Gene Symbol: AP2A2
Description: adaptor related protein complex 2 subunit alpha 2
Alias: ADTAB, CLAPA2, HIP-9, HIP9, HYPJ, AP-2 complex subunit alpha-2, 100 kDa coated vesicle protein C, adapter-related protein complex 2 subunit alpha-2, adaptin, alpha B, adaptor related protein complex 2 alpha 2 subunit, alpha-adaptin C; Huntingtin interacting protein J, alpha2-adaptin, clathrin assembly protein complex 2 alpha-C large chain, clathrin-associated/assembly/adaptor protein, large, alpha 2, huntingtin yeast partner J, huntingtin-interacting protein 9, plasma membrane adaptor HA2/AP2 adaptin alpha C subunit
Species: human
Products:     AP2A2

Top Publications

  1. Batonick M, Favre M, Boge M, Spearman P, Honing S, Thali M. Interaction of HIV-1 Gag with the clathrin-associated adaptor AP-2. Virology. 2005;342:190-200 pubmed
    ..Together these data attribute a role to the AP-2 complex in the regulation of HIV-1 assembly/release. ..
  2. Bean A, Davanger S, Chou M, Gerhardt B, Tsujimoto S, Chang Y. Hrs-2 regulates receptor-mediated endocytosis via interactions with Eps15. J Biol Chem. 2000;275:15271-8 pubmed
    ..These data show that Hrs-2 regulates endocytosis, delineate a biochemical pathway (Hrs-2-Eps15-AP2) in which Hrs-2 functions, and suggest that Hrs-2 acts to provide communication between endo- and exocytic processes. ..
  3. Benmerah A, Begue B, Dautry Varsat A, Cerf Bensussan N. The ear of alpha-adaptin interacts with the COOH-terminal domain of the Eps 15 protein. J Biol Chem. 1996;271:12111-6 pubmed
    ..Our data indicate that this specific part of AP-2 binds to a cellular component and provide the tools for investigating the functions of the association between AP-2 and Eps15. ..
  4. Robinson M. Cloning of cDNAs encoding two related 100-kD coated vesicle proteins (alpha-adaptins). J Cell Biol. 1989;108:833-42 pubmed
    ..Antipeptide antibodies are now being raised to find out whether the proteins are localized in functionally distinct populations of endocytic coated vesicles. ..
  5. David C, McPherson P, Mundigl O, De Camilli P. A role of amphiphysin in synaptic vesicle endocytosis suggested by its binding to dynamin in nerve terminals. Proc Natl Acad Sci U S A. 1996;93:331-5 pubmed
    ..These findings support a role of amphiphysin in synaptic vesicle endocytosis. ..
  6. van Delft S, Schumacher C, Hage W, Verkleij A, van Bergen en Henegouwen P. Association and colocalization of Eps15 with adaptor protein-2 and clathrin. J Cell Biol. 1997;136:811-21 pubmed
    ..These findings suggest that Eps15 may play a critical role in the recruitment of active EGF receptors into coated pit regions before endocytosis of ligand-occupied EGF receptors. ..
  7. Checkley M, Luttge B, Freed E. HIV-1 envelope glycoprotein biosynthesis, trafficking, and incorporation. J Mol Biol. 2011;410:582-608 pubmed publisher
    ..Here, we review our current understanding of HIV-1 Env glycoprotein trafficking and incorporation into virions. ..
  8. Byland R, Vance P, Hoxie J, Marsh M. A conserved dileucine motif mediates clathrin and AP-2-dependent endocytosis of the HIV-1 envelope protein. Mol Biol Cell. 2007;18:414-25 pubmed
  9. Berlioz Torrent C, Shacklett B, Erdtmann L, Delamarre L, Bouchaert I, Sonigo P, et al. Interactions of the cytoplasmic domains of human and simian retroviral transmembrane proteins with components of the clathrin adaptor complexes modulate intracellular and cell surface expression of envelope glycoproteins. J Virol. 1999;73:1350-61 pubmed

More Information


  1. Chen H, Fre S, Slepnev V, Capua M, Takei K, Butler M, et al. Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis. Nature. 1998;394:793-7 pubmed
    ..We propose that epsin may participate, together with Eps15, in the molecular rearrangement of the clathrin coats that are required for coated-pit invagination and vesicle fission. ..
  2. Rowland K, Saelao P, Wang Y, Fulton J, Liebe G, McCarron A, et al. Association of Candidate Genes with Response to Heat and Newcastle Disease Virus. Genes (Basel). 2018;9: pubmed publisher
    ..i>SLC5A1, HSPB1, HSPA2, HSPA8, IFRD1, IL18R1, IL1R1, AP2A2, and TOLLIP...
  3. Wang S, Ma Z, Zhang Y, Ding Y, Chen Z, Wang L. A genetic variant near adaptor-related protein complex 2 alpha 2 subunit gene is associated with coronary artery disease in a Chinese population. BMC Cardiovasc Disord. 2018;18:161 pubmed publisher
    Adaptor-related protein complex 2 alpha 2 subunit (AP2A2) gene encodes a protein-a subunit of the AP-2 adaptor protein complex...
  4. Riffo Campos A, Fuentes Trillo A, Tang W, Soriano Z, de Marco G, Rentero Garrido P, et al. In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men: pilot results from the Aragon Workers Health Study. Philos Trans R Soc Lond B Biol Sci. 2018;373: pubmed publisher
    ..g. SSTR5, HDAC4, AP2A2, CXCL12 and SSTR4)...
  5. Chen C, Nguyen B, Mitchell G, Margolis S, Ma D, Portnoy D. The Listeriolysin O PEST-like Sequence Co-opts AP-2-Mediated Endocytosis to Prevent Plasma Membrane Damage during Listeria Infection. Cell Host Microbe. 2018;23:786-795.e5 pubmed publisher
    ..LLO interacts with Ap2a2, an adaptor protein involved in endocytosis, via its PEST-like sequence, and Ap2a2-dependent endocytosis is ..
  6. Saafan H, Foerster S, Parra Guillén Z, Hammer E, Michaelis M, Cinatl J, et al. Utilising the EGFR interactome to identify mechanisms of drug resistance in non-small cell lung cancer - Proof of concept towards a systems pharmacology approach. Eur J Pharm Sci. 2016;94:20-32 pubmed publisher
    ..with an increase of protein levels of members of the clathrin-associated adaptor protein family AP2 (AP2A1, AP2A2, AP2B1), structural proteins of cytoskeleton rearrangement as well as signalling molecules such as Shc...
  7. Poorhosseini S, Hashemi M, Alipour Olyaei N, Izadi A, Moslemi E, Ravesh Z, et al. New Gene Profiling in Determination of Breast Cancer Recurrence and Prognosis in Iranian Women. Asian Pac J Cancer Prev. 2016;17:155-60 pubmed
    ..The objective of this study was to examine the gene expression profiles of SIRT3, HRAS, LSP1, SCUBE2 and AP2A2 in Iranian women with BC...
  8. Krieger J, Taylor P, Gajadhar A, Guha A, Moran M, McGlade C. Identification and selected reaction monitoring (SRM) quantification of endocytosis factors associated with Numb. Mol Cell Proteomics. 2013;12:499-514 pubmed publisher
    ..Hence, quantitative mass spectrometric analysis of Numb protein-protein interactions has provided new insights into the assembly and regulation of protein complexes important in development and cancer. ..
  9. Lindwasser O, Smith W, Chaudhuri R, Yang P, Hurley J, Bonifacino J. A diacidic motif in human immunodeficiency virus type 1 Nef is a novel determinant of binding to AP-2. J Virol. 2008;82:1166-74 pubmed
  10. Kadlecova Z, Spielman S, Loerke D, Mohanakrishnan A, Reed D, Schmid S. Regulation of clathrin-mediated endocytosis by hierarchical allosteric activation of AP2. J Cell Biol. 2017;216:167-179 pubmed publisher
    ..Thus, we speculate that AP2 has evolved as a key regulatory node to coordinate CCP formation and cargo sorting and ensure high spatial and temporal regulation of CME. ..
  11. Lu W, Ziff E. PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron. 2005;47:407-21 pubmed
    ..We suggest that the PICK1 interaction with ABP/GRIP is a critical step in controlling GluR2 trafficking. ..
  12. Yano H, Lee F, Kong H, Chuang J, Arevalo J, Perez P, et al. Association of Trk neurotrophin receptors with components of the cytoplasmic dynein motor. J Neurosci. 2001;21:RC125 pubmed
    ..The association of Trk receptors with components of cytoplasmic dynein suggests that transport of neurotrophins during vesicular trafficking may occur through a direct interaction of the Trk receptor with the dynein motor machinery. ..
  13. Rappoport J, Taha B, Lemeer S, Benmerah A, Simon S. The AP-2 complex is excluded from the dynamic population of plasma membrane-associated clathrin. J Biol Chem. 2003;278:47357-60 pubmed
    ..These results suggest that colocalized clathrin/AP-2 puncta may represent loci for coated pit production and that previous models that assumed AP-2 was retained within clathrin coats during endocytosis may need to be re-evaluated. ..
  14. Rosenthal J, Chen H, Slepnev V, Pellegrini L, Salcini A, Di Fiore P, et al. The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module. J Biol Chem. 1999;274:33959-65 pubmed
    ..The epsins define a new protein family implicated in membrane dynamics at the cell surface. ..
  15. Mizutani A, Saitoh M, Imamura T, Miyazawa K, Miyazono K. Arkadia complexes with clathrin adaptor AP2 and regulates EGF signalling. J Biochem. 2010;148:733-41 pubmed publisher
    ..Arkadia thus appears to regulate EGF signalling by modulating endocytosis of EGFR through interaction with AP2 complex. ..
  16. Slepnev V, Ochoa G, Butler M, De Camilli P. Tandem arrangement of the clathrin and AP-2 binding domains in amphiphysin 1 and disruption of clathrin coat function by amphiphysin fragments comprising these sites. J Biol Chem. 2000;275:17583-9 pubmed
  17. Ramjaun A, Micheva K, Bouchelet I, McPherson P. Identification and characterization of a nerve terminal-enriched amphiphysin isoform. J Biol Chem. 1997;272:16700-6 pubmed
    ..Further, both proteins bind directly to clathrin in an SH3 domain-independent manner. Taken together, these data suggest that amphiphysin II may participate with amphiphysin I in the regulation of synaptic vesicle endocytosis. ..
  18. Mankouri J, Taneja T, Smith A, Ponnambalam S, Sivaprasadarao A. Kir6.2 mutations causing neonatal diabetes prevent endocytosis of ATP-sensitive potassium channels. EMBO J. 2006;25:4142-51 pubmed
    ..The data imply that endocytosis of KATP channels plays a crucial role in the (patho)-physiology of insulin secretion...
  19. Brett T, Traub L, Fremont D. Accessory protein recruitment motifs in clathrin-mediated endocytosis. Structure. 2002;10:797-809 pubmed
    ..A mechanism of clathrin assembly regulation is suggested by three different AP-2 engagement modes. ..
  20. Leprince C, Romero F, Cussac D, Vayssiere B, Berger R, Tavitian A, et al. A new member of the amphiphysin family connecting endocytosis and signal transduction pathways. J Biol Chem. 1997;272:15101-5 pubmed
    ..This hypothesis is strengthened by the ability of BRAMP2 to interact with the p21(ras) exchange factor SOS, in vitro, as a possible point of interconnection between the endocytic and signaling pathways. ..
  21. Miller S, Mathiasen S, Bright N, Pierre F, Kelly B, Kladt N, et al. CALM regulates clathrin-coated vesicle size and maturation by directly sensing and driving membrane curvature. Dev Cell. 2015;33:163-75 pubmed publisher
    ..CALM is thus a major factor in controlling CCV size and maturation and hence in determining the rates of endocytic cargo uptake. ..
  22. Shimada A, Yamaguchi A, Kohda D. Structural basis for the recognition of two consecutive mutually interacting DPF motifs by the SGIP1 μ homology domain. Sci Rep. 2016;6:19565 pubmed publisher
    ..Thus, consecutive and singly scattered DPF motifs play distinct roles in μHD binding. ..
  23. Roxrud I, Raiborg C, Pedersen N, Stang E, Stenmark H. An endosomally localized isoform of Eps15 interacts with Hrs to mediate degradation of epidermal growth factor receptor. J Cell Biol. 2008;180:1205-18 pubmed publisher
    ..These results indicate that Eps15b is an endosomally localized isoform of Eps15 that is present in the Hrs complex via direct Hrs interaction and important for the sorting function of this complex. ..
  24. Palicharla V, Maddika S. HACE1 mediated K27 ubiquitin linkage leads to YB-1 protein secretion. Cell Signal. 2015;27:2355-62 pubmed publisher
    ..In summary, we identified a novel functional role for non-canonical ubiquitin linkages in mediating protein secretion. ..
  25. McMahon H, Wigge P, Smith C. Clathrin interacts specifically with amphiphysin and is displaced by dynamin. FEBS Lett. 1997;413:319-22 pubmed
    ..Dynamin, which interacts with the SH3 domain of Amph2, displaces clathrin from the N-terminus. We propose a model that may explain how clathrin and dynamin are recruited to non-overlapping sites of the coated pit. ..
  26. Collins B, McCoy A, Kent H, Evans P, Owen D. Molecular architecture and functional model of the endocytic AP2 complex. Cell. 2002;109:523-35 pubmed
    ..A model for AP2 recruitment and activation is proposed. ..
  27. Stove V, Van de Walle I, Naessens E, Coene E, Stove C, Plum J, et al. Human immunodeficiency virus Nef induces rapid internalization of the T-cell coreceptor CD8alphabeta. J Virol. 2005;79:11422-33 pubmed
    ..The Nef-mediated internalization of receptors, such as CD4, major histocompatibility complex class I, CD28, and CD8alphabeta, may contribute to the subversion of the host immune system and progression towards AIDS. ..
  28. Boll W, Rapoport I, Brunner C, Modis Y, Prehn S, Kirchhausen T. The mu2 subunit of the clathrin adaptor AP-2 binds to FDNPVY and YppØ sorting signals at distinct sites. Traffic. 2002;3:590-600 pubmed
    ..These results suggest the possibility that low-density lipoprotein receptor uptake may be modulated specifically and independently of other proteins in the clathrin pathway. ..
  29. Morris S, Cooper J. Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2. Traffic. 2001;2:111-23 pubmed
    ..These findings suggest that in addition to previously reported signal-transduction functions, Dab2 could also act as an adaptor protein that may regulate protein trafficking...
  30. von Bredow B, Arias J, Heyer L, Gardner M, Farzan M, Rakasz E, et al. Envelope Glycoprotein Internalization Protects Human and Simian Immunodeficiency Virus-Infected Cells from Antibody-Dependent Cell-Mediated Cytotoxicity. J Virol. 2015;89:10648-55 pubmed publisher
  31. Vermeire J, Vanbillemont G, Witkowski W, Verhasselt B. The Nef-infectivity enigma: mechanisms of enhanced lentiviral infection. Curr HIV Res. 2011;9:474-89 pubmed
    ..Hereby we aim to contribute to a better understanding of this highly conserved and therapeutically attractive Nef function. ..
  32. Boehm M, Aguilar R, Bonifacino J. Functional and physical interactions of the adaptor protein complex AP-4 with ADP-ribosylation factors (ARFs). EMBO J. 2001;20:6265-76 pubmed
    ..These observations establish AP-4 as an ARF1 effector and suggest a novel mode of interaction between ARF1 and an AP complex involving both constitutive and regulated interactions. ..
  33. Scheele U, Kalthoff C, Ungewickell E. Multiple interactions of auxilin 1 with clathrin and the AP-2 adaptor complex. J Biol Chem. 2001;276:36131-8 pubmed
    ..The multiple protein-protein interactions of auxilin 1 suggest that its function in endocytic trafficking may be more complex than previously anticipated. ..
  34. Kirchhausen T. Clathrin. Annu Rev Biochem. 2000;69:699-727 pubmed
    ..This review summarizes and illustrates the recent structural results and outlines what is known about coated-vesicle assembly in the context of this information. ..
  35. Knuehl C, Chen C, Manalo V, Hwang P, Ota N, Brodsky F. Novel binding sites on clathrin and adaptors regulate distinct aspects of coat assembly. Traffic. 2006;7:1688-700 pubmed
    ..Thus, the distinct sites for clathrin-adaptor interactions perform distinct functions, revealing new aspects to regulation of CCV formation. ..
  36. Traub L, Downs M, Westrich J, Fremont D. Crystal structure of the alpha appendage of AP-2 reveals a recruitment platform for clathrin-coat assembly. Proc Natl Acad Sci U S A. 1999;96:8907-12 pubmed
  37. Jullien Flores V, Mahe Y, Mirey G, Leprince C, Meunier Bisceuil B, Sorkin A, et al. RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis. J Cell Sci. 2000;113 ( Pt 16):2837-44 pubmed
  38. Scorilas A, Levesque M, Ashworth L, Diamandis E. Cloning, physical mapping and structural characterization of the human alpha(A)-adaptin gene. Gene. 2002;289:191-9 pubmed
    ..It is also ubiquitously expressed in tissues and in ZR-75-1 breast cancer cells and LNCaP prostate carcinoma cells as a smaller variant generated by splicing out of an exon encoding 22 amino acids in the hinge region of the protein. ..
  39. Vendeville A, Rayne F, Bonhoure A, Bettache N, Montcourrier P, Beaumelle B. HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses. Mol Biol Cell. 2004;15:2347-60 pubmed
    ..Hence, Tat enters T cells essentially like diphtheria toxin, using clathrin-mediated endocytosis before low-pH-induced and Hsp90-assisted endosomal translocation. Cell responses are then induced from the cytosol. ..
  40. Santos da Silva E, Mulinge M, Perez Bercoff D. The frantic play of the concealed HIV envelope cytoplasmic tail. Retrovirology. 2013;10:54 pubmed publisher
    ..It also considers the cellular and viral proteins that have been described to interact with the gp41-CT, with a particular focus on subtype-related polymorphisms. ..
  41. Smith C, Lau K, Rahmani Z, Dho S, Brothers G, She Y, et al. aPKC-mediated phosphorylation regulates asymmetric membrane localization of the cell fate determinant Numb. EMBO J. 2007;26:468-80 pubmed
    ..These results suggest a model in which phosphorylation of Numb by aPKC regulates its polarized distribution in epithelial cells as well as during asymmetric cell divisions. ..
  42. Garcia J, Miller A. Serine phosphorylation-independent downregulation of cell-surface CD4 by nef. Nature. 1991;350:508-11 pubmed
    ..Also, nef can downregulate a CD4 triple mutant (Ser----Ala) that is neither phosphorylated nor down-regulated by phorbol esters, indicating that nef is acting by a different mechanism. ..
  43. Ono A. HIV-1 Assembly at the Plasma Membrane: Gag Trafficking and Localization. Future Virol. 2009;4:241-257 pubmed
    ..In addition, findings on Gag association with specific plasma membrane domains are discussed in light of potential roles in cell-to-cell transmission. ..
  44. Wollscheid H, Biancospino M, He F, Magistrati E, Molteni E, Lupia M, et al. Diverse functions of myosin VI elucidated by an isoform-specific α-helix domain. Nat Struct Mol Biol. 2016;23:300-308 pubmed publisher
    ..Thus, the α2-linker acts like a molecular switch that assigns myosin VI to distinct endocytic (myosin VI(long)) or migratory (myosin VI(short)) functional roles. ..
  45. Faber P, Barnes G, Srinidhi J, Chen J, Gusella J, MacDonald M. Huntingtin interacts with a family of WW domain proteins. Hum Mol Genet. 1998;7:1463-74 pubmed
    ..The emergence of this class of proteins as huntingtin partners argues that a WW domain-mediated process, such as non-receptor signaling, protein degradation or pre-mRNA splicing, may participate in HD pathogenesis. ..
  46. Okabayashi Y, Sugimoto Y, Totty N, Hsuan J, Kido Y, Sakaguchi K, et al. Interaction of Shc with adaptor protein adaptins. J Biol Chem. 1996;271:5265-9 pubmed
    ..Thus, this study indicates the specific interaction of Shc with alpha- and beta-adaptin components of plasma membrane adaptor proteins that are thought to be involved in receptor endocytosis. ..
  47. Lee J, Cho M, Hersh C, McDonald M, Crapo J, Bakke P, et al. Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease. Respir Res. 2014;15:113 pubmed publisher
    ..We found genome-wide significant associations with CB COPD on 4q22.1 (FAM13A) and 11p15.5 (EFCAB4A, CHID1 and AP2A2), and a locus associated with CB within COPD subjects on 1q23.3 (RPL31P11 and ATF6)...
  48. Masuyama N, Kuronita T, Tanaka R, Muto T, Hirota Y, Takigawa A, et al. HM1.24 is internalized from lipid rafts by clathrin-mediated endocytosis through interaction with alpha-adaptin. J Biol Chem. 2009;284:15927-41 pubmed publisher
    ..24 but not of the transferrin receptor. Taken together, our findings suggest that clathrin-dependent endocytosis of human HM1.24 from the cell surface lipid rafts is mediated by direct interaction with alpha-adaptin. ..
  49. Lubben N, Sahlender D, Motley A, Lehner P, Benaroch P, Robinson M. HIV-1 Nef-induced down-regulation of MHC class I requires AP-1 and clathrin but not PACS-1 and is impeded by AP-2. Mol Biol Cell. 2007;18:3351-65 pubmed
    ..We propose that depleting AP-2 potentiates Nef activity by altering the membrane composition and dynamics of endosomes and causing increased delivery of HLA-A2 to a prelysosomal compartment. ..
  50. Bukrinskaya A. HIV-1 matrix protein: a mysterious regulator of the viral life cycle. Virus Res. 2007;124:1-11 pubmed
    ..It is suggested that two MA fractions possess diverse functions and are involved in different stages of virus morphogenesis as key regulators of the viral life cycle. ..
  51. Schmidt U, Briese S, Leicht K, Schurmann A, Joost H, Al Hasani H. Endocytosis of the glucose transporter GLUT8 is mediated by interaction of a dileucine motif with the beta2-adaptin subunit of the AP-2 adaptor complex. J Cell Sci. 2006;119:2321-31 pubmed
  52. 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. ..
  53. Gallicchio M, Bach L. Advanced glycation end products inhibit Na+ K+ ATPase in proximal tubule epithelial cells: role of cytosolic phospholipase A2alpha and phosphatidylinositol 4-phosphate 5-kinase gamma. Biochim Biophys Acta. 2010;1803:919-30 pubmed publisher
    ..Elucidation of new intracellular AGE signaling pathways may lead to improved therapies for diabetic nephropathy...
  54. Chaudhuri R, Mattera R, Lindwasser O, Robinson M, Bonifacino J. A basic patch on alpha-adaptin is required for binding of human immunodeficiency virus type 1 Nef and cooperative assembly of a CD4-Nef-AP-2 complex. J Virol. 2009;83:2518-30 pubmed publisher
    ..This cooperativity explains how Nef is able to efficiently downregulate CD4 despite weak binary interactions between components of the tripartite complex. ..