sec-16A.1 (ZK512.5) encodes the Caenorhabditis elegans SEC-16 protein, a large (1232 aa), largely disordered member of the SEC16 family carrying the conserved central domain and the C-terminal Sec23-binding domain. SEC-16 is a peripheral scaffold of endoplasmic reticulum exit sites (ERES), the ER subdomains where COPII vesicles bud. In the germline and oocytes it marks ERES puncta, binds directly to the N-terminus of the hexameric TFG-1 protein, and is required for TFG-1 and the COPII subunit SEC-13 to assemble at these sites; SEC-16 and TFG-1 co-fractionate in large complexes that also contain COPII subunits. Depletion of SEC-16 disrupts ERES and COPII puncta, mislocalizes the Golgi marker RAB-6, and prevents embryo production, consistent with a conserved role in organizing COPII-dependent export of secretory cargo from the ER toward the Golgi.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005515 protein binding | IPI PMID:21478858 TFG-1 function in protein secretion and oncogenesis. | REMOVE | Summary: Direct binding of SEC-16 to TFG-1 (Q9U1W1) was shown by co-immunoprecipitation and GST pull-down with recombinant proteins. The interaction is real and functionally important for ERES organization, but bare protein binding is uninformative. Reason: Per the protein-binding policy, the generic GO:0005515 row is removed as uninformative; removal does not dispute the SEC-16/TFG-1 interaction. The functional content of the interaction (scaffolding of COPII/TFG-1 at ERES) is captured by the protein-membrane adaptor activity and ER exit site annotations and in core_functions. Supporting Evidence: PMID:21478858 We found that a GST-fusion to SEC-16, but not GST alone, was capable of binding to recombinant TFG-1 PMID:21478858 These data confirm a direct biochemical association between SEC-16 and TFG-1. |
| GO:0005783 endoplasmic reticulum | EXP PMID:21478858 TFG-1 function in protein secretion and oncogenesis. | ACCEPT | Summary: Immunofluorescence shows SEC-16 at ER exit sites, a subdomain of the ER, in the germline and oocytes. Reason: Root organelle term with direct evidence; the ER claim holds because ERES are part of the ER. The sub-compartment (GO:0070971 ER exit site) is annotated separately and is kept alongside, per the organelle policy. Supporting Evidence: PMID:21478858 We conclude that TFG-1 localizes to ER exit sites with both SEC-16 and COPII machinery. |
| GO:0005783 endoplasmic reticulum | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic ER annotation from the UniProt subcellular location (itself based on PMID:21478858) and an ARBA rule. Reason: The source of this row is the curated UniProt subcellular location (Endoplasmic reticulum, ECO:0000269 PubMed:21478858); the organelle claim is sound because SEC-16 sits on ER exit sites. Kept consistent with the EXP row; the ERES sub-compartment is annotated separately. Supporting Evidence: PMID:21478858 We conclude that TFG-1 localizes to ER exit sites with both SEC-16 and COPII machinery. |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | EXP PMID:23840591 The ArfGEF GBF-1 Is Required for ER Structure, Secretion and... | MARK AS OVER ANNOTATED | Summary: UniProt cites Ackema et al. 2013 for ERGIC localization. In the full text, SEC-16 is used only as an ERES marker adjacent to GBF-1 and the cis-Golgi; the paper does not mention an ERGIC or localize SEC-16 to one. Reason: The full text of PMID:23840591 (cached) supports ER exit site localization, which is already annotated (GO:0070971, IDA from this same paper). ERGIC is a distinct post-ER compartment; nothing in the paper places SEC-16 there, and SEC16-family proteins are ERES-resident scaffolds. The ERGIC claim therefore exceeds the evidence. Not REMOVE, because the observation (SEC-16 puncta at the ER-Golgi interface close to the Golgi) is genuine and the curator may have read "t-ER-Golgi unit" proximity as ERGIC. Supporting Evidence: PMID:23840591 GBF-1 was localized juxtaposed to the ERES marker SEC-16. PMID:23840591 However, in all analyzed oocytes SEC-16 still localized in marked patches on close to the Golgi |
| GO:0005793 endoplasmic reticulum-Golgi intermediate compartment | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Electronic mapping of the UniProt "Endoplasmic reticulum-Golgi intermediate compartment" subcellular location, which rests on PMID:23840591. Reason: Same claim as the EXP row, inherited from the same UniProt statement; the underlying paper supports ER exit site rather than ERGIC localization. Supporting Evidence: file:worm/sec-16A.1/sec-16A.1-deep-research-manual.md The paper does not describe SEC-16 in an ERGIC PMID:23840591 GBF-1 was localized juxtaposed to the ERES marker SEC-16. |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that SEC16-family proteins participate in COPII-mediated ER-to-Golgi transport; the donor set includes sec-16A.1 itself (WB), yeast Sec16, human SEC16A/B, fly and trypanosome orthologs. Reason: sec-16A.1 is a clear SEC16-family member (Sec16 central and Sec23-binding domains) and its own IMP evidence supports the process; Sec16 scaffolds COPII coat assembly at ERES, a direct contribution to vesicle formation. Its appearance among the IBA sources reflects its own experimental grounding. Supporting Evidence: PMID:21478858 Sec16 interacts with all COPII coat components, potentially serving as a scaffold for their recruitment file:worm/sec-16A.1/sec-16A.1-uniprot.txt Belongs to the SEC16 family. |
| GO:0006888 endoplasmic reticulum to Golgi vesicle-mediated transport | IMP PMID:21478858 TFG-1 function in protein secretion and oncogenesis. | ACCEPT | Summary: SEC-16 RNAi abolishes normal ERES/COPII (SEC-13) puncta and shifts the Golgi marker RAB-6 to enlarged endosome-like structures; SEC-16 is required for embryo production along with COPII subunits. Reason: Loss-of-function evidence combined with SEC-16's direct role in assembling COPII at ERES (remaining SEC-16 continues to recruit COPII in proportion to its level) shows the protein does part of the work of COPII vesicle formation, not merely that it is needed. Core process. Supporting Evidence: PMID:21478858 Depletion of SEC-16 led to nearly complete loss of puncta labeled by TFG-1, and the few structures that were observed appeared abnormally large and did not co-stain for the COPII component SEC-13 PMID:21478858 following depletion of either SEC-16 or TFG-1, RAB-6 accumulated on fewer, large punctate structures in the germline that also harbored RAB-5, suggesting that RAB-6 localization was shifted from the Golgi to enlarged early endosomes PMID:21478858 indicating that the remaining SEC-16 on ER exit sites can continue to recruit COPII components in the absence of TFG-1 |
| GO:0012507 ER to Golgi transport vesicle membrane | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Phylogenetic inference that SEC16-family proteins act on ER-to-Golgi COPII vesicle membranes, grounded in yeast Sec16. Reason: The function of Sec16 is executed at the ER exit site before and during budding; the worm experiments place SEC-16 stably at ERES puncta, and ERES persist (with SEC-16) independently of downstream Golgi factors. No data for the worm protein place it on released ER-to-Golgi vesicles, and the metazoan SEC16 subfamily is characterized as an ERES-resident scaffold rather than a vesicle component. The ERES location (GO:0070971) already captures where the protein is active. Propagation Review Root cause: PROPAGATION BAD Failure modes: COMPARTMENT OR COMPLEX MISMATCH Sources checked: SGD:S000006006 · Sec16 (yeast) SUPPORTS SOURCE BUT NOT TARGET Yeast Sec16 vesicle-membrane association is not shown for the worm protein, which is observed only at ERES. PANTHER:PTN000333928 SUPPORTS SOURCE BUT NOT TARGET Supporting Evidence: PMID:21478858 We conclude that TFG-1 localizes to ER exit sites with both SEC-16 and COPII machinery. PMID:23840591 However, in all analyzed oocytes SEC-16 still localized in marked patches on close to the Golgi |
| GO:0043495 protein-membrane adaptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference that SEC16-family proteins link COPII/ERES proteins to the ER membrane, grounded in yeast Sec16. Reason: Consistent with the conserved Sec16 scaffold role and with worm data: SEC-16 is required to anchor TFG-1 and COPII (SEC-13) at ERES, binds TFG-1 directly, and recruits COPII in proportion to its own level on ERES. sec-16A.1 retains the Sec16 central and Sec23-binding domains, so it falls within the clade at which PAINT placed this function. This is the best available GO term for the scaffolding activity. Supporting Evidence: PMID:21478858 We conclude that TFG-1 requires SEC-16 for its localization, while SEC-16 requires TFG-1 to accumulate normally on ER exit sites. PMID:21478858 indicating that the remaining SEC-16 on ER exit sites can continue to recruit COPII components in the absence of TFG-1 file:worm/sec-16A.1/sec-16A.1-uniprot.txt Pfam; PF12931; TPR_Sec16; 1. |
| GO:0070971 endoplasmic reticulum exit site | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic inference of ERES localization, which is directly confirmed for the worm protein (WB is among the sources). Reason: ERES is the defining location of SEC16-family proteins and is directly shown for SEC-16 in two independent C. elegans studies. Supporting Evidence: PMID:21478858 We conclude that TFG-1 localizes to ER exit sites with both SEC-16 and COPII machinery. |
| GO:0070971 endoplasmic reticulum exit site | IDA PMID:21478858 TFG-1 function in protein secretion and oncogenesis. | ACCEPT | Summary: Immunofluorescence with anti-SEC-16 antibodies shows SEC-16 on ER exit site puncta in oocytes, colocalizing with TFG-1 and adjacent to COPII SEC-13. Reason: Direct experimental localization; this is the core location of the protein. Supporting Evidence: PMID:21478858 TFG-1 antibodies stained punctate structures throughout the cytoplasm of oocytes, 85% of which co-localized with SEC-16 on ER exit sites |
| GO:0070971 endoplasmic reticulum exit site | IDA PMID:23840591 The ArfGEF GBF-1 Is Required for ER Structure, Secretion and... | ACCEPT | Summary: SEC-16 immunostaining marks ERES patches juxtaposed to GBF-1 and the cis-Golgi in oocytes. Reason: Independent direct localization confirming ERES residence. Supporting Evidence: PMID:23840591 GBF-1 was localized juxtaposed to the ERES marker SEC-16. |
Loading supporting content…
Download this section (compressed HTML)Q: Does worm SEC-16 bind SEC-23/SEC-24 and SEC-13/SEC-31 directly through its central and C-terminal domains, as shown for yeast and mammalian Sec16?
Q: How are functions divided between sec-16A.1 and the other C. elegans Sec16-family loci, and is sec-16A.1 the only one acting at germline ERES?
Q: Should UniProt revise the ERGIC subcellular location for P34643, given that the cited paper (PMID:23840591) uses SEC-16 only as an ER exit site marker?
Experiment: Pull-down of recombinant SEC-16 domains with purified SEC-23/SEC-24 and SEC-13/SEC-31, and tissue-specific degron depletion of endogenously tagged SEC-16 followed by cargo-export (e.g. RUSH-type) assays in intestine and hypodermis.
Hypothesis: SEC-16 binds COPII subunits directly and is required for ER export in somatic secretory tissues as well as the germline.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)