npp-20 (Y77E11A.13) encodes the single Caenorhabditis elegans ortholog of SEC13, a small six-bladed WD40 beta-propeller protein of the Sec13/Seh1 family. Like its yeast and human counterparts, NPP-20/SEC-13 is a dual-purpose structural subunit: it is a nucleoporin of the Y-shaped outer-ring subcomplex of the nuclear pore complex, and it is the propeller partner of SEC-31 in the outer cage layer of the COPII vesicle coat at endoplasmic reticulum exit sites. In the worm germline SEC-13 is seen both on nuclear envelopes and next to SEC-16-marked ER exit sites, and native SEC-13 exists in a SEC-13/SEC-31 heterotetramer and larger TFG-1-dependent assemblies. Depletion of NPP-20 blocks nuclear import of the CENP-C ortholog HCP-4 in prophase, disrupts nuclear morphology and reformation after the first embryonic mitosis, blocks cytokinesis and causes fully penetrant embryonic lethality; partial depletion arrests larvae at L2-L3. By orthology it is also expected to be a subunit of the GATOR2 complex that promotes TORC1 signalling on the lysosome, and npp-20 was recovered in a nonsense-mediated mRNA decay screen, although neither role has been dissected in the worm.
Definition: The action of a molecule that contributes to the structural integrity of a COPII vesicle coat, such as the Sec13-Sec31 heterotetramer that forms the outer cage of the coat.
Justification: GO has structural-constituent terms for the nuclear pore and other assemblies but none for the COPII coat. SEC13 is a structural subunit of both the nuclear pore outer ring and the COPII outer cage, so refining structural molecule activity to the nuclear pore term alone would leave its COPII role without a molecular function.
Parent term: structural molecule activity
Supporting Evidence:
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005198 structural molecule activity | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA from the SEC13 clade (yeast Sec13p). Sec13 propellers are structural subunits of both the NPC outer ring and the COPII outer cage. Reason: Correct but general. The best-established structural role in the worm is as a nucleoporin (NPC localization, nuclear import and nuclear-morphology phenotypes), so the specific child structural constituent of nuclear pore (GO:0017056) is proposed. The COPII-cage structural role is captured by the COPII vesicle coat component rows; GO has no structural-constituent term for the COPII coat, so one is proposed in proposed_new_terms and listed as the second replacement. Proposed replacements: structural constituent of nuclear pore structural constituent of COPII vesicle coat Supporting Evidence: PMID:12937276 Of 20 assigned C. elegans nucleoporin genes, 17 were found to be essential for embryonic development either alone or in combination. file:worm/npp-20/npp-20-uniprot.txt Belongs to the WD repeat SEC13 family. |
| GO:0005198 structural molecule activity | IEA GO_REF:0000002 | MODIFY | Summary: InterPro2GO mapping from the Sec13/Seh1 family signature (IPR037363). Reason: Same claim as the IBA row; correct but general. Refine to structural constituent of nuclear pore (GO:0017056) and the proposed COPII coat structural-constituent term, consistent with the IBA row. Proposed replacements: structural constituent of nuclear pore structural constituent of COPII vesicle coat Supporting Evidence: file:worm/npp-20/npp-20-uniprot.txt Belongs to the WD repeat SEC13 family. |
| GO:0005643 nuclear pore | IDA PMID:12937276 Caenorhabditis elegans nucleoporins Nup93 and Nup205 determi... | ACCEPT | Summary: Galy et al. 2003 surveyed all C. elegans nucleoporins; full text (PMC284812, read via the PMC web page; cache is abstract-only) states the nucleoporins were confirmed to localize to the nuclear periphery by antibodies or GFP fusions (Supplementary Figure 1). Witte et al. 2011 independently show SEC-13 on germline nuclear envelopes. Reason: NPC membership is a core, conserved function of SEC13 and is directly supported in the worm. Supporting Evidence: PMID:12937276 To obtain insight into the structure and function of NPCs of multicellular organisms, we have initiated an extensive analysis of Caenorhabditis elegans nucleoporins. PMID:21478858 In control animals, the COPII subunit SEC-13 is found in close apposition to SEC-16 labeled exit sites and on the nuclear envelopes of proliferating germ nuclei |
| GO:0005643 nuclear pore | IEA GO_REF:0000044 | ACCEPT | Summary: SubCell mapping of "Nucleus, nuclear pore complex" (UniProt evidence PubMed:21478858). Reason: Consistent with the IDA row and with SEC13 orthologs in yeast and human. Supporting Evidence: PMID:21478858 while localization of SEC-13 to the nuclear envelope was largely unaffected |
| GO:0005765 lysosomal membrane | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: SubCell mapping of "Lysosome membrane", itself by similarity to human SEC13 (P55735), reflecting the GATOR2 pool on the lysosomal surface. Reason: Plausible by orthology (SEC13 is a GATOR2 subunit acting on lysosomal Rag GTPases) but not examined in C. elegans; peripheral to the NPC/COPII core. Supporting Evidence: PMID:23723238 inhibition of GATOR2 subunits (Mios, WDR24, WDR59, Seh1L, and Sec13) suppresses mTORC1 signaling |
| GO:0005765 lysosomal membrane | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS from human SEC13 (P55735), a GATOR2 subunit at the lysosome. Reason: Same claim as the IEA row; reasonable orthology transfer of the GATOR2 location, not tested in the worm. Supporting Evidence: PMID:23723238 inhibition of GATOR2 subunits (Mios, WDR24, WDR59, Seh1L, and Sec13) suppresses mTORC1 signaling |
| GO:0005789 endoplasmic reticulum membrane | EXP PMID:21478858 TFG-1 function in protein secretion and oncogenesis. | ACCEPT | Summary: Witte et al. 2011 localize SEC-13 by immunofluorescence and immuno-EM next to SEC-16-marked ER exit sites in the germline, as the COPII outer-coat subunit. Reason: Direct worm evidence for the COPII pool on the cytoplasmic face of the ER at exit sites. Supporting Evidence: PMID:21478858 Dual immuno-gold labeling with TFG-1 and SEC-13 antibodies indicated that both proteins localize to an identical area next to ER exit sites, although the SEC-13 labeling was more discrete |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: SubCell mapping of "Endoplasmic reticulum membrane" (UniProt evidence PubMed:21478858). Reason: Consistent with the EXP row. Supporting Evidence: PMID:21478858 In control animals, the COPII subunit SEC-13 is found in close apposition to SEC-16 labeled exit sites |
| GO:0006606 protein import into nucleus | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA; npp-20 itself (WB:WBGene00003806) is among the experimental sources, which is expected rather than circular. Reason: Supported by the worm IMP (HCP-4 import) and by the conserved NPC scaffold role. Supporting Evidence: PMID:28122936 Following the knockdown of NPP-10, NPP-13 and NPP-20, HCP-4 remains in the cytosol throughout prophase due to stalled import. |
| GO:0006606 protein import into nucleus | IMP PMID:28122936 Nucleoporins NPP-10, NPP-13 and NPP-20 are required for HCP-... | ACCEPT | Summary: NPP-20 RNAi stalls nuclear import of HCP-4/CENP-C during prophase in early embryos. Reason: Direct worm evidence for a role in nuclear protein import, consistent with NPC scaffold membership. Supporting Evidence: PMID:28122936 Following the knockdown of NPP-10, NPP-13 and NPP-20, HCP-4 remains in the cytosol throughout prophase due to stalled import. |
| GO:0006997 nucleus organization | IMP PMID:12937276 Caenorhabditis elegans nucleoporins Nup93 and Nup205 determi... | KEEP AS NON CORE | Summary: In the full text (PMC284812), npp-20(RNAi) embryos have very irregular nuclear morphology, and depletion of CeSec13 among other nucleoporins seemed to completely block nuclear formation after the first mitosis (Figure 1N, Table 1). Reason: Real phenotype and plausible for a nucleoporin (post-mitotic nuclear/NPC reassembly), but the specific step NPP-20 performs is not defined and the authors note pleiotropy; non-core. Supporting Evidence: PMID:12937276 In several cases, depletion of nucleoporins by RNAi caused severe defects in nuclear appearance. file:worm/npp-20/npp-20-uniprot.txt Cytokinesis is blocked and nucleus formation is impaired after the first embryonic mitosis (PubMed:12937276) |
| GO:0009792 embryo development ending in birth or egg hatching | IMP PMID:12937276 Caenorhabditis elegans nucleoporins Nup93 and Nup205 determi... | KEEP AS NON CORE | Summary: npp-20(RNAi) gives 100% embryonic lethality (Table 1, n = 588, full text). Reason: Essentiality phenotype; reflects requirement of NPC and COPII functions rather than a developmental role. Supporting Evidence: PMID:12937276 Of 20 assigned C. elegans nucleoporin genes, 17 were found to be essential for embryonic development either alone or in combination. |
| GO:0009792 embryo development ending in birth or egg hatching | IMP PMID:28122936 Nucleoporins NPP-10, NPP-13 and NPP-20 are required for HCP-... | KEEP AS NON CORE | Summary: NPP-20 knockdown causes severe chromosomal defects in the early embryo and embryonic lethality. Reason: Same claim as the PMID:12937276 row; essentiality phenotype, non-core. Supporting Evidence: PMID:28122936 affects early steps in centromere formation and sister centromere resolution, and results in severe chromosomal defects in the early embryo. |
| GO:0010973 positive regulation of division septum assembly | IMP PMID:12937276 Caenorhabditis elegans nucleoporins Nup93 and Nup205 determi... | MODIFY | Summary: Flagged by Wei et al. 2020 (PMID:32470107) as a taxon-implausible term. The full text of Galy et al. 2003 (PMC284812; cache is abstract-only) states that RNAi against CeSec13R caused additional severe defects in embryonic appearance and blocked cytokinesis, which the authors attribute to pleiotropic Sec13 functions (NPC and COPII). UniProt has synced this as curated disruption-phenotype text. The curator evidently mapped this animal cytokinesis block onto a division-septum term. Reason: The observation is a genuine experimental phenotype, so the row should not be removed, but division septum assembly is defined for fungal/bacterial septation and does not occur in a nematode embryo. The animal-appropriate term for a block in the first embryonic division is mitotic cytokinesis (GO:0000281). This role is non-core and probably indirect (e.g. COPII-dependent membrane supply), as the authors themselves suggest. Proposed replacements: mitotic cytokinesis Supporting Evidence: file:worm/npp-20/npp-20-uniprot.txt Cytokinesis is blocked and nucleus formation is impaired after the first embryonic mitosis (PubMed:12937276) PMID:12937276 In several cases, depletion of nucleoporins by RNAi caused severe defects in nuclear appearance. |
| GO:0012507 ER to Golgi transport vesicle membrane | IEA GO_REF:0000044 | ACCEPT | Summary: SubCell mapping of "COPII-coated vesicle membrane" (by similarity to human SEC13). Reason: SEC-13 is a COPII outer-coat subunit with SEC-31 in the worm, so it is on the cytoplasmic face of COPII vesicles. Supporting Evidence: PMID:21478858 which likely corresponds to a SEC-13-SEC-31 heterotetramer that was described previously |
| GO:0030127 COPII vesicle coat | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from yeast Sec13p and human SEC13; worm SEC-13 forms a SEC-13-SEC-31 complex at ER exit sites. Reason: Core, conserved function, corroborated by worm biochemical and localization data. Supporting Evidence: PMID:21478858 which likely corresponds to a SEC-13-SEC-31 heterotetramer that was described previously PMID:21478858 In control animals, the COPII subunit SEC-13 is found in close apposition to SEC-16 labeled exit sites |
| GO:0031080 nuclear pore outer ring | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA placed at a deep Sec13/Seh1 node with yeast, human and trypanosome evidence. Reason: Sec13 is a conserved Y-complex (Nup84/Nup107-160) subunit; NPP-20 is classified as a C. elegans nucleoporin and localizes to the NPC. Supporting Evidence: PMID:12937276 To obtain insight into the structure and function of NPCs of multicellular organisms, we have initiated an extensive analysis of Caenorhabditis elegans nucleoporins. |
| GO:0032008 positive regulation of TOR signaling | IBA GO_REF:0000033 | MODIFY | Summary: PAINT IBA from yeast Sec13p (SEACAT) and human SEC13 (GATOR2), which promote TORC1 activity by inhibiting GATOR1/SEACIT. Reason: The orthology-based inference is reasonable (C. elegans has GATOR2 subunit orthologs) but untested in the worm, and the donor evidence is specifically for TORC1, so refine to positive regulation of TORC1 signaling (GO:1904263). Non-core relative to the NPC/COPII roles. Proposed replacements: positive regulation of TORC1 signaling Supporting Evidence: PMID:23723238 inhibition of GATOR2 subunits (Mios, WDR24, WDR59, Seh1L, and Sec13) suppresses mTORC1 signaling |
| GO:0051169 nuclear transport | IC PMID:12937276 Caenorhabditis elegans nucleoporins Nup93 and Nup205 determi... | ACCEPT | Summary: Inferred by curator from nuclear pore localization. Reason: A nucleoporin of the NPC scaffold participates in nucleocytoplasmic transport generally (import and export); the broader term remains informative alongside protein import into nucleus. Supporting Evidence: PMID:12937276 Nuclear pore complexes (NPCs) span the nuclear envelope and mediate communication between the nucleus and the cytoplasm. |
| GO:0090114 COPII-coated vesicle budding | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT IBA from yeast Sec13p and human SEC13; Sec13-Sec31 forms the outer cage that drives COPII vesicle budding. Reason: Core conserved function; worm SEC-13 is recruited to ER exit sites with SEC-31 and SEC-16. Supporting Evidence: PMID:21478858 When activated by the Sec12 exchange factor, Sar1 recruits the Sec23-Sec24 complex, which forms an adaptor layer for Sec13-Sec31 lattice assembly, completing the COPII coat |
| GO:1990893 mitotic chromosome centromere condensation | IMP PMID:28122936 Nucleoporins NPP-10, NPP-13 and NPP-20 are required for HCP-... | MARK AS OVER ANNOTATED | Summary: NPP-20 knockdown impairs early centromere formation and sister-centromere resolution, which the authors explain by stalled nuclear import of HCP-4/CENP-C. Reason: The centromere phenotype is a downstream consequence of the nuclear import defect (already captured by protein import into nucleus); NPP-20 does none of the work of centromere chromatin compaction. Abstract-only cache, but the abstract explicitly attributes the phenotype to failed HCP-4 import. Supporting Evidence: PMID:28122936 These results indicate that correct timing of the availability of HCP-4 by nuclear import is essential. |
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Download this section (compressed HTML)Q: Is the cytokinesis block in npp-20(RNAi) one-cell embryos due to loss of COPII-dependent membrane delivery, NPC/nuclear defects, or a direct role at the furrow?
Q: Does NPP-20 act in a worm GATOR2 complex (with WDR-24, WDR-59 and MIOS orthologs) to promote TORC1 signalling, and is it found on lysosomes in C. elegans?
Q: Is the NMD requirement for npp-20 a direct function or a secondary consequence of NPC (mRNA export) or ER/COPII defects?
Q: Should UniProt/GO replace GO:0010973 positive regulation of division septum assembly on Q9N4A7 with mitotic cytokinesis (GO:0000281), given that the source paper reports an animal cytokinesis block?
Experiment: Time-lapse imaging of furrow ingression and plasma-membrane addition in partial npp-20(RNAi) embryos, compared with sec-31, sec-23 and Y-complex nucleoporin (npp-5, npp-15) depletion, to separate COPII from NPC contributions to the cytokinesis defect.
Type: RNAi phenotyping with live imaging
Experiment: Endogenously tagged NPP-20 co-immunoprecipitation/mass spectrometry and lysosomal co-localization in starved versus fed animals, with TORC1 readouts, to test GATOR2 membership in C. elegans.
Type: proteomics and cell biology
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