UniProt functional annotation for P17427



	UniProt functional annotation for P17427

UniProt code: P17427.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

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. {ECO:0000269|PubMed:10459011, ECO:0000269|PubMed:14745134, ECO:0000269|PubMed:15473838, ECO:0000269|PubMed:23676497}.

Subunit: Adaptor 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) (PubMed:19140243). Binds EPN1, EPS15, AMPH, SNAP91 and BIN1 (PubMed:10380931, PubMed:10430869, PubMed:12057195). Interacts with clathrin (PubMed:10459011). Interacts with HIP1 (By similarity). Interacts with DGKD (PubMed:17880279). Interacts with DENND1A, DENND1B and DENND1C (PubMed:20154091). Interacts with FCHO1 and DAB2 (PubMed:11247302, PubMed:22484487). Interacts with ATAT1; this interaction is required for efficient alpha- tubulin acetylation by ATAT1 (PubMed:24097348). Interacts with KIAA1107 (PubMed:29262337). Together with AP2B1 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Interacts with CLN3 (via dileucine motif) (By similarity). Interacts with ABCB11; this interaction regulates cell membrane expresion of ABCB11 through its internalization in a clathrin- dependent manner and its subsequent degradation (By similarity). {ECO:0000250|UniProtKB:O94973, ECO:0000269|PubMed:10380931, ECO:0000269|PubMed:10430869, ECO:0000269|PubMed:10459011, ECO:0000269|PubMed:11247302, ECO:0000269|PubMed:12057195, ECO:0000269|PubMed:17880279, ECO:0000269|PubMed:19140243, ECO:0000269|PubMed:20154091, ECO:0000269|PubMed:22484487, ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:24097348, ECO:0000269|PubMed:29262337}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:14530274, ECO:0000269|PubMed:17035303}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Membrane, coated pit {ECO:0000269|PubMed:17035303}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. 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:0000269|PubMed:17035303}.

Tissue specificity: Expressed in the brain (at protein level). {ECO:0000269|PubMed:23676497}.

Similarity: Belongs to the adaptor complexes large subunit family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



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. {ECO:0000269\|PubMed:10459011, ECO:0000269\|PubMed:14745134, ECO:0000269\|PubMed:15473838, ECO:0000269\|PubMed:23676497}.


Subunit:		Adaptor 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) (PubMed:19140243). Binds EPN1, EPS15, AMPH, SNAP91 and BIN1 (PubMed:10380931, PubMed:10430869, PubMed:12057195). Interacts with clathrin (PubMed:10459011). Interacts with HIP1 (By similarity). Interacts with DGKD (PubMed:17880279). Interacts with DENND1A, DENND1B and DENND1C (PubMed:20154091). Interacts with FCHO1 and DAB2 (PubMed:11247302, PubMed:22484487). Interacts with ATAT1; this interaction is required for efficient alpha- tubulin acetylation by ATAT1 (PubMed:24097348). Interacts with KIAA1107 (PubMed:29262337). Together with AP2B1 and AP2M1, it interacts with ADAM10; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (PubMed:23676497). Interacts with CLN3 (via dileucine motif) (By similarity). Interacts with ABCB11; this interaction regulates cell membrane expresion of ABCB11 through its internalization in a clathrin- dependent manner and its subsequent degradation (By similarity). {ECO:0000250\|UniProtKB:O94973, ECO:0000269\|PubMed:10380931, ECO:0000269\|PubMed:10430869, ECO:0000269\|PubMed:10459011, ECO:0000269\|PubMed:11247302, ECO:0000269\|PubMed:12057195, ECO:0000269\|PubMed:17880279, ECO:0000269\|PubMed:19140243, ECO:0000269\|PubMed:20154091, ECO:0000269\|PubMed:22484487, ECO:0000269\|PubMed:23676497, ECO:0000269\|PubMed:24097348, ECO:0000269\|PubMed:29262337}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:14530274, ECO:0000269\|PubMed:17035303}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. Membrane, coated pit {ECO:0000269\|PubMed:17035303}; Peripheral membrane protein {ECO:0000305}; Cytoplasmic side {ECO:0000305}. 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:0000269\|PubMed:17035303}.
Tissue specificity:		Expressed in the brain (at protein level). {ECO:0000269\|PubMed:23676497}.
Similarity:		Belongs to the adaptor complexes large subunit family. {ECO:0000305}.