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.