Gene Symbol: Ap2a2
Description: adaptor-related protein complex 2, alpha 2 subunit
Alias: AP-2 complex subunit alpha-2, 100 kDa coated vesicle protein C, adapter-related protein complex 2 alpha-2 subunit, adapter-related protein complex 2 subunit alpha-2, adaptor protein complex AP-2 subunit alpha-2, adaptor protein complex AP-2, alpha 2 subunit, adaptor-related protein complex 2 subunit alpha-2, alpha-adaptin C, alpha2-adaptin, clathrin assembly protein complex 2 alpha-C large chain, plasma membrane adaptor HA2/AP2 adaptin alpha C subunit
Species: rat
Products:     Ap2a2

Top Publications

  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. 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. ..
  3. Chapman E, Desai R, Davis A, Tornehl C. Delineation of the oligomerization, AP-2 binding, and synprint binding region of the C2B domain of synaptotagmin. J Biol Chem. 1998;273:32966-72 pubmed
    ..These studies provide the first structural information regarding C2B target protein recognition and provide the means to selectively disrupt synaptotagmin-effector interactions for functional studies. ..
  4. Di Paolo G, Sankaranarayanan S, Wenk M, Daniell L, Perucco E, Caldarone B, et al. Decreased synaptic vesicle recycling efficiency and cognitive deficits in amphiphysin 1 knockout mice. Neuron. 2002;33:789-804 pubmed
    ..These defects correlate with increased mortality due to rare irreversible seizures and with major learning deficits, suggesting a critical role of amphiphysin for higher brain functions. ..
  5. Tucker K, Nathanson K, Kirchhausen T. Sequence of the rat alpha c large chain of the clathrin associated protein complex AP-2. Nucleic Acids Res. 1990;18:5306 pubmed
  6. Scheele U, Alves J, Frank R, Duwel M, Kalthoff C, Ungewickell E. Molecular and functional characterization of clathrin- and AP-2-binding determinants within a disordered domain of auxilin. J Biol Chem. 2003;278:25357-68 pubmed
    ..Like AP180, auxilin also directly interacts with the ear domain of beta-adaptin. On the basis of our data, we propose a refined model for the uncoating mechanism of clathrin-coated vesicles. ..
  7. Jarousse N, Kelly R. The AP2 binding site of synaptotagmin 1 is not an internalization signal but a regulator of endocytosis. J Cell Biol. 2001;154:857-66 pubmed
    ..We propose that internalization of synaptotagmin 1 is regulated in this way to allow it to couple the processes of endocytosis and calcium-mediated exocytosis in cells of the neuroendocrine lineage. ..
  8. Bahler M, Klein R, Wang J, Benfenati F, Greengard P. A novel synaptic vesicle-associated phosphoprotein: SVAPP-120. J Neurochem. 1991;57:423-30 pubmed
    ..In addition, aldolase, a glycolytic enzyme, and alpha c-adaptin, a clathrin assembly-promoting protein, were identified on purified synaptic vesicles by direct protein sequencing. ..
  9. Duncker S, Franz C, Kuhn S, Schulte U, Campanelli D, Brandt N, et al. Otoferlin couples to clathrin-mediated endocytosis in mature cochlear inner hair cells. J Neurosci. 2013;33:9508-19 pubmed publisher
    ..We suggest that an otoferlin-AP-2 interaction drives Ca(2+)- and stimulus-dependent compensating CME in mature IHCs. ..

More Information


  1. Collaco A, Jakab R, Hegan P, Mooseker M, Ameen N. Alpha-AP-2 directs myosin VI-dependent endocytosis of cystic fibrosis transmembrane conductance regulator chloride channels in the intestine. J Biol Chem. 2010;285:17177-87 pubmed publisher
    ..The findings support alpha-AP-2 in directing myosin VI-dependent endocytosis of CFTR and a requirement for myosin VI in membrane invagination and coated pit formation in enterocytes. ..
  2. Mishra S, Keyel P, Hawryluk M, Agostinelli N, Watkins S, Traub L. Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor. EMBO J. 2002;21:4915-26 pubmed
  3. Drake M, Downs M, Traub L. Epsin binds to clathrin by associating directly with the clathrin-terminal domain. Evidence for cooperative binding through two discrete sites. J Biol Chem. 2000;275:6479-89 pubmed
  4. 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. ..
  5. Kirchhausen T, Nathanson K, Matsui W, Vaisberg A, Chow E, Burne C, et al. Structural and functional division into two domains of the large (100- to 115-kDa) chains of the clathrin-associated protein complex AP-2. Proc Natl Acad Sci U S A. 1989;86:2612-6 pubmed
    ..Their amino-terminal domains are relatively invariant whereas their carboxyl-terminal domains are variable in both sequence and length. We propose that the variable domains select receptors for inclusion in coated vesicles. ..
  6. Kalthoff C, Alves J, Urbanke C, Knorr R, Ungewickell E. Unusual structural organization of the endocytic proteins AP180 and epsin 1. J Biol Chem. 2002;277:8209-16 pubmed
  7. Ritter B, Denisov A, Philie J, Allaire P, Legendre Guillemin V, Zylbergold P, et al. The NECAP PHear domain increases clathrin accessory protein binding potential. EMBO J. 2007;26:4066-77 pubmed
    ..Our data uncover a striking convergence of two evolutionarily and structurally distinct modules to recognize a common peptide motif and promote efficient endocytosis. ..
  8. Tokumitsu H, Hatano N, Yokokura S, Sueyoshi Y, Nozaki N, Kobayashi R. Phosphorylation of Numb regulates its interaction with the clathrin-associated adaptor AP-2. FEBS Lett. 2006;580:5797-801 pubmed
    ..These findings suggest a novel mechanism for the regulation of Numb-mediated endocytosis, namely through direct phosphorylation. ..
  9. Zhang Y, Moheban D, Conway B, Bhattacharyya A, Segal R. Cell surface Trk receptors mediate NGF-induced survival while internalized receptors regulate NGF-induced differentiation. J Neurosci. 2000;20:5671-8 pubmed
    ..Thus, interactions between Trk receptor tyrosine kinases and intracellular signaling molecules are dictated both by phosphotyrosine motifs within the receptors and by the intracellular location of phosphorylated receptors. ..
  10. Chen C, Brodsky F. Huntingtin-interacting protein 1 (Hip1) and Hip1-related protein (Hip1R) bind the conserved sequence of clathrin light chains and thereby influence clathrin assembly in vitro and actin distribution in vivo. J Biol Chem. 2005;280:6109-17 pubmed
    ..Together these results suggest that the roles of Hip1 and Hip1R in affecting clathrin assembly and actin distribution are mediated by their interaction with the conserved sequence of clathrin light chains. ..
  11. Saheki Y, De Camilli P. Synaptic vesicle endocytosis. Cold Spring Harb Perspect Biol. 2012;4:a005645 pubmed publisher
  12. Ting S, Deneault E, Hope K, Cellot S, Chagraoui J, Mayotte N, et al. Asymmetric segregation and self-renewal of hematopoietic stem and progenitor cells with endocytic Ap2a2. Blood. 2012;119:2510-22 pubmed publisher
    ..screen on a subcohort of candidate polarity genes, which revealed 6 novel positive regulators of HSC function: Ap2a2, Gpsm2, Tmod1, Kif3a, Racgap1, and Ccnb1...
  13. Lavezzari G, McCallum J, Lee R, Roche K. Differential binding of the AP-2 adaptor complex and PSD-95 to the C-terminus of the NMDA receptor subunit NR2B regulates surface expression. Neuropharmacology. 2003;45:729-37 pubmed
  14. 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. ..
  15. 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. ..
  16. Burman J, Wasiak S, Ritter B, de Heuvel E, McPherson P. Aftiphilin is a component of the clathrin machinery in neurons. FEBS Lett. 2005;579:2177-84 pubmed
    ..Aftiphilin is also found at synapses where it co-localizes with synaptophysin and AP-2. Our data suggest a role for aftiphilin in clathrin-mediated trafficking in neurons. ..
  17. Walther K, Diril M, Jung N, Haucke V. Functional dissection of the interactions of stonin 2 with the adaptor complex AP-2 and synaptotagmin. Proc Natl Acad Sci U S A. 2004;101:964-9 pubmed
    ..We hypothesize that stonin 2 may function as an AP-2-dependent sorting adaptor for synaptic vesicle recycling. ..
  18. Chen H, Slepnev V, Di Fiore P, De Camilli P. The interaction of epsin and Eps15 with the clathrin adaptor AP-2 is inhibited by mitotic phosphorylation and enhanced by stimulation-dependent dephosphorylation in nerve terminals. J Biol Chem. 1999;274:3257-60 pubmed
  19. Smith K, Muir J, Rao Y, Browarski M, Gruenig M, Sheehan D, et al. Stabilization of GABA(A) receptors at endocytic zones is mediated by an AP2 binding motif within the GABA(A) receptor ?3 subunit. J Neurosci. 2012;32:2485-98 pubmed publisher
    ..Thus, AP2 binding to an RRR motif in the GABA(A)R ?3-subunit ICD regulates GABA(A)R residency time at EZs, steady-state synaptic receptor levels, and pathological loss of GABA(A)Rs from synapses during simulated ischemia. ..
  20. Voglmaier S, Keen J, Murphy J, Ferris C, Prestwich G, Snyder S, et al. Inositol hexakisphosphate receptor identified as the clathrin assembly protein AP-2. Biochem Biophys Res Commun. 1992;187:158-63 pubmed
    ..The IP6 receptor protein analyzed by SDS-PAGE contains a series of subunits which are the same as those of AP-2. Antibodies to AP-2 react with the IP6 receptor protein in immunoblot analysis...