SLY1 (SLEEPY1; UniProt name GID2; locus At4g24210) is a small F-box protein that serves as the substrate-recognition subunit of the SCF(SLY1) E3 ubiquitin ligase, together with the SKP1-like proteins ASK1/ASK2, CULLIN1 and a RING-box protein. It is the Arabidopsis ortholog of rice GID2. Its N-terminal F-box binds ASK proteins, and its C-terminal region (GGF and LSL motifs) binds the GRAS domain of the nuclear DELLA growth repressors (GAI, RGA, RGL2 and others). When bioactive gibberellin binds the GID1 receptor and the GA-GID1 complex captures the DELLA N-terminal domain, DELLA binding to SLY1 is strongly enhanced; SCF(SLY1) then polyubiquitinates the DELLA, which is degraded by the 26S proteasome, relieving DELLA repression of growth. Cryo-EM structures of GA3-GID1A-RGA-SLY1-ASK complexes show that GID1A and SLY1 bind RGA through separate surfaces. sly1 loss-of-function mutants over-accumulate DELLAs and are GA-insensitive semi-dwarfs with reduced fertility, delayed flowering and strong seed dormancy, whereas gain-of-function alleles (sly1-d, sly1gar2-1) bind DELLAs more strongly and enhance GA signaling. The paralog SNEEZY/SLY2 can partly substitute when overexpressed. SLY1 is nuclear and widely expressed.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:15155881 The Arabidopsis F-box protein SLEEPY1 targets gibberellin si... | MODIFY | Summary: Direct binding of SLY1 to the DELLA protein GAI (Q9LQT8) via the DELLA GRAS domain; this is the substrate-recognition step by which the F-box subunit recruits DELLAs to SCF(SLY1). Reason: The interaction is the substrate-adaptor activity of an F-box protein: SLY1 links the DELLA substrate to the SKP1/ASK-CUL1 core of the SCF E3 ligase and confers substrate specificity. The informative MF is ubiquitin-like ligase-substrate adaptor activity rather than generic protein binding. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:15155881 SLY1 interacts directly with RGA and GA INSENSITIVE (GAI, a closely related DELLA protein) via their C-terminal GRAS domain PMID:15161962 SLY1 (the wild-type form) and sly1gar2-1 both confer substrate specificity on this complex via specific binding to the DELLA proteins |
| GO:0005515 protein binding | IPI PMID:15155881 The Arabidopsis F-box protein SLEEPY1 targets gibberellin si... | MODIFY | Summary: Direct binding of SLY1 to the DELLA protein RGA (Q9SLH3) via the DELLA GRAS domain; this is the substrate-recognition step by which the F-box subunit recruits DELLAs to SCF(SLY1). Reason: The interaction is the substrate-adaptor activity of an F-box protein: SLY1 links the DELLA substrate to the SKP1/ASK-CUL1 core of the SCF E3 ligase and confers substrate specificity. The informative MF is ubiquitin-like ligase-substrate adaptor activity rather than generic protein binding. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:15155881 SLY1 interacts directly with RGA and GA INSENSITIVE (GAI, a closely related DELLA protein) via their C-terminal GRAS domain PMID:15161962 SLY1 (the wild-type form) and sly1gar2-1 both confer substrate specificity on this complex via specific binding to the DELLA proteins |
| GO:0005515 protein binding | IPI PMID:15161962 The Arabidopsis mutant sleepy1gar2-1 protein promotes plant ... | REMOVE | Summary: Interaction of SLY1 with the SKP1-like protein ASK2/SKP1B (Q9FHW7) through its F-box, the contact that assembles SLY1 into the SCF complex. Reason: Generic protein binding is uninformative; SLY1-ASK association is represented by part_of SCF ubiquitin ligase complex (GO:0019005) and the adaptor activity. Removal does not mean the interaction is false. Supporting Evidence: PMID:15161962 SLY1 (the wild-type form) and sly1gar2-1 both confer substrate specificity on this complex via specific binding to the DELLA proteins |
| GO:0005515 protein binding | IPI PMID:15161962 The Arabidopsis mutant sleepy1gar2-1 protein promotes plant ... | MODIFY | Summary: Direct binding of SLY1 to the DELLA protein GAI (Q9LQT8) via the DELLA GRAS domain; this is the substrate-recognition step by which the F-box subunit recruits DELLAs to SCF(SLY1). Reason: The interaction is the substrate-adaptor activity of an F-box protein: SLY1 links the DELLA substrate to the SKP1/ASK-CUL1 core of the SCF E3 ligase and confers substrate specificity. The informative MF is ubiquitin-like ligase-substrate adaptor activity rather than generic protein binding. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:15161962 SLY1 (the wild-type form) and sly1gar2-1 both confer substrate specificity on this complex via specific binding to the DELLA proteins |
| GO:0005515 protein binding | IPI PMID:15161962 The Arabidopsis mutant sleepy1gar2-1 protein promotes plant ... | MODIFY | Summary: Direct binding of SLY1 to the DELLA protein RGA (Q9SLH3) via the DELLA GRAS domain; this is the substrate-recognition step by which the F-box subunit recruits DELLAs to SCF(SLY1). Reason: The interaction is the substrate-adaptor activity of an F-box protein: SLY1 links the DELLA substrate to the SKP1/ASK-CUL1 core of the SCF E3 ligase and confers substrate specificity. The informative MF is ubiquitin-like ligase-substrate adaptor activity rather than generic protein binding. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:15161962 SLY1 (the wild-type form) and sly1gar2-1 both confer substrate specificity on this complex via specific binding to the DELLA proteins |
| GO:0005515 protein binding | IPI PMID:16709201 Identification and characterization of Arabidopsis gibberell... | REMOVE | Summary: Association of SLY1 with the GA receptor GID1B (Q9LYC1) in yeast multi-hybrid assays, where DELLA bridges the GA-GID1 receptor to SLY1. Reason: Generic protein binding is uninformative; the association is DELLA-bridged within the GA-GID1-DELLA-SCF(SLY1) complex (cryo-EM shows RGA binds GID1A and SLY1 through non-overlapping surfaces). Removal does not mean the association is false. Supporting Evidence: PMID:16709201 A two-hybrid yeast system only showed in vivo interaction in the presence of GA(4) between each AtGID1 and the Arabidopsis DELLA proteins PMID:40542507 RGA interacts with GID1A and SLY1 through nonoverlapping binding surfaces |
| GO:0005515 protein binding | IPI PMID:16709201 Identification and characterization of Arabidopsis gibberell... | REMOVE | Summary: Association of SLY1 with the GA receptor GID1A (Q9MAA7) in yeast multi-hybrid assays, where DELLA bridges the GA-GID1 receptor to SLY1. Reason: Generic protein binding is uninformative; the association is DELLA-bridged within the GA-GID1-DELLA-SCF(SLY1) complex (cryo-EM shows RGA binds GID1A and SLY1 through non-overlapping surfaces). Removal does not mean the association is false. Supporting Evidence: PMID:16709201 A two-hybrid yeast system only showed in vivo interaction in the presence of GA(4) between each AtGID1 and the Arabidopsis DELLA proteins PMID:40542507 RGA interacts with GID1A and SLY1 through nonoverlapping binding surfaces |
| GO:0005515 protein binding | IPI PMID:17194763 Genetic characterization and functional analysis of the GID1... | MODIFY | Summary: Direct binding of SLY1 to the DELLA protein GAI (Q9LQT8) via the DELLA GRAS domain; this is the substrate-recognition step by which the F-box subunit recruits DELLAs to SCF(SLY1). Reason: The interaction is the substrate-adaptor activity of an F-box protein: SLY1 links the DELLA substrate to the SKP1/ASK-CUL1 core of the SCF E3 ligase and confers substrate specificity. The informative MF is ubiquitin-like ligase-substrate adaptor activity rather than generic protein binding. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:17194763 the GA-GID1 complex promotes the interaction between RGA and the F-box protein SLY1 PMID:15161962 SLY1 (the wild-type form) and sly1gar2-1 both confer substrate specificity on this complex via specific binding to the DELLA proteins |
| GO:0005515 protein binding | IPI PMID:17194763 Genetic characterization and functional analysis of the GID1... | REMOVE | Summary: Association of SLY1 with the GA receptor GID1A (Q9MAA7) in yeast multi-hybrid assays, where DELLA bridges the GA-GID1 receptor to SLY1. Reason: Generic protein binding is uninformative; the association is DELLA-bridged within the GA-GID1-DELLA-SCF(SLY1) complex (cryo-EM shows RGA binds GID1A and SLY1 through non-overlapping surfaces). Removal does not mean the association is false. Supporting Evidence: PMID:17194763 the GA-GID1 complex promotes the interaction between RGA and the F-box protein SLY1 PMID:40542507 RGA interacts with GID1A and SLY1 through nonoverlapping binding surfaces |
| GO:0005515 protein binding | IPI PMID:17194763 Genetic characterization and functional analysis of the GID1... | MODIFY | Summary: Direct binding of SLY1 to the DELLA protein RGA (Q9SLH3) via the DELLA GRAS domain; this is the substrate-recognition step by which the F-box subunit recruits DELLAs to SCF(SLY1). Reason: The interaction is the substrate-adaptor activity of an F-box protein: SLY1 links the DELLA substrate to the SKP1/ASK-CUL1 core of the SCF E3 ligase and confers substrate specificity. The informative MF is ubiquitin-like ligase-substrate adaptor activity rather than generic protein binding. Proposed replacements: ubiquitin-like ligase-substrate adaptor activity Supporting Evidence: PMID:17194763 the GA-GID1 complex promotes the interaction between RGA and the F-box protein SLY1 PMID:15161962 SLY1 (the wild-type form) and sly1gar2-1 both confer substrate specificity on this complex via specific binding to the DELLA proteins |
| GO:0005515 protein binding | IPI PMID:19500306 Differential expression and affinities of Arabidopsis gibber... | REMOVE | Summary: Association of SLY1 with the GA receptor GID1B (Q9LYC1) in yeast multi-hybrid assays, where DELLA bridges the GA-GID1 receptor to SLY1. Reason: Generic protein binding is uninformative; the association is DELLA-bridged within the GA-GID1-DELLA-SCF(SLY1) complex (cryo-EM shows RGA binds GID1A and SLY1 through non-overlapping surfaces). Removal does not mean the association is false. Supporting Evidence: PMID:19500306 We then evaluated the affinity of the AtGID1-DELLA interaction by a competitive yeast three-hybrid system PMID:40542507 RGA interacts with GID1A and SLY1 through nonoverlapping binding surfaces |
| GO:0005515 protein binding | IPI PMID:19500306 Differential expression and affinities of Arabidopsis gibber... | REMOVE | Summary: Association of SLY1 with the GA receptor GID1A (Q9MAA7) in yeast multi-hybrid assays, where DELLA bridges the GA-GID1 receptor to SLY1. Reason: Generic protein binding is uninformative; the association is DELLA-bridged within the GA-GID1-DELLA-SCF(SLY1) complex (cryo-EM shows RGA binds GID1A and SLY1 through non-overlapping surfaces). Removal does not mean the association is false. Supporting Evidence: PMID:19500306 We then evaluated the affinity of the AtGID1-DELLA interaction by a competitive yeast three-hybrid system PMID:40542507 RGA interacts with GID1A and SLY1 through nonoverlapping binding surfaces |
| GO:0005515 protein binding | IPI PMID:21798944 Evidence for network evolution in an Arabidopsis interactome... | REMOVE | Summary: Interaction of SLY1 with the SKP1-like protein ASK2/SKP1B (Q9FHW7) through its F-box, the contact that assembles SLY1 into the SCF complex. Reason: Generic protein binding is uninformative; SLY1-ASK association is represented by part_of SCF ubiquitin ligase complex (GO:0019005) and the adaptor activity. Removal does not mean the interaction is false. Supporting Evidence: PMID:21798944 We tested all pair-wise combinations of proteins encoded by these constructs (space 1) with an improved high-throughput binary interactome mapping pipeline based on the yeast two-hybrid (Y2H) system |
| GO:0005515 protein binding | IPI PMID:32612234 Extensive signal integration by the phytohormone protein net... | REMOVE | Summary: High-throughput yeast two-hybrid interaction of SLY1 with GAI (Q9LQT8) from the phytohormone interactome map. Reason: Generic protein binding is uninformative; the SLY1-DELLA substrate-adaptor relationship is captured by GO:1990756 from focused studies. Removal does not mean the interaction is false. Supporting Evidence: PMID:32612234 we experimentally generated a systems-level map of the Arabidopsis phytohormone signalling network, consisting of more than 2,000 binary protein-protein interactions |
| GO:0005634 nucleus | IDA PMID:15155881 The Arabidopsis F-box protein SLEEPY1 targets gibberellin si... | ACCEPT | Summary: Nuclear localization of SLY1 (IDA). Reason: SLY1 is experimentally nuclear, matching the nuclear location of its DELLA substrates. Supporting Evidence: PMID:15155881 SLY1 is a nuclear-localized F-box component of the SCF SLY1 E3 ubiquitin ligase |
| GO:0005634 nucleus | IEA GO_REF:0000120 | ACCEPT | Summary: Nuclear localization of SLY1 (IEA). Reason: SLY1 is experimentally nuclear, matching the nuclear location of its DELLA substrates. Supporting Evidence: PMID:15155881 SLY1 is a nuclear-localized F-box component of the SCF SLY1 E3 ubiquitin ligase |
| GO:0005634 nucleus | ISM GO_REF:0000122 | ACCEPT | Summary: Nuclear localization of SLY1 (ISM). Reason: SLY1 is experimentally nuclear, matching the nuclear location of its DELLA substrates. Supporting Evidence: PMID:15155881 SLY1 is a nuclear-localized F-box component of the SCF SLY1 E3 ubiquitin ligase |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cytoplasmic location inferred from a broad eukaryotic F-box node (seeded by AT1G21760 and human FBXO9). Reason: Not contradicted (SCF components are nucleocytoplasmic), but SLY1 has been localized experimentally to the nucleus, where its DELLA substrates act; a cytoplasmic pool has no demonstrated role in GA signaling. Supporting Evidence: PMID:15155881 SLY1 is a nuclear-localized F-box component of the SCF SLY1 E3 ubiquitin ligase |
| GO:0009740 gibberellic acid mediated signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Participation in GA signaling, inferred from the land-plant SLY1/GID2 node (PTN001767709) seeded by rice GID2; directly supported in Arabidopsis by sly1 GA-insensitive phenotypes and DELLA over-accumulation. Reason: Core process: SCF(SLY1)-mediated DELLA degradation is the transducing step of the GA signaling pathway. Supporting Evidence: PMID:12724538 The Arabidopsis SLY1 (SLEEPY1) gene positively regulates gibberellin (GA) signaling PMID:12724538 sly1 mutations cause a significant increase in RGA protein accumulation even after GA treatment |
| GO:0009845 seed germination | IMP PMID:17384169 Seed germination of GA-insensitive sleepy1 mutants does not ... | KEEP AS NON CORE | Summary: sly1 mutant seeds show germination defects (strong dormancy), rescued by after-ripening. Reason: Real GA-dependent developmental output downstream of DELLA degradation, not the molecular core function; acts_upstream_of_or_within qualifier appropriate. Supporting Evidence: PMID:17384169 Unlike ga1-3, the GA-insensitive sly1 mutants show variable seed dormancy |
| GO:0009937 regulation of gibberellic acid mediated signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: InterPro-based (IPR044184, SLY1/SNE F-box family) annotation to regulation of GA signaling. Reason: Correct but non-directional; SLY1 is a positive effector of GA signaling (loss-of-function causes GA insensitivity, gain-of-function sly1-d and sly1gar2-1 enhance GA signaling). The more precise term positive regulation of gibberellic acid mediated signaling pathway is supported experimentally. Proposed replacements: positive regulation of gibberellic acid mediated signaling pathway Supporting Evidence: PMID:12724538 The Arabidopsis SLY1 (SLEEPY1) gene positively regulates gibberellin (GA) signaling |
| GO:0009939 positive regulation of gibberellic acid mediated signaling pathway | IMP PMID:12724538 The Arabidopsis SLEEPY1 gene encodes a putative F-box subuni... | ACCEPT | Summary: sly1 loss-of-function mutants are GA-insensitive dwarfs that over-accumulate RGA, establishing SLY1 as a positive regulator of GA signaling. Reason: Core role, directly supported by mutant phenotype and suppression by rga. Supporting Evidence: PMID:12724538 The Arabidopsis SLY1 (SLEEPY1) gene positively regulates gibberellin (GA) signaling PMID:12724538 an rga null allele partially suppresses the sly1-10 mutant phenotype |
| GO:0010162 seed dormancy process | IMP PMID:17384169 Seed germination of GA-insensitive sleepy1 mutants does not ... | KEEP AS NON CORE | Summary: sly1 mutants have increased seed dormancy, alleviated by after-ripening. Reason: Downstream physiological output of GA signaling; SLY1 acts upstream of dormancy via DELLA (RGL2) regulation and ABA. Non-core. Supporting Evidence: PMID:17384169 Seed lots with high seed dormancy after-ripened slowly, with stronger alleles requiring more time |
| GO:0016567 protein ubiquitination | IEA GO_REF:0000041 | ACCEPT | Summary: Protein ubiquitination via UniPathway mapping; SCF(SLY1) polyubiquitinates DELLA proteins. Reason: Consistent with SLY1 acting as the substrate adaptor of an SCF E3 ligase; a broader parent of the SCF-dependent catabolic process annotation. Supporting Evidence: PMID:15155881 These findings suggested that SLY1 recruits RGA to the SCFSLY1 E3 ligase complex for ubiquitination and subsequent degradation by the 26S proteasome |
| GO:0019005 SCF ubiquitin ligase complex | IBA GO_REF:0000033 | ACCEPT | Summary: SLY1 is the F-box subunit of SCF(SLY1), containing ASK1/ASK2 and CUL1 (IBA). Reason: Directly supported by co-immunoprecipitation of SLY1 with ASK1/2 and AtCUL1 and by the cryo-EM SLY1-ASK1/ASK2 complexes. Supporting Evidence: PMID:15161962 SLY1 is a subunit of an Arabidopsis SCF SLY1 E3 ubiquitin ligase complex that contains the highly conserved ASK1/2 and AtCUL1 subunits PMID:21163960 Like HA-SLY1, HA-SNE interacted with the CULLIN1 subunit of the SCF complex, and this interaction required the F-box domain |
| GO:0019005 SCF ubiquitin ligase complex | IEA GO_REF:0000120 | ACCEPT | Summary: SLY1 is the F-box subunit of SCF(SLY1), containing ASK1/ASK2 and CUL1 (IEA). Reason: Directly supported by co-immunoprecipitation of SLY1 with ASK1/2 and AtCUL1 and by the cryo-EM SLY1-ASK1/ASK2 complexes. Supporting Evidence: PMID:15161962 SLY1 is a subunit of an Arabidopsis SCF SLY1 E3 ubiquitin ligase complex that contains the highly conserved ASK1/2 and AtCUL1 subunits PMID:21163960 Like HA-SLY1, HA-SNE interacted with the CULLIN1 subunit of the SCF complex, and this interaction required the F-box domain |
| GO:0019005 SCF ubiquitin ligase complex | IPI PMID:15161962 The Arabidopsis mutant sleepy1gar2-1 protein promotes plant ... | ACCEPT | Summary: SLY1 is the F-box subunit of SCF(SLY1), containing ASK1/ASK2 and CUL1 (IPI). Reason: Directly supported by co-immunoprecipitation of SLY1 with ASK1/2 and AtCUL1 and by the cryo-EM SLY1-ASK1/ASK2 complexes. Supporting Evidence: PMID:15161962 SLY1 is a subunit of an Arabidopsis SCF SLY1 E3 ubiquitin ligase complex that contains the highly conserved ASK1/2 and AtCUL1 subunits PMID:21163960 Like HA-SLY1, HA-SNE interacted with the CULLIN1 subunit of the SCF complex, and this interaction required the F-box domain |
| GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process | IBA GO_REF:0000033 | ACCEPT | Summary: SCF-dependent proteasomal degradation, inferred from the eukaryotic F-box node; in Arabidopsis SCF(SLY1) targets DELLAs for 26S proteasome-dependent destruction. Reason: Core process: SLY1 is required for GA-induced proteasomal DELLA degradation (RGA, GAI, RGL2 over-accumulate in sly1). Supporting Evidence: PMID:15161962 promotes plant growth by targeting DELLA protein nuclear growth repressors for destruction in the proteasome PMID:12724538 sly1 mutations cause a significant increase in RGA protein accumulation even after GA treatment |
| GO:1990756 ubiquitin-like ligase-substrate adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: F-box substrate-adaptor activity inferred from a broad eukaryotic F-box node (PTN000305657); SLY1 has direct experimental support for binding DELLA substrates and conferring substrate specificity on SCF(SLY1). Reason: Core molecular function of SLY1, supported by direct DELLA binding, ASK/CUL1 association via the F-box, and the cryo-EM GA3-GID1A-RGA-SLY1-ASK1 structure. Supporting Evidence: PMID:15161962 SLY1 (the wild-type form) and sly1gar2-1 both confer substrate specificity on this complex via specific binding to the DELLA proteins PMID:15155881 SLY1 interacts directly with RGA and GA INSENSITIVE (GAI, a closely related DELLA protein) via their C-terminal GRAS domain PMID:40768360 Contrary to prior models, SLY1 binds the GRAS domain |
Loading supporting content…
Download this section (compressed HTML)Q: How much of SLY1-dependent GA signaling in seeds and stems is mediated by proteasomal DELLA degradation versus SLY1-independent, proteolysis-independent GID1 inhibition of DELLA?
Q: Does SLY1 show preference among the five DELLA proteins (e.g. RGL2 versus RGA) that explains the different abilities of SLY1 and SNE to rescue sly1 phenotypes?
Q: Which RING-box and neddylation components are required for SCF(SLY1) activity on DELLAs in vivo?
Experiment: Reconstitute SCF(SLY1) (SLY1, ASK1, CUL1, RBX1) with E1/E2 in vitro and measure GA- and GID1-dependent polyubiquitination of each DELLA protein to define substrate preference quantitatively.
Experiment: Introduce structure-guided point mutations in the SLY1 GRAS-binding surface identified by cryo-EM and test DELLA turnover and growth rescue in sly1-10.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)