ARNT encodes aryl hydrocarbon receptor nuclear translocator, also known as HIF-1 beta, a broadly expressed nuclear bHLH-PAS transcription factor subunit. ARNT dimerizes with AHR, HIF-alpha proteins, and other bHLH-PAS partners through PAS-domain interfaces, and the resulting complexes bind cis-regulatory DNA elements such as xenobiotic/dioxin response elements and hypoxia response elements to regulate RNA polymerase II transcription. Through these heterodimeric complexes, ARNT participates in xenobiotic response, hypoxia adaptation, angiogenic and metabolic gene regulation, and selected immune and developmental transcriptional programs. The primary molecular roles are sequence-specific regulatory DNA binding and partner-specific transcription factor dimerization in the nucleus.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: regulation of transcription by RNA polymerase II is supported by ARNT-containing AHR and HIF transcriptional regulatory complexes. Reason: ARNT-containing heterodimers activate and regulate RNA polymerase II target genes in hypoxia and xenobiotic-response pathways. This is a central biological role of the protein. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: nucleus is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0034751 aryl hydrocarbon receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: aryl hydrocarbon receptor complex is directly supported for ARNT-containing AHR complexes. Reason: ARNT is the required nuclear translocator/dimerization partner of AHR and is a structural component of the DNA-binding AHR complex. Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with ARNT-containing AHR and HIF transcription factor complexes binding regulatory DNA. Reason: ARNT is a bHLH-PAS transcription factor subunit. Primary AHR and HIF studies show ARNT-containing heterodimers binding DRE/XRE or HRE-like regulatory DNA and activating transcription. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0001666 response to hypoxia | IEA GO_REF:0000117 | ACCEPT | Summary: response to hypoxia is supported through ARNT/HIF transcriptional response to low oxygen. Reason: ARNT is HIF-1 beta, the constitutive dimerization partner for HIF-alpha proteins. Loss of ARNT/HIF-1 beta disrupts hypoxia-inducible VEGF expression, and HIF-alpha:ARNT complexes drive hypoxia transcriptional programs. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | MODIFY | Summary: The broad DNA-binding transcription factor annotation is directionally correct but should be represented by RNA polymerase II-specific DNA-binding transcription factor terms. Reason: ARNT is not a generic transcription factor; its curated role is as a bHLH-PAS subunit of RNA polymerase II regulatory complexes that bind defined cis-regulatory DNA elements. A more specific Pol II DNA-binding transcription factor term is preferable. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: nucleus is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000120 | MODIFY | Summary: Transcription regulator complex is true but too broad. Reason: ARNT is part of RNA polymerase II transcription regulatory complexes, including AHR-ARNT and HIF-alpha:ARNT complexes. The Pol II-specific complex term is more informative. Proposed replacements: RNA polymerase II transcription regulator complex Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005737 cytoplasm | IEA GO_REF:0000120 | REMOVE | Summary: Cytoplasm is not supported as a stable ARNT localization in the reviewed evidence. Reason: ARNT is principally nuclear and functions in nuclear transcription factor complexes. Cytoplasmic AHR trafficking should not be transferred to ARNT as a cytoplasmic localization without direct evidence. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | MODIFY | Summary: The annotation is directionally correct but too broad. Reason: ARNT regulates RNA polymerase II transcription as part of AHR/HIF-family complexes, so the Pol II-specific transcription regulation term already present in GOA is preferable. Proposed replacements: regulation of transcription by RNA polymerase II Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0030522 intracellular receptor signaling pathway | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: Intracellular receptor signaling pathway is plausible but broad for ARNT. Reason: ARNT contributes to ligand-activated AHR signaling, but ARNT itself is not the ligand-binding receptor. More specific AHR complex, AHR binding, and transcription regulation annotations better capture the function. Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000002 | MODIFY | Summary: Generic protein dimerization is supported but should be replaced by the more informative heterodimerization activity. Reason: ARNT primarily functions by heterodimerizing with AHR, HIF1A/EPAS1, and other bHLH-PAS partners. The broad dimerization term loses the biologically important partner-specific heterodimer context. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). |
| GO:0005515 protein binding | IPI PMID:10395741 Interactions of nuclear receptor coactivator/corepressor pro... | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:11018023 CLIF, a novel cycle-like factor, regulates the circadian osc... | MODIFY | Summary: The interaction evidence is real, but the GO term protein binding is uninformative for ARNT. Reason: For ARNT, these interaction papers support bHLH-PAS transcription factor heterodimerization or AHR binding rather than a generic protein-binding molecular function. Replace with an informative dimerization or AHR-binding term where appropriate. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. |
| GO:0005515 protein binding | IPI PMID:14668441 Structural basis for PAS domain heterodimerization in the ba... | MODIFY | Summary: The interaction evidence is real, but the GO term protein binding is uninformative for ARNT. Reason: For ARNT, these interaction papers support bHLH-PAS transcription factor heterodimerization or AHR binding rather than a generic protein-binding molecular function. Replace with an informative dimerization or AHR-binding term where appropriate. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. |
| GO:0005515 protein binding | IPI PMID:19129502 Artificial ligand binding within the HIF2alpha PAS-B domain ... | MODIFY | Summary: The interaction evidence is real, but the GO term protein binding is uninformative for ARNT. Reason: For ARNT, these interaction papers support bHLH-PAS transcription factor heterodimerization or AHR binding rather than a generic protein-binding molecular function. Replace with an informative dimerization or AHR-binding term where appropriate. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. |
| GO:0005515 protein binding | IPI PMID:20562859 Network organization of the human autophagy system. | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:20603618 RKTG inhibits angiogenesis by suppressing MAPK-mediated auto... | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:20932347 Increased accumulation of hypoxia-inducible factor-1Ξ± with r... | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:21620138 Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypo... | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:23434853 Allosteric inhibition of hypoxia inducible factor-2 with sma... | MODIFY | Summary: The interaction evidence is real, but the GO term protein binding is uninformative for ARNT. Reason: For ARNT, these interaction papers support bHLH-PAS transcription factor heterodimerization or AHR binding rather than a generic protein-binding molecular function. Replace with an informative dimerization or AHR-binding term where appropriate. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. |
| GO:0005515 protein binding | IPI PMID:24434214 Cbx4 governs HIF-1Ξ± to potentiate angiogenesis of hepatocell... | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:24981860 Human-chromatin-related protein interactions identify a deme... | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: The generic protein binding annotation is not informative as a gene-function statement. Reason: The interaction may be experimentally detected, but protein binding alone does not describe ARNT molecular function and several cited records come from large-scale or pathway-context interaction studies. ARNT function is better captured by specific transcription factor dimerization, AHR binding, DNA binding, and transcription regulatory complex terms. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005515 protein binding | IPI PMID:9704006 Transcriptionally active heterodimer formation of an Arnt-li... | MODIFY | Summary: The interaction evidence is real, but the GO term protein binding is uninformative for ARNT. Reason: For ARNT, these interaction papers support bHLH-PAS transcription factor heterodimerization or AHR binding rather than a generic protein-binding molecular function. Replace with an informative dimerization or AHR-binding term where appropriate. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: RNA polymerase II cis-regulatory region sequence-specific DNA binding is consistent with ARNT-containing AHR and HIF transcription factor complexes binding regulatory DNA. Reason: ARNT is a bHLH-PAS transcription factor subunit. Primary AHR and HIF studies show ARNT-containing heterodimers binding DRE/XRE or HRE-like regulatory DNA and activating transcription. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0004879 nuclear receptor activity | IEA GO_REF:0000107 | MODIFY | Summary: Nuclear receptor activity is not an ideal term for ARNT. Reason: ARNT does not itself bind ligand as a receptor. The evidence supports ARNT contribution to AHR-containing transcription factor complexes, so AHR binding and RNA polymerase II DNA-binding transcription factor activity are better replacements. Proposed replacements: aryl hydrocarbon receptor binding DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. |
| GO:0033235 positive regulation of protein sumoylation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of protein sumoylation is not supported as a core ARNT function in this review. Reason: ARNT can be present in HIF/AHR regulatory contexts where partner proteins are post-translationally modified, but the reviewed primary ARNT function is transcription-factor dimerization and DNA binding. This electronic transfer should not be promoted in the PN review without direct ARNT-specific evidence. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt Required for activity of the AHR. Upon ligand binding, AHR translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE). file:human/ARNT/ARNT-uniprot.txt The heterodimer binds to core DNA sequence 5'-TACGTG-3' within the hypoxia response element (HRE) of target gene promoters and functions as a transcriptional regulator of the adaptive response to hypoxia. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | MODIFY | Summary: sequence-specific DNA binding is true but less specific than the supported Pol II cis-regulatory DNA-binding role. Reason: The primary evidence concerns ARNT-containing AHR/HIF transcription factor complexes binding DRE/XRE or HRE cis-regulatory elements. The annotation should use the Pol II cis-regulatory DNA-binding term rather than a generic sequence-specific DNA-binding term. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0046982 protein heterodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: ARNT heterodimerization is a core molecular function. Reason: Multiple structural and functional studies show ARNT forming heterodimers with AHR and HIF-alpha proteins through bHLH-PAS/PAS-B interfaces; these heterodimers are the active transcriptional regulatory complexes. Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| GO:1990837 sequence-specific double-stranded DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: sequence-specific double-stranded DNA binding is consistent with ARNT-containing AHR and HIF transcription factor complexes binding regulatory DNA. Reason: ARNT is a bHLH-PAS transcription factor subunit. Primary AHR and HIF studies show ARNT-containing heterodimers binding DRE/XRE or HRE-like regulatory DNA and activating transcription. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0005634 nucleus | IDA PMID:10085255 Induction and nuclear translocation of hypoxia-inducible fac... | ACCEPT | Summary: nucleus is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:23033253 Identification of Cys255 in HIF-1Ξ± as a novel site for devel... | ACCEPT | Summary: regulation of transcription by RNA polymerase II is supported by ARNT-containing AHR and HIF transcriptional regulatory complexes. Reason: ARNT-containing heterodimers activate and regulate RNA polymerase II target genes in hypoxia and xenobiotic-response pathways. This is a central biological role of the protein. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:23033253 Identification of Cys255 in HIF-1Ξ± as a novel site for devel... | ACCEPT | Summary: ARNT is part of RNA polymerase II transcription regulator complexes. Reason: HIF and AHR transcription complexes contain ARNT and regulate Pol II target genes through HRE/DRE regulatory elements. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0006357 regulation of transcription by RNA polymerase II | NAS PMID:23434853 Allosteric inhibition of hypoxia inducible factor-2 with sma... | ACCEPT | Summary: regulation of transcription by RNA polymerase II is supported by ARNT-containing AHR and HIF transcriptional regulatory complexes. Reason: ARNT-containing heterodimers activate and regulate RNA polymerase II target genes in hypoxia and xenobiotic-response pathways. This is a central biological role of the protein. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| GO:0071456 cellular response to hypoxia | NAS PMID:30429208 Inherent DNA-binding specificities of the HIF-1Ξ± and HIF-2Ξ± ... | ACCEPT | Summary: cellular response to hypoxia is supported through ARNT/HIF transcriptional response to low oxygen. Reason: ARNT is HIF-1 beta, the constitutive dimerization partner for HIF-alpha proteins. Loss of ARNT/HIF-1 beta disrupts hypoxia-inducible VEGF expression, and HIF-alpha:ARNT complexes drive hypoxia transcriptional programs. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. |
| GO:0090575 RNA polymerase II transcription regulator complex | IPI PMID:23434853 Allosteric inhibition of hypoxia inducible factor-2 with sma... | ACCEPT | Summary: ARNT is part of RNA polymerase II transcription regulator complexes. Reason: HIF and AHR transcription complexes contain ARNT and regulate Pol II target genes through HRE/DRE regulatory elements. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: nucleoplasm is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0006805 xenobiotic metabolic process | TAS Reactome:R-HSA-8937144 | ACCEPT | Summary: Xenobiotic metabolic process is supported through the AHR-ARNT transcriptional response. Reason: ARNT is required for ligand-activated AHR transcriptional complexes that bind xenobiotic response elements and induce detoxification/metabolic genes. This is a core AHR-ARNT biological role. Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. file:human/ARNT/ARNT-uniprot.txt Required for activity of the AHR. Upon ligand binding, AHR translocates into the nucleus, where it heterodimerizes with ARNT and induces transcription by binding to xenobiotic response elements (XRE). |
| GO:0016604 nuclear body | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nuclear body localization is HPA-supported but peripheral to ARNT function. Reason: The localization may describe an observed nuclear subcompartment signal, but ARNT core function is in transcription factor complexes and regulatory DNA binding rather than nuclear-body biology. Supporting Evidence: GO_REF:0000052 [HPA immunofluorescence-derived GO cellular-component annotation] |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | TAS Reactome:R-HSA-8937177 | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific captures the transcription-factor activity of ARNT-containing RNA polymerase II regulatory complexes. Reason: The activity is best interpreted as the activity of ARNT-containing heterodimers. ARNT contributes DNA-binding and PAS-dimerization surfaces to AHR/HIF complexes that regulate Pol II target genes. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. |
| GO:0045821 positive regulation of glycolytic process | IDA PMID:8089148 Transcriptional regulation of genes encoding glycolytic enzy... | KEEP AS NON CORE | Summary: Positive regulation of glycolysis is a supported downstream HIF pathway output, but not ARNT molecular core function. Reason: The cited study shows HIF-1-mediated induction of glycolytic enzyme genes under hypoxia. Because ARNT is HIF-1 beta, this is biologically plausible, but it is a downstream transcriptional program rather than a direct proteostasis or adaptor role. Supporting Evidence: PMID:8089148 RNAs encoding the glycolytic enzymes aldolase A (ALDA), phosphoglycerate kinase 1 (PGK1), and pyruvate kinase M were induced by exposure of Hep3B or HeLa cells to inducers of HIF-1 PMID:8089148 These results support the role of HIF-1 as a mediator of adaptive responses to hypoxia |
| GO:0034599 cellular response to oxidative stress | IDA PMID:8089148 Transcriptional regulation of genes encoding glycolytic enzy... | MARK AS OVER ANNOTATED | Summary: Cellular response to oxidative stress is too indirect for the cited ARNT/HIF glycolysis paper. Reason: PMID:8089148 supports HIF-dependent hypoxia-responsive glycolytic gene transcription, not a direct ARNT role in oxidative-stress response. Hypoxia-response annotations already capture the supported biology. Supporting Evidence: PMID:8089148 These results support the role of HIF-1 as a mediator of adaptive responses to hypoxia |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:8089148 Transcriptional regulation of genes encoding glycolytic enzy... | ACCEPT | Summary: positive regulation of transcription by RNA polymerase II is supported by ARNT-containing AHR and HIF transcriptional regulatory complexes. Reason: ARNT-containing heterodimers activate and regulate RNA polymerase II target genes in hypoxia and xenobiotic-response pathways. This is a central biological role of the protein. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| 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 plausible through AHR-ARNT epithelial signaling, but it is not a core ARNT molecular function. Reason: The cited study supports microbiota-derived indole metabolites activating AHR-dependent IL-10 receptor regulation and anti-inflammatory pathways. ARNT is the AHR transcriptional partner, but the anti-inflammatory phenotype is pathway-level and context-specific. 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. PMID:29454749 This work defines a novel role of indole metabolites in anti-inflammatory pathways mediated by epithelial IL-10 signaling |
| GO:0004879 nuclear receptor activity | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | MODIFY | Summary: Nuclear receptor activity is not an ideal term for ARNT. Reason: ARNT does not itself bind ligand as a receptor. The evidence supports ARNT contribution to AHR-containing transcription factor complexes, so AHR binding and RNA polymerase II DNA-binding transcription factor activity are better replacements. Proposed replacements: aryl hydrocarbon receptor binding DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. |
| GO:0005515 protein binding | IPI PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | MODIFY | Summary: The interaction evidence is real, but the GO term protein binding is uninformative for ARNT. Reason: For ARNT, these interaction papers support bHLH-PAS transcription factor heterodimerization or AHR binding rather than a generic protein-binding molecular function. Replace with an informative dimerization or AHR-binding term where appropriate. Proposed replacements: aryl hydrocarbon receptor binding protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. |
| GO:0005634 nucleus | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: nucleus is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| 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 directly supported for ARNT-containing AHR complexes. Reason: ARNT is the required nuclear translocator/dimerization partner of AHR and is a structural component of the DNA-binding AHR complex. Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. |
| 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 supported by ARNT-containing AHR and HIF transcriptional regulatory complexes. Reason: ARNT-containing heterodimers activate and regulate RNA polymerase II target genes in hypoxia and xenobiotic-response pathways. This is a central biological role of the protein. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| GO:0046982 protein heterodimerization activity | IDA PMID:34521881 The role of DNA-binding and ARNT dimerization on the nucleo-... | ACCEPT | Summary: ARNT heterodimerization is a core molecular function. Reason: Multiple structural and functional studies show ARNT forming heterodimers with AHR and HIF-alpha proteins through bHLH-PAS/PAS-B interfaces; these heterodimers are the active transcriptional regulatory complexes. Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| 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 consistent with ARNT-containing AHR and HIF transcription factor complexes binding regulatory DNA. Reason: ARNT is a bHLH-PAS transcription factor subunit. Primary AHR and HIF studies show ARNT-containing heterodimers binding DRE/XRE or HRE-like regulatory DNA and activating transcription. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:29454749 Microbiota-Derived Indole Metabolites Promote Human and Muri... | MODIFY | Summary: The broad DNA-binding transcription factor annotation is directionally correct but should be represented by RNA polymerase II-specific DNA-binding transcription factor terms. Reason: ARNT is not a generic transcription factor; its curated role is as a bHLH-PAS subunit of RNA polymerase II regulatory complexes that bind defined cis-regulatory DNA elements. A more specific Pol II DNA-binding transcription factor term is preferable. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005634 nucleus | IC PMID:28602820 Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene... | ACCEPT | Summary: nucleus is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1234167 | ACCEPT | Summary: nucleoplasm is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-1234171 | ACCEPT | Summary: nucleoplasm is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8936851 | ACCEPT | Summary: nucleoplasm is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8937177 | ACCEPT | Summary: nucleoplasm is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9634850 | ACCEPT | Summary: nucleoplasm is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:7539918 Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS h... | ACCEPT | Summary: RNA polymerase II-specific DNA-binding transcription factor binding is a supported molecular interaction function for ARNT. Reason: ARNT is the common dimerization partner for AHR/HIF-family DNA-binding transcription factors. Specific transcription-factor binding and AHR-binding terms are more informative than generic protein binding. Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. |
| 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 a supported molecular interaction function for ARNT. Reason: ARNT is the common dimerization partner for AHR/HIF-family DNA-binding transcription factors. Specific transcription-factor binding and AHR-binding terms are more informative than generic protein binding. Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. |
| GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding | IPI PMID:10692439 Cardiovascular basic helix loop helix factor 1, a novel tran... | ACCEPT | Summary: RNA polymerase II-specific DNA-binding transcription factor binding is a supported molecular interaction function for ARNT. Reason: ARNT is the common dimerization partner for AHR/HIF-family DNA-binding transcription factors. Specific transcription-factor binding and AHR-binding terms are more informative than generic protein binding. Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IDA PMID:23275542 2,3,7,8-Tetrachlorodibenzo-p-dioxin poly(ADP-ribose) polymer... | MODIFY | Summary: cis-regulatory region sequence-specific DNA binding is true but less specific than the supported Pol II cis-regulatory DNA-binding role. Reason: The primary evidence concerns ARNT-containing AHR/HIF transcription factor complexes binding DRE/XRE or HRE cis-regulatory elements. The annotation should use the Pol II cis-regulatory DNA-binding term rather than a generic sequence-specific DNA-binding term. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:7539918 Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS h... | MODIFY | Summary: sequence-specific DNA binding is true but less specific than the supported Pol II cis-regulatory DNA-binding role. Reason: The primary evidence concerns ARNT-containing AHR/HIF transcription factor complexes binding DRE/XRE or HRE cis-regulatory elements. The annotation should use the Pol II cis-regulatory DNA-binding term rather than a generic sequence-specific DNA-binding term. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:7539918 Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS h... | ACCEPT | Summary: positive regulation of transcription by RNA polymerase II is supported by ARNT-containing AHR and HIF transcriptional regulatory complexes. Reason: ARNT-containing heterodimers activate and regulate RNA polymerase II target genes in hypoxia and xenobiotic-response pathways. This is a central biological role of the protein. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: Chromatin localization is consistent with ARNT as a DNA-binding transcription factor subunit. Reason: AHR-ARNT and HIF-alpha:ARNT complexes bind regulatory DNA in chromatin to regulate Pol II transcription. Supporting Evidence: PMID:30429208 both HIFβΞ± isoforms bind chromatin in a stoichiometric ratio with HIFβ1Ξ² PMID:28396409 mammalian AHR-ARNT heterodimer in complex with the DRE |
| 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 captures the transcription-factor activity of ARNT-containing RNA polymerase II regulatory complexes. Reason: The activity is best interpreted as the activity of ARNT-containing heterodimers. ARNT contributes DNA-binding and PAS-dimerization surfaces to AHR/HIF complexes that regulate Pol II target genes. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. |
| GO:0005515 protein binding | IPI PMID:16181639 Structural basis of ARNT PAS-B dimerization: use of a common... | MODIFY | Summary: The interaction evidence is real, but the GO term protein binding is uninformative for ARNT. Reason: For ARNT, these interaction papers support bHLH-PAS transcription factor heterodimerization or AHR binding rather than a generic protein-binding molecular function. Replace with an informative dimerization or AHR-binding term where appropriate. Proposed replacements: protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. |
| GO:0005515 protein binding | IPI PMID:28396409 Structural hierarchy controlling dimerization and target DNA... | MODIFY | Summary: The interaction evidence is real, but the GO term protein binding is uninformative for ARNT. Reason: For ARNT, these interaction papers support bHLH-PAS transcription factor heterodimerization or AHR binding rather than a generic protein-binding molecular function. Replace with an informative dimerization or AHR-binding term where appropriate. Proposed replacements: aryl hydrocarbon receptor binding protein heterodimerization activity Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. |
| GO:0042803 protein homodimerization activity | IDA PMID:16181639 Structural basis of ARNT PAS-B dimerization: use of a common... | KEEP AS NON CORE | Summary: ARNT PAS-B homodimerization is experimentally observed but is not the main physiological ARNT function. Reason: The cited structural study reports concentration-dependent self-association of the ARNT PAS-B domain, but the established cellular functions are heterodimeric AHR/HIF-family transcription complexes. Supporting Evidence: PMID:16181639 this domain self-associates in a concentration-dependent manner PMID:16181639 the interface used in this homodimeric complex is very similar to that used in the formation of heterodimer |
| GO:0046982 protein heterodimerization activity | IDA PMID:16181639 Structural basis of ARNT PAS-B dimerization: use of a common... | ACCEPT | Summary: ARNT heterodimerization is a core molecular function. Reason: Multiple structural and functional studies show ARNT forming heterodimers with AHR and HIF-alpha proteins through bHLH-PAS/PAS-B interfaces; these heterodimers are the active transcriptional regulatory complexes. Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28396409 Structural hierarchy controlling dimerization and target DNA... | ACCEPT | Summary: sequence-specific double-stranded DNA binding is consistent with ARNT-containing AHR and HIF transcription factor complexes binding regulatory DNA. Reason: ARNT is a bHLH-PAS transcription factor subunit. Primary AHR and HIF studies show ARNT-containing heterodimers binding DRE/XRE or HRE-like regulatory DNA and activating transcription. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0090575 RNA polymerase II transcription regulator complex | IDA PMID:7539918 Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS h... | ACCEPT | Summary: ARNT is part of RNA polymerase II transcription regulator complexes. Reason: HIF and AHR transcription complexes contain ARNT and regulate Pol II target genes through HRE/DRE regulatory elements. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0090575 RNA polymerase II transcription regulator complex | IDA PMID:8756616 Activation of vascular endothelial growth factor gene transc... | ACCEPT | Summary: ARNT is part of RNA polymerase II transcription regulator complexes. Reason: HIF and AHR transcription complexes contain ARNT and regulate Pol II target genes through HRE/DRE regulatory elements. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:7539918 Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS h... | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific captures the transcription-factor activity of ARNT-containing RNA polymerase II regulatory complexes. Reason: The activity is best interpreted as the activity of ARNT-containing heterodimers. ARNT contributes DNA-binding and PAS-dimerization surfaces to AHR/HIF complexes that regulate Pol II target genes. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:8756616 Activation of vascular endothelial growth factor gene transc... | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific captures the transcription-factor activity of ARNT-containing RNA polymerase II regulatory complexes. Reason: The activity is best interpreted as the activity of ARNT-containing heterodimers. ARNT contributes DNA-binding and PAS-dimerization surfaces to AHR/HIF complexes that regulate Pol II target genes. Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. |
| GO:0001666 response to hypoxia | IDA PMID:8756616 Activation of vascular endothelial growth factor gene transc... | ACCEPT | Summary: response to hypoxia is supported through ARNT/HIF transcriptional response to low oxygen. Reason: ARNT is HIF-1 beta, the constitutive dimerization partner for HIF-alpha proteins. Loss of ARNT/HIF-1 beta disrupts hypoxia-inducible VEGF expression, and HIF-alpha:ARNT complexes drive hypoxia transcriptional programs. Supporting Evidence: PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:30429208 In contrast, HIFβΞ² is constitutively expressed 11. In hypoxia, HIFβΞ± polypeptides escape destruction and are able to associate with HIFβΞ² to drive transcriptional responses 4. |
| GO:0001938 positive regulation of endothelial cell proliferation | IC PMID:8756616 Activation of vascular endothelial growth factor gene transc... | MARK AS OVER ANNOTATED | Summary: Endothelial proliferation is downstream of VEGF induction and too indirect for ARNT. Reason: PMID:8756616 supports HIF-1-dependent VEGF transcription and loss of hypoxic VEGF induction in ARNT-deficient cells. Endothelial proliferation is a downstream biological consequence, not a direct ARNT gene-product function. Supporting Evidence: PMID:8756616 These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells. |
| GO:0005634 nucleus | IDA PMID:8089148 Transcriptional regulation of genes encoding glycolytic enzy... | ACCEPT | Summary: nucleus is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
| GO:0010575 positive regulation of vascular endothelial growth factor production | IDA PMID:8756616 Activation of vascular endothelial growth factor gene transc... | KEEP AS NON CORE | Summary: Positive regulation of VEGF production is supported as a downstream HIF-1 transcriptional output. Reason: ARNT/HIF-1 beta is required for hypoxia-induced VEGF expression, but this is a pathway output rather than ARNT molecular core function. Supporting Evidence: PMID:8756616 VEGF mRNA was not induced by hypoxia in mutant cells that do not express the HIF-1beta (ARNT) subunit. PMID:8756616 These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells. |
| GO:0017162 aryl hydrocarbon receptor binding | IPI PMID:9079689 Characterization of a subset of the basic-helix-loop-helix-P... | ACCEPT | Summary: aryl hydrocarbon receptor binding is a supported molecular interaction function for ARNT. Reason: ARNT is the common dimerization partner for AHR/HIF-family DNA-binding transcription factors. Specific transcription-factor binding and AHR-binding terms are more informative than generic protein binding. Supporting Evidence: PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors including hypoxia-inducible factors (HIF)18, single-minded proteins (SIM)19 or the estrogen receptor (ER)20. PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. |
| GO:0030949 positive regulation of vascular endothelial growth factor receptor signaling pathway | IC PMID:8756616 Activation of vascular endothelial growth factor gene transc... | MARK AS OVER ANNOTATED | Summary: VEGF receptor signaling is a downstream inference from VEGF production and should not be asserted for ARNT. Reason: The experimental evidence supports ARNT/HIF-dependent VEGF transcription, not direct positive regulation of VEGF receptor signaling by ARNT. Supporting Evidence: PMID:8756616 These findings implicate HIF-1 in the activation of VEGF transcription in hypoxic cells. |
| GO:0045648 positive regulation of erythrocyte differentiation | IC PMID:1448077 A nuclear factor induced by hypoxia via de novo protein synt... | MARK AS OVER ANNOTATED | Summary: positive regulation of erythrocyte differentiation is an indirect downstream annotation from early hypoxia/EPO enhancer work. Reason: PMID:1448077 identifies a hypoxia-inducible enhancer-binding factor for erythropoietin regulation but does not specifically establish ARNT as directly regulating erythrocyte differentiation or hormone biosynthesis. Modern ARNT annotations should emphasize HIF/AHR transcription-factor activity and hypoxia response. Supporting Evidence: PMID:1448077 We have identified a 50-nucleotide enhancer from the human erythropoietin gene 3'-flanking sequence which can mediate a sevenfold transcriptional induction in response to hypoxia PMID:1448077 Factor binding was induced by hypoxia |
| GO:0046886 positive regulation of hormone biosynthetic process | IDA PMID:1448077 A nuclear factor induced by hypoxia via de novo protein synt... | MARK AS OVER ANNOTATED | Summary: positive regulation of hormone biosynthetic process is an indirect downstream annotation from early hypoxia/EPO enhancer work. Reason: PMID:1448077 identifies a hypoxia-inducible enhancer-binding factor for erythropoietin regulation but does not specifically establish ARNT as directly regulating erythrocyte differentiation or hormone biosynthesis. Modern ARNT annotations should emphasize HIF/AHR transcription-factor activity and hypoxia response. Supporting Evidence: PMID:1448077 We have identified a 50-nucleotide enhancer from the human erythropoietin gene 3'-flanking sequence which can mediate a sevenfold transcriptional induction in response to hypoxia PMID:1448077 Factor binding was induced by hypoxia |
| GO:0046982 protein heterodimerization activity | IPI PMID:9079689 Characterization of a subset of the basic-helix-loop-helix-P... | ACCEPT | Summary: ARNT heterodimerization is a core molecular function. Reason: Multiple structural and functional studies show ARNT forming heterodimers with AHR and HIF-alpha proteins through bHLH-PAS/PAS-B interfaces; these heterodimers are the active transcriptional regulatory complexes. Supporting Evidence: PMID:16181639 ARNT is a promiscuous bHLH-PAS (Per-ARNT-Sim) protein that forms heterodimeric transcriptional regulator complexes with several other bHLH-PAS subunits. PMID:16181639 we have solved the solution structure of the corresponding PAS domain of ARNT and show that it utilizes a very similar interface for the interaction with the HIF-2alpha PAS domain. PMID:1317062 The ligand-bound receptor activates Cyp 1a1 gene transcription through interaction with specific DNA sequences, termed xenobiotic responsive elements (XREs). PMID:28396409 We determined the crystal structure of the mammalian AHR-ARNT heterodimer in complex with the DRE. |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:10777486 Role of hypoxia-inducible factor-1 in transcriptional activa... | MODIFY | Summary: The broad DNA-binding transcription factor annotation is directionally correct but should be represented by RNA polymerase II-specific DNA-binding transcription factor terms. Reason: ARNT is not a generic transcription factor; its curated role is as a bHLH-PAS subunit of RNA polymerase II regulatory complexes that bind defined cis-regulatory DNA elements. A more specific Pol II DNA-binding transcription factor term is preferable. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0003700 DNA-binding transcription factor activity | TAS PMID:1317062 Identification of the Ah receptor nuclear translocator prote... | MODIFY | Summary: The broad DNA-binding transcription factor annotation is directionally correct but should be represented by RNA polymerase II-specific DNA-binding transcription factor terms. Reason: ARNT is not a generic transcription factor; its curated role is as a bHLH-PAS subunit of RNA polymerase II regulatory complexes that bind defined cis-regulatory DNA elements. A more specific Pol II DNA-binding transcription factor term is preferable. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding DNA-binding transcription factor activity, RNA polymerase II-specific Supporting Evidence: PMID:1317062 Arnt is now shown to be a structural component of the XRE binding form of the Ah receptor. PMID:7539918 HIF-1 beta is a series of ARNT gene products, which can thus heterodimerize with either HIF-1 alpha or AHR. PMID:28396409 The AHR forms a transcriptionally active heterodimer with ARNT (AHR nuclear translocator), which recognizes the dioxin response element (DRE) in the promoter of downstream genes. |
| GO:0005634 nucleus | TAS PMID:1317062 Identification of the Ah receptor nuclear translocator prote... | ACCEPT | Summary: nucleus is a supported nuclear localization for ARNT. Reason: ARNT functions in nuclear transcription factor complexes and is reported as nuclear by UniProt, primary AHR/HIF studies, Reactome complex events, and HPA-derived nucleoplasm annotations. Supporting Evidence: file:human/ARNT/ARNT-uniprot.txt SUBCELLULAR LOCATION: Nucleus PMID:1317062 Arnt and the ligand-binding subunit of the receptor were extracted as a complex from the nuclei of cells treated with ligand. PMID:34521881 ARNT is a nuclear protein that acts as dimerization partner for several transcription factors |
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Download this section (compressed HTML)Q: Does any primary literature directly show ARNT functioning as a Cul4A/Cul4B ubiquitin-like ligase substrate adaptor, or is the PN workbook row reflecting AHR/ARNT/TBL3 complex context rather than ARNT molecular activity?
Q: Should generic ARNT protein-binding annotations from large-scale interactome studies be replaced systematically with partner-specific transcription factor binding or heterodimerization terms where the original evidence supports that interpretation?
Q: For downstream HIF outputs such as VEGF production, glycolytic gene expression, and erythropoietin-related phenotypes, which annotations should remain on ARNT as pathway-level non-core annotations rather than direct core gene-product functions?
Experiment: Test epitope-tagged ARNT for stable association with DDB1, CUL4A/CUL4B, RBX1, DDA1, and candidate CRL4 substrates under conditions that preserve known AHR/HIF complexes. Compare with positive-control DCAF substrate receptors and require substrate ubiquitination or degradation evidence before assigning GO:1990756.
Hypothesis: ARNT does not directly act as a CRL4 substrate adaptor.
Type: co-immunoprecipitation and ubiquitination assay
Experiment: Re-curate ARNT interaction papers by partner class (AHR, HIF1A, EPAS1, NPAS/SIM factors, co-regulators) and validate whether each supports GO:0046982, GO:0061629, or GO:0017162 instead of generic GO:0005515.
Hypothesis: ARNT protein-binding annotations can be converted to informative transcription-factor dimerization annotations.
Type: literature curation audit
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