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Gene Review

AP2M1  -  adaptor-related protein complex 2, mu 1...

Homo sapiens

Synonyms: AP-2 complex subunit mu, AP-2 mu chain, AP50, Adaptin-mu2, Adaptor protein complex AP-2 subunit mu, ...
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Disease relevance of AP2M1

  • The binding domain of AP50 (residues 164-435) was expressed in Escherichia coli and purified [1].
  • In addition, EIAV late domain mutants containing mutations that have previously been shown to abrogate budding also exhibit marked decreases in AP-50 binding efficiencies [2].
  • We therefore developed a hemolysis test with rabbit erythrocytes (E), which have an activating surface for the alternative complement pathway and express abundant amounts of Galalpha1-3Gal, and used this assay in addition to the standard complement tests CH50 and AP50 [3].
  • DESIGN: Classical (CH50) and alternative (AP50) complement activity and serum levels of factors C1q, C3, C4, C3d, B, D, and P in CAPD patients were compared to normal controls and to children with preterminal renal failure [4].
  • The purpose of this study was to design specific PCR primers for five phylotypes AP12, AP21, AP24, AP50, and RP58, which are deeply branched particularly in the phylogenetic tree, and determine the prevalence of these phylotypes in 45 patients with periodontitis and 18 healthy subjects [5].

High impact information on AP2M1

  • We also found that AP50 bound to a CTLA-4 peptide containing unphosphorylated Y201 but not to a peptide containing phosphorylated Y201 [6].
  • The B cell coreceptor CD22 associates with AP50, a clathrin-coated pit adapter protein, via tyrosine-dependent interaction [7].
  • This inhibition is not reversed upon treatment of the AP50-depleted enzyme with dithiothreitol in the absence of AP50 [8].
  • We have previously shown that the 50-kDa subunit of the clathrin assembly complex AP-2 (AP50) stoichiometrically binds to and is immunoprecipitated with the vacuolar (H+)-ATPase (V-ATPase) from clathrin-coated vesicles (Myers, M., and Forgac, M. (1993) J. Biol. Chem. 268, 9184-9186) [8].
  • We now report that treatment of stripped coated vesicles with cystine results in a purified V-ATPase complex lacking the AP50 polypeptide [8].

Biological context of AP2M1

  • Chromosomal in situ hybridization of a human genomic clone demonstrated that the CLAPM1 gene mapped to chromosome region 3q28 [9].
  • Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression [10].
  • This interaction was further characterized using yeast two-hybrid analysis revealing that Tyr(843) and surrounding amino acids in the cytoplasmic tail of CD22 comprise the primary binding site for AP50 [7].
  • The medium chain mu 2 subunit (AP50) of the clathrin-associated adapter protein complex 2 (AP-2) interacts specifically with the tyrosine-based signals of several integral membrane proteins through the consensus sequence YXXPhi, where X can be any residue and Phi is a large hydrophobic residue [1].
  • In the HFOV group, AP50 remained significantly higher than in the CV group, reflecting less complement activation, and platelet function analysis remained significantly lower, reflecting better platelet function [11].

Anatomical context of AP2M1


Associations of AP2M1 with chemical compounds

  • Removal of AP50 can be reversed upon treatment of the vesicles with dithiothreitol [8].
  • The H deficiency was defined by undetectable CH50 and AP50, and low levels of H, C3 and B (less than 10% of normal levels) [12].
  • The levels of C3 and C4 and the CH50 and AP50 were found to be within the normal range [13].
  • SUBJECTS AND METHODS: We measured the complement system's activities (CH50 and AP50) as well as its various components (C1q,r,s, C2-C9, Factor B, and properdin) in 25 preterm infants [gestational age (GA) 28-33 weeks], 35 preterm infants (GA 34-36 weeks), 50 full-term newborn infants (GA 37-42 weeks), and 49 healthy adults as control subjects [14].

Physical interactions of AP2M1

  • The cytoplasmic domain of CTLA-4 was found to specifically bind to AP50, the medium chain subunit of AP-2 in both yeast two-hybrid and coimmunoprecipitation assays [10].

Regulatory relationships of AP2M1

  • Together these data suggest that the interaction of CTLA-4 with AP50 plays an important role in regulating the cell surface expression of CTLA-4 [10].

Other interactions of AP2M1

  • We have determined human chromosomal locations of genes for a large AP2 beta (CLAPB1) and a medium (CLAPM1) AP subunit and of a novel clathrin-binding protein, VCP, that binds clathrin simultaneously with APs [9].
  • Disruption of the clathrin-mediated endocytosis with the dominant-negative mutants Eps15 or AP-50 abolished the ivermectin potentiation of wild-type P2X(4) channel currents [15].

Analytical, diagnostic and therapeutic context of AP2M1

  • AP50 and CH50 values fell to about 60% of the initial levels in control experiments, whereas they remained at 80% of the initial levels during perfusion of hDAF livers [16].
  • RESULTS: CH50, AP50, C3, and B were not significantly different from the control group in both the CAPD and preterminal groups [4].


  1. Study of the interaction of the medium chain mu 2 subunit of the clathrin-associated adapter protein complex 2 with cytotoxic T-lymphocyte antigen 4 and CD28. Follows, E.R., McPheat, J.C., Minshull, C., Moore, N.C., Pauptit, R.A., Rowsell, S., Stacey, C.L., Stanway, J.J., Taylor, I.W., Abbott, W.M. Biochem. J. (2001) [Pubmed]
  2. Equine infectious anemia virus Gag polyprotein late domain specifically recruits cellular AP-2 adapter protein complexes during virion assembly. Puffer, B.A., Watkins, S.C., Montelaro, R.C. J. Virol. (1998) [Pubmed]
  3. Activation of complement pathways in xenotransplantation: an in vitro study. Walpen, A.J., Mohacsi, P., Frey, C., Roos, A., Daha, M.R., Rieben, R. Transpl. Immunol. (2002) [Pubmed]
  4. The serum complement system in children on continuous ambulatory peritoneal dialysis. Reddingius, R.E., Schröder, C.H., Daha, M.R., Monnens, L.A. Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. (1993) [Pubmed]
  5. Detection of novel oral phylotypes associated with periodontitis. Sakamoto, M., Huang, Y., Umeda, M., Ishikawa, I., Benno, Y. FEMS Microbiol. Lett. (2002) [Pubmed]
  6. Interaction of CTLA-4 with AP50, a clathrin-coated pit adaptor protein. Zhang, Y., Allison, J.P. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  7. The B cell coreceptor CD22 associates with AP50, a clathrin-coated pit adapter protein, via tyrosine-dependent interaction. John, B., Herrin, B.R., Raman, C., Wang, Y.N., Bobbitt, K.R., Brody, B.A., Justement, L.B. J. Immunol. (2003) [Pubmed]
  8. Activity and in vitro reassembly of the coated vesicle (H+)-ATPase requires the 50-kDa subunit of the clathrin assembly complex AP-2. Liu, Q., Feng, Y., Forgac, M. J. Biol. Chem. (1994) [Pubmed]
  9. Chromosome localization of human genes for clathrin adaptor polypeptides AP2 beta and AP50 and the clathrin-binding protein, VCP. Druck, T., Gu, Y., Prabhala, G., Cannizzaro, L.A., Park, S.H., Huebner, K., Keen, J.H. Genomics (1995) [Pubmed]
  10. Interaction of CTLA-4 with the clathrin-associated protein AP50 results in ligand-independent endocytosis that limits cell surface expression. Chuang, E., Alegre, M.L., Duckett, C.S., Noel, P.J., Vander Heiden, M.G., Thompson, C.B. J. Immunol. (1997) [Pubmed]
  11. Early activation of inflammation and clotting in the preterm lamb with neonatal RDS: comparison of conventional ventilation and high frequency oscillatory ventilation. Jaarsma, A.S., Braaksma, M.A., Geven, W.B., Van Oeveren, W., Oetomo, S.B. Pediatr. Res. (2001) [Pubmed]
  12. H deficiency in two brothers with atypical dense intramembranous deposit disease. Levy, M., Halbwachs-Mecarelli, L., Gubler, M.C., Kohout, G., Bensenouci, A., Niaudet, P., Hauptmann, G., Lesavre, P. Kidney Int. (1986) [Pubmed]
  13. C4, BF, C3 allele distribution and complement activity in healthy aged people and centenarians. Bellavia, D., Fradà, G., Di Franco, P., Feo, S., Franceschi, C., Sansoni, P., Brai, M. J. Gerontol. A Biol. Sci. Med. Sci. (1999) [Pubmed]
  14. The development of the complement system after 28 weeks' gestation. Wolach, B., Dolfin, T., Regev, R., Gilboa, S., Schlesinger, M. Acta Paediatr. (1997) [Pubmed]
  15. Functional properties of internalization-deficient P2X4 receptors reveal a novel mechanism of ligand-gated channel facilitation by ivermectin. Toulmé, E., Soto, F., Garret, M., Boué-Grabot, E. Mol. Pharmacol. (2006) [Pubmed]
  16. Immunopathological observations after xenogeneic liver perfusions using donor pigs transgenic for human decay-accelerating factor. Pascher, A., Poehlein, C., Storck, M., Prestel, R., Mueller-Hoecker, J., White, D.J., Abendroth, D., Hammer, C. Transplantation (1997) [Pubmed]
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