| Category | Key points | Key sources (author year journal) | URL | Publication date | Evidence ID(s) |
|---|---|---|---|---|---|
| Identity | Human GET1 corresponds to WRB (tryptophan-rich basic protein; also called congenital heart disease 5 protein), the metazoan homolog of yeast Get1, matching UniProt O00258. It is a core component of the ER receptor/insertase for tail-anchored (TA) proteins. | Vilardi 2011 *Journal of Cell Science*; Farkas & Bohnsack 2021 *J Cell Biol* | https://doi.org/10.1242/jcs.084277; https://doi.org/10.1083/jcb.202105004 | 2011-04; 2021-07 | (pqac-00000006, pqac-00000002) |
| Localization | WRB is an ER-resident integral membrane protein with a cytosol-exposed coiled-coil domain that docks TRC40/ASNA1. Reviews and primary studies consistently place the functional WRB/CAML receptor in the ER membrane. | Vilardi 2011 *Journal of Cell Science*; Pool 2022 *Int J Mol Sci* | https://doi.org/10.1242/jcs.084277; https://doi.org/10.3390/ijms23073773 | 2011-04; 2022-03 | (pqac-00000006, pqac-00000001) |
| Mechanism | WRB functions as the Get1-like insertase/receptor that receives TA substrates from TRC40/ASNA1 and helps release the substrate TMD for insertion into the ER bilayer. Structural work supports a membrane-embedded hydrophilic groove/channel mechanism analogous to other Oxa1/YidC-family insertases. | McDowell et al. 2020 *Molecular Cell*; Heo et al. 2023 *Cell Reports* | https://doi.org/10.1016/j.molcel.2020.08.012; https://doi.org/10.1016/j.celrep.2022.111921 | 2020-10; 2023-01 | (pqac-00000004, pqac-00000007, pqac-00000000) |
| Partners | The core mammalian receptor is the WRB/CAML complex; WRB directly engages TRC40/ASNA1 through its coiled-coil domain, while CAML acts as the Get2 analog and cooperates in substrate delivery/insertion. WRB and CAML are mutually stabilizing and function as an obligate receptor complex. | Vilardi 2011 *Journal of Cell Science*; Farkas & Bohnsack 2021 *J Cell Biol* | https://doi.org/10.1242/jcs.084277; https://doi.org/10.1083/jcb.202105004 | 2011-04; 2021-07 | (pqac-00000006, pqac-00000002, pqac-00000003) |
| Recent structural findings 2023 | 2023 work on human GET insertase showed conformational plasticity, a hydrophilic groove in hsGet1/WRB, and membrane thinning near the insertion site. Reported values include local thinning from ~4.35 nm to ~2.25 nm and a ~15° coiled-coil rotation/tilt associated with gating changes. | McDowell et al. 2023 *Nature Communications* | https://doi.org/10.1038/s41467-023-42867-2 | 2023-11 | (pqac-00000008, pqac-00000020) |
| Proteomics client spectra 2023 | Quantitative proteomics in human cells found TRC/GET clients enriched for proteins with central or C-terminal TMHs and unexpectedly many multispanning membrane proteins. For insertase preference in TA insertion, the ranking reported was Wrb >> TRAM1 >> Sec61 > EMC > TRAP > Sec63. | Jung & Zimmermann 2023 *Int J Mol Sci* | https://doi.org/10.3390/ijms241814166 | 2023-09 | (pqac-00000009) |
| Quality control link 2023 | Proteotoxic stress and polyQ inclusions disrupt the BAG6–UBL4A pretargeting complex upstream of WRB/CAML, linking TA-protein biogenesis to proteostasis and aggregate-associated pathology. BAG6/UBL4A normally helps shield hydrophobic TMDs and route clients either to WRB/CAML-mediated insertion or degradation. | Hagiwara et al. 2023 *Biochemical Journal* | https://doi.org/10.1042/bcj20230267 | 2023-10 | (pqac-00000010) |
| Phenotypes-Disease | WRB has been linked mechanistically to sensory phenotypes in vertebrate models: defective WRB impairs insertion of TA clients such as otoferlin and disrupts photoreceptor/hair-cell synaptic function, hearing, and vision. The WRB locus also lies in a chromosome 21 congenital heart disease region, but direct human WRB disease causality remains less established than for other TRC-pathway genes. | Rivera-Monroy et al. 2016 *Scientific Reports*; Vogl et al. 2016 *EMBO Journal*; Vilardi 2011 *Journal of Cell Science* | https://doi.org/10.1038/srep39464; https://doi.org/10.15252/embj.201593565; https://doi.org/10.1242/jcs.084277 | 2016-12; 2016-12; 2011-04 | (pqac-00000012, pqac-00000016, pqac-00000017, pqac-00000018, pqac-00000019) |


*Table: This table summarizes the main functional annotation evidence for human GET1/WRB (UniProt O00258), including identity, localization, molecular mechanism, partners, and recent 2023 developments. It is useful as a compact evidence map linking core biological claims to specific sources and context IDs.*