Annotation inferences using phylogenetic trees

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

Gene Ontology annotation based on curation of immunofluorescence data

Electronic Gene Ontology annotations created by transferring manual GO annotations between related proteins based on shared sequence features

GO_REF:0000120

Combined Automated Annotation using Multiple IEA Methods

PMID:17382883

Identification of a targeting factor for posttranslational membrane protein insertion into the ER.

Identified the cytosolic TMD recognition complex (TRC); the 40 kDa ATPase subunit TRC40 is Asna-1, which targets TA proteins for ER insertion with release dependent on ATP hydrolysis.

PMID:19056867

Large-scale proteomics and phosphoproteomics of urinary exosomes.

PMID:21444755

WRB is the receptor for TRC40/Asna1-mediated insertion of tail-anchored proteins into the ER membrane.

TRC40/Asna1 (Get3 in yeast) is a conserved cytosolic ATPase that recognizes the TMD of TA proteins and delivers them to the ER membrane receptor WRB.

PMID:21516116

Next-generation sequencing to generate interactome datasets.

PMID:21911467

Insight into bacterial virulence mechanisms against host immune response via the Yersinia pestis-human protein-protein interaction network.

PMID:23041287

Molecular machinery for insertion of tail-anchored membrane proteins into the endoplasmic reticulum membrane in mammalian cells.

CAML and WRB are components of the TRC40 receptor complex; TRC40 is an ATPase targeting newly synthesized TA proteins to the ER for insertion.

PMID:23610396

Precise timing of ATPase activation drives targeting of tail-anchored proteins.

Get3 coordinates delivery of TA proteins to the ER; the Get4/5 loading complex locks Get3 in the ATP-bound state while the TA substrate activates Get3's ATPase ~100-fold, and Get3 harnesses ATP energy to drive TA membrane localization.

PMID:25416956

A proteome-scale map of the human interactome network.

PMID:25535373

Bag6 complex contains a minimal tail-anchor-targeting module and a mock BAG domain.

The minimal Bag6 complex facilitates TA substrate transfer from SGTA to TRC40, the loading step of the GET pathway.

PMID:28514442

Architecture of the human interactome defines protein communities and disease networks.

PMID:31461301

Biallelic Variants in ASNA1, Encoding a Cytosolic Targeting Factor of Tail-Anchored Proteins, Cause Rapidly Progressive Pediatric Cardiomyopathy.

ASNA1 (TRC40/GET3) is a ubiquitously expressed cytosolic chaperone mediating TA-protein insertion into the ER; the disease Val163Ala mutant captures TA but is inefficient in facilitating insertion, and asna1-null zebrafish develop cardiac failure.

PMID:32296183

A reference map of the human binary protein interactome.

PMID:32910895

Structural Basis of Tail-Anchored Membrane Protein Biogenesis by the GET Insertase Complex.

Cryo-EM of the GET insertase complex; the WRB/CAML (Get1/Get2) insertase captures the TA from the cytoplasmic chaperone GET3/TRC40 that GET3 binds as a homodimer.

PMID:33961781

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

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

PMID:8884272

Isolation of the ATP-binding human homolog of the arsA component of the bacterial arsenite transporter.

Isolated the human homolog of bacterial arsA (hARSA-I/ASNA1) and showed it is an ATPase analogous to bacterial ArsA.

PMID:9712828

Biochemical characterization of the human arsenite-stimulated ATPase (hASNA-I).

Recombinant hASNA-I exhibits basal ATPase activity (modestly arsenite-stimulated; antimonite does not stimulate), with measured ATP kinetics.

PMID:9736449

Dual cytoplasmic and nuclear distribution of the novel arsenite-stimulated human ATPase (hASNA-I).

Early study reporting a cytoplasmic, perinuclear, and nucleolar distribution of the arsenite-stimulated ATPase.

PMID:34264263

Capture and delivery of tail-anchored proteins to the endoplasmic reticulum.

Comprehensive review of the GET/TRC pathway; GET3/TRC40 is the central cytosolic homodimeric ATPase that captures TA substrates, shields the hydrophobic TMD, and delivers them to the ER WRB/CAML receptor-insertase for insertion.

PMID:36640319

The Get1/2 insertase forms a channel to mediate the insertion of tail-anchored proteins into the ER.

Get3 (TRC40) delivers TA proteins to the Get1/2 channel; Get3 binding seals the dynamically opening Get1/2 channel, and channel activity is required to release TA proteins from Get3 for insertion, defining the GET3-to-insertase handoff step.

PMID:37963916

The GET insertase exhibits conformational plasticity and induces membrane thinning.

Structures and simulations of human and C. thermophilum Get1/Get2/Get3 show that the gating interaction between Get2 helix alpha3' and Get3 drives conformational changes in both Get3 and the Get1/Get2 heterotetramer, promoting Get3 opening, nucleotide release, and TA substrate transfer to the membrane.

file:human/GET3/GET3-uniprot.txt

UniProt entry O43681 (GET3_HUMAN), ATPase ASNA1/TRC40

ATPase required for post-translational delivery of TA proteins to the ER; recognizes the TA TMD in the cytosol, targets to the GET1/WRB-CAMLG/GET2 receptor where ATP hydrolysis drives release/insertion; component of the GET complex; cytoplasmic/ER/nucleolar.