Q3UHJ0 · AAK1_MOUSE

  • Protein
    AP2-associated protein kinase 1
  • Gene
    Aak1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein 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. Preferentially, may phosphorylate substrates on threonine residues. Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes. Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes. Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity.

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 Componentcalyx of Held
Cellular Componentcell leading edge
Cellular Componentclathrin complex
Cellular Componentclathrin-coated pit
Cellular Componentclathrin-coated vesicle
Cellular Componentcytosol
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 Processpositive regulation of Notch signaling pathway
Biological Processpresynaptic endocytosis
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
    • Synonyms
      Kiaa1048

Organism names

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

Accessions

  • Primary accession
    Q3UHJ0
  • Secondary accessions
    • B2RUJ0
    • Q3TY53
    • Q6ZPZ6
    • Q80XP6

Proteomes

Organism-specific databases

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

Phenotypes & Variants

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 62 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Chemistry

PTM/Processing

Features

Showing features for modified residue, chain.

TypeIDPosition(s)Description
Modified residue1N-acetylmethionine
ChainPRO_00002505791-959AP2-associated protein kinase 1
Modified residue14Phosphoserine
Modified residue234Phosphotyrosine
Modified residue235Phosphoserine
Modified residue354Phosphothreonine
Modified residue389Phosphothreonine
Modified residue391Omega-N-methylarginine
Modified residue441Phosphothreonine
Modified residue604Phosphothreonine
Modified residue616Phosphoserine
Modified residue618Phosphothreonine
Modified residue621Phosphoserine
Modified residue622Phosphoserine
Modified residue635Phosphoserine
Modified residue648Phosphoserine
Modified residue651Phosphothreonine
Modified residue729Phosphoserine
Modified residue844Phosphoserine
Modified residue935Phosphoserine
Modified residue936Phosphoserine

Post-translational modification

Autophosphorylated.

Keywords

Proteomic databases

PTM databases

Expression

Gene expression 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 isoform 2 (By similarity).
Interacts with membrane-bound activated NOTCH1 but not with the inactive full-length form of NOTCH1 (PubMed:21464124).
Preferentially interacts with monoubiquitinated activated NOTCH1 compared to the non-ubiquitinated form (PubMed:21464124).

Protein-protein interaction databases

Chemistry

Miscellaneous

Family & Domains

Features

Showing features for region, compositional bias, domain.

TypeIDPosition(s)Description
Region1-27Disordered
Compositional bias11-27Polar residues
Domain46-315Protein kinase
Region340-385Disordered
Compositional bias353-382Polar residues
Region398-514Disordered
Compositional bias400-432Polar residues
Compositional bias444-480Polar residues
Compositional bias487-514Polar residues
Region578-630Disordered
Compositional bias591-625Polar residues
Region662-699Disordered
Region727-763Disordered
Compositional bias734-753Polar residues
Region821-958Clathrin-binding domain (CBD)
Region836-857Disordered
Compositional bias841-857Polar residues
Region923-943Disordered
Compositional bias925-943Polar residues

Sequence similarities

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

Phylogenomic databases

Family and domain databases

Sequence & Isoform

Align isoforms (2)
  • Sequence status
    Complete

This entry describes 2 isoforms produced by Alternative splicing.

Q3UHJ0-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    959
  • Mass (Da)
    103,346
  • Last updated
    2006-10-03 v2
  • Checksum
    B7D666EFD56D097A
MKKFFDSRREQGSSGLGSGSSGGGGSSSGLGSGYIGRVFGIGRQQVTVDEVLAEGGFALVFLVRTSNGVKCALKRMFVNNEHDLQVCKREIQIMRDLSGHKNIVGYIDSSINNVSSGDVWEVLILMDFCRGGQVVNLMNQRLQTGFTENEVLQIFCDTCEAVARLHQCKTPIIHRDLKVENILLHDRGHYVLCDFGSATNKFQNPQAEGVNAVEDEIKKYTTLSYRAPEMVNLYSGKIITTKADIWALGCLLYKLCYFTLPFGESQVAICDGSFTIPDNSRYSQDMHCLIRYMLEPDPDKRPDIYQVSYFSFKLLKKECPVPNVQNSPIPAKLPEPVKASEAAVKKTQPKARLTDPIPTTETSIAPRQRPKAGQTQPNPGILPIQPALTPRKRATVQPLPQAAGPSNQPGLLPSVSQPKAQATPSQPLQSSQPKQPQAPPTPQQTPATQTQGLPTQAQATPQHQQQHLLKQQQQQQQQPQQPTAPPQPAGTFYQQQQQQQQQQAQTQQFQAVHPAAQQPVTAQFPVGSQGGAQQQLMQNFYHQQQQQQQQQQQLMAQQAALQQKTAVVVPQSQAQPATAPQAAAAQEPGQIQAPVRQQPKVQTTPPPTIQGQKVGSLTPPSSPKTQRAGHRRILSDVTHSAVFGVPASKSTQLLQAAAAEASLNKSKSATTTPSGSPRTSQQNVSNASEGSTWNPFDDDNFSKLTAEELLNKDFAKLGEGKLPEKLGGSAESLIPGFQPTQGDAFTTPSFSAGTAEKRKGGQAVDSGIPLLSVSDPFIPLQVPDAPEKLIEGLKSPDTSLLLPDLLPMTDPFGSTSDAVIDKADVAVESLIPGLEPPVAQRLPSQTESVTSNRTDSLTGEDSLLDCSLLSNPTAGLLEEFAPIALSAPTHKAAEDSNLISGFGVAEGSEKVAEDEFDPIPVLITKNTQGGHSRNSSGSSESSLPNLARSLLLVDQLIDL

Q3UHJ0-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
A0A0N4SVA1A0A0N4SVA1_MOUSEAak1121
A0A571BDM4A0A571BDM4_MOUSEAak1237
A0A571BEI2A0A571BEI2_MOUSEAak1510

Features

Showing features for compositional bias, sequence conflict, alternative sequence.

TypeIDPosition(s)Description
Compositional bias11-27Polar residues
Sequence conflict79in Ref. 1; BAE27867
Compositional bias353-382Polar residues
Compositional bias400-432Polar residues
Compositional bias444-480Polar residues
Compositional bias487-514Polar residues
Alternative sequenceVSP_020670509-589in isoform 2
Compositional bias591-625Polar residues
Sequence conflict686in Ref. 3; BAC98082
Sequence conflict733in Ref. 2; AAI41177
Compositional bias734-753Polar residues
Compositional bias841-857Polar residues
Compositional bias925-943Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AK147363
EMBL· GenBank· DDBJ
BAE27867.1
EMBL· GenBank· DDBJ
mRNA
AK158879
EMBL· GenBank· DDBJ
BAE34710.1
EMBL· GenBank· DDBJ
mRNA
BC043125
EMBL· GenBank· DDBJ
AAH43125.1
EMBL· GenBank· DDBJ
mRNA
BC141176
EMBL· GenBank· DDBJ
AAI41177.1
EMBL· GenBank· DDBJ
mRNA
AK129272
EMBL· GenBank· DDBJ
BAC98082.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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