adaptor protein complex gamma subunits


Summary: A family of large adaptin protein subunits of approximately 90 KDa in size. They have been primarily found as components of ADAPTOR PROTEIN COMPLEX 1.

Top Publications

  1. Zizioli D, Meyer C, Guhde G, Saftig P, Von Figura K, Schu P. Early embryonic death of mice deficient in gamma-adaptin. J Biol Chem. 1999;274:5385-90 pubmed
    ..Free beta1- or micro1 chains were not detectable, indicating that they are unstable unless they are part of AP-1 complexes. Heterozygous mice weigh less then their wild-type littermates and show impaired T cell development. ..
  2. Page L, Robinson M. Targeting signals and subunit interactions in coated vesicle adaptor complexes. J Cell Biol. 1995;131:619-30 pubmed
    ..These results indicate that the adaptor subunits act in concert to target the complex to the appropriate membrane. ..
  3. Seaman M, Ball C, Robinson M. Targeting and mistargeting of plasma membrane adaptors in vitro. J Cell Biol. 1993;123:1093-105 pubmed
    ..Intracellular sequestration of PM adaptor receptors may provide the cell with a mechanism for up-regulating endocytosis following a burst of exocytosis. ..
  4. Seaman M, Sowerby P, Robinson M. Cytosolic and membrane-associated proteins involved in the recruitment of AP-1 adaptors onto the trans-Golgi network. J Biol Chem. 1996;271:25446-51 pubmed
    ..These proteins are all candidates for components of the adaptor docking site on the trans-Golgi network membrane. ..
  5. Robinson M. Cloning and expression of gamma-adaptin, a component of clathrin-coated vesicles associated with the Golgi apparatus. J Cell Biol. 1990;111:2319-26 pubmed
  6. Lewin D, Sheff D, Ooi C, Whitney J, Yamamoto E, Chicione L, et al. Cloning, expression, and localization of a novel gamma-adaptin-like molecule. FEBS Lett. 1998;435:263-8 pubmed
    ..Together, these results suggest that gamma2-adaptin plays a role in membrane transport distinct from that played by gamma-adaptin. ..
  7. FOLSCH H, Pypaert M, Schu P, Mellman I. Distribution and function of AP-1 clathrin adaptor complexes in polarized epithelial cells. J Cell Biol. 2001;152:595-606 pubmed
  8. Dell Angelica E, Puertollano R, Mullins C, Aguilar R, Vargas J, Hartnell L, et al. GGAs: a family of ADP ribosylation factor-binding proteins related to adaptors and associated with the Golgi complex. J Cell Biol. 2000;149:81-94 pubmed
    ..Disruption of both GGA genes in yeast resulted in impaired trafficking of carboxypeptidase Y to the vacuole. These observations suggest that GGAs are components of ARF-regulated coats that mediate protein trafficking at the TGN. ..
  9. Hirst J, Lui W, Bright N, Totty N, Seaman M, Robinson M. A family of proteins with gamma-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome. J Cell Biol. 2000;149:67-80 pubmed
    ..These results indicate that the function of the GGAs is to facilitate the trafficking of proteins between the TGN and the vacuole, or its mammalian equivalent, the lysosome. ..

More Information


  1. Page L, Sowerby P, Lui W, Robinson M. Gamma-synergin: an EH domain-containing protein that interacts with gamma-adaptin. J Cell Biol. 1999;146:993-1004 pubmed
    ..The presence of an EH domain suggests that gamma-synergin links the AP-1 complex to another protein or proteins. ..
  2. Takatsu H, Sakurai M, Shin H, Murakami K, Nakayama K. Identification and characterization of novel clathrin adaptor-related proteins. J Biol Chem. 1998;273:24693-700 pubmed
    ..These data suggest that gamma2-adaptin constitute a novel adaptor-related complex that participates in a transport step different from that of AP-1. ..
  3. Tao X, Lu Y, Qiu S, Wang Y, Qin J, Fan Z. AP1G1 is involved in cetuximab-mediated downregulation of ASCT2-EGFR complex and sensitization of human head and neck squamous cell carcinoma cells to ROS-induced apoptosis. Cancer Lett. 2017;408:33-42 pubmed publisher
    ..These findings suggest a new therapeutic strategy to overcome cetuximab resistance in cancer cells through combination of cetuximab, which co-targets ASCT2 along with EGFR, with an ROS-inducing agent. ..
  4. Antrobus R, Borner G. Improved elution conditions for native co-immunoprecipitation. PLoS ONE. 2011;6:e18218 pubmed publisher
    ..The method was developed for rabbit polyclonal antibodies, but also performed well with the tested goat and mouse antibodies. Hence we expect the soft elution protocol to be widely applicable. ..
  5. Albrecht M, Hoffmann D, Evert B, Schmitt I, Wullner U, Lengauer T. Structural modeling of ataxin-3 reveals distant homology to adaptins. Proteins. 2003;50:355-70 pubmed
    ..Our database searches also identified an as yet uncharacterized family of proteins, which we named josephins because of their pronounced homology to the Josephin domain of ataxin-3. ..
  6. Shinotsuka C, Yoshida Y, Kawamoto K, Takatsu H, Nakayama K. Overexpression of an ADP-ribosylation factor-guanine nucleotide exchange factor, BIG2, uncouples brefeldin A-induced adaptor protein-1 coat dissociation and membrane tubulation. J Biol Chem. 2002;277:9468-73 pubmed
    ..These observations indicate that BFA-induced AP-1 dissociation from TGN membranes and tubulation of TGN membranes are not coupled events and suggest that a BFA target other than ARF-GEFs exists in the cell. ..
  7. Janvier K, Craig H, Le Gall S, Benarous R, Guatelli J, Schwartz O, et al. Nef-induced CD4 downregulation: a diacidic sequence in human immunodeficiency virus type 1 Nef does not function as a protein sorting motif through direct binding to beta-COP. J Virol. 2001;75:3971-6 pubmed
    ..Additional studies are thus required to characterize the residues of Nef involved in the binding to beta-COP and to evaluate the contribution of this interaction to the Nef-induced perturbations of membrane trafficking. ..
  8. Poussu A, Lohi O, Lehto V. Vear, a novel Golgi-associated protein with VHS and gamma-adaptin "ear" domains. J Biol Chem. 2000;275:7176-83 pubmed
    ..Tissue-specific function of Vear is suggested by its high level of expression in kidney, muscle, and heart. ..
  9. Sugiura T, Kato Y, Kubo Y, Tsuji A. Mutation in an adaptor protein PDZK1 affects transport activity of organic cation transporter OCTNs and oligopeptide transporter PEPT2. Drug Metab Pharmacokinet. 2006;21:375-83 pubmed
  10. Nogi T, Shiba Y, Kawasaki M, Shiba T, Matsugaki N, Igarashi N, et al. Structural basis for the accessory protein recruitment by the gamma-adaptin ear domain. Nat Struct Biol. 2002;9:527-31 pubmed
  11. Lui W, Collins B, Hirst J, Motley A, Millar C, Schu P, et al. Binding partners for the COOH-terminal appendage domains of the GGAs and gamma-adaptin. Mol Biol Cell. 2003;14:2385-98 pubmed
    ..By overexpressing wild-type GGA and gamma appendage domains in cells, we can drive p56 and gamma-synergin, respectively, into the cytosol, suggesting a possible mechanism for selectively disrupting the two pathways. ..
  12. Faucherre A, Desbois P, Satre V, Lunardi J, Dorseuil O, Gacon G. Lowe syndrome protein OCRL1 interacts with Rac GTPase in the trans-Golgi network. Hum Mol Genet. 2003;12:2449-56 pubmed
    ..Moreover, loss of OCRL1 RhoGAP and the resulting alteration in Rho pathways may contribute to mental retardation in Lowe syndrome, as illustrated in other forms of X-linked mental retardation...
  13. Ang A, FOLSCH H, Koivisto U, Pypaert M, Mellman I. The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in polarized Madin-Darby canine kidney cells. J Cell Biol. 2003;163:339-50 pubmed
    ..However, expression of active Rab8 caused a selective dissociation of AP-1B complexes, reflecting the specificity of Rab8 for AP-1B-dependent transport...
  14. Kim M, Hersh L. The vesicular acetylcholine transporter interacts with clathrin-associated adaptor complexes AP-1 and AP-2. J Biol Chem. 2004;279:12580-7 pubmed
    ..There appear to be two endocytosis motifs, one involving the adaptor protein 1 binding site and the other involving the adaptor protein 2 binding site. These results suggest a complex trafficking pathway for VAChT. ..
  15. Lambert C, Döring T, Prange R. Hepatitis B virus maturation is sensitive to functional inhibition of ESCRT-III, Vps4, and gamma 2-adaptin. J Virol. 2007;81:9050-60 pubmed
    ..Together, these results demonstrate that HBV exploits the MVB machinery with the aid of gamma 2-adaptin. ..
  16. Döring T, Gotthardt K, Stieler J, Prange R. ?2-Adaptin is functioning in the late endosomal sorting pathway and interacts with ESCRT-I and -III subunits. Biochim Biophys Acta. 2010;1803:1252-64 pubmed publisher
    ..These observations identify ?2-adaptin as a critical factor in MVB trafficking, which likely is involved in endosome-to-lysosome maturation. ..
  17. Bogan J, Lodish H. Two compartments for insulin-stimulated exocytosis in 3T3-L1 adipocytes defined by endogenous ACRP30 and GLUT4. J Cell Biol. 1999;146:609-20 pubmed
  18. Ooi C, Moreira J, Dell Angelica E, Poy G, Wassarman D, Bonifacino J. Altered expression of a novel adaptin leads to defective pigment granule biogenesis in the Drosophila eye color mutant garnet. EMBO J. 1997;16:4508-18 pubmed
    ..Thus, the eye pigmentation defect in the Drosophila garnet mutant may be attributed to compromised function of a coat protein involved in intracellular transport processes required for biogenesis or function of pigment granules. ..
  19. Ritter B, Denisov A, Philie J, Deprez C, Tung E, Gehring K, et al. Two WXXF-based motifs in NECAPs define the specificity of accessory protein binding to AP-1 and AP-2. EMBO J. 2004;23:3701-10 pubmed
    ..These studies provide a structural basis for the specific recruitment of accessory proteins to appropriate sites of clathrin-coated vesicle formation. ..
  20. Greenberg M, Bronson S, Lock M, Neumann M, Pavlakis G, Skowronski J. Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation. EMBO J. 1997;16:6964-76 pubmed
    ..This evidence supports a model whereby Nef recruits CD4 to the endocytic machinery via AP-2-containing clathrin coats at the plasma membrane. ..
  21. Park M, Song K, Reichardt I, Kim H, Mayer U, Stierhof Y, et al. Arabidopsis ?-adaptin subunit AP1M of adaptor protein complex 1 mediates late secretory and vacuolar traffic and is required for growth. Proc Natl Acad Sci U S A. 2013;110:10318-23 pubmed publisher
    ..Thus, AP-1 is crucial in post-Golgi trafficking in plant cells and required for cell division and plant growth. ..
  22. Jürgens M, Vörös J, Rautureau G, Shepherd D, Pye V, Muldoon J, et al. The hepatitis B virus preS1 domain hijacks host trafficking proteins by motif mimicry. Nat Chem Biol. 2013;9:540-7 pubmed publisher
    ..The preS1-?2-EAR interaction was relatively weak and efficiently outcompeted by a synthetic peptide. Our data provide the structural road map for developing peptidomimetic antivirals targeting the ?2-EAR-preS1 interaction. ..
  23. Duncan M, Costaguta G, Payne G. Yeast epsin-related proteins required for Golgi-endosome traffic define a gamma-adaptin ear-binding motif. Nat Cell Biol. 2003;5:77-81 pubmed
    ..On the basis of our results and the established roles of epsin and epsin-related proteins in endocytosis, we propose that ENTH-domain-containing proteins are a universal component of CCV formation. ..
  24. Kalthoff C, Groos S, Kohl R, Mahrhold S, Ungewickell E. Clint: a novel clathrin-binding ENTH-domain protein at the Golgi. Mol Biol Cell. 2002;13:4060-73 pubmed
    ..Our results suggest that Clint might participate in the formation of clathrin-coated vesicles at the level of the trans-Golgi network and remains associated with the vesicles longer than clathrin and adaptors. ..
  25. Hu T, Kao C, Hudson R, Chen A, Draper R. Inhibition of secretion by 1,3-Cyclohexanebis(methylamine), a dibasic compound that interferes with coatomer function. Mol Biol Cell. 1999;10:921-33 pubmed
  26. Weixel K, Bradbury N. Endocytic adaptor complexes bind the C-terminal domain of CFTR. Pflugers Arch. 2001;443 Suppl 1:S70-4 pubmed
    ..Thus, we demonstrate that CFTR is endocytosed via clathrin-coated vesicles, and that targeting of CFTR to these structures is mediated by binding of the AP-2 adaptor complex to the C-terminal domain of CFTR. ..
  27. Deneka M, Neeft M, Popa I, van Oort M, Sprong H, Oorschot V, et al. Rabaptin-5alpha/rabaptin-4 serves as a linker between rab4 and gamma(1)-adaptin in membrane recycling from endosomes. EMBO J. 2003;22:2645-57 pubmed
    ..Collectively, our data show that rab4-GTP acts as a scaffold for a rabaptin-5alpha- gamma(1)-adaptin complex on recycling endosomes and that interactions between rab4, rabaptin-5alpha and gamma(1)-adaptin regulate membrane recycling. ..
  28. Martin S, Ramm G, Lyttle C, Meerloo T, Stoorvogel W, James D. Biogenesis of insulin-responsive GLUT4 vesicles is independent of brefeldin A-sensitive trafficking. Traffic. 2000;1:652-60 pubmed
    ..However, neither this pathway, nor any other BFA-sensitive pathway, appears to play a major role in insulin-dependent recruitment of GLUT4 to the cell surface. ..
  29. Inoue M, Shiba T, Ihara K, Yamada Y, Hirano S, Kamikubo H, et al. Molecular basis for autoregulatory interaction between GAE domain and hinge region of GGA1. Traffic. 2007;8:904-13 pubmed
  30. Puertollano R, Martinez Menarguez J, Batista A, Ballesta J, Alonso M. An intact dilysine-like motif in the carboxyl terminus of MAL is required for normal apical transport of the influenza virus hemagglutinin cargo protein in epithelial Madin-Darby canine kidney cells. Mol Biol Cell. 2001;12:1869-83 pubmed
    ..These results indicate that the carboxyl-terminal RWKSS sequence modulates the distribution of MAL in clathrin-coated elements and is necessary for HA transport to the apical surface. ..
  31. Wasiak S, Denisov A, Han Z, Leventis P, de Heuvel E, Boulianne G, et al. Characterization of a gamma-adaptin ear-binding motif in enthoprotin. FEBS Lett. 2003;555:437-42 pubmed
    ..NMR studies of the gamma-ear in complex with a synthetic peptide from enthoprotin provide structural details of the binding site for TGN accessory proteins within the gamma-ear. ..
  32. Peyrard M, Parveneh S, Lagercrantz S, Ekman M, Fransson I, Sahlén S, et al. Cloning, expression pattern, and chromosomal assignment to 16q23 of the human gamma-adaptin gene (ADTG). Genomics. 1998;50:275-80 pubmed
    ..e., the medium (AP47) and small (AP19) subunits, to chromosomes 19 and 7, respectively. Expression analysis of these genes in human tissues revealed ubiquitously expressed transcripts of approximately 2.5 and 1.5 kb, respectively. ..
  33. Chen A, Hu T, Mikoryak C, Draper R. Retrograde transport of protein toxins under conditions of COPI dysfunction. Biochim Biophys Acta. 2002;1589:124-39 pubmed
    ..In addition, the results suggest that certain toxins containing a KDEL motif may use either the COPI-dependent or COPI-independent pathway of retrograde transport. ..
  34. Moreno R. Differential expression of lysosomal associated membrane protein (LAMP-1) during mammalian spermiogenesis. Mol Reprod Dev. 2003;66:202-9 pubmed
    ..None of the studied proteins is present in epididymal spermatozoa. Our results suggest that the CI-MPR could be involved in membrane trafficking and/or acrosomal shaping during spermiogenesis. ..
  35. Neubrand V, Will R, Mobius W, Poustka A, Wiemann S, Schu P, et al. Gamma-BAR, a novel AP-1-interacting protein involved in post-Golgi trafficking. EMBO J. 2005;24:1122-33 pubmed
    ..This suggests that the direct interaction of 2c18 and gamma1-adaptin is crucial for membrane association and thus the function of the AP-1 complex in living cells. We propose to name this protein gamma-BAR. ..
  36. Wong S, Santambrogio L, Strominger J. Caspases and nitric oxide broadly regulate dendritic cell maturation and surface expression of class II MHC proteins. Proc Natl Acad Sci U S A. 2004;101:17783-8 pubmed
  37. Schledzewski K, Brinkmann H, Mendel R. Phylogenetic analysis of components of the eukaryotic vesicle transport system reveals a common origin of adaptor protein complexes 1, 2, and 3 and the F subcomplex of the coatomer COPI. J Mol Evol. 1999;48:770-8 pubmed
    ..The situation encountered today is the result of successive rounds of coordinated gene duplications of both the large and the small/medium subunits, with F-COPI being the first that separated from the ancestral pre-F-COPI...
  38. Hartmann Stühler C, Prange R. Hepatitis B virus large envelope protein interacts with gamma2-adaptin, a clathrin adaptor-related protein. J Virol. 2001;75:5343-51 pubmed
    ..Together, the results suggest a role for gamma2-adaptin in L-mediated processes of viral biogenesis and/or pathogenesis, such as facilitating and guiding HBV assembly. ..
  39. Mercanti V, Blanc C, Lefkir Y, Cosson P, Letourneur F. Acidic clusters target transmembrane proteins to the contractile vacuole in Dictyostelium cells. J Cell Sci. 2006;119:837-45 pubmed
    ..Together our results suggest the existence of an AP-1-dependent selective transport to the contractile vacuole in Dictyostelium. ..
  40. Orzech E, Livshits L, Leyt J, Okhrimenko H, Reich V, Cohen S, et al. Interactions between adaptor protein-1 of the clathrin coat and microtubules via type 1a microtubule-associated proteins. J Biol Chem. 2001;276:31340-8 pubmed
  41. Horikawa H, Kneussel M, El Far O, Betz H. Interaction of synaptophysin with the AP-1 adaptor protein gamma-adaptin. Mol Cell Neurosci. 2002;21:454-62 pubmed
    ..Our results are consistent with synaptophysin serving as a docking site for AP-1 during clathrin-dependent vesicle budding and/or kinesin-based transport reactions. ..
  42. Rost M, Mann S, Lambert C, Döring T, Thomé N, Prange R. Gamma-adaptin, a novel ubiquitin-interacting adaptor, and Nedd4 ubiquitin ligase control hepatitis B virus maturation. J Biol Chem. 2006;281:29297-308 pubmed
    ..Together, these data indicate that an enveloped DNA virus exploits a new ubiquitin receptor together with endosomal pathway functions for egress from hepatocytes. ..
  43. Hirst J, Lindsay M, Robinson M. GGAs: roles of the different domains and comparison with AP-1 and clathrin. Mol Biol Cell. 2001;12:3573-88 pubmed
    ..Together with results from other studies, our findings suggest that the GGAs act as monomeric adaptors, with the four domains involved in cargo selection, membrane localization, clathrin binding, and accessory protein recruitment. ..
  44. Yamaguchi T, Nakayama K, Hatsuzawa K, Tani K, Himeno M, Tagaya M. ADP-ribosylation factor-1 is sensitive to N-ethylmaleimide. J Biochem. 1998;124:1229-36 pubmed
    ..Concomitant with inactivation, 0.85 mol of N-ethylmaleimide was incorporated into 1 mol of ARF1. ARF1 contains only one cysteine residue (Cys-159), which is located near the base moiety of the bound guanine nucleotide. ..
  45. Miller G, Mattera R, Bonifacino J, Hurley J. Recognition of accessory protein motifs by the gamma-adaptin ear domain of GGA3. Nat Struct Biol. 2003;10:599-606 pubmed
  46. Takatsu H, Yoshino K, Nakayama K. Adaptor gamma ear homology domain conserved in gamma-adaptin and GGA proteins that interact with gamma-synergin. Biochem Biophys Res Commun. 2000;271:719-25 pubmed
  47. Perrin L, Laura P, Lacas Gervais S, Sandra L, Gilleron J, Jérôme G, et al. Rab4b controls an early endosome sorting event by interacting with the ?-subunit of the clathrin adaptor complex 1. J Cell Sci. 2013;126:4950-62 pubmed publisher
    ..The data also uncover a novel type of endosomes, characterised by low abundance of either early or recycling endocytic markers, which could potentially be generated in cell types that naturally express high level of Rab4b. ..
  48. Wadehra M, Goodglick L, Braun J. The tetraspan protein EMP2 modulates the surface expression of caveolins and glycosylphosphatidyl inositol-linked proteins. Mol Biol Cell. 2004;15:2073-83 pubmed
    ..These findings suggest that EMP2 facilitates the formation and surface trafficking of lipid rafts bearing GPI-APs, and reduces caveolin expression, resulting in impaired formation of caveolae. ..
  49. Wang E, Pennington J, Goldenring J, Hunziker W, Dunn K. Brefeldin A rapidly disrupts plasma membrane polarity by blocking polar sorting in common endosomes of MDCK cells. J Cell Sci. 2001;114:3309-21 pubmed
  50. Mattera R, Ritter B, Sidhu S, McPherson P, Bonifacino J. Definition of the consensus motif recognized by gamma-adaptin ear domains. J Biol Chem. 2004;279:8018-28 pubmed
    ..These findings shed light on the mechanism of accessory protein recruitment to trans-Golgi network and endosomal clathrin coats. ..
  51. Karlsson K, Carlsson S. Sorting of lysosomal membrane glycoproteins lamp-1 and lamp-2 into vesicles distinct from mannose 6-phosphate receptor/gamma-adaptin vesicles at the trans-Golgi network. J Biol Chem. 1998;273:18966-73 pubmed
    ..The results indicate that membrane proteins containing tyrosine-based motifs for sorting at the TGN are segregated from clathrin-coated vesicles containing MPRs. ..
  52. Kametaka S, Kametaka A, Yonekura S, Haruta M, Takenoshita S, Goto S, et al. AP-1 clathrin adaptor and CG8538/Aftiphilin are involved in Notch signaling during eye development in Drosophila melanogaster. J Cell Sci. 2012;125:634-48 pubmed publisher
    ..These results suggest that AP-1 and Aftiphilin are cooperatively involved in the intracellular trafficking of Notch during eye development in Drosophila. ..
  53. O Callaghan D, Ivings L, Weiss J, Ashby M, Tepikin A, Burgoyne R. Differential use of myristoyl groups on neuronal calcium sensor proteins as a determinant of spatio-temporal aspects of Ca2+ signal transduction. J Biol Chem. 2002;277:14227-37 pubmed
    ..These results demonstrate that closely related Ca(2+) sensor proteins use their myristoyl groups in distinct ways in vivo in a manner that will determine the time course of Ca(2+) signal transduction. ..