Gene Symbol: GET3
Description: guanine nucleotide exchange factor GET3
Alias: ARR4, guanine nucleotide exchange factor GET3
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Metz J, W├Ąchter A, Schmidt B, Bujnicki J, Schwappach B. The yeast Arr4p ATPase binds the chloride transporter Gef1p when copper is available in the cytosol. J Biol Chem. 2006;281:410-7 pubmed
    ..Comparison of the deltaarr4 with the deltaarr4deltagef1 strain suggests that Arr4p antagonizes the function of Gef1p. ..
  2. Suloway C, Rome M, Clemons W. Tail-anchor targeting by a Get3 tetramer: the structure of an archaeal homologue. EMBO J. 2012;31:707-19 pubmed publisher
    ..The central player is the ATPase Get3, which in its free form exists as a dimer. Biochemical evidence suggests a role for a tetramer of Get3...
  3. Mariappan M, Mateja A, Dobosz M, Bove E, Hegde R, Keenan R. The mechanism of membrane-associated steps in tail-anchored protein insertion. Nature. 2011;477:61-6 pubmed publisher
    ..We show that a committed targeting complex, formed by a TA protein bound to the chaperone ATPase Get3, is initially recruited to the membrane through an interaction with Get2...
  4. Stefer S, Reitz S, Wang F, Wild K, Pang Y, Schwarz D, et al. Structural basis for tail-anchored membrane protein biogenesis by the Get3-receptor complex. Science. 2011;333:758-62 pubmed publisher
    ..C-terminal membrane anchor and are posttranslationally delivered to the endoplasmic reticulum (ER) membrane by the Get3 adenosine triphosphatase interacting with the hetero-oligomeric Get1/2 receptor...
  5. Chang Y, Chuang Y, Ho Y, Cheng M, Sun Y, Hsiao C, et al. Crystal structure of Get4-Get5 complex and its interactions with Sgt2, Get3, and Ydj1. J Biol Chem. 2010;285:9962-70 pubmed publisher
    b>Get3, Get4, and Get5 in Saccharomyces cerevisiae participate in the insertion of tail-anchored proteins into the endoplasmic reticulum membrane...
  6. Schuldiner M, Metz J, Schmid V, Denic V, Rakwalska M, Schmitt H, et al. The GET complex mediates insertion of tail-anchored proteins into the ER membrane. Cell. 2008;134:634-45 pubmed publisher
    ..Here we show that Get3, the yeast homolog of the TA-interacting factor Asna1/Trc40, specifically recognizes TMDs of TA proteins destined ..
  7. Shen J, Hsu C, Kang B, Rosen B, Bhattacharjee H. The Saccharomyces cerevisiae Arr4p is involved in metal and heat tolerance. Biometals. 2003;16:369-78 pubmed
    ..This article reports the function of the Saccharomyces cerevisiae homologue encoded by ARR4 gene (YDL100c ORF)...
  8. Auld K, Hitchcock A, Doherty H, Frietze S, Huang L, Silver P. The conserved ATPase Get3/Arr4 modulates the activity of membrane-associated proteins in Saccharomyces cerevisiae. Genetics. 2006;174:215-27 pubmed
    ..extragenic suppressors of a temperature-sensitive npl4 allele and the subsequent analysis of one suppressor, GET3/ARR4. The GET3 gene encodes an ATPase with homology to the regulatory component of the bacterial arsenic pump...
  9. Mateja A, Szlachcic A, Downing M, Dobosz M, Mariappan M, Hegde R, et al. The structural basis of tail-anchored membrane protein recognition by Get3. Nature. 2009;461:361-6 pubmed publisher
    ..Instead, tail-anchored proteins are targeted post-translationally by a conserved ATPase termed Get3. The mechanistic basis for tail-anchored protein recognition or targeting by Get3 is not known...

More Information


  1. Wang F, Brown E, Mak G, Zhuang J, Denic V. A chaperone cascade sorts proteins for posttranslational membrane insertion into the endoplasmic reticulum. Mol Cell. 2010;40:159-71 pubmed publisher
    ..Biochemical reconstitution with purified components demonstrates that TRC tethers and enzymatically activates Get3 to selectively hand off ER-bound TA proteins to Get3...
  2. Kohl C, Tessarz P, von der Malsburg K, Zahn R, Bukau B, Mogk A. Cooperative and independent activities of Sgt2 and Get5 in the targeting of tail-anchored proteins. Biol Chem. 2011;392:601-8 pubmed publisher
    ..Furthermore, overproduction of Sgt2 becomes toxic to get3? but not to get5? cells...
  3. NEAL S, Mak R, Bennett E, HAMPTON R. A Cdc48 "Retrochaperone" Function Is Required for the Solubility of Retrotranslocated, Integral Membrane Endoplasmic Reticulum-associated Degradation (ERAD-M) Substrates. J Biol Chem. 2017;292:3112-3128 pubmed publisher
    ..Thus, in addition to the long known ATP-dependent extraction of ERAD substrates during retrotranslocation, the Cdc48 complex is generally and critically needed for the solubility of retrotranslocated ERAD-M intermediates. ..
  4. Okreglak V, Walter P. The conserved AAA-ATPase Msp1 confers organelle specificity to tail-anchored proteins. Proc Natl Acad Sci U S A. 2014;111:8019-24 pubmed publisher
    ..Our data suggest that Msp1 functions in local organelle surveillance by extracting mistargeted proteins, ensuring the fidelity of organelle specific-localization of TA proteins. ..
  5. Ast T, Cohen G, Schuldiner M. A network of cytosolic factors targets SRP-independent proteins to the endoplasmic reticulum. Cell. 2013;152:1134-45 pubmed publisher
    ..These findings highlight the underappreciated complexity of SRP-independent translocation, which enables this pathway to efficiently cope with its extensive substrate flux...
  6. Powis K, Schrul B, Tienson H, Gostimskaya I, Breker M, High S, et al. Get3 is a holdase chaperone and moves to deposition sites for aggregated proteins when membrane targeting is blocked. J Cell Sci. 2013;126:473-83 pubmed publisher
    ..Here we show that the ATPase Get3, which accommodates the hydrophobic tail anchor of clients, has a dual function: promoting tail-anchored protein ..
  7. Chartron J, Suloway C, Zaslaver M, Clemons W. Structural characterization of the Get4/Get5 complex and its interaction with Get3. Proc Natl Acad Sci U S A. 2010;107:12127-32 pubmed publisher
    ..identified in the early steps of the pathway mediating TA substrate delivery to the cytoplasmic targeting factor Get3. Here we report a crystal structure of Get4 and an N-terminal fragment of Get5 from Saccharomyces cerevisae...
  8. Suloway C, Chartron J, Zaslaver M, Clemons W. Model for eukaryotic tail-anchored protein binding based on the structure of Get3. Proc Natl Acad Sci U S A. 2009;106:14849-54 pubmed publisher
    The Get3 ATPase directs the delivery of tail-anchored (TA) proteins to the endoplasmic reticulum (ER)...
  9. Mateja A, Paduch M, Chang H, Szydlowska A, Kossiakoff A, Hegde R, et al. Protein targeting. Structure of the Get3 targeting factor in complex with its membrane protein cargo. Science. 2015;347:1152-5 pubmed publisher
    ..During transit, their hydrophobic transmembrane domains (TMDs) are chaperoned by the cytosolic targeting factor Get3, but the molecular nature of the functional Get3-TA protein targeting complex remains unknown...
  10. Yamagata A, Mimura H, Sato Y, Yamashita M, Yoshikawa A, Fukai S. Structural insight into the membrane insertion of tail-anchored proteins by Get3. Genes Cells. 2010;15:29-41 pubmed publisher
    ..The membrane insertion of TA proteins is mediated by the highly conserved ATPase Get3. Here we report the crystal structures of Get3 in ADP-bound and nucleotide-free forms at 3.0 A and 2...
  11. Wang F, Whynot A, Tung M, Denic V. The mechanism of tail-anchored protein insertion into the ER membrane. Mol Cell. 2011;43:738-50 pubmed publisher
    ..b>Get3 is an ATPase that delivers TA proteins to the ER by interacting with the Get1-Get2 transmembrane complex, but how ..
  12. Hu J, Li J, Qian X, Jin Z, Fu Z, Sha B. Preliminary X-ray crystallographic studies of yeast Get3. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:489-91 pubmed publisher
    ..the ER membrane requires the cooperation of the Golgi ER-trafficking (GET) complex, which contains Get1, Get2 and Get3. Get3 is a cytosolic ATPase which can recognize and bind the TMD of the TA proteins...
  13. Chang Y, Lin T, Li Y, Huang Y, Sun Y, Hsiao C. Interaction surface and topology of Get3-Get4-Get5 protein complex, involved in targeting tail-anchored proteins to endoplasmic reticulum. J Biol Chem. 2012;287:4783-9 pubmed publisher
    ..Here, we investigated the interactions between Get3 and the Get4-Get5 complex from Saccharomyces cerevisiae...
  14. Joshi A, Fei N, Greenberg M. Get1p and Get2p are required for maintenance of mitochondrial morphology and normal cardiolipin levels. FEMS Yeast Res. 2016;16: pubmed publisher
    ..The genetic interactions observed in this study identify novel physiological modifiers that are required for maintenance of CL levels and mitochondrial morphology. ..
  15. Kiktev D, Patterson J, Muller S, Bariar B, Pan T, Chernoff Y. Regulation of chaperone effects on a yeast prion by cochaperone Sgt2. Mol Cell Biol. 2012;32:4960-70 pubmed publisher
    ..Our data implicate Sgt2 as an amyloid "sensor" and a regulator of chaperone targeting to different types of aggregation-prone proteins. ..
  16. Chen Y, Umanah G, Dephoure N, Andrabi S, Gygi S, Dawson T, et al. Msp1/ATAD1 maintains mitochondrial function by facilitating the degradation of mislocalized tail-anchored proteins. EMBO J. 2014;33:1548-64 pubmed publisher
  17. Rome M, Rao M, Clemons W, Shan S. Precise timing of ATPase activation drives targeting of tail-anchored proteins. Proc Natl Acad Sci U S A. 2013;110:7666-71 pubmed publisher
    ..In eukaryotic cells, the highly conserved ATPase, guided entry of tail-anchored protein 3 (Get3), coordinates the delivery of TA proteins to the endoplasmic reticulum...
  18. Yeh Y, Lin T, Li Y, Tung J, Lin C, Hsiao C. Structural and functional characterization of ybr137wp implicates its involvement in the targeting of tail-anchored proteins to membranes. Mol Cell Biol. 2014;34:4500-12 pubmed publisher
    ..pathway is comprised of Sgt2, Get4, and Get5 and facilitates the loading of nascent tail-anchored proteins onto the Get3 ATPase. Multiple pulldown assays also indicated that Ybr137wp associates with this complex in vivo...
  19. Voth W, Schick M, Gates S, Li S, Vilardi F, Gostimskaya I, et al. The protein targeting factor Get3 functions as ATP-independent chaperone under oxidative stress conditions. Mol Cell. 2014;56:116-27 pubmed publisher
    ..Here we show that Get3, a protein involved in ATP-dependent targeting of tail-anchored (TA) proteins under nonstress conditions, turns ..
  20. Gristick H, Rao M, Chartron J, Rome M, Shan S, Clemons W. Crystal structure of ATP-bound Get3-Get4-Get5 complex reveals regulation of Get3 by Get4. Nat Struct Mol Biol. 2014;21:437-42 pubmed publisher
    ..which the Get4-Get5 complex mediates the handover of tail-anchor (TA) substrates from the cochaperone Sgt2 to the Get3 ATPase, the central targeting factor...
  21. Hu J, Li J, Qian X, Denic V, Sha B. The crystal structures of yeast Get3 suggest a mechanism for tail-anchored protein membrane insertion. PLoS ONE. 2009;4:e8061 pubmed publisher
    ..TA proteins into the ER membrane requires the Golgi ER trafficking (GET) complex which contains Get1, Get2 and Get3. Get3 is an ATPase that recognizes and binds the C-terminal transmembrane domain (TMD) of the TA proteins...
  22. Wereszczynski J, McCammon J. Nucleotide-dependent mechanism of Get3 as elucidated from free energy calculations. Proc Natl Acad Sci U S A. 2012;109:7759-64 pubmed publisher
    ..At the center of this mechanism is the Get3 homodimer, which transfers a TA protein between the two GET phases by leveraging energy gained in ATP binding and ..
  23. Lee M, Dohlman H. Coactivation of G protein signaling by cell-surface receptors and an intracellular exchange factor. Curr Biol. 2008;18:211-5 pubmed publisher
    ..Here we report the discovery of a nonreceptor GEF, Arr4. Like receptors, Arr4 binds directly to the G protein,accelerates guanine-nucleotide exchange, and stabilizes the ..
  24. Kubota K, Yamagata A, Sato Y, Goto Ito S, Fukai S. Get1 stabilizes an open dimer conformation of get3 ATPase by binding two distinct interfaces. J Mol Biol. 2012;422:366-75 pubmed publisher
    ..The GET complex is composed of the homodimeric Get3 ATPase and its heterooligomeric receptor, Get1/2...