GET3

GET3 (ASNA1; also known as TRC40 and arsenite-stimulated ATPase) is the central cytosolic ATPase of the GET/TRC pathway for post-translational targeting of tail-anchored (TA) membrane proteins to the endoplasmic reticulum (ER). It is a homodimeric P-loop NTPase of the ArsA/ArsA-like ATPase family. GET3 selectively recognizes and binds the single C-terminal transmembrane domain (TMD) of newly synthesized TA proteins in the cytosol, receiving them via the BAG6/UBL4A/GET4 pre-targeting and bridging machinery (and from the cochaperone SGTA), and shields the hydrophobic TMD as a soluble carrier/chaperone. ATP binding drives the homodimer into a closed state that captures the substrate; the GET3-TA complex then docks at the ER-membrane receptor-insertase formed by GET1/WRB and CAMLG/GET2, and ATP hydrolysis triggers TA release for insertion into the lipid bilayer, after which GET3 returns to the cytosol for another round. GET3 is thus the targeting factor and TMD chaperone of the pathway, not the membrane insertase itself. It was originally isolated as the human homolog of bacterial ArsA, an arsenite/antimonite-stimulated ATPase, but its physiological role is TA-protein biogenesis. Loss-of-function variants cause an autosomal recessive, rapidly progressive infantile dilated cardiomyopathy. GET3 acts predominantly in the cytoplasm and transiently at the ER membrane.

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.