HNF1A (hepatocyte nuclear factor 1-alpha) is a homeodomain transcription activator, with an atypical POU-specific domain and an N-terminal dimerization domain, expressed in liver, kidney, intestine and pancreatic islets. It binds the inverted palindrome GTTAATNATTAAC as a homodimer or heterodimer with HNF1B and, together with the coactivator DCoH/PCBD1 (forming a heterotetramer), CBP/p300 and partner factors such as HNF4A, activates RNA polymerase II transcription of tissue-specific target genes, including hepatic plasma-protein and drug-metabolism genes, the renal glucose cotransporter SGLT2, and genes of beta-cell glucose metabolism and insulin secretion. Heterozygous loss-of-function variants cause maturity-onset diabetes of the young type 3 (MODY3), a primary insulin-secretion defect with low renal glucose threshold, and have been reported in some neonates with hyperinsulinaemic hypoglycaemia; somatic biallelic inactivation causes familial and sporadic hepatocellular adenomas.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of transcription by RNA polymerase II (electronic). Reason: HNF1A is principally an activator; repression of some targets is plausible but secondary. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0000785 chromatin | IEA GO_REF:0000107 | ACCEPT | Summary: Chromatin. Reason: Appropriate location for a DNA-bound transcription factor. Supporting Evidence: PMID:15961790 HNF1alpha and HNF1beta, which bind to this site, play an important part in the |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: Chromatin. Reason: Appropriate location for a DNA-bound transcription factor. Supporting Evidence: PMID:15961790 HNF1alpha and HNF1beta, which bind to this site, play an important part in the |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:12453420 Diabetes mutations delineate an atypical POU domain in HNF-1... | ACCEPT | Summary: Transcription cis-regulatory region binding (IDA). Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: PMID:12453420 cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved PMID:15961790 HNF1alpha and HNF1beta, which bind to this site, play an important part in the |
| GO:0000976 transcription cis-regulatory region binding | IDA PMID:15961790 Control of ACAT2 liver expression by HNF1. | ACCEPT | Summary: Transcription cis-regulatory region binding (IDA). Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: PMID:12453420 cocrystallized human HNF-1alpha 83-279 with a high-affinity promoter and solved PMID:15961790 HNF1alpha and HNF1beta, which bind to this site, play an important part in the |
| 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. Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| 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. Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| 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. Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| GO:0001221 transcription coregulator binding | IEA GO_REF:0000107 | ACCEPT | Summary: Transcription coregulator binding (electronic). Reason: HNF1A binds the coactivator DCoH/PCBD1 through its dimerization domain, and CBP/p300. Supporting Evidence: PMID:10966642 which binds the coactivator, dimerization cofactor of HNF-1 (DCoH) |
| GO:0001223 transcription coactivator binding | IEA GO_REF:0000107 | ACCEPT | Summary: Transcription coactivator binding (electronic). Reason: HNF1A dimerization domain binds the coactivator DCoH (PCBD1), forming a heterotetramer that enhances activity. Supporting Evidence: PMID:10966642 which binds the coactivator, dimerization cofactor of HNF-1 (DCoH) file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific. Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: DNA-binding transcription activator activity, RNA polymerase II-specific. Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| GO:0001750 photoreceptor outer segment | IEA GO_REF:0000107 | REMOVE | Summary: Photoreceptor outer segment (electronic transfer from rodent). Reason: HNF1A is a nuclear transcription factor not expressed as a photoreceptor outer-segment protein; this electronic transfer is biologically implausible and unsupported for the human protein. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, |
| GO:0001889 liver development | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Liver development (InterPro). Reason: HNF1A regulates hepatocyte gene expression and Hnf1a-null mice have liver dysfunction; a developmental/tissue role downstream of its TF activity. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt expression of multiple genes, especially in pancreatic islet cells and |
| GO:0003677 DNA binding | IDA PMID:1989880 Identification and cloning of TCF-1, a T lymphocyte-specific... | UNDECIDED | Summary: DNA binding (IDA, TCF-1 cloning paper). Reason: The cited paper (Oosterwegel et al. 1991) clones TCF-1, a T-lymphocyte-specific HMG-box transcription factor (TCF7), not HNF1A, which is a homeodomain protein; the annotation probably arises from the shared historical alias TCF1. The activity itself is correct for HNF1A and is supported by other annotations (e.g. PMID:12453420), but this evidence line cannot be verified as an HNF1A assay. Supporting Evidence: PMID:1989880 TCF-1 contained a single |
| GO:0003677 DNA binding | IEA GO_REF:0000120 | ACCEPT | Summary: DNA binding (electronic). Reason: Correct general term for a sequence-specific DNA-binding TF. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| GO:0003682 chromatin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Chromatin binding. Reason: Acceptable general term for a DNA-binding TF. Supporting Evidence: PMID:15961790 HNF1alpha and HNF1beta, which bind to this site, play an important part in the |
| GO:0003690 double-stranded DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Double-stranded DNA binding. Reason: HNF1A binds double-stranded promoter DNA as a dimer. Supporting Evidence: PMID:12453420 Two identical protein molecules are bound to the |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:11980910 Mirk protein kinase is activated by MKK3 and functions as a ... | ACCEPT | Summary: DNA-binding transcription factor activity (IDA). Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: PMID:11980910 DCoH stabilizes file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:1989880 Identification and cloning of TCF-1, a T lymphocyte-specific... | UNDECIDED | Summary: DNA-binding transcription factor activity (IDA, TCF-1 cloning paper). Reason: The cited paper (Oosterwegel et al. 1991) clones TCF-1, a T-lymphocyte-specific HMG-box transcription factor (TCF7), not HNF1A, which is a homeodomain protein; the annotation probably arises from the shared historical alias TCF1. The activity itself is correct for HNF1A and is supported by other annotations (e.g. PMID:12453420), but this evidence line cannot be verified as an HNF1A assay. Supporting Evidence: PMID:1989880 TCF-1 contained a single |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000120 | ACCEPT | Summary: DNA-binding transcription factor activity (electronic). Reason: HNF1A is a homeodomain (POU-homeodomain-like) transcription activator that binds the inverted palindrome GTTAATNATTAAC as a dimer and activates tissue-specific RNA polymerase II transcription in liver, kidney, intestine and islets; core activity. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| GO:0005515 protein binding | IPI PMID:11980910 Mirk protein kinase is activated by MKK3 and functions as a ... | REMOVE | Summary: Protein binding (IPI; e.g. Mirk/DYRK1B, SPOP, coactivators, interactome screens). Reason: Uninformative. Functionally relevant partners (DCoH/PCBD1 coactivator) are covered by coactivator-binding and complex terms; removal does not imply the interactions are false. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005515 protein binding | IPI PMID:14500717 Serine/threonine kinase Mirk/Dyrk1B is an inhibitor of epith... | REMOVE | Summary: Protein binding (IPI; e.g. Mirk/DYRK1B, SPOP, coactivators, interactome screens). Reason: Uninformative. Functionally relevant partners (DCoH/PCBD1 coactivator) are covered by coactivator-binding and complex terms; removal does not imply the interactions are false. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005515 protein binding | IPI PMID:19264593 Prospero-related homeobox protein (Prox1) inhibits hepatitis... | REMOVE | Summary: Protein binding (IPI; e.g. Mirk/DYRK1B, SPOP, coactivators, interactome screens). Reason: Uninformative. Functionally relevant partners (DCoH/PCBD1 coactivator) are covered by coactivator-binding and complex terms; removal does not imply the interactions are false. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005515 protein binding | IPI PMID:21988832 Toward an understanding of the protein interaction network o... | REMOVE | Summary: Protein binding (IPI; e.g. Mirk/DYRK1B, SPOP, coactivators, interactome screens). Reason: Uninformative. Functionally relevant partners (DCoH/PCBD1 coactivator) are covered by coactivator-binding and complex terms; removal does not imply the interactions are false. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: Protein binding (IPI; e.g. Mirk/DYRK1B, SPOP, coactivators, interactome screens). Reason: Uninformative. Functionally relevant partners (DCoH/PCBD1 coactivator) are covered by coactivator-binding and complex terms; removal does not imply the interactions are false. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005515 protein binding | IPI PMID:35140242 Human transcription factor protein interaction networks. | REMOVE | Summary: Protein binding (IPI; e.g. Mirk/DYRK1B, SPOP, coactivators, interactome screens). Reason: Uninformative. Functionally relevant partners (DCoH/PCBD1 coactivator) are covered by coactivator-binding and complex terms; removal does not imply the interactions are false. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005515 protein binding | IPI PMID:35140242 Human transcription factor protein interaction networks. | REMOVE | Summary: Protein binding (IPI; e.g. Mirk/DYRK1B, SPOP, coactivators, interactome screens). Reason: Uninformative. Functionally relevant partners (DCoH/PCBD1 coactivator) are covered by coactivator-binding and complex terms; removal does not imply the interactions are false. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005515 protein binding | IPI PMID:35512704 Systematic discovery of mutation-directed neo-protein-protei... | REMOVE | Summary: Protein binding (IPI; e.g. Mirk/DYRK1B, SPOP, coactivators, interactome screens). Reason: Uninformative. Functionally relevant partners (DCoH/PCBD1 coactivator) are covered by coactivator-binding and complex terms; removal does not imply the interactions are false. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005634 nucleus | EXP PMID:10966642 Structural basis of dimerization, coactivator recognition an... | ACCEPT | Summary: Nucleus. Reason: HNF1A acts in the nucleus. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, |
| GO:0005634 nucleus | EXP PMID:38018242 SPOP inhibits HBV transcription and replication by ubiquitin... | ACCEPT | Summary: Nucleus. Reason: HNF1A acts in the nucleus. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleus. Reason: HNF1A acts in the nucleus. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, |
| GO:0005634 nucleus | IDA PMID:15355349 The HNF1beta transcription factor has several domains involv... | ACCEPT | Summary: Nucleus. Reason: HNF1A acts in the nucleus. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nucleus. Reason: HNF1A acts in the nucleus. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, |
| GO:0005667 transcription regulator complex | IEA GO_REF:0000107 | ACCEPT | Summary: Transcription regulator complex. Reason: HNF1A forms a heterotetramer with the coactivator DCoH/PCBD1. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt PCBD1; formed by a dimer of dimers (By similarity) |
| GO:0005737 cytoplasm | IDA PMID:15355349 The HNF1beta transcription factor has several domains involv... | KEEP AS NON CORE | Summary: Cytoplasm (IDA, transfected HeLa/Xenopus domain-swap study). Reason: Nuclear-import mapping in HNF1 domain-swap constructs; a cytoplasmic pool is not where HNF1A functions. Supporting Evidence: PMID:15355349 we located a nuclear localization signal in |
| GO:0005737 cytoplasm | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cytoplasm (electronic). Reason: Non-functional location for a nuclear TF. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of transcription by RNA polymerase II. Reason: Core process. Supporting Evidence: PMID:10330009 HNF-1alpha and HNF-4 had a synergistic effect on alpha1-AT gene expression |
| GO:0006357 regulation of transcription by RNA polymerase II | IDA PMID:10330009 Regulation of alpha1-antitrypsin gene expression in human in... | ACCEPT | Summary: Regulation of transcription by RNA polymerase II. Reason: Core process. Supporting Evidence: PMID:10330009 HNF-1alpha and HNF-4 had a synergistic effect on alpha1-AT gene expression |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000002 | ACCEPT | Summary: Regulation of transcription by RNA polymerase II. Reason: Core process. Supporting Evidence: PMID:10330009 HNF-1alpha and HNF-4 had a synergistic effect on alpha1-AT gene expression |
| GO:0006366 transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Transcription by RNA polymerase II (electronic). Reason: HNF1A regulates rather than executes transcription; the regulation terms are more accurate. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0010628 positive regulation of gene expression | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of gene expression. Reason: Correct, general. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0010918 positive regulation of mitochondrial membrane potential | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of mitochondrial membrane potential (electronic from rodent beta-cell data). Reason: Loss of HNF1A function impairs beta-cell glucose metabolism and mitochondrial energetics via target genes; indirect. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt years of age), a primary defect in insulin secretion and frequent |
| GO:0030073 insulin secretion | IEA GO_REF:0000002 | MARK AS OVER ANNOTATED | Summary: Insulin secretion (InterPro2GO). Reason: HNF1A does not take part in the secretion machinery; it regulates the beta-cell gene program, and loss causes a secretory defect (MODY3). The InterPro mapping over-reaches. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt years of age), a primary defect in insulin secretion and frequent |
| GO:0030262 apoptotic nuclear changes | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Apoptotic nuclear changes (electronic). Reason: Rodent dominant-negative HNF1A beta-cell data; apoptosis follows loss of the target program and HNF1A does not execute nuclear apoptotic changes. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0031016 pancreas development | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Pancreas development (InterPro2GO). Reason: HNF1A is expressed in developing and mature islets; a developmental, non-core role. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt expression of multiple genes, especially in pancreatic islet cells and |
| GO:0032024 positive regulation of insulin secretion | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of insulin secretion (electronic from rodent). Reason: HNF1A sustains insulin secretion indirectly through transcription of beta-cell metabolic genes; MODY3 is a primary insulin-secretion defect. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt years of age), a primary defect in insulin secretion and frequent file:human/HNF1A/HNF1A-uniprot.txt expression of multiple genes, especially in pancreatic islet cells and |
| GO:0032991 protein-containing complex | IDA PMID:11980910 Mirk protein kinase is activated by MKK3 and functions as a ... | ACCEPT | Summary: Protein-containing complex. Reason: HNF1A forms complexes with DCoH-family coactivators and Mirk kinase. Supporting Evidence: PMID:11980910 Mirk, DCoHm, and HNF1alpha formed a complex |
| GO:0032991 protein-containing complex | IEA GO_REF:0000107 | ACCEPT | Summary: Protein-containing complex. Reason: HNF1A forms complexes with DCoH-family coactivators and Mirk kinase. Supporting Evidence: PMID:11980910 Mirk, DCoHm, and HNF1alpha formed a complex |
| GO:0035565 regulation of pronephros size | IMP NOT PMID:15355349 The HNF1beta transcription factor has several domains involv... | ACCEPT | Summary: NOT regulation of pronephros size (IMP, Xenopus). Reason: In Xenopus embryos HNF1alpha overexpression, unlike HNF1beta, had no effect on pronephros development; the negative annotation is consistent with the abstract. Supporting Evidence: PMID:15355349 defective pronephros development, while HNF1alpha has no effect |
| GO:0035623 renal D-glucose absorption | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Renal D-glucose absorption. Reason: HNF1A controls renal glucose reabsorption by regulating expression of the SGLT2 cotransporter; it acts upstream as a TF. Supporting Evidence: PMID:11269503 HNF1alpha plays a key role in PMID:11269503 MODY3 patients are also characterized by a |
| GO:0035623 renal D-glucose absorption | IMP PMID:11269503 HNF1alpha controls renal glucose reabsorption in mouse and m... | KEEP AS NON CORE | Summary: Renal D-glucose absorption. Reason: HNF1A controls renal glucose reabsorption by regulating expression of the SGLT2 cotransporter; it acts upstream as a TF. Supporting Evidence: PMID:11269503 HNF1alpha plays a key role in PMID:11269503 MODY3 patients are also characterized by a |
| GO:0042593 glucose homeostasis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Glucose homeostasis (electronic). Reason: HNF1A loss causes MODY3; indirect organism-level role. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt years of age), a primary defect in insulin secretion and frequent |
| GO:0042593 glucose homeostasis | IMP PMID:11269503 HNF1alpha controls renal glucose reabsorption in mouse and m... | KEEP AS NON CORE | Summary: Glucose homeostasis (IMP). Reason: Supported by human MODY3 renal and beta-cell phenotypes; indirect consequence of HNF1A transcriptional activity. Supporting Evidence: PMID:11269503 HNF1alpha plays a key role in |
| GO:0042593 glucose homeostasis | IMP PMID:15277395 Polymorphic variations in the neurogenic differentiation-1, ... | KEEP AS NON CORE | Summary: Glucose homeostasis (IMP). Reason: Supported by human MODY3 renal and beta-cell phenotypes; indirect consequence of HNF1A transcriptional activity. Supporting Evidence: PMID:11269503 HNF1alpha plays a key role in |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Identical protein binding (electronic). Reason: HNF1A homodimerises via its N-terminal dimerization domain; structural prerequisite of DNA binding. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Binds DNA as a dimer (PubMed:12453420) |
| GO:0043066 negative regulation of apoptotic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Negative regulation of apoptotic process (electronic). Reason: Rodent beta-cell studies; indirect. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt expression of multiple genes, especially in pancreatic islet cells and |
| GO:0043565 sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Sequence-specific DNA binding. Reason: Correct; binds GTTAATNATTAAC. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Binds to the inverted palindrome 5 |
| GO:0045120 pronucleus | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Pronucleus (electronic from mouse). Reason: Detection in zygote pronuclei is a developmental expression observation of uncertain significance; HNF1A function is in differentiated liver, kidney, gut and islet nuclei. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:11980910 Mirk protein kinase is activated by MKK3 and functions as a ... | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: Core process. Supporting Evidence: PMID:15961790 HNF1alpha and HNF1beta, which bind to this site, play an important part in the PMID:11980910 DCoH stabilizes |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:12453420 Diabetes mutations delineate an atypical POU domain in HNF-1... | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: Core process. Supporting Evidence: PMID:15961790 HNF1alpha and HNF1beta, which bind to this site, play an important part in the PMID:11980910 DCoH stabilizes |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:1989880 Identification and cloning of TCF-1, a T lymphocyte-specific... | UNDECIDED | Summary: Positive regulation of DNA-templated transcription (IDA, TCF-1 cloning paper). Reason: The cited paper (Oosterwegel et al. 1991) clones TCF-1, a T-lymphocyte-specific HMG-box transcription factor (TCF7), not HNF1A, which is a homeodomain protein; the annotation probably arises from the shared historical alias TCF1. The activity itself is correct for HNF1A and is supported by other annotations (e.g. PMID:12453420), but this evidence line cannot be verified as an HNF1A assay. Supporting Evidence: PMID:1989880 TCF-1 contained a single |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: Positive regulation of DNA-templated transcription. Reason: Core process. Supporting Evidence: PMID:15961790 HNF1alpha and HNF1beta, which bind to this site, play an important part in the PMID:11980910 DCoH stabilizes |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Core process. Supporting Evidence: PMID:10330009 HNF-1alpha and HNF-4 had a synergistic effect on alpha1-AT gene expression file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | ACCEPT | Summary: Positive regulation of transcription by RNA polymerase II. Reason: Core process. Supporting Evidence: PMID:10330009 HNF-1alpha and HNF-4 had a synergistic effect on alpha1-AT gene expression file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0046983 protein dimerization activity | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Protein dimerization activity. Reason: HNF1A binds DNA as a dimer; structural property. Supporting Evidence: PMID:12453420 Two identical protein molecules are bound to the file:human/HNF1A/HNF1A-uniprot.txt Binds DNA as a dimer (PubMed:12453420) |
| GO:0046983 protein dimerization activity | IPI PMID:12453420 Diabetes mutations delineate an atypical POU domain in HNF-1... | KEEP AS NON CORE | Summary: Protein dimerization activity. Reason: HNF1A binds DNA as a dimer; structural property. Supporting Evidence: PMID:12453420 Two identical protein molecules are bound to the file:human/HNF1A/HNF1A-uniprot.txt Binds DNA as a dimer (PubMed:12453420) |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Positive regulation of PI3K/AKT signal transduction (electronic). Reason: Indirect downstream readout; not a function of HNF1A. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0060261 positive regulation of transcription initiation by RNA polymerase II | IEA GO_REF:0000117 | ACCEPT | Summary: Positive regulation of transcription initiation by RNA polymerase II. Reason: Consistent with HNF1A transactivation; accepted. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0060261 positive regulation of transcription initiation by RNA polymerase II | IGI PMID:15355349 The HNF1beta transcription factor has several domains involv... | ACCEPT | Summary: Positive regulation of transcription initiation by RNA polymerase II. Reason: Consistent with HNF1A transactivation; accepted. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0071233 cellular response to L-leucine | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cellular response to L-leucine (electronic from rodent). Reason: Expression/readout-based; no evidence HNF1A carries out a step of the leucine response. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0071333 cellular response to glucose stimulus | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cellular response to glucose stimulus (electronic). Reason: Rodent beta-cell data; indirect consequence of the HNF1A-driven metabolic gene program. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt expression of multiple genes, especially in pancreatic islet cells and |
| GO:0072752 cellular response to rapamycin | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Cellular response to rapamycin (electronic from rodent). Reason: Expression-change based; not a function of HNF1A. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:0098708 D-glucose import across plasma membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: D-glucose import across plasma membrane. Reason: Indirect, via transcription of glucose transporter genes (SGLT2) in kidney. Supporting Evidence: PMID:11269503 HNF1alpha plays a key role in |
| GO:0098708 D-glucose import across plasma membrane | IMP PMID:11269503 HNF1alpha controls renal glucose reabsorption in mouse and m... | KEEP AS NON CORE | Summary: D-glucose import across plasma membrane. Reason: Indirect, via transcription of glucose transporter genes (SGLT2) in kidney. Supporting Evidence: PMID:11269503 HNF1alpha plays a key role in |
| GO:1902031 regulation of NADP metabolic process | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Regulation of NADP metabolic process (electronic from rodent). Reason: Downstream metabolic readout of target-gene regulation; annotating each downstream metabolic change over-annotates a transcription factor. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:1903799 negative regulation of miRNA processing | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Negative regulation of miRNA processing (electronic). Reason: Indirect, single-study rodent inference; not supported as an HNF1A function in human. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt Transcriptional activator that regulates the tissue specific |
| GO:2001171 positive regulation of ATP biosynthetic process | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Positive regulation of ATP biosynthetic process (electronic from rodent). Reason: Indirect, via HNF1A target genes of beta-cell glucose metabolism. Supporting Evidence: file:human/HNF1A/HNF1A-uniprot.txt years of age), a primary defect in insulin secretion and frequent |
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Download this section (compressed HTML)Q: Is neonatal hyperinsulinism a genuine feature of HNF1A haploinsufficiency, given that the cohort that established the HNF4A association found no excess neonatal hypoglycaemia in HNF1A carriers?
Experiment: Compare fetal-stage glucose-stimulated insulin secretion and HNF1A target expression in human stem-cell-derived beta cells heterozygous for HNF1A versus HNF4A loss-of-function, to test whether HNF1A haploinsufficiency can cause transient hypersecretion.
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