P17427 · AP2A2_MOUSE
- ProteinAP-2 complex subunit alpha-2
- GeneAp2a2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids938 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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
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
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 11-12 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) (UniProtKB | ChEBI) | ||||
Sequence: RG | ||||||
Binding site | 43 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 53 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) (UniProtKB | ChEBI) | ||||
Sequence: Y | ||||||
Binding site | 57-61 | a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) (UniProtKB | ChEBI) | ||||
Sequence: KYVCK |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | AP-2 adaptor complex | |
Cellular Component | cytoplasmic side of plasma membrane | |
Cellular Component | cytoplasmic vesicle | |
Cellular Component | membrane coat | |
Cellular Component | postsynapse | |
Cellular Component | secretory granule | |
Cellular Component | synaptic vesicle | |
Molecular Function | clathrin adaptor activity | |
Molecular Function | disordered domain specific binding | |
Molecular Function | kinase binding | |
Molecular Function | phosphatidylinositol binding | |
Molecular Function | protein domain specific binding | |
Molecular Function | protein kinase binding | |
Molecular Function | protein serine/threonine kinase binding | |
Molecular Function | protein-containing complex binding | |
Biological Process | clathrin-dependent endocytosis | |
Biological Process | intracellular protein transport | |
Biological Process | postsynaptic neurotransmitter receptor internalization | |
Biological Process | regulation of hematopoietic stem cell differentiation | |
Biological Process | synaptic vesicle endocytosis | |
Biological Process | vesicle-mediated transport |
Keywords
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAP-2 complex subunit alpha-2
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP17427
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Membrane, coated pit ; Peripheral membrane protein
Note: AP-2 appears to be excluded from internalizing CCVs and to disengage from sites of endocytosis seconds before internalization of the nascent CCV.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 21 | Reduces interaction with CD4 endocytosis signal motif; when associated with AP2S1 S-15. | ||||
Sequence: R → E | ||||||
Mutagenesis | 31 | Reduces phosphatidylinositol binding. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 32 | Reduces phosphatidylinositol binding. | ||||
Sequence: R → Q | ||||||
Mutagenesis | 35 | Reduces phosphatidylinositol binding. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 45 | Reduces phosphatidylinositol binding. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 55 | Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-56 and Q-57. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 56 | Strongly reduces phosphatidylinositol binding. | ||||
Sequence: K → E | ||||||
Mutagenesis | 56 | Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-55 and Q-57. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 57 | Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-55 and Q-56. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 61 | Reduces phosphatidylinositol binding. | ||||
Sequence: K → Q | ||||||
Mutagenesis | 727 | No effect on DENND1A-,DENND1B- nor DENND1C-binding. | ||||
Sequence: K → A | ||||||
Mutagenesis | 782 | Reduces DENND1A- and DENND1C-binding. | ||||
Sequence: Q → A | ||||||
Mutagenesis | 837 | Reduces SNAP91, AMPH and BIN1 binding. Abolishes AMPH and SNAP91 binding; when associated with A-916. Abolishes EPN1 and EPS15 binding; when associated with A-905. | ||||
Sequence: F → A | ||||||
Mutagenesis | 840 | Abolishes AMPH, BIN1, DGKD, EPS15, EPN1, auxilin and SNAP91 binding. | ||||
Sequence: W → A | ||||||
Mutagenesis | 849 | No effect. | ||||
Sequence: E → A | ||||||
Mutagenesis | 905 | Strongly reduces AMPH, SNAP91, auxilin and BIN1 binding. Abolishes EPN1 and EPS15 binding; when associated with A-837. | ||||
Sequence: R → A | ||||||
Mutagenesis | 907 | Strongly reduces AMPH, SNAP91 and BIN1 binding. Slightly reduces EPS15 and auxilin binding. | ||||
Sequence: E → A | ||||||
Mutagenesis | 916 | Strongly reduces AMPH and SNAP91 binding. Abolishes DENND1B-binding; no effect on DENND1A-, nor DENND1C-binding. Abolishes AMPH and SNAP91 binding; when associated with A-837. | ||||
Sequence: R → A | ||||||
Mutagenesis | 920 | Abolishes AMPH and BIN1 binding. Reduces EPS15, SNAP91 and auxilin binding. | ||||
Sequence: R → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 43 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000193733 | 1-938 | AP-2 complex subunit alpha-2 | |||
Sequence: MPAVSKGDGMRGLAVFISDIRNCKSKEAEIKRINKELANIRSKFKGDKALDGYSKKKYVCKLLFIFLLGHDIDFGHMEAVNLLSSNRYTEKQIGYLFISVLVNSNSELIRLINNAIKNDLASRNPTFMGLALHCIANVGSREMAEAFAGEIPKILVAGDTMDSVKQSAALCLLRLYRTSPDLVPMGDWTSRVVHLLNDQHLGVVTAATSLITTLAQKNPEEFKTSVSLAVSRLSRIVTSASTDLQDYTYYFVPAPWLSVKLLRLLQCYPPPDPAVRGRLTECLETILNKAQEPPKSKKVQHSNAKNAVLFEAISLIIHHDSEPNLLVRACNQLGQFLQHRETNLRYLALESMCTLASSEFSHEAVKTHIETVINALKTERDVSVRQRAVDLLYAMCDRSNAQQIVAEMLSYLETADYSIREEIVLKVAILAEKYAVDYTWYVDTILNLIRIAGDYVSEEVWYRVIQIVINRDDVQGYAAKTVFEALQAPACHENLVKVGGYILGEFGNLIAGDPRSSPLIQFNLLHSKFHLCSVPTRALLLSTYIKFVNLFPEVKATIQDVLRSDSQLKNADVELQQRAVEYLRLSTVASTDILATVLEEMPPFPERESSILAKLKKKKGPSTVTDLEETKRERSIDVNGGPEPVPASTSAASTPSPSADLLGLGAVPPAPTGPPPSSGGGLLVDVFSDSASAVAPLAPGSEDNFARFVCKNNGVLFENQLLQIGLKSEFRQNLGRMFIFYGNKTSTQFLNFTPTLICADDLQTNLNLQTKPVDPTVDGGAQVQQVVNIECISDFTEAPVLNIQFRYGGTFQNVSVKLPITLNKFFQPTEMASQDFFQRWKQLSNPQQEVQNIFKAKHPMDTEITKAKIIGFGSALLEEVDPNPANFVGAGIIHTKTTQIGCLLRLEPNLQAQMYRLTLRTSKDTVSQRLCELLSEQF |
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in the brain (at protein level).
Gene expression databases
Interaction
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 expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (By similarity).
Interacts with Cacfd1 (PubMed:29288152).
Interacts with DNAJC6 (PubMed:11470803).
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 expression of ABCB11 through its internalization in a clathrin-dependent manner and its subsequent degradation (By similarity).
Interacts with Cacfd1 (PubMed:29288152).
Interacts with DNAJC6 (PubMed:11470803).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 615-638 | Basic and acidic residues | ||||
Sequence: LKKKKGPSTVTDLEETKRERSIDV | ||||||
Region | 615-681 | Disordered | ||||
Sequence: LKKKKGPSTVTDLEETKRERSIDVNGGPEPVPASTSAASTPSPSADLLGLGAVPPAPTGPPPSSGGG |
Sequence similarities
Belongs to the adaptor complexes large subunit family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length938
- Mass (Da)104,017
- Last updated2011-07-27 v2
- Checksum183FE8DFE199DBCA
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A0J9YUA7 | A0A0J9YUA7_MOUSE | Ap2a2 | 131 |
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 615-638 | Basic and acidic residues | ||||
Sequence: LKKKKGPSTVTDLEETKRERSIDV | ||||||
Sequence conflict | 858-859 | in Ref. 4; AAH10597 | ||||
Sequence: HP → LE | ||||||
Sequence conflict | 889-890 | in Ref. 1; CAA33097 and 5; AAB62703 | ||||
Sequence: GA → VL |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X14972 EMBL· GenBank· DDBJ | CAA33097.1 EMBL· GenBank· DDBJ | mRNA | ||
AK088500 EMBL· GenBank· DDBJ | BAC40392.1 EMBL· GenBank· DDBJ | mRNA | ||
AC158224 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC102524 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC010597 EMBL· GenBank· DDBJ | AAH10597.1 EMBL· GenBank· DDBJ | mRNA | ||
AF006990 EMBL· GenBank· DDBJ | AAB62703.1 EMBL· GenBank· DDBJ | mRNA |