Protein: AP-2 complex subunit alpha-2 (100 kDa coated vesicle protein C) (Adaptor protein complex AP-2 subunit alpha-2) (Adaptor-related protein complex 2 subunit alpha-2) (Alpha-adaptin C) (Alpha2-adaptin) (Clathrin assembly protein complex 2 alpha-C large chain) (Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit) (Q0VCK5)
Organism: Bos taurus (Bovine)
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 (By similarity). 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).
Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P17427}; Peripheral membrane protein {ECO:0000250|UniProtKB:P17427}; Cytoplasmic side {ECO:0000250|UniProtKB:P17427}. Membrane, coated pit {ECO:0000250|UniProtKB:P17427}; Peripheral membrane protein {ECO:0000250|UniProtKB:P17427}; Cytoplasmic side {ECO:0000250|UniProtKB:P17427}. Note=AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV. {ECO:0000250|UniProtKB:P17427}.
Sequence: MPAVSKGDGMRGLAVFISDIRNCKSKEAEIKRINKELANIRSKFKGDKALDGYSKKKYVCKLLFIFLLGHDIDFGHMEAVNLLSSNRYTEKQIGYLFISVLVNSNSELIRLINNAIKNDLASRNPTFMGLALHCIANVGSREMAEAFAGEIPKILVAGDTMDSVKQSAALCLLRLHRASPDLVPVGDWTSRVVHLLNDQHLGVVTAATSLITTLAQKNPEEFKTSVSLAVSRLSRIVTSASTDLQDYTYYFVPAPWLSVKLLRLLQCYPPPEDPAVRGRLTECLEAILNKAQEPPKSKKVQHSNAKNAVLFEAISLVTHHDSEPNLLVRACNQLGQFLQHRETNLRYLALESMCTLASSEFSHEAVKTHIETVINALKTERDVSVRQRAVDLLYAMCDRSNAQQIVAEMLSYLETADYSIREEIVLKVAILAEKYAVDYTWYVDTILNLIRIAGDYVSEEVWYRVIQIVINRDDVQGYAAKTVFEALQAPACHENLVKVGGYILGEFGNLIAGDPRSSPLTQFHLLHSKFHLCSVPTRALLLSTYIKFVNLFPEVKGTIQDVLRSDSQLKNADVELQQRAVEYLRLSTVASTDILATVLEEMPPFPERESSILAKLKKKKGPSTVTDLEEAKRERSADVNGGPEPALASTSAVSTPSPSADLLGLGAAPPVPAGPPPSSGGLLVDVFSDSPSAAAPLAPGSEDNFARFVCKNNGVLFENQLLQIGLKSEFRQNLGRMFIFYGNKTSTQFLNFTPTLICSDDLQANLSLQTKPVDPTVDGGAQVQQAVNIECVSDFTEAPVLNIQFRYGGTFQNVSVKLPITLNKFFQPTEMASQDFFQRWKQLSNPQQEVQSIFKAKHPMDTEVTKAKIIGFGSALLEEVDPNPANFVGAGIIHTRTAQIGCLLRLEPNLQAQMYRLTLRTSRETVSQRLCELLSEQF
InterPro domains: - IPR016024: Armadillo-type fold (homologous_superfamily) [9-588]
- IPR012295: TBP domain superfamily (homologous_superfamily) [826-938]
- IPR050840: Adaptor Complexes Large Subunit (family) [15-917]
- IPR013041: Clathrin adaptor, appendage, Ig-like subdomain superfamily (homologous_superfamily) [696-824]
- IPR008152: Clathrin adaptor, alpha/beta/gamma-adaptin, appendage, Ig-like subdomain (domain) [706-819]
- IPR003164: Clathrin adaptor, alpha-adaptin, appendage, C-terminal subdomain (domain) [825-934]
- IPR009028: Coatomer/calthrin adaptor appendage, C-terminal subdomain (homologous_superfamily) [825-938]
- IPR011989: Armadillo-like helical (homologous_superfamily) [1-621]
- IPR002553: Clathrin/coatomer adaptor, adaptin-like, N-terminal (domain) [30-588]
- IPR017104: Adaptor protein complex AP-2, alpha subunit (family) [3-938]
Interaction partners: - AP-2 complex subunit sigma
- AP-2 complex subunit mu
- AP-1 complex subunit beta-1
- Clathrin heavy chain 1
- AP-2 complex subunit alpha
- Clathrin light chain A
- AP-2 complex subunit mu
- Huntingtin
- Trans-golgi network protein 2
- Epidermal growth factor receptor substrate 15
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0060090 (molecular adaptor activity), GO:0030674 (protein-macromolecule adaptor activity), GO:0005515 (protein binding), GO:0030276 (clathrin binding), GO:0140312 (cargo adaptor activity), GO:0035615 (clathrin adaptor activity)
Biological Process (BP): GO:0008150 (biological process), GO:0051179 (localization), GO:0051234 (establishment of localization), GO:0006810 (transport), GO:0016192 (vesicle-mediated transport), GO:0006897 (endocytosis), GO:0006898 (receptor-mediated endocytosis), GO:0072583 (clathrin-dependent endocytosis)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0016020 (membrane), GO:0071944 (cell periphery), GO:0005737 (cytoplasm), GO:0098796 (membrane protein complex), GO:0012505 (endomembrane system), GO:0005905 (clathrin-coated pit), GO:0031090 (organelle membrane), GO:0030141 (secretory granule), GO:0030117 (membrane coat), GO:0031410 (cytoplasmic vesicle), GO:0043229 (intracellular organelle), GO:0048475 (coated membrane), GO:0030119 (AP-type membrane coat adaptor complex), GO:0098797 (plasma membrane protein complex), GO:0098590 (plasma membrane region), GO:0043227 (membrane-bounded organelle), GO:0005886 (plasma membrane), GO:0030139 (endocytic vesicle), GO:0099503 (secretory vesicle), GO:0030132 (clathrin coat of coated pit), GO:0043231 (intracellular membrane-bounded organelle), GO:0030118 (clathrin coat), GO:0098588 (bounding membrane of organelle), GO:0030131 (clathrin adaptor complex), GO:0012506 (vesicle membrane), GO:0030120 (vesicle coat), GO:0030135 (coated vesicle), GO:0030122 (AP-2 adaptor complex), GO:0031982 (vesicle), GO:0030659 (cytoplasmic vesicle membrane), GO:0030666 (endocytic vesicle membrane), GO:0097708 (intracellular vesicle), GO:0030125 (clathrin vesicle coat), GO:0030136 (clathrin-coated vesicle), GO:0030662 (coated vesicle membrane), GO:0045334 (clathrin-coated endocytic vesicle), GO:0030669 (clathrin-coated endocytic vesicle membrane), GO:0030128 (clathrin coat of endocytic vesicle), GO:0030665 (clathrin-coated vesicle membrane)