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Overview

Uniprot IDP84092
Protein NameAP-2 complex subunit mu
Gene NameAp2m1
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
224 NDKIVIEKQGKGTAD
256 HQCVRLSKFDSERSI
312 VVIKSNFKPSLLAQK
345 MKGKAKYKASENAIV
405 GLKVRYLKVFEPKLN
410 YLKVFEPKLNYSDHD
59 RTSFFHVKRSNIWLA

Function

Component of the adaptor protein complex 2 (AP-2) (PubMed:14745134, PubMed:15473838). Adaptor protein complexes function in protein transport via transport vesicles in different membrane traffic pathways (PubMed:14745134, PubMed:15473838). Adaptor protein complexes are vesicle coat components and appear to be involved in cargo selection and vesicle formation (PubMed:14745134, PubMed:15473838). 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:14745134, PubMed:15473838). The clathrin lattice serves as a mechanical scaffold but is itself unable to bind directly to membrane components (PubMed:14745134, PubMed:15473838). 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:14745134, PubMed:15473838). AP-2 also serves as a cargo receptor to selectively sort the membrane proteins involved in receptor-mediated endocytosis (PubMed:14745134, PubMed:15473838). AP-2 seems to play a role in the recycling of synaptic vesicle membranes from the presynaptic surface (By similarity). 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 (PubMed:15985462). AP-2 may also play a role in maintaining normal post-endocytic trafficking through the ARF6-regulated, non-clathrin pathway (By similarity). During long-term potentiation in hippocampal neurons, AP-2 is responsible for the endocytosis of ADAM10 (By similarity). The AP-2 mu (AP2M1) subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs (PubMed:15985462). 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:11516654, PubMed:15985462). The membrane-specific phosphorylation event appears to involve assembled clathrin which activates the AP-2 mu kinase AAK1 (By similarity). Plays a role in endocytosis of frizzled family members upon Wnt signaling (PubMed:20947020)

Protein Sequence

10 MIGGLFIYNH 20 KGEVLISRVY 30 RDDIGRNAVD 40 AFRVNVIHAR 50 QQVRSPVTNI 60 ARTSFFHVKR 70 SNIWLAAVTK 80 QNVNAAMVFE 90 FLYKMCDVMA 100 AYFGKISEEN 110 IKNNFVLIYE 120 LLDEILDFGY 130 PQNSETGALK 140 TFITQQGIKS 150 QHQTKEEQSQ 160 ITSQVTGQIG 170 WRREGIKYRR 180 NELFLDVLES 190 VNLLMSPQGQ 200 VLSAHVSGRV 210 VMKSYLSGMP 220 ECKFGMNDKI 230 VIEKQGKGTA 240 DETSKSGKQS 250 IAIDDCTFHQ 260 CVRLSKFDSE 270 RSISFIPPDG 280 EFELMRYRTT 290 KDIILPFRVI 300 PLVREVGRTK 310 LEVKVVIKSN 320 FKPSLLAQKI 330 EVRIPTPLNT 340 SGVQVICMKG 350 KAKYKASENA 360 IVWKIKRMAG 370 MKESQISAEI 380 ELLPTNDKKK 390 WARPPISMNF 400 EVPFAPSGLK 410 VRYLKVFEPK 420 LNYSDHDVIK 430 WVRYIGRSGI YETRC

Gene Ontology

Classification GO ID Description
Cellular Component GO:0030121 AP-1 adaptor complex
Cellular Component GO:0030122 AP-2 adaptor complex
Cellular Component GO:0005905 clathrin-coated pit
Cellular Component GO:0005829 cytosol
Cellular Component GO:0098894 extrinsic component of presynaptic endocytic zone membrane
Cellular Component GO:0098978 glutamatergic synapse
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0098794 postsynapse
Cellular Component GO:0045202 synapse
Cellular Component GO:0008021 synaptic vesicle
Cellular Component GO:0043195 terminal bouton
Molecular Function GO:0035615 clathrin adaptor activity
Molecular Function GO:0097718 disordered domain specific binding
Molecular Function GO:0008289 lipid binding
Molecular Function GO:0050750 low-density lipoprotein particle receptor binding
Molecular Function GO:0005048 signal sequence binding
Molecular Function GO:0044325 transmembrane transporter binding
Biological Process GO:0072583 clathrin-dependent endocytosis
Biological Process GO:0006896 Golgi to vacuole transport
Biological Process GO:0006886 intracellular protein transport
Biological Process GO:1903077 negative regulation of protein localization to plasma membrane
Biological Process GO:0002092 positive regulation of receptor internalization
Biological Process GO:1900244 positive regulation of synaptic vesicle endocytosis
Biological Process GO:0098884 postsynaptic neurotransmitter receptor internalization
Biological Process GO:0065003 protein-containing complex assembly
Biological Process GO:0031623 receptor internalization
Biological Process GO:0097494 regulation of vesicle size
Biological Process GO:0048488 synaptic vesicle endocytosis
Biological Process GO:0006900 vesicle budding from membrane

Reference

[1] 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.