TEAD1 (TEF-1) is a nuclear sequence-specific DNA-binding transcription factor of the TEA/ATTS domain family. Its N-terminal TEA domain recognizes M-CAT/GT-IIC-type enhancer elements (GGAATG core), and its C-terminal YAP-binding (transactivation) domain docks the transcriptional coactivators YAP1 and WWTR1/TAZ and the vestigial-like cofactors (VGLL1-4). Because YAP and TAZ lack DNA-binding activity, TEAD1 and its paralogs TEAD2-4 are the main DNA-binding partners that bring these Hippo-regulated coactivators to promoters and enhancers, activating genes such as CTGF/CCN2 that drive cell proliferation, epithelial-mesenchymal transition and oncogenic growth; VGLL4 competes with YAP for TEAD binding and represses this output. TEAD1 is expressed broadly, highest in skeletal muscle, acts in muscle-gene regulation via M-CAT elements and in cardiac development, and the Y406H substitution in its YAP-binding interface, which abolishes YAP binding, causes Sveinsson chorioretinal atrophy. TEAD1 activity is also modulated post-translationally, for example by AARS1-catalyzed lactylation of K108. Evolutionarily, TEA-domain transcription factors are older than animals (they occur in fungi), and a single Scalloped/TEAD ortholog in the unicellular holozoan Capsaspora binds the Capsaspora Yorkie ortholog and co-activates a Hippo-responsive reporter, so the TEAD-coactivator partnership predates animals, whereas roles in organ growth and tissue development are animal-specific uses of this ancient module.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000785 chromatin | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass-based assignment of TEAD1 (TEA domain class 3.6.1) to chromatin. Reason: A sequence-specific DNA-binding transcription factor that occupies promoters genome-wide in ChIP-on-chip is chromatin-associated; YAP and TEAD1 co-occupy most bound promoters in MCF10A cells. Supporting Evidence: PMID:18579750 Interestingly, our results demonstrated that YAP and TEAD1 co-occupy >80% of the promoters pulled down by either of them |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for RNA polymerase II cis-regulatory region sequence-specific DNA binding, placed on the TEA-domain family node PTN000216669 whose descendants include Drosophila scalloped and budding yeast TEC1. Reason: Sequence-specific binding to M-CAT/GT-IIC (GGAATG core) enhancer elements via the TEA domain is the defining activity of the family and is conserved from fungi to mammals. The IBD sits on a node that includes fungal TEA-domain proteins, consistent with TEA-domain DNA binding being older than the Holozoa. TEAD1 appearing among the donors reflects its own experimental support. Supporting Evidence: PMID:20123905 TEAD contains an N-terminal TEA DNA-binding domain ( Anbanandam et al. 2006 ) and a C-terminal region responsible for YAP interaction file:human/TEAD1/TEAD1-uniprot.txt SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates PMID:38729842 TEAD family members were identified in Drosophila, the filamentous fungus A. nidulans, and S. cerevisiae (Figure 2), and were found to regulate wing development, [37], sporulation [38], and pseudohyphal growth [39], respectively. |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse Tead1. Reason: Consistent with direct human evidence for promoter/enhancer binding (ChIP at CTGF and miR-222 promoters). Supporting Evidence: PMID:18579750 Interestingly, our results demonstrated that YAP and TEAD1 co-occupy >80% of the promoters pulled down by either of them |
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IMP PMID:26045994 miR-222/VGLL4/YAP-TEAD1 regulatory loop promotes proliferati... | ACCEPT | Summary: Knockdown plus ChIP in gastric cancer cells showing TEAD1 occupies two predicted TEAD sites in the miR-222 promoter. Reason: ChIP shows TEAD1 at the predicted sites in an RNA polymerase II-transcribed regulatory region, and knockdown reduces reporter activity driven by that region. The specific target (miR-222) is context-specific, but the molecular function is the canonical TEAD activity. Supporting Evidence: PMID:26045994 ChIP results revealed that TEAD1 factually binds to Site A and Site B within the potential miR-222 promoter ( Figure 4D ). PMID:26045994 These results factually imply TEAD1 could physically bind to the promoter region of miR-222 to promote its transcription in GC cells. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA for RNA polymerase II-specific DNA-binding transcription factor activity on the TEA-domain family node. Reason: Core activity. TEAD1 binds cognate enhancer sites and regulates Pol II target genes (CTGF and others) in partnership with YAP/TAZ; the activity is ancestral to the TEA-domain family. Supporting Evidence: PMID:18579750 Since YAP does not have DNA-binding activity, these data strongly indicate that TEAD plays a major role in mediating the binding of YAP to gene promoters. PMID:18579750 We cloned the CTGF promoter into a basic luciferase reporter and found that it was potently activated by YAP but not by YAP-S94A, and the activation was further enhanced by TEAD1 coexpression ( Fig. 3B ). |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IMP PMID:26045994 miR-222/VGLL4/YAP-TEAD1 regulatory loop promotes proliferati... | ACCEPT | Summary: TEAD1 knockdown reduces miR-222 promoter-driven reporter activity and endogenous miR-222; ChIP places TEAD1 on the promoter. Reason: Binding plus loss-of-function effect on the target supports TF activity, albeit in a single cancer-cell context. Supporting Evidence: PMID:26045994 As shown, TEAD1 knockdown significantly downregulated miR-222 expression in BGC-823, MGC-803 and HGC-27 GC cell lines ( Figure 4B ), accompanied with VGLL4 upregulation ( Figure 4C ). PMID:26045994 These results factually imply TEAD1 could physically bind to the promoter region of miR-222 to promote its transcription in GC cells. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | ISA GO_REF:0000113 | ACCEPT | Summary: TFClass-based assignment of DbTF activity. Reason: TEAD1 is a bona fide TEA-domain DNA-binding transcription factor. Supporting Evidence: file:human/TEAD1/TEAD1-uniprot.txt SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates |
| GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse of DNA-binding transcription activator activity, RNA polymerase II-specific. Reason: TEAD1 activates CTGF and other Pol II targets when bound by YAP/TAZ; TEAD1 coexpression enhances YAP-driven CTGF reporter activity. Activation is coactivator-dependent (TEAD1 can also take part in repression with VGLL4), but activation is the best-documented output. Supporting Evidence: PMID:18579750 We cloned the CTGF promoter into a basic luciferase reporter and found that it was potently activated by YAP but not by YAP-S94A, and the activation was further enhanced by TEAD1 coexpression ( Fig. 3B ). PMID:18579750 TEAD1 was not present in our Gal4-TF library, but it could also be potently activated by YAP ( Fig. 1A ). |
| GO:0003677 DNA binding | TAS PMID:8396764 Both a ubiquitous factor mTEF-1 and a distinct muscle-specif... | MODIFY | Summary: Traceable author statement from the cloning of mouse mTEF-1 as the ubiquitous M-CAT (A element) binding factor of the beta-myosin heavy chain promoter. Reason: DNA binding is correct but uninformative; the paper (abstract-only in cache) shows binding of the TEF-1 product to a specific cis-regulatory element (the M-CAT-containing A element) of a Pol II promoter, which is captured by the more specific cis-regulatory region binding term already supported by IBA and experimental rows. Proposed replacements: RNA polymerase II cis-regulatory region sequence-specific DNA binding Supporting Evidence: PMID:8396764 The in vitro transcription/translation product of mTEF-1 cDNA bound to the A element, and the DNA binding property of mTEF-1 was identical to that of the A2 factor. |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:18579750 TEAD mediates YAP-dependent gene induction and growth contro... | ACCEPT | Summary: Zhao et al. 2008: TEAD1 activated by YAP in Gal4 reporter, co-occupies promoters with YAP by ChIP-on-chip, and enhances CTGF promoter activation. Reason: Direct human evidence for TEAD1 as the DNA-binding factor that recruits YAP to target promoters. Note that the knockdown experiments in this paper used shRNAs targeting TEAD1, TEAD3 and TEAD4 together, so the TEAD1-specific evidence is the ChIP, reporter and dominant-negative TEAD1-deltaC data. Supporting Evidence: PMID:18579750 Since YAP does not have DNA-binding activity, these data strongly indicate that TEAD plays a major role in mediating the binding of YAP to gene promoters. PMID:18579750 TEAD1 was not present in our Gal4-TF library, but it could also be potently activated by YAP ( Fig. 1A ). PMID:18579750 Indeed, these shRNAs were able to knock down TEAD1, TEAD3, and TEAD4 concurrently but not TEAD2 (Supplemental Fig. S1C). |
| GO:0003700 DNA-binding transcription factor activity | IDA PMID:19324877 TEAD transcription factors mediate the function of TAZ in ce... | ACCEPT | Summary: Zhang et al. 2009: TEAD1 is activated by TAZ, and dominant-negative TEAD1-deltaC (retaining the DNA-binding domain) blocks TAZ activation of the CTGF promoter. Reason: Supports TEAD1 DNA-binding TF activity as the mediator of TAZ output. Supporting Evidence: PMID:19324877 TEAD1 is not in the library but was also confirmed to be activated by TAZ separately PMID:19324877 TEAD1 ΞC functions as a dominant negative probably by competing with endogenous TEAD for binding to target gene promoters. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro2GO from TEA/ATTS domain (IPR000818) and TEF family (IPR016361). Reason: TEA domain mapping to DNA-binding TF activity is sound. Supporting Evidence: PMID:20123905 TEAD contains an N-terminal TEA DNA-binding domain ( Anbanandam et al. 2006 ) and a C-terminal region responsible for YAP interaction |
| GO:0003700 DNA-binding transcription factor activity | IMP PMID:20123905 Structural insights into the YAP and TEAD complex. | ACCEPT | Summary: Li et al. 2010: TEAD1 Y406A/Y406H mutants (YAP-binding interface 3) cannot be activated by YAP in Gal4-TEAD1 and CTGF reporter assays. Reason: Mutational evidence that TEAD1 transcriptional output on a TEAD-site promoter depends on its coactivator interface; consistent with TF activity. Supporting Evidence: PMID:20123905 The ability of Y406A and Y406H to be activated by YAP was abolished in both Gal4-TEAD1 and CTGF reporter assays |
| GO:0005515 protein binding | IPI PMID:15140898 Vgl-4, a novel member of the vestigial-like family of transc... | MODIFY | Summary: Co-immunoprecipitation of TEF-1 (TEAD1) with mouse Vgl-4 (VGLL4). Reason: Generic protein binding is uninformative. VGLL4 is a vestigial-like transcription cofactor that binds TEF-1 factors through TDU motifs and modulates TEF-1-dependent transcription, so the interaction is captured by transcription coregulator binding (VGLL4 acts as a corepressor of TEAD in later work, hence coregulator rather than coactivator). Proposed replacements: transcription coregulator binding Supporting Evidence: PMID:15140898 Like other Vgl factors, Vgl-4 physically interacts with TEF-1 in an immunoprecipitation assay. |
| GO:0005515 protein binding | IPI PMID:18579750 TEAD mediates YAP-dependent gene induction and growth contro... | MODIFY | Summary: Zhao et al. 2008: YAP-TEAD1 physical interaction; YAP S94A loses TEAD binding. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:18579750 Since YAP does not have DNA-binding activity, these data strongly indicate that TEAD plays a major role in mediating the binding of YAP to gene promoters. PMID:20123905 YAP and TEAD form a heterodimer |
| GO:0005515 protein binding | IPI PMID:19324877 TEAD transcription factors mediate the function of TAZ in ce... | MODIFY | Summary: Zhang et al. 2009: TAZ (WWTR1) affinity purification identifies all four TEADs including TEAD1. Reason: Generic protein binding is uninformative. WWTR1/TAZ is a transcriptional coactivator, and TEAD1 is activated by TAZ; the informative TEAD1 function is transcription coactivator binding. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:19324877 Notably, all four TEAD family members, TEAD1, TEAD2, TEAD3, and TEAD4, were identified with high scores. PMID:19324877 TEAD1 is not in the library but was also confirmed to be activated by TAZ separately |
| GO:0005515 protein binding | IPI PMID:22863277 Regulation of the Hippo-YAP pathway by G-protein-coupled rec... | MODIFY | Summary: Yu et al. 2012: LPA enhances YAP-TEAD1 interaction. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:22863277 LPA also enhanced the interaction between YAP and the nuclear-localized TEAD1, a transcription factor target of YAP/TAZ (Figure 3C). |
| GO:0005515 protein binding | IPI PMID:24255178 Protein interaction network of the mammalian Hippo pathway r... | MODIFY | Summary: Couzens et al. 2013: Hippo pathway AP-MS interaction network (abstract-only in cache) records TEAD1-YAP1. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. The cached abstract does not mention TEAD1, but the YAP1-TEAD1 interaction is independently established. Proposed replacements: transcription coactivator binding Supporting Evidence: Reactome:R-HSA-2032775 In the nucleus the YAP1 transcriptional coactivator can bind any one of the four TEAD transcription factors to form a complex. |
| GO:0005515 protein binding | IPI PMID:24581491 Hippo signaling regulates microprocessor and links cell-dens... | MODIFY | Summary: Mori et al. 2014: YAP/TEAD1 interaction used as a control in Microprocessor study; the YAP/p72 complex lacks TEAD1. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:24581491 Co-IPs revealed that the YAP/p72 complex does not contain TEAD1 (Figure S2G). |
| GO:0005515 protein binding | IPI PMID:24882516 Mutant Gq/11 promote uveal melanoma tumorigenesis by activat... | MODIFY | Summary: Feng et al. 2014: Gq knockdown reduces YAP-TEAD interaction in uveal melanoma cells. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:24882516 In Gq knockdown cells, the interaction of YAP and TEAD was decreased while Gq knockdown had no effect on TEAD1 expression (Figure 3C). |
| GO:0005515 protein binding | IPI PMID:25751139 AMPK modulates Hippo pathway activity to regulate energy hom... | MODIFY | Summary: Mo et al. 2015: release from energy stress increases YAP-TEAD1 interaction. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:25751139 while increasing its interaction with TEAD1 (Figure 2C) |
| GO:0005515 protein binding | IPI PMID:25751140 Cellular energy stress induces AMPK-mediated regulation of Y... | MODIFY | Summary: Wang et al. 2015: AMPK-mediated YAP S94 phosphorylation disrupts YAP-TEAD complex formation. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:25751140 an essential function of S94 in YAP-TEAD complex formation by forming a hydrogen bond with Y406 in TEAD1 |
| GO:0005515 protein binding | IPI PMID:25796446 Aerobic glycolysis tunes YAP/TAZ transcriptional activity. | REMOVE | Summary: Enzo et al. 2015 (abstract-only in cache): phosphofructokinase (PFKM) binds TEADs. Reason: Generic protein binding with a metabolic enzyme partner; no informative TEAD1 molecular function follows from the PFK1 interaction, and the cached abstract does not resolve which TEAD paralog was assayed. Removal does not dispute the reported interaction. Supporting Evidence: PMID:25796446 binds the YAP/TAZ transcriptional cofactors TEADs and promotes their functional and biochemical cooperation with YAP/TAZ. |
| GO:0005515 protein binding | IPI PMID:25796446 Aerobic glycolysis tunes YAP/TAZ transcriptional activity. | MODIFY | Summary: Enzo et al. 2015 (abstract-only in cache): TEAD interaction with PFKM and YAP1. Reason: The YAP1 component of this IPI row is captured by transcription coactivator binding; the PFKM component is uninformative (see the PFKM-only row). Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:25796446 binds the YAP/TAZ transcriptional cofactors TEADs and promotes their functional and biochemical cooperation with YAP/TAZ. |
| GO:0005515 protein binding | IPI PMID:26258633 Genome-wide association between YAP/TAZ/TEAD andΒ AP-1 at enh... | MODIFY | Summary: Zanconato et al. 2015: YAP/TAZ/TEAD and AP-1 at enhancers; YAP1-TEAD1 interaction. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. Proposed replacements: transcription coactivator binding Supporting Evidence: Reactome:R-HSA-2032775 In the nucleus the YAP1 transcriptional coactivator can bind any one of the four TEAD transcription factors to form a complex. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | REMOVE | Summary: BioPlex AP-MS (Huttlin et al. 2017): TEAD1-RAD51. Reason: High-throughput interaction with RAD51 with no functional follow-up; generic protein binding conveys no TEAD1 function. Removal does not mean the interaction is false. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | REMOVE | Summary: BioPlex dual-cell-line network (Huttlin et al. 2021): TEAD1-RAD51. Reason: As for the 2017 BioPlex row: uninformative high-throughput protein binding. |
| GO:0005515 protein binding | IPI PMID:35140242 Human transcription factor protein interaction networks. | MODIFY | Summary: Goos et al. 2022 human TF interaction network: TEAD1-YAP1. Reason: Generic protein binding is uninformative. The partner, YAP1, is a transcriptional coactivator that lacks DNA binding and is recruited to promoters by TEADs; the YAP-binding domain of TEAD1 forms a heterodimer with YAP. The informative molecular function on the TEAD1 side is transcription coactivator binding. The interaction itself is not in doubt. Proposed replacements: transcription coactivator binding Supporting Evidence: Reactome:R-HSA-2032775 In the nucleus the YAP1 transcriptional coactivator can bind any one of the four TEAD transcription factors to form a complex. |
| GO:0005515 protein binding | IPI PMID:9869635 Molecular interactions between Vestigial and Scalloped promo... | MODIFY | Summary: Simmonds et al. 1998: Drosophila Vestigial binds directly to human TEF-1 in vitro. Reason: Generic protein binding is uninformative. Vestigial is a transcriptional intermediary factor (coactivator) of Scalloped and binds the TEF-1 C-terminal half; this is transcription coactivator binding. Cross-species (fly Vg with human TEF-1), but the interface is the conserved YAP/VGLL-binding domain. Proposed replacements: transcription coactivator binding Supporting Evidence: PMID:9869635 In vitro, Vg binds directly to both Sd and its human homolog, Transcription Enhancer Factor-1. PMID:9869635 which implies that Vg is a tissue-specific transcriptional intermediary factor of Sd. |
| GO:0005634 nucleus | IDA PMID:38512451 The alanyl-tRNA synthetase AARS1 moonlights as a lactyltrans... | ACCEPT | Summary: Nuclear localization of TEAD1 (with AARS1/YAP) in gastric cancer cells by fractionation. Reason: TEAD1 is a nuclear transcription factor. Supporting Evidence: PMID:38512451 cellular fractionation assay clearly demonstrated that such interaction mainly occurred in the nucleus file:human/TEAD1/TEAD1-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt subcellular location mapping (Nucleus). Reason: Correct. Supporting Evidence: file:human/TEAD1/TEAD1-uniprot.txt SUBCELLULAR LOCATION: Nucleus |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence: nucleoplasm. Reason: Consistent with nuclear TF function. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2032775 | ACCEPT | Summary: Reactome reaction R-HSA-2032775 places TEAD1 complexes in the nucleoplasm. Reason: TEAD1-YAP/TAZ complexes assemble on target genes in the nucleus; nucleoplasm is appropriate. Supporting Evidence: Reactome:R-HSA-2032775 In the nucleus the YAP1 transcriptional coactivator can bind any one of the four TEAD transcription factors to form a complex. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-2032781 | ACCEPT | Summary: Reactome reaction R-HSA-2032781 places TEAD1 complexes in the nucleoplasm. Reason: TEAD1-YAP/TAZ complexes assemble on target genes in the nucleus; nucleoplasm is appropriate. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8951676 | ACCEPT | Summary: Reactome reaction R-HSA-8951676 places TEAD1 complexes in the nucleoplasm. Reason: TEAD1-YAP/TAZ complexes assemble on target genes in the nucleus; nucleoplasm is appropriate. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-8951695 | ACCEPT | Summary: Reactome reaction R-HSA-8951695 places TEAD1 complexes in the nucleoplasm. Reason: TEAD1-YAP/TAZ complexes assemble on target genes in the nucleus; nucleoplasm is appropriate. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9618559 | ACCEPT | Summary: Reactome reaction R-HSA-9618559 places TEAD1 complexes in the nucleoplasm. Reason: TEAD1-YAP/TAZ complexes assemble on target genes in the nucleus; nucleoplasm is appropriate. |
| GO:0005654 nucleoplasm | TAS Reactome:R-HSA-9909654 | ACCEPT | Summary: Reactome reaction R-HSA-9909654 places TEAD1 complexes in the nucleoplasm. Reason: TEAD1-YAP/TAZ complexes assemble on target genes in the nucleus; nucleoplasm is appropriate. |
| GO:0005667 transcription regulator complex | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: part of transcription regulator complex (TEA-domain family node). Reason: TEAD1 forms heterodimeric transcription regulator complexes with YAP/TAZ and VGLL cofactors; the more specific TEAD-YAP complex is separately annotated. Supporting Evidence: PMID:20123905 YAP and TEAD form a heterodimer |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro combined IEA for regulation of DNA-templated transcription. Reason: Broad but correct. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: regulation of transcription by RNA polymerase II. Reason: Correct and at an appropriate level for the family; ancestral to TEA-domain proteins including fungal members. Supporting Evidence: PMID:38729842 TEAD family members were identified in Drosophila, the filamentous fungus A. nidulans, and S. cerevisiae (Figure 2), and were found to regulate wing development, [37], sporulation [38], and pseudohyphal growth [39], respectively. |
| GO:0030307 positive regulation of cell growth | IDA PMID:18579750 TEAD mediates YAP-dependent gene induction and growth contro... | MODIFY | Summary: Zhao et al. 2008: TEAD1-YAP-S94A fusion stimulates NIH-3T3 cell growth (cell number) and rescues target gene expression. Reason: The assays measure cell number/proliferation, not an increase in cell size (the GO meaning of cell growth). The process is also an output of YAP/TAZ-TEAD target genes (e.g. CTGF), so it is non-core for TEAD1. Positive regulation of cell population proliferation better describes what was measured. TEAD1 alone did not stimulate growth. Proposed replacements: positive regulation of cell population proliferation Supporting Evidence: PMID:18579750 Interestingly, this fusion protein stimulated NIH-3T3 cell growth as effectively as the wild-type YAP, while neither TEAD1 nor YAP-S94A stimulated cell growth ( Fig. 2A ). |
| GO:0035329 hippo signaling | IBA GO_REF:0000033 | ACCEPT | Summary: IBA on TEAD node PTN000931330 (donors include TEAD1-4 and mouse Tead1). Reason: TEAD1 is the DNA-binding transcription factor through which YAP/TAZ, the Hippo-regulated coactivators, act; GO convention annotates the TEAD/Sd effector transcription factors to hippo signaling. Accepted as the pathway context of the core TF activity. Supporting Evidence: PMID:18579750 Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP. |
| GO:0035329 hippo signaling | IDA PMID:18579750 TEAD mediates YAP-dependent gene induction and growth contro... | ACCEPT | Summary: Zhao et al. 2008: TEAD mediates YAP-dependent gene induction downstream of the Hippo pathway. Reason: TEAD1 is the DNA-binding transcription factor through which YAP/TAZ, the Hippo-regulated coactivators, act; GO convention annotates the TEAD/Sd effector transcription factors to hippo signaling. Accepted as the pathway context of the core TF activity. Supporting Evidence: PMID:18579750 Our study reveals TEAD as a new component in the Hippo pathway playing essential roles in mediating biological functions of YAP. PMID:18579750 Since YAP does not have DNA-binding activity, these data strongly indicate that TEAD plays a major role in mediating the binding of YAP to gene promoters. |
| GO:0035329 hippo signaling | IDA PMID:19324877 TEAD transcription factors mediate the function of TAZ in ce... | ACCEPT | Summary: Zhang et al. 2009: TEADs mediate TAZ function. Reason: TEAD1 is the DNA-binding transcription factor through which YAP/TAZ, the Hippo-regulated coactivators, act; GO convention annotates the TEAD/Sd effector transcription factors to hippo signaling. Accepted as the pathway context of the core TF activity. Supporting Evidence: PMID:19324877 TEAD1 ΞC functions as a dominant negative probably by competing with endogenous TEAD for binding to target gene promoters. |
| GO:0035329 hippo signaling | IEA GO_REF:0000120 | ACCEPT | Summary: ARBA/InterPro combined IEA (TEF family IPR016361). Reason: TEAD1 is the DNA-binding transcription factor through which YAP/TAZ, the Hippo-regulated coactivators, act; GO convention annotates the TEAD/Sd effector transcription factors to hippo signaling. Accepted as the pathway context of the core TF activity. |
| GO:0035329 hippo signaling | NAS PMID:21808241 The Hippo pathway in organ size control, tissue regeneration... | ACCEPT | Summary: Zhao et al. 2011 review: TEADs are critical partners of YAP/TAZ. Reason: TEAD1 is the DNA-binding transcription factor through which YAP/TAZ, the Hippo-regulated coactivators, act; GO convention annotates the TEAD/Sd effector transcription factors to hippo signaling. Accepted as the pathway context of the core TF activity. Supporting Evidence: PMID:21808241 The TEAD family transcription factors were found to be critical partners of YAP and TAZ in the regulation of gene expression |
| GO:0045893 positive regulation of DNA-templated transcription | IMP PMID:20123905 Structural insights into the YAP and TEAD complex. | ACCEPT | Summary: Li et al. 2010: TEAD1 interface mutants abolish YAP-driven reporter activation. Reason: Positive regulation of transcription by TEAD1-YAP; the Pol II-specific child (also annotated) is more precise. Supporting Evidence: PMID:20123905 The ability of Y406A and Y406H to be activated by YAP was abolished in both Gal4-TEAD1 and CTGF reporter assays |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IDA PMID:20123905 Structural insights into the YAP and TEAD complex. | ACCEPT | Summary: Li et al. 2010: TEAD1-YAP complex activates the CTGF promoter reporter. Reason: CTGF is a Pol II gene; TEAD1 with YAP activates it. Supporting Evidence: PMID:20123905 The ability of Y406A and Y406H to be activated by YAP was abolished in both Gal4-TEAD1 and CTGF reporter assays PMID:20123905 The TEAD family of transcription factors binds directly to and mediates YAP-induced gene expression. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | ACCEPT | Summary: Ensembl Compara transfer from mouse. Reason: Consistent with human data. Supporting Evidence: PMID:18579750 We cloned the CTGF promoter into a basic luciferase reporter and found that it was potently activated by YAP but not by YAP-S94A, and the activation was further enhanced by TEAD1 coexpression ( Fig. 3B ). |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:25796446 Aerobic glycolysis tunes YAP/TAZ transcriptional activity. | ACCEPT | Summary: Enzo et al. 2015 (abstract-only in cache): PFK1 promotes TEAD cooperation with YAP/TAZ; TEAD-dependent transcription. Reason: Consistent with TEAD1 activator function; the full text was not available to us, so we defer to the curator. Supporting Evidence: PMID:25796446 binds the YAP/TAZ transcriptional cofactors TEADs and promotes their functional and biochemical cooperation with YAP/TAZ. |
| GO:0048568 embryonic organ development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA on node PTN000931329 (mouse donors) for embryonic organ development. Reason: TEAD1 is described as involved in cardiac development and TEADs act in many developing organs as YAP/TAZ partners, so the term is plausible for vertebrate TEAD1. It is a downstream developmental outcome of a broadly used transcription factor, and an animal-specific recruitment of an older TF activity (no organs exist in unicellular holozoans). Non-core. |
| GO:0065003 protein-containing complex assembly | IMP PMID:20123905 Structural insights into the YAP and TEAD complex. | MARK AS OVER ANNOTATED | Summary: Li et al. 2010: TEAD1 interface mutations prevent YAP-TEAD complex formation. Reason: The evidence shows that TEAD1 binds YAP through interface 3 (a binding activity and complex membership, already captured by TEAD-YAP complex and coactivator binding). Annotating the generic process protein-containing complex assembly for each binding partner adds no information and over-states the evidence for an assembly process. Supporting Evidence: PMID:20123905 coimmunoprecipitation between YAP and TEAD1 mutants showed that TEAD1-Y406H was unable to interact with YAP |
| GO:0140552 TEAD-YAP complex | IDA PMID:20123905 Structural insights into the YAP and TEAD complex. | ACCEPT | Summary: Li et al. 2010: crystal structure of YAP(50-171)-TEAD1(194-411) heterodimer. Reason: Direct structural and biochemical evidence for the TEAD1-YAP complex. Supporting Evidence: PMID:20123905 YAP and TEAD form a heterodimer PMID:20123905 The TEAD family of transcription factors binds directly to and mediates YAP-induced gene expression. |
| GO:0140552 TEAD-YAP complex | IPI PMID:25384421 Targeting Hippo pathway by specific interruption of YAP-TEAD... | ACCEPT | Summary: Zhou et al. 2015 (abstract-only in cache): YAP-like cyclic peptides occupy TEAD interface 3; TEAD1 Y406H abolishes YAP-TEAD interaction in xenografts. Reason: Consistent with TEAD1 membership of the TEAD-YAP complex. Supporting Evidence: PMID:25384421 we report a significant reduction in tumor growth rate in a hepatocellular carcinoma xenograft model after introducing the dominant-negative mutation (Y406H) of TEAD1 to abolish YAP-TEAD interaction. |
| GO:1902895 positive regulation of miRNA transcription | IMP PMID:26045994 miR-222/VGLL4/YAP-TEAD1 regulatory loop promotes proliferati... | KEEP AS NON CORE | Summary: Gastric cancer cells: TEAD1 binds and activates the miR-222 promoter. Reason: A specific target gene in one cancer context; the generic Pol II TF activity covers the molecular role. Retained as a documented but non-core regulatory output. Supporting Evidence: PMID:26045994 As shown, TEAD1 knockdown significantly downregulated miR-222 expression in BGC-823, MGC-803 and HGC-27 GC cell lines ( Figure 4B ), accompanied with VGLL4 upregulation ( Figure 4C ). PMID:26045994 These results factually imply TEAD1 could physically bind to the promoter region of miR-222 to promote its transcription in GC cells. |
| GO:1990837 sequence-specific double-stranded DNA binding | IDA PMID:28473536 Impact of cytosine methylation on DNA binding specificities ... | ACCEPT | Summary: Yin et al. 2017 methyl-SELEX of 542 human TFs. Reason: The cached text does not include the per-TF results, but TEAD1 sequence-specific binding to GGAATG-type motifs is well established; we defer to the curator, who had the supplementary data. Supporting Evidence: file:human/TEAD1/TEAD1-uniprot.txt SPH and GT-IIC 'enhansons' (5'-GTGGAATGT-3') and activates |
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Download this section (compressed HTML)Q: Does Capsaspora coSd bind DNA at GGAATG-type sites and occupy the promoters of the 'core Hippo' genes deregulated in coYki, coHpo and coWts mutants? Current evidence for a premetazoan Sd-Yki transcriptional module is heterologous (Drosophila S2R+ cells and fly eye) plus a coYki TEAD-binding point mutant (PMID:22832104, PMID:38517944).
Q: Do choanoflagellate Sd/TEAD orthologs bind their Yorkie orthologs, given that S. rosetta and M. brevicollis Yorkie lack conserved TEAD-binding helix residues (PMID:38729842)? If not, the TEAD-Yorkie link may have been lost or remodelled in choanoflagellates.
Q: Which of the experiments attributed to TEAD1 are paralog-specific? Key knockdowns in PMID:18579750 and PMID:19324877 used a shRNA hitting TEAD1, TEAD3 and TEAD4 together; TEAD1-specific evidence rests on ChIP, reporter, dominant-negative and structural data.
Q: Is the VGLL4/Tgi-TEAD default-repression mode, whose components are both present in Capsaspora (PMID:38729842), functional there, and should human TEAD1 carry a repressor-side term in addition to activator activity?
Experiment: CUT&RUN or ChIP-seq of tagged coSd in wild-type, coYki-/- and coWts-/- Capsaspora cells, with motif analysis for GGAATG-type sites, combined with coSd knockout or a coSd YAP-binding-interface (Y406-equivalent) mutant to test whether it phenocopies coYki loss.
Hypothesis: Capsaspora coSd is the DNA-binding partner that mediates coYki transcriptional output in Capsaspora.
Type: genomics and genetics
Experiment: Single-paralog CRISPR knockouts and rescue with TEAD1 versus TEAD4 cDNAs in MCF10A cells, followed by RNA-seq and YAP ChIP-seq, to separate TEAD1-specific from redundant TEAD functions.
Hypothesis: Human TEAD1 has paralog-specific target genes not shared with TEAD2-4.
Type: genetic perturbation and genomics
Experiment: Cross-species complementation of sd mutant fly tissue and of coSd-deficient Capsaspora with human TEAD1, reading out Hippo-responsive reporters and target genes.
Hypothesis: Human TEAD1 can complement loss of the Capsaspora or Drosophila Sd ortholog for Yorkie-dependent transcription.
Type: complementation
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