DAF-4 is the only type II TGF-beta-family serine/threonine receptor kinase in C. elegans, an ortholog of BMPR2. It is a single-pass transmembrane protein that serves two TGF-beta-like pathways. With the type I receptor DAF-1 it receives the TGF-beta-like ligand DAF-7, which is secreted by ASI sensory neurons. This signal prevents dauer arrest and also affects lifespan, feeding quiescence and other behaviors. With the type I receptor SMA-6 it receives the BMP-like ligand DBL-1, and this Sma/Mab signaling controls body size, male tail patterning, M-lineage fate and epidermal antimicrobial peptide expression. DAF-4 binds BMP-2 and BMP-4 when expressed in COS cells. It is found at the basolateral plasma membrane and recycles through an ARF-6-dependent, retromer-independent route, and its surface levels depend on the tetraspanins TSP-12 and TSP-14. Alternative polyadenylation produces a truncated, ligand-binding-domain-only form that antagonizes DAF-4 signaling.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0002119 nematode larval development | IMP PMID:15254038 Alternative polyadenylation results in a truncated daf-4 BMP... | KEEP AS NON CORE | Summary: daf-4 promotes non-dauer larval development [PMID:15254038]. Reason: Broad parent of the dauer decision. Accurate, but the dauer-specific terms say more. Supporting Evidence: PMID:15254038 The DAF-4 receptor kinase, which promotes larval development, is encoded by a 2.9 kb mRNA |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Protein kinase activity (InterPro). Reason: Correct but general. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0004675 transmembrane receptor protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Transmembrane receptor Ser/Thr kinase activity (InterPro/EC). Reason: As above. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0004675 transmembrane receptor protein serine/threonine kinase activity | ISS PMID:8413626 The daf-4 gene encodes a bone morphogenetic protein receptor... | ACCEPT | Summary: Transmembrane receptor Ser/Thr kinase activity [PMID:8413626]. Reason: Core activity: DAF-4 is the only type II receptor kinase in C. elegans, shared by the DAF-7 and DBL-1 pathways. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases file:worm/daf-4/daf-4-deep-research-falcon.md Worm-specific literature independently identifies DAF-4 as the **sole type-II TGF-Ξ²-family receptor** shared by the DAF-7/dauer and DBL-1/BMP (Sma/Mab) pathways |
| GO:0005024 transforming growth factor beta receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: IBA for TGF-beta receptor activity. Reason: DAF-4 is the type II receptor for both the TGF-beta-like DAF-7 (with DAF-1) and the BMP-like DBL-1 (with SMA-6) [PMID:9847239]. TGF-beta receptor activity fits the DAF-7 role. BMP receptor activity (GO:0098821) fits the DBL-1 role and the BMP-2/4 binding. Supporting Evidence: PMID:9847239 In C. elegans, the TGFbeta-like type II receptor daf-4 is required for two distinct signaling pathways PMID:9847239 In association with the type I receptor daf-1, it functions in the dauer pathway |
| GO:0005515 protein binding | IPI PMID:14992718 Systematic interactome mapping and genetic perturbation anal... | REMOVE | Summary: Yeast two-hybrid interactions from a TGF-beta interactome map [PMID:14992718]. Reason: Generic protein binding is uninformative. The partners include a mitochondrial ATP synthase subunit (ATP-2), whose relevance is unclear. Supporting Evidence: PMID:14992718 Yeast two-hybrid (Y2H) screens starting with known DAF-7/TGF-beta pathway components defined a network of 71 interactions among 59 proteins |
| GO:0005515 protein binding | IPI PMID:14992718 Systematic interactome mapping and genetic perturbation anal... | REMOVE | Summary: Yeast two-hybrid interactions from a TGF-beta interactome map [PMID:14992718]. Reason: Generic protein binding is uninformative. The partners include a mitochondrial ATP synthase subunit (ATP-2), whose relevance is unclear. Supporting Evidence: PMID:14992718 Yeast two-hybrid (Y2H) screens starting with known DAF-7/TGF-beta pathway components defined a network of 71 interactions among 59 proteins |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding by the kinase domain. Reason: Consistent with a type II receptor Ser/Thr kinase. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0005886 plasma membrane | EXP PMID:21408209 A bow-tie genetic architecture for morphogenesis suggested b... | ACCEPT | Summary: DAF-4::YFP at plasma membranes of tail tip hypodermal cells [PMID:21408209]. Reason: Direct localization. Supporting Evidence: PMID:21408209 Consistent with this hypothesis, DAF-4::YFP fusion protein localizes to the plasma membranes of hyp8β11 during tail tip morphogenesis (Figure 2D) |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane. Reason: DAF-4::GFP is at the basolateral plasma membrane [PMID:24550286]. Supporting Evidence: PMID:24550286 We found that both SMA-6::GFP and DAF-4::GFP, visualized in otherwise wild-type intact living animals, localized to the basolateral plasma membrane, where they are in position to receive signaling molecules secreted by neurons |
| GO:0005886 plasma membrane | IDA PMID:9334330 The DAF-3 Smad protein antagonizes TGF-beta-related receptor... | ACCEPT | Summary: DAF-4/GFP is membrane-localized [PMID:9334330]. Reason: Direct localization. Supporting Evidence: PMID:9334330 The pattern of DAF-4/GFP expression is similar to that of DAF-3/GFP, except that DAF-4/GFP is localized to membranes, consistent with its role as a receptor |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane (UniProt subcellular location). Reason: As above; cell-surface DAF-4 levels depend on tetraspanin-mediated recycling [PMID:31988138]. Supporting Evidence: PMID:24550286 We found that both SMA-6::GFP and DAF-4::GFP, visualized in otherwise wild-type intact living animals, localized to the basolateral plasma membrane, where they are in position to receive signaling molecules secreted by neurons PMID:31988138 Animals lacking both TSP-12 and TSP-14 exhibit reduced cell-surface levels of the BMP type II receptor DAF-4/BMPRII |
| GO:0007178 cell surface receptor protein serine/threonine kinase signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Cell surface receptor protein Ser/Thr kinase signaling pathway. Reason: Correct parent term. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0008340 determination of adult lifespan | IMP PMID:17900898 The C. elegans TGF-beta Dauer pathway regulates longevity vi... | KEEP AS NON CORE | Summary: daf-4 mutants are long-lived [PMID:17900898]. Reason: DAF-7 pathway mutants extend lifespan through insulin signaling and DAF-16. This is an indirect organismal output. Supporting Evidence: PMID:17900898 we observed a significant increase in lifespan in daf-7, daf-1, daf-4, daf-8, and daf-14 mutants relative to wild type worms under the same conditions |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane. Reason: Correct but general. Supporting Evidence: PMID:9334330 The pattern of DAF-4/GFP expression is similar to that of DAF-3/GFP, except that DAF-4/GFP is localized to membranes, consistent with its role as a receptor |
| GO:0018991 egg-laying behavior | IMP PMID:10625546 Targets of TGF-beta signaling in Caenorhabditis elegans daue... | KEEP AS NON CORE | Summary: Egg-laying defects in daf-4 mutants [PMID:10625546]. Reason: Pleiotropic phenotype of the DAF-7 pathway, which acts through the nervous system [PMID:10625546]. Supporting Evidence: PMID:10625546 indicate cell-nonautonomous function of daf-4, arguing against direct DAF-7 signaling to tissues throughout the animal |
| GO:0022604 regulation of cell morphogenesis | IMP PMID:24690231 CEH-28 activates dbl-1 expression and TGF-Ξ² signaling in the... | KEEP AS NON CORE | Summary: daf-4 mutants have defective g1 gland cell morphology [PMID:24690231]. Reason: Non-core, R-Smad-independent output of DBL-1 signaling. Supporting Evidence: PMID:24690231 Identical gland cell defects are observed in sma-6 and daf-4 mutants defective in the receptor for DBL-1 |
| GO:0030509 BMP signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: BMP signaling pathway. Reason: Core process: DAF-4 is the type II receptor for DBL-1 [PMID:9847239]. Supporting Evidence: PMID:9847239 In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1 |
| GO:0030509 BMP signaling pathway | IC PMID:8413626 The daf-4 gene encodes a bone morphogenetic protein receptor... | ACCEPT | Summary: BMP signaling pathway, inferred from BMP binding [PMID:8413626]. Reason: Consistent with the DBL-1 pathway role. Supporting Evidence: PMID:8413626 When expressed in monkey COS cells, the daf-4 receptor binds human BMP-2 and BMP-4 |
| GO:0030513 positive regulation of BMP signaling pathway | IMP PMID:15254038 Alternative polyadenylation results in a truncated daf-4 BMP... | MARK AS OVER ANNOTATED | Summary: Based on the alternative daf-4 transcript study [PMID:15254038]. Reason: Full-length DAF-4 is itself the type II receptor of the pathway. Its participation is captured by the BMP signaling pathway annotations, and calling it a positive regulator of its own pathway overstates the case. The cited work concerns the DAF-7/dauer pathway. Supporting Evidence: PMID:15254038 The DAF-4 receptor kinase, which promotes larval development, is encoded by a 2.9 kb mRNA |
| GO:0030514 negative regulation of BMP signaling pathway | IMP PMID:15254038 Alternative polyadenylation results in a truncated daf-4 BMP... | KEEP AS NON CORE | Summary: A truncated, ligand-binding-domain-only DAF-4 from alternative polyadenylation antagonizes DAF-4 signaling [PMID:15254038]. Reason: Supported for the short isoform (2.0 kb transcript) as a decoy receptor. This is an isoform-specific regulatory role, separate from the core receptor kinase function of the full-length protein. Supporting Evidence: PMID:15254038 These data suggest that a polypeptide encoded by the 2.0 kb transcript can function as an antagonist of full-length DAF-4 signaling |
| GO:0030536 larval feeding behavior | IMP PMID:18316030 Insulin, cGMP, and TGF-beta signals regulate food intake and... | KEEP AS NON CORE | Summary: TGF-beta signaling regulates satiety quiescence and food intake [PMID:18316030]. Reason: A real neuronal output of DAF-7 signaling, but pleiotropic and non-core for the receptor. Supporting Evidence: PMID:18316030 This hypothesized satiety-induced quiescence is regulated by peptide signals such as insulin and TGF-beta |
| GO:0036122 BMP binding | IPI PMID:8413626 The daf-4 gene encodes a bone morphogenetic protein receptor... | ACCEPT | Summary: DAF-4 expressed in COS cells binds human BMP-2 and BMP-4 [PMID:8413626]. Reason: Directly supported ligand-binding activity. It is consistent with DAF-4 being a BMPR2-like type II receptor for DBL-1. Supporting Evidence: PMID:8413626 When expressed in monkey COS cells, the daf-4 receptor binds human BMP-2 and BMP-4 |
| GO:0036122 BMP binding | IPI PMID:8413626 The daf-4 gene encodes a bone morphogenetic protein receptor... | ACCEPT | Summary: DAF-4 expressed in COS cells binds human BMP-2 and BMP-4 [PMID:8413626]. Reason: Directly supported ligand-binding activity. It is consistent with DAF-4 being a BMPR2-like type II receptor for DBL-1. Supporting Evidence: PMID:8413626 When expressed in monkey COS cells, the daf-4 receptor binds human BMP-2 and BMP-4 |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:10625546 Targets of TGF-beta signaling in Caenorhabditis elegans daue... | ACCEPT | Summary: daf-4 mutants are small [PMID:12717735, PMID:10625546]. Reason: Core output of DBL-1/Sma/Mab signaling through DAF-4 and SMA-6. Supporting Evidence: PMID:12717735 DBL-1 ligand, DAF-4 type II receptor, SMA-6 type I receptor, and SMA-2, SMA-3, and SMA-4 Smads PMID:9847239 In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1 |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:12717735 Genetic screen for small body size mutants in C. elegans rev... | ACCEPT | Summary: daf-4 mutants are small [PMID:12717735, PMID:10625546]. Reason: Core output of DBL-1/Sma/Mab signaling through DAF-4 and SMA-6. Supporting Evidence: PMID:12717735 DBL-1 ligand, DAF-4 type II receptor, SMA-6 type I receptor, and SMA-2, SMA-3, and SMA-4 Smads PMID:9847239 In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1 |
| GO:0040024 dauer larval development | IGI PMID:10887089 A Caenorhabditis elegans type I TGF beta receptor can functi... | ACCEPT | Summary: daf-1/daf-7 genetic interactions in dauer development [PMID:10887089]. Reason: As above. Supporting Evidence: PMID:10887089 A daf-1 mutation enhances dauer formation in a daf-4 null background |
| GO:0040024 dauer larval development | IGI PMID:10887089 A Caenorhabditis elegans type I TGF beta receptor can functi... | ACCEPT | Summary: daf-1/daf-7 genetic interactions in dauer development [PMID:10887089]. Reason: As above. Supporting Evidence: PMID:10887089 A daf-1 mutation enhances dauer formation in a daf-4 null background |
| GO:0040024 dauer larval development | IMP PMID:10625546 Targets of TGF-beta signaling in Caenorhabditis elegans daue... | ACCEPT | Summary: daf-4 mutants are dauer-constitutive [PMID:8413626, PMID:10887089, PMID:10625546]. Reason: A hallmark phenotype; DAF-4 acts with DAF-1 in DAF-7 signaling that prevents dauer development. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases PMID:10887089 The daf-4 gene encodes a type II bone morphogenetic protein receptor in Caenorhabditis elegans that regulates dauer larva formation, body size and male tail patterning |
| GO:0040024 dauer larval development | IMP PMID:10887089 A Caenorhabditis elegans type I TGF beta receptor can functi... | ACCEPT | Summary: daf-4 mutants are dauer-constitutive [PMID:8413626, PMID:10887089, PMID:10625546]. Reason: A hallmark phenotype; DAF-4 acts with DAF-1 in DAF-7 signaling that prevents dauer development. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases PMID:10887089 The daf-4 gene encodes a type II bone morphogenetic protein receptor in Caenorhabditis elegans that regulates dauer larva formation, body size and male tail patterning |
| GO:0040024 dauer larval development | IMP PMID:12717735 Genetic screen for small body size mutants in C. elegans rev... | ACCEPT | Summary: daf-4 mutants are dauer-constitutive [PMID:8413626, PMID:10887089, PMID:10625546]. Reason: A hallmark phenotype; DAF-4 acts with DAF-1 in DAF-7 signaling that prevents dauer development. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases PMID:10887089 The daf-4 gene encodes a type II bone morphogenetic protein receptor in Caenorhabditis elegans that regulates dauer larva formation, body size and male tail patterning |
| GO:0040024 dauer larval development | IMP PMID:15254038 Alternative polyadenylation results in a truncated daf-4 BMP... | ACCEPT | Summary: daf-4 mutants are dauer-constitutive [PMID:8413626, PMID:10887089, PMID:10625546]. Reason: A hallmark phenotype; DAF-4 acts with DAF-1 in DAF-7 signaling that prevents dauer development. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases PMID:10887089 The daf-4 gene encodes a type II bone morphogenetic protein receptor in Caenorhabditis elegans that regulates dauer larva formation, body size and male tail patterning |
| GO:0040024 dauer larval development | IMP PMID:8413626 The daf-4 gene encodes a bone morphogenetic protein receptor... | ACCEPT | Summary: daf-4 mutants are dauer-constitutive [PMID:8413626, PMID:10887089, PMID:10625546]. Reason: A hallmark phenotype; DAF-4 acts with DAF-1 in DAF-7 signaling that prevents dauer development. Supporting Evidence: PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases PMID:10887089 The daf-4 gene encodes a type II bone morphogenetic protein receptor in Caenorhabditis elegans that regulates dauer larva formation, body size and male tail patterning |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | KEEP AS NON CORE | Summary: daf-4 suppresses the sma-9 M-lineage phenotype [PMID:25978409]. Reason: Downstream developmental context of Sma/Mab signaling. Supporting Evidence: PMID:25978409 As shown in Table 2, our suppressor screen successfully and specifically identified mutations in all core members and known modulators of the Sma/Mab pathway |
| GO:0043053 dauer entry | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: daf-4 is a dauer-constitutive gene in the epistasis pathway for dauer formation [PMID:1732156]. Reason: DAF-4 controls the dauer entry decision as the DAF-7 type II receptor. Its activity inhibits entry, so negative regulation of dauer larval development (also annotated) is the more precise description. Supporting Evidence: PMID:1732156 Many of the genes could be interpreted to lie in a simple linear epistasis pathway PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0043053 dauer entry | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: daf-4 is a dauer-constitutive gene in the epistasis pathway for dauer formation [PMID:1732156]. Reason: DAF-4 controls the dauer entry decision as the DAF-7 type II receptor. Its activity inhibits entry, so negative regulation of dauer larval development (also annotated) is the more precise description. Supporting Evidence: PMID:1732156 Many of the genes could be interpreted to lie in a simple linear epistasis pathway PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0043053 dauer entry | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: daf-4 is a dauer-constitutive gene in the epistasis pathway for dauer formation [PMID:1732156]. Reason: DAF-4 controls the dauer entry decision as the DAF-7 type II receptor. Its activity inhibits entry, so negative regulation of dauer larval development (also annotated) is the more precise description. Supporting Evidence: PMID:1732156 Many of the genes could be interpreted to lie in a simple linear epistasis pathway PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0043053 dauer entry | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: daf-4 is a dauer-constitutive gene in the epistasis pathway for dauer formation [PMID:1732156]. Reason: DAF-4 controls the dauer entry decision as the DAF-7 type II receptor. Its activity inhibits entry, so negative regulation of dauer larval development (also annotated) is the more precise description. Supporting Evidence: PMID:1732156 Many of the genes could be interpreted to lie in a simple linear epistasis pathway PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0043053 dauer entry | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: daf-4 is a dauer-constitutive gene in the epistasis pathway for dauer formation [PMID:1732156]. Reason: DAF-4 controls the dauer entry decision as the DAF-7 type II receptor. Its activity inhibits entry, so negative regulation of dauer larval development (also annotated) is the more precise description. Supporting Evidence: PMID:1732156 Many of the genes could be interpreted to lie in a simple linear epistasis pathway PMID:8413626 The daf-4 gene, which acts to inhibit dauer larva formation and promote growth, encodes a receptor protein kinase similar to the daf-1, activin and TGF-beta receptor serine/threonine kinases |
| GO:0043235 signaling receptor complex | IBA GO_REF:0000033 | MODIFY | Summary: Signaling receptor complex. Reason: DAF-4 forms receptor complexes with DAF-1 (DAF-7 pathway) and SMA-6 (DBL-1 pathway) [PMID:9847239]. The term is correct but general. BMP receptor complex is the more informative term for the DAF-4/SMA-6 complex, a homo- or heterodimer of type I and type II BMP receptor subunits. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000583675 Β· PTN000583675 SUPPORTS TRANSFER TGF-beta receptor family node; the receptor-complex assertion transfers correctly, but a BMP-specific complex term is more informative for DAF-4. Proposed replacements: BMP receptor complex Supporting Evidence: PMID:9847239 In association with the type I receptor daf-1, it functions in the dauer pathway PMID:9847239 In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1 |
| GO:0045087 innate immune response | IMP PMID:19198592 Neuroimmune regulation of antimicrobial peptide expression b... | KEEP AS NON CORE | Summary: DBL-1 pathway signaling induces epidermal antifungal peptides [PMID:19198592]. Reason: A non-core output of DBL-1 signaling received through DAF-4. Supporting Evidence: PMID:19198592 neuronal expression of the transforming growth factor-beta homolog DBL-1 promoted cnc-2 expression in the epidermis in a dose-dependent paracrine way |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:19198592 Neuroimmune regulation of antimicrobial peptide expression b... | MARK AS OVER ANNOTATED | Summary: Target-gene expression depends on DAF-4 pathway activity [PMID:19198592, PMID:9834189]. Reason: DAF-4 is a membrane receptor kinase. Transcription is regulated by the downstream Smads (and DAF-3/DAF-5 de-repression), so this is an indirect effect. Supporting Evidence: PMID:9834189 daf-3's repressor activity is negatively regulated by TGFbeta-like signaling PMID:19198592 neuronal expression of the transforming growth factor-beta homolog DBL-1 promoted cnc-2 expression in the epidermis in a dose-dependent paracrine way |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:9834189 The DAF-3 Smad binds DNA and represses gene expression in th... | MARK AS OVER ANNOTATED | Summary: Target-gene expression depends on DAF-4 pathway activity [PMID:19198592, PMID:9834189]. Reason: DAF-4 is a membrane receptor kinase. Transcription is regulated by the downstream Smads (and DAF-3/DAF-5 de-repression), so this is an indirect effect. Supporting Evidence: PMID:9834189 daf-3's repressor activity is negatively regulated by TGFbeta-like signaling PMID:19198592 neuronal expression of the transforming growth factor-beta homolog DBL-1 promoted cnc-2 expression in the epidermis in a dose-dependent paracrine way |
| GO:0050832 defense response to fungus | IMP PMID:19198592 Neuroimmune regulation of antimicrobial peptide expression b... | KEEP AS NON CORE | Summary: Defense response to fungus [PMID:19198592]. Reason: As above. Supporting Evidence: PMID:19198592 neuronal expression of the transforming growth factor-beta homolog DBL-1 promoted cnc-2 expression in the epidermis in a dose-dependent paracrine way |
| GO:0061065 regulation of dauer larval development | IGI PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: Regulation of dauer larval development (epistasis) [PMID:1732156]. Reason: As above. Supporting Evidence: PMID:1732156 Many of the genes could be interpreted to lie in a simple linear epistasis pathway |
| GO:0061065 regulation of dauer larval development | IMP PMID:1732156 Genetic analysis of chemosensory control of dauer formation ... | ACCEPT | Summary: Regulation of dauer larval development [PMID:1732156]. Reason: Core DAF-7 pathway role. Supporting Evidence: PMID:1732156 Many of the genes could be interpreted to lie in a simple linear epistasis pathway |
| GO:0061067 negative regulation of dauer larval development | IMP PMID:6583682 A pheromone-induced developmental switch in Caenorhabditis e... | ACCEPT | Summary: daf-4 mutations are dauer-constitutive [PMID:6583682]. Reason: Core DAF-7 pathway output; DAF-4 signaling prevents dauer development. Supporting Evidence: PMID:6583682 All known mutations in daf-4 (eight alleles) and daf-7 (five alleles) produce a ts dauer-constitutive phenotype |
| GO:0071363 cellular response to growth factor stimulus | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular response to growth factor stimulus. Reason: Broad but correct. Supporting Evidence: PMID:8413626 When expressed in monkey COS cells, the daf-4 receptor binds human BMP-2 and BMP-4 |
| GO:0110039 positive regulation of nematode male tail tip morphogenesis | IMP PMID:21408209 A bow-tie genetic architecture for morphogenesis suggested b... | ACCEPT | Summary: DAF-4 is required for male tail tip morphogenesis [PMID:21408209]. Reason: Supported by RNAi, mutant phenotypes and DAF-4::YFP at tail tip cell membranes. Male tail patterning is a hallmark output of the Sma/Mab pathway. Supporting Evidence: PMID:21408209 Taken together, the RNAi results, loss-of-function mutant phenotypes and expression patterns of sma-3 and daf-4 suggest that TGF-Ξ² signaling is required during tail tip morphogenesis |
| GO:1903998 regulation of eating behavior | IMP PMID:18316030 Insulin, cGMP, and TGF-beta signals regulate food intake and... | KEEP AS NON CORE | Summary: Regulation of eating behavior (satiety quiescence) [PMID:18316030]. Reason: As above. Supporting Evidence: PMID:18316030 This hypothesized satiety-induced quiescence is regulated by peptide signals such as insulin and TGF-beta |
| GO:0098821 BMP receptor activity | IC PMID:8413626 The daf-4 gene encodes a bone morphogenetic protein receptor... | NEW | Summary: DAF-4 binds BMP-2/BMP-4 and is the type II receptor kinase for the BMP-like ligand DBL-1 [PMID:8413626, PMID:9847239]. Reason: BMP receptor activity (a child of transmembrane receptor Ser/Thr kinase activity) follows from the direct BMP binding and the receptor kinase architecture together with the DBL-1 pathway genetics. It is more informative than the existing generic receptor-kinase terms. Supporting Evidence: PMID:8413626 When expressed in monkey COS cells, the daf-4 receptor binds human BMP-2 and BMP-4 PMID:9847239 In addition, it is also required for body size determination and male tail patterning, roles which do not require daf-1 |
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Download this section (compressed HTML)Q: Does DAF-4 directly bind DAF-7 and DBL-1 with distinct affinities, and how is partner choice between DAF-1 and SMA-6 achieved in cells that express all three receptors?
Q: Is the truncated, ligand-binding-domain-only DAF-4 secreted, and does it also antagonize DBL-1 signaling?
Experiment: Reconstitute DAF-4/SMA-6 and DAF-4/DAF-1 receptor complexes in cells and measure ligand-dependent GS-domain phosphorylation of each type I receptor by DAF-4.
Hypothesis: DAF-4 kinase activity phosphorylates SMA-6 and DAF-1 in a ligand-specific way, and DAF-1 retains partial DAF-4-independent signaling.
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