P17427 · AP2A2_MOUSE

  • Protein
    AP-2 complex subunit alpha-2
  • Gene
    Ap2a2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site11-12a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) (UniProtKB | ChEBI)
Binding site43a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) (UniProtKB | ChEBI)
Binding site53a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) (UniProtKB | ChEBI)
Binding site57-61a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular ComponentAP-2 adaptor complex
Cellular Componentcytoplasmic side of plasma membrane
Cellular Componentcytoplasmic vesicle
Cellular Componentmembrane coat
Cellular Componentpostsynapse
Cellular Componentsecretory granule
Cellular Componentsynaptic vesicle
Molecular Functionclathrin adaptor activity
Molecular Functiondisordered domain specific binding
Molecular Functionkinase binding
Molecular Functionphosphatidylinositol binding
Molecular Functionprotein domain specific binding
Molecular Functionprotein kinase binding
Molecular Functionprotein serine/threonine kinase binding
Molecular Functionprotein-containing complex binding
Biological Processclathrin-dependent endocytosis
Biological Processintracellular protein transport
Biological Processpostsynaptic neurotransmitter receptor internalization
Biological Processregulation of hematopoietic stem cell differentiation
Biological Processsynaptic vesicle endocytosis
Biological Processvesicle-mediated transport

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    AP-2 complex subunit alpha-2
  • Alternative names
    • 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

Gene names

    • Name
      Ap2a2
    • Synonyms
      Adtab

Organism names

  • Taxonomic identifier
  • Strains
    • NOD
    • C57BL/6J
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P17427
  • Secondary accessions
    • Q8C2J5
    • Q921V0

Proteomes

Organism-specific databases

Subcellular Location

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

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis21Reduces interaction with CD4 endocytosis signal motif; when associated with AP2S1 S-15.
Mutagenesis31Reduces phosphatidylinositol binding.
Mutagenesis32Reduces phosphatidylinositol binding.
Mutagenesis35Reduces phosphatidylinositol binding.
Mutagenesis45Reduces phosphatidylinositol binding.
Mutagenesis55Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-56 and Q-57.
Mutagenesis56Strongly reduces phosphatidylinositol binding.
Mutagenesis56Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-55 and Q-57.
Mutagenesis57Strongly reduces phosphatidylinositol binding. Abolishes phosphatidylinositol binding; when associated with Q-55 and Q-56.
Mutagenesis61Reduces phosphatidylinositol binding.
Mutagenesis727No effect on DENND1A-,DENND1B- nor DENND1C-binding.
Mutagenesis782Reduces DENND1A- and DENND1C-binding.
Mutagenesis837Reduces 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.
Mutagenesis840Abolishes AMPH, BIN1, DGKD, EPS15, EPN1, auxilin and SNAP91 binding.
Mutagenesis849No effect.
Mutagenesis905Strongly reduces AMPH, SNAP91, auxilin and BIN1 binding. Abolishes EPN1 and EPS15 binding; when associated with A-837.
Mutagenesis907Strongly reduces AMPH, SNAP91 and BIN1 binding. Slightly reduces EPS15 and auxilin binding.
Mutagenesis916Strongly 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.
Mutagenesis920Abolishes AMPH and BIN1 binding. Reduces EPS15, SNAP91 and auxilin binding.

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.

Go to variant viewer

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00001937331-938AP-2 complex subunit alpha-2

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).
View interactors in UniProtKB
View CPX-5153 in Complex Portal

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for compositional bias, region.

TypeIDPosition(s)Description
Compositional bias615-638Basic and acidic residues
Region615-681Disordered

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    938
  • Mass (Da)
    104,017
  • Last updated
    2011-07-27 v2
  • Checksum
    183FE8DFE199DBCA
MPAVSKGDGMRGLAVFISDIRNCKSKEAEIKRINKELANIRSKFKGDKALDGYSKKKYVCKLLFIFLLGHDIDFGHMEAVNLLSSNRYTEKQIGYLFISVLVNSNSELIRLINNAIKNDLASRNPTFMGLALHCIANVGSREMAEAFAGEIPKILVAGDTMDSVKQSAALCLLRLYRTSPDLVPMGDWTSRVVHLLNDQHLGVVTAATSLITTLAQKNPEEFKTSVSLAVSRLSRIVTSASTDLQDYTYYFVPAPWLSVKLLRLLQCYPPPDPAVRGRLTECLETILNKAQEPPKSKKVQHSNAKNAVLFEAISLIIHHDSEPNLLVRACNQLGQFLQHRETNLRYLALESMCTLASSEFSHEAVKTHIETVINALKTERDVSVRQRAVDLLYAMCDRSNAQQIVAEMLSYLETADYSIREEIVLKVAILAEKYAVDYTWYVDTILNLIRIAGDYVSEEVWYRVIQIVINRDDVQGYAAKTVFEALQAPACHENLVKVGGYILGEFGNLIAGDPRSSPLIQFNLLHSKFHLCSVPTRALLLSTYIKFVNLFPEVKATIQDVLRSDSQLKNADVELQQRAVEYLRLSTVASTDILATVLEEMPPFPERESSILAKLKKKKGPSTVTDLEETKRERSIDVNGGPEPVPASTSAASTPSPSADLLGLGAVPPAPTGPPPSSGGGLLVDVFSDSASAVAPLAPGSEDNFARFVCKNNGVLFENQLLQIGLKSEFRQNLGRMFIFYGNKTSTQFLNFTPTLICADDLQTNLNLQTKPVDPTVDGGAQVQQVVNIECISDFTEAPVLNIQFRYGGTFQNVSVKLPITLNKFFQPTEMASQDFFQRWKQLSNPQQEVQNIFKAKHPMDTEITKAKIIGFGSALLEEVDPNPANFVGAGIIHTKTTQIGCLLRLEPNLQAQMYRLTLRTSKDTVSQRLCELLSEQF

Computationally mapped potential isoform sequences

There is 1 potential isoform mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0J9YUA7A0A0J9YUA7_MOUSEAp2a2131

Features

Showing features for compositional bias, sequence conflict.

TypeIDPosition(s)Description
Compositional bias615-638Basic and acidic residues
Sequence conflict858-859in Ref. 4; AAH10597
Sequence conflict889-890in Ref. 1; CAA33097 and 5; AAB62703

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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