MGP Database

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MGP000574

UniProt Annotations

Entry Information
Gene Nameadaptor-related protein complex 2, mu 1 subunit
Protein EntryAP2M1_HUMAN
UniProt IDQ96CW1
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q96CW1-1; Sequence=Displayed; Name=2; IsoId=Q96CW1-2; Sequence=VSP_034599;
FunctionComponent 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 mu subunit binds to transmembrane cargo proteins; it recognizes the Y-X-X-Phi motifs. 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 'Tyr-156' in membrane- associated AP-2. 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 (By similarity). {ECO:0000250}.
InteractionP27958:- (xeno); NbExp=4; IntAct=EBI-297683, EBI-6377335; P00533:EGFR; NbExp=4; IntAct=EBI-297683, EBI-297353;
Sequence CautionSequence=BAA09762.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
SimilarityBelongs to the adaptor complexes medium subunit family. {ECO:0000305}.
SimilarityContains 1 MHD (mu homology) domain. {ECO:0000255|PROSITE-ProRule:PRU00404}.
Subcellular LocationCell membrane. Membrane, coated pit; Peripheral membrane protein; Cytoplasmic side. 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}.
SubunitAdaptor protein complex 2 (AP-2) is a heterotetramer composed of two large adaptins (alpha-type subunit AP2A1 or AP2A2 and beta-type subunit AP2B1), a medium adaptin (mu-type subunit AP2M1) and a small adaptin (sigma-type subunit AP2S1). Interacts with ATP6V1H and MEGF10. Interacts with EGFR. Interacts with F2R. Interacts with PIP5K1C; tyrosine phosphorylation of PIP5K1C weakens the interaction (By similarity). Interacts with KIAA0319; required for clathrin-mediated endocytosis of KIAA0319. Interacts with DVL2 (via DEP domain) (By similarity). {ECO:0000250}.
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