dbl-1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005125 cytokine activity	IBA GO_REF:0000033	ACCEPT	Summary: DBL-1 functions as a secreted signaling molecule similar to cytokines, activating receptor-mediated signaling cascades. As a TGF-beta/BMP superfamily member, it acts as a paracrine signal from neurons to hypodermal cells. The IBA annotation is phylogenetically sound given DBL-1's membership in the TGF-beta superfamily. Reason: DBL-1 is a secreted signaling ligand that activates receptor-mediated pathways, consistent with cytokine activity. The IBA annotation correctly captures this molecular function based on phylogenetic inference from BMP family members. Supporting Evidence: PMID:9847238 DBL-1 acts as a dose-dependent regulator of these processes file:worm/dbl-1/dbl-1-deep-research-falcon.md model: Edison Scientific Literature
GO:0005615 extracellular space	IBA GO_REF:0000033	ACCEPT	Summary: DBL-1 is a secreted protein that signals from neurons to hypodermal cells in a paracrine manner. As a TGF-beta/BMP family member, it is processed and secreted to act on target cells expressing cognate receptors. Reason: DBL-1 is established as a secreted ligand that acts non-cell-autonomously. UniProt annotation indicates "Secreted" subcellular location. The protein signals from neurons to the hypodermis, requiring extracellular localization for its function. Supporting Evidence: PMID:12397107 As dbl-1 is expressed primarily in the nervous system, these results suggest a model in which postembryonic growth of hypodermal cells is regulated by TGFbeta-related signaling from the nervous system to the hypodermis
GO:0030509 BMP signaling pathway	IBA GO_REF:0000033	ACCEPT	Summary: DBL-1 is the ligand of the C. elegans BMP-like (Sma/Mab) signaling pathway. This is a core function of the protein, established through extensive genetic and biochemical studies. Reason: DBL-1 is the founding member of the C. elegans BMP pathway. PMID:9847238 identified it as a BMP homolog, and subsequent studies confirmed it signals through SMA-6 receptor and SMAD proteins. This is the central molecular function of DBL-1. Supporting Evidence: PMID:9847238 We cloned the dbl-1 gene, a C. elegans homolog of Drosophila decapentaplegic and vertebrate BMP genes PMID:12717735 In the nematode Caenorhabditis elegans, a TGFbeta-related signaling pathway regulates body size and male tail morphogenesis
GO:0005576 extracellular region	IEA GO_REF:0000120	ACCEPT	Summary: IEA annotation based on InterPro domain and UniProt subcellular location. DBL-1 is a secreted protein, so this annotation is correct but less specific than GO:0005615 (extracellular space) which is also annotated. Reason: As a secreted TGF-beta ligand, DBL-1 is correctly annotated to extracellular region. This is a broader term than extracellular space but accurately reflects the protein's localization after secretion. Supporting Evidence: PMID:9847238 A BMP homolog acts as a dose-dependent regulator of body size and male tail patterning in Caenorhabditis elegans
GO:0008083 growth factor activity	IEA GO_REF:0000120	ACCEPT	Summary: DBL-1 acts as a dose-dependent regulator of body size, functioning as a growth factor. Loss-of-function causes reduced body size while overexpression causes increased body size. Reason: DBL-1 functions as a classical growth factor - it is a secreted signaling molecule that regulates cell and organism size in a dose-dependent manner. PMID:9847238 demonstrates both loss-of-function (small) and gain-of-function (large) body size phenotypes. Supporting Evidence: PMID:9847238 Loss-of-function mutations in dbl-1 cause markedly reduced body size and defective male copulatory structures
GO:0010628 positive regulation of gene expression	IMP PMID:18158917 Regulation of rnt-1 expression mediated by the opposing effe...	ACCEPT	Summary: PMID:18158917 shows DBL-1 is required for counteracting BRO-1-mediated repression of rnt-1 expression at postembryonic stages, and ectopic DBL-1 expression induces rnt-1 transcription. Reason: The publication demonstrates DBL-1 positively regulates rnt-1 gene expression, opposing the repressive activity of BRO-1. This is a well-characterized regulatory relationship where DBL-1/TGF-beta signaling activates downstream gene expression. Supporting Evidence: PMID:18158917 we found that the TGFbeta homolog, DBL-1, was required for counteracting the repressive activity of BRO-1 at postembryonic stages
GO:0019216 regulation of lipid metabolic process	IMP PMID:29162682 Caenorhabditis elegans DBL-1/BMP Regulates Lipid Accumulatio...	ACCEPT	Summary: PMID:29162682 demonstrates DBL-1 regulates lipid accumulation in C. elegans. Both loss and gain of DBL-1 function result in reduced lipid stores. DBL-1 acts upstream of insulin/IGF-1 signaling in lipid metabolism. Reason: This is a well-established secondary function of DBL-1. The study shows dbl-1 mutants have reduction in neutral lipids, and demonstrates epistatic relationship with DAF-2/insulin signaling for lipid regulation. Supporting Evidence: PMID:29162682 Similarly, we observed a decrease in dbl-1 mutants by ∼35% compared to wild type PMID:29162682 genetic evidence indicates that DBL-1/BMP functions upstream of Insulin/IGF-1 Signaling in lipid metabolism
GO:0022604 regulation of cell morphogenesis	IMP PMID:24690231 CEH-28 activates dbl-1 expression and TGF-β signaling in the...	ACCEPT	Summary: PMID:24690231 shows dbl-1 mutants exhibit morphological defects in g1 gland cells located adjacent to M4 neuron in the pharynx, and these defects can be partially rescued by M4-specific expression of dbl-1. Reason: The study demonstrates DBL-1 is required for proper gland cell morphology via an R-Smad-independent TGF-beta signaling mechanism. This represents a distinct morphogenetic function of DBL-1. Supporting Evidence: PMID:24690231 both ceh-28 and dbl-1 mutants exhibit morphological defects in the g1 gland cells located adjacent to M4 in the pharynx, and these defects can be partially rescued by M4-specific expression of dbl-1 in these mutants
GO:0045944 positive regulation of transcription by RNA polymerase II	IMP PMID:19198592 Neuroimmune regulation of antimicrobial peptide expression b...	ACCEPT	Summary: PMID:19198592 demonstrates neuronal expression of DBL-1 promotes transcription of antimicrobial peptide genes (cnc-2 caenacin) in the epidermis in a dose-dependent paracrine manner. Reason: The study shows DBL-1 activates transcription of antimicrobial peptide genes in the epidermis. As TGF-beta signaling ultimately activates SMAD-mediated transcription, this annotation accurately reflects DBL-1's role in promoting gene expression. 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: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: PMID:28068334 demonstrates tetraspanins TSP-12 and TSP-14 promote BMP signaling through ADAM10/SUP-17, with genetic interactions involving dbl-1 pathway components. The IGI evidence reflects genetic interactions showing positive regulation of TGF-beta signaling. Reason: While the annotation captures DBL-1's role in promoting BMP signaling, DBL-1 itself IS the TGF-beta pathway ligand rather than a regulator of the pathway. The more accurate annotation would be "BMP signaling pathway" (GO:0030509) which is already annotated. This annotation is somewhat circular - DBL-1 doesn't regulate TGF-beta signaling, it IS the signal. Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:28068334 Here, we show that TSP-12 and TSP-14 function redundantly in BMP signaling by regulating the cell surface localization of the ADAM10
GO:0042661 regulation of mesodermal cell fate specification	IGI PMID:25978409 Promotion of bone morphogenetic protein signaling by tetrasp...	KEEP AS NON CORE	Summary: PMID:25978409 describes the role of the Sma/Mab pathway (including DBL-1) in regulating the postembryonic M lineage mesoderm development. Mutations in Sma/Mab pathway components suppress sma-9 M lineage defects. Reason: While the Sma/Mab pathway involving DBL-1 does affect M lineage patterning, this is demonstrated primarily through suppression of sma-9 mutant phenotypes rather than direct regulation. The core function of DBL-1 is body size regulation and male tail patterning; M lineage effects are more peripheral. Supporting Evidence: PMID:25978409 We have shown that mutations in the core components of the Sma/Mab pathway (Fig 2A) do not cause any M lineage defect on their own, but they suppress the dorsoventral patterning defects of sma-9 mutants
GO:0010468 regulation of gene expression	IMP PMID:17526726 Specificity and complexity of the Caenorhabditis elegans inn...	ACCEPT	Summary: PMID:17526726 shows DBL-1 pathway regulates expression of distinct but overlapping sets of antimicrobial genes as part of the C. elegans innate immune response. Reason: DBL-1/TGF-beta signaling regulates gene expression as part of its mechanism of action. The study demonstrates immune pathway signaling by DBL-1 affects antimicrobial gene expression patterns. Supporting Evidence: PMID:17526726 we found that different immune response pathways regulate expression of distinct but overlapping sets of antimicrobial genes
GO:0050832 defense response to fungus	IMP PMID:19198592 Neuroimmune regulation of antimicrobial peptide expression b...	ACCEPT	Summary: PMID:19198592 demonstrates DBL-1 promotes antifungal defense by activating expression of caenacin antimicrobial peptides in the epidermis in response to Drechmeria coniospora fungal infection. Reason: This is a well-characterized immune function of DBL-1. The study shows neuronal DBL-1 activates epidermal antimicrobial peptide expression during fungal infection via a non-canonical TGF-beta pathway. Supporting Evidence: PMID:19198592 After being infected by the fungus Drechmeria coniospora, Caenorhabditis elegans produces antimicrobial peptides in its epidermis PMID:19198592 The caenacin (cnc) genes enhanced survival after fungal infection
GO:0050829 defense response to Gram-negative bacterium	IMP PMID:17975555 A conserved Toll-like receptor is required for Caenorhabditi...	ACCEPT	Summary: PMID:17975555 demonstrates the role of TOL-1 and associated pathways including DBL-1 in defense against Salmonella enterica (Gram-negative bacterium) infection. Reason: DBL-1 contributes to innate immune defense against bacterial pathogens. UniProt annotation indicates "Plays a protective role in response to infection by the Gram-negative bacterium S.marcescens, by activating expression of genes involved in innate immunity." Supporting Evidence: PMID:17975555 tol-1(nr2033) mutants are killed by the human pathogen Salmonella enterica
GO:0050830 defense response to Gram-positive bacterium	IMP PMID:17975555 A conserved Toll-like receptor is required for Caenorhabditi...	ACCEPT	Summary: The annotation suggests DBL-1 is involved in defense against Gram-positive bacteria based on PMID:17975555, though the paper primarily focuses on Gram-negative Salmonella. Reason: DBL-1 is part of the C. elegans innate immune response system. UniProt annotation indicates involvement in antibacterial defense. The broader innate immune role of DBL-1 signaling encompasses responses to both Gram-negative and Gram-positive bacteria. Supporting Evidence: PMID:17975555 The results indicate that TOL-1 has a direct role in defence response to certain Gram-negative bacteria
GO:0005615 extracellular space	ISS PMID:9847238 A BMP homolog acts as a dose-dependent regulator of body siz...	ACCEPT	Summary: ISS annotation based on similarity to BMP proteins which are secreted ligands. PMID:9847238 identified DBL-1 as a BMP homolog. Duplicate of the IBA annotation. Reason: This annotation is correct based on homology to secreted BMP ligands. DBL-1 signals from neurons to target cells, requiring extracellular localization. Keeping both ISS and IBA provides independent evidence support. Supporting Evidence: PMID:9847238 a C. elegans homolog of Drosophila decapentaplegic and vertebrate BMP genes
GO:0030509 BMP signaling pathway	ISS PMID:9847238 A BMP homolog acts as a dose-dependent regulator of body siz...	ACCEPT	Summary: ISS annotation based on sequence similarity to BMP ligands. PMID:9847238 established DBL-1 as a BMP homolog. Duplicate of IBA annotation. Reason: DBL-1 is the ligand of the C. elegans BMP (Sma/Mab) pathway. This is the core function of the protein, supported by both phylogenetic (IBA) and sequence similarity (ISS) evidence. Supporting Evidence: PMID:9847238 Evidence from genetic interactions indicates that these effects are mediated by a Smad signaling pathway, for which DBL-1 is a previously unidentified ligand
GO:0070700 BMP receptor binding	ISS PMID:9847238 A BMP homolog acts as a dose-dependent regulator of body siz...	ACCEPT	Summary: ISS annotation based on homology to BMP ligands that bind BMP receptors. DBL-1 signals through the SMA-6 type I receptor and DAF-4 type II receptor. Reason: As a BMP ligand, DBL-1 must bind to its cognate receptors (SMA-6 and DAF-4) to transduce signals. This molecular function is correctly inferred from homology to vertebrate BMPs that bind BMP receptors. Supporting Evidence: PMID:9847238 Evidence from genetic interactions indicates that these effects are mediated by a Smad signaling pathway PMID:11784045 One of these pathways regulates body length and is composed of the ligand DBL-1, serine/threonine protein kinase receptors SMA-6 and DAF-4
GO:0040018 positive regulation of multicellular organism growth	IMP PMID:12571101 Cyclic GMP-dependent protein kinase EGL-4 controls body size...	ACCEPT	Summary: PMID:12571101 shows EGL-4/cGMP-dependent protein kinase represses body size through DBL-1/TGF-beta pathway. Genetic analysis places DBL-1 as a positive regulator of body growth. Reason: DBL-1 positively regulates body size - loss-of-function causes small body size and overexpression causes large body size. This is the primary phenotypic function of DBL-1. Supporting Evidence: PMID:12571101 Experiments on genetic interaction suggest that the cGMP-EGL-4 signaling pathway represses body size and lifespan through DBL-1/TGF-beta and insulin pathways, respectively
GO:0045087 innate immune response	IMP PMID:19198592 Neuroimmune regulation of antimicrobial peptide expression b...	ACCEPT	Summary: PMID:19198592 demonstrates DBL-1 functions in neuroimmune regulation, activating antimicrobial peptide expression in epidermis during pathogen infection. Reason: DBL-1 contributes to innate immunity by activating antimicrobial peptide genes via a noncanonical TGF-beta signaling pathway. This is a well-established secondary function of DBL-1. Supporting Evidence: PMID:19198592 antifungal defenses are coordinately regulated by a cell-autonomous p38 cascade and a distinct cytokine-like transforming growth factor-beta signal from the nervous system
GO:0032877 positive regulation of DNA endoreduplication	IMP PMID:12019225 Increased or decreased levels of Caenorhabditis elegans lon-...	ACCEPT	Summary: PMID:12019225 shows dbl-1 loss-of-function causes decreased hypodermal nuclear ploidy (endoreduplication) in hyp7 syncytial cells, indicating DBL-1 positively regulates this process. Reason: The study demonstrates that dbl-1 mutants have reduced ploidy in hypodermal nuclei, indicating DBL-1 promotes endoreduplication. This contributes to the body size phenotype. Supporting Evidence: PMID:12019225 loss-of-function mutations in dbl-1 and lon-1, respectively, cause a decrease or increase in the ploidy of nuclei in the hypodermal syncytial cell, hyp7
GO:0040018 positive regulation of multicellular organism growth	IGI PMID:12051826 lon-1 regulates Caenorhabditis elegans body size downstream ...	ACCEPT	Summary: PMID:12051826 demonstrates lon-1 is a downstream target of DBL-1 signaling that regulates body size. Genetic analysis shows lon-1 acts downstream of dbl-1 in the Sma/Mab pathway. Reason: Genetic interactions between dbl-1 and lon-1 confirm DBL-1's role in body size regulation. lon-1 mRNA is up-regulated when dbl-1 signaling is reduced, showing negative regulation by the pathway. Supporting Evidence: PMID:12051826 lon-1 regulates body size morphogenesis PMID:12051826 lon-1 lies downstream of the Sma/Mab signaling cascade
GO:0040018 positive regulation of multicellular organism growth	IGI PMID:17240342 Glypican LON-2 is a conserved negative regulator of BMP-like...	ACCEPT	Summary: PMID:17240342 shows LON-2 glypican negatively regulates BMP-like signaling by potentially binding to DBL-1 and attenuating ligand-receptor interactions. Reason: Genetic analysis places lon-2 upstream of dbl-1 as a negative regulator. The interaction between LON-2 and DBL-1 confirms DBL-1's role in promoting growth. Supporting Evidence: PMID:17240342 LON-2 negatively regulates a BMP-like signaling pathway that controls body length in C. elegans PMID:17240342 lon-2 acts genetically upstream of the BMP-like gene dbl-1
GO:0040018 positive regulation of multicellular organism growth	IMP PMID:12397107 The expression of TGFbeta signal transducers in the hypoderm...	ACCEPT	Summary: PMID:12397107 demonstrates dbl-1 loss-of-function causes reduced body size due to decreased postembryonic growth, with hypodermal blast cell size most affected. Reason: This study provides detailed characterization of body size regulation by DBL-1, showing the signaling pathway acts in hypodermis to regulate growth. Supporting Evidence: PMID:12397107 Loss of function of the signaling ligand (dbl-1), receptors (daf-4 and sma-6) or Smads (sma-2, sma-3 and sma-4) results in viable, but smaller animals because of a reduction in postembryonic growth
GO:0040018 positive regulation of multicellular organism growth	IMP PMID:12717735 Genetic screen for small body size mutants in C. elegans rev...	ACCEPT	Summary: PMID:12717735 identifies dbl-1 mutations in a genetic screen for small body size mutants, confirming its role in growth regulation. Reason: Forward genetic screen confirms dbl-1 as a key regulator of body size within the TGF-beta pathway. Supporting Evidence: PMID:12717735 Among 34 Small mutants, many mutations disrupt genes encoding recognizable components of the TGFbeta pathway: DBL-1 ligand
GO:0045138 nematode male tail tip morphogenesis	IMP PMID:12717735 Genetic screen for small body size mutants in C. elegans rev...	ACCEPT	Summary: PMID:12717735 shows dbl-1 mutants have male tail morphogenesis defects including ray fusions and abnormal spicules. Reason: Male tail patterning is a core function of DBL-1, affecting sensory ray formation and mating structures. This is one of the two primary phenotypes (along with body size) of the Sma/Mab pathway. Supporting Evidence: PMID:9847238 Loss-of-function mutations in dbl-1 cause markedly reduced body size and defective male copulatory structures 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
GO:0002119 nematode larval development	IMP PMID:12397107 The expression of TGFbeta signal transducers in the hypoderm...	KEEP AS NON CORE	Summary: PMID:12397107 shows dbl-1 mutants have reduced postembryonic growth affecting larval development stages. Reason: While dbl-1 affects larval development through its role in body size regulation, this is a broad developmental term. The core function is specifically body size and male tail regulation rather than general larval development. Supporting Evidence: PMID:12397107 viable, but smaller animals because of a reduction in postembryonic growth
GO:0045793 positive regulation of cell size	IMP PMID:12397107 The expression of TGFbeta signal transducers in the hypoderm...	ACCEPT	Summary: PMID:12397107 shows DBL-1 pathway affects cell size rather than cell number, with hypodermal blast cell size proportional to body size. Reason: DBL-1 regulates body size by affecting cell size rather than cell number. This is a well-characterized mechanism of DBL-1 action. Supporting Evidence: PMID:12397107 different tissues are reduced in size by different proportions, with hypodermal blast cell size most closely proportional to body size
GO:0046622 positive regulation of organ growth	IMP PMID:12397107 The expression of TGFbeta signal transducers in the hypoderm...	ACCEPT	Summary: PMID:12397107 demonstrates tissue-specific effects of DBL-1 on organ size, particularly hypodermis which is the primary target tissue. Reason: DBL-1 regulates organ size as part of its body size regulatory function. Different organs are affected to different degrees by dbl-1 mutations. Supporting Evidence: PMID:12397107 different tissues are reduced in size by different proportions
GO:0040018 positive regulation of multicellular organism growth	IGI PMID:15840165 C. elegans serine-threonine kinase KIN-29 modulates TGFbeta ...	ACCEPT	Summary: PMID:15840165 shows KIN-29 modulates TGF-beta signaling with genetic interactions demonstrating it acts downstream of dbl-1 but upstream of lon-1 target gene. Reason: Genetic epistasis analysis confirms dbl-1's position in the growth regulatory pathway. KIN-29 can suppress dbl-1 overexpression phenotype. Supporting Evidence: PMID:15840165 kin-29 is able to suppress the long mutant phenotype generated by animals over-expressing the ligand dbl-1 PMID:15840165 These data suggest that kin-29 genetically interacts with Sma/Mab pathway signaling downstream of dbl-1 but upstream of lon-1
GO:0040018 positive regulation of multicellular organism growth	IMP PMID:11784045 Hypodermal expression of Caenorhabditis elegans TGF-beta typ...	ACCEPT	Summary: PMID:11784045 demonstrates hypodermal expression of the DBL-1 receptor SMA-6 is essential for body length, confirming DBL-1's role in growth regulation. Reason: This study establishes the tissue-specific requirements for DBL-1 signaling in body size regulation, confirming DBL-1 as a growth-promoting signal. Supporting Evidence: PMID:11784045 One of these pathways regulates body length and is composed of the ligand DBL-1, serine/threonine protein kinase receptors SMA-6 and DAF-4

Gene Description

Existing Annotations Review

Core Functions

DBL-1 binds to SMA-6 (type I receptor) and DAF-4 (type II receptor) to activate downstream signaling. This leads to male tail patterning, affecting sensory ray formation, spicule development, and other male-specific copulatory structures.

DBL-1 functions in neuroimmune regulation, activating antimicrobial peptide expression in epidermis during fungal and bacterial infection via a TGF-beta signaling pathway.

References

Suggested Questions for Experts

Suggested Experiments

Tags

Deep Research

Falcon

📄 View Raw YAML