AAK1 Gene: AP2 Associated Kinase 1
A key regulator of clathrin-mediated endocytosis and potential therapeutic target in neurological disorders and cancer
Gene Information Card
| Symbol | AAK1 |
|---|---|
| Full Name | AP2 Associated Kinase 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 2q34 |
| NCBI Gene ID | 22848 ncbi.nlm.nih.gov/gene/22848 |
| Ensembl ID | ENSG00000115977 |
| UniProt ID | Q2M2I8 |
| OMIM ID | 610363 |
| HGNC ID | 19679 |
| Aliases | KIAA1048, MGC87469 |
Description
AAK1 (AP2 Associated Kinase 1) encodes a serine/threonine kinase that phosphorylates the mu2 subunit of the AP2 adaptor complex, regulating clathrin-mediated endocytosis. It is involved in synaptic vesicle recycling, receptor internalization, and intracellular trafficking. AAK1 has been implicated in neurological disorders, viral infections, and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Schizophrenia | AAK1 variants may alter synaptic vesicle dynamics, affecting neurotransmission | GWAS association (PMID: 25056061) |
| Parkinson disease | AAK1 expression changes in dopaminergic neurons may contribute to endocytic dysfunction | Expression studies (PMID: 25621951) |
| Hepatitis C virus infection | AAK1 phosphorylates AP2 to facilitate HCV entry; inhibition blocks viral replication | Functional studies (PMID: 23376921) |
| Lung cancer | AAK1 overexpression correlates with poor prognosis; promotes tumor growth via endocytic signaling | Expression and survival analysis (COSMIC, TCGA) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | High |
| Testis | 8.7 | Medium |
| Lung | 6.3 | Medium |
| Liver | 4.1 | Low |
| Heart | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 12.5 | High expression in embryonic kidney cells |
| SH-SY5Y | 14.1 | Neuroblastoma cell line; high expression |
| A549 | 7.2 | Lung carcinoma; moderate expression |
| HepG2 | 5.0 | Hepatocellular carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1553G>A (p.Arg518Gln) | Missense | <0.01% | Unknown; found in cancer samples (COSMIC) |
| c.2144C>T (p.Pro715Leu) | Missense | <0.01% | Unknown; reported in ClinVar |
| c.1234_1235insA | Frameshift | <0.01% | Loss of function; predicted truncation |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations predicted to cause loss of kinase activity or protein truncation, impairing AP2 phosphorylation and endocytosis.
Gain of Function (GOF)
Not well characterized; some missense variants may increase kinase activity, but evidence is limited.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004672 - protein kinase activity | • GO:0005524 - ATP binding |
| • GO:0006897 - endocytosis | • GO:0016301 - kinase activity |
| • GO:0032051 - clathrin binding | • GO:0043231 - intracellular membrane-bounded organelle |
Pathways
• Clathrin-mediated endocytosis (Reactome: R-HSA-8856825)
• AP2 adaptor complex phosphorylation (Reactome: R-HSA-8856828)
• Synaptic vesicle recycling (KEGG: hsa04721)
Protein Summary
AAK1 is a 961-amino acid serine/threonine kinase with an N-terminal kinase domain and a C-terminal domain that binds clathrin and AP2. It phosphorylates the mu2 subunit of AP2, enhancing its affinity for cargo and promoting clathrin-coated vesicle formation. AAK1 is ubiquitously expressed, with highest levels in brain and testis. It plays critical roles in synaptic vesicle recycling, receptor internalization, and viral entry. Dysregulation is linked to neurological disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| AAK1 Knockout HEK293 Cell Line | EDJ-KQ269 | Human | 22848 | Details Get a Quote |
| AAK1 Knockout A-549 Cell Line | EDC07782 | Human | 22848 | Details Get a Quote |
| AAK1 Knockout HCT 116 Cell Line | EDJ-KQ41012 | Human | 22848 | Details Get a Quote |
| AAK1 Knockout HeLa Cell Line | EDJ-KQ41013 | Human | 22848 | Details Get a Quote |
| AAK1（p.S624A） Point Mutation in A-549 Cell Line | EDC03233 | Human | 22848 | Details Get a Quote |
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