id: O00258
gene_symbol: GET1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: GET1 (WRB; also known as congenital heart disease 5 protein/CHD5 and tryptophan-rich basic protein) is a multi-pass endoplasmic reticulum (ER) membrane protein that is the membrane receptor for the cytosolic ATPase GET3/TRC40 in the GET (guided entry of tail-anchored proteins) pathway. This pathway delivers tail-anchored (TA) membrane proteins, which carry a single C-terminal transmembrane domain, to the ER for post-translational insertion. GET1/WRB has three transmembrane helices and a cytosolic coiled-coil domain (residues ~39-97) that docks the TA-loaded GET3/TRC40 homodimer at the membrane. Together with CAMLG/GET2, GET1 forms a heterotetrameric insertase that, with bound GET3, accepts the TA substrate and catalyzes its insertion into the ER lipid bilayer through a hydrophilic groove, mechanistically related to the YidC/Oxa1 insertase superfamily and the ER membrane protein complex (EMC). GET1 and CAMLG are mutually dependent for stable expression and correct topology, and GET1 is required for the proper integration of its partner CAMLG into the ER membrane. The protein is broadly expressed and resides in the ER membrane.
alternative_products:
- name: '1'
  id: O00258-1
- name: '2'
  id: O00258-2
  sequence_note: VSP_043081
existing_annotations:
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: Phylogenetic (IBA) annotation of GET1's defining biological process, the insertion of tail-anchored membrane proteins into the ER membrane. Conserved across the WRB/GET1 family and supported by direct experimental evidence.
    action: ACCEPT
    reason: Core biological process; GET1/WRB is the ER receptor of the GET pathway that inserts TA proteins, supported by IDA/IMP and the UniProt function.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: Required for the post-translational delivery of tail-anchored
    - reference_id: PMID:36640319
      supporting_text: the Get1/2 channel functions as an insertase for insertion of TMDs and as a translocase for translocation of C-terminal hydrophilic segments
    - reference_id: PMID:37963916
      supporting_text: the Get3 chaperone captures the TA protein substrate and delivers it to the Get1/Get2 membrane protein complex (GET insertase), which then inserts the substrate via a membrane-embedded hydrophilic groove
- term:
    id: GO:0043495
    label: protein-membrane adaptor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: This is the PAN-GO/GO_Central molecular function used for the GET3 receptor across orthologs, capturing GET1/WRB's role of coupling the soluble GET3/TRC40 chaperone to the ER membrane so that the TA substrate can be inserted. GET1 provides the membrane docking site (its coiled-coil) for the cytosolic targeting factor.
    action: ACCEPT
    reason: Represents the informative membrane-insertase-receptor molecular function of GET1; the coiled-coil domain docks GET3/TRC40 at the membrane.
    supported_by:
    - reference_id: PMID:21444755
      supporting_text: We identify the coiled-coil domain of WRB as the binding site for TRC40/Asna1
- term:
    id: GO:0043529
    label: GET complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: GET1/WRB is a constitutive subunit of the GET complex (GET1/WRB + CAMLG/GET2 + GET3/TRC40). Conserved across the family and directly demonstrated structurally.
    action: ACCEPT
    reason: Core cellular component; GET1 is a defining subunit of the GET insertase complex.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: Component of the Golgi to ER traffic (GET) complex, which is
        composed of GET1/WRB, CAMLG/GET2 and GET3/TRC40
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of the ER membrane localization from the UniProt subcellular location, consistent with the experimental EXP evidence.
    action: ACCEPT
    reason: Correct compartment; GET1 is an experimentally established multi-pass ER membrane protein.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro-based electronic assignment of the TA-protein ER insertion process, consistent with the experimental evidence.
    action: ACCEPT
    reason: Correct core process; redundant with IDA/IMP/IBA evidence.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: Required for the post-translational delivery of tail-anchored
- term:
    id: GO:0090150
    label: establishment of protein localization to membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: ARBA machine-learning electronic annotation of the generic parent process; GET1 establishes localization of TA proteins to the ER membrane. Correct but less specific than GO:0071816.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic parent of the specific TA-insertion process that better captures GET1's role.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: Required for the post-translational delivery of tail-anchored
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: High-throughput human binary interactome (HuRI/Y2H) capturing many IntAct partners of GET1 (e.g. APOA2, TFRC, CD53, AQP1, HMOX2, SLC7A1); several are themselves TA/membrane proteins and plausible insertase substrates, but the bare protein binding term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records real Y2H interactions but bare protein binding is uninformative; the informative MF is captured by GO:0043495.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: 'O00258; P02652: APOA2'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: NAS
  original_reference_id: PMID:32910895
  qualifier: located_in
  review:
    summary: ComplexPortal NAS assertion of ER membrane localization from the cryo-EM structural study of the human GET insertase complex.
    action: ACCEPT
    reason: Correct compartment; consistent with experimental EXP localization.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0043529
    label: GET complex
  evidence_type: IPI
  original_reference_id: PMID:32910895
  qualifier: part_of
  review:
    summary: ComplexPortal IPI assignment of GET complex membership from the cryo-EM structure of the human WRB/CAML/TRC40 insertase complex.
    action: ACCEPT
    reason: Core cellular component; directly demonstrated structurally.
    supported_by:
    - reference_id: PMID:32910895
      supporting_text: Get3 binding to the membrane insertase supports heterotetramer formation
- term:
    id: GO:0045048
    label: protein insertion into ER membrane
  evidence_type: NAS
  original_reference_id: PMID:23041287
  qualifier: involved_in
  review:
    summary: ComplexPortal NAS assertion of the (parent) ER protein-insertion process; GET1/WRB with CAML synergistically inserts TA proteins into the ER membrane.
    action: ACCEPT
    reason: Correct; parent of GO:0071816 and consistent with experimental evidence.
    supported_by:
    - reference_id: PMID:23041287
      supporting_text: CAML and WRB synergistically insert TA proteins into the membrane
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: EXP
  original_reference_id: PMID:21444755
  qualifier: located_in
  review:
    summary: Direct experimental evidence that WRB is an ER-resident membrane protein, established in the study that identified WRB as the TRC40 receptor.
    action: ACCEPT
    reason: Core, experimentally demonstrated localization.
    supported_by:
    - reference_id: PMID:21444755
      supporting_text: WRB is an ER-resident membrane protein
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31417168
  qualifier: enables
  review:
    summary: IPI annotation capturing the WRB-CAMLG (P49069) interaction. This reflects the genuine, functionally central GET1-CAMLG association, but the GO term used is the uninformative bare protein binding.
    action: KEEP_AS_NON_CORE
    reason: Records the real and important CAMLG interaction, but bare protein binding is uninformative; the functional MF is captured by GO:0043495 and complex membership by GO:0043529.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: Interacts with CAMLG (via C-terminus)
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32187542
  qualifier: enables
  review:
    summary: IPI annotation capturing the WRB-CAMLG (P49069) interaction from the study on orphan subunit recognition by the WRB/CAML complex. Functionally meaningful interaction but the bare protein binding term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real CAMLG interaction; bare protein binding is uninformative per curation guidelines.
    supported_by:
    - reference_id: file:human/GET1/GET1-uniprot.txt
      supporting_text: Interacts with CAMLG (via C-terminus)
- term:
    id: GO:0045048
    label: protein insertion into ER membrane
  evidence_type: IMP
  original_reference_id: PMID:31417168
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence that WRB is required for correct integration of CAML into the ER; WRB acts catalytically to assist CAML topogenesis/insertion.
    action: ACCEPT
    reason: Correct; supported by IMP. WRB-dependent ER insertion (here of CAML) reflects its insertase-receptor role.
    supported_by:
    - reference_id: PMID:31417168
      supporting_text: WRB ... acts catalytically to assist the topogenesis of CAML
- term:
    id: GO:0045048
    label: protein insertion into ER membrane
  evidence_type: IDA
  original_reference_id: PMID:32187542
  qualifier: involved_in
  review:
    summary: Direct evidence that WRB can correct the topology of (and thereby insert) CAML both in vitro and in cells, supporting GET1's ER protein-insertion role.
    action: ACCEPT
    reason: Core process; directly demonstrated. Parent of the more specific TA-insertion term.
    supported_by:
    - reference_id: PMID:32187542
      supporting_text: When present, WRB can correct the topology of CAML both in vitro and in cells
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IDA
  original_reference_id: PMID:31417168
  qualifier: involved_in
  review:
    summary: Without sufficient WRB, CAML fails to adopt its correct topology, generating aberrant topoforms that cluster and are degraded by the proteasome; WRB therefore stabilizes/correctly integrates CAML. This is a real but secondary consequence of GET1's insertase-receptor function.
    action: KEEP_AS_NON_CORE
    reason: Supported by IDA but represents WRB-dependent stabilization of one specific partner (CAML), secondary to the core TA-insertion function.
    supported_by:
    - reference_id: PMID:31417168
      supporting_text: these congregate in ER-associated clusters and are degraded by the proteasome
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IDA
  original_reference_id: PMID:32187542
  qualifier: involved_in
  review:
    summary: WRB-mediated correction of CAML topology stabilizes CAML; consistent with the partner-stabilization phenotype. Secondary to the core insertase-receptor function.
    action: KEEP_AS_NON_CORE
    reason: Real but secondary partner-stabilization effect, not the core function of GET1.
    supported_by:
    - reference_id: PMID:32187542
      supporting_text: When present, WRB can correct the topology of CAML both in vitro and in cells
- term:
    id: GO:0043529
    label: GET complex
  evidence_type: IDA
  original_reference_id: PMID:32910895
  qualifier: part_of
  review:
    summary: The cryo-EM structure directly resolves GET1/WRB within the GET insertase complex, forming a heterotetramer with CAML that binds the GET3 homodimer.
    action: ACCEPT
    reason: Core cellular component, structurally demonstrated.
    supported_by:
    - reference_id: PMID:32910895
      supporting_text: Get3 binding to the membrane insertase supports heterotetramer formation
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IDA
  original_reference_id: PMID:27226539
  qualifier: involved_in
  review:
    summary: Direct evidence that in-vitro-synthesized CAML and WRB together are sufficient to confer TA-insertion competence to liposomes, establishing GET1's core role in TA-protein ER insertion.
    action: ACCEPT
    reason: Core biological process with direct experimental (IDA) support.
    supported_by:
    - reference_id: PMID:27226539
      supporting_text: in vitro synthesized CAML and WRB together were sufficient to confer insertion competence to liposomes
- term:
    id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
  evidence_type: IMP
  original_reference_id: PMID:23041287
  qualifier: involved_in
  review:
    summary: Mutant-phenotype evidence that CAML and WRB synergistically insert TA proteins into the ER membrane, establishing GET1 as a component of the TRC40 receptor complex driving TA insertion.
    action: ACCEPT
    reason: Core biological process with IMP support.
    supported_by:
    - reference_id: PMID:23041287
      supporting_text: CAML and WRB synergistically insert TA proteins into the membrane
- term:
    id: GO:0043529
    label: GET complex
  evidence_type: IPI
  original_reference_id: PMID:23041287
  qualifier: part_of
  review:
    summary: Mass-spectrometry/IPI identification of GET1/WRB in the TRC40 receptor (GET) complex together with CAMLG and GET3.
    action: ACCEPT
    reason: Core cellular component; directly demonstrated by complex identification.
    supported_by:
    - reference_id: PMID:23041287
      supporting_text: CAML and WRB as components of the TRC40 receptor complex
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:9544840
  qualifier: located_in
  review:
    summary: The original 1998 cDNA characterization reported predominant nuclear immunofluorescence localization, before the protein's function was known. This was not reproduced and is contradicted by the later function-defining study, which establishes ER membrane residence and could not detect nuclear WRB. GET1/WRB is a multi-pass ER membrane protein with no established nuclear function.
    action: MARK_AS_OVER_ANNOTATED
    reason: Superseded by experimental ER membrane localization; the early nuclear immunofluorescence result was not reproduced and is inconsistent with GET1's multi-pass ER membrane topology.
    supported_by:
    - reference_id: PMID:21444755
      supporting_text: We have not been able to detect WRB in untransfected RPE-1 or HeLa cells using our anti-WRB antibodies
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: TAS
  original_reference_id: PMID:9544840
  qualifier: located_in
  isoform: O00258-1
  review:
    summary: Duplicate of the early nuclear localization assertion; same provenance and same conclusion. GET1/WRB localizes to the ER membrane, not the nucleus.
    action: MARK_AS_OVER_ANNOTATED
    reason: Superseded by the experimentally established ER membrane localization; not reproduced.
    supported_by:
    - reference_id: PMID:21444755
      supporting_text: WRB is an ER-resident membrane protein
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:21444755
  title: WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane.
  findings:
  - statement: Identifies WRB/CHD5 as the ER membrane receptor for TRC40/Asna1 and maps the WRB coiled-coil domain as the TRC40 docking site; WRB is ER-resident, not nuclear.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Function-defining study identifying GET1/WRB as the GET3/TRC40 ER receptor and establishing ER (not nuclear) localization.
- id: PMID:23041287
  title: Molecular machinery for insertion of tail-anchored membrane proteins into the endoplasmic reticulum membrane in mammalian cells.
  findings:
  - statement: WRB and CAML synergistically insert TA proteins into the ER membrane and together constitute the mammalian TRC40 receptor complex.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes the WRB/CAML receptor complex and its synergistic TA-insertion activity.
- id: PMID:27226539
  title: 'Tail-anchored Protein Insertion in Mammals: FUNCTION AND RECIPROCAL INTERACTIONS OF THE TWO SUBUNITS OF THE TRC40 RECEPTOR.'
  findings:
  - statement: In-vitro-synthesized CAML and WRB together are sufficient to confer TA-insertion competence to liposomes; the two subunits are reciprocally dependent.
    reference_section_type: RESULTS
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Demonstrates sufficiency of WRB+CAML for TA insertion in a reconstituted system.
- id: PMID:31417168
  title: The WRB Subunit of the Get3 Receptor is Required for the Correct Integration of its Partner CAML into the ER.
  findings:
  - statement: WRB acts catalytically to assist CAML topogenesis; without sufficient WRB, CAML adopts aberrant topoforms that cluster and are degraded by the proteasome.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Source of the protein insertion (of CAML) and protein stabilization annotations; WRB and CAML are mutually dependent.
- id: PMID:32187542
  title: Differential Modes of Orphan Subunit Recognition for the WRB/CAML Complex.
  findings:
  - statement: The WRB/CAML complex is an essential insertase for tail-anchored proteins; WRB can correct the topology of CAML in vitro and in cells.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Describes WRB/CAML as an essential TA insertase and WRB-mediated CAML topology correction.
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings:
  - statement: High-throughput Y2H (HuRI) interactome; source of the IntAct protein binding partners of GET1.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Bare protein binding Y2H hits; many partners are membrane/TA proteins but the term is uninformative.
- id: PMID:32910895
  title: Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET Insertase Complex.
  findings:
  - statement: Cryo-EM of the human WRB/CAML/TRC40 complex; WRB and CAML form a phosphatidylinositol-stabilized heterotetramer that binds the GET3 homodimer, with an insertion mechanism related to YidC and the EMC.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Definitive structure of the human GET insertase complex.
- id: PMID:9544840
  title: Identification and characterization of a new human cDNA from chromosome 21q22.3 encoding a basic nuclear protein.
  findings:
  - statement: Original cDNA characterization reporting predominant nuclear immunofluorescence localization; not reproduced and superseded by later ER membrane localization.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: LOW
    correctness: DISPUTED
    review_notes: Source of the nucleus annotation; the nuclear localization was not reproduced and is contradicted by later work establishing ER membrane residence.
- id: PMID:34264263
  title: Capture and delivery of tail-anchored proteins to the endoplasmic reticulum.
  findings:
  - statement: Comprehensive review of the GET/TRC pathway; GET1/WRB with CAMLG/GET2 forms the ER membrane receptor-insertase that receives TA substrates from the cytosolic ATPase GET3/TRC40 and mediates their insertion into the ER bilayer.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (J Cell Biol 2021, 220:8). Authoritative pathway review framing GET1/WRB as the ER receptor-insertase subnit of the GET pathway.
- id: PMID:36640319
  title: The Get1/2 insertase forms a channel to mediate the insertion of tail-anchored proteins into the ER.
  findings:
  - statement: Reconstitution shows the Get1/2 (WRB/CAML) complex forms a dynamic aqueous channel (~2.5 nm, corresponding to two Get1/2 complexes) that is sealed by Get3 and whose channel activity is required to release TA proteins from Get3 for insertion; functions as both insertase and translocase for C-terminal hydrophilic tails.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (Cell Rep 2022, 42:111921). Mechanistic evidence that the GET1/2 insertase acts as a channel-forming insertase/translocase; directly supports GET1's TA-insertion role (yeast Get1/2, conserved in mammalian WRB/CAML).
- id: PMID:37963916
  title: The GET insertase exhibits conformational plasticity and induces membrane thinning.
  findings:
  - statement: Structures, simulations and functional data of human and C. thermophilum Get1/Get2/Get3 show the GET insertase fold is conserved, induces local lipid bilayer thinning near the hydrophilic groove to lower the insertion barrier, and that gating between Get2 helix alpha3' and Get3 drives conformational changes across the Get1/Get2 heterotetramer.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (Nat Commun 2023, 14:7355). Modern structural support for GET1/WRB as an active membrane insertase (not a static receptor) that remodels the bilayer; includes human Get1/Get2/Get3.
- id: file:human/GET1/GET1-uniprot.txt
  title: UniProt entry O00258 (GET1_HUMAN), Guided entry of tail-anchored proteins factor 1
  findings:
  - statement: GET1/WRB is the ER membrane receptor for GET3/TRC40 in the GET complex (GET1/WRB + CAMLG/GET2 + GET3/TRC40); multi-pass ER membrane protein required for post-translational delivery of TA proteins to the ER.
    reference_section_type: OTHER
core_functions:
- description: Membrane-insertase receptor of the GET pathway that docks the cytosolic GET3/TRC40 targeting factor at the ER membrane via its coiled-coil domain, enabling post-translational insertion of tail-anchored membrane proteins.
  molecular_function:
    id: GO:0043495
    label: protein-membrane adaptor activity
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: PMID:21444755
    supporting_text: We identify the coiled-coil domain of WRB as the binding site for TRC40/Asna1
  directly_involved_in:
  - id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
- description: Subunit of the GET (WRB/CAML/TRC40) insertase complex that, together with CAMLG/GET2, forms a heterotetramer accepting GET3-delivered tail-anchored proteins and inserting them into the ER lipid bilayer.
  molecular_function:
    id: GO:0043495
    label: protein-membrane adaptor activity
  in_complex:
    id: GO:0043529
    label: GET complex
  supported_by:
  - reference_id: PMID:27226539
    supporting_text: in vitro synthesized CAML and WRB together were sufficient to confer insertion competence to liposomes
  directly_involved_in:
  - id: GO:0071816
    label: tail-anchored membrane protein insertion into ER membrane
proposed_new_terms: []
suggested_questions:
- question: Does GET1/WRB contribute substrate selectivity for particular tail-anchored proteins, or is selectivity entirely determined upstream by GET3/TRC40?
- question: Are the many HuRI Y2H interactors of GET1 (membrane/TA proteins such as TFRC, AQP1, SLC7A1) genuine insertase substrates, and could GET1 interactomics be used to define its physiological client repertoire?
suggested_experiments:
- description: Reconstitute purified WRB, CAML and GET3/TRC40 into proteoliposomes and measure insertion kinetics for a panel of TA substrates of differing transmembrane-domain hydrophobicity to define GET1's role in substrate handoff and insertion efficiency.
- description: Use proximity labeling (BioID/TurboID) from endogenously tagged WRB in human cells to map its in vivo TA-protein client network and distinguish genuine substrates from incidental Y2H hits.