Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

AAK1 (Q2M2I8) - Overview - Molecular Target Synopsis

Protein


AAK1, AP2-associated protein kinase 1
Enzyme Classification 2.7.11.1
UniProt Q2M2I8

Also Known as AAK1_HUMAN, AAK1, KIAA1048

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. Interacts with alpha-adaptin, AP-2, clathrin, NUMB and EPS15 isoform 2. Interacts with membrane-bound activated NOTCH1 but not with the inactive full-length form of NOTCH1. Preferentially interacts with monoubiquitinated activated NOTCH1 compared to the non-ubiquitinated form.

5TE0
CRYSTAL STRUCTURE OF ADAPTOR PROTEIN 2 ASSOCIATED KINASE (AAK1) IN COMPLEX WITH BIBF 1120
RCSB/PDB
Inspect Structure
See all 3D Structures for AAK1

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: AAK1 is active in the following subcellular-locations: cell membrane, clathrin-coated pit, membrane.
GO terms: AAK1 is active in the following subcellular-locations: cell leading edge, clathrin-coated pit, clathrin-coated vesicle, cytosol, extrinsic component of plasma membrane, nucleus, terminal bouton.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project AAK1 has gain in 1 cell-lines, loss in 0 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: CCRF_CEM, SK_MEL_28, SF_268

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: NCI-H209, NCI-H1581, A-375

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: HSMM, NHLF, HUVEC

(see details)

RNA Interference


AAK1 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB453, SCC36. (see details)

3D Structures


For AAK1 there are:
3 structures (5 chains) solved
3 are solved in complex with at least one small molecule ligand
1 are solved with an approved drug

AAK1 is solved in complex with the approved drug(s):

XIN/NINTEDANIB (5TE0_A).

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


AAK1 has been screened with 143 compounds (204 bioactivities), 18 compounds have bioactivities that show binding affinity of <= 500nM (30 bioactivities). (see details)