F1SPM8 · AAK1_PIG

  • Protein
    AP2-associated protein kinase 1
  • Gene
    AAK1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    5/5

Function

function

Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages of endocytosis (PubMed:11877457).
Preferentially, may phosphorylate substrates on threonine residues (By similarity).
Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (By similarity).
Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (By similarity).
Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (By similarity).

Catalytic activity

Activity regulation

Stimulated by clathrin.

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site52-60ATP (UniProtKB | ChEBI)
Binding site74ATP (UniProtKB | ChEBI)
Active site176Proton acceptor

GO annotations

AspectTerm
Cellular Componentcell leading edge
Cellular Componentclathrin-coated pit
Cellular Componentclathrin-coated vesicle
Cellular Componentplasma membrane
Cellular Componentpresynapse
Cellular Componentterminal bouton
Molecular FunctionAP-2 adaptor complex binding
Molecular FunctionATP binding
Molecular FunctionNotch binding
Molecular Functionprotein serine kinase activity
Molecular Functionprotein serine/threonine kinase activity
Biological Processendocytosis
Biological Processpositive regulation of Notch signaling pathway
Biological Processprotein phosphorylation
Biological Processprotein stabilization
Biological Processregulation of clathrin-dependent endocytosis
Biological Processregulation of protein localization

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    AP2-associated protein kinase 1
  • EC number
  • Alternative names
    • Adaptor-associated kinase 1

Gene names

    • Name
      AAK1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Suina > Suidae > Sus

Accessions

  • Primary accession
    F1SPM8

Proteomes

Subcellular Location

Cell membrane
; Peripheral membrane protein
Presynapse
Note: Active when found in clathrin-coated pits at the plasma membrane. In neuronal cells, enriched at presynaptic terminals. In non-neuronal cells, enriched at leading edge of migrating cells.

Keywords

PTM/Processing

Features

Showing features for modified residue, chain.

TypeIDPosition(s)Description
Modified residue1N-acetylmethionine
ChainPRO_00004133621-968AP2-associated protein kinase 1
Modified residue14Phosphoserine
Modified residue234Phosphotyrosine
Modified residue235Phosphoserine
Modified residue354Phosphothreonine
Modified residue389Phosphothreonine
Modified residue391Omega-N-methylarginine
Modified residue613Phosphothreonine
Modified residue625Phosphoserine
Modified residue627Phosphothreonine
Modified residue630Phosphoserine
Modified residue631Phosphoserine
Modified residue644Phosphoserine
Modified residue657Phosphoserine
Modified residue660Phosphothreonine
Modified residue694Phosphotyrosine
Modified residue738Phosphoserine
Modified residue853Phosphoserine
Modified residue944Phosphoserine
Modified residue945Phosphoserine

Post-translational modification

Autophosphorylated.

Keywords

Proteomic databases

Interaction

Subunit

Interacts (via CBD domain) with clathrin (By similarity).
Interacts with AP-2 complex (By similarity).
Interacts with NUMB (By similarity).
Interacts with alpha-adaptin (By similarity).
Interacts with EPS15 (By similarity).
Interacts with membrane-bound activated NOTCH1 but not with the inactive full-length form of NOTCH1 (By similarity).
Preferentially interacts with monoubiquitinated activated NOTCH1 compared to the non-ubiquitinated form (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, domain, compositional bias.

TypeIDPosition(s)Description
Region1-25Disordered
Domain46-315Protein kinase
Region327-485Disordered
Compositional bias353-382Polar residues
Compositional bias400-419Polar residues
Compositional bias420-449Pro residues
Compositional bias450-472Polar residues
Region578-640Disordered
Compositional bias600-632Polar residues
Region671-708Disordered
Region830-967Clathrin-binding domain (CBD)
Region843-862Disordered
Region929-952Disordered
Compositional bias936-952Polar residues

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    968
  • Mass (Da)
    104,310
  • Last updated
    2011-10-19 v2
  • Checksum
    4F07200E056E047D
MKKFFDSRREQGGSGLGSGSSGGGGSTSGLGSGYIGRVFGIGRQQVTVDEVLAEGGFAIVFLVRTSNGMKCALKRMFVNNEHDLQVCKREIQIMRDLSGHKNIVGYIDSSINNVSSGDVWEVLILMDFCRGGQVVNLMNQRLQTGFTESEVLQIFCDTCEAVARLHQCKTPIIHRDLKVENILLHDRGHYVLCDFGSATNKFQNPQTEGVNAVEDEIKKYTTLSYRAPEMVNLYSGKIITTKADIWALGCLLYKLCYFTLPFGESQVAICDGNFTIPDNSRYSQDMHCLIRYMLEPDPDKRPDIYQVSFFSFKLLKKECPVPNVQNSPIPAKLPEPVKASEAAAKKTQPKARLTDPIPTTETSIAPRQRPKAGQTQPNPGILPIQPALTPRKRAMVQPPPQVAGSSNQPGLLASVPQPKTQAPPSQPLPQSQAKQPQAPPAPQQPPSAPAQGLPAQAQATPQHQQQLFLKQQPQPPQPQPQAQAPPVKSLKFYPFYPMCKGRQTVSSQFQAVHPAAQQPAIAQFPAVSQGSSQQQLIQNFYQQQQQQQQQQQLATTLHQQQLLTQQAALQQKTTVAAIQPPQAQPATASQPPPAQEPAQIQAPVRQQPKVQTTPPPAIQGQKLGSLTPPSSPKAQRAGHRRILSDVTHSAVFGVPASKSTQLLQAAAAEASLNKSKSATTTPSGSPRASQQNVYNPSEGSTWNPFDDDNFSKLTAEELLNKDFAKLGEGKHPEKLGGSAESLIPGFQPTQGDAFAASSFAAGTAEKRKGGQAVDSSLPLLSVSDPFIPLQVPDAPEKLIEGLKSPDTSLLLPDLLPMTDPFGSTSDAVIEKADVAVESLIPGLEPPVPQRLPSQTESVASNRTDSLTGEDALIDCSLLSNPTTDLLEEFAPIAISAPAHKAAEDSNLISGFDVPEGSDKVAEDEFDPIPVLITKNPQGGHSRNSSGSSESSLPNLARSLLLVDQLIDL

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias353-382Polar residues
Compositional bias400-419Polar residues
Compositional bias420-449Pro residues
Compositional bias450-472Polar residues
Compositional bias600-632Polar residues
Compositional bias936-952Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
CU467585
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
FS674854
EMBL· GenBank· DDBJ
-mRNA No translation available.

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