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HMDB Protein ID HMDBP14128
Secondary Accession Numbers None
Name AP-2 complex subunit mu
  1. AP-2 mu chain
  2. Adaptin-mu2
  3. Adaptor protein complex AP-2 subunit mu
  4. Adaptor-related protein complex 2 subunit mu
  5. Clathrin assembly protein complex 2 mu medium chain
  6. Clathrin coat assembly protein AP50
  7. Clathrin coat-associated protein AP50
  8. HA2 50 kDa subunit
  9. Plasma membrane adaptor AP-2 50 kDa protein
Gene Name AP2M1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Component of the adaptor protein complex 2 (AP-2) (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 is involved in clathrin-dependent endocytosis in which cargo proteins are incorporated into vesicles surrounded by clathrin (clathrin-coated vesicles, CCVs) which are destined for fusion with the early endosome (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). Clathrin-associated adaptor protein (AP) complexes which can bind directly to both the clathrin lattice and to the lipid and protein components of membranes are considered to be the major clathrin adaptors contributing the CCV formation (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis (PubMed:16581796). AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface (PubMed:12694563, PubMed:12952941, PubMed:14745134, PubMed:14985334, PubMed:15473838, PubMed:31104773). AP-2 recognizes Y-X-X-[FILMV] (Y-X-X-Phi) and [ED]-X-X-X-L-[LI] endocytosis signal motifs within the cytosolic tails of transmembrane cargo molecules (By similarity). AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway (PubMed:19033387). During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs (By similarity). The surface region interacting with to the Y-X-X-Phi motif is inaccessible in cytosolic AP-2, but becomes accessible through a conformational change following phosphorylation of AP-2 mu subunit at Thr-156 in membrane-associated AP-2 (PubMed:11877457). The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (PubMed:11877457). Plays a role in endocytosis of frizzled family members upon Wnt signaling (By similarity).
  • Endocrine and other factor-regulated calcium reabsorption
  • Endocytosis
  • Huntington disease
  • Synaptic vesicle cycle
Reactions Not Available
GO Classification
Biological Process
membrane organization
receptor internalization
ephrin receptor signaling pathway
intracellular protein transport
Wnt signaling pathway, planar cell polarity pathway
low-density lipoprotein particle clearance
vesicle-mediated transport
negative regulation of protein localization to plasma membrane
antigen processing and presentation of exogenous peptide antigen via MHC class II
cellular protein-containing complex assembly
low-density lipoprotein particle receptor catabolic process
regulation of defense response to virus by virus
regulation of vesicle size
vesicle budding from membrane
clathrin-dependent endocytosis
Cellular Component
endolysosome membrane
clathrin-coated endocytic vesicle membrane
extracellular vesicular exosome
plasma membrane
coated pit
AP-2 adaptor complex
endocytic vesicle membrane
cytoplasmic vesicle
lysosomal membrane
clathrin-coated endocytic vesicle
intracellular membrane-bounded organelle
Molecular Function
lipid binding
ion channel binding
low-density lipoprotein particle receptor binding
clathrin adaptor activity
signal sequence binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 435
Molecular Weight 49654.34
Theoretical pI 9.542
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q96CW1
UniProtKB/Swiss-Prot Entry Name AP2M1_HUMAN
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
General References
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  5. Geyer M, Yu H, Mandic R, Linnemann T, Zheng YH, Fackler OT, Peterlin BM: Subunit H of the V-ATPase binds to the medium chain of adaptor protein complex 2 and connects Nef to the endocytic machinery. J Biol Chem. 2002 Aug 9;277(32):28521-9. Epub 2002 May 24. [PubMed:12032142 ]
  6. Suzuki E, Nakayama M: MEGF10 is a mammalian ortholog of CED-1 that interacts with clathrin assembly protein complex 2 medium chain and induces large vacuole formation. Exp Cell Res. 2007 Oct 15;313(17):3729-42. Epub 2007 Jul 3. [PubMed:17643423 ]
  7. Zhou H, Di Palma S, Preisinger C, Peng M, Polat AN, Heck AJ, Mohammed S: Toward a comprehensive characterization of a human cancer cell phosphoproteome. J Proteome Res. 2013 Jan 4;12(1):260-71. doi: 10.1021/pr300630k. Epub 2012 Dec 18. [PubMed:23186163 ]
  8. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460 ]
  9. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569 ]
  10. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [PubMed:25944712 ]
  11. Jullien-Flores V, Mahe Y, Mirey G, Leprince C, Meunier-Bisceuil B, Sorkin A, Camonis JH: RLIP76, an effector of the GTPase Ral, interacts with the AP2 complex: involvement of the Ral pathway in receptor endocytosis. J Cell Sci. 2000 Aug;113 ( Pt 16):2837-44. [PubMed:10910768 ]
  12. Ricotta D, Conner SD, Schmid SL, von Figura K, Honing S: Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals. J Cell Biol. 2002 Mar 4;156(5):791-5. doi: 10.1083/jcb.200111068. Epub 2002 Mar 4. [PubMed:11877457 ]
  13. Nakatsu F, Ohno H: Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct. 2003 Oct;28(5):419-29. doi: 10.1247/csf.28.419. [PubMed:14745134 ]
  14. Motley A, Bright NA, Seaman MN, Robinson MS: Clathrin-mediated endocytosis in AP-2-depleted cells. J Cell Biol. 2003 Sep 1;162(5):909-18. doi: 10.1083/jcb.200305145. [PubMed:12952941 ]
  15. Owen DJ, Collins BM, Evans PR: Adaptors for clathrin coats: structure and function. Annu Rev Cell Dev Biol. 2004;20:153-91. doi: 10.1146/annurev.cellbio.20.010403.104543. [PubMed:15473838 ]
  16. Huang F, Khvorova A, Marshall W, Sorkin A: Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference. J Biol Chem. 2004 Apr 16;279(16):16657-61. doi: 10.1074/jbc.C400046200. Epub 2004 Feb 25. [PubMed:14985334 ]
  17. Paing MM, Johnston CA, Siderovski DP, Trejo J: Clathrin adaptor AP2 regulates thrombin receptor constitutive internalization and endothelial cell resensitization. Mol Cell Biol. 2006 Apr;26(8):3231-42. doi: 10.1128/MCB.26.8.3231-3242.2006. [PubMed:16581796 ]
  18. Levecque C, Velayos-Baeza A, Holloway ZG, Monaco AP: The dyslexia-associated protein KIAA0319 interacts with adaptor protein 2 and follows the classical clathrin-mediated endocytosis pathway. Am J Physiol Cell Physiol. 2009 Jul;297(1):C160-8. doi: 10.1152/ajpcell.00630.2008. Epub 2009 May 6. [PubMed:19419997 ]
  19. Marcello E, Saraceno C, Musardo S, Vara H, de la Fuente AG, Pelucchi S, Di Marino D, Borroni B, Tramontano A, Perez-Otano I, Padovani A, Giustetto M, Gardoni F, Di Luca M: Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease. J Clin Invest. 2013 Jun;123(6):2523-38. doi: 10.1172/JCI65401. Epub 2013 May 8. [PubMed:23676497 ]
  20. Rapetti-Mauss R, O'Mahony F, Sepulveda FV, Urbach V, Harvey BJ: Oestrogen promotes KCNQ1 potassium channel endocytosis and postendocytic trafficking in colonic epithelium. J Physiol. 2013 Jun 1;591(11):2813-31. doi: 10.1113/jphysiol.2013.251678. Epub 2013 Mar 25. [PubMed:23529131 ]
  21. Kliche J, Kuss H, Ali M, Ivarsson Y: Cytoplasmic short linear motifs in ACE2 and integrin beta3 link SARS-CoV-2 host cell receptors to mediators of endocytosis and autophagy. Sci Signal. 2021 Jan 12;14(665). pii: 14/665/eabf1117. doi: 10.1126/scisignal.abf1117. [PubMed:33436498 ]
  22. Follows ER, McPheat JC, Minshull C, Moore NC, Pauptit RA, Rowsell S, Stacey CL, Stanway JJ, Taylor IW, Abbott WM: 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. Biochem J. 2001 Oct 15;359(Pt 2):427-34. doi: 10.1042/0264-6021:3590427. [PubMed:11583591 ]
  23. Helbig I, Lopez-Hernandez T, Shor O, Galer P, Ganesan S, Pendziwiat M, Rademacher A, Ellis CA, Humpfer N, Schwarz N, Seiffert S, Peeden J, Shen J, Sterbova K, Hammer TB, Moller RS, Shinde DN, Tang S, Smith L, Poduri A, Krause R, Benninger F, Helbig KL, Haucke V, Weber YG: A Recurrent Missense Variant in AP2M1 Impairs Clathrin-Mediated Endocytosis and Causes Developmental and Epileptic Encephalopathy. Am J Hum Genet. 2019 Jun 6;104(6):1060-1072. doi: 10.1016/j.ajhg.2019.04.001. Epub 2019 May 16. [PubMed:31104773 ]