SMA-9 is the C. elegans homolog of Drosophila Schnurri and the vertebrate HIVEP/ZAS proteins. It is a large nuclear zinc-finger protein produced as many alternatively spliced isoforms, and it acts as a transcriptional cofactor of the DBL-1/BMP-like Sma/Mab pathway. Genetically it is a downstream component needed for body size and for patterning of the male tail sensory rays and spicules, but its activity is more restricted in time and cell type than that of the core pathway. Fusion experiments indicated that SMA-9 acts mainly as a transcriptional repressor in body size control. Separate regions of the protein have intrinsic repressor and activator activity, and both contribute to male tail patterning. Genome-wide ChIP-seq places SMA-9 on chromatin at many sites shared with SMA-3. Its direct targets include both activated and repressed genes, and several targets act in cuticle collagen secretion. In the postembryonic mesoderm (M lineage) SMA-9 has an opposite, antagonistic role. It specifies dorsal fates (the M-derived coelomocytes) by opposing BMP signaling on the dorsal side, partly by repressing BMP-dependent expression of the FOXD factor UNC-130. Loss of sma-9 causes a dorsal-to-ventral fate transformation that is suppressed by loss of the core pathway.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: RNA polymerase II cis-regulatory region sequence-specific DNA binding, from the Schnurri/HIVEP node. Reason: Schnurri/HIVEP zinc-finger proteins can bind DNA, and SMA-9 has the conserved zinc fingers. However, SMA-9 is described as a transcriptional cofactor of the Smads, and direct sequence-specific DNA binding by SMA-9 has not been demonstrated. The PAINT inference is plausible, but it is not the best description of SMA-9 function. Supporting Evidence: PMID:14627718 encodes the C. elegans homolog of Schnurri, a large zinc finger transcription factor that regulates dpp target genes in Drosophila PMID:14627718 We propose that SMA-9 isoforms function as transcriptional cofactors that confer specific responses to DBL-1 pathway activation. |
| GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: IBA: DNA-binding transcription factor activity, RNA polymerase II-specific. Reason: SMA-9 is homologous to zinc-finger transcription factors, but its demonstrated role is as a Smad transcriptional cofactor (corepressor or coactivator). Kept as non-core. The core MF is captured by transcription corepressor activity. Supporting Evidence: PMID:14627718 encodes the C. elegans homolog of Schnurri, a large zinc finger transcription factor that regulates dpp target genes in Drosophila PMID:14627718 We propose that SMA-9 isoforms function as transcriptional cofactors that confer specific responses to DBL-1 pathway activation. |
| GO:0003676 nucleic acid binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO: nucleic acid binding, from zinc-finger domains. Reason: Generic and uninformative, but not wrong. Non-core. |
| GO:0003713 transcription coactivator activity | IMP PMID:17397820 Transcriptional repressor and activator activities of SMA-9 ... | ACCEPT | Summary: Transcription coactivator activity (IMP), from activator- and repressor-fusion experiments. Reason: SMA-9 regions have intrinsic activator activity in yeast, and activator function contributes to male tail patterning in vivo. Secondary to the repressor activity used in body size control. Supporting Evidence: PMID:17397820 We further show that different SMA-9 regions have intrinsic repressor and activator activities using a yeast transcription assay. PMID:17397820 In contrast, both activator and repressor functions contribute to male tail patterning. |
| GO:0003714 transcription corepressor activity | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA: transcription corepressor activity. Reason: Consistent with the experimental evidence that SMA-9 acts primarily as a repressor. Supporting Evidence: PMID:17397820 SMA-9 acts primarily as a transcriptional repressor in body size regulation in vivo |
| GO:0003714 transcription corepressor activity | IMP PMID:17397820 Transcriptional repressor and activator activities of SMA-9 ... | ACCEPT | Summary: Transcription corepressor activity (IMP). Reason: Fusions to known repressor domains show that SMA-9 acts primarily as a transcriptional repressor in body size regulation, and SMA-9 regions have intrinsic repressor activity. This is the core MF, and it matches the module. Supporting Evidence: PMID:17397820 SMA-9 acts primarily as a transcriptional repressor in body size regulation in vivo PMID:17397820 We further show that different SMA-9 regions have intrinsic repressor and activator activities using a yeast transcription assay. |
| GO:0005634 nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: nucleus. Reason: SMA-9 is a nuclear zinc-finger cofactor. Supporting Evidence: PMID:14627718 We propose that SMA-9 isoforms function as transcriptional cofactors that confer specific responses to DBL-1 pathway activation. |
| GO:0005634 nucleus | IDA PMID:14627718 The Caenorhabditis elegans schnurri homolog sma-9 mediates s... | ACCEPT | Summary: Nucleus (IDA), from the sma-9 cloning paper. Reason: UniProt cites this paper for the nuclear localization of SMA-9. This is consistent with its cofactor role. Supporting Evidence: PMID:14627718 We propose that SMA-9 isoforms function as transcriptional cofactors that confer specific responses to DBL-1 pathway activation. |
| GO:0005634 nucleus | IDA PMID:16790477 An antagonistic role for the C. elegans Schnurri homolog SMA... | ACCEPT | Summary: Nucleus (IDA). Reason: Nuclear localization fits SMA-9's role as a transcriptional cofactor in the M lineage. Supporting Evidence: PMID:16790477 Our studies have uncovered an unexpected role of SMA-9 in antagonizing the TGFbeta signaling pathway during mesodermal patterning |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: Nucleus (UniProt subcellular location mapping). Reason: Consistent with the experimental data. |
| GO:0006357 regulation of transcription by RNA polymerase II | IBA GO_REF:0000033 | ACCEPT | Summary: IBA: regulation of transcription by RNA polymerase II. Reason: SMA-9 regulates transcription of target genes such as unc-130. Supporting Evidence: PMID:29155044 However, our data showed that SMA-9 actively represses BMP-dependent UNC-130 expression. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IGI PMID:12717735 Genetic screen for small body size mutants in C. elegans rev... | MODIFY | Summary: Transforming growth factor beta receptor signaling pathway (IGI), from genetic placement in the Sma/Mab pathway. Reason: SMA-9 acts downstream in the DBL-1 pathway. DBL-1 is BMP-related, and the specific child term BMP signaling pathway is the appropriate term, as the module uses. Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:14627718 sma-9 acts as a downstream component and is required in the DBL-1 signaling pathway |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IGI PMID:12717735 Genetic screen for small body size mutants in C. elegans rev... | MODIFY | Summary: Transforming growth factor beta receptor signaling pathway (IGI), from genetic placement in the Sma/Mab pathway. Reason: SMA-9 acts downstream in the DBL-1 pathway. DBL-1 is BMP-related, and the specific child term BMP signaling pathway is the appropriate term, as the module uses. Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:14627718 sma-9 acts as a downstream component and is required in the DBL-1 signaling pathway |
| GO:0008270 zinc ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: InterPro2GO: zinc ion binding. Reason: The C2H2 zinc fingers imply zinc binding. Structural, not functional. Non-core. |
| GO:0008340 determination of adult lifespan | IMP PMID:25407930 SMAD Transcription Factor, Sma-9, Attunes TGF-Ξ² Signaling Ca... | UNDECIDED | Summary: Determination of adult lifespan (IMP), from an amyloid-beta model study. Reason: The cached record is abstract-only. The abstract describes a modulatory role of SMA-9 in an amyloid-beta transgenic model but not the specific readout behind this annotation, so it cannot be verified here. |
| GO:0010628 positive regulation of gene expression | IMP PMID:25407930 SMAD Transcription Factor, Sma-9, Attunes TGF-Ξ² Signaling Ca... | KEEP AS NON CORE | Summary: Positive regulation of gene expression (IMP). Reason: SMA-9 has activator activity (PMID:17397820), so a positive effect on gene expression is plausible. The specific evidence from this abstract-only paper cannot be verified. Kept as non-core and generic. Supporting Evidence: PMID:17397820 We further show that different SMA-9 regions have intrinsic repressor and activator activities using a yeast transcription assay. |
| GO:0010629 negative regulation of gene expression | IMP PMID:25407930 SMAD Transcription Factor, Sma-9, Attunes TGF-Ξ² Signaling Ca... | ACCEPT | Summary: Negative regulation of gene expression (IMP), from the amyloid-beta model study. Reason: Consistent with SMA-9's established repressor activity, though this paper's readout cannot be verified from the abstract. Accepted because negative regulation of gene expression by SMA-9 is independently established (unc-130, PMID:29155044). Supporting Evidence: PMID:17397820 SMA-9 acts primarily as a transcriptional repressor in body size regulation in vivo |
| GO:0010629 negative regulation of gene expression | IMP PMID:29155044 The forkhead transcription factor UNC-130/FOXD integrates bo... | ACCEPT | Summary: Negative regulation of gene expression (IMP): repression of unc-130 in the M lineage. Reason: SMA-9 represses BMP-dependent unc-130 expression in the early and dorsal M lineage. Supporting Evidence: PMID:29155044 However, our data showed that SMA-9 actively represses BMP-dependent UNC-130 expression. PMID:29155044 Nevertheless, our results indicate that SMA-9 normally functions to repress unc-130 expression in the early M lineage (1-M to 4-M stage) and in dorsal M lineage cells (8-M stage onward). |
| GO:0030514 negative regulation of BMP signaling pathway | IMP PMID:16790477 An antagonistic role for the C. elegans Schnurri homolog SMA... | ACCEPT | Summary: Negative regulation of BMP signaling pathway (IMP). Reason: SMA-9 antagonizes Sma/Mab signaling in the M lineage: core pathway mutations suppress the sma-9 M lineage defect. Supporting Evidence: PMID:16790477 Our studies have uncovered an unexpected role of SMA-9 in antagonizing the TGFbeta signaling pathway during mesodermal patterning PMID:16790477 Surprisingly, mutations in the core components of the Sma/Mab TGFbeta signaling pathway suppressed the M lineage defects of sma-9 mutants without suppressing their body size defects. |
| GO:0030514 negative regulation of BMP signaling pathway | IMP PMID:29155044 The forkhead transcription factor UNC-130/FOXD integrates bo... | ACCEPT | Summary: Negative regulation of BMP signaling pathway (IMP). Reason: SMA-9 represses BMP-dependent unc-130 expression, and the de-repression in sma-9 mutants requires BMP signaling. Supporting Evidence: PMID:29155044 However, our data showed that SMA-9 actively represses BMP-dependent UNC-130 expression. PMID:29155044 Thus the de-repression of unc-130 expression in the M lineage of sma-9 mutants requires BMP signaling. |
| GO:0034605 cellular response to heat | IMP PMID:25407930 SMAD Transcription Factor, Sma-9, Attunes TGF-Ξ² Signaling Ca... | UNDECIDED | Summary: Cellular response to heat (acts upstream of or within, IMP), from the amyloid-beta model study. Reason: The cached record is abstract-only. The abstract describes a modulatory role of SMA-9 in an amyloid-beta transgenic model but not the specific readout behind this annotation, so it cannot be verified here. |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:12717735 Genetic screen for small body size mutants in C. elegans rev... | ACCEPT | Summary: Positive regulation of multicellular organism growth (IMP). Reason: sma-9 mutants are small, and SMA-9 acts downstream in the DBL-1 pathway, mainly as a repressor, to promote body size. Supporting Evidence: PMID:12717735 Four of these 11 genes, sma-9, sma-14, sma-16, and sma-20 affect male tail morphogenesis as well as body size. PMID:17397820 SMA-9 acts primarily as a transcriptional repressor in body size regulation in vivo |
| GO:0040018 positive regulation of multicellular organism growth | IMP PMID:17397820 Transcriptional repressor and activator activities of SMA-9 ... | ACCEPT | Summary: Positive regulation of multicellular organism growth (IMP). Reason: sma-9 mutants are small, and SMA-9 acts downstream in the DBL-1 pathway, mainly as a repressor, to promote body size. Supporting Evidence: PMID:12717735 Four of these 11 genes, sma-9, sma-14, sma-16, and sma-20 affect male tail morphogenesis as well as body size. PMID:17397820 SMA-9 acts primarily as a transcriptional repressor in body size regulation in vivo |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:16790477 An antagonistic role for the C. elegans Schnurri homolog SMA... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:28068334 Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with ... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:28068334 Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with ... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:28068334 Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with ... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IGI PMID:28068334 Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with ... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IGI with Sma/Mab pathway genes and modulators). Reason: sma-9 mutants show a dorsal-to-ventral M lineage fate transformation that is suppressed by loss of core Sma/Mab pathway components and modulators. SMA-9 specifies dorsal M lineage fate by antagonizing BMP signaling. This is a well-established core role. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage PMID:25978409 Mutations in the Sma/Mab pathway fully restore the sma-9(0) M lineage phenotype back to that of wild-type animals |
| GO:0042661 regulation of mesodermal cell fate specification | IMP PMID:16790477 An antagonistic role for the C. elegans Schnurri homolog SMA... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IMP). Reason: Loss of sma-9 causes a dorsal-to-ventral fate transformation in the M lineage. Supporting Evidence: PMID:16790477 In addition to a small body size, sma-9 mutant animals exhibit a dorsal-to-ventral fate transformation within the M lineage. |
| GO:0042661 regulation of mesodermal cell fate specification | IMP PMID:28068334 Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with ... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IMP). Reason: The sma-9 M lineage defect (loss of M-derived coelomocytes) is the basis of the Susm assay. Supporting Evidence: PMID:28068334 Loss-of-function mutations in any of these core members will result in a small body size, male tail sensory ray formation defects [17], reduced expression of the RAD-SMAD reporter [18], and suppression of the sma-9(cc604) M lineage defect [19]. |
| GO:0042661 regulation of mesodermal cell fate specification | IMP PMID:29155044 The forkhead transcription factor UNC-130/FOXD integrates bo... | ACCEPT | Summary: Regulation of mesodermal cell fate specification (IMP). Reason: SMA-9 represses unc-130 to allow dorsal M lineage fates. Supporting Evidence: PMID:29155044 Nevertheless, our results indicate that SMA-9 normally functions to repress unc-130 expression in the early M lineage (1-M to 4-M stage) and in dorsal M lineage cells (8-M stage onward). |
| GO:0045138 nematode male tail tip morphogenesis | IMP PMID:12717735 Genetic screen for small body size mutants in C. elegans rev... | ACCEPT | Summary: Nematode male tail tip morphogenesis (IMP). Reason: sma-9 affects male tail morphogenesis (ray and spicule patterning). Both its activator and repressor activities contribute. Supporting Evidence: PMID:12717735 Four of these 11 genes, sma-9, sma-14, sma-16, and sma-20 affect male tail morphogenesis as well as body size. PMID:17397820 In contrast, both activator and repressor functions contribute to male tail patterning. |
| GO:0045138 nematode male tail tip morphogenesis | IMP PMID:17397820 Transcriptional repressor and activator activities of SMA-9 ... | ACCEPT | Summary: Nematode male tail tip morphogenesis (IMP). Reason: sma-9 affects male tail morphogenesis (ray and spicule patterning). Both its activator and repressor activities contribute. Supporting Evidence: PMID:12717735 Four of these 11 genes, sma-9, sma-14, sma-16, and sma-20 affect male tail morphogenesis as well as body size. PMID:17397820 In contrast, both activator and repressor functions contribute to male tail patterning. |
| GO:0045892 negative regulation of DNA-templated transcription | IEA GO_REF:0000108 | ACCEPT | Summary: Negative regulation of DNA-templated transcription (inferred from the corepressor MF). Reason: Consistent with SMA-9 repressor activity. Supporting Evidence: PMID:17397820 SMA-9 acts primarily as a transcriptional repressor in body size regulation in vivo |
| GO:0045893 positive regulation of DNA-templated transcription | IEA GO_REF:0000108 | ACCEPT | Summary: Positive regulation of DNA-templated transcription (inferred from the coactivator MF). Reason: Consistent with SMA-9 activator activity in male tail patterning. Supporting Evidence: PMID:17397820 In contrast, both activator and repressor functions contribute to male tail patterning. |
| GO:0048337 positive regulation of mesodermal cell fate specification | IGI PMID:21307099 The C. elegans SoxC protein SEM-2 opposes differentiation fa... | KEEP AS NON CORE | Summary: Positive regulation of mesodermal cell fate specification (IGI with sem-2), from the SoxC M lineage study. Reason: SEM-2 promotes the ventral sex myoblast fate, and SMA-9 opposes it to allow dorsal coelomocyte fates. The genetic interaction supports a role of SMA-9 in M lineage fate. The direction ('positive') depends on which fate is considered. The parent regulation term is the more robust description. Supporting Evidence: PMID:21307099 We found that SEM-2/SoxC is both necessary and sufficient to promote a proliferating blast cell fate, the sex myoblast fate, over a differentiated striated bodywall muscle fate. |
| GO:0048337 positive regulation of mesodermal cell fate specification | IMP PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp... | KEEP AS NON CORE | Summary: Positive regulation of mesodermal cell fate specification (IMP). Reason: SMA-9 is required for dorsal M lineage (coelomocyte) fate, which supports a positive role for that fate. Overlaps the regulation term. Supporting Evidence: PMID:25978409 Mutations in sma-9 lead to a dorsal-to-ventral fate transformation in the M lineage |
| GO:0071363 cellular response to growth factor stimulus | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA: cellular response to growth factor stimulus. Reason: Broad. Non-core. |
| GO:0141091 transforming growth factor beta receptor superfamily signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA: transforming growth factor beta receptor superfamily signaling pathway. Reason: A correct parent of BMP signaling for this Sma/Mab pathway component. Supporting Evidence: PMID:14627718 sma-9 acts as a downstream component and is required in the DBL-1 signaling pathway |
| GO:1900182 positive regulation of protein localization to nucleus | IMP PMID:25407930 SMAD Transcription Factor, Sma-9, Attunes TGF-Ξ² Signaling Ca... | UNDECIDED | Summary: Positive regulation of protein localization to nucleus (IMP), from the amyloid-beta model study. Reason: The cached record is abstract-only. The abstract describes a modulatory role of SMA-9 in an amyloid-beta transgenic model but not the specific readout behind this annotation, so it cannot be verified here. |
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Download this section (compressed HTML)Q: How does the same SMA-9 protein mediate DBL-1 output in body size but antagonize it in the dorsal M lineage? Do different isoforms or partners explain this?
Q: Does SMA-9 bind DNA directly through its zinc fingers, as Drosophila Schnurri does in Mad/Medea silencer complexes, or is it recruited only through Smads?
Q: Genome-wide data (Vora et al. 2025) suggest that most genes co-regulated by SMA-9 and SMA-3 are activated by both. How does this square with the earlier conclusion that SMA-9 acts primarily as a repressor in body size control?
Experiment: ChIP-seq or CUT&RUN of isoform-specific tagged SMA-9 alongside SMA-3 to determine co-occupancy and direct targets (e.g. unc-130, lon-1).
Experiment: EMSA or SELEX with SMA-9 zinc-finger regions, alone and with SMA-3/SMA-4, to test for direct sequence-specific DNA binding.
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