SEC62 (also TLOC1, translocation protein 1) is a multi-pass endoplasmic reticulum membrane protein and an auxiliary component of the Sec61 translocon. Together with SEC63 it forms the SEC62-SEC63 complex that promotes translocation of precursor polypeptides into the ER, with a particular role in the post-translational import of small presecretory proteins bearing short, weakly hydrophobic signal peptides. SEC62 acts as a membrane targeting receptor that positions newly synthesized precursors into the Sec61 channel and helps trigger channel opening for translocation into the ER lumen. SEC62 has two transmembrane helices with N- and C-terminal cytoplasmic domains and interacts with the translocon core (e.g. SEC61B). In addition to its translocation role, SEC62 functions as a receptor in recovery-phase ER-phagy (reticulophagy), interacting with autophagy LC3/GABARAP-family proteins to mediate selective degradation of ER following stress. SEC62 is broadly expressed and is amplified in several cancers.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005789 endoplasmic reticulum membrane | IBA GO_REF:0000033 | ACCEPT | Summary: SEC62 is an integral ER membrane protein that acts at the ER membrane as a translocon-associated factor. ER membrane is its core site of action, conserved across the SEC62 family. Reason: Core cellular component; SEC62 functions at the ER membrane in association with the Sec61 translocon. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0008320 protein transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: As part of the translocon machinery, SEC62 contributes to transmembrane transport of precursor polypeptides into the ER, positioning them into the Sec61 channel. This molecular function is conserved across the family. Reason: Core molecular function in the context of the translocon; SEC62 helps move precursor polypeptides across the ER membrane. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex, triggering channel opening for polypeptide translocation to the ER lumen. |
| GO:0031204 post-translational protein targeting to membrane, translocation | IBA GO_REF:0000033 | ACCEPT | Summary: SEC62 mediates post-translational transport of precursor polypeptides across the ER membrane; this is its defining biological process, conserved across the family. Reason: Core biological process; SEC62 is a translocation/post-translational targeting factor of the ER translocon. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000120 | ACCEPT | Summary: Electronic assignment of ER membrane localization from the UniProt subcellular location, consistent with the multi-pass ER membrane topology. Reason: Correct core localization; redundant with IBA/IDA ER membrane evidence. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0015031 protein transport | IEA GO_REF:0000002 | ACCEPT | Summary: SEC62 mediates protein transport into the ER; protein transport is a correct but generic parent of the specific post-translational translocation process. Reason: Correct general biological process; the specific GO:0031204 better captures SEC62's translocation role. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER). |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: BioPlex proteome-scale interactome capture; bare protein binding is uninformative for core function. Reason: High-throughput interactome interaction; uninformative bare term not elevated to core per guidelines. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Q99442; O95166: GABARAP |
| GO:0005515 protein binding | IPI PMID:37219487 Large-scale phosphomimetic screening identifies phospho-modu... | KEEP AS NON CORE | Summary: Phosphomimetic motif-based interaction screen; bare protein binding is uninformative. Reason: High-throughput interaction screen; uninformative bare term not elevated to core. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Q99442; O95166: GABARAP |
| GO:0005789 endoplasmic reticulum membrane | IDA PMID:22375059 Different effects of Sec61Ξ±, Sec62 and Sec63 depletion on tr... | ACCEPT | Summary: Direct functional study (Sec61/Sec62/Sec63 depletion) places SEC62 active at the ER membrane in ER protein transport. Reason: Core site of action with direct experimental support. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0061709 reticulophagy | IMP PMID:31006538 Intrinsically Disordered Protein TEX264 Mediates ER-phagy. | KEEP AS NON CORE | Summary: SEC62 acts in recovery-phase ER-phagy (reticulophagy), consistent with its interaction with the autophagy protein GABARAP. This is a genuine but secondary role distinct from its core translocon function. Reason: Real ER-phagy role supported by GABARAP interaction, but distinct from and secondary to the core translocon/translocation function. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Q99442; O95166: GABARAP |
| GO:0031204 post-translational protein targeting to membrane, translocation | IMP PMID:29719251 Chaperone-Mediated Sec61 Channel Gating during ER Import of ... | ACCEPT | Summary: SEC62 is a membrane-targeting component for small presecretory proteins during their import into the ER; this study demonstrates its role in chaperone-mediated Sec61 channel gating. Reason: Core biological process with direct experimental (IMP) support; SEC62 targets/translocates small presecretory precursors. Supporting Evidence: PMID:29719251 Sec62 have all been characterized as membrane-targeting components for small presecretory proteins |
| GO:0006620 post-translational protein targeting to endoplasmic reticulum membrane | IMP PMID:22375059 Different effects of Sec61Ξ±, Sec62 and Sec63 depletion on tr... | ACCEPT | Summary: SEC62 mediates post-translational targeting of precursors to the ER membrane; supported by depletion studies of ER transport components. Reason: Core biological process; specific post-translational ER targeting role with experimental (IMP) support. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides. |
| GO:0016020 membrane | IDA PMID:22375059 Different effects of Sec61Ξ±, Sec62 and Sec63 depletion on tr... | KEEP AS NON CORE | Summary: SEC62 is a membrane protein; "membrane" is a correct but generic parent of the specific ER membrane localization. Reason: Correct but generic; ER membrane (GO:0005789) is the more specific and informative localization. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Multi-pass membrane protein |
| GO:0005791 rough endoplasmic reticulum | ISS GO_REF:0000024 | ACCEPT | Summary: SEC62 localizes to the rough ER, consistent with its role at the translocon where translating/translocating ribosomes engage the membrane. Reason: Correct and more specific ER subcompartment localization, consistent with translocon association. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0038023 signaling receptor activity | TAS PMID:9020021 Identification of a human cDNA homologue to the Drosophila t... | MARK AS OVER ANNOTATED | Summary: SEC62 is a translocon-associated targeting receptor for presecretory proteins, not a signal-transduction (signaling) receptor. The "signaling receptor activity" term mischaracterizes its receptor role; this is a legacy ProtInc annotation. Reason: SEC62 functions as a precursor-targeting receptor at the translocon, not a signal-transduction receptor; signaling receptor activity over-extends/misframes its molecular function. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides. |
| GO:0005783 endoplasmic reticulum | TAS PMID:9020021 Identification of a human cDNA homologue to the Drosophila t... | ACCEPT | Summary: SEC62 is an ER protein; ER localization is correct (the ER membrane is the more specific compartment). Reason: Correct compartment; redundant with the more specific ER membrane annotations. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane |
| GO:0006613 cotranslational protein targeting to membrane | TAS PMID:9020021 Identification of a human cDNA homologue to the Drosophila t... | KEEP AS NON CORE | Summary: SEC62 participates in protein targeting to the ER membrane; while its hallmark is post-translational import of small precursors, it is associated with the translocon during cotranslational translocation as well. Reason: SEC62's defining role is post-translational translocation; cotranslational targeting is a less specific/less central aspect of its function captured better by the post-translational terms. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex |
| GO:0016020 membrane | TAS PMID:9020021 Identification of a human cDNA homologue to the Drosophila t... | KEEP AS NON CORE | Summary: SEC62 is a membrane protein; "membrane" is a generic parent of the specific ER membrane localization. Reason: Correct but generic; the specific ER membrane (GO:0005789) is the informative localization. Supporting Evidence: file:human/SEC62/SEC62-uniprot.txt Multi-pass membrane protein |
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Download this section (compressed HTML)Q: How is SEC62's translocation function at the Sec61 translocon mechanistically coupled to its separate role as an ER-phagy receptor, and are these activities temporally or spatially partitioned?
Q: What determines SEC62's selectivity for small presecretory proteins with short, apolar signal peptides over SRP-dependent substrates?
Experiment: Reconstitute post-translational import of a defined small presecretory protein with purified Sec61 channel plus/minus SEC62/SEC63 to quantify SEC62's contribution to channel gating and precursor positioning.
Experiment: Separation-of-function mutagenesis of the SEC62 GABARAP/LC3-interacting region versus translocon-binding regions to dissect its ER-phagy role from its translocation role in cells.
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