SMA-6 is the type I serine/threonine receptor kinase of the DBL-1 BMP-like Sma/Mab pathway in C. elegans. It is a single-pass transmembrane protein with an extracellular ligand-binding domain, a GS domain and a cytoplasmic kinase domain. Together with the shared type II receptor DAF-4, it receives the neuronally secreted ligand DBL-1 and phosphorylates the R-Smads SMA-2 and SMA-3, which act with the co-Smad SMA-4 to regulate transcription. SMA-6 is expressed mainly in the hypodermis, pharynx and intestine and sits at the basolateral plasma membrane. Hypodermal expression is necessary and sufficient for normal body length. Receptor levels and signaling depend on AP-2-mediated endocytosis and retromer-dependent recycling, and SMA-10/LRIG, tetraspanins and DRAG-1/UNC-40 promote signaling at the receptor level. sma-6 mutants are small and males have abnormal tails, but they are not dauer-constitutive. Pathway outputs also include antimicrobial peptide expression, M-lineage patterning and pharyngeal gland morphology. Sma/Mab signaling also limits reproductive span, and sma-6 mutants, like other pathway mutants, reproduce for substantially longer while maintaining oocyte and germline quality.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | ACCEPT | Summary: Protein kinase activity (InterPro). Reason: Correct but general; SMA-6 is a transmembrane receptor Ser/Thr kinase. Supporting Evidence: PMID:9847239 We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6 |
| GO:0004674 protein serine/threonine kinase activity | ISS PMID:9847239 Specificity of TGFbeta signaling is conferred by distinct ty... | ACCEPT | Summary: Protein Ser/Thr kinase activity by similarity to type I receptors. Reason: Correct parent of the receptor kinase activity. Supporting Evidence: PMID:9847239 We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6 |
| GO:0004675 transmembrane receptor protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Transmembrane receptor protein Ser/Thr kinase activity. Reason: SMA-6 is the type I receptor kinase of the DBL-1 pathway [PMID:9847239]. The more specific BMP receptor activity (GO:0098821) is used in core_functions. Supporting Evidence: PMID:9847239 We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6 file:worm/sma-6/sma-6-deep-research-falcon.md Independent worm literature consistently identifies SMA-6 as the **type I receptor for the DBL-1/BMP-like Sma/Mab signaling pathway** |
| GO:0005515 protein binding | IPI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | REMOVE | Summary: Split-ubiquitin/yeast interactions of SMA-6 with tetraspanins TSP-12 and TSP-14 [PMID:25978409]. Reason: Generic protein binding is uninformative. The interaction may well be real and relevant to receptor trafficking, but it does not specify a molecular function. Supporting Evidence: PMID:25978409 In addition, SMA-6 can associate with both TSP-12 and TSP-14, but not TSP-21 |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding by the protein kinase domain. Reason: Consistent with the active Ser/Thr kinase domain of a type I receptor. Supporting Evidence: file:worm/sma-6/sma-6-deep-research-falcon.md Independent worm literature consistently identifies SMA-6 as the **type I receptor for the DBL-1/BMP-like Sma/Mab signaling pathway** |
| GO:0005634 nucleus | IEA GO_REF:0000108 | REMOVE | Summary: Nucleus inferred automatically from the 'maintenance of protein location in nucleus' annotation. Reason: SMA-6 is a single-pass transmembrane receptor kinase at the plasma membrane and in endosomes [PMID:24550286]. The nuclear-retention phenotype concerns its downstream substrate SMA-3, not SMA-6 itself [PMID:12397107]. A nuclear location for SMA-6 is not supported. Supporting Evidence: PMID:12397107 we find that SMA-3::GFP is nuclear localized in all of these tissues, and that nuclear localization is enhanced by SMA-6 activity 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 | IBA GO_REF:0000033 | ACCEPT | Summary: SMA-6 is at the plasma membrane. Reason: SMA-6::GFP is at the basolateral plasma membrane of intestinal cells and cycles through endosomes [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 | ISS PMID:9847239 Specificity of TGFbeta signaling is conferred by distinct ty... | ACCEPT | Summary: Plasma membrane location by similarity to type I receptors. Reason: Confirmed experimentally [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: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 of BMP signaling pathway. Supporting Evidence: PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0007399 nervous system development | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: IBA for nervous system development. Reason: SMA-6 is expressed and needed mainly in hypodermis, pharynx and intestine, and hypodermal expression is enough for body size [PMID:11784045]. No nervous-system-development role has been shown for SMA-6; the term reflects functions of vertebrate and fly type I receptors. Propagation Review Root cause: PROPAGATION BAD Failure modes: CONTEXT OR TISSUE MISMATCH Sources checked: PANTHER:PTN002758232 · PTN002758232 SUPPORTS SOURCE BUT NOT TARGET Type I receptor node; neural-development roles come from vertebrate/fly members. SMA-6 acts in hypodermis, intestine and pharynx. Supporting Evidence: PMID:11784045 hypodermal expression of SMA-6 is necessary and sufficient for the growth and maintenance of body length |
| GO:0016020 membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Membrane (single-pass type I receptor). Reason: Correct but general; plasma membrane is more precise [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:0016361 activin receptor activity, type I | IBA GO_REF:0000033 | MODIFY | Summary: IBA asserting activin type I receptor activity. Reason: SMA-6 is a type I receptor kinase, so the receptor-kinase part of the IBA is sound. Its ligand is the BMP-like DBL-1 [PMID:9847239, PMID:12051826], and C. elegans has no activin. BMP receptor activity is the correct ligand-specific term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000583887 · PTN000583887 SUPPORTS SOURCE BUT NOT TARGET Activin/TGF-beta type I receptor node (Babo/ALK4/5/7-like). SMA-6 signals for the BMP-like ligand DBL-1, and C. elegans has no activin ligand, so the activin-specific part of the term does not transfer. Proposed replacements: BMP receptor activity Supporting Evidence: PMID:9847239 We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6 PMID:12051826 The ligand of the pathway, dbl-1, transmits its signal through two receptor serine threonine kinases, daf-4 and sma-6 |
| GO:0022604 regulation of cell morphogenesis | IMP PMID:24690231 CEH-28 activates dbl-1 expression and TGF-β signaling in the... | KEEP AS NON CORE | Summary: sma-6 mutants have defective g1 pharyngeal gland cell morphology [PMID:24690231]. Reason: Supported genetic result for a receptor of M4-neuron-derived DBL-1. It is a non-core, R-Smad-independent output. 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:0030155 regulation of cell adhesion | IMP PMID:12679110 The roles of an ephrin and a semaphorin in patterning cell-c... | KEEP AS NON CORE | Summary: Ectopic ray cell contacts in sma-6 mutants [PMID:12679110]. Reason: This reflects the role of TGF-beta signaling in specifying ray identity, which in turn shapes adherens-junction contacts among ray cells. SMA-6 acts indirectly. Supporting Evidence: PMID:12679110 Ectopic contacts also occur in mutants in regulatory genes that specify ray morphological identity |
| GO:0030509 BMP signaling pathway | ISS PMID:9847239 Specificity of TGFbeta signaling is conferred by distinct ty... | ACCEPT | Summary: SMA-6 acts in the DBL-1 BMP-like Sma/Mab pathway [PMID:9847239]. Reason: Core process. Supporting Evidence: PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway file:worm/sma-6/sma-6-deep-research-falcon.md Independent worm literature consistently identifies SMA-6 as the **type I receptor for the DBL-1/BMP-like Sma/Mab signaling pathway** |
| GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway | IGI PMID:28068334 Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with ... | MODIFY | Summary: Genetic interaction of sma-6 with sup-17 (ADAM10) in BMP signaling [PMID:28068334]. Reason: SMA-6 is the receptor that carries out the signaling, not a regulator of it. The genetics place sup-17 in the BMP pathway with sma-6, so SMA-6 itself belongs in BMP signaling pathway. Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:28068334 We found that sup-17(n1258); dbl-1(wk70), sup-17(n1258); sma-6(jj1) and sup-17(n1258); sma-3(jj3) double mutants were as small as the corresponding dbl-1(wk70), sma-6(jj1) or sma-3(jj3) single mutants, respectively (Fig 3F) |
| GO:0032924 activin receptor signaling pathway | IBA GO_REF:0000033 | MODIFY | Summary: IBA asserting activin receptor signaling pathway. Reason: SMA-6 transduces DBL-1 (BMP-like) signals through the Smads SMA-2/3/4 [PMID:9847239]. BMP signaling pathway is the right term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000583887 · PTN000583887 SUPPORTS SOURCE BUT NOT TARGET Activin/TGF-beta type I receptor node (Babo/ALK4/5/7-like). SMA-6 signals for the BMP-like ligand DBL-1, and C. elegans has no activin ligand, so the activin-specific part of the term does not transfer. Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0036122 BMP binding | IDA PMID:17240342 Glypican LON-2 is a conserved negative regulator of BMP-like... | ACCEPT | Summary: BMP binding [PMID:17240342]. Reason: The cached text is abstract-only and does not describe the SMA-6 assay itself. Ligand binding is expected for a BMP type I receptor, so the call is deferred to the curator. Supporting Evidence: PMID:17240342 We show that the LON-2 protein binds BMP2 in vitro |
| GO:0040018 positive regulation of multicellular organism growth | IGI PMID:12051826 lon-1 regulates Caenorhabditis elegans body size downstream ... | ACCEPT | Summary: Genetic interactions of sma-6 with lon-1 and kin-29 in body size [PMID:12051826, PMID:15840165]. Reason: Consistent with SMA-6's core role in DBL-1-driven growth. Supporting Evidence: PMID:12051826 we show that lon-1 lies downstream of the Sma/Mab signaling cascade and demonstrate that lon-1 mRNA levels are up-regulated in sma-6-null mutant animals PMID:15840165 Additionally, using a weak allele of sma-6, we generated a sma-6(e1482)unc4(e120); kin-29(wk61) double mutant and examined its body size |
| GO:0040018 positive regulation of multicellular organism growth | IGI PMID:15840165 C. elegans serine-threonine kinase KIN-29 modulates TGFbeta ... | ACCEPT | Summary: Genetic interactions of sma-6 with lon-1 and kin-29 in body size [PMID:12051826, PMID:15840165]. Reason: Consistent with SMA-6's core role in DBL-1-driven growth. Supporting Evidence: PMID:12051826 we show that lon-1 lies downstream of the Sma/Mab signaling cascade and demonstrate that lon-1 mRNA levels are up-regulated in sma-6-null mutant animals PMID:15840165 Additionally, using a weak allele of sma-6, we generated a sma-6(e1482)unc4(e120); kin-29(wk61) double mutant and examined its body size |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:11784045 Hypodermal expression of Caenorhabditis elegans TGF-beta typ... | ACCEPT | Summary: sma-6 mutants are small [PMID:9847239, PMID:11784045]. Reason: Core organismal output: hypodermal SMA-6 is necessary and sufficient for body length. Supporting Evidence: PMID:11784045 hypodermal expression of SMA-6 is necessary and sufficient for the growth and maintenance of body length PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:12051826 lon-1 regulates Caenorhabditis elegans body size downstream ... | ACCEPT | Summary: sma-6 mutants are small [PMID:9847239, PMID:11784045]. Reason: Core organismal output: hypodermal SMA-6 is necessary and sufficient for body length. Supporting Evidence: PMID:11784045 hypodermal expression of SMA-6 is necessary and sufficient for the growth and maintenance of body length PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:12571101 Cyclic GMP-dependent protein kinase EGL-4 controls body size... | ACCEPT | Summary: sma-6 mutants are small [PMID:9847239, PMID:11784045]. Reason: Core organismal output: hypodermal SMA-6 is necessary and sufficient for body length. Supporting Evidence: PMID:11784045 hypodermal expression of SMA-6 is necessary and sufficient for the growth and maintenance of body length PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:12717735 Genetic screen for small body size mutants in C. elegans rev... | ACCEPT | Summary: sma-6 mutants are small [PMID:9847239, PMID:11784045]. Reason: Core organismal output: hypodermal SMA-6 is necessary and sufficient for body length. Supporting Evidence: PMID:11784045 hypodermal expression of SMA-6 is necessary and sufficient for the growth and maintenance of body length PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:15840165 C. elegans serine-threonine kinase KIN-29 modulates TGFbeta ... | ACCEPT | Summary: sma-6 mutants are small [PMID:9847239, PMID:11784045]. Reason: Core organismal output: hypodermal SMA-6 is necessary and sufficient for body length. Supporting Evidence: PMID:11784045 hypodermal expression of SMA-6 is necessary and sufficient for the growth and maintenance of body length PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:9847239 Specificity of TGFbeta signaling is conferred by distinct ty... | ACCEPT | Summary: sma-6 mutants are small [PMID:9847239, PMID:11784045]. Reason: Core organismal output: hypodermal SMA-6 is necessary and sufficient for body length. Supporting Evidence: PMID:11784045 hypodermal expression of SMA-6 is necessary and sufficient for the growth and maintenance of body length PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0040024 dauer larval development | IGI PMID:15840165 C. elegans serine-threonine kinase KIN-29 modulates TGFbeta ... | KEEP AS NON CORE | Summary: sma-6 mutations enhance dauer formation of daf-7 mutants [PMID:15840165, PMID:9847239]. Reason: sma-6 mutants are not dauer-constitutive by themselves [PMID:9847239]. The genetic enhancement reflects crosstalk between the Sma/Mab and dauer TGF-beta pathways, not a core SMA-6 role. Supporting Evidence: PMID:15840165 At 15°C and 20°C, kin-29(oy38) is able to enhance dauer formation of daf-7(e1372) similar to the enhancement observed in sma-6(wk7); daf-7(e1372) mutant animals PMID:9847239 However, mutations in sma-6, sma-2, sma-3, or sma-4 do not produce constitutive dauers |
| GO:0040024 dauer larval development | IGI PMID:9847239 Specificity of TGFbeta signaling is conferred by distinct ty... | KEEP AS NON CORE | Summary: sma-6 mutations enhance dauer formation of daf-7 mutants [PMID:15840165, PMID:9847239]. Reason: sma-6 mutants are not dauer-constitutive by themselves [PMID:9847239]. The genetic enhancement reflects crosstalk between the Sma/Mab and dauer TGF-beta pathways, not a core SMA-6 role. Supporting Evidence: PMID:15840165 At 15°C and 20°C, kin-29(oy38) is able to enhance dauer formation of daf-7(e1372) similar to the enhancement observed in sma-6(wk7); daf-7(e1372) mutant animals PMID:9847239 However, mutations in sma-6, sma-2, sma-3, or sma-4 do not produce constitutive dauers |
| GO:0045087 innate immune response | IMP PMID:19198592 Neuroimmune regulation of antimicrobial peptide expression b... | KEEP AS NON CORE | Summary: DBL-1 signaling is needed for antifungal peptide (cnc-2) induction [PMID:19198592]. Reason: SMA-6 receives a neuronal DBL-1 signal that regulates epidermal antimicrobial peptide genes. This is a real but non-core output of the pathway. 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:0045138 nematode male tail tip morphogenesis | IGI PMID:9847239 Specificity of TGFbeta signaling is conferred by distinct ty... | ACCEPT | Summary: Genetic interaction in male tail morphogenesis [PMID:9847239]. Reason: As for the IMP rows. Supporting Evidence: PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0045138 nematode male tail tip morphogenesis | IMP PMID:12679110 The roles of an ephrin and a semaphorin in patterning cell-c... | ACCEPT | Summary: sma-6 mutant males have abnormal male tails (Mab) [PMID:9847239, PMID:12717735]. Reason: Male tail patterning is one of the two hallmark outputs of the Sma/Mab pathway. Tail-tip and ray defects are seen in pathway mutants. Supporting Evidence: PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0045138 nematode male tail tip morphogenesis | IMP PMID:12717735 Genetic screen for small body size mutants in C. elegans rev... | ACCEPT | Summary: sma-6 mutant males have abnormal male tails (Mab) [PMID:9847239, PMID:12717735]. Reason: Male tail patterning is one of the two hallmark outputs of the Sma/Mab pathway. Tail-tip and ray defects are seen in pathway mutants. Supporting Evidence: PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0045138 nematode male tail tip morphogenesis | IMP PMID:9847239 Specificity of TGFbeta signaling is conferred by distinct ty... | ACCEPT | Summary: sma-6 mutant males have abnormal male tails (Mab) [PMID:9847239, PMID:12717735]. Reason: Male tail patterning is one of the two hallmark outputs of the Sma/Mab pathway. Tail-tip and ray defects are seen in pathway mutants. Supporting Evidence: PMID:9847239 Mutations in sma-6 generate the reduced body size (Sma) and abnormal mail tail (Mab) phenotypes identical to those observed in daf-4 and sma-2, sma-3, sma-4 mutants (C. elegans Smads), indicating that they function in a common signaling pathway |
| GO:0045732 positive regulation of protein catabolic process | IMP PMID:12397107 The expression of TGFbeta signal transducers in the hypoderm... | MARK AS OVER ANNOTATED | Summary: SMA-3 protein levels are negatively regulated by Sma/Mab pathway activity [PMID:12397107]. Reason: An indirect consequence of pathway activity on Smad turnover; SMA-6 has no shown role in protein catabolism. Supporting Evidence: PMID:12397107 SMA-3 protein accumulation was found to be negatively regulated by the level of Sma/Mab pathway activity |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:12679110 The roles of an ephrin and a semaphorin in patterning cell-c... | MARK AS OVER ANNOTATED | Summary: Expression of target genes (e.g. cnc-2) depends on DBL-1 pathway activity [PMID:19198592, PMID:12679110]. Reason: SMA-6 is a membrane receptor kinase. Its effect on transcription runs through the Smads SMA-2/3/4, which are the direct transcriptional regulators, so this is an indirect effect. 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: Expression of target genes (e.g. cnc-2) depends on DBL-1 pathway activity [PMID:19198592, PMID:12679110]. Reason: SMA-6 is a membrane receptor kinase. Its effect on transcription runs through the Smads SMA-2/3/4, which are the direct transcriptional regulators, so this is an indirect effect. 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:0048179 activin receptor complex | IBA GO_REF:0000033 | MODIFY | Summary: IBA asserting membership of an activin receptor complex. Reason: SMA-6 forms a ligand-receptor complex with the type II receptor DAF-4 for the BMP-like ligand DBL-1 [PMID:9847239, PMID:20502686]. BMP receptor complex is the appropriate term. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN000583887 · PTN000583887 SUPPORTS SOURCE BUT NOT TARGET Activin/TGF-beta type I receptor node (Babo/ALK4/5/7-like). SMA-6 signals for the BMP-like ligand DBL-1, and C. elegans has no activin ligand, so the activin-specific part of the term does not transfer. Proposed replacements: BMP receptor complex Supporting Evidence: PMID:12051826 The ligand of the pathway, dbl-1, transmits its signal through two receptor serine threonine kinases, daf-4 and sma-6 PMID:20502686 SMA-10 physically binds the DBL-1 receptors SMA-6 and DAF-4 and enhances signaling in vitro |
| GO:0048185 activin binding | IBA GO_REF:0000033 | MODIFY | Summary: IBA asserting activin binding. Reason: C. elegans lacks activin. SMA-6's relevant ligand is the BMP-family DBL-1, and BMP binding is separately annotated (IDA). Replace with BMP binding. Propagation Review Root cause: PROPAGATION BAD Failure modes: LINEAGE OR TAXON MISMATCH Sources checked: PANTHER:PTN000583887 · PTN000583887 SUPPORTS SOURCE BUT NOT TARGET Activin/TGF-beta type I receptor node (Babo/ALK4/5/7-like). SMA-6 signals for the BMP-like ligand DBL-1, and C. elegans has no activin ligand, so the activin-specific part of the term does not transfer. Proposed replacements: BMP binding Supporting Evidence: PMID:9847239 We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6 |
| GO:0050830 defense response to Gram-positive bacterium | IMP PMID:24972867 Orthosiphon stamineus protects Caenorhabditis elegans agains... | KEEP AS NON CORE | Summary: sma-6(wk7) mutants are hypersensitive to S. aureus [PMID:24972867]. Reason: Non-core immunity phenotype of a pathway receptor mutant. Supporting Evidence: PMID:24972867 Additionally, we found that the pmk-1 (km25), daf-16 (mu86) and sma-6 (wk7) mutants were also hypersensitive to S |
| 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 (D. coniospora) [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:0051457 maintenance of protein location in nucleus | IMP PMID:12397107 The expression of TGFbeta signal transducers in the hypoderm... | MARK AS OVER ANNOTATED | Summary: SMA-3 nuclear localization is enhanced by SMA-6 activity [PMID:12397107]. Reason: Nuclear accumulation of SMA-3 is the normal result of receptor-mediated R-Smad phosphorylation. It is part of BMP signaling, not a separate process that SMA-6 carries out. The term implies a nuclear-retention activity that SMA-6, a membrane receptor, does not have. Supporting Evidence: PMID:12397107 we find that SMA-3::GFP is nuclear localized in all of these tissues, and that nuclear localization is enhanced by SMA-6 activity |
| GO:0071363 cellular response to growth factor stimulus | IBA GO_REF:0000033 | ACCEPT | Summary: Cellular response to growth factor stimulus. Reason: Broad but correct for a receptor of the TGF-beta-family ligand DBL-1. Supporting Evidence: PMID:9847239 We have cloned and characterized a novel type I receptor and show that it is encoded by sma-6 |
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Download this section (compressed HTML)Q: Does SMA-6 bind DBL-1 directly with measurable affinity, and how do SMA-10, tetraspanins and DRAG-1 change ligand-receptor complex assembly?
Q: How is SMA-6 signaling to the Smads separated from the R-Smad-independent output in g1 gland cell morphology?
Experiment: Show in vitro, with purified receptor kinase, that SMA-6 phosphorylates the C-terminal SSXS motifs of SMA-2/SMA-3, and that DAF-4 phosphorylates the SMA-6 GS domain.
Hypothesis: SMA-6 is the direct R-Smad kinase of the Sma/Mab pathway, as for vertebrate BMPR1.
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