CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001511
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 AP-2 complex subunit alpha-2 
Protein Synonyms/Alias
 100 kDa coated vesicle protein C; Adapter-related protein complex 2 alpha-2 subunit; Adaptor protein complex AP-2 subunit alpha-2; Alpha-adaptin C; Alpha2-adaptin; Clathrin assembly protein complex 2 alpha-C large chain; Huntingtin yeast partner J; Huntingtin-interacting protein 9; HIP-9; Huntingtin-interacting protein J; Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit 
Gene Name
 AP2A2 
Gene Synonyms/Alias
 ADTAB; CLAPA2; HIP9; HYPJ; KIAA0899 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
35AEIKRINKELANIRSacetylation[1]
117RLINNAIKNDLASRNubiquitination[2, 3]
377ETVINALKTERDVSVubiquitination[3, 4]
555VNLFPEVKPTIQDVLubiquitination[3, 4]
619LAKLKKKKGPSTVTDubiquitination[3, 5, 6]
631VTDLEDTKRDRSVDVubiquitination[3, 4, 5, 7]
712NFARFVCKNNGVLFEubiquitination[5]
842QDFFQRWKQLSNPQQubiquitination[2]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [3] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [4] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [5] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094] 
Functional Description
 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. 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). 
Sequence Annotation
 REGION 5 80 Lipid-binding.
 BINDING 43 43 Phosphatidylinositol lipid headgroup (By
 BINDING 53 53 Phosphatidylinositol lipid headgroup (By
 BINDING 57 57 Phosphatidylinositol lipid headgroup (By
 BINDING 58 58 Phosphatidylinositol lipid headgroup (By
 BINDING 61 61 Phosphatidylinositol lipid headgroup (By
 MOD_RES 808 808 Phosphotyrosine (By similarity).  
Keyword
 Alternative splicing; Cell membrane; Coated pit; Complete proteome; Endocytosis; Lipid-binding; Membrane; Phosphoprotein; Protein transport; Reference proteome; Transport. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 939 AA 
Protein Sequence
MPAVSKGDGM RGLAVFISDI RNCKSKEAEI KRINKELANI RSKFKGDKAL DGYSKKKYVC 60
KLLFIFLLGH DIDFGHMEAV NLLSSNRYTE KQIGYLFISV LVNSNSELIR LINNAIKNDL 120
ASRNPTFMGL ALHCIASVGS REMAEAFAGE IPKVLVAGDT MDSVKQSAAL CLLRLYRTSP 180
DLVPMGDWTS RVVHLLNDQH LGVVTAATSL ITTLAQKNPE EFKTSVSLAV SRLSRIVTSA 240
STDLQDYTYY FVPAPWLSVK LLRLLQCYPP PDPAVRGRLT ECLETILNKA QEPPKSKKVQ 300
HSNAKNAVLF EAISLIIHHD SEPNLLVRAC NQLGQFLQHR ETNLRYLALE SMCTLASSEF 360
SHEAVKTHIE TVINALKTER DVSVRQRAVD LLYAMCDRSN APQIVAEMLS YLETADYSIR 420
EEIVLKVAIL AEKYAVDYTW YVDTILNLIR IAGDYVSEEV WYRVIQIVIN RDDVQGYAAK 480
TVFEALQAPA CHENLVKVGG YILGEFGNLI AGDPRSSPLI QFHLLHSKFH LCSVPTRALL 540
LSTYIKFVNL FPEVKPTIQD VLRSDSQLRN ADVELQQRAV EYLRLSTVAS TDILATVLEE 600
MPPFPERESS ILAKLKKKKG PSTVTDLEDT KRDRSVDVNG GPEPAPASTS AVSTPSPSAD 660
LLGLGAAPPA PAGPPPSSGG SGLLVDVFSD SASVVAPLAP GSEDNFARFV CKNNGVLFEN 720
QLLQIGLKSE FRQNLGRMFI FYGNKTSTQF LNFTPTLICS DDLQPNLNLQ TKPVDPTVEG 780
GAQVQQVVNI ECVSDFTEAP VLNIQFRYGG TFQNVSVQLP ITLNKFFQPT EMASQDFFQR 840
WKQLSNPQQE VQNIFKAKHP MDTEVTKAKI IGFGSALLEE VDPNPANFVG AGIIHTKTTQ 900
IGCLLRLEPN LQAQMYRLTL RTSKEAVSQR LCELLSAQF 939 
Gene Ontology
 GO:0030122; C:AP-2 adaptor complex; NAS:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
 GO:0008565; F:protein transporter activity; IEA:InterPro.
 GO:0019886; P:antigen processing and presentation of exogenous peptide antigen via MHC class II; TAS:Reactome.
 GO:0007411; P:axon guidance; TAS:Reactome.
 GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0006886; P:intracellular protein transport; NAS:UniProtKB.
 GO:0042059; P:negative regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0050690; P:regulation of defense response to virus by virus; TAS:Reactome.
 GO:0007268; P:synaptic transmission; TAS:Reactome.
 GO:0016032; P:viral reproduction; TAS:Reactome. 
Interpro
 IPR017104; AP2_complex_asu.
 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR002553; Clathrin/coatomer_adapt-like_N.
 IPR013038; Clathrin_a-adaptin_app_Ig-like.
 IPR003164; Clathrin_a-adaptin_app_sub_C.
 IPR008152; Clathrin_a/b/g-adaptin_app_Ig.
 IPR015873; Clathrin_a/coatomer_app_sub_C.
 IPR009028; Coatomer/calthrin_app_sub_C.
 IPR013041; Coatomer/clathrin_app_Ig-like. 
Pfam
 PF01602; Adaptin_N
 PF02296; Alpha_adaptin_C
 PF02883; Alpha_adaptinC2 
SMART
 SM00809; Alpha_adaptinC2 
PROSITE
  
PRINTS