Existing Annotations Review

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 transmembrane protein 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 Sec61α, 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 Sec61α, 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. PMID:32133789
GO:0016020 membrane	IDA PMID:22375059 Different effects of Sec61α, 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

Core Functions

Translocon-associated ER membrane protein that mediates post-translational translocation of precursor polypeptides into the ER, acting as a targeting receptor for small presecretory proteins and positioning them into the Sec61 channel.

Molecular Function:

transmembrane protein transporter activity

Directly Involved In:

post-translational protein targeting to membrane, translocation

Cellular Locations:

endoplasmic reticulum 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.
PMID:29719251
Sec62 have all been characterized as membrane-targeting components for small presecretory proteins

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:22375059

Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells.

Depletion of Sec61alpha, Sec62 and Sec63 has different effects on cotranslational and post-translational transport of polypeptides into the ER; establishes SEC62 as an ER-membrane translocation component.

PMID:29719251

Chaperone-Mediated Sec61 Channel Gating during ER Import of Small Precursor Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier.

Sec62 is a membrane-targeting component for small presecretory proteins, while Sec63 and the lumenal chaperone BiP act as auxiliary translocation components during chaperone-mediated Sec61 channel gating.

PMID:31006538

Intrinsically Disordered Protein TEX264 Mediates ER-phagy.

ER-phagy receptor study (TEX264); the SEC62 reticulophagy annotation reflects SEC62's documented recovery-ER-phagy role and its GABARAP/LC3 interaction.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:37219487

Large-scale phosphomimetic screening identifies phospho-modulated motif-based protein interactions.

PMID:24304694

Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62 gene silencing in human tumor cells.

SEC62 regulates the major ER Ca2+ leak channel Sec61 via a direct, Ca2+-sensitive interaction (Biacore); a Ca2+-binding motif in SEC62 is essential for this function. SEC62 silencing elevates cytosolic Ca2+ and increases thapsigargin-evoked ER Ca2+ leakage, and calmodulin antagonists (trifluoperazine, ophiobolin A) phenocopy SEC62 depletion (impaired migration, ER-stress sensitization). SEC62 is overexpressed in prostate, lung and thyroid cancers and correlates with reduced survival.

PMID:32133789

Identification of signal peptide features for substrate specificity in human Sec62/Sec63-dependent ER protein import.

Using an unbiased proteomics approach in intact human cells, 22 novel Sec62/Sec63 substrates were identified in addition to ERj3; these substrates share signal peptides with comparatively longer but less hydrophobic H-regions and lower C-region polarity, and the combination of a slowly gating signal peptide plus a downstream translocation-disruptive positively charged cluster is decisive for the Sec62/Sec63 (and BiP) requirement. The human Sec62/Sec63 complex may support Sec61 opening either by direct interaction with the cytosolic N-terminus of Sec61alpha or via recruitment of BiP to ER-lumenal loop 7 of Sec61alpha.

PMID:41009394

Rules of Engagement for Components of Membrane Protein Biogenesis at the Human Endoplasmic Reticulum.

Review/article hybrid using siRNA depletion of individual ER targeting and insertion components (including SEC62/SEC63) combined with label-free quantitative proteomics to define client types and rules of engagement for components of the human ER protein biogenesis machinery, placing SEC62 as a substrate-selective Sec61 translocon effector.

PMID:9020021

Identification of a human cDNA homologue to the Drosophila translocation protein 1 (Dtrp1).

Cloning of human HTP1/SEC62 (translocation protein 1), homologue of yeast/Drosophila Sec62p, an ER protein-translocation component expressed in many tissues.

file:human/SEC62/SEC62-uniprot.txt

UniProt entry Q99442 (SEC62_HUMAN), Translocation protein SEC62

SEC62 mediates post-translational transport of precursor polypeptides across the ER, acts as a targeting receptor for small presecretory proteins, positions them into the Sec61 channel and triggers channel opening; multi-pass ER membrane protein; auxiliary component of the Sec61 translocon with SEC63; interacts with GABARAP (ER-phagy).

Suggested Experiments

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.

Deep Research

Falcon

(SEC62-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 34 citations 2 artifacts 2026-06-12T02:52:51.341120

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000019 The schematic model describing Sec62 regulation of the Sec61 calcium leak and its interaction with calmodulin (CaM) is shown in Fig (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Human SEC62 (UniProt Q99442) — functional annotation and biomedical relevance

0) Target verification (critical disambiguation)

The target is human SEC62 (synonym TLOC1), UniProt Q99442, an ER membrane protein in the SEC62 family that functions with the Sec61 protein-conducting channel and Sec63 as part of the mammalian ER translocation machinery. This identity is explicitly aligned with UniProt Q99442 in mechanistic Sec61-translocon literature and is consistent with SEC62 being an ER translocon-associated factor in human cells. (zimmermann2025rulesofengagement pages 32-33)

1) Key concepts and current understanding (definitions and core biology)

1.1 SEC62 as a Sec61-associated translocon component

Definition/role. In mammalian cells, most secretory and membrane proteins enter the ER through the Sec61 channel. A subset of substrates require auxiliary effectors that help the channel gate/open. SEC62 is an ER-membrane translocon component that, together with SEC63, forms a Sec61-associated Sec62/Sec63 complex that supports substrate-specific ER import, particularly in contexts described as post-translational translocation or “difficult-to-gate” signal peptides. (zimmermann2025rulesofengagement pages 32-33, schorr2020identificationofsignal pages 1-2)

Mechanistic model (import/gating). Based on in-cell substrate studies and mechanistic experiments, the Sec62/Sec63 complex is proposed to support Sec61 opening for certain precursor polypeptides either (i) via interaction with the cytosolic N-terminus of Sec61α or (ii) through recruitment of BiP (HSPA5/GRP78) to engage a binding site on Sec61α (luminal loop 7) to promote productive translocation. (schorr2020identificationofsignal pages 1-2)

1.2 Substrate specificity: “rules” for SEC62/SEC63-dependent import

A major advance in understanding SEC62 biology is the identification of signal-peptide features that predict dependence on SEC62/SEC63:

SEC62/SEC63 clients tend to have signal peptides with comparatively longer but less hydrophobic H-regions and lower C-region polarity. (schorr2020identificationofsignal pages 1-2)
A key determinant for SEC62/SEC63 requirement is the combination of a slowly gating signal peptide plus a downstream positively charged cluster that disrupts translocation. (schorr2019proteomicsidentifiessignal pages 1-4, schorr2020identificationofsignal pages 1-2)

These features were experimentally linked to additional requirements for BiP and to sensitivity to Sec61-channel inhibitors in at least some substrates (e.g., ERj3/DNAJB11). (schorr2019proteomicsidentifiessignal pages 1-4, schorr2020identificationofsignal pages 10-13)

1.3 SEC62 in ER Ca2+ homeostasis: regulating Sec61 Ca2+ leak with calmodulin

Concept. The Sec61 channel is also recognized as a major passive ER Ca2+ leak pathway whose permeability depends on its gating state. SEC62 has an additional, non-canonical role: regulation of Sec61-mediated Ca2+ efflux from the ER, functionally coupled to calmodulin (CaM) signaling. (linxweiler2013targetingcellmigration pages 10-12, linxweiler2017let’stalkabout pages 6-7)

Direct evidence and model. In human tumor cell systems, SEC62 was shown to regulate Ca2+ leakage via a direct, Ca2+-sensitive interaction with the Sec61 complex (assayed biochemically), and a Ca2+-binding motif/EF-hand-like element in SEC62 was required for function. SEC62 depletion increased basal cytosolic Ca2+ (reported as at least ~two-fold) and enhanced thapsigargin-evoked Ca2+ responses, consistent with increased leak. (linxweiler2013targetingcellmigration pages 1-2, linxweiler2013targetingcellmigration pages 2-4)

A mechanistic model proposes that SEC62 acts as a local Ca2+ sensor near Sec61: Ca2+ leaking through Sec61 is sensed by SEC62, which then facilitates occupation of a cytosolic regulatory site by Ca2+-CaM that helps seal/close the Sec61 pore to limit continued Ca2+ leak. (linxweiler2013targetingcellmigration pages 10-12, linxweiler2013targetingcellmigration pages 12-13)

A schematic of this model and the predicted effects of SEC62 knockdown, thapsigargin, and calmodulin antagonism is provided in Linxweiler et al. (Figure 7). (linxweiler2013targetingcellmigration media 9094901c)

1.4 SEC62 and recovER-phagy (ER stress recovery-associated ER-phagy)

Definition. “recovER-phagy” is described in the recent ER-autophagy literature as an ER turnover pathway engaged during recovery from ER stress, distinct from starvation-induced ER-phagy.

SEC62’s role. SEC62 is repeatedly described as an ER-phagy receptor/adaptor that mediates ER turnover during recovery from ER stress (recovER-phagy), thereby linking ER protein import capacity and ER quality control. (nurlaila2026visitingtransloconsseca pages 4-6, urban2025functionallydiversifiedbip pages 33-36)

Recent framing (2023–2024). Contemporary reviews on ER autophagy and disease (e.g., FEBS Journal review on ER autophagy routes; beta-cell autophagy review) include SEC62 among identified ER-phagy receptors and explicitly associate it with recovery-from-stress ER turnover. (urban2025functionallydiversifiedbip pages 33-36)

2) Recent developments and latest research (prioritizing 2023–2024)

Because much of SEC62’s core mechanistic work (Sec61 gating; Ca2+-leak control) is anchored in earlier primary literature, the 2023–2024 landscape is dominated by:

1) Refined conceptual integration of SEC62 into ER-phagy frameworks (ER-phagy/ERLAD/secretory pathway quality control), where SEC62-mediated recovER-phagy is treated as a distinct recovery program. (urban2025functionallydiversifiedbip pages 33-36)

2) Expansion of disease contexts in which ER-phagy and ER-stress adaptation are discussed, including neurodegeneration and metabolic disease reviews that list SEC62 as an ER-phagy receptor involved in stress recovery. (urban2025functionallydiversifiedbip pages 33-36)

3) New pathway linkages reported in 2024 experimental systems (e.g., Sec62-PERK axis described in a toxicology/cell-biology model), illustrating continuing exploration of SEC62 in ER stress signaling networks—though these are not necessarily human cancer contexts and may be cell-type/species specific in experimental design. (urban2025functionallydiversifiedbip pages 33-36)

3) Cellular localization, complexes, and pathways

3.1 Localization

SEC62 is consistently treated as an ER membrane protein (translocon-associated). (zimmermann2025rulesofengagement pages 32-33, zimmermann2022theendoplasmicreticulum pages 1-2)

3.2 Core physical/functional interactions

Key partners and axes supported by experimental and review-level evidence in the retrieved corpus include:

Sec61 complex: SEC62 interacts with Sec61 and influences both substrate import and channel gating/Ca2+ leak. (linxweiler2013targetingcellmigration pages 10-12, linxweiler2013targetingcellmigration pages 1-2)
SEC63 and BiP (HSPA5/GRP78): SEC62/SEC63 cooperate to enable productive translocation for substrates with “slowly gating” signal peptides; BiP engagement is mechanistically implicated, and Sec63’s BiP-related functionality is critical for certain clients (e.g., pre-ERj3). (schorr2020identificationofsignal pages 10-13, schorr2020identificationofsignal pages 1-2)
Calmodulin (CaM): SEC62-related phenotypes in Ca2+ homeostasis and migration can be phenocopied by CaM antagonists (notably trifluoperazine), supporting a functional SEC62–CaM–Sec61 regulatory loop. (linxweiler2013targetingcellmigration pages 10-12, linxweiler2013targetingcellmigration pages 12-13)

3.3 Pathways (functional placement)

Protein biogenesis / secretory pathway entry: Sec61-mediated translocation with substrate-specific assistance by Sec62/Sec63; BiP-dependent gating for certain precursors. (schorr2020identificationofsignal pages 1-2)
ER Ca2+ homeostasis / signaling: Sec61 Ca2+ leak regulation, with SEC62 as a modulatory component in cancer-associated phenotypes (migration, stress tolerance). (linxweiler2013targetingcellmigration pages 10-12, linxweiler2017let’stalkabout pages 6-7)
ER quality control via selective autophagy: recovER-phagy as an ER-stress recovery program. (nurlaila2026visitingtransloconsseca pages 4-6, urban2025functionallydiversifiedbip pages 33-36)

4) Current applications and real-world implementations

4.1 SEC62 as a biomarker/oncogene candidate in 3q26-amplified cancers

SEC62 is located at chromosome 3q26 and is described as frequently amplified/overexpressed in cancers (including breast cancer in a review context), with overexpression correlating with invasive behavior and poor prognosis. (nurlaila2026visitingtransloconssec pages 4-6, nurlaila2026visitingtransloconsseca pages 4-6)

A clinical implementation pattern described in the literature is IHC/Western-based assessment of SEC62 abundance in tumors, motivating risk stratification and guiding exploration of SEC62-targeted strategies. (linxweiler2013targetingcellmigration pages 1-2, zimmermann2022theendoplasmicreticulum pages 1-2)

4.2 Pharmacological phenocopy of SEC62 inhibition via calmodulin antagonists

In human tumor cell models, trifluoperazine (TFP) (a clinically used calmodulin antagonist) phenocopied SEC62 depletion, inhibiting cell migration and increasing sensitivity to thapsigargin-induced ER stress. (linxweiler2013targetingcellmigration pages 10-12, linxweiler2013targetingcellmigration pages 12-13)

In a more translational framing, a 2022 review summarizes that TFP reduced tumor growth and metastatic potential in murine models and discusses combination concepts with SERCA-targeting agents (thapsigargin analogs). (zimmermann2022theendoplasmicreticulum pages 1-2)

4.3 Targeting ER Ca2+ homeostasis with SERCA-directed agents

The Sec62-centered therapeutic logic often intersects with ER Ca2+ manipulation; a 2022 review notes that phase II clinical trials had been initiated for mipsagargin/G202 (a thapsigargin prodrug targeting Ca2+ homeostasis), while also highlighting that SEC62-overexpressing tumors may show reduced responsiveness/resistance in cell-line experiments, motivating combination strategies. (zimmermann2022theendoplasmicreticulum pages 1-2)

5) Expert opinions and authoritative synthesis (how experts frame SEC62)

Authoritative reviews and synthesis pieces in the retrieved corpus consistently frame SEC62 as:

1) A substrate-selective translocation co-factor for Sec61, whose involvement can be predicted from signal peptide features and downstream sequence context. (zimmermann2025rulesofengagement pages 32-33, schorr2020identificationofsignal pages 1-2)
2) A modulator of Sec61 Ca2+ leak and therefore a bridge between protein import and Ca2+-dependent phenotypes such as migration and stress tolerance. (linxweiler2013targetingcellmigration pages 10-12, linxweiler2017let’stalkabout pages 6-7)
3) A contributor to ER stress recovery programs via recovER-phagy, which is increasingly discussed as a distinct ER-proteostasis route. (nurlaila2026visitingtransloconsseca pages 4-6, urban2025functionallydiversifiedbip pages 33-36)

6) Relevant statistics and data (recent studies and key quantitative findings)

6.1 Proteomics-defined substrate scope (SEC62 depletion in human cells)

A proteomics analysis after SEC62 knockdown reported that SEC62 depletion significantly altered steady-state levels of 329 proteins (208 down; 121 up; q < 0.05), with enrichment for proteins bearing cleavable signal peptides and N-glycosylated proteins among negatively affected proteins, supporting SEC62’s role in ER import for a subset of secretory pathway clients. (schorr2020identificationofsignal pages 7-8)

Additionally, a substrate specificity study identified 22 novel Sec62/Sec63 substrates and proposed definable signal peptide determinants (longer/less hydrophobic H-region; lower C-region polarity; slowly gating SP plus downstream positive charges) for engagement of the Sec62/Sec63 machinery. (schorr2020identificationofsignal pages 1-2)

6.2 Quantitative Ca2+ / functional phenotypes

SEC62 depletion was reported to cause at least a two-fold increase in basal cytosolic Ca2+ and increased ER Ca2+ leakage following thapsigargin, consistent with SEC62 regulating Sec61 Ca2+ leak. (linxweiler2013targetingcellmigration pages 1-2)

6.3 Pan-cancer alteration prevalence and survival (large cohort summary)

A review summarizing cancer datasets reported SEC62 alterations (mostly amplifications) in 2,595 of >72,000 cancer patients screened, and a survival analysis of 40,006 patients reported median survival 54.2 months (SEC62-altered) versus 95.6 months (unaltered). (sicking2021complexityandspecificity pages 29-32)

6.4 NSCLC cohort size in SEC62 survival analysis

In a primary NSCLC-focused study, Sec62 protein levels were quantified by western blot in 70 NSCLC patients (35 adenocarcinoma; 35 squamous cell carcinoma) and used to stratify Kaplan–Meier survival analyses using a relative Sec62 metric (rSec62). (linxweiler2013targetingcellmigration pages 1-2)

Summary table (evidence-backed functional annotation)

The table below consolidates SEC62 functions, mechanisms, and translational relevance supported by the retrieved evidence.

Functional axis	Key claims/definitions	Representative evidence (brief)	Key quantitative data (if any)	Primary sources (include DOI URLs and years)
ER translocation	Human SEC62 (UniProt Q99442) is an ER membrane component of the Sec61/Sec62/Sec63 machinery that supports substrate-specific protein import into the ER, especially when Sec61 channel opening is difficult; it acts with Sec63 and can promote Sec61 gating directly and/or via BiP recruitment. (zimmermann2025rulesofengagement pages 32-33, schorr2020identificationofsignal pages 10-13, schorr2020identificationofsignal pages 1-2)	In intact human cells, loss of SEC62 impaired import of selected precursors such as pre-ERj3; disruption of Sec62/Sec63 function prevented productive signal-peptide insertion into Sec61, and BiP-dependent rescue experiments supported a channel-gating role. (schorr2020identificationofsignal pages 10-13, schorr2020identificationofsignal pages 1-2)	SEC62 knockdown significantly altered 329 proteins (208 down, 121 up; q < 0.05), with enrichment for cleavable signal peptide and N-glycosylated proteins among negatively affected proteins. (schorr2020identificationofsignal pages 7-8)	Schorr et al., 2020, FEBS J., DOI: https://doi.org/10.1111/febs.15274 (2020); Zimmermann, 2025, Int J Mol Sci, DOI: https://doi.org/10.3390/ijms26188823 (2025)
Substrate specificity	SEC62/Sec63-dependent clients share signal peptides with comparatively longer but less hydrophobic hydrophobic regions and lower C-region polarity; dependence is strongly associated with slowly gating signal peptides plus downstream positively charged, translocation-disruptive clusters. (schorr2019proteomicsidentifiessignal pages 1-4, schorr2020identificationofsignal pages 1-2)	Proteomics in human cells identified a shared signal-peptide signature among SEC62/Sec63 clients; for ERj3, these features also conferred BiP dependence and sensitivity to a Sec61 inhibitor. (schorr2019proteomicsidentifiessignal pages 1-4, schorr2020identificationofsignal pages 1-2)	22 novel SEC62/Sec63 substrates were identified; among affected SEC62-depletion substrates, 21 had cleavable signal peptides and 29 had TMHs; 22 precursors overlapped between SEC62 and SEC63 depletion datasets. (schorr2020identificationofsignal pages 7-8, schorr2020identificationofsignal pages 1-2)	Schorr et al., 2020, FEBS J., DOI: https://doi.org/10.1111/febs.15274 (2020); Schorr et al., 2019, bioRxiv, DOI: https://doi.org/10.1101/867762 (2019)
ER Ca2+ homeostasis	SEC62 helps regulate Sec61-mediated ER Ca2+ leak in cooperation with cytosolic calmodulin (CaM); a Ca2+-binding motif/EF-hand in SEC62 is required for this function, and SEC62 is proposed to sense local Ca2+ and facilitate Ca2+-CaM-dependent channel closure. (linxweiler2013targetingcellmigration pages 10-12, linxweiler2013targetingcellmigration pages 12-13, zimmermann2022theendoplasmicreticulum pages 1-2)	Biacore/SPR and functional Ca2+ imaging supported a direct, Ca2+-sensitive interaction of Sec62 with the Sec61 complex; SEC62 silencing elevated basal cytosolic Ca2+ and increased thapsigargin-evoked Ca2+ release, while CaM antagonists phenocopied SEC62 depletion. A schematic model is available in Fig. 7. (linxweiler2013targetingcellmigration pages 1-2, linxweiler2013targetingcellmigration pages 2-4, linxweiler2013targetingcellmigration media 9094901c)	SEC62 depletion caused at least a two-fold increase in basal cytosolic Ca2+; assays used 1 μM thapsigargin for short-term Ca2+ imaging, 6–10 nM thapsigargin for proliferation assays, 4–8 μM TFP in functional assays. (linxweiler2013targetingcellmigration pages 1-2, linxweiler2013targetingcellmigration pages 2-4)	Linxweiler et al., 2013, BMC Cancer, DOI: https://doi.org/10.1186/1471-2407-13-574 (2013); Zimmermann et al., 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.1014271 (2022); Parys & Van Coppenolle, 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.991149 (2022)
recovER-phagy	SEC62 also functions as an ER-phagy receptor/adaptor during recovery from ER stress (“recovER-phagy”), linking ER protein import capacity to selective ER turnover and quality control. (nurlaila2026visitingtransloconsseca pages 4-6, urban2025functionallydiversifiedbip pages 36-39, urban2025functionallydiversifiedbip pages 33-36)	Recent reviews summarize SEC62 among ER-phagy receptors and specifically note its role in recovery-phase ER turnover rather than generic starvation-induced ER-phagy. (urban2025functionallydiversifiedbip pages 33-36)	No SEC62-specific 2023–2024 quantitative flux values were retrieved in context; available recent context is primarily review-level or cites the foundational 2016/2019 work. (urban2025functionallydiversifiedbip pages 36-39, urban2025functionallydiversifiedbip pages 33-36)	Knupp et al., 2023, FEBS J., DOI: https://doi.org/10.1111/febs.16986 (2023); Yasasilka & Lee, 2024, J Diabetes Investig., DOI: https://doi.org/10.1111/jdi.14184 (2024)
Cancer/clinical relevance	SEC62 is located on chromosome 3q/3q26, is frequently amplified/overexpressed in multiple tumors, and overexpression is associated with increased migration, invasion, stress tolerance, metastatic behavior, and poorer prognosis. (nurlaila2026visitingtransloconssec pages 4-6, nurlaila2026visitingtransloconsseca pages 4-6, korner2022antagonizingsec62function pages 1-2, zimmermann2022theendoplasmicreticulum pages 1-2)	SEC62 silencing inhibited cancer-cell migration across several tumor types, whereas overexpression stimulated migration and tumor growth-related phenotypes; reviews and mechanistic summaries describe SEC62 as a driver oncogene candidate in 3q26-amplified cancers. (sicking2021complexityandspecificity pages 29-32, linxweiler2017let’stalkabout pages 6-7, korner2022antagonizingsec62function pages 1-2)	In a pan-cancer summary, SEC62 alterations were reported in 2,595 of >72,000 cancer patients, mostly amplifications; median survival was 54.2 months with SEC62 alterations vs 95.6 months without. In one NSCLC study, 70 patients (35 AC, 35 SCC) were analyzed by western blot/Kaplan-Meier using rSec62. (sicking2021complexityandspecificity pages 29-32, linxweiler2013targetingcellmigration pages 1-2)	Linxweiler et al., 2013, BMC Cancer, DOI: https://doi.org/10.1186/1471-2407-13-574 (2013); Linxweiler et al., 2017, Signal Transduct Target Ther, DOI: https://doi.org/10.1038/sigtrans.2017.2 (2017); Körner et al., 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.880004 (2022); Zimmermann et al., 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.1014271 (2022)
Pharmacological targeting	SEC62-overexpressing tumors may be functionally targeted by calmodulin antagonists, especially trifluoperazine (TFP), which phenocopy SEC62 silencing; SERCA-targeting agents such as thapsigargin analogs/mipsagargin have also been discussed in combination strategies focused on ER Ca2+ homeostasis. (linxweiler2013targetingcellmigration pages 10-12, linxweiler2013targetingcellmigration pages 12-13, zimmermann2022theendoplasmicreticulum pages 1-2)	TFP and ophiobolin A inhibited migration and increased sensitivity to thapsigargin-induced ER stress similarly to SEC62 depletion; murine tumor models reviewed in 2022 showed TFP reduced tumor growth and metastatic potential. (linxweiler2013targetingcellmigration pages 10-12, zimmermann2022theendoplasmicreticulum pages 1-2)	Experimental conditions included 8 μM TFP with 10 nM or 0.1 nM thapsigargin in PC3 cells and 4 μM TFP in migration assays; mipsagargin/G202 had entered phase II trials, though SEC62-overexpressing cells may be less responsive. (linxweiler2013targetingcellmigration pages 10-12, zimmermann2022theendoplasmicreticulum pages 1-2)	Linxweiler et al., 2013, BMC Cancer, DOI: https://doi.org/10.1186/1471-2407-13-574 (2013); Zimmermann et al., 2022, Front Physiol, DOI: https://doi.org/10.3389/fphys.2022.1014271 (2022)

Table: This table summarizes the main experimentally supported functional axes of human SEC62/Q99442, including its roles in ER protein translocation, calcium homeostasis, recovER-phagy, and cancer relevance. It also highlights quantitative findings and source papers useful for downstream annotation or evidence review.

Concluding functional annotation (concise)

Human SEC62/Q99442 is a multi-functional ER membrane translocon component that (i) supports Sec61-mediated ER import for a substrate-defined subset of proteins via Sec62/Sec63/BiP-assisted gating, (ii) modulates Sec61-dependent ER Ca2+ leak via a Ca2+-sensitive SEC62–Sec61 interaction coupled to calmodulin regulation, and (iii) contributes to ER homeostasis through recovery-from-stress ER turnover (recovER-phagy). These mechanistic functions are linked to cancer cell phenotypes (migration, invasion, stress tolerance) and motivate biomarker and therapeutic concepts for SEC62-overexpressing (3q26-amplified) tumors. (schorr2020identificationofsignal pages 1-2, linxweiler2013targetingcellmigration pages 10-12, zimmermann2022theendoplasmicreticulum pages 1-2)

References

(zimmermann2025rulesofengagement pages 32-33): Richard Zimmermann. Rules of engagement for components of membrane protein biogenesis at the human endoplasmic reticulum. Sep 2025. URL: https://doi.org/10.3390/ijms26188823, doi:10.3390/ijms26188823. This article has 2 citations.
(schorr2020identificationofsignal pages 1-2): Stefan Schorr, Duy Nguyen, Sarah Haßdenteufel, Nagarjuna Nagaraj, Adolfo Cavalié, Markus Greiner, Petra Weissgerber, Marisa Loi, Adrienne W. Paton, James C. Paton, Maurizio Molinari, Friedrich Förster, Johanna Dudek, Sven Lang, Volkhard Helms, and Richard Zimmermann. Identification of signal peptide features for substrate specificity in human sec62/sec63‐dependent er protein import. The FEBS Journal, 287:4612-4640, Mar 2020. URL: https://doi.org/10.1111/febs.15274, doi:10.1111/febs.15274. This article has 51 citations.
(schorr2019proteomicsidentifiessignal pages 1-4): Stefan Schorr, Duy Nguyen, Sarah Haßdenteufel, Nagarjuna Nagaraj, Adolfo Cavalié, Markus Greiner, Petra Weissgerber, Marisa Loi, Adrienne W. Paton, James C. Paton, Maurizio Molinari, Friedrich Förster, Johanna Dudek, Sven Lang, Volkhard Helms, and Richard Zimmermann. Proteomics identifies signal peptide features determining the substrate specificity in human sec62/sec63-dependent er protein import. bioRxiv, Dec 2019. URL: https://doi.org/10.1101/867762, doi:10.1101/867762. This article has 11 citations.
(schorr2020identificationofsignal pages 10-13): Stefan Schorr, Duy Nguyen, Sarah Haßdenteufel, Nagarjuna Nagaraj, Adolfo Cavalié, Markus Greiner, Petra Weissgerber, Marisa Loi, Adrienne W. Paton, James C. Paton, Maurizio Molinari, Friedrich Förster, Johanna Dudek, Sven Lang, Volkhard Helms, and Richard Zimmermann. Identification of signal peptide features for substrate specificity in human sec62/sec63‐dependent er protein import. The FEBS Journal, 287:4612-4640, Mar 2020. URL: https://doi.org/10.1111/febs.15274, doi:10.1111/febs.15274. This article has 51 citations.
(linxweiler2013targetingcellmigration pages 10-12): Maximilian Linxweiler, Stefan Schorr, Nico Schäuble, Martin Jung, Johannes Linxweiler, Frank Langer, Hans-Joachim Schäfers, Adolfo Cavalié, Richard Zimmermann, and Markus Greiner. Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of sec62 gene silencing in human tumor cells. BMC Cancer, 13:574-574, Dec 2013. URL: https://doi.org/10.1186/1471-2407-13-574, doi:10.1186/1471-2407-13-574. This article has 100 citations and is from a peer-reviewed journal.
(linxweiler2017let’stalkabout pages 6-7): Maximilian Linxweiler, Bernhard Schick, and Richard Zimmermann. Let’s talk about secs: sec61, sec62 and sec63 in signal transduction, oncology and personalized medicine. Signal Transduction and Targeted Therapy, Apr 2017. URL: https://doi.org/10.1038/sigtrans.2017.2, doi:10.1038/sigtrans.2017.2. This article has 225 citations and is from a peer-reviewed journal.
(linxweiler2013targetingcellmigration pages 1-2): Maximilian Linxweiler, Stefan Schorr, Nico Schäuble, Martin Jung, Johannes Linxweiler, Frank Langer, Hans-Joachim Schäfers, Adolfo Cavalié, Richard Zimmermann, and Markus Greiner. Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of sec62 gene silencing in human tumor cells. BMC Cancer, 13:574-574, Dec 2013. URL: https://doi.org/10.1186/1471-2407-13-574, doi:10.1186/1471-2407-13-574. This article has 100 citations and is from a peer-reviewed journal.
(linxweiler2013targetingcellmigration pages 2-4): Maximilian Linxweiler, Stefan Schorr, Nico Schäuble, Martin Jung, Johannes Linxweiler, Frank Langer, Hans-Joachim Schäfers, Adolfo Cavalié, Richard Zimmermann, and Markus Greiner. Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of sec62 gene silencing in human tumor cells. BMC Cancer, 13:574-574, Dec 2013. URL: https://doi.org/10.1186/1471-2407-13-574, doi:10.1186/1471-2407-13-574. This article has 100 citations and is from a peer-reviewed journal.
(linxweiler2013targetingcellmigration pages 12-13): Maximilian Linxweiler, Stefan Schorr, Nico Schäuble, Martin Jung, Johannes Linxweiler, Frank Langer, Hans-Joachim Schäfers, Adolfo Cavalié, Richard Zimmermann, and Markus Greiner. Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of sec62 gene silencing in human tumor cells. BMC Cancer, 13:574-574, Dec 2013. URL: https://doi.org/10.1186/1471-2407-13-574, doi:10.1186/1471-2407-13-574. This article has 100 citations and is from a peer-reviewed journal.
(linxweiler2013targetingcellmigration media 9094901c): Maximilian Linxweiler, Stefan Schorr, Nico Schäuble, Martin Jung, Johannes Linxweiler, Frank Langer, Hans-Joachim Schäfers, Adolfo Cavalié, Richard Zimmermann, and Markus Greiner. Targeting cell migration and the endoplasmic reticulum stress response with calmodulin antagonists: a clinically tested small molecule phenocopy of sec62 gene silencing in human tumor cells. BMC Cancer, 13:574-574, Dec 2013. URL: https://doi.org/10.1186/1471-2407-13-574, doi:10.1186/1471-2407-13-574. This article has 100 citations and is from a peer-reviewed journal.
(nurlaila2026visitingtransloconsseca pages 4-6): I Nurlaila, D Hardianto, and N Karimah. Visiting translocons sec roles in antigen presentation in breast cancer: major translocons. Unknown journal, 2026.
(urban2025functionallydiversifiedbip pages 33-36): Nicholas D. Urban, Shannon M. Lacy, Kate M. Van Pelt, Benedict Abdon, Zachary Mattiola, Adam Klaiss, Sarah Tabler, and Matthias C. Truttmann. Functionally diversified bip orthologs control body growth, reproduction, stress resistance, aging, and er-phagy in caenorhabditis elegans. bioRxiv, Jan 2025. URL: https://doi.org/10.1101/2025.01.14.633073, doi:10.1101/2025.01.14.633073. This article has 4 citations.
(zimmermann2022theendoplasmicreticulum pages 1-2): Julia S. M. Zimmermann, Johannes Linxweiler, Julia C. Radosa, Maximilian Linxweiler, and Richard Zimmermann. The endoplasmic reticulum membrane protein sec62 as potential therapeutic target in sec62 overexpressing tumors. Frontiers in Physiology, Oct 2022. URL: https://doi.org/10.3389/fphys.2022.1014271, doi:10.3389/fphys.2022.1014271. This article has 20 citations.
(nurlaila2026visitingtransloconssec pages 4-6): I Nurlaila, D Hardianto, and N Karimah. Visiting translocons sec roles in antigen presentation in breast cancer: major translocons. Unknown journal, 2026.
(schorr2020identificationofsignal pages 7-8): Stefan Schorr, Duy Nguyen, Sarah Haßdenteufel, Nagarjuna Nagaraj, Adolfo Cavalié, Markus Greiner, Petra Weissgerber, Marisa Loi, Adrienne W. Paton, James C. Paton, Maurizio Molinari, Friedrich Förster, Johanna Dudek, Sven Lang, Volkhard Helms, and Richard Zimmermann. Identification of signal peptide features for substrate specificity in human sec62/sec63‐dependent er protein import. The FEBS Journal, 287:4612-4640, Mar 2020. URL: https://doi.org/10.1111/febs.15274, doi:10.1111/febs.15274. This article has 51 citations.
(sicking2021complexityandspecificity pages 29-32): Mark Sicking, Sven Lang, Florian Bochen, Andreas Roos, Joost P. H. Drenth, Muhammad Zakaria, Richard Zimmermann, and Maximilian Linxweiler. Complexity and specificity of sec61-channelopathies: human diseases affecting gating of the sec61 complex. Cells, 10:1036, Apr 2021. URL: https://doi.org/10.3390/cells10051036, doi:10.3390/cells10051036. This article has 46 citations.
(urban2025functionallydiversifiedbip pages 36-39): Nicholas D. Urban, Shannon M. Lacy, Kate M. Van Pelt, Benedict Abdon, Zachary Mattiola, Adam Klaiss, Sarah Tabler, and Matthias C. Truttmann. Functionally diversified bip orthologs control body growth, reproduction, stress resistance, aging, and er-phagy in caenorhabditis elegans. bioRxiv, Jan 2025. URL: https://doi.org/10.1101/2025.01.14.633073, doi:10.1101/2025.01.14.633073. This article has 4 citations.
(korner2022antagonizingsec62function pages 1-2): Sandrina Körner, Tillman Pick, Florian Bochen, Silke Wemmert, Christina Körbel, Michael D. Menger, Adolfo Cavalié, Jan-Philipp Kühn, Bernhard Schick, and Maximilian Linxweiler. Antagonizing sec62 function in intracellular ca2+ homeostasis represents a novel therapeutic strategy for head and neck cancer. Frontiers in Physiology, Aug 2022. URL: https://doi.org/10.3389/fphys.2022.880004, doi:10.3389/fphys.2022.880004. This article has 12 citations.

Artifacts

Edison artifact artifact-00

Citations

zimmermann2025rulesofengagement pages 32-33
schorr2020identificationofsignal pages 1-2
urban2025functionallydiversifiedbip pages 33-36
zimmermann2022theendoplasmicreticulum pages 1-2
schorr2020identificationofsignal pages 7-8
linxweiler2013targetingcellmigration pages 1-2
sicking2021complexityandspecificity pages 29-32
schorr2019proteomicsidentifiessignal pages 1-4
schorr2020identificationofsignal pages 10-13
linxweiler2013targetingcellmigration pages 10-12
linxweiler2013targetingcellmigration pages 2-4
linxweiler2013targetingcellmigration pages 12-13
nurlaila2026visitingtransloconsseca pages 4-6
nurlaila2026visitingtransloconssec pages 4-6
urban2025functionallydiversifiedbip pages 36-39
https://doi.org/10.1111/febs.15274
https://doi.org/10.3390/ijms26188823
https://doi.org/10.1101/867762
https://doi.org/10.1186/1471-2407-13-574
https://doi.org/10.3389/fphys.2022.1014271
https://doi.org/10.3389/fphys.2022.991149
https://doi.org/10.1111/febs.16986
https://doi.org/10.1111/jdi.14184
https://doi.org/10.1038/sigtrans.2017.2
https://doi.org/10.3389/fphys.2022.880004
https://doi.org/10.3390/ijms26188823,
https://doi.org/10.1111/febs.15274,
https://doi.org/10.1101/867762,
https://doi.org/10.1186/1471-2407-13-574,
https://doi.org/10.1038/sigtrans.2017.2,
https://doi.org/10.1101/2025.01.14.633073,
https://doi.org/10.3389/fphys.2022.1014271,
https://doi.org/10.3390/cells10051036,
https://doi.org/10.3389/fphys.2022.880004,

📚 Additional Documentation

Notes

(SEC62-notes.md)

SEC62 (Q99442) review notes

Identity / overview

SEC62 (TLOC1, translocation protein 1) is a multi-pass ER membrane protein and an auxiliary component of
the Sec61 translocon. With SEC63 it forms the SEC62-SEC63 complex that supports translocation of precursor
polypeptides into the ER, particularly the post-translational import of small presecretory proteins with
short, weakly hydrophobic signal peptides. SEC62 also serves as a receptor/regulator that positions
precursors into the Sec61 channel and helps trigger channel opening. Independently, SEC62 acts in
recovery-phase ER-phagy (reticulophagy) via an LC3/GABARAP-interacting region.

UniProt FUNCTION: "Mediates post-translational transport of precursor polypeptides across endoplasmic
reticulum (ER). Proposed to act as a targeting receptor for small presecretory proteins containing short
and apolar signal peptides. 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" [file:human/SEC62/SEC62-uniprot.txt].
SUBUNIT: "The ER translocon complex that consists of channel-forming core components SEC61A1, SEC61B and
SEC61G and different auxiliary components such as SEC62 and SEC63. Interacts with SEC61B"
[file:human/SEC62/SEC62-uniprot.txt].
SUBCELLULAR LOCATION: "Endoplasmic reticulum membrane ... Multi-pass membrane protein"
[file:human/SEC62/SEC62-uniprot.txt]. Topology: cytoplasmic 1-196, TM 197-217, lumenal 218-234, TM
235-255, cytoplasmic 256-399 (two TM helices).
INTERACTION: SEC62-GABARAP (O95166) [file:human/SEC62/SEC62-uniprot.txt] — consistent with ER-phagy role.

Key functional evidence

Translocation function: PMID:22375059 (Lang et al.) "Different effects of Sec61α, Sec62 and Sec63
depletion on transport of polypeptides into the endoplasmic reticulum" — FUNCTION evidence.
Small-precursor import / Sec61 channel gating: PMID:29719251 "Sec62 have all been characterized as
membrane-targeting components for small presecretory proteins, whereas Sec63 and the lumenal chaperone
BiP act as auxiliary translocation components" PMID:29719251.
ER-phagy (reticulophagy): PMID:31006538 (TEX264 ER-phagy paper; cached abstract is about TEX264, but
the SEC62 IMP reticulophagy annotation by MGI reflects SEC62's documented recovery-ER-phagy role and its
GABARAP interaction). Abstract-only cache; defer to curator.
Original cloning: PMID:9020021 "HTP1 (for human translocation protein 1) ... 36.3% identical ... to
Drosophila homologue of Sec62p" PMID:9020021.

Annotation review decisions

Core MF: protein transmembrane transporter activity (GO:0008320) as part of translocon-associated
positioning of precursors; the legacy signaling receptor activity (GO:0038023, TAS, old ProtInc) is a
mis-framing — SEC62 is a translocon-associated targeting receptor, not a signal-transduction receptor.
MARK_AS_OVER_ANNOTATED.
Core BP: post-translational protein targeting to membrane, translocation (GO:0031204) /
post-translational protein targeting to ER membrane (GO:0006620); cotranslational targeting (GO:0006613,
TAS) is partially correct but SEC62's hallmark is post-translational small-precursor import — ACCEPT but
non-primary.
Core CC: ER membrane (GO:0005789); rough ER (GO:0005791, ISS) and ER (GO:0005783) accepted; generic
"membrane" (GO:0016020) KEEP_AS_NON_CORE.
GO:0061709 reticulophagy (IMP): genuine secondary role; KEEP_AS_NON_CORE (not the core translocon
function).
protein binding (GO:0005515) IPI rows: high-throughput captures (PMID:33961781, PMID:37219487).
KEEP_AS_NON_CORE.

Disease / other

SEC62 is amplified/overexpressed in prostate and lung (and other) cancers (located at 3q26 amplicon);
this is a disease/expression association, not a clean GO biological process.

Falcon deep-research findings (incorporated 2026-06)

Substrate-specificity "rules": SEC62/SEC63 clients share signal peptides with longer but
less hydrophobic H-regions and lower C-region polarity; a slowly gating signal peptide plus
a downstream positively charged cluster is decisive for SEC62/SEC63 (and BiP) dependence
PMID:32133789.
22 novel SEC62/SEC63 substrates identified in intact human cells by unbiased proteomics, in
addition to ERj3 PMID:32133789.
Two proposed gating models: the SEC62/SEC63 complex may support Sec61 opening either by direct
interaction with the cytosolic N-terminus of Sec61alpha or via recruitment of BiP to ER-lumenal
loop 7 of Sec61alpha PMID:32133789.
SEC62 knockdown proteomics altered steady-state levels of ~329 proteins (208 down, 121 up;
q<0.05), enriched for cleavable signal-peptide and N-glycosylated proteins (Falcon; cf. PMID:32133789).
Calcium / calmodulin role reaffirmed (already in review via PMID:24304694): SEC62 regulates the
Sec61 Ca2+ leak via a Ca2+-sensitive interaction; SEC62 depletion >=2-fold increases basal cytosolic
Ca2+; CaM antagonists (trifluoperazine) phenocopy SEC62 silencing [PMID:24304694, Linxweiler 2013 BMC Cancer, doi:10.1186/1471-2407-13-574].
recovER-phagy reaffirmed (already in review via GO:0061709): SEC62 acts as an ER-phagy receptor
during recovery from ER stress, distinct from starvation-induced ER-phagy (Falcon review framing).
Pan-cancer context (3q26 amplicon): SEC62 alterations (mostly amplifications) reported in 2,595 of

72,000 cancer patients; SEC62-altered median survival 54.2 vs 95.6 months unaltered
[Sicking et al. 2021 Cells, doi:10.3390/cells10051036 — not added as ref (disease/expression context)].
Zimmermann 2025 review frames SEC62 as a substrate-selective Sec61 translocon effector
[PMID:41009394, doi:10.3390/ijms26188823] — added as reference.
No new mechanistic structural finding for SEC62 itself beyond the substrate-specificity work;
Falcon's 2023-2024 "novelty" for SEC62 is mainly conceptual integration into ER-phagy/Ca2+ frameworks.

Pn Notes

(SEC62-pn-notes.md)

SEC62 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q99442
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-11
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/SEC62/SEC62-ai-review.yaml
AIGR review HTML: missing - genes/human/SEC62/SEC62-ai-review.html
Gene notes: present - genes/human/SEC62/SEC62-notes.md
GOA TSV: present - genes/human/SEC62/SEC62-goa.tsv
UniProt record: present - genes/human/SEC62/SEC62-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/SEC62.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/SEC62.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/SEC62/SEC62-deep-research-falcon.md

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 10; KEEP_AS_NON_CORE: 6; MARK_AS_OVER_ANNOTATED: 1

PN Consistency Summary

Consistency: Strong agreement. Deep research, notes, and review YAML all describe SEC62 as a Sec61-translocon-associated targeting receptor for small presecretory proteins (post-translational import) plus a recovery-phase ER-phagy receptor (GABARAP/LC3). PN's three rows (translocon component, ERphagy receptor, microreticulophagy) map cleanly onto the review's translocation core + non-core reticulophagy. No contradictions.
PN story / NEW pressure: PN's two roles are already in GOA/review. Translocon: review has GO:0031204, GO:0006620, GO:0008320, GO:0015031. ERphagy: review keeps GO:0061709 (KEEP_AS_NON_CORE). The one PN-projected term absent from GOA is GO:0005784 Sec61 translocon complex (verified real; definition explicitly admits translocon-associated/TRAP proteins, so SEC62 qualifies). Defensible ADD as a CC. Conclude: ADD GO:0005784 (translocon-associated, not channel-core); ERphagy/transport already captured.
Evidence alignment: Excellent overlap. PN row 2 titles ("Translocon component Sec62 acts in ER turnover during stress recovery"; "Selective Autophagy: ATG8...LIR...Cargo Receptors") match the review's reticulophagy framing (review cites PMID:31006538). Translocon evidence (PMID:22375059, 29719251, 32133789) is review-only but congruent. No divergence.
Verdict: CONSISTENT. One actionable gap: add Sec61 translocon complex CC.

Full Consistency Review

UniProt: Q99442 · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE
PN placement: ER proteostasis|Protein transport|SEC61 channel complex component; also ALP|Autophagy substrate selection|Selective autophagy receptor|ERphagy and ALP|Microautophagy|Microreticulophagy; PN-node mapping: group mapped, ok_for_propagation_to_go, GO:0005784 (Sec61 translocon complex); class GO:0015031 (protein transport); ERphagy type mapped GO:0061709 (reticulophagy); microreticulophagy = context_only/too_broad.
Consistency: Strong agreement. Deep research, notes, and review YAML all describe SEC62 as a Sec61-translocon-associated targeting receptor for small presecretory proteins (post-translational import) plus a recovery-phase ER-phagy receptor (GABARAP/LC3). PN's three rows (translocon component, ERphagy receptor, microreticulophagy) map cleanly onto the review's translocation core + non-core reticulophagy. No contradictions.
PN story / NEW pressure: PN's two roles are already in GOA/review. Translocon: review has GO:0031204, GO:0006620, GO:0008320, GO:0015031. ERphagy: review keeps GO:0061709 (KEEP_AS_NON_CORE). The one PN-projected term absent from GOA is GO:0005784 Sec61 translocon complex (verified real; definition explicitly admits translocon-associated/TRAP proteins, so SEC62 qualifies). Defensible ADD as a CC. Conclude: ADD GO:0005784 (translocon-associated, not channel-core); ERphagy/transport already captured.
Mapping strategy: Mapping is sound. GO:0005784 is appropriately specific (the dossier's more_specific_than_existing_goa is correct — GOA has only ER membrane/rough ER/ER). GO:0015031 protein transport is a defensibly broad class-level target (not over-reaching like the TOMM20/HSPA8 precedent, since it's flagged generic). Microreticulophagy correctly held context_only. No mapping change needed.
Evidence alignment: Excellent overlap. PN row 2 titles ("Translocon component Sec62 acts in ER turnover during stress recovery"; "Selective Autophagy: ATG8...LIR...Cargo Receptors") match the review's reticulophagy framing (review cites PMID:31006538). Translocon evidence (PMID:22375059, 29719251, 32133789) is review-only but congruent. No divergence.
Verdict: CONSISTENT. One actionable gap: add Sec61 translocon complex CC.
Recommended edits: [YAML] Add GO:0005784 Sec61 translocon complex (part_of/located_in, translocon-associated) to SEC62 existing_annotations/core_functions, matching the PN-projected term and the verified GO definition (TRAP-inclusive).

PN Dossier Context

review_batch: proteostasis-batch-2026-06-11
review_yaml: genes/human/SEC62/SEC62-ai-review.yaml
PN workbook rows: 3

PN row 1: ER proteostasis | Protein transport | SEC61 channel complex component

UniProt: Q99442
In branches: ER, ALP
PN-node mapping records (path + ancestors):
- [group] ER proteostasis|Protein transport|SEC61 channel complex component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0005784 Sec61 translocon complex]
  rationale: This PN group denotes SEC61 translocon components. The GO Sec61 translocon complex term is the direct cellular-component target.
- [class] ER proteostasis|Protein transport
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0015031 protein transport]
  rationale: The PN ER Protein transport class groups ER-targeting and ER-insertion pathways. GO protein transport is the appropriate propagation target, while the source class remains ER-specific and broader than any single GO transport subtype.
- [branch] ER proteostasis
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | ERphagy

UniProt: Q99442
In branches: ER, ALP
Notes: Receptor for selective autophagy. An ER-resident autophagy receptor. Contains a conserved LC3-interacting region in the C-terminal cytosolic domain that is required for its function in recovER-phagy, but is dispensable for its function in the protein translocation machinery. Active in ERphagy
PN references (titles):
- Selective Autophagy: ATG8 Family Proteins, LIR Motifs and Cargo Receptors - ScienceDirect
- Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery
PN-node mapping records (path + ancestors):
- [type] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|ERphagy
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0061709 reticulophagy]
  rationale: The PN uses the community label ERphagy for selective autophagy of the endoplasmic reticulum, while GO uses the synonym reticulophagy. Receptor members of this PN category are suitable for propagation to the GO reticulophagy process.
- [group] Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad PN taxonomy container. The descendants mix components, regulators, context labels, and mechanistic leaves, so propagation should come only from narrower curated nodes.
- [class] Autophagy-Lysosome Pathway|Autophagy substrate selection
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a broad substrate-selection container. GO has useful targets for specific receptor, cargo-adaptor, and selective-autophagy leaves, but this class mixes marking, recognition, receptor regulation, and unknown roles and should not propagate as one term.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

PN row 3: Autophagy-Lysosome Pathway | Microautophagy | Microreticulophagy

UniProt: Q99442
In branches: ER, ALP
PN-node mapping records (path + ancestors):
- [group] Autophagy-Lysosome Pathway|Microautophagy|Microreticulophagy
  status=context_only scope=too_broad_to_propagate GO=[GO:0061709 reticulophagy]
  rationale: This group is an ER-autophagy context, but the source label is microreticulophagy and the members mix core autophagy factors with SEC62. Reticulophagy is kept as context only pending a more specific GO term or gene-level review.
- [class] Autophagy-Lysosome Pathway|Microautophagy
  status=context_only scope=too_broad_to_propagate GO=[GO:0016237 microautophagy]
  rationale: The class names a real GO process, but the subtree includes machinery components and mitochondrion-derived-vesicle contexts as well as process labels. Propagation is restricted to narrower nodes.
- [branch] Autophagy-Lysosome Pathway
  status=no_mapping scope= GO=[]
  rationale: Reviewed as the top-level PN branch. It is a project taxonomy umbrella rather than a direct GO assertion; all propagation must come from manually curated child nodes.

Projected GO annotations (3)

GO:0015031 protein transport | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Protein transport
GO:0005784 Sec61 translocon complex | scope=ok_for_propagation_to_go | goa_status=more_specific_than_existing_goa | from=ER proteostasis|Protein transport|SEC61 channel complex component
GO:0061709 reticulophagy | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=Autophagy-Lysosome Pathway|Autophagy substrate selection|Selective autophagy receptor|ERphagy

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: Q99442
gene_symbol: SEC62
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: 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.
existing_annotations:
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    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.
    action: ACCEPT
    reason: Core cellular component; SEC62 functions at the ER membrane in association with the Sec61 translocon.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0008320
    label: transmembrane protein transporter activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Core molecular function in the context of the translocon; SEC62 helps move precursor polypeptides across the ER membrane.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 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.
- term:
    id: GO:0031204
    label: post-translational protein targeting to membrane, translocation
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: SEC62 mediates post-translational transport of precursor polypeptides across the ER membrane; this is its defining biological process, conserved across the family.
    action: ACCEPT
    reason: Core biological process; SEC62 is a translocation/post-translational targeting factor of the ER translocon.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER).
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: located_in
  review:
    summary: Electronic assignment of ER membrane localization from the UniProt subcellular location, consistent with the multi-pass ER membrane topology.
    action: ACCEPT
    reason: Correct core localization; redundant with IBA/IDA ER membrane evidence.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0015031
    label: protein transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: SEC62 mediates protein transport into the ER; protein transport is a correct but generic parent of the specific post-translational translocation process.
    action: ACCEPT
    reason: Correct general biological process; the specific GO:0031204 better captures SEC62's translocation role.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: Mediates post-translational transport of precursor polypeptides across endoplasmic reticulum (ER).
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex proteome-scale interactome capture; bare protein binding is uninformative for core function.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome interaction; uninformative bare term not elevated to core per guidelines.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 'Q99442; O95166: GABARAP'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:37219487
  qualifier: enables
  review:
    summary: Phosphomimetic motif-based interaction screen; bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction screen; uninformative bare term not elevated to core.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 'Q99442; O95166: GABARAP'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IDA
  original_reference_id: PMID:22375059
  qualifier: is_active_in
  review:
    summary: Direct functional study (Sec61/Sec62/Sec63 depletion) places SEC62 active at the ER membrane in ER protein transport.
    action: ACCEPT
    reason: Core site of action with direct experimental support.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0061709
    label: reticulophagy
  evidence_type: IMP
  original_reference_id: PMID:31006538
  qualifier: acts_upstream_of_or_within
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Real ER-phagy role supported by GABARAP interaction, but distinct from and secondary to the core translocon/translocation function.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 'Q99442; O95166: GABARAP'
- term:
    id: GO:0031204
    label: post-translational protein targeting to membrane, translocation
  evidence_type: IMP
  original_reference_id: PMID:29719251
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Core biological process with direct experimental (IMP) support; SEC62 targets/translocates small presecretory precursors.
    supported_by:
    - reference_id: PMID:29719251
      supporting_text: Sec62 have all been characterized as membrane-targeting components for small presecretory proteins
- term:
    id: GO:0006620
    label: post-translational protein targeting to endoplasmic reticulum membrane
  evidence_type: IMP
  original_reference_id: PMID:22375059
  qualifier: acts_upstream_of_or_within
  review:
    summary: SEC62 mediates post-translational targeting of precursors to the ER membrane; supported by depletion studies of ER transport components.
    action: ACCEPT
    reason: Core biological process; specific post-translational ER targeting role with experimental (IMP) support.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides.
    - reference_id: PMID:32133789
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:22375059
  qualifier: located_in
  review:
    summary: SEC62 is a membrane protein; "membrane" is a correct but generic parent of the specific ER membrane localization.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; ER membrane (GO:0005789) is the more specific and informative localization.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: Multi-pass membrane protein
- term:
    id: GO:0005791
    label: rough endoplasmic reticulum
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: SEC62 localizes to the rough ER, consistent with its role at the translocon where translating/translocating ribosomes engage the membrane.
    action: ACCEPT
    reason: Correct and more specific ER subcompartment localization, consistent with translocon association.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0038023
    label: signaling receptor activity
  evidence_type: TAS
  original_reference_id: PMID:9020021
  qualifier: enables
  review:
    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.
    action: MARK_AS_OVER_ANNOTATED
    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.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: Proposed to act as a targeting receptor for small presecretory proteins containing short and apolar signal peptides.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: TAS
  original_reference_id: PMID:9020021
  qualifier: located_in
  review:
    summary: SEC62 is an ER protein; ER localization is correct (the ER membrane is the more specific compartment).
    action: ACCEPT
    reason: Correct compartment; redundant with the more specific ER membrane annotations.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0006613
    label: cotranslational protein targeting to membrane
  evidence_type: TAS
  original_reference_id: PMID:9020021
  qualifier: involved_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: Targets and properly positions newly synthesized presecretory proteins into the SEC61 channel-forming translocon complex
- term:
    id: GO:0016020
    label: membrane
  evidence_type: TAS
  original_reference_id: PMID:9020021
  qualifier: located_in
  review:
    summary: SEC62 is a membrane protein; "membrane" is a generic parent of the specific ER membrane localization.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the specific ER membrane (GO:0005789) is the informative localization.
    supported_by:
    - reference_id: file:human/SEC62/SEC62-uniprot.txt
      supporting_text: Multi-pass membrane protein
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:22375059
  title: Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides
    into the endoplasmic reticulum of mammalian cells.
  findings:
  - statement: Depletion of Sec61alpha, Sec62 and Sec63 has different effects on cotranslational and post-translational transport of polypeptides into the ER; establishes SEC62 as an ER-membrane translocation component.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Direct functional study of SEC62 in ER protein transport; source of ER-membrane localization and post-translational ER targeting annotations.
- id: PMID:29719251
  title: Chaperone-Mediated Sec61 Channel Gating during ER Import of Small Precursor
    Proteins Overcomes Sec61 Inhibitor-Reinforced Energy Barrier.
  findings:
  - statement: Sec62 is a membrane-targeting component for small presecretory proteins, while Sec63 and the lumenal chaperone BiP act as auxiliary translocation components during chaperone-mediated Sec61 channel gating.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes SEC62's role in targeting/translocating small presecretory proteins and gating the Sec61 channel.
- id: PMID:31006538
  title: Intrinsically Disordered Protein TEX264 Mediates ER-phagy.
  findings:
  - statement: ER-phagy receptor study (TEX264); the SEC62 reticulophagy annotation reflects SEC62's documented recovery-ER-phagy role and its GABARAP/LC3 interaction.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Cached abstract focuses on TEX264; the curated SEC62 reticulophagy IMP annotation reflects SEC62's ER-phagy receptor function (consistent with its GABARAP interaction).
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human
    interactome.
  findings: []
- id: PMID:37219487
  title: Large-scale phosphomimetic screening identifies phospho-modulated motif-based
    protein interactions.
  findings: []
- id: PMID:24304694
  title: 'Targeting cell migration and the endoplasmic reticulum stress response with
    calmodulin antagonists: a clinically tested small molecule phenocopy of SEC62 gene
    silencing in human tumor cells.'
  findings:
  - statement: SEC62 regulates the major ER Ca2+ leak channel Sec61 via a direct, Ca2+-sensitive
      interaction (Biacore); a Ca2+-binding motif in SEC62 is essential for this function.
      SEC62 silencing elevates cytosolic Ca2+ and increases thapsigargin-evoked ER Ca2+
      leakage, and calmodulin antagonists (trifluoperazine, ophiobolin A) phenocopy SEC62
      depletion (impaired migration, ER-stress sensitization). SEC62 is overexpressed in
      prostate, lung and thyroid cancers and correlates with reduced survival.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:24304694, BMC Cancer 2013, doi:10.1186/1471-2407-13-574).
      Establishes a non-translocation role for SEC62 in regulating Sec61-mediated ER Ca2+
      leak through a direct Ca2+-sensitive SEC62-Sec61 interaction coupled to calmodulin;
      not previously represented in this review. Abstract-only (not in publications/ cache),
      so no verbatim supporting_text added to annotations.
- id: PMID:32133789
  title: Identification of signal peptide features for substrate specificity in human
    Sec62/Sec63-dependent ER protein import.
  findings:
  - statement: Using an unbiased proteomics approach in intact human cells, 22 novel
      Sec62/Sec63 substrates were identified in addition to ERj3; these substrates share
      signal peptides with comparatively longer but less hydrophobic H-regions and lower
      C-region polarity, and the combination of a slowly gating signal peptide plus a
      downstream translocation-disruptive positively charged cluster is decisive for the
      Sec62/Sec63 (and BiP) requirement. The human Sec62/Sec63 complex may support Sec61
      opening either by direct interaction with the cytosolic N-terminus of Sec61alpha or
      via recruitment of BiP to ER-lumenal loop 7 of Sec61alpha.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:32133789, FEBS J 2020, doi:10.1111/febs.15274;
      published version of the Schorr et al. 2019 bioRxiv preprint doi:10.1101/867762).
      Defines the signal-peptide "rules of engagement" for SEC62/SEC63-dependent ER import
      and the direct-Sec61-interaction vs BiP-recruitment gating models. Not in publications/
      cache, so reference id added without verbatim supporting_text.
- id: PMID:41009394
  title: Rules of Engagement for Components of Membrane Protein Biogenesis at the Human
    Endoplasmic Reticulum.
  findings:
  - statement: Review/article hybrid using siRNA depletion of individual ER targeting and
      insertion components (including SEC62/SEC63) combined with label-free quantitative
      proteomics to define client types and rules of engagement for components of the
      human ER protein biogenesis machinery, placing SEC62 as a substrate-selective Sec61
      translocon effector.
    reference_section_type: OTHER
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:41009394, Int J Mol Sci 2025, doi:10.3390/ijms26188823).
      Recent authoritative synthesis framing SEC62 as a substrate-selective Sec61 translocon
      effector. Not in publications/ cache; reference id added without verbatim supporting_text.
- id: PMID:9020021
  title: Identification of a human cDNA homologue to the Drosophila translocation
    protein 1 (Dtrp1).
  findings:
  - statement: Cloning of human HTP1/SEC62 (translocation protein 1), homologue of yeast/Drosophila Sec62p, an ER protein-translocation component expressed in many tissues.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Original identification of human SEC62; source of legacy ProtInc ER/membrane/cotranslational-targeting and (mis-framed) signaling-receptor annotations.
- id: file:human/SEC62/SEC62-uniprot.txt
  title: UniProt entry Q99442 (SEC62_HUMAN), Translocation protein SEC62
  findings:
  - statement: SEC62 mediates post-translational transport of precursor polypeptides across the ER, acts as a targeting receptor for small presecretory proteins, positions them into the Sec61 channel and triggers channel opening; multi-pass ER membrane protein; auxiliary component of the Sec61 translocon with SEC63; interacts with GABARAP (ER-phagy).
    reference_section_type: OTHER
core_functions:
- description: Translocon-associated ER membrane protein that mediates post-translational translocation of precursor polypeptides into the ER, acting as a targeting receptor for small presecretory proteins and positioning them into the Sec61 channel.
  molecular_function:
    id: GO:0008320
    label: transmembrane protein transporter activity
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/SEC62/SEC62-uniprot.txt
    supporting_text: 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.
  - reference_id: PMID:29719251
    supporting_text: Sec62 have all been characterized as membrane-targeting components for small presecretory proteins
  directly_involved_in:
  - id: GO:0031204
    label: post-translational protein targeting to membrane, translocation
proposed_new_terms: []
suggested_questions:
- question: 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?
- question: What determines SEC62's selectivity for small presecretory proteins with short, apolar signal peptides over SRP-dependent substrates?
suggested_experiments:
- description: 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.
- description: 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.

SEC62

Gene Description

Existing Annotations Review

Core Functions

Translocon-associated ER membrane protein that mediates post-translational translocation of precursor polypeptides into the ER, acting as a targeting receptor for small presecretory proteins and positioning them into the Sec61 channel.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research report: Human SEC62 (UniProt Q99442) — functional annotation and biomedical relevance

0) Target verification (critical disambiguation)

1) Key concepts and current understanding (definitions and core biology)

1.1 SEC62 as a Sec61-associated translocon component

1.2 Substrate specificity: “rules” for SEC62/SEC63-dependent import

1.3 SEC62 in ER Ca2+ homeostasis: regulating Sec61 Ca2+ leak with calmodulin

1.4 SEC62 and recovER-phagy (ER stress recovery-associated ER-phagy)

2) Recent developments and latest research (prioritizing 2023–2024)

3) Cellular localization, complexes, and pathways

3.1 Localization

3.2 Core physical/functional interactions

3.3 Pathways (functional placement)

4) Current applications and real-world implementations

4.1 SEC62 as a biomarker/oncogene candidate in 3q26-amplified cancers

4.2 Pharmacological phenocopy of SEC62 inhibition via calmodulin antagonists

4.3 Targeting ER Ca2+ homeostasis with SERCA-directed agents

5) Expert opinions and authoritative synthesis (how experts frame SEC62)

6) Relevant statistics and data (recent studies and key quantitative findings)

6.1 Proteomics-defined substrate scope (SEC62 depletion in human cells)

6.2 Quantitative Ca2+ / functional phenotypes

6.3 Pan-cancer alteration prevalence and survival (large cohort summary)

6.4 NSCLC cohort size in SEC62 survival analysis

Summary table (evidence-backed functional annotation)

Concluding functional annotation (concise)

Artifacts

Citations

📚 Additional Documentation

Notes

SEC62 (Q99442) review notes

Identity / overview

Key functional evidence

Annotation review decisions

Disease / other

Falcon deep-research findings (incorporated 2026-06)

Pn Notes

SEC62 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: ER proteostasis | Protein transport | SEC61 channel complex component

PN row 2: Autophagy-Lysosome Pathway | Autophagy substrate selection | Selective autophagy receptor | ERphagy

PN row 3: Autophagy-Lysosome Pathway | Microautophagy | Microreticulophagy

Projected GO annotations (3)

Note

📄 View Raw YAML