Tchem AAK1 AP2-associated protein kinase 1

Protein Summary

Description

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. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. 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. Adaptor-related protein complex 2 (AP-2 complexes) functions during receptor-mediated endocytosis to trigger clathrin assembly, interact with membrane-bound receptors, and recruit encodytic accessory factors. This gene encodes a member of the SNF1 subfamily of Ser/Thr protein kinases. The protein interacts with and phosphorylates a subunit of the AP-2 complex, which promotes binding of AP-2 to sorting signals found in membrane-bound receptors and subsequent receptor endocytosis. Its kinase activity is stimulated by clathrin. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q2M2I8
• Q4ZFZ3
• Q53RX6
• Q9UPV4

Gene Name

• AAK1

Ensembl ID

• ENST00000406297
• ENSP00000385181
• ENSG00000115977
• ENST00000409085
• ENSP00000386456

Symbol

• KIAA1048

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
drug perturbation	1
disease perturbation	0.99
transcription factor perturbation	0.98
kinase perturbation	0.97
molecular function	0.96

Protein Classes

PANTHER Classes

Protein / Transferase / Kinase / Protein Kinase / Non-receptor Serine/threonine Protein Kinase / Ap2-associated Protein Kinase 1

DTO Classes

Protein / Kinase / Protein Kinase / Other Group / Nak Family / Ap2-associated Protein Kinase 1

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 91.32   (req: < 5)

Gene RIFs: 12   (req: <= 3)

Antibodies: 326   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 91.32   (req: >= 5)

Gene RIFs: 12   (req: > 3)

Antibodies: 326   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 13

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 58

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 3