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Identification
HMDB Protein ID HMDBP14130
Secondary Accession Numbers None
Name AP-2 complex subunit alpha-2
Synonyms
  1. 100 kDa coated vesicle protein C
  2. Adaptor protein complex AP-2 subunit alpha-2
  3. Adaptor-related protein complex 2 subunit alpha-2
  4. Alpha-adaptin C
  5. Alpha2-adaptin
  6. Clathrin assembly protein complex 2 alpha-C large chain
  7. Huntingtin yeast partner J
  8. Huntingtin-interacting protein 9
  9. Huntingtin-interacting protein J
  10. Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit
  11. HIP-9
Gene Name AP2A2
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Component of the adaptor protein complex 2 (AP-2). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways. Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation. 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. The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components. 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. AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis. AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface. 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. AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway. During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (PubMed:23676497). The AP-2 alpha subunit binds polyphosphoinositide-containing lipids, positioning AP-2 on the membrane. The AP-2 alpha subunit acts via its C-terminal appendage domain as a scaffolding platform for endocytic accessory proteins. The AP-2 alpha and AP-2 sigma subunits are thought to contribute to the recognition of the [ED]-X-X-X-L-[LI] motif (By similarity).
Pathways
  • Endocrine and other factor-regulated calcium reabsorption
  • Endocytosis
  • Huntington disease
  • Synaptic vesicle cycle
Reactions Not Available
GO Classification
Biological Process
neutrophil degranulation
membrane organization
ephrin receptor signaling pathway
intracellular protein transport
Wnt signaling pathway, planar cell polarity pathway
low-density lipoprotein particle clearance
receptor-mediated endocytosis
antigen processing and presentation of exogenous peptide antigen via MHC class II
low-density lipoprotein particle receptor catabolic process
regulation of defense response to virus by virus
clathrin-dependent endocytosis
Cellular Component
endolysosome membrane
cytosol
clathrin-coated endocytic vesicle membrane
plasma membrane
ficolin-1-rich granule membrane
AP-2 adaptor complex
secretory granule membrane
endocytic vesicle membrane
cytoplasmic vesicle
clathrin-coated endocytic vesicle
Molecular Function
protein kinase binding
lipid binding
disordered domain specific binding
clathrin adaptor activity
cargo adaptor activity
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 939
Molecular Weight 103959.37
Theoretical pI 6.965
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID O94973
UniProtKB/Swiss-Prot Entry Name AP2A2_HUMAN
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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  3. Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T: Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones. DNA Res. 2002 Jun 30;9(3):99-106. [PubMed:12168954 ]
  4. Nagase T, Ishikawa K, Suyama M, Kikuno R, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. XII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1998 Dec 31;5(6):355-64. [PubMed:10048485 ]
  5. Waelter S, Scherzinger E, Hasenbank R, Nordhoff E, Lurz R, Goehler H, Gauss C, Sathasivam K, Bates GP, Lehrach H, Wanker EE: The huntingtin interacting protein HIP1 is a clathrin and alpha-adaptin-binding protein involved in receptor-mediated endocytosis. Hum Mol Genet. 2001 Aug 15;10(17):1807-17. [PubMed:11532990 ]
  6. Faber PW, Barnes GT, Srinidhi J, Chen J, Gusella JF, MacDonald ME: Huntingtin interacts with a family of WW domain proteins. Hum Mol Genet. 1998 Sep;7(9):1463-74. [PubMed:9700202 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. Hinrichsen L, Harborth J, Andrees L, Weber K, Ungewickell EJ: Effect of clathrin heavy chain- and alpha-adaptin-specific small inhibitory RNAs on endocytic accessory proteins and receptor trafficking in HeLa cells. J Biol Chem. 2003 Nov 14;278(46):45160-70. doi: 10.1074/jbc.M307290200. Epub 2003 Sep 6. [PubMed:12960147 ]
  13. Kyttala A, Yliannala K, Schu P, Jalanko A, Luzio JP: AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein CLN3 via its dileucine motif. J Biol Chem. 2005 Mar 18;280(11):10277-83. doi: 10.1074/jbc.M411862200. Epub 2004 Dec 13. [PubMed:15598649 ]
  14. Lau AW, Chou MM: The adaptor complex AP-2 regulates post-endocytic trafficking through the non-clathrin Arf6-dependent endocytic pathway. J Cell Sci. 2008 Dec 15;121(Pt 24):4008-17. doi: 10.1242/jcs.033522. Epub 2008 Nov 25. [PubMed:19033387 ]
  15. Hayashi H, Inamura K, Aida K, Naoi S, Horikawa R, Nagasaka H, Takatani T, Fukushima T, Hattori A, Yabuki T, Horii I, Sugiyama Y: AP2 adaptor complex mediates bile salt export pump internalization and modulates its hepatocanalicular expression and transport function. Hepatology. 2012 Jun;55(6):1889-900. doi: 10.1002/hep.25591. [PubMed:22262466 ]
  16. Umasankar PK, Sanker S, Thieman JR, Chakraborty S, Wendland B, Tsang M, Traub LM: Distinct and separable activities of the endocytic clathrin-coat components Fcho1/2 and AP-2 in developmental patterning. Nat Cell Biol. 2012 Apr 8;14(5):488-501. doi: 10.1038/ncb2473. [PubMed:22484487 ]
  17. Montagnac G, Meas-Yedid V, Irondelle M, Castro-Castro A, Franco M, Shida T, Nachury MV, Benmerah A, Olivo-Marin JC, Chavrier P: alphaTAT1 catalyses microtubule acetylation at clathrin-coated pits. Nature. 2013 Oct 24;502(7472):567-70. doi: 10.1038/nature12571. Epub 2013 Oct 6. [PubMed:24097348 ]
  18. Piccini A, Castroflorio E, Valente P, Guarnieri FC, Aprile D, Michetti C, Bramini M, Giansante G, Pinto B, Savardi A, Cesca F, Bachi A, Cattaneo A, Wren JD, Fassio A, Valtorta F, Benfenati F, Giovedi S: APache Is an AP2-Interacting Protein Involved in Synaptic Vesicle Trafficking and Neuronal Development. Cell Rep. 2017 Dec 19;21(12):3596-3611. doi: 10.1016/j.celrep.2017.11.073. [PubMed:29262337 ]