twr encodes the Drosophila SEC11-family catalytic subunit of the endoplasmic reticulum signal peptidase complex (SPC), a peptidase S26B (Ser-His dyad) protease anchored in the ER membrane as a single-pass type II protein with its active site in the lumen. Together with the accessory subunits Spase12 (SPCS1), Spase25 (SPCS2) and Spase22-23 (SPCS3), it cleaves N-terminal signal peptides from secretory and membrane proteins as they are translocated into the ER, a step required for their maturation and correct localization.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004252 serine-type endopeptidase activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro peptidase S26B mapping to serine-type endopeptidase activity. Reason: SEC11-family signal peptidases are serine endopeptidases using a Ser-His catalytic dyad. The term describes the catalytic mechanism and is complementary to, not a parent of, signal peptidase activity, so it is retained as accurate. Supporting Evidence: file:DROME/twr/twr-uniprot.txt Belongs to the peptidase S26B family. |
| GO:0005783 endoplasmic reticulum | ISS GO_REF:0000024 | MODIFY | Summary: Sequence-similarity transfer of ER localization from yeast Sec11 (SGD:S000001461). Reason: Correct but general; the SPC catalytic subunit is an integral ER membrane protein. The gene already carries GO:0005789 endoplasmic reticulum membrane. Proposed replacements: endoplasmic reticulum membrane Supporting Evidence: file:DROME/twr/twr-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0005787 signal peptidase complex | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of signal peptidase complex membership (yeast Sec11, human SEC11A/SEC11C and other donors) via PTN000086750. Reason: twr is the SEC11 catalytic subunit of the SPC; complex membership is accepted for all four fly SPC subunits. Supporting Evidence: PMID:23573290 The Drosophila SPC comprises four proteins: Spase18/21, Spase22/23, Spase25 and Spase12. |
| GO:0005787 signal peptidase complex | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA prediction of signal peptidase complex. Reason: Correct core complex membership. twr (Spase18/21) is listed among the four Drosophila SPC subunits and is the Sec11 homolog; the curated UniRule (RuleBase) SUBUNIT statement in the record agrees. The record's FUNCTION line is an ARBA prediction and is not cited. Supporting Evidence: PMID:23573290 The Drosophila SPC comprises four proteins: Spase18/21, Spase22/23, Spase25 and Spase12. PMID:23573290 Spase18/21 is homologous to yeast Sec11, as well as mammalian SPC18 and SPC21 file:DROME/twr/twr-uniprot.txt SUBUNIT: Component of the signal peptidase complex. |
| GO:0005787 signal peptidase complex | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of SPC membership from yeast Sec11. Reason: Correct core complex membership. |
| GO:0005787 signal peptidase complex | NAS PMID:23573290 Drosophila signal peptidase complex member Spase12 is requir... | ACCEPT | Summary: Author statement listing the fly SPC subunits. Reason: Correct core complex membership. Supporting Evidence: PMID:23573290 The Drosophila SPC comprises four proteins: Spase18/21, Spase22/23, Spase25 and Spase12. |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated assignment of ER membrane localization. Reason: The SPC is embedded in the ER membrane. Two lines agree - the fly SPC is described as part of the ER translocation machinery with its catalytic residues in the ER lumen (statements about the complex and its mammalian homologs, not a fly localization assay), and the sequence carries a single predicted transmembrane helix (UniRule RuleBase feature). The record's SUBCELLULAR LOCATION line is an ARBA prediction and is not cited. Supporting Evidence: PMID:23573290 SPC18, SPC21, and SPC22/23 have catalytic function and the residues required for cleavage activity are localized to the ER lumen PMID:23573290 A vital component of the translocation machinery is the signal peptidase complex (SPC)--which is conserved from yeast to mammals--and functions to cleave the signal peptide sequence (SP) of secretory and membrane proteins entering the ER. file:DROME/twr/twr-uniprot.txt TRANSMEM 24..42 |
| GO:0005789 endoplasmic reticulum membrane | NAS PMID:23573290 Drosophila signal peptidase complex member Spase12 is requir... | ACCEPT | Summary: Author statement placing the SPC in the ER translocation machinery. Reason: Correct core location. Supporting Evidence: PMID:23573290 A vital component of the translocation machinery is the signal peptidase complex (SPC)--which is conserved from yeast to mammals--and functions to cleave the signal peptide sequence (SP) of secretory and membrane proteins entering the ER. |
| GO:0008233 peptidase activity | IBA GO_REF:0000033 | MODIFY | Summary: PAINT inference of peptidase activity (yeast Sec11, human SEC11A/C and other donors) via PTN000086749. Reason: Correct but general; the specific activity of the SEC11 subunit is GO:0009003 signal peptidase activity, a descendant of peptidase activity that the gene already carries. Proposed replacements: signal peptidase activity Supporting Evidence: file:DROME/twr/twr-uniprot.txt Catalytic component of the signal peptidase complex (SPC) which catalyzes the cleavage of N-terminal signal sequences from nascent proteins |
| GO:0008233 peptidase activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro peptidase S26 mapping to peptidase activity. Reason: Correct but general; refine to GO:0009003 signal peptidase activity, already annotated. Proposed replacements: signal peptidase activity |
| GO:0008233 peptidase activity | ISS GO_REF:0000024 | MODIFY | Summary: Sequence-similarity transfer of peptidase activity from yeast Sec11. Reason: Correct but general; refine to GO:0009003 signal peptidase activity, already annotated. Proposed replacements: signal peptidase activity |
| GO:0009003 signal peptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: Combined automated assignment of signal peptidase activity (EC 3.4.21.89). Reason: Core activity of the SEC11 catalytic subunit: cleavage of N-terminal signal peptides from proteins translocated into the ER. Support is family membership (peptidase S26B, PANTHER SEC11 catalytic subunit family, PROSITE signal peptidase I serine active-site pattern) plus the homology of Spase18/21 to Sec11/SPC18/SPC21, whose catalytic role is stated for the mammalian and yeast subunits; there is no fly enzymatic assay. The record's FUNCTION line is an ARBA prediction and is not cited. Supporting Evidence: file:DROME/twr/twr-uniprot.txt SIMILARITY: Belongs to the peptidase S26B family. file:DROME/twr/twr-uniprot.txt PANTHER; PTHR10806; SIGNAL PEPTIDASE COMPLEX CATALYTIC SUBUNIT SEC11; 1. file:DROME/twr/twr-uniprot.txt PROSITE; PS00501; SPASE_I_1; 1. PMID:23573290 Spase18/21 is homologous to yeast Sec11, as well as mammalian SPC18 and SPC21 PMID:23573290 SPC18, SPC21, and SPC22/23 have catalytic function |
| GO:0012505 endomembrane system | HDA PMID:19317464 Mapping organelle proteins and protein complexes in Drosophi... | MODIFY | Summary: Organelle proteomics placing twr in the endomembrane system (abstract-only cache). Reason: Correct but general; the specific location is the ER membrane, which the gene already carries. Proposed replacements: endoplasmic reticulum membrane |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to membrane. Reason: Correct but general; refine to GO:0005789 endoplasmic reticulum membrane, already annotated. Proposed replacements: endoplasmic reticulum membrane |
| GO:0017171 serine hydrolase activity | HDA PMID:33827210 A Superfamily-wide Activity Atlas of Serine Hydrolases in &l... | MODIFY | Summary: Activity-based profiling of Drosophila serine hydrolases (high-throughput; abstract-only cache). Reason: Correct but general; serine hydrolase activity is an ancestor of serine-type endopeptidase activity, which the gene already carries and which reflects its S26B peptidase mechanism. Proposed replacements: serine-type endopeptidase activity |
| GO:0051604 protein maturation | IBA GO_REF:0000033 | MODIFY | Summary: PAINT inference of protein maturation (yeast Sec11 and human SEC11A/C donors) via PTN000086750. Reason: Correct (GO's obsolete signal peptide processing term was redirected to protein maturation), but the more specific GO:0016485 protein processing, maturation by peptide-bond cleavage, describes signal peptide removal exactly. Same refinement for all fly SPC subunits. Proposed replacements: protein processing Supporting Evidence: PMID:23573290 Processing by the signal peptidase complex (SPC) is critical to the localization and function of secretory and membrane proteins which must enter the endoplasmic reticulum (ER) before they can be directed to their final destination. |
| GO:0051604 protein maturation | IEA GO_REF:0000002 | MODIFY | Summary: InterPro mapping to protein maturation. Reason: Correct but general; refine to GO:0016485 protein processing (signal peptide cleavage). Proposed replacements: protein processing |
| GO:0051604 protein maturation | ISS GO_REF:0000024 | MODIFY | Summary: Sequence-similarity transfer of protein maturation from yeast Sec11. Reason: Correct but general; refine to GO:0016485 protein processing (signal peptide cleavage). Proposed replacements: protein processing |
Loading supporting content…
Download this section (compressed HTML)Q: Does Drosophila express a second SEC11 paralog (as SEC11A/SEC11C in mammals), and do the resulting SPC variants differ in substrate preference?
Experiment: Profile signal-peptide cleavage of reporter secretory proteins in twr loss-of-function clones to define substrates that depend on the fly SPC catalytic subunit.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)