F1SPM8 · AAK1_PIG
- ProteinAP2-associated protein kinase 1
- GeneAAK1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids968 (go to sequence)
- Protein existenceEvidence at transcript level
- Annotation score5/5
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).
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
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
Stimulated by clathrin.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cell leading edge | |
Cellular Component | clathrin-coated pit | |
Cellular Component | clathrin-coated vesicle | |
Cellular Component | plasma membrane | |
Cellular Component | presynapse | |
Cellular Component | terminal bouton | |
Molecular Function | AP-2 adaptor complex binding | |
Molecular Function | ATP binding | |
Molecular Function | Notch binding | |
Molecular Function | protein serine kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Biological Process | endocytosis | |
Biological Process | positive regulation of Notch signaling pathway | |
Biological Process | protein phosphorylation | |
Biological Process | protein stabilization | |
Biological Process | regulation of clathrin-dependent endocytosis | |
Biological Process | regulation of protein localization |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameAP2-associated protein kinase 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Laurasiatheria > Artiodactyla > Suina > Suidae > Sus
Accessions
- Primary accessionF1SPM8
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
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
- Cellular component
PTM/Processing
Features
Showing features for modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Modified residue | 1 | N-acetylmethionine | ||||
Sequence: M | ||||||
Chain | PRO_0000413362 | 1-968 | AP2-associated protein kinase 1 | |||
Sequence: MKKFFDSRREQGGSGLGSGSSGGGGSTSGLGSGYIGRVFGIGRQQVTVDEVLAEGGFAIVFLVRTSNGMKCALKRMFVNNEHDLQVCKREIQIMRDLSGHKNIVGYIDSSINNVSSGDVWEVLILMDFCRGGQVVNLMNQRLQTGFTESEVLQIFCDTCEAVARLHQCKTPIIHRDLKVENILLHDRGHYVLCDFGSATNKFQNPQTEGVNAVEDEIKKYTTLSYRAPEMVNLYSGKIITTKADIWALGCLLYKLCYFTLPFGESQVAICDGNFTIPDNSRYSQDMHCLIRYMLEPDPDKRPDIYQVSFFSFKLLKKECPVPNVQNSPIPAKLPEPVKASEAAAKKTQPKARLTDPIPTTETSIAPRQRPKAGQTQPNPGILPIQPALTPRKRAMVQPPPQVAGSSNQPGLLASVPQPKTQAPPSQPLPQSQAKQPQAPPAPQQPPSAPAQGLPAQAQATPQHQQQLFLKQQPQPPQPQPQAQAPPVKSLKFYPFYPMCKGRQTVSSQFQAVHPAAQQPAIAQFPAVSQGSSQQQLIQNFYQQQQQQQQQQQLATTLHQQQLLTQQAALQQKTTVAAIQPPQAQPATASQPPPAQEPAQIQAPVRQQPKVQTTPPPAIQGQKLGSLTPPSSPKAQRAGHRRILSDVTHSAVFGVPASKSTQLLQAAAAEASLNKSKSATTTPSGSPRASQQNVYNPSEGSTWNPFDDDNFSKLTAEELLNKDFAKLGEGKHPEKLGGSAESLIPGFQPTQGDAFAASSFAAGTAEKRKGGQAVDSSLPLLSVSDPFIPLQVPDAPEKLIEGLKSPDTSLLLPDLLPMTDPFGSTSDAVIEKADVAVESLIPGLEPPVPQRLPSQTESVASNRTDSLTGEDALIDCSLLSNPTTDLLEEFAPIAISAPAHKAAEDSNLISGFDVPEGSDKVAEDEFDPIPVLITKNPQGGHSRNSSGSSESSLPNLARSLLLVDQLIDL | ||||||
Modified residue | 14 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 234 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 235 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 354 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 389 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 391 | Omega-N-methylarginine | ||||
Sequence: R | ||||||
Modified residue | 613 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 625 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 627 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 630 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 631 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 644 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 657 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 660 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 694 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 738 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 853 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 944 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 945 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Autophosphorylated.
Keywords
- PTM
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-25 | Disordered | ||||
Sequence: MKKFFDSRREQGGSGLGSGSSGGGG | ||||||
Domain | 46-315 | Protein kinase | ||||
Sequence: VTVDEVLAEGGFAIVFLVRTSNGMKCALKRMFVNNEHDLQVCKREIQIMRDLSGHKNIVGYIDSSINNVSSGDVWEVLILMDFCRGGQVVNLMNQRLQTGFTESEVLQIFCDTCEAVARLHQCKTPIIHRDLKVENILLHDRGHYVLCDFGSATNKFQNPQTEGVNAVEDEIKKYTTLSYRAPEMVNLYSGKIITTKADIWALGCLLYKLCYFTLPFGESQVAICDGNFTIPDNSRYSQDMHCLIRYMLEPDPDKRPDIYQVSFFSFKLL | ||||||
Region | 327-485 | Disordered | ||||
Sequence: SPIPAKLPEPVKASEAAAKKTQPKARLTDPIPTTETSIAPRQRPKAGQTQPNPGILPIQPALTPRKRAMVQPPPQVAGSSNQPGLLASVPQPKTQAPPSQPLPQSQAKQPQAPPAPQQPPSAPAQGLPAQAQATPQHQQQLFLKQQPQPPQPQPQAQAP | ||||||
Compositional bias | 353-382 | Polar residues | ||||
Sequence: LTDPIPTTETSIAPRQRPKAGQTQPNPGIL | ||||||
Compositional bias | 400-419 | Polar residues | ||||
Sequence: PQVAGSSNQPGLLASVPQPK | ||||||
Compositional bias | 420-449 | Pro residues | ||||
Sequence: TQAPPSQPLPQSQAKQPQAPPAPQQPPSAP | ||||||
Compositional bias | 450-472 | Polar residues | ||||
Sequence: AQGLPAQAQATPQHQQQLFLKQQ | ||||||
Region | 578-640 | Disordered | ||||
Sequence: IQPPQAQPATASQPPPAQEPAQIQAPVRQQPKVQTTPPPAIQGQKLGSLTPPSSPKAQRAGHR | ||||||
Compositional bias | 600-632 | Polar residues | ||||
Sequence: IQAPVRQQPKVQTTPPPAIQGQKLGSLTPPSSP | ||||||
Region | 671-708 | Disordered | ||||
Sequence: SLNKSKSATTTPSGSPRASQQNVYNPSEGSTWNPFDDD | ||||||
Region | 830-967 | Clathrin-binding domain (CBD) | ||||
Sequence: EKADVAVESLIPGLEPPVPQRLPSQTESVASNRTDSLTGEDALIDCSLLSNPTTDLLEEFAPIAISAPAHKAAEDSNLISGFDVPEGSDKVAEDEFDPIPVLITKNPQGGHSRNSSGSSESSLPNLARSLLLVDQLID | ||||||
Region | 843-862 | Disordered | ||||
Sequence: LEPPVPQRLPSQTESVASNR | ||||||
Region | 929-952 | Disordered | ||||
Sequence: PVLITKNPQGGHSRNSSGSSESSL | ||||||
Compositional bias | 936-952 | Polar residues | ||||
Sequence: PQGGHSRNSSGSSESSL |
Sequence similarities
Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length968
- Mass (Da)104,310
- Last updated2011-10-19 v2
- Checksum4F07200E056E047D
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 353-382 | Polar residues | ||||
Sequence: LTDPIPTTETSIAPRQRPKAGQTQPNPGIL | ||||||
Compositional bias | 400-419 | Polar residues | ||||
Sequence: PQVAGSSNQPGLLASVPQPK | ||||||
Compositional bias | 420-449 | Pro residues | ||||
Sequence: TQAPPSQPLPQSQAKQPQAPPAPQQPPSAP | ||||||
Compositional bias | 450-472 | Polar residues | ||||
Sequence: AQGLPAQAQATPQHQQQLFLKQQ | ||||||
Compositional bias | 600-632 | Polar residues | ||||
Sequence: IQAPVRQQPKVQTTPPPAIQGQKLGSLTPPSSP | ||||||
Compositional bias | 936-952 | Polar residues | ||||
Sequence: PQGGHSRNSSGSSESSL |
Keywords
- Technical term