stlB

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0006633 fatty acid biosynthetic process	IBA GO_REF:0000033	REMOVE	Summary: Phylogenetic inference of fatty acid biosynthesis from type I FAS family members. StlB contains FAS-like catalytic domains but is a hybrid polyketide synthase whose physiological output is the acylphloroglucinol backbone of DIF-1, not free fatty acids. Reason: This IBA is an over-propagation from the metazoan type I FAS family. The N-terminal FAS-like module of StlB only generates a hexanoyl starter that is channeled internally to the C-terminal type III PKS domain to build a polyketide; StlB does not produce fatty acids as pathway products. Polyketide biosynthetic process and DIF-1 biosynthetic process capture the true biology. Propagation Review Root cause: PROPAGATION BAD Failure modes: FUNCTIONAL DIVERGENCE Sources checked: PANTHER:PTN001711534 · PANTHER node for the type I FAS / PKS family SUPPORTS SOURCE BUT NOT TARGET Fatty acid biosynthesis reflects canonical type I FAS members; StlB is a hybrid FAS-type III PKS that makes a polyketide (DIF-1 backbone), not fatty acids Supporting Evidence: PMID:16906151 Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) PMID:16906151 this type III PKS efficiently synthesizes PCP
GO:0004315 3-oxoacyl-[acyl-carrier-protein] synthase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO annotation from the ketoacyl synthase (KS) domain signature. StlB does contain a functional beta-ketoacyl synthase (condensing) domain used to elongate the acyl intermediate, so this is a genuine component activity, but it is not the distinctive core function of the protein. Reason: The KS domain and its condensation (3-oxoacyl-ACP synthase) chemistry are real parts of the StlB catalytic cycle, but the enzyme's defining function is synthesis of the DIF-1 acylphloroglucinol backbone (THPH synthase). This domain-level activity is best kept as non-core supporting machinery. Supporting Evidence: PMID:16906151 Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs)
GO:0006633 fatty acid biosynthetic process	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: InterPro2GO annotation from the ketoacyl synthase active-site signature. As with the IBA, this reflects FAS-like domains rather than the actual product of StlB, which is a polyketide (DIF-1 backbone). Reason: The FAS-like domains of StlB build a hexanoyl intermediate that is fed into the type III PKS domain to make an acylphloroglucinol; the enzyme does not release fatty acids. Annotating fatty acid biosynthetic process over-states a housekeeping-lipid role that StlB does not play. Supporting Evidence: PMID:16906151 the acylphloroglucinol skeleton of both DIF-1 and its in vivo degradation product DIF-3
GO:0016210 naringenin-chalcone synthase activity	IEA GO_REF:0000120	MODIFY	Summary: Electronic annotation derived from the C-terminal type III (chalcone-synthase-like) PKS domain and its EC 2.3.1.74 mapping. The domain is homologous to plant chalcone synthase, but the demonstrated physiological product of StlB is an acylphloroglucinol (THPH), not naringenin chalcone. Reason: The type III PKS domain is CHS-like, but experimentally StlB (Steely2) synthesizes the acylphloroglucinol backbone (THPH/PCP) of DIF-1, not a chalcone. The more accurate molecular function is THPH synthase activity. Proposed replacements: THPH synthase activity Supporting Evidence: PMID:16906151 the acylphloroglucinol skeleton of both DIF-1 and its in vivo degradation product DIF-3
GO:0016491 oxidoreductase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO annotation from the enoyl reductase / ketoreductase domains. StlB contains ER and KR domains that perform reductive tailoring of the growing chain, so oxidoreductase activity is present but generic. Reason: The ER and KR domains are genuine oxidoreductase modules within the FAS-like part of StlB, but this is a very general activity that reflects component chemistry rather than the enzyme's distinctive THPH-synthesizing function. Supporting Evidence: PMID:16906151 Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs)
GO:0016740 transferase activity	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: Very high-level root transferase term propagated from InterPro. Not informative about the specific function of StlB. Reason: transferase activity is an uninformative superclass. StlB has specific, better-characterized transferase/acyltransferase and synthase activities; the bare root term adds no curation value.
GO:0016746 acyltransferase activity	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO annotation from the acyltransferase (malonyl-CoA:ACP transacylase, MAT) domain. StlB has a functional AT/MAT domain that loads malonyl units, so acyltransferase activity is a real component activity. Reason: The AT/MAT domain genuinely catalyzes acyl transfer during chain loading, but this is supporting machinery for the core THPH synthase function rather than a distinctive activity by itself. Supporting Evidence: PMID:16906151 Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs)
GO:0031177 phosphopantetheine binding	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: InterPro2GO annotation from the carrier (acyl-carrier-protein) domain. StlB contains a phosphopantetheine-attachment (carrier) domain that tethers the growing acyl/polyketide chain, so this cofactor-binding activity is correct but ancillary. Reason: The ACP/carrier domain of StlB is post-translationally modified with phosphopantetheine and binds it covalently, consistent with this annotation. It is a genuine but accessory feature supporting substrate channeling rather than the enzyme's core synthase function.
GO:0044550 secondary metabolite biosynthetic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA machine-learning annotation. DIF-1 and related acylphloroglucinols are secondary metabolites, so this high-level process term is correct. Reason: StlB produces the polyketide backbone of DIF-1, a bona fide secondary metabolite, so involvement in secondary metabolite biosynthetic process is accurate, if more general than polyketide/DIF-1 biosynthetic process. Supporting Evidence: PMID:16906151 responsible for biosynthesis of the DIF acylphloroglucinol scaffold
GO:0106265 THPH synthase activity	IEA GO_REF:0000116	ACCEPT	Summary: Rhea-based electronic annotation of THPH synthase activity (hexanoyl-CoA + 3 malonyl-CoA -> 2,4,6-trihydroxyphenylhexan-1-one). This is the experimentally demonstrated core activity of StlB. Reason: THPH synthase activity is exactly the reaction StlB (Steely2) was shown to catalyze, producing the acylphloroglucinol precursor of DIF-1. The electronic Rhea annotation agrees with the experimental evidence. Supporting Evidence: PMID:16906151 this type III PKS efficiently synthesizes PCP
GO:0009813 flavonoid biosynthetic process	IEA GO_REF:0000041	REMOVE	Summary: UniPathway-based electronic annotation propagated from the chalcone synthase EC 2.3.1.74 mapping to the plant flavonoid pathway. Dictyostelium does not make flavonoids; StlB makes the DIF-1 acylphloroglucinol backbone. Reason: Flavonoid biosynthesis is a plant-specific pathway. This annotation is an artifact of mapping the CHS-like domain / EC 2.3.1.74 onto the flavonoid UniPathway. StlB has no role in flavonoid biosynthesis in the amoeba; its product feeds DIF-1 (secondary metabolite / polyketide) biosynthesis. Supporting Evidence: PMID:16906151 the acylphloroglucinol skeleton of both DIF-1 and its in vivo degradation product DIF-3
GO:0016210 naringenin-chalcone synthase activity	EXP PMID:16906151 Biosynthesis of Dictyostelium discoideum differentiation-ind...	MODIFY	Summary: Experimental annotation based on the CHS-like C-terminal type III PKS domain assayed in vitro. Although the domain is homologous to chalcone synthase (EC 2.3.1.74) and can act as an iterative type III PKS, the product demonstrated for StlB is an acylphloroglucinol (THPH/PCP), not naringenin chalcone. Reason: The demonstrated reaction is synthesis of the acylphloroglucinol skeleton of DIF-1 via three polyketide extensions and a Claisen cyclization, captured precisely by THPH synthase activity. naringenin-chalcone synthase names a specific plant reaction the enzyme does not physiologically perform, so the term should be updated to the demonstrated activity. Proposed replacements: THPH synthase activity Supporting Evidence: PMID:16906151 the acylphloroglucinol skeleton of both DIF-1 and its in vivo degradation product DIF-3
GO:0106265 THPH synthase activity	EXP PMID:16906151 Biosynthesis of Dictyostelium discoideum differentiation-ind...	ACCEPT	Summary: Experimental demonstration that the StlB (Steely2) C-terminal type III PKS synthesizes PCP/THPH, the acylphloroglucinol skeleton of DIF-1, via three polyketide extensions of a hexanoyl starter and a CHS-like intramolecular Claisen condensation. This is the defining molecular function of StlB. Reason: In vitro assays of the isolated C-terminal domain and in vivo knockout plus PCP rescue directly establish StlB as the THPH/PCP synthase of the DIF-1 pathway. This is the core activity. Supporting Evidence: PMID:16906151 this type III PKS efficiently synthesizes PCP PMID:16906151 confirms Steely2-mediated catalysis of PCP biosynthesis in vivo
GO:0018893 dibenzofuran metabolic process	IMP PMID:36252029 Yellow polyketide pigment suppresses premature hatching in s...	MODIFY	Summary: This term appears to be a chemical mis-mapping. DIF-1 is a chlorinated acylphloroglucinol (an alkylphenone), not a dibenzofuran, and the cited paper is about the pks5-derived dictyodenes and mentions StlB only as being required for DIF-1 synthesis. The intended biology is StlB's role in producing the DIF-1 polyketide. Reason: dibenzofuran metabolic process is chemically inappropriate for the DIF-1 acylphloroglucinol product of StlB, and PMID:36252029 does not characterize dibenzofuran metabolism by StlB. The supported biology, that StlB is required for DIF-1 synthesis, is better represented by DIF-1 biosynthetic process. Proposed replacements: DIF-1 biosynthetic process Supporting Evidence: PMID:36252029 StlB is required for the synthesis of differentiation-inducing factor I
GO:0031149 sorocarp stalk cell differentiation	IGI PMID:24096661 Steely enzymes are involved in prestalk and prespore pattern...	ACCEPT	Summary: Genetic-interaction evidence (with stlA) that Steely polyketides drive prestalk/stalk differentiation. DIF-1, the product of the StlB pathway, is the major stalk cell inducer, and the stlA/stlB double knockout loses pstA marker expression. Reason: Loss of Steely-derived polyketides (including DIF-1 from StlB) impairs prestalk/stalk cell differentiation, supporting involvement in sorocarp stalk cell differentiation. This is a genuine developmental role of StlB acting through DIF-1. Supporting Evidence: PMID:24096661 a product of SteelyB, was identified as the major stalk cell inducer PMID:24096661 the stlA and stlB double-knockout mutant lost pstA marker gene expression
GO:0048102 autophagic cell death	IMP PMID:25518941 c-di-GMP induction of Dictyostelium cell death requires the ...	KEEP AS NON CORE	Summary: stlB disruption (and cerulenin inhibition of polyketide synthesis) almost completely prevents c-di-GMP-induced vacuolar cell death, showing that an stlB-dependent polyketide (DIF-1) is required for this developmental cell death. StlB acts upstream via DIF-1 rather than directly executing cell death. Reason: The requirement for StlB in developmental (vacuolar/autophagic) cell death is an indirect, downstream consequence of DIF-1 production, not a core molecular function of the enzyme. It is a valid acts_upstream_of_or_within annotation but non-core. Supporting Evidence: PMID:25518941 the stlB-initiated biosynthetic cascade included at least one polyketide required for the major part of cell death induction by c-di-GMP
GO:0010628 positive regulation of gene expression	IGI PMID:27305283 Stalk cell differentiation without polyketides in the cellul...	KEEP AS NON CORE	Summary: DIF-1, produced via StlB, induces prestalk gene expression; in the stlA/stlB double knockout, prestalk gene expression is reduced. StlB thereby acts upstream of positive regulation of prestalk gene expression. Reason: This is a downstream, DIF-1-mediated transcriptional effect rather than a core molecular function of StlB. The generic term is a valid acts_upstream_of_or_within annotation but is non-core. Supporting Evidence: PMID:27305283 expression of prestalk genes is also reduced PMID:18402932 induces the expression of a subset of prestalk genes
GO:0010629 negative regulation of gene expression	IGI PMID:27305283 Stalk cell differentiation without polyketides in the cellul...	KEEP AS NON CORE	Summary: DIF-1, produced via StlB, represses prespore gene expression, so StlB acts upstream of negative regulation of gene expression through its DIF-1 product. Reason: Repression of prespore genes is a downstream, DIF-1-mediated transcriptional effect, not a core molecular function of StlB. Valid as an acts_upstream_of_or_within annotation but non-core. Supporting Evidence: PMID:18402932 represses the expression of all tested prespore genes
GO:0031149 sorocarp stalk cell differentiation	IMP PMID:18402932 DIF-1 induces the basal disc of the Dictyostelium fruiting b...	ACCEPT	Summary: The stlB (PKS) null mutant, which makes no DIF-1, has ~35% fewer prestalk cells and a specific deficit of prestalk-O cells and anterior-like cells, with rescue by exogenous DIF-1. StlB is required, via DIF-1, for prestalk/stalk cell differentiation. Reason: Direct mutant phenotype shows StlB (through DIF-1) is needed for normal prestalk/stalk cell differentiation, supporting this annotation. Supporting Evidence: PMID:18402932 Both methyltransferase null and PKS null mutants produced only approximately 65% of the wild-type proportion of prestalk cells PMID:18402932 The backbone of DIF-1 consists of a 12-carbon polyketide produced by the steely B (stlB) PKS
GO:0031288 sorocarp morphogenesis	IMP PMID:18402932 DIF-1 induces the basal disc of the Dictyostelium fruiting b...	KEEP AS NON CORE	Summary: The stlB null mutant forms strikingly abnormal fruiting bodies lacking the basal disc, with a rudimentary lower cup and a spore mass that slips down the stalk; these defects are corrected by DIF-1. StlB is required, via DIF-1, for normal sorocarp morphogenesis. Reason: The morphogenesis defects are downstream developmental consequences of losing DIF-1, an indirect role of the enzyme. It is a valid acts_upstream_of_or_within annotation but non-core relative to the molecular synthase function. Supporting Evidence: PMID:18402932 The basal disc is almost entirely absent from the PKS null mutant fruiting bodies PMID:18402932 DIF-1 is required for slug migration and crucially for the formation of the lower cup and basal disc of the fruiting body
GO:0030639 polyketide biosynthetic process	IDA PMID:16906151 Biosynthesis of Dictyostelium discoideum differentiation-ind...	ACCEPT	Summary: Direct assay evidence that StlB is an iterative polyketide synthase producing the acylphloroglucinol (PCP/THPH) polyketide. This is a core biological process for StlB. Reason: In vitro and in vivo evidence establishes StlB as a polyketide synthase building the DIF-1 acylphloroglucinol backbone, directly supporting involvement in polyketide biosynthetic process. Supporting Evidence: PMID:16906151 this type III PKS efficiently synthesizes PCP
GO:0031148 DIF-1 biosynthetic process	IMP PMID:16906151 Biosynthesis of Dictyostelium discoideum differentiation-ind...	ACCEPT	Summary: StlB (Steely2) is the missing DIF-pathway PCP synthase; the Steely2 null fails to accumulate DIF-1 and is rescued by exogenous PCP, identifying StlB as catalyzing the committed first step of DIF-1 biosynthesis. This is a core biological process for StlB. Reason: Genetic and biochemical evidence directly place StlB at the start of the DIF-1 biosynthetic pathway, producing the acylphloroglucinol scaffold that is then chlorinated and methylated to DIF-1. Supporting Evidence: PMID:16906151 our definitive identification of Steely2 as the missing DIF-pathway PCP synthase (DAPS) PMID:16906151 confirms Steely2-mediated catalysis of PCP biosynthesis in vivo

Gene Description

Existing Annotations Review

Core Functions

References

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