Transcription factor AP-2 beta (TFAP2B) is a sequence-specific DNA-binding transcription factor of the AP-2 family. It binds GCC(N3)GGC-type elements as a homodimer or as a heterodimer with AP-2alpha (TFAP2A), formed through a conserved C-terminal helix-span-helix domain beside a basic DNA-binding region, and mainly activates RNA polymerase II target genes with the coactivator CITED2 and p300/CBP; it also represses selected targets. SUMOylation and the inhibitor KCTD1 dampen its activity. In vertebrate embryos AP-2beta is a neural crest specifier: it is switched on in neural crest progenitors at the onset of specification, downstream of the neural plate border factors Pax3, Zic1 and AP-2alpha/AP-2gamma, and as a TFAP2A/TFAP2B heterodimer it opens and activates crest specification enhancers while repressing TFAP2C. In chick cranial crest it activates Ets1 and, with Sox8 and Ets1, confers cranial chondrogenic potential. It later supports the survival of sympathetic neuron progenitors and noradrenergic neurons, enteric neuron numbers, and the development of the ductus arteriosus smooth muscle, the face and the limbs; in the kidney it is required for survival of distal tubule and collecting duct epithelia. Heterozygous dominant-negative or haploinsufficient TFAP2B variants cause Char syndrome (patent ductus arteriosus, facial dysmorphism, fifth-finger anomalies) and isolated patent ductus arteriosus. Much of its developmental function overlaps with AP-2alpha, and the degree of redundancy differs between species.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000122 negative regulation of transcription by RNA polymerase II | IDA PMID:7559606 Transcription factor AP-2 regulates human insulin-like growt... | REMOVE | Summary: Duan & Clemmons 1995 used a human AP-2 (AP-2alpha) expression construct and 'AP-2B', a dominant-negative AP-2 form, on the IGFBP5 promoter. AP-2B is an alternatively spliced product of the AP-2alpha gene (TFAP2A), not AP-2beta. Reason: Name confusion visible in the cached text. The repression attributed here is the effect of AP-2B, a dominant-negative AP-2alpha splice isoform that lacks the dimerization domain, on AP-2 activity. It is not repression by TFAP2B. Buettner et al. 1993 show AP-2B is spliced from the single AP-2 (TFAP2A) gene. AP-2beta (TFAP2B) was first cloned in the preceding month (PMID:7555706). TFAP2B-mediated repression is supported elsewhere (chick TFAP2C, mouse Bmp4), so removing this row loses nothing true. Supporting Evidence: PMID:7559606 In AP-2 abundant fibroblasts, expression of AP-2B, a dominant-negative inhibitor of AP-2, suppressed IGFBP-5 promoter activity. PMID:8321221 Analysis of overlapping genomic clones spanning the entire AP-2 gene proves that AP-2A and AP-2B transcripts are alternatively spliced from the same gene. |
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass-based location of a DNA-binding transcription factor on chromatin. Reason: AP-2beta binds cis-regulatory DNA and occupies enhancers in vivo (chick CUT&RUN); chromatin is its site of action. Supporting Evidence: PMID:31848212 Together, these data support the idea that TFAP2B is required for the recruitment of TFAP2A to specification loci. file:human/TFAP2B/TFAP2B-deep-research-falcon.md Chromatin immunoprecipitation at human target promoters independently supports a nuclear transcriptional role. |
| GO:0000977 RNA polymerase II transcription regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: Pol II regulatory region sequence-specific DNA binding, inherited across the AP-2 family node. Reason: Sequence-specific binding to GCC(N3)GGC elements is the defining activity of the AP-2 family, and AP-2beta shows it directly. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IDA PMID:7555706 Cloning and characterization of a second AP-2 transcription ... | ACCEPT | Summary: AP-2beta binds AP-2 consensus sites (EMSA) and drives an AP-2-dependent reporter. Reason: Direct evidence for sequence-specific binding of Pol II cis-regulatory elements, the core DNA-binding activity. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse Tfap2b of cis-regulatory sequence-specific DNA binding. Reason: Consistent with direct human data (PMID:7555706) and mouse Bmp2/Bmp4 promoter binding. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IDA PMID:7555706 Cloning and characterization of a second AP-2 transcription ... | ACCEPT | Summary: AP-2beta is a sequence-specific Pol II transcription factor (binding plus reporter transactivation). Reason: Correct core MF; the more specific activator term GO:0001228 is also annotated. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of Pol II DNA-binding TF activity from mouse Tfap2b. Reason: Correct core MF, supported by direct human evidence. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass (AP-2 family, class 1.3.1) assignment as a Pol II DNA-binding TF. Reason: Correct family-level MF, consistent with experimental data. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0000987 cis-regulatory region sequence-specific DNA binding | IDA PMID:16373396 Intronic polymorphisms within TFAP2B regulate transcriptiona... | ACCEPT | Summary: Tsukada 2006: an intronic TFAP2B enhancer and TFAP2B-driven adipocytokine expression; the curator recorded cis-regulatory DNA binding. Reason: The cached abstract does not describe the binding assay, so the specific evidence cannot be checked here (abstract only). The activity is well established for AP-2beta (PMID:7555706), so the annotation is accepted in deference to the curator. Supporting Evidence: PMID:16373396 In an experiment using adenovirus vectors encoding TFAP2B, the expression of TNF-alpha gene was shown to be elevated in the TFAP2B overexpressing cells compared with those in control cells. PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: Pol II-specific transcription activator activity across the AP-2 family node (human TFAP2A/B/C and mouse orthologs as evidence). Reason: Activator activity is the core, conserved molecular function of AP-2beta. The target appearing among the IBA sources reflects its own experimental grounding. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. PMID:11694877 We show that CITED2 interacts with and co-activates all isoforms of transcription factor AP-2 (TFAP2). |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IDA PMID:7559606 Transcription factor AP-2 regulates human insulin-like growt... | ACCEPT | Summary: Activator activity attributed to TFAP2B from a study of AP-2 regulation of the IGFBP5 promoter (PMID:7559606), which appears to concern AP-2 alpha; the activity itself is established for AP-2 beta. Reason: Activator activity is the core function of AP-2 beta and is accepted on the phylogenetic, electronic and similarity rows of this review, so the claim stands on this row as well. The defect lies in the row's reference: the cited study describes activation by an AP-2 expression construct, that is AP-2 alpha, and the AP-2B it mentions is a dominant-negative splice isoform of AP-2 alpha, so the paper does not appear to assay AP-2 beta; only the abstract is available. That is recorded as a source defect rather than expressed by removing a true annotation; transactivation by AP-2 beta itself was shown when the factor was cloned. Supporting Evidence: PMID:7559606 The possible role of AP-2 was examined by cotransfection of AP-2-deficient HepG2 cells with the IGFBP-5 promoter construct and a human AP-2 expression construct. PMID:7559606 In AP-2 abundant fibroblasts, expression of AP-2B, a dominant-negative inhibitor of AP-2, suppressed IGFBP-5 promoter activity. PMID:8321221 Analysis of overlapping genomic clones spanning the entire AP-2 gene proves that AP-2A and AP-2B transcripts are alternatively spliced from the same gene. PMID:7555706 transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer of Pol II activator activity from mouse Tfap2b (IDA PMID:7555706, PMID:21829553). Reason: Core MF. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Tfap2b: Pol II activator activity. Reason: Core MF, conserved. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. PMID:21829553 due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b |
| GO:0001822 kidney development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Tfap2b knockout: polycystic kidneys and apoptosis of distal tubule and collecting duct epithelia. Reason: Mouse Tfap2b is required non-redundantly for terminal survival and function of distal nephron epithelia, and AP-2beta is the main AP-2 in adult kidney. Kidney development is accepted; the specific tubule terms carry the precise role. Note Char syndrome patients do not show the renal phenotype. Supporting Evidence: PMID:9271117 AP-2beta -/- mice complete embryonic development and die at postnatal days 1 and 2 because of polycystic kidney disease. PMID:12695560 our studies reveal essential, nonredundant roles of AP-2 beta in renal tubular functions |
| GO:0003677 DNA binding | TAS PMID:12072434 Transcription factor AP-2 interacts with the SUMO-conjugatin... | ACCEPT | Summary: TAS: AP-2 factors bind DNA. Reason: True but general; more specific DNA-binding terms are also annotated. Supporting Evidence: PMID:12072434 All AP-2 factors appear to be capable of binding very similar DNA recognition sites |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:11505339 Novel TFAP2B mutations that cause Char syndrome provide a ge... | ACCEPT | Summary: Char syndrome basic-domain mutants fail to bind DNA and act as dominant negatives, implying wild-type TFAP2B DNA-binding TF activity. Reason: Correct general MF; GO:0001228 is the more precise term. Supporting Evidence: PMID:11505339 Functional analyses of the four mutants disclosed that two, R225C and R225S, failed to bind target sequence in vitro and that all four had dominant negative effects when expressed in eukaryotic cells. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:12169688 The role of Sp1 and AP-2 in basal and protein kinase A--indu... | ACCEPT | Summary: Uchida 2002: AP-2 binds and activates the rat SPT promoter (footprinting, gel shift, reporter). Reason: The abstract does not say which AP-2 paralog was expressed (abstract only), so assignment to AP-2beta cannot be checked here. The function is correct for AP-2beta, so the annotation is accepted in deference to the curator. Supporting Evidence: PMID:12169688 By using a luciferase reporter assay with HepG2 cells, DNase I footprinting analysis, and gel shift experiments, we identified the binding sites for Sp1 and AP-2 within the regions -125 to -89 and -14 to +10, respectively. PMID:12169688 Expression of AP-2 caused a marked increase in the basal promoter activity to about the same level as that achieved by PKA. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:16373396 Intronic polymorphisms within TFAP2B regulate transcriptiona... | ACCEPT | Summary: Tsukada 2006: TFAP2B overexpression raises TNF-alpha expression in adipocytes. Reason: Consistent with AP-2beta DNA-binding TF activity; general term. Supporting Evidence: PMID:16373396 In an experiment using adenovirus vectors encoding TFAP2B, the expression of TNF-alpha gene was shown to be elevated in the TFAP2B overexpressing cells compared with those in control cells. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro (TF_AP-2 domain) mapping to DNA-binding TF activity. Reason: Correct domain-based inference. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0003700 DNA-binding transcription factor activity | NAS PMID:8661133 Chromosomal mapping of the human and mouse homologues of two... | ACCEPT | Summary: Chromosomal mapping paper describing AP-2beta as an AP-2 family transcription factor. Reason: Correct family-level statement; superseded by experimental rows. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0005515 protein binding | IPI PMID:11694877 Cardiac malformations, adrenal agenesis, neural crest defect... | MODIFY | Summary: CITED2 binds and co-activates all TFAP2 isoforms. Reason: Generic protein binding is uninformative. CITED2 is a transcriptional coactivator recruited through the conserved HSH dimerization domain, so the informative MF is transcription coactivator binding, as in the TFAP2A review. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:11694877 We show that CITED2 interacts with and co-activates all isoforms of transcription factor AP-2 (TFAP2). |
| GO:0005515 protein binding | IPI PMID:12072434 Transcription factor AP-2 interacts with the SUMO-conjugatin... | REMOVE | Summary: Two-hybrid interaction of AP-2 factors with the SUMO E2 UBC9 (UBE2I); AP-2 is SUMOylated, which lowers activity. Reason: The interaction makes AP-2 a SUMOylation substrate; it is not a function AP-2beta performs. Generic protein binding is uninformative and no better MF applies (same decision as for TFAP2A and Xenopus sox10). Supporting Evidence: PMID:12072434 In a two-hybrid screen for proteins interacting with AP-2 factors, we have identified the UBC9 gene that encodes the E2 (ubiquitin carrier protein)-conjugating enzyme for the small ubiquitin-like modifier, SUMO. |
| GO:0005515 protein binding | IPI PMID:12586840 Physical and functional interactions among AP-2 transcriptio... | MODIFY | Summary: CITED2 binds the TFAP2 dimerization domain conserved in TFAP2A/B/C and links them to p300/CBP. Reason: Replace uninformative protein binding with transcription coactivator binding (CITED2 is a TFAP2 coactivator). Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:12586840 CITED2 interacted with the dimerization domain of TFAP2C, which is highly conserved in TFAP2A/B. PMID:11694877 We show that CITED2 interacts with and co-activates all isoforms of transcription factor AP-2 (TFAP2). |
| GO:0005515 protein binding | IPI PMID:19115315 The interaction of KCTD1 with transcription factor AP-2alpha... | MODIFY | Summary: KCTD1 binds the three major AP-2 proteins and inhibits their transactivation. Reason: KCTD1 acts as a transcriptional repressor of AP-2 factors; transcription corepressor binding is the informative term, as in the TFAP2A review. Proposed replacements: transcription corepressor binding Supporting Evidence: PMID:19115315 Finally, we found that KCTD1 interacted with three major members of the AP-2 family and inhibited their transcriptional activities. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput yeast two-hybrid interaction with YWHAG from a neurodegenerative-disease interactome screen. Reason: Generic protein binding from a large-scale Y2H screen carries no functional information, and the paper does not test a functional consequence for TFAP2B. Removal does not mean the interaction is false. Supporting Evidence: PMID:32814053 Interactome maps are valuable resources to elucidate protein function and disease mechanisms. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput yeast two-hybrid interaction with SETDB1 from a neurodegenerative-disease interactome screen. Reason: Generic protein binding from a large-scale Y2H screen carries no functional information, and the paper does not test a functional consequence for TFAP2B. Removal does not mean the interaction is false. Supporting Evidence: PMID:32814053 Interactome maps are valuable resources to elucidate protein function and disease mechanisms. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput yeast two-hybrid interaction with LMO3 from a neurodegenerative-disease interactome screen. Reason: Generic protein binding from a large-scale Y2H screen carries no functional information, and the paper does not test a functional consequence for TFAP2B. Removal does not mean the interaction is false. Supporting Evidence: PMID:32814053 Interactome maps are valuable resources to elucidate protein function and disease mechanisms. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: High-throughput yeast two-hybrid interaction with KAT5 from a neurodegenerative-disease interactome screen. Reason: Generic protein binding from a large-scale Y2H screen carries no functional information, and the paper does not test a functional consequence for TFAP2B. Removal does not mean the interaction is false. Supporting Evidence: PMID:32814053 Interactome maps are valuable resources to elucidate protein function and disease mechanisms. |
| GO:0005515 protein binding | IPI PMID:7555706 Cloning and characterization of a second AP-2 transcription ... | MODIFY | Summary: The conserved AP-2beta C-terminal HSH domain is sufficient for AP-2alpha/AP-2beta interaction. Reason: The interaction is dimerization through the HSH domain. Replace protein binding with protein heterodimerization activity (AP-2alpha/beta) and homodimerization activity. In vivo TFAP2A/B heterodimers are the crest-specification complex in chick. Proposed replacements: protein heterodimerization activity protein homodimerization activity Supporting Evidence: PMID:7555706 A C-terminal domain known to mediate homodimerization of the previously cloned AP-2 alpha transcription activator is highly conserved and sufficient to mediate interaction between the two proteins. PMID:31848212 Pulldown of TFAP2A with streptavidin beads resulted in co-IP of both FLAG-tagged TFAP2B and TFAP2C, confirming that these factors form heterodimers in avian embryos |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: nucleus. Reason: Nuclear transcription factor. Supporting Evidence: Reactome:R-HSA-8864278 AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. |
| GO:0005634 nucleus | IC PMID:12169688 The role of Sp1 and AP-2 in basal and protein kinase A--indu... | ACCEPT | Summary: Inferred by curator from DNA-binding TF activity. Reason: Nuclear location follows from TF activity. Supporting Evidence: PMID:12169688 By using a luciferase reporter assay with HepG2 cells, DNase I footprinting analysis, and gel shift experiments, we identified the binding sites for Sp1 and AP-2 within the regions -125 to -89 and -14 to +10, respectively. |
| GO:0005634 nucleus | IDA PMID:20607706 AP2 transcription factor induces apoptosis in retinoblastoma... | ACCEPT | Summary: Nuclear TFAP2B protein in human retina/retinoblastoma cells (immunostaining). Reason: Direct observation of nuclear localization. Supporting Evidence: PMID:20607706 TFAP2A and TFAP2B, which map to chromosome arm 6p, are expressed in the amacrine and horizontal cells of human retina |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated nucleus annotation. Reason: Correct. Supporting Evidence: Reactome:R-HSA-8864278 AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. |
| GO:0005634 nucleus | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Tfap2b: nucleus. Reason: Correct. Supporting Evidence: Reactome:R-HSA-8864278 AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8864278 | ACCEPT | Summary: Reactome reaction (Reactome:R-HSA-8864278) placing TFAP2B dimers and complexes in the nucleoplasm. Reason: Nucleoplasm is consistent with a nuclear transcription factor. Supporting Evidence: Reactome:R-HSA-8864278 AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8864307 | ACCEPT | Summary: Reactome reaction (Reactome:R-HSA-8864307) placing TFAP2B dimers and complexes in the nucleoplasm. Reason: Nucleoplasm is consistent with a nuclear transcription factor. Supporting Evidence: Reactome:R-HSA-8864278 AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8864343 | ACCEPT | Summary: Reactome reaction (Reactome:R-HSA-8864343) placing TFAP2B dimers and complexes in the nucleoplasm. Reason: Nucleoplasm is consistent with a nuclear transcription factor. Supporting Evidence: Reactome:R-HSA-8864278 AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8864595 | ACCEPT | Summary: Reactome reaction (Reactome:R-HSA-8864595) placing TFAP2B dimers and complexes in the nucleoplasm. Reason: Nucleoplasm is consistent with a nuclear transcription factor. Supporting Evidence: Reactome:R-HSA-8864278 AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9836275 | ACCEPT | Summary: Reactome reaction (Reactome:R-HSA-9836275) placing TFAP2B dimers and complexes in the nucleoplasm. Reason: Nucleoplasm is consistent with a nuclear transcription factor. Supporting Evidence: Reactome:R-HSA-8864278 AP-2 family members are able to form homo- and heterodimers through the interaction of their C-terminal helix-span-helix (HSH) motifs. |
| GO:0006006 glucose metabolic process | IMP PMID:15940393 Genetic variations in the gene encoding TFAP2B are associate... | MARK AS OVER ANNOTATED | Summary: Japanese/UK association of TFAP2B variants with type 2 diabetes. Reason: The rows rest on genetic association of TFAP2B variants with type 2 diabetes, insulin sensitivity and adiposity, plus TFAP2B overexpression in adipocytes. Association is not a loss-of-function phenotype, and any effect on glucose handling is indirect, through adipocyte gene regulation. AP-2beta does not carry out glucose metabolism. The papers are abstract-only here, so the rows are marked over-annotated rather than removed. Supporting Evidence: PMID:15940393 several variations within TFAP2B were significantly associated with type 2 diabetes |
| GO:0006006 glucose metabolic process | IMP PMID:16373396 Intronic polymorphisms within TFAP2B regulate transcriptiona... | MARK AS OVER ANNOTATED | Summary: Intronic TFAP2B variants change enhancer activity; TFAP2B overexpression raises TNF-alpha in adipocytes. Reason: The rows rest on genetic association of TFAP2B variants with type 2 diabetes, insulin sensitivity and adiposity, plus TFAP2B overexpression in adipocytes. Association is not a loss-of-function phenotype, and any effect on glucose handling is indirect, through adipocyte gene regulation. AP-2beta does not carry out glucose metabolism. The papers are abstract-only here, so the rows are marked over-annotated rather than removed. Supporting Evidence: PMID:16373396 In an experiment using adenovirus vectors encoding TFAP2B, the expression of TNF-alpha gene was shown to be elevated in the TFAP2B overexpressing cells compared with those in control cells. |
| GO:0006006 glucose metabolic process | IMP PMID:19325541 The transcription factor TFAP2B is associated with insulin r... | MARK AS OVER ANNOTATED | Summary: Association of TFAP2B variation with insulin sensitivity and adiposity in adolescents. Reason: The rows rest on genetic association of TFAP2B variants with type 2 diabetes, insulin sensitivity and adiposity, plus TFAP2B overexpression in adipocytes. Association is not a loss-of-function phenotype, and any effect on glucose handling is indirect, through adipocyte gene regulation. AP-2beta does not carry out glucose metabolism. The papers are abstract-only here, so the rows are marked over-annotated rather than removed. Supporting Evidence: PMID:19325541 both insulin sensitivity, as measured from levels of fasting glucose and insulin, and central adiposity, estimated by subscapular skinfold thickness, were significantly associated to genetic variability in TFAP2B |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro mapping: regulation of DNA-templated transcription. Reason: Correct, general. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0006357 regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara: regulation of transcription by RNA polymerase II. Reason: Correct, general. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0007399 nervous system development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: nervous system development. Reason: Correct at family level (AP-2beta acts in sympathetic, enteric and locus coeruleus neurons and midbrain), but broad; TFAP2B's specific neural roles are captured by sympathetic nervous system development and the crest specification term. Supporting Evidence: PMID:21539825 In the AP-2Ξ² knockout only sympathetic ganglia (SG) are targeted, leading to a reduction in ganglion size by about 40%, which is also caused by apoptotic death of neural crest progenitors. PMID:8989526 Specific AP-2 beta signals were detected in the midbrain, sympathetic ganglia, adrenal medulla, and cornea. |
| GO:0007423 sensory organ development | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara transfer of sensory organ development; the mouse source is an expression-pattern (IEP) annotation. Reason: Derived from embryonic expression in sensory neuron regions, not a functional result. No TFAP2B-specific sensory organ phenotype is established in the cited evidence. Supporting Evidence: PMID:8989526 Specific AP-2 beta signals were detected in the midbrain, sympathetic ganglia, adrenal medulla, and cornea. |
| GO:0008284 positive regulation of cell population proliferation | IDA PMID:17525748 Comparative expression profiling identifies an in vivo targe... | KEEP AS NON CORE | Summary: In alveolar rhabdomyosarcoma cells TFAP2B is a PAX3/FKHR target that mediates survival. Reason: Tumour cell-line context. The cached abstract reports the anti-apoptotic role; any proliferation effect is a cell-context consequence, not a core developmental function. Supporting Evidence: PMID:17525748 TFAP2B was validated as direct target gene mediating the anti-apoptotic function of PAX3/FKHR. |
| GO:0008284 positive regulation of cell population proliferation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of positive regulation of proliferation (mouse source from the same aRMS study). Reason: Context-dependent; opposite effects reported in retinoblastoma cells. Not core. Supporting Evidence: PMID:17525748 TFAP2B was validated as direct target gene mediating the anti-apoptotic function of PAX3/FKHR. |
| GO:0008285 negative regulation of cell population proliferation | IDA PMID:20607706 AP2 transcription factor induces apoptosis in retinoblastoma... | KEEP AS NON CORE | Summary: TFAP2B overexpression in retinoblastoma cells induces apoptosis and inhibits proliferation. Reason: Overexpression in a tumour line; kept as non-core, matching the TFAP2A review of the same paper. Supporting Evidence: PMID:20607706 Transfection of TFAP2A and TFAP2B expression constructs into retinoblastoma cells induces apoptosis and inhibits proliferation. |
| GO:0010467 gene expression | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer of 'gene expression' (mouse source: Et-1 and Hif2a ductal expression depend on Tfap2b). Reason: True but uninformative; the specific activity is captured by positive regulation of transcription by RNA polymerase II. Supporting Evidence: PMID:18635823 Our data indicate that Tfap2beta, Et-1, and Hif2alpha act in a transcriptional network during ductal smooth muscle development |
| GO:0010842 retina layer formation | IEP PMID:20607706 AP2 transcription factor induces apoptosis in retinoblastoma... | MARK AS OVER ANNOTATED | Summary: TFAP2B expression in amacrine and horizontal cells of human retina. Reason: Expression only (IEP); no evidence that TFAP2B forms retinal layers. Matches the TFAP2A review. Supporting Evidence: PMID:20607706 TFAP2A and TFAP2B, which map to chromosome arm 6p, are expressed in the amacrine and horizontal cells of human retina |
| GO:0030510 regulation of BMP signaling pathway | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara transfer: regulation of BMP signaling pathway (mouse Bmp2/Bmp4 promoter control). Reason: Tfap2b regulates Bmp2 and Bmp4 transcription in limb buds; the effect on signalling is downstream of transcriptional control. Valid but non-core. Supporting Evidence: PMID:21829553 due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b |
| GO:0030510 regulation of BMP signaling pathway | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse: regulation of BMP signaling via Bmp2/Bmp4 transcription. Reason: As above: indirect, through ligand gene expression. Supporting Evidence: PMID:21829553 due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b |
| GO:0035136 forelimb morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara: forelimb morphogenesis (mouse IMP). Reason: Mouse Tfap2b nulls have postaxial polydactyly and Char syndrome patients have hand anomalies, so the role is conserved; it is a pleiotropic developmental output of the TF, kept as non-core. Supporting Evidence: PMID:21829553 Lack of Tfap2b resulted in bilateral postaxial accessory digits. PMID:10802654 Our work shows that TFAP2B has a role in ductal, facial and limb development and suggests that Char syndrome results from derangement of neural-crest-cell derivatives. |
| GO:0035136 forelimb morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse: forelimb morphogenesis. Reason: Mouse Tfap2b nulls have postaxial polydactyly and Char syndrome patients have hand anomalies, so the role is conserved; it is a pleiotropic developmental output of the TF, kept as non-core. Supporting Evidence: PMID:21829553 Lack of Tfap2b resulted in bilateral postaxial accessory digits. PMID:10802654 Our work shows that TFAP2B has a role in ductal, facial and limb development and suggests that Char syndrome results from derangement of neural-crest-cell derivatives. |
| GO:0035137 hindlimb morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara: hindlimb morphogenesis (mouse IMP). Reason: Mouse Tfap2b nulls have postaxial polydactyly and Char syndrome patients have hand anomalies, so the role is conserved; it is a pleiotropic developmental output of the TF, kept as non-core. Supporting Evidence: PMID:21829553 Lack of Tfap2b resulted in bilateral postaxial accessory digits. |
| GO:0035137 hindlimb morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse: hindlimb morphogenesis. Reason: Mouse Tfap2b nulls have postaxial polydactyly and Char syndrome patients have hand anomalies, so the role is conserved; it is a pleiotropic developmental output of the TF, kept as non-core. Supporting Evidence: PMID:21829553 Lack of Tfap2b resulted in bilateral postaxial accessory digits. |
| GO:0035909 aorta morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara: aorta morphogenesis (mouse patent ductus). Reason: The mouse source is the open ductus arteriosus phenotype. The ductus is part of the great-vessel system, but ductus arteriosus closure captures the specific role; aorta morphogenesis is kept as non-core. Supporting Evidence: PMID:21829553 Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. |
| GO:0035909 aorta morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from mouse: aorta morphogenesis. Reason: The mouse source is the open ductus arteriosus phenotype. The ductus is part of the great-vessel system, but ductus arteriosus closure captures the specific role; aorta morphogenesis is kept as non-core. Supporting Evidence: PMID:21829553 Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. |
| GO:0042127 regulation of cell population proliferation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: regulation of cell population proliferation. Reason: Context-dependent effects on proliferation in cell lines; not a core developmental function. Matches the TFAP2A review. Supporting Evidence: PMID:20607706 Transfection of TFAP2A and TFAP2B expression constructs into retinoblastoma cells induces apoptosis and inhibits proliferation. |
| GO:0042803 protein homodimerization activity | IPI PMID:11505339 Novel TFAP2B mutations that cause Char syndrome provide a ge... | ACCEPT | Summary: Char syndrome mutants and wild-type TFAP2B: dominant-negative effects imply homodimer formation. Reason: AP-2 proteins bind DNA as dimers; Char mutants dimerize with wild-type TFAP2B and poison it, directly showing homodimerization. Supporting Evidence: PMID:11505339 Functional analyses of the four mutants disclosed that two, R225C and R225S, failed to bind target sequence in vitro and that all four had dominant negative effects when expressed in eukaryotic cells. PMID:10802654 Dimerization of both mutants with normal TFAP2B adversely affected transactivation, demonstrating a dominant-negative mechanism. |
| GO:0043066 negative regulation of apoptotic process | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: negative regulation of apoptotic process (mouse Tfap2b and human TFAP2B evidence). Reason: Survival of developing cell populations is a recurrent in vivo role of AP-2beta: distal nephron epithelia and sympathetic progenitors die in mouse knockouts, with loss of bcl-2 family expression. Supporting Evidence: PMID:9271117 At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. PMID:21539825 In the AP-2Ξ² knockout only sympathetic ganglia (SG) are targeted, leading to a reduction in ganglion size by about 40%, which is also caused by apoptotic death of neural crest progenitors. |
| GO:0043066 negative regulation of apoptotic process | IDA PMID:17525748 Comparative expression profiling identifies an in vivo targe... | ACCEPT | Summary: TFAP2B mediates the anti-apoptotic function of PAX3/FKHR in alveolar rhabdomyosarcoma cells. Reason: Tumour context, but the anti-apoptotic activity matches the physiological pro-survival role of AP-2beta in kidney epithelia and sympathetic progenitors, so the term is accepted consistently with the IBA/ISS rows. Supporting Evidence: PMID:17525748 TFAP2B was validated as direct target gene mediating the anti-apoptotic function of PAX3/FKHR. |
| GO:0043066 negative regulation of apoptotic process | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse: negative regulation of apoptotic process (renal epithelia). Reason: Mouse knockout shows massive apoptosis of distal tubule and collecting duct epithelia with loss of bcl-X(L), bcl-w and bcl-2. Supporting Evidence: PMID:9271117 At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. |
| GO:0043525 positive regulation of neuron apoptotic process | IDA PMID:20607706 AP2 transcription factor induces apoptosis in retinoblastoma... | MARK AS OVER ANNOTATED | Summary: TFAP2B overexpression induces apoptosis of retinoblastoma cells. Reason: Overexpression in a tumour line; physiological TFAP2B function is pro-survival in neurons and epithelia. Matches the TFAP2A review. Supporting Evidence: PMID:20607706 Transfection of TFAP2A and TFAP2B expression constructs into retinoblastoma cells induces apoptosis and inhibits proliferation. PMID:21539825 In the AP-2Ξ² knockout only sympathetic ganglia (SG) are targeted, leading to a reduction in ganglion size by about 40%, which is also caused by apoptotic death of neural crest progenitors. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:11505339 Novel TFAP2B mutations that cause Char syndrome provide a ge... | ACCEPT | Summary: Wild-type TFAP2B binds target sequence; basic-domain Char mutants do not. Reason: Direct support for sequence-specific DNA binding. Supporting Evidence: PMID:11505339 Functional analyses of the four mutants disclosed that two, R225C and R225S, failed to bind target sequence in vitro and that all four had dominant negative effects when expressed in eukaryotic cells. |
| GO:0043565 sequence-specific DNA binding | IDA PMID:12169688 The role of Sp1 and AP-2 in basal and protein kinase A--indu... | ACCEPT | Summary: AP-2 binding site footprinted and gel-shifted in the rat SPT promoter. Reason: Paralog not stated in the abstract; correct function for AP-2beta, accepted in deference to the curator. Supporting Evidence: PMID:12169688 By using a luciferase reporter assay with HepG2 cells, DNase I footprinting analysis, and gel shift experiments, we identified the binding sites for Sp1 and AP-2 within the regions -125 to -89 and -14 to +10, respectively. |
| GO:0043588 skin development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara: skin development (mouse source is an expression annotation). Reason: AP-2beta is expressed in skin and, together with AP-2alpha, is needed in mouse ectoderm for skin differentiation; the TFAP2B-alone role is not established. Supporting Evidence: PMID:35333176 loss of these AP-2 proteins affects both skin differentiation as well as multiple signaling pathways |
| GO:0045444 fat cell differentiation | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara: fat cell differentiation (mouse IEP source). Reason: Expression rising with adipocyte differentiation is not evidence that TFAP2B drives the differentiation. IEP is weak support for a process. Supporting Evidence: PMID:16373396 TFAP2B was preferentially expressed in adipose cells in a differentiation-dependent manner |
| GO:0045444 fat cell differentiation | IEP PMID:16373396 Intronic polymorphisms within TFAP2B regulate transcriptiona... | MARK AS OVER ANNOTATED | Summary: TFAP2B is expressed in adipocytes in a differentiation-dependent manner. Reason: Expression rising with adipocyte differentiation is not evidence that TFAP2B drives the differentiation. IEP is weak support for a process. Supporting Evidence: PMID:16373396 TFAP2B was preferentially expressed in adipose cells in a differentiation-dependent manner |
| GO:0045595 regulation of cell differentiation | IDA PMID:20607706 AP2 transcription factor induces apoptosis in retinoblastoma... | MARK AS OVER ANNOTATED | Summary: TFAP2B loss in retinoblastoma proposed to block amacrine/horizontal differentiation. Reason: Inference from tumour expression and overexpression; matches the TFAP2A review. Supporting Evidence: PMID:20607706 Transfection of TFAP2A and TFAP2B expression constructs into retinoblastoma cells induces apoptosis and inhibits proliferation. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:20607706 AP2 transcription factor induces apoptosis in retinoblastoma... | KEEP AS NON CORE | Summary: Negative regulation of transcription from the retinoblastoma study. Reason: The cached abstract does not show repression, but AP-2beta does repress selected targets elsewhere (TFAP2C in chick crest; Bmp4 in mouse limb). Kept as a context-dependent, non-core activity. Supporting Evidence: PMID:31848212 TFAP2B overexpression resulted in the strong down-regulation of TFAP2C mRNA levels in the neural folds, whereas TFAP2A expression remained unchanged PMID:21829553 due to direct control of Bmp2 and Bmp4 promoter activity by Tfap2b |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:11505339 Novel TFAP2B mutations that cause Char syndrome provide a ge... | ACCEPT | Summary: Wild-type TFAP2B transactivates; Char mutants act as dominant negatives. Reason: Activator function is core. Supporting Evidence: PMID:11505339 Functional analyses of the four mutants disclosed that two, R225C and R225S, failed to bind target sequence in vitro and that all four had dominant negative effects when expressed in eukaryotic cells. PMID:10802654 Dimerization of both mutants with normal TFAP2B adversely affected transactivation, demonstrating a dominant-negative mechanism. |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:16373396 Intronic polymorphisms within TFAP2B regulate transcriptiona... | ACCEPT | Summary: TFAP2B overexpression raises TNF-alpha expression in adipocytes. Reason: Positive transcriptional regulation is core; GO:0045944 is the more specific term. Supporting Evidence: PMID:16373396 In an experiment using adenovirus vectors encoding TFAP2B, the expression of TNF-alpha gene was shown to be elevated in the TFAP2B overexpressing cells compared with those in control cells. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: positive regulation of transcription by RNA polymerase II. Reason: Core process of the AP-2 activators; human renal tubular cells provide a recent ChIP-plus-reporter example (S100A16). Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. file:human/TFAP2B/TFAP2B-deep-research-falcon.md TFAP2B overexpression raised promoter-reporter activity and endogenous S100A16 RNA and protein |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:12169688 The role of Sp1 and AP-2 in basal and protein kinase A--indu... | ACCEPT | Summary: AP-2 activates the SPT promoter. Reason: Correct; paralog not stated in the abstract, accepted in deference to the curator. Supporting Evidence: PMID:12169688 Expression of AP-2 caused a marked increase in the basal promoter activity to about the same level as that achieved by PKA. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:7555706 Cloning and characterization of a second AP-2 transcription ... | ACCEPT | Summary: AP-2beta transactivates an AP-2-dependent reporter. Reason: Core process. Supporting Evidence: PMID:7555706 AP-2 beta binds specifically to a series of well-characterized AP-2 binding sites, consensus to the sequence G/CCCN3GGC, and transactivates transcription from a reporter plasmid under the control of an AP-2-dependent promoter. |
| GO:0046982 protein heterodimerization activity | IPI PMID:11505339 Novel TFAP2B mutations that cause Char syndrome provide a ge... | ACCEPT | Summary: Char mutants dimerize with wild-type TFAP2B; AP-2beta heterodimerizes with AP-2alpha. Reason: Heterodimerization with AP-2alpha is shown biochemically (PMID:7555706) and in vivo in chick crest, where TFAP2A/B heterodimers are the specification complex. Supporting Evidence: PMID:7555706 A C-terminal domain known to mediate homodimerization of the previously cloned AP-2 alpha transcription activator is highly conserved and sufficient to mediate interaction between the two proteins. PMID:31848212 Pulldown of TFAP2A with streptavidin beads resulted in co-IP of both FLAG-tagged TFAP2B and TFAP2C, confirming that these factors form heterodimers in avian embryos |
| GO:0048485 sympathetic nervous system development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse Tfap2b: sympathetic nervous system development. Reason: Mouse Tfap2b is needed for survival of sympathetic progenitors (ganglia about 40% smaller) and for locus coeruleus neurons; with Tfap2a the ganglia are lost. In human neuroblastoma cells TFAP2B drives noradrenergic differentiation. A core crest-derivative role. Supporting Evidence: PMID:21539825 In the AP-2Ξ² knockout only sympathetic ganglia (SG) are targeted, leading to a reduction in ganglion size by about 40%, which is also caused by apoptotic death of neural crest progenitors. PMID:21539825 The elimination of both AP-2Ξ± and AP-2Ξ² results in the virtually complete absence of sympathetic and sensory ganglia due to apoptotic cell death of migrating NCC. PMID:26598443 In IMR-32 cells, TFAP2B induced neuronal differentiation, which was accompanied by up-regulation of the catecholamine biosynthesizing enzyme genes DBH and TH |
| GO:0048745 smooth muscle tissue development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara: smooth muscle tissue development (mouse ductal smooth muscle). Reason: Tfap2b is part of the ductal smooth muscle transcriptional network; the specific consequence is captured by ductus arteriosus closure. Supporting Evidence: PMID:18635823 Our data indicate that Tfap2beta, Et-1, and Hif2alpha act in a transcriptional network during ductal smooth muscle development |
| GO:0050796 regulation of insulin secretion | IMP PMID:15940393 Genetic variations in the gene encoding TFAP2B are associate... | MARK AS OVER ANNOTATED | Summary: TFAP2B variants associated with type 2 diabetes. Reason: Based on genetic association studies of insulin resistance/type 2 diabetes. Association with insulin sensitivity is not evidence that TFAP2B regulates insulin secretion, and no beta-cell function of TFAP2B is shown. Abstract-only papers, so marked over-annotated rather than removed. Supporting Evidence: PMID:15940393 several variations within TFAP2B were significantly associated with type 2 diabetes |
| GO:0050796 regulation of insulin secretion | IMP PMID:19325541 The transcription factor TFAP2B is associated with insulin r... | MARK AS OVER ANNOTATED | Summary: TFAP2B variation associated with insulin sensitivity in adolescents. Reason: Based on genetic association studies of insulin resistance/type 2 diabetes. Association with insulin sensitivity is not evidence that TFAP2B regulates insulin secretion, and no beta-cell function of TFAP2B is shown. Abstract-only papers, so marked over-annotated rather than removed. Supporting Evidence: PMID:19325541 both insulin sensitivity, as measured from levels of fasting glucose and insulin, and central adiposity, estimated by subscapular skinfold thickness, were significantly associated to genetic variability in TFAP2B |
| GO:0072017 distal tubule development | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara: distal tubule development. Reason: Mouse Tfap2b knockouts lose distal tubule and collecting duct epithelia by apoptosis and develop terminal renal failure; the role is non-redundant in mouse. Supporting Evidence: PMID:9271117 At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. PMID:12695560 our studies reveal essential, nonredundant roles of AP-2 beta in renal tubular functions |
| GO:0072017 distal tubule development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse: distal tubule development. Reason: Mouse Tfap2b knockouts lose distal tubule and collecting duct epithelia by apoptosis and develop terminal renal failure; the role is non-redundant in mouse. Supporting Evidence: PMID:9271117 At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. PMID:12695560 our studies reveal essential, nonredundant roles of AP-2 beta in renal tubular functions |
| GO:0072044 collecting duct development | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara: collecting duct development. Reason: Mouse Tfap2b knockouts lose distal tubule and collecting duct epithelia by apoptosis and develop terminal renal failure; the role is non-redundant in mouse. Supporting Evidence: PMID:9271117 At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. PMID:12695560 our studies reveal essential, nonredundant roles of AP-2 beta in renal tubular functions |
| GO:0072044 collecting duct development | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse: collecting duct development. Reason: Mouse Tfap2b knockouts lose distal tubule and collecting duct epithelia by apoptosis and develop terminal renal failure; the role is non-redundant in mouse. Supporting Evidence: PMID:9271117 At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. PMID:12695560 our studies reveal essential, nonredundant roles of AP-2 beta in renal tubular functions |
| GO:0072210 metanephric nephron development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Ensembl Compara: metanephric nephron development (mouse source is an expression annotation). Reason: Nephron induction and early differentiation are normal in knockouts; the role is late survival of distal segments, captured by the tubule terms. Supporting Evidence: PMID:9271117 At the end of embryonic development expression of bcl-X(L), bcl-w, and bcl-2 is down-regulated in parallel to massive apoptotic death of collecting duct and distal tubular epithelia. |
| GO:0097070 ductus arteriosus closure | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara: ductus arteriosus closure. Reason: Human TFAP2B loss of function causes patent ductus arteriosus (Char syndrome, PDA2), and the mouse Tfap2b knockout ductus fails to close. Tfap2b drives the ductal smooth muscle programme. A core developmental role. Supporting Evidence: PMID:21829553 Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. PMID:10802654 Our work shows that TFAP2B has a role in ductal, facial and limb development and suggests that Char syndrome results from derangement of neural-crest-cell derivatives. |
| GO:0097070 ductus arteriosus closure | ISS GO_REF:0000024 | ACCEPT | Summary: ISS from mouse: ductus arteriosus closure. Reason: Human TFAP2B loss of function causes patent ductus arteriosus (Char syndrome, PDA2), and the mouse Tfap2b knockout ductus fails to close. Tfap2b drives the ductal smooth muscle programme. A core developmental role. Supporting Evidence: PMID:21829553 Histological examination of ductus arteriosus from Tfap2b knockout mice 6 hours after birth revealed that they were not closed. PMID:18635823 We found that Tfap2beta, a transcription factor associated with patent ductus arteriosus in humans, was uniquely expressed in mouse ductal smooth muscle. PMID:10802654 Our work shows that TFAP2B has a role in ductal, facial and limb development and suggests that Char syndrome results from derangement of neural-crest-cell derivatives. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: Methylation-sensitive HT-SELEX of human TFs including TFAP2B yields a sequence-specific dsDNA motif. Reason: Direct in vitro sequence-specific double-stranded DNA binding. Supporting Evidence: PMID:28473536 By analysis of 542 human TFs with methylation-sensitive SELEX |
| GO:0014036 neural crest cell fate specification | ISS PMID:31848212 Heterodimerization of TFAP2 pioneer factors drives epigenomi... | NEW | Summary: AP-2beta is a neural crest specifier. In chick it comes on only at the onset of specification, heterodimerizes with TFAP2A, recruits TFAP2A to specification enhancers (FOXD3 NC1, SOX9, SNAI2, SOX10), represses TFAP2C to complete the partner switch, and is required and rate-limiting for specification; knockdown spares the neural plate border. In frog, Pax3 and Zic1 activate tfap2b directly. Reason: Human TFAP2B has no neural crest term. Layer: crest specifier, not border specifier, so GO:0014036 (the project convention for specifiers) rather than the proposed border term; TFAP2B is absent at border stages and its knockdown leaves border markers intact. GO:0014034 is not added because GO:0014036 is part_of it. Participation: TFAP2B is a DNA-binding heterodimer partner that itself occupies, and targets TFAP2A to, specification enhancers, so it does part of the work. Comparator (QuickGO 2026-10-08): no TFAP2B ortholog in any species carries a crest-branch term, but zebrafish tfap2a and tfap2c carry GO:0014036 (IMP/IGI) and frog crest specifiers (sox10, sox9-a, sox8, snai2) carry it. The absence is explained: the paralog-specific evidence is a 2020 chick paper and chicken TFAP2B has no manual curation, while mouse and zebrafish single mutants are masked by TFAP2A redundancy. ISS because the experiments are on chick TFAP2B. Caveat for sign-off: in mouse TFAP2B is redundant with TFAP2A, so necessity is shown only in chick; human Char syndrome is a disorder of crest derivatives. Supporting Evidence: PMID:31848212 TFAP2B transcripts were not detected until just before the onset of specification, when the gene became robustly expressed in the neural crest lineage PMID:31848212 TFAP2B knockdown produced no effects on the neural plate border but resulted in the disruption of the specification program PMID:31848212 Together, these data support the idea that TFAP2B is required for the recruitment of TFAP2A to specification loci. PMID:31848212 These results indicate that TFAP2B is specialized in its ability to promote neural crest specification. PMID:31848212 this manipulation resulted in a premature onset of specification, with early activity of NC1 in the reprogrammed side of the embryo PMID:24360906 We demonstrated that the neural border specifiers Pax3 and Zic1 are direct upstream regulators of neural crest specifiers Snail1/2, Foxd3, Twist1, and Tfap2b. PMID:10802654 Our work shows that TFAP2B has a role in ductal, facial and limb development and suggests that Char syndrome results from derangement of neural-crest-cell derivatives. |
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Download this section (compressed HTML)Q: The crest-specification role of TFAP2B is necessary only in chick; in mouse TFAP2B is redundant with TFAP2A and no AP-2alpha/beta heterodimer function is irreplaceable. Is ISS transfer of GO:0014036 from chick to human acceptable, or should the term sit on chicken TFAP2B only (currently unreviewed TrEMBL)?
Q: Do TFAP2A/TFAP2B heterodimers occupy crest specification enhancers in human (hPSC-derived) or mouse neural crest, as in chick?
Q: Zebrafish tfap2b crispants have fewer enteric neurons and one human TFAP2B haploinsufficient patient has intestinal pseudo-obstruction. Is the evidence enough for enteric nervous system development (GO:0048484) on human TFAP2B, or should it wait for replication?
Q: Duan & Clemmons 1995 (PMID:7559606) is about AP-2alpha and its dominant-negative splice isoform 'AP-2B'. Should other TFAP2B annotations sourced from papers that use the 'AP-2B' name be audited for the same confusion?
Q: The Sox8-Tfap2b-Ets1 cranial circuit reprograms trunk crest only in combination. Does TFAP2B carry a cranial skeletal/chondrogenic process term on its own (e.g. GO:0048701), or is this a property of the circuit best represented in a GO-CAM?
Experiment: CUT&RUN for TFAP2B and TFAP2A (with and without TFAP2B knockdown) in human pluripotent stem cell-derived neural crest, to test whether TFAP2B redirects TFAP2A to specification enhancers in human.
Experiment: Conditional neural-crest Tfap2b deletion in a Tfap2a-heterozygous mouse background, scored at specification stages (Foxd3, Sox10, Snai2), to expose a mammalian specification role masked by redundancy.
Experiment: Express lamprey Tfap2 and amphioxus AP-2 in chick in place of TFAP2B to ask whether the single pre-duplication AP-2 can perform the TFAP2B-specific recruitment of TFAP2A to specification enhancers.
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