820 Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene... | ACCEPT | Summary: sequence-specific double-stranded DNA binding is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0005634 nucleus | IDA PMID:17329248 Phosphodiesterase 2A forms a complex with the co-chaperone X... | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005829 cytosol | IDA PMID:17329248 Phosphodiesterase 2A forms a complex with the co-chaperone X... | ACCEPT | Summary: cytosol localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0071320 cellular response to cAMP | IDA PMID:17329248 Phosphodiesterase 2A forms a complex with the co-chaperone X... | KEEP AS NON CORE | Summary: cellular response to cAMP reflects a specific regulatory input into AHR trafficking through the PDE2A/XAP2/cAMP pathway rather than a core evolved function. Reason: The cited study supports cAMP/forskolin effects on AHR nuclear translocation, but these stimulus-response annotations are context-specific and secondary to the receptor/transcription-factor function. Supporting Evidence: PMID:17329248 Binding of PDE2A to XAP2 inhibited TCDD- and cAMP-induced nuclear translocation of AhR in Hepa1c1c7 hepatocytes. |
| GO:1904322 cellular response to forskolin | IDA PMID:17329248 Phosphodiesterase 2A forms a complex with the co-chaperone X... | KEEP AS NON CORE | Summary: cellular response to forskolin reflects a specific regulatory input into AHR trafficking through the PDE2A/XAP2/cAMP pathway rather than a core evolved function. Reason: The cited study supports cAMP/forskolin effects on AHR nuclear translocation, but these stimulus-response annotations are context-specific and secondary to the receptor/transcription-factor function. Supporting Evidence: PMID:17329248 Binding of PDE2A to XAP2 inhibited TCDD- and cAMP-induced nuclear translocation of AhR in Hepa1c1c7 hepatocytes. |
| GO:1904613 cellular response to 2,3,7,8-tetrachlorodibenzodioxine | IDA PMID:17329248 Phosphodiesterase 2A forms a complex with the co-chaperone X... | ACCEPT | Summary: cellular response to 2,3,7,8-tetrachlorodibenzodioxine is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:0001223 transcription coactivator binding | IPI PMID:15641800 Induced alpha-helix structure in the aryl hydrocarbon recept... | ACCEPT | Summary: transcription coactivator binding is supported by AHR transactivation-domain interactions with general transcription machinery and coactivators/coregulators. Reason: These binding annotations are more informative than generic protein binding and connect directly to AHR transcriptional regulation. They should be retained as molecular-function annotations supporting the core transactivation mechanism. Supporting Evidence: PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. |
| GO:0017025 TBP-class protein binding | IPI PMID:15641800 Induced alpha-helix structure in the aryl hydrocarbon recept... | ACCEPT | Summary: TBP-class protein binding is supported by AHR transactivation-domain interactions with general transcription machinery and coactivators/coregulators. Reason: These binding annotations are more informative than generic protein binding and connect directly to AHR transcriptional regulation. They should be retained as molecular-function annotations supporting the core transactivation mechanism. Supporting Evidence: PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. |
| GO:0032991 protein-containing complex | IMP PMID:15641800 Induced alpha-helix structure in the aryl hydrocarbon recept... | MODIFY | Summary: The evidence concerns AHR interactions with transcriptional machinery and complex formation, but the term protein-containing complex is too generic for curation. Reason: AHR participates in defined receptor/transcription complexes. Replacing the generic complex term with aryl hydrocarbon receptor complex better captures the biology supported by the cited interaction and transcriptional evidence. Proposed replacements: aryl hydrocarbon receptor complex Supporting Evidence: PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8937169 | ACCEPT | Summary: nucleoplasm localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8937177 | ACCEPT | Summary: nucleoplasm localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8937191 | ACCEPT | Summary: nucleoplasm localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8936849 | ACCEPT | Summary: cytosol localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005829 cytosol | TAS Reactome:R-HSA-8937169 | ACCEPT | Summary: cytosol localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0009636 response to toxic substance | IDA PMID:7961644 Dioxin binding activities of polymorphic forms of mouse and ... | ACCEPT | Summary: response to toxic substance is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:0032922 circadian regulation of gene expression | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Circadian regulation is a supported secondary AHR context through bHLH-PAS transcription-factor cross-talk, but not the primary function. Reason: AHR can intersect circadian transcriptional regulation, but the principal conserved function remains ligand-activated AHR:ARNT transcriptional control of xenobiotic/endogenous-ligand response genes. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0045892 negative regulation of DNA-templated transcription | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of DNA-templated transcription is supported in specific AHR contexts such as circadian/cross-talk and repressor interactions, but it is not the primary AHR output. Reason: The core AHR role is ligand-activated transcriptional regulation, usually represented by positive target-gene activation. Negative regulation occurs in specific contexts and should be retained as a secondary, context-dependent function. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:12213388 This review addresses novel findings relating to AHR functions that have resulted from experimental approaches markedly outside traditional receptor analyses. |
| GO:0045893 positive regulation of DNA-templated transcription | ISS GO_REF:0000024 | ACCEPT | Summary: positive regulation of DNA-templated transcription is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0070888 E-box binding | ISS GO_REF:0000024 | MODIFY | Summary: AHR binds AHR response elements/dioxin response elements with an E-box-like bHLH-PAS recognition mode, but the E-box binding term is less exact for AHR than cis-regulatory region sequence-specific DNA binding. Reason: The transferred mouse annotation is directionally related but should be generalized to the better supported AHR response element/cis-regulatory sequence-specific DNA binding activity for human AHR. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005634 nucleus | IDA PMID:23275542 2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymer... | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:15681594 Constitutive activation and environmental chemical induction... | ACCEPT | Summary: transcription cis-regulatory region binding is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0003677 DNA binding | IDA PMID:15681594 Constitutive activation and environmental chemical induction... | MODIFY | Summary: AHR DNA binding is real, but the generic DNA binding term is less precise than the available cis-regulatory-region sequence-specific DNA-binding terms. Reason: The evidence supports AHR binding to AHR response elements/xenobiotic response elements in regulatory DNA, not undifferentiated DNA binding. A more specific cis-regulatory sequence-specific DNA-binding term should be used. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0005634 nucleus | IDA PMID:15681594 Constitutive activation and environmental chemical induction... | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005737 cytoplasm | IDA PMID:15681594 Constitutive activation and environmental chemical induction... | ACCEPT | Summary: cytoplasm localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:15681594 Constitutive activation and environmental chemical induction... | ACCEPT | Summary: regulation of transcription by RNA polymerase II is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0010468 regulation of gene expression | IDA PMID:15681594 Constitutive activation and environmental chemical induction... | MODIFY | Summary: The B-cell study supports AHR-dependent transcriptional/gene-expression regulation, but the term regulation of gene expression is very broad. Reason: AHR is a DNA-binding transcription factor. The more precise RNA polymerase II transcription-regulation term better represents the evidence than generic gene-expression regulation. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0030888 regulation of B cell proliferation | IDA PMID:15681594 Constitutive activation and environmental chemical induction... | KEEP AS NON CORE | Summary: regulation of B cell proliferation is supported as a downstream immunological context of AHR activation, especially through microbial or tryptophan-derived ligands. Reason: AHR has substantial immune biology, but these process terms are cell-type- and disease-context-dependent outputs of AHR signaling rather than the core molecular function of the gene product. Supporting Evidence: PMID:32818467 IL4I1 activates the AHR through the generation of indole metabolites and kynurenic acid. PMID:29454749 Administration of indole metabolites showed prominent induction of IL-10R1 on cultured intestinal epithelia that was explained by activation of the aryl hydrocarbon receptor. PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0003677 DNA binding | TAS PMID:8246913 Cloning and expression of a human Ah receptor cDNA. | MODIFY | Summary: AHR DNA binding is real, but the generic DNA binding term is less precise than the available cis-regulatory-region sequence-specific DNA-binding terms. Reason: The evidence supports AHR binding to AHR response elements/xenobiotic response elements in regulatory DNA, not undifferentiated DNA binding. A more specific cis-regulatory sequence-specific DNA-binding term should be used. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0005634 nucleus | TAS PMID:8246913 Cloning and expression of a human Ah receptor cDNA. | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0001568 blood vessel development | NAS PMID:19538249 The aryl hydrocarbon receptor: a perspective on potential ro... | MARK AS OVER ANNOTATED | Summary: blood vessel development is biologically connected to AHR pleiotropy but is too broad or indirect for a core AHR annotation. Reason: AHR affects development, cell cycle, apoptosis, and organism-level phenotypes through transcriptional programs, but these high-level process annotations risk implying a direct pathway role that is not supported by the specific evidence used here. Supporting Evidence: PMID:12213388 This review addresses novel findings relating to AHR functions that have resulted from experimental approaches markedly outside traditional receptor analyses. |
| GO:0003677 DNA binding | TAS PMID:19538249 The aryl hydrocarbon receptor: a perspective on potential ro... | MODIFY | Summary: AHR DNA binding is real, but the generic DNA binding term is less precise than the available cis-regulatory-region sequence-specific DNA-binding terms. Reason: The evidence supports AHR binding to AHR response elements/xenobiotic response elements in regulatory DNA, not undifferentiated DNA binding. A more specific cis-regulatory sequence-specific DNA-binding term should be used. Proposed replacements: cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0005667 transcription regulator complex | TAS PMID:19538249 The aryl hydrocarbon receptor: a perspective on potential ro... | MODIFY | Summary: AHR is part of transcriptional regulatory complexes, but this broad cellular-component term is less informative than the existing AHR complex terms. Reason: The relevant complex is the AHR receptor/transcription-factor complex, particularly ligand-activated AHR:ARNT. The more specific AHR complex terms should be used rather than the generic transcription regulator complex term. Proposed replacements: aryl hydrocarbon receptor complex Supporting Evidence: PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0006805 xenobiotic metabolic process | TAS PMID:19538249 The aryl hydrocarbon receptor: a perspective on potential ro... | ACCEPT | Summary: xenobiotic metabolic process is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
| GO:0034752 cytosolic aryl hydrocarbon receptor complex | TAS PMID:19538249 The aryl hydrocarbon receptor: a perspective on potential ro... | ACCEPT | Summary: cytosolic aryl hydrocarbon receptor complex is an appropriate AHR complex annotation. AHR forms cytosolic chaperone-associated complexes before activation and nuclear AHR:ARNT complexes after ligand-induced activation. Reason: AHR complex membership is central to the receptor activation cycle. The receptor is maintained in a cytosolic HSP90/XAP2/p23 complex before activation and forms an AHR:ARNT DNA-bound complex in the nucleus after ligand activation. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:11259606 The molecular chaperone complex hsp90-p23 interacts with the dioxin receptor PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005515 protein binding | IPI PMID:9079689 Characterization of a subset of the basic-helix-loop-helix-P... | MODIFY | Summary: The protein binding annotation reflects AHR interactions with ARNT/related bHLH-PAS partners, but the generic term should be refined. Reason: AHR:ARNT or related heterodimerization is the informative activity supported by the interaction evidence. The review therefore proposes protein heterodimerization activity rather than generic protein binding. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0051879 Hsp90 protein binding | IDA PMID:9079689 Characterization of a subset of the basic-helix-loop-helix-P... | ACCEPT | Summary: Hsp90 binding is a well-supported part of inactive AHR cytosolic complex formation and receptor trafficking control. Reason: AHR binding to the HSP90 chaperone complex is mechanistically important for receptor conformation, cytoplasmic retention, and ligand-dependent nuclear import. This is an informative molecular-function annotation. Supporting Evidence: PMID:11259606 The molecular chaperone complex hsp90-p23 interacts with the dioxin receptor |
| GO:0003700 DNA-binding transcription factor activity | NAS PMID:9170146 Human Ah receptor (AHR) gene: localization to 7p15 and sugge... | ACCEPT | Summary: DNA-binding transcription factor activity is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:11782478 Differential activities of murine single minded 1 (SIM1) and... | ACCEPT | Summary: DNA-binding transcription factor activity is supported by the DNA-bound AHR:ARNT transcription-factor complex and by functional assays showing loss of AHR-mediated gene activation when DNA-binding or dimerization interfaces are disrupted. Reason: AHR directly binds cis-regulatory response elements as a heterodimer with ARNT and regulates RNA polymerase II target genes. These DNA-binding/transcription-factor activity terms describe the core activated AHR mechanism. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:15681594 AhR nuclear translocation, constitutive DNA binding, and induction of an AhR-regulated gene, CYP1A1, in stimulated B cells in the absence of exogenous ligands suggested constitutive AhR activation. |
| GO:0004879 nuclear receptor activity | IDA PMID:10395741 Interactions of nuclear receptor coactivator/corepressor pro... | ACCEPT | Summary: AHR is a ligand-activated intracellular receptor/transcription factor. Ligand binding, nuclear translocation, ARNT heterodimerization, and target-gene activation are all well supported. Reason: Although AHR is a bHLH-PAS receptor rather than a classical steroid-receptor-family member, GO nuclear receptor activity appropriately captures its ligand-activated receptor function in the nucleus. This is a core molecular function. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0005634 nucleus | IDA PMID:10395741 Interactions of nuclear receptor coactivator/corepressor pro... | ACCEPT | Summary: nucleus localization is consistent with AHR biology: inactive AHR is predominantly cytoplasmic/cytosolic in a chaperone complex and ligand activation drives nuclear/nucleoplasmic accumulation and chromatin-associated transcriptional activity. Reason: These cellular-component annotations reflect the normal ligand-dependent trafficking cycle of AHR rather than separate functions. The 2021 live-cell analysis directly supports cytoplasmic localization and nuclear translocation; chromatin/nuclear annotations are consistent with the DNA-bound AHR:ARNT transcription-factor complex. Supporting Evidence: PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. PMID:28602820 AHR is activated by xenobiotics, notably dioxin |
| GO:0006355 regulation of DNA-templated transcription | IDA PMID:10395741 Interactions of nuclear receptor coactivator/corepressor pro... | ACCEPT | Summary: regulation of DNA-templated transcription is consistent with AHR acting as a ligand-activated transcription factor that regulates RNA polymerase II target genes after nuclear AHR:ARNT complex formation. Reason: Transcriptional regulation is the central biological output of activated AHR. The term is broad in some cases, but the direction and process are supported by ligand-induced target gene activation and by cofactor/transactivation-domain evidence. Supporting Evidence: PMID:28602820 AHR is activated by xenobiotics, notably dioxin PMID:10395741 These results confirmed functional and physical interactions of AhR/Arnt with ERAP 140 and SMRT in breast cancer cells. PMID:15641800 the acidic Q-rich region bound to components of the general transcription machinery |
| GO:0006915 apoptotic process | TAS PMID:12213388 Role of the aryl hydrocarbon receptor in cell cycle regulati... | MARK AS OVER ANNOTATED | Summary: apoptotic process is biologically connected to AHR pleiotropy but is too broad or indirect for a core AHR annotation. Reason: AHR affects development, cell cycle, apoptosis, and organism-level phenotypes through transcriptional programs, but these high-level process annotations risk implying a direct pathway role that is not supported by the specific evidence used here. Supporting Evidence: PMID:12213388 This review addresses novel findings relating to AHR functions that have resulted from experimental approaches markedly outside traditional receptor analyses. |
| GO:0009410 response to xenobiotic stimulus | IDA PMID:7961644 Dioxin binding activities of polymorphic forms of mouse and ... | ACCEPT | Summary: response to xenobiotic stimulus is a core AHR pathway outcome. AHR binds xenobiotic ligands such as TCDD/dioxin-related compounds and induces detoxification and response genes. Reason: AHR does not enzymatically metabolize xenobiotics itself, but GO biological-process annotations correctly capture its upstream receptor/transcription-factor role in xenobiotic response and metabolism programs. Supporting Evidence: PMID:7961644 This result provides the first direct evidence that the cDNA-encoded protein binds the ligand specifically. PMID:34521881 The human aryl hydrocarbon receptor (AHR) is predominantly located in the cytoplasm, while activation depends on its nuclear translocation. |
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Download this section (compressed HTML)Q: Does endogenous human AHR directly function as a CRL4/CUL4A-CUL4B substrate adaptor, or is the PN UPS placement better interpreted as broad complex/domain context plus AHR turnover rather than an AHR molecular function?
Q: Which immune and developmental AHR outputs should be treated as broadly physiological annotations versus ligand-, tissue-, or disease-specific non-core contexts?
Q: Now that AHR:ARNT:DNA structures define the PAS-B domain as the principal ligand-binding pocket and reveal a PAS-B/PAS-B heterodimer interface, should a ligand-binding molecular-function term (e.g., a small-molecule/xenobiotic sensor activity) be added to better capture AHR ligand recognition distinct from its DNA-binding and dimerization activities?
Experiment: Reconstitute candidate DDB1-CUL4A/CUL4B-AHR/ARNT/TBL3 assemblies and test whether AHR directly recruits a defined substrate for ubiquitination, including CUL4 dependence, AHR mutant controls, and comparison with established DCAF substrate receptors.
Hypothesis: AHR should only receive GO:1990756 if it directly bridges a substrate to a CUL4 ubiquitin-ligase complex.
Type: in vitro ubiquitination and complex reconstitution
Experiment: Use endogenous-tagged AHR cells with proteasome inhibition, CUL4/DDB1 perturbation, and quantitative IP-MS/proximity labeling to distinguish AHR as a CUL4 substrate, a stable CRL4 complex component, or a substrate-recruiting adaptor.
Hypothesis: The PN AHR UPS projection may reflect regulated degradation of AHR rather than substrate-adaptor activity by AHR.
Type: endogenous proteomics and perturbation assay
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