Rasp (also called Skinny hedgehog, Sightless or Central missing) is a multipass membrane-bound O-acyltransferase (MBOAT) family protein, the Drosophila ortholog of Hedgehog acyltransferase (HHAT). It acts in the secretory pathway of signal-producing cells to attach palmitate to the N-terminal cysteine of secreted ligands, producing an amide-linked N-palmitoyl cysteine. Rasp palmitoylates the cholesterol- modified Hedgehog signaling domain, a modification required for full Hedgehog activity, so rasp mutants have segment-polarity and imaginal disc patterning defects although Hedgehog is still produced and cholesterol-modified. Rasp also palmitoylates the N-terminal cysteine of the EGFR ligand Spitz, which tethers Spitz to the plasma membrane, restricts its diffusion and is required for its developmental functions. Rasp does not act on Wingless, which is acylated by the related enzyme Porcupine.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: Endoplasmic reticulum (phylogenetic inference). Reason: MBOAT acyltransferases including HHAT act in the ER; Rasp acts in the secretory pathway. Supporting Evidence: PMID:11486055 ski encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of Hh |
| GO:0005829 cytosol | TAS Reactome:R-DME-209357 | MODIFY | Summary: Reactome places the Rasp palmitoylation reaction in the cytosol. Reason: Rasp is a multipass membrane protein acting in the secretory pathway on a lumenal substrate, not a cytosolic protein; the location Rasp already carries (IBA) is endoplasmic reticulum. Proposed replacements: endoplasmic reticulum Supporting Evidence: PMID:11861468 Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. |
| GO:0007224 smoothened signaling pathway | TAS Reactome:R-DME-209392 | KEEP AS NON CORE | Summary: Reactome places Rasp in the Hedgehog pathway. Reason: Rasp acts in Hh-producing cells to mature the ligand rather than in Smoothened-initiated transduction; the core process is patched ligand maturation (same decision as disp). Supporting Evidence: PMID:11861468 The requirement of rasp is restricted only to those cells that produce Hh |
| GO:0007225 patched ligand maturation | IGI PMID:11748147 Distinct roles of Central missing and Dispatched in sending ... | ACCEPT | Summary: cmn (rasp) regulates Hh activity independently of cholesterol modification. Reason: Hh maturation by acylation. Supporting Evidence: PMID:11748147 cmn regulates the activity of Hh in a manner that is independent of cholesterol modification |
| GO:0007225 patched ligand maturation | IMP PMID:11486055 Skinny hedgehog, an acyltransferase required for palmitoylat... | ACCEPT | Summary: Rasp-dependent palmitoylation is required for Hh activity. Reason: N-terminal palmitoylation is a posttranslational modification of Hh required for its activity, matching the term. Supporting Evidence: PMID:11486055 further demonstrate that this lipid modification is required for the embryonic and larval patterning activities of the Hh signal |
| GO:0007225 patched ligand maturation | IMP PMID:11509241 Sightless has homology to transmembrane acyltransferases and... | ACCEPT | Summary: sit is required in Hh-producing cells to generate active Hh. Reason: Hh maturation. Supporting Evidence: PMID:11509241 sit acts in the cells that produce Hh, but does not affect hh transcription, Hh cleavage, or the accumulation of Hh protein |
| GO:0007225 patched ligand maturation | IMP PMID:11748147 Distinct roles of Central missing and Dispatched in sending ... | ACCEPT | Summary: cmn (rasp) regulates Hh activity independently of cholesterol modification. Reason: Hh maturation by acylation. Supporting Evidence: PMID:11748147 cmn regulates the activity of Hh in a manner that is independent of cholesterol modification |
| GO:0007225 patched ligand maturation | IMP PMID:11861468 Rasp, a putative transmembrane acyltransferase, is required ... | ACCEPT | Summary: Rasp-dependent acylation generates fully active Hh. Reason: Hh maturation. Supporting Evidence: PMID:11861468 Our results suggest that Rasp-dependent acylation is necessary to generate a fully active Hh protein. |
| GO:0007367 segment polarity determination | IMP PMID:11486055 Skinny hedgehog, an acyltransferase required for palmitoylat... | KEEP AS NON CORE | Summary: rasp/ski/sit is a segment-polarity gene. Reason: Developmental consequence of reduced Hh activity. Supporting Evidence: PMID:11861468 we have identified rasp, a novel Drosophila segment polarity gene |
| GO:0007367 segment polarity determination | IMP PMID:11509241 Sightless has homology to transmembrane acyltransferases and... | KEEP AS NON CORE | Summary: rasp/ski/sit is a segment-polarity gene. Reason: Developmental consequence of reduced Hh activity. Supporting Evidence: PMID:11861468 we have identified rasp, a novel Drosophila segment polarity gene |
| GO:0007367 segment polarity determination | IMP PMID:11861468 Rasp, a putative transmembrane acyltransferase, is required ... | KEEP AS NON CORE | Summary: rasp/ski/sit is a segment-polarity gene. Reason: Developmental consequence of reduced Hh activity. Supporting Evidence: PMID:11861468 we have identified rasp, a novel Drosophila segment polarity gene |
| GO:0016020 membrane | IEA GO_REF:0000044 | MODIFY | Summary: Rasp is a multipass membrane protein. Reason: Correct but general; as an MBOAT enzyme acting in the secretory pathway, the specific location is the endoplasmic reticulum membrane (human HHAT is at the ER membrane). Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:11861468 Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. |
| GO:0016020 membrane | NAS PMID:11486055 Skinny hedgehog, an acyltransferase required for palmitoylat... | MODIFY | Summary: Rasp is a multipass membrane protein. Reason: Correct but general; as an MBOAT enzyme acting in the secretory pathway, the specific location is the endoplasmic reticulum membrane (human HHAT is at the ER membrane). Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:11861468 Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. |
| GO:0016020 membrane | NAS PMID:11509241 Sightless has homology to transmembrane acyltransferases and... | MODIFY | Summary: Rasp is a multipass membrane protein. Reason: Correct but general; as an MBOAT enzyme acting in the secretory pathway, the specific location is the endoplasmic reticulum membrane (human HHAT is at the ER membrane). Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:11861468 Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. |
| GO:0016020 membrane | NAS PMID:11861468 Rasp, a putative transmembrane acyltransferase, is required ... | MODIFY | Summary: Rasp is a multipass membrane protein. Reason: Correct but general; as an MBOAT enzyme acting in the secretory pathway, the specific location is the endoplasmic reticulum membrane (human HHAT is at the ER membrane). Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: PMID:11861468 Molecular analysis reveals that rasp encodes a multipass transmembrane protein that has homology to a family of membrane bound O-acyl transferases. |
| GO:0016409 palmitoyltransferase activity | IBA GO_REF:0000033 | ACCEPT | Summary: Rasp is a palmitoyltransferase. Reason: Palmitoyltransferase activity is the most specific term in the current ontology that is chemically correct for Rasp, which forms an amide (N-palmitoyl) linkage to the N-terminal cysteine; its child GO:0019706 specifies transfer to sulfur. Same reasoning as the human HHAT review. Supporting Evidence: PMID:11486055 Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification |
| GO:0016409 palmitoyltransferase activity | TAS Reactome:R-DME-209357 | ACCEPT | Summary: Rasp is a palmitoyltransferase. Reason: Palmitoyltransferase activity is the most specific term in the current ontology that is chemically correct for Rasp, which forms an amide (N-palmitoyl) linkage to the N-terminal cysteine; its child GO:0019706 specifies transfer to sulfur. Same reasoning as the human HHAT review. Supporting Evidence: PMID:11486055 Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification |
| GO:0016746 acyltransferase activity | IMP PMID:11486055 Skinny hedgehog, an acyltransferase required for palmitoylat... | MODIFY | Summary: Rasp is an acyltransferase (MBOAT family). Reason: Correct but general; the transferred acyl group is palmitate, so the specific chemically correct term is palmitoyltransferase activity (GO:0016409), which Rasp already carries. GO:0019706 is not used as the target because it specifies an S-linked product, whereas Rasp forms an N-linked amide (GO:0018009). Proposed replacements: palmitoyltransferase activity Supporting Evidence: PMID:11486055 Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification |
| GO:0016746 acyltransferase activity | IMP PMID:11509241 Sightless has homology to transmembrane acyltransferases and... | MODIFY | Summary: Rasp is an acyltransferase (MBOAT family). Reason: Correct but general; the transferred acyl group is palmitate, so the specific chemically correct term is palmitoyltransferase activity (GO:0016409), which Rasp already carries. GO:0019706 is not used as the target because it specifies an S-linked product, whereas Rasp forms an N-linked amide (GO:0018009). Proposed replacements: palmitoyltransferase activity Supporting Evidence: PMID:11486055 Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification |
| GO:0016746 acyltransferase activity | NAS PMID:11861468 Rasp, a putative transmembrane acyltransferase, is required ... | MODIFY | Summary: Rasp is an acyltransferase (MBOAT family). Reason: Correct but general; the transferred acyl group is palmitate, so the specific chemically correct term is palmitoyltransferase activity (GO:0016409), which Rasp already carries. GO:0019706 is not used as the target because it specifies an S-linked product, whereas Rasp forms an N-linked amide (GO:0018009). Proposed replacements: palmitoyltransferase activity Supporting Evidence: PMID:11486055 Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification |
| GO:0018009 N-terminal peptidyl-L-cysteine N-palmitoylation | IDA PMID:11509241 Sightless has homology to transmembrane acyltransferases and... | ACCEPT | Summary: Sightless (Rasp) may acylate the Hh N-terminal cysteine. Reason: Core process; deferring to the curator's IDA call from the full text. Supporting Evidence: PMID:11509241 The Sit protein could act by acylating Hh or by promoting other modifications or trafficking event |
| GO:0018009 N-terminal peptidyl-L-cysteine N-palmitoylation | IDA PMID:11861468 Rasp, a putative transmembrane acyltransferase, is required ... | ACCEPT | Summary: Rasp-dependent acylation of the Hh N-terminal cysteine. Reason: Core process. Supporting Evidence: PMID:11861468 Our results suggest that Rasp-dependent acylation is necessary to generate a fully active Hh protein. |
| GO:0018009 N-terminal peptidyl-L-cysteine N-palmitoylation | IMP PMID:11486055 Skinny hedgehog, an acyltransferase required for palmitoylat... | ACCEPT | Summary: Rasp is required for amino-terminal palmitoylation of Hh. Reason: Core process; the palmitate is amide-linked to the N-terminal cysteine. Supporting Evidence: PMID:11486055 Hh proteins from ski mutant cells retain carboxyl-terminal cholesterol modification but lack amino-terminal palmitate modification |
| GO:0019706 protein-cysteine S-palmitoyltransferase activity | IDA PMID:16459296 Palmitoylation of the EGFR ligand Spitz by Rasp increases Sp... | ACCEPT | Summary: Rasp promotes palmitate addition to the N-terminal cysteine of Spitz. Reason: Experimental evidence that Rasp palmitoylates the N-terminal cysteine of Spitz. Caveat - GO:0019706 strictly specifies transfer to a sulfur atom, whereas the stable Rasp/HHAT product is an amide to the alpha-amino group of the N-terminal cysteine (captured by GO:0018009); a transient S-palmitoyl intermediate followed by S-to-N shift has been proposed but is not established. The experimental curator annotation is accepted, but this term should not be propagated or used as the target of MODIFYs (the human HHAT review makes the same point and uses GO:0016409 for broader rows). Supporting Evidence: PMID:16459296 In cultured cells, Rasp promotes palmitate addition to the N-terminal cysteine residue of Spitz |
| GO:0019706 protein-cysteine S-palmitoyltransferase activity | IMP PMID:11486055 Skinny hedgehog, an acyltransferase required for palmitoylat... | ACCEPT | Summary: Hh from ski (rasp) mutant cells lacks N-terminal palmitate. Reason: Experimental evidence for Rasp-dependent N-terminal palmitoylation of Hh. Caveat - GO:0019706 strictly specifies transfer to a sulfur atom, whereas the stable Rasp/HHAT product is an amide to the alpha-amino group of the N-terminal cysteine (captured by GO:0018009); a transient S-palmitoyl intermediate followed by S-to-N shift has been proposed but is not established. The experimental curator annotation is accepted, but this term should not be propagated or used as the target of MODIFYs (the human HHAT review makes the same point and uses GO:0016409 for broader rows). Supporting Evidence: PMID:11486055 Our results suggest that ski encodes an enzyme that acts within the secretory pathway to catalyze amino-terminal palmitoylation of Hh |
| GO:0038004 epidermal growth factor receptor ligand maturation | IMP PMID:16459296 Palmitoylation of the EGFR ligand Spitz by Rasp increases Sp... | ACCEPT | Summary: Rasp palmitoylates Spitz, required for its activity. Reason: Core process - maturation of the EGFR ligand Spitz by palmitoylation. Supporting Evidence: PMID:16459296 We show here that rasp is also essential for the developmental functions of Spitz, a ligand for the Drosophila epidermal growth factor receptor (EGFR). |
| GO:0038004 epidermal growth factor receptor ligand maturation | IMP PMID:23902690 Trafficking of the EGFR ligand Spitz regulates its signaling... | ACCEPT | Summary: N-terminal palmitate tethers the Spitz signaling domain to the membrane. Reason: Spitz maturation includes Rasp-dependent palmitoylation. Supporting Evidence: PMID:23902690 This domain is modified with an N-terminal palmitate group that tethers it to the plasma membrane. |
| GO:0046843 dorsal appendage formation | IMP PMID:24531791 A genetic screen based on in vivo RNA imaging reveals centro... | KEEP AS NON CORE | Summary: rasp allele recovered in a screen for oogenesis/gurken mRNA localization defects. Reason: Dorsal appendage formation depends on EGFR signaling in follicle cells, consistent with Rasp's role in EGFR ligand palmitoylation; a peripheral developmental phenotype. Supporting Evidence: PMID:24531791 including alleles of elg1, scaf6, quemao, nudE, Tsc2/gigas, rasp, and Chd5/Wrb |
| GO:0048100 wing disc anterior/posterior pattern formation | IMP PMID:11509241 Sightless has homology to transmembrane acyltransferases and... | KEEP AS NON CORE | Summary: rasp is required for Hh-dependent wing disc patterning. Reason: Developmental consequence of reduced Hh activity. Supporting Evidence: PMID:11861468 Analysis of the rasp mutant phenotype, in both the embryo and wing imaginal disc demonstrates that rasp does not disrupt Wnt/Wingless signaling but is specifically required for Hh signaling. |
| GO:0048100 wing disc anterior/posterior pattern formation | IMP PMID:11861468 Rasp, a putative transmembrane acyltransferase, is required ... | KEEP AS NON CORE | Summary: rasp is required for Hh-dependent wing disc patterning. Reason: Developmental consequence of reduced Hh activity. Supporting Evidence: PMID:11861468 Analysis of the rasp mutant phenotype, in both the embryo and wing imaginal disc demonstrates that rasp does not disrupt Wnt/Wingless signaling but is specifically required for Hh signaling. |
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Download this section (compressed HTML)Q: Rasp and HHAT attach palmitate to the alpha-amino group of the N-terminal cysteine, giving an amide (GO:0018009), and a transient S-palmitoyl intermediate followed by an S-to-N shift has not been established. Should experimental rows on protein-cysteine S-palmitoyltransferase activity (GO:0019706) for Rasp, which the generated Alliance description repeats, be moved to palmitoyltransferase activity (GO:0016409), or should GO add an N-terminal cysteine N-palmitoyltransferase activity term?
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Download this section (compressed HTML)rasp (rasp) encodes an acyltransferase enzyme that adds essential N-terminal palmitate modifications to the secreted signaling domains of the products of hh and spi. The modification of the product of spi appears to increase the local concentration of the ligand by restricting its diffusion.
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