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Overview

Uniprot IDO94973
Protein NameAP-2 complex subunit alpha-2
Gene NameAP2A2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
6 **MPAVSKGDGMRGL
619 LAKLKKKKGPSTVTD

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)

Protein Sequence

10 MPAVSKGDGM 20 RGLAVFISDI 30 RNCKSKEAEI 40 KRINKELANI 50 RSKFKGDKAL 60 DGYSKKKYVC 70 KLLFIFLLGH 80 DIDFGHMEAV 90 NLLSSNRYTE 100 KQIGYLFISV 110 LVNSNSELIR 120 LINNAIKNDL 130 ASRNPTFMGL 140 ALHCIASVGS 150 REMAEAFAGE 160 IPKVLVAGDT 170 MDSVKQSAAL 180 CLLRLYRTSP 190 DLVPMGDWTS 200 RVVHLLNDQH 210 LGVVTAATSL 220 ITTLAQKNPE 230 EFKTSVSLAV 240 SRLSRIVTSA 250 STDLQDYTYY 260 FVPAPWLSVK 270 LLRLLQCYPP 280 PDPAVRGRLT 290 ECLETILNKA 300 QEPPKSKKVQ 310 HSNAKNAVLF 320 EAISLIIHHD 330 SEPNLLVRAC 340 NQLGQFLQHR 350 ETNLRYLALE 360 SMCTLASSEF 370 SHEAVKTHIE 380 TVINALKTER 390 DVSVRQRAVD 400 LLYAMCDRSN 410 APQIVAEMLS 420 YLETADYSIR 430 EEIVLKVAIL 440 AEKYAVDYTW 450 YVDTILNLIR 460 IAGDYVSEEV 470 WYRVIQIVIN 480 RDDVQGYAAK 490 TVFEALQAPA 500 CHENLVKVGG 510 YILGEFGNLI 520 AGDPRSSPLI 530 QFHLLHSKFH 540 LCSVPTRALL 550 LSTYIKFVNL 560 FPEVKPTIQD 570 VLRSDSQLRN 580 ADVELQQRAV 590 EYLRLSTVAS 600 TDILATVLEE 610 MPPFPERESS 620 ILAKLKKKKG 630 PSTVTDLEDT 640 KRDRSVDVNG 650 GPEPAPASTS 660 AVSTPSPSAD 670 LLGLGAAPPA 680 PAGPPPSSGG 690 SGLLVDVFSD 700 SASVVAPLAP 710 GSEDNFARFV 720 CKNNGVLFEN 730 QLLQIGLKSE 740 FRQNLGRMFI 750 FYGNKTSTQF 760 LNFTPTLICS 770 DDLQPNLNLQ 780 TKPVDPTVEG 790 GAQVQQVVNI 800 ECVSDFTEAP 810 VLNIQFRYGG 820 TFQNVSVQLP 830 ITLNKFFQPT 840 EMASQDFFQR 850 WKQLSNPQQE 860 VQNIFKAKHP 870 MDTEVTKAKI 880 IGFGSALLEE 890 VDPNPANFVG 900 AGIIHTKTTQ 910 IGCLLRLEPN 920 LQAQMYRLTL 930 RTSKEAVSQR LCELLSAQF

Gene Ontology

Classification GO ID Description
Cellular Component GO:0030122 AP-2 adaptor complex
Cellular Component GO:0045334 clathrin-coated endocytic vesicle
Cellular Component GO:0030669 clathrin-coated endocytic vesicle membrane
Cellular Component GO:0009898 cytoplasmic side of plasma membrane
Cellular Component GO:0031410 cytoplasmic vesicle
Cellular Component GO:0005829 cytosol
Cellular Component GO:0030666 endocytic vesicle membrane
Cellular Component GO:0036020 endolysosome membrane
Cellular Component GO:0101003 ficolin-1-rich granule membrane
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0098794 postsynapse
Cellular Component GO:0098793 presynapse
Cellular Component GO:0030667 secretory granule membrane
Molecular Function GO:0035615 clathrin adaptor activity
Molecular Function GO:0097718 disordered domain specific binding
Molecular Function GO:0008289 lipid binding
Molecular Function GO:0019901 protein kinase binding
Biological Process GO:0072583 clathrin-dependent endocytosis
Biological Process GO:0006886 intracellular protein transport
Biological Process GO:0098884 postsynaptic neurotransmitter receptor internalization
Biological Process GO:0048488 synaptic vesicle endocytosis
Biological Process GO:0016192 vesicle-mediated transport

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.