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Overview

Uniprot ID	D3ZUY8
Protein Name	AP-2 complex subunit alpha
Gene Name	Ap2a1
Organism	Rattus norvegicus

Kla Sites from experimental identification

Position	Flanking peptide
177	LCLLRLYKASPDLVP
277	PPEDAAVKGRLVECL
6	**MPAVSKGDGMRGL
620	LAKLKRKKGPGAASA

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. 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

Protein Sequence

10 MPAVSKGDGM 20 RGLAVFISDI 30 RNCKSKEAEI 40 KRINKELANI 50 RSKFKGDKAL 60 DGYSKKKYVC 70 KLLFIFLLGH 80 DIDFGHMEAV 90 NLLSSNKYTE 100 KQIGYLFISV 110 LVNSNSELIR 120 LINNAIKNDL 130 ASRNPTFMCL 140 ALHCIANVGS 150 REMGEAFAAD 160 IPRILVAGDS 170 MDSVKQSAAL 180 CLLRLYKASP 190 DLVPMGEWTA 200 RVVHLLNDQH 210 MGVVTAAVSL 220 ITCLCKKNPD 230 DFKTCVSLAV 240 SRLSRIVSSA 250 STDLQDYTYY 260 FVPAPWLSVK 270 LLRLLQCYPP 280 PEDAAVKGRL 290 VECLETVLNK 300 AQEPPKSKKV 310 QHSNAKNAIL 320 FETISLIIHY 330 DSEPNLLVRA 340 CNQLGQFLQH 350 RETNLRYLAL 360 ESMCTLASSE 370 FSHEAVKTHI 380 DTVINALKTE 390 RDVSVRQRAA 400 DLLYAMCDRS 410 NAKQIVSEML 420 RYLETADYAI 430 REEIVLKVAI 440 LAEKYAVDYS 450 WYVDTILNLI 460 RIAGDYVSEE 470 VWYRVLQIVT 480 NRDDVQGYAA 490 KTVFEALQAP 500 ACHENMVKVG 510 GYILGEFGNL 520 IAGDPRSSPP 530 VQFSLLHSKF 540 HLCSVATRAL 550 LLSTYIKFIN 560 LFPETKATIQ 570 GVLRAGSQLR 580 NADVELQQRA 590 VEYLTLSSVA 600 STDVLATVLE 610 EMPPFPERES 620 SILAKLKRKK 630 GPGAASALDD 640 SRRDTSSNDI 650 NGGVEPTPSN 660 VSTPSPSADL 670 LGLRAAPPPA 680 APPAPVGGNL 690 LVDVFSDGPT 700 AQPSLGPTPE 710 EAFLSELEPP 720 APESPMTLLA 730 DPAPAADPGP 740 EDIGPPIPEA 750 DELLNKFVCK 760 NSGVLFENQL 770 LQIGVKSEFR 780 QNLGRMYLFY 790 GNKTSVQFQS 800 FLPTVVHPGD 810 LQTQLAVQTK 820 RVAAQVDGGA 830 QVQQVLNIEC 840 LRDFLTPPLL 850 SVRFRYGGTA 860 QSLTLKLPVT 870 INKFFQPTEM 880 AAQDFFQRWK 890 QLSLPLQEAQ 900 KIFKANHPMD 910 AEVTKAKLLG 920 FGSALLDNVD 930 PNPENFVGAG 940 IIQTKALQVG 950 CLLRLEPNAQ 960 AQMYRLTLRT 970 SKEPVSRHLC ELLAQQF

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0030122	AP-2 adaptor complex
Molecular Function	GO:0035615	clathrin adaptor activity
Biological Process	GO:0072583	clathrin-dependent endocytosis
Biological Process	GO:0006886	intracellular protein transport

Reference

[1] Yao Y, Bade R, Li G, Zhang A, Zhao H et al.. Global-Scale Profiling of Differential Expressed Lysine-Lactylated Proteins in the Cerebral Endothelium of Cerebral Ischemia-Reperfusion Injury Rats.. Cell Mol Neurobiol 43(5):1989-2004. 2023 Jul. PMID: 36030297.

[2] Sheng L, Xu H, Wang Y, Ni J, Xiang T et al.. Systematic analysis of lysine lactylation in nucleus pulposus cells.. iScience 27(11):111157. 2024 Nov 15. PMID: 39524337.

[3] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.