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Details on Person UniProt:Q2M2I8-1 AAK1
| Class:Id | ReferenceIsoform:8968638 |
|---|---|
| _chainChangeLog | chain:1-961 added on Fri February 17 2017 |
| _displayName | UniProt:Q2M2I8-1 AAK1 |
| _timestamp | 2025-02-21 18:53:50 |
| chain | chain:1-961 |
| checksum | 1FB44D0FDEF6CAD0 |
| comment | 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, PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:17494869, PubMed:25653444). Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate substrates on threonine residues (PubMed:11877457, PubMed:18657069). Regulates phosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligand complexes (PubMed:12952931). Phosphorylates NUMB and regulates its cellular localization, promoting NUMB localization to endosomes (PubMed:18657069). Binds to and stabilizes the activated form of NOTCH1, increases its localization in endosomes and regulates its transcriptional activity (PubMed:21464124).FUNCTION (Microbial infection) By regulating clathrin-mediated endocytosis, AAK1 plays a role in the entry of hepatitis C virus as well as for the lifecycle of other viruses such as Ebola and Dengue.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY REGULATION Stimulated by clathrin.SUBUNIT Interacts (via CBD domain) with clathrin (PubMed:14617351, PubMed:17494869). Interacts with AP-2 complex (PubMed:12952931, PubMed:14617351, PubMed:17494869). Interacts with NUMB (PubMed:18657069). Interacts with alpha-adaptin (By similarity). Interacts with EPS15 isoform 2 (PubMed:21464124). 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).INTERACTION 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.ALTERNATIVE PRODUCTS Detected in brain, heart and liver. Isoform 1 is the predominant isoform in brain.PTM Autophosphorylated.PHARMACEUTICAL By regulating the entry of hepatitis C virus as well as the lifecycle of other viruses such as Ebola and Dengue, AAK1 is a potential drug target for developing antiviral therapies.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.SEQUENCE CAUTION Extended N-terminus. |
| created | [InstanceEdit:8964659] Weiser, JD |
| description | recommendedName: AP2-associated protein kinase 1 ecNumber evidence="8 9 10 11 14 15"2.7.11.1 alternativeName: Adaptor-associated kinase 1 |
| geneName | AAK1 KIAA1048 |
| identifier | Q2M2I8 |
| isoformParent | |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing ATP-binding Cell membrane Cell projection Coated pit Endocytosis Kinase Membrane Methylation Nucleotide-binding Pharmaceutical Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Synapse Transferase |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | AAK1 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8987665] ENSEMBL:ENSG00000115977 AAK1 [Homo sapiens] |
| secondaryIdentifier | AAK1_HUMAN Q4ZFZ3 Q53RX6 Q9UPV4 |
| sequenceLength | 961 |
| species | [Species:48887] Homo sapiens |
| variantIdentifier | Q2M2I8-1 |
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No pathways have been reviewed or authored by UniProt:Q2M2I8-1 AAK1 (8968638)
