Ser

UniProt ID: P18168
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Ser (Serrate) encodes a DSL-family transmembrane ligand of the Drosophila Notch receptor, the ortholog of vertebrate Jagged. Its extracellular region contains an N-terminal MNNL/DSL domain, 14 EGF-like repeats and a cysteine-rich region. Serrate binds Notch EGF repeats 11-12 with an affinity similar to Delta, and its signaling competence depends on Mind bomb/Neuralized-mediated ubiquitination and endocytosis via a conserved intracellular motif. Serrate also cis-inhibits Notch in the same cell. Glycosylation of Notch by Fringe reduces responsiveness to Serrate while potentiating Delta signaling, which restricts Serrate-Notch signaling to the dorsal/ventral boundary of the wing disc. Serrate signaling contributes to wing margin formation, leg segmentation, eye development, embryonic denticle patterning, salivary gland and tracheal development, glial proliferation and crystal cell specification during hematopoiesis.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005112 Notch binding
IBA
GO_REF:0000033
ACCEPT
Summary: Serrate binds Notch in trans via the same EGF repeats (11-12) of Notch that bind Delta (IBA).
Reason: Direct Serrate-Notch binding is shown by cell aggregation and soluble ectodomain binding assays, with affinity similar to Delta-Notch; binding is modulated by Ofut1 and Fringe. Core molecular function of the ligand.
Supporting Evidence:
PMID:1657403
We report a novel molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, and show that the same two EGF repeats of Notch also constitute a Serrate binding domain.
PMID:10504334
Contrary to previous suggestions, our evidence implies that the interactions between Serrate and Notch are similar in affinity to those between Delta and Notch.
GO:0005112 Notch binding
IDA
PMID:10504334
Ligand-receptor interactions and trans-endocytosis of Delta,...
ACCEPT
Summary: Serrate binds Notch in trans via the same EGF repeats (11-12) of Notch that bind Delta (IDA).
Reason: Direct Serrate-Notch binding is shown by cell aggregation and soluble ectodomain binding assays, with affinity similar to Delta-Notch; binding is modulated by Ofut1 and Fringe. Core molecular function of the ligand.
Supporting Evidence:
PMID:10504334
Ligand-receptor interactions and trans-endocytosis of Delta, Serrate and Notch: members of the Notch signalling pathway in Drosophila
PMID:1657403
We report a novel molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, and show that the same two EGF repeats of Notch also constitute a Serrate binding domain.
GO:0005112 Notch binding
IDA
PMID:12909620
Modulation of notch-ligand binding by protein O-fucosyltrans...
ACCEPT
Summary: Serrate binds Notch in trans via the same EGF repeats (11-12) of Notch that bind Delta (IDA).
Reason: Direct Serrate-Notch binding is shown by cell aggregation and soluble ectodomain binding assays, with affinity similar to Delta-Notch; binding is modulated by Ofut1 and Fringe. Core molecular function of the ligand.
Supporting Evidence:
PMID:12909620
To investigate the molecular basis for the requirement for O-linked fucose on Notch, we assayed the ability of tagged, soluble forms of the Notch extracellular domain to bind to its ligands, Delta and Serrate
PMID:1657403
We report a novel molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, and show that the same two EGF repeats of Notch also constitute a Serrate binding domain.
PMID:10504334
Contrary to previous suggestions, our evidence implies that the interactions between Serrate and Notch are similar in affinity to those between Delta and Notch.
GO:0005112 Notch binding
IDA
PMID:17923477
In vitro reconstitution of the modulation of Drosophila Notc...
ACCEPT
Summary: Serrate binds Notch in trans via the same EGF repeats (11-12) of Notch that bind Delta (IDA).
Reason: Direct Serrate-Notch binding is shown by cell aggregation and soluble ectodomain binding assays, with affinity similar to Delta-Notch; binding is modulated by Ofut1 and Fringe. Core molecular function of the ligand.
Supporting Evidence:
PMID:17923477
In vitro glycosylation and ligand binding studies establish that the addition of N-acetylglucosamine onto O-fucose in vitro is sufficient both to enhance Notch binding to the Delta ligand and to inhibit Notch binding to the Serrate ligand
PMID:1657403
We report a novel molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, and show that the same two EGF repeats of Notch also constitute a Serrate binding domain.
PMID:10504334
Contrary to previous suggestions, our evidence implies that the interactions between Serrate and Notch are similar in affinity to those between Delta and Notch.
GO:0005112 Notch binding
IEA
GO_REF:0000002
ACCEPT
Summary: Serrate binds Notch in trans via the same EGF repeats (11-12) of Notch that bind Delta (IEA).
Reason: Direct Serrate-Notch binding is shown by cell aggregation and soluble ectodomain binding assays, with affinity similar to Delta-Notch; binding is modulated by Ofut1 and Fringe. Core molecular function of the ligand.
Supporting Evidence:
PMID:1657403
We report a novel molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, and show that the same two EGF repeats of Notch also constitute a Serrate binding domain.
PMID:10504334
Contrary to previous suggestions, our evidence implies that the interactions between Serrate and Notch are similar in affinity to those between Delta and Notch.
GO:0005112 Notch binding
IPI
PMID:20203305
Gene deletion screen for cardiomyopathy in adult Drosophila ...
ACCEPT
Summary: Serrate binds Notch in trans via the same EGF repeats (11-12) of Notch that bind Delta (IPI).
Reason: Direct Serrate-Notch binding is shown by cell aggregation and soluble ectodomain binding assays, with affinity similar to Delta-Notch; binding is modulated by Ofut1 and Fringe. Core molecular function of the ligand.
Supporting Evidence:
PMID:20203305
To test this hypothesis, we conducted cell-aggregation assays with cells expressing Notch, Delta, Serrate or Wry and examined the ability of Notch to bind different ligands
PMID:1657403
We report a novel molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, and show that the same two EGF repeats of Notch also constitute a Serrate binding domain.
PMID:10504334
Contrary to previous suggestions, our evidence implies that the interactions between Serrate and Notch are similar in affinity to those between Delta and Notch.
GO:0005509 calcium ion binding
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Calcium ion binding inferred from calcium-binding EGF-like domains (InterPro).
Reason: Structural property of the EGF repeats; not the core function.
GO:0005515 protein binding
IPI
PMID:15829515
The ubiquitin ligase Drosophila Mind bomb promotes Notch sig...
REMOVE
Summary: Generic protein binding (IPI) with the E3 ubiquitin ligase Mind bomb.
Reason: Uninformative; Serrate is the ubiquitination substrate of Mib1. The functionally relevant ligand activity is captured by Notch binding. Removal does not imply the interaction is false.
Supporting Evidence:
PMID:15829515
The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta
GO:0005771 multivesicular body
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Serrate is endocytosed and found in vesicles, endosomes and multivesicular bodies.
Reason: Mib1/Neuralized-dependent endocytosis is required for Serrate signaling competence and also mediates turnover. Endosomal localization is documented but regulatory; non-core.
Supporting Evidence:
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0005886 plasma membrane
IDA
PMID:16643882
Notch pathway repression by vestigial is required to promote...
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (IDA).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:16643882
Moreover, close examination of the cellular location of several of the main actors of the N pathway (Notch, Delta, neuralized, Serrate, Mind bomb1 and fringe) during dorsal longitudinal muscle development enabled us to find that Notch receptor can play multiple roles in adult myogenesis
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0005886 plasma membrane
IDA
PMID:1840519
The Drosophila gene Serrate encodes an EGF-like transmembran...
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (IDA).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:1840519
The Drosophila gene Serrate encodes an EGF-like transmembrane protein with a complex expression pattern in embryos and wing discs
GO:0005886 plasma membrane
IEA
GO_REF:0000044
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (IEA).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0005886 plasma membrane
TAS
Reactome:R-DME-2076706
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (TAS).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0005886 plasma membrane
TAS
Reactome:R-DME-209226
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (TAS).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0005938 cell cortex
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Serrate detected at the apical cortex of wing imaginal cells.
Reason: Correct but less informative than apical plasma membrane; non-core.
GO:0007154 cell communication
IEA
GO_REF:0000002
KEEP AS NON CORE
Summary: Electronic annotation to cell communication.
Reason: Correct but very general; the specific process is Notch signaling.
GO:0007166 cell surface receptor signaling pathway
IEA
GO_REF:0000117
MODIFY
Summary: Electronic annotation to cell surface receptor signaling pathway.
Reason: Correct but generic; Serrate acts specifically in the Notch signaling pathway (GO:0007219), already annotated with experimental evidence.
Proposed replacements: Notch signaling pathway
Supporting Evidence:
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
GO:0007219 Notch signaling pathway
IEA
GO_REF:0000002
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IEA).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IGI
PMID:35264151
Ubiquitylation is required for the incorporation of the Notc...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IGI).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:35264151
Due to relief of cis-inhibition, N signalling is induced in the Dl Ser double mutant cells at the clone boundary (arrowhead)
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IGI
PMID:9310337
A dominant-negative form of Serrate acts as a general antago...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IGI).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:9310337
A dominant-negative form of Serrate acts as a general antagonist of Notch activation
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IGI
PMID:9553038
Delta and Serrate are redundant Notch ligands required for a...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IGI).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:9553038
Delta and Serrate are redundant Notch ligands required for asymmetric cell divisions within the Drosophila sensory organ lineage
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IMP
PMID:16093323
The interplay between DSL proteins and ubiquitin ligases in ...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IMP).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:16093323
Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IMP
PMID:16125166
Serrate-Notch signaling defines the scope of the initial den...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IMP).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:16125166
Serrate-Notch signaling defines the scope of the initial denticle field by modulating EGFR activation
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IMP
PMID:1657403
Specific EGF repeats of Notch mediate interactions with Delt...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IMP).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:1657403
Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IMP
PMID:20203305
Gene deletion screen for cardiomyopathy in adult Drosophila ...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IMP).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:20203305
Wry contains EGF repeats and a transmembrane domain but does not possess a DSL (Delta-Serrate-Lag) domain (Online Figure IV), suggesting that it may be involved in Notch signaling
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IMP
PMID:23970418
A Serrate-Notch-Canoe complex mediates essential interaction...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IMP).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:23970418
A Serrate-Notch-Canoe complex mediates essential interactions between glia and neuroepithelial cells during Drosophila optic lobe development
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IMP
PMID:28960177
Ubiquitylation-independent activation of Notch signalling by...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IMP).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:28960177
Notch receptors are hetero-dimeric type 1 trans-membrane proteins, which are activated through ligands of the Delta/Serrate/Lag2 (DSL) protein family
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IMP
PMID:8756291
The intracellular deletions of Delta and Serrate define domi...
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IMP).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:8756291
The intracellular deletions of Delta and Serrate define dominant negative forms of the Drosophila Notch ligands
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007219 Notch signaling pathway
IMP
PMID:9202123
Fringe modulates Notch-ligand interactions.
ACCEPT
Summary: Serrate is a Notch ligand and a core component of the Notch signaling pathway (IMP).
Reason: Serrate binds and activates Notch; its signaling competence requires Mib1/Neuralized-dependent endocytosis. Participation in the Notch pathway is core.
Supporting Evidence:
PMID:9202123
Three genes, fringe (fng), Serrate (Ser) and Delta (Dl), are involved in the cellular interactions leading to Notch activation
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0007423 sensory organ development
IMP
PMID:16093323
The interplay between DSL proteins and ubiquitin ligases in ...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'sensory organ development'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:16093323
Simultaneous absence of neuralized and mib1 completely abolishes Notch signaling in both aforementioned contexts, making it likely that ubiquitination is a prerequisite for Delta/Serrate signaling
GO:0007435 salivary gland morphogenesis
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'salivary gland morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0007435 salivary gland morphogenesis
IMP
PMID:12798300
Specification of cell fates within the salivary gland primor...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'salivary gland morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:12798300
In conflict with this model, we find that three genes, dead ringer (dri), Serrate (Ser), and trh itself, are expressed in the duct independently of trh
GO:0007436 larval salivary gland morphogenesis
IMP
PMID:12798300
Specification of cell fates within the salivary gland primor...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'larval salivary gland morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:12798300
In conflict with this model, we find that three genes, dead ringer (dri), Serrate (Ser), and trh itself, are expressed in the duct independently of trh
GO:0007476 imaginal disc-derived wing morphogenesis
IMP
PMID:15829515
The ubiquitin ligase Drosophila Mind bomb promotes Notch sig...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'imaginal disc-derived wing morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:15829515
The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta
GO:0007480 imaginal disc-derived leg morphogenesis
IMP
PMID:10357942
Composite signalling from Serrate and Delta establishes leg ...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'imaginal disc-derived leg morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:10357942
Composite signalling from Serrate and Delta establishes leg segments in Drosophila through Notch
GO:0008587 imaginal disc-derived wing margin morphogenesis
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'imaginal disc-derived wing margin morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0008587 imaginal disc-derived wing margin morphogenesis
IMP
PMID:1657403
Specific EGF repeats of Notch mediate interactions with Delt...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'imaginal disc-derived wing margin morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:1657403
Specific EGF repeats of Notch mediate interactions with Delta and Serrate: implications for Notch as a multifunctional receptor
GO:0008587 imaginal disc-derived wing margin morphogenesis
IMP
PMID:9202123
Fringe modulates Notch-ligand interactions.
KEEP AS NON CORE
Summary: Ser IMP annotation to 'imaginal disc-derived wing margin morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:9202123
Three genes, fringe (fng), Serrate (Ser) and Delta (Dl), are involved in the cellular interactions leading to Notch activation
GO:0009986 cell surface
IDA
PMID:20203305
Gene deletion screen for cardiomyopathy in adult Drosophila ...
ACCEPT
Summary: Serrate is a cell-surface transmembrane protein.
Reason: Consistent with its role as a membrane-tethered ligand.
Supporting Evidence:
PMID:20203305
The membrane-spanning Notch (N) receptor is stimulated by the ligands Delta (Dl) or Serrate (Ser), which are present on the surface of neighboring cells
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0009986 cell surface
IEA
GO_REF:0000117
ACCEPT
Summary: Serrate is a cell-surface transmembrane protein.
Reason: Consistent with its role as a membrane-tethered ligand.
Supporting Evidence:
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0010008 endosome membrane
EXP
PMID:20176925
Notch ligand activity is modulated by glycosphingolipid memb...
KEEP AS NON CORE
Summary: Serrate is endocytosed and found in vesicles, endosomes and multivesicular bodies.
Reason: Mib1/Neuralized-dependent endocytosis is required for Serrate signaling competence and also mediates turnover. Endosomal localization is documented but regulatory; non-core.
Supporting Evidence:
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors
GO:0010008 endosome membrane
IEA
GO_REF:0000120
KEEP AS NON CORE
Summary: Serrate is endocytosed and found in vesicles, endosomes and multivesicular bodies.
Reason: Mib1/Neuralized-dependent endocytosis is required for Serrate signaling competence and also mediates turnover. Endosomal localization is documented but regulatory; non-core.
Supporting Evidence:
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0014009 glial cell proliferation
IMP
PMID:23970418
A Serrate-Notch-Canoe complex mediates essential interaction...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'glial cell proliferation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:23970418
Ser is tissue-autonomously required in the glia where it activates Notch to regulate its proliferation, and non-autonomously in the neuroepithelium where Ser induces Notch signaling to avoid the premature activation of the EGFR-Ras pathway and hence of L'sc
GO:0016020 membrane
IEA
GO_REF:0000002
ACCEPT
Summary: Serrate is a cell-surface transmembrane protein.
Reason: Consistent with its role as a membrane-tethered ligand.
Supporting Evidence:
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0016324 apical plasma membrane
EXP
PMID:15760269
Two distinct E3 ubiquitin ligases have complementary functio...
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (EXP).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:15760269
Signaling by the Notch ligands Delta (Dl) and Serrate (Ser) regulates a wide variety of essential cell-fate decisions during animal development
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0016324 apical plasma membrane
EXP
PMID:15829515
The ubiquitin ligase Drosophila Mind bomb promotes Notch sig...
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (EXP).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:15829515
The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0016324 apical plasma membrane
EXP
PMID:1840519
The Drosophila gene Serrate encodes an EGF-like transmembran...
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (EXP).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:1840519
The Drosophila gene Serrate encodes an EGF-like transmembrane protein with a complex expression pattern in embryos and wing discs
GO:0016324 apical plasma membrane
EXP
PMID:20176925
Notch ligand activity is modulated by glycosphingolipid memb...
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (EXP).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0016324 apical plasma membrane
IDA
PMID:17006545
Role of conserved intracellular motifs in Serrate signalling...
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (IDA).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:17006545
Serrate) are transmembrane proteins whose signalling competence is regulated by the endocytosis-promoting E3 ubiquitin ligases, Mindbomb1 and Neuralized
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0016324 apical plasma membrane
IEA
GO_REF:0000120
ACCEPT
Summary: Serrate is a single-pass type I transmembrane protein at the plasma membrane, enriched apically in epithelia (IEA).
Reason: Surface presentation is required for trans-activation of Notch on neighbouring cells.
Supporting Evidence:
PMID:1840519
Antibodies directed against part of the extracellular region confirm the localization of the protein in the membrane.
GO:0016330 second mitotic wave involved in compound eye morphogenesis
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'second mitotic wave involved in compound eye morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0016330 second mitotic wave involved in compound eye morphogenesis
IMP
PMID:23970418
A Serrate-Notch-Canoe complex mediates essential interaction...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'second mitotic wave involved in compound eye morphogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:23970418
Ser is tissue-autonomously required in the glia where it activates Notch to regulate its proliferation, and non-autonomously in the neuroepithelium where Ser induces Notch signaling to avoid the premature activation of the EGFR-Ras pathway and hence of L'sc
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Serrate protein detected on axons/neuronal projections.
Reason: Reported localization (UniProt cites PMID:1840519); Serrate also signals in glia-neuron interactions. Not a core site of function.
GO:0030673 axolemma
IDA
PMID:1840519
The Drosophila gene Serrate encodes an EGF-like transmembran...
KEEP AS NON CORE
Summary: Serrate protein detected on axons/neuronal projections.
Reason: Reported localization (UniProt cites PMID:1840519); Serrate also signals in glia-neuron interactions. Not a core site of function.
Supporting Evidence:
PMID:1840519
The Drosophila gene Serrate encodes an EGF-like transmembrane protein with a complex expression pattern in embryos and wing discs
GO:0030718 germ-line stem cell population maintenance
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'germ-line stem cell population maintenance'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0030718 germ-line stem cell population maintenance
IGI
PMID:17070683
Stem cells signal to the niche through the Notch pathway in ...
KEEP AS NON CORE
Summary: Ser IGI annotation to 'germ-line stem cell population maintenance'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:17070683
Conversely, when GCSs do not produce functional Notch ligands, Delta and Serrate, the TGF-beta pathway is not activated in the GSCs, and they differentiate and subsequently leave the niche
GO:0031982 vesicle
EXP
PMID:15829515
The ubiquitin ligase Drosophila Mind bomb promotes Notch sig...
KEEP AS NON CORE
Summary: Serrate is endocytosed and found in vesicles, endosomes and multivesicular bodies.
Reason: Mib1/Neuralized-dependent endocytosis is required for Serrate signaling competence and also mediates turnover. Endosomal localization is documented but regulatory; non-core.
Supporting Evidence:
PMID:15829515
We find that D-mib uses its ubiquitin ligase activity to promote DSL ligand activity, an activity that is correlated with its ability to induce the endocytosis and degradation of both Delta and Serrate (see also Le Borgne et al., 2005)
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0031982 vesicle
EXP
PMID:1840519
The Drosophila gene Serrate encodes an EGF-like transmembran...
KEEP AS NON CORE
Summary: Serrate is endocytosed and found in vesicles, endosomes and multivesicular bodies.
Reason: Mib1/Neuralized-dependent endocytosis is required for Serrate signaling competence and also mediates turnover. Endosomal localization is documented but regulatory; non-core.
Supporting Evidence:
PMID:1840519
The Drosophila gene Serrate encodes an EGF-like transmembrane protein with a complex expression pattern in embryos and wing discs
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0031982 vesicle
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: Serrate is endocytosed and found in vesicles, endosomes and multivesicular bodies.
Reason: Mib1/Neuralized-dependent endocytosis is required for Serrate signaling competence and also mediates turnover. Endosomal localization is documented but regulatory; non-core.
Supporting Evidence:
PMID:20176925
Endocytosis of the transmembrane ligands Delta (Dl) and Serrate (Ser) is required for the proper activation of Notch receptors.
GO:0035017 cuticle pattern formation
IMP
PMID:16125166
Serrate-Notch signaling defines the scope of the initial den...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'cuticle pattern formation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:16125166
Serrate-Notch signaling defines the scope of the initial denticle field by modulating EGFR activation
GO:0035167 larval lymph gland hemopoiesis
IEP
PMID:12569125
A Serrate-expressing signaling center controls Drosophila he...
KEEP AS NON CORE
Summary: Serrate is expressed in a lymph gland signaling center (posterior signaling center-like cells) that controls hematopoiesis (IEP).
Reason: The expression pattern plus functional data from the same study (crystal cell specification) support involvement of Serrate-Notch signaling in lymph gland hematopoiesis; non-core developmental context.
Supporting Evidence:
PMID:12569125
The expression of Serrate marks a discrete cluster of cells in the lymph gland, a signaling center, with functional similarities to stromal signaling in mammalian hematopoiesis
GO:0035204 negative regulation of lamellocyte differentiation
IMP
PMID:24318532
An unexpected link between notch signaling and ROS in restri...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'negative regulation of lamellocyte differentiation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:24318532
In larval stages, Notch signaling regulates commitment to crystal cell lineage ( Duvic et al. 2002 ; Lebestky et al. 2003 ); in procrystal cells, the Notch receptor is activated by Serrate (Ser), expressed in the niche cells
GO:0035214 eye-antennal disc development
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'eye-antennal disc development'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0035214 eye-antennal disc development
IMP
PMID:17090721
Lobe and Serrate are required for cell survival during early...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'eye-antennal disc development'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:17090721
Here, we show that Lobe (L) and the Notch (N) ligand Serrate (Ser), which are both involved in ventral eye growth, are required for cell survival in the early eye disc
GO:0036011 imaginal disc-derived leg segmentation
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'imaginal disc-derived leg segmentation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0036011 imaginal disc-derived leg segmentation
IMP
PMID:10357895
Notch-mediated segmentation and growth control of the Drosop...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'imaginal disc-derived leg segmentation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:10357895
This segmentation process requires the participation of the Notch ligands, Serrate and Delta, as well as Fringe
GO:0042063 gliogenesis
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'gliogenesis'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0042688 crystal cell differentiation
IMP
PMID:12445385
Notch signaling controls lineage specification during Drosop...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'crystal cell differentiation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:12445385
We demonstrate that, in this process, Serrate, not Delta, is the Notch ligand
GO:0042688 crystal cell differentiation
IMP
PMID:12569125
A Serrate-expressing signaling center controls Drosophila he...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'crystal cell differentiation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:12569125
We also find that a signaling center expressing the ligand Serrate is important for differentiation and proliferation of larval hemocytes in Drosophila . Results and Discussion Notch and Su(H) are required for hemocyte proliferation and development Morphological and molecular differentiation of hemocytes can be monitored in the larval lymph gland ( Shrestha and Gateff 1982 )
GO:0043005 neuron projection
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Serrate protein detected on axons/neuronal projections.
Reason: Reported localization (UniProt cites PMID:1840519); Serrate also signals in glia-neuron interactions. Not a core site of function.
GO:0043208 glycosphingolipid binding
IDA
PMID:20176925
Notch ligand activity is modulated by glycosphingolipid memb...
KEEP AS NON CORE
Summary: The Serrate extracellular domain binds glycosphingolipids in vitro via a conserved GSL-binding motif.
Reason: Direct biochemical evidence; the interaction modulates ligand endocytosis and signaling activity. Regulatory, non-core.
Supporting Evidence:
PMID:20176925
Our genetic and biochemical analysis of Ξ±4GT1 function indicates that specific changes in glycosphingolipid (GSL) composition can rescue the defects in Dl and Ser trafficking and signaling seen upon inhibition of mib1 activity, thereby establishing a new functional link between GSLs and Notch signaling
GO:0043208 glycosphingolipid binding
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: The Serrate extracellular domain binds glycosphingolipids in vitro via a conserved GSL-binding motif.
Reason: Direct biochemical evidence; the interaction modulates ligand endocytosis and signaling activity. Regulatory, non-core.
GO:0045179 apical cortex
IDA
PMID:15760269
Two distinct E3 ubiquitin ligases have complementary functio...
KEEP AS NON CORE
Summary: Serrate detected at the apical cortex of wing imaginal cells.
Reason: Correct but less informative than apical plasma membrane; non-core.
Supporting Evidence:
PMID:15760269
We therefore conclude that D-mib and neur have distinct and complementary functions in Drosophila.D-mib Co-Localizes with Dl and Ser at the Apical CortexWe next studied the subcellular localization of D-mib (Figure 3)
GO:0045179 apical cortex
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Serrate detected at the apical cortex of wing imaginal cells.
Reason: Correct but less informative than apical plasma membrane; non-core.
GO:0046331 lateral inhibition
IEA
GO_REF:0000117
ACCEPT
Summary: Serrate participates, partly redundantly with Delta, in Notch-mediated lateral inhibition.
Reason: As a DSL ligand, Serrate directly mediates Notch activation during lateral inhibition in sensory organ development (redundant with Delta).
GO:0046331 lateral inhibition
IMP
PMID:16093323
The interplay between DSL proteins and ubiquitin ligases in ...
ACCEPT
Summary: Serrate participates, partly redundantly with Delta, in Notch-mediated lateral inhibition.
Reason: As a DSL ligand, Serrate directly mediates Notch activation during lateral inhibition in sensory organ development (redundant with Delta).
Supporting Evidence:
PMID:16093323
Of the two Notch ligands Delta and Serrate, only the former was thought to participate in this process
GO:0048018 receptor ligand activity
IDA
PMID:20203305
Gene deletion screen for cardiomyopathy in adult Drosophila ...
ACCEPT
Summary: Serrate acts as a ligand that activates the Notch receptor.
Reason: Serrate trans-activates Notch (e.g. dorsal-to-ventral signaling at the wing D/V boundary, crystal cell specification). Core activity.
Supporting Evidence:
PMID:20203305
Importantly, Wry lacks a DSL (Delta-Serrate-Lag) domain that is common feature to the other Drosophila Notch ligands
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:12569125
Serrate signaling through the Notch pathway is critical in the regulation of Lz expression and the specification of crystal cell precursors, thus providing a key distinction between the two lineages.
file:DROME/Ser/Ser-deep-research-falcon.md
When Serrate and Notch are co-expressed on the same cell surface, their cis-interaction sequesters Notch
GO:0048018 receptor ligand activity
IEA
GO_REF:0000117
ACCEPT
Summary: Serrate acts as a ligand that activates the Notch receptor.
Reason: Serrate trans-activates Notch (e.g. dorsal-to-ventral signaling at the wing D/V boundary, crystal cell specification). Core activity.
Supporting Evidence:
PMID:9202123
Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
PMID:12569125
Serrate signaling through the Notch pathway is critical in the regulation of Lz expression and the specification of crystal cell precursors, thus providing a key distinction between the two lineages.
file:DROME/Ser/Ser-deep-research-falcon.md
When Serrate and Notch are co-expressed on the same cell surface, their cis-interaction sequesters Notch
GO:0048100 wing disc anterior/posterior pattern formation
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'wing disc anterior/posterior pattern formation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0048100 wing disc anterior/posterior pattern formation
IMP
PMID:23152840
Sequential Notch signalling at the boundary of fringe expres...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'wing disc anterior/posterior pattern formation'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:23152840
It appears that mutual signalling from dorsal to ventral and ventral to dorsal cells by the Notch ligands Serrate (Ser) and Delta (Dl) respectively establishes a symmetric domain of Wg that straddles the D/V boundary
GO:0048468 cell development
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'cell development'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0048749 compound eye development
IMP
PMID:17090721
Lobe and Serrate are required for cell survival during early...
KEEP AS NON CORE
Summary: Ser IMP annotation to 'compound eye development'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
Supporting Evidence:
PMID:17090721
Here, we show that Lobe (L) and the Notch (N) ligand Serrate (Ser), which are both involved in ventral eye growth, are required for cell survival in the early eye disc
GO:0051093 negative regulation of developmental process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'negative regulation of developmental process'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.
GO:0051239 regulation of multicellular organismal process
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Ser IEA annotation to 'regulation of multicellular organismal process'. Serrate is a Notch ligand, and perturbing Serrate alters this developmental process through loss or misregulation of Notch signaling.
Reason: Serrate (Jagged ortholog) is a transmembrane DSL ligand of Notch; its requirement in this context reflects Serrate-Notch signaling there. The annotation is biologically sound but records a downstream developmental outcome rather than the core ligand activity; kept as non-core.

Core Functions

Membrane-bound DSL ligand: Serrate binds Notch in trans (EGF repeats 11-12) and, through Mind bomb/Neuralized-dependent endocytosis, activates Notch in neighbouring cells; Fringe glycosylation of Notch reduces Serrate responsiveness.

Molecular Function:
Notch binding
Directly Involved In:
Supporting Evidence:
  • PMID:1657403
    We report a novel molecular interaction between Notch and Serrate, another EGF-homologous transmembrane protein containing a region of striking similarity to Delta, and show that the same two EGF repeats of Notch also constitute a Serrate binding domain.
  • PMID:10504334
    Contrary to previous suggestions, our evidence implies that the interactions between Serrate and Notch are similar in affinity to those between Delta and Notch.
  • PMID:9202123
    This is achieved by fng through a cell-autonomous mechanism that inhibits a cell's ability to respond to Serrate protein and potentiates its ability to respond to Delta protein.

Receptor ligand activity: Serrate trans-activates Notch, e.g. in wing D/V boundary signaling and crystal cell specification.

Molecular Function:
receptor ligand activity
Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • PMID:9202123
    Ser and Dl encode transmembrane ligands for Notch, whereas fng encodes a pioneer protein.
  • PMID:17006545
    The second, a novel motif, is necessary for interactions with Mindbomb1/Neuralized and is strictly required for Serrate to trans-activate and internalise efficiently but not for it to inhibit Notch signalling.
  • PMID:12569125
    Serrate signaling through the Notch pathway is critical in the regulation of Lz expression and the specification of crystal cell precursors, thus providing a key distinction between the two lineages.

References

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Suggested Questions for Experts

Q: Which structural features of Serrate (cysteine-rich region, DOS-like EGF repeats) account for its differential sensitivity to Fringe-modified Notch compared with Delta?

Suggested Experiments

Experiment: Compare endogenous Serrate and Delta cis-inhibition strength at the wing D/V boundary using ligand alleles specifically defective in trans-activation (Mib1/Neur-binding motif mutants).

Deep Research

Falcon

(Ser-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(Ser-notes.md)

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