InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: AAK1

Summary

InnateDB Protein

IDBP-295668.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

AAK1

Protein Name

AP2 associated kinase 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000386456

InnateDB Gene

IDBG-54929 (AAK1)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000269PubMed:12952931, ECO:0000269PubMed:17494869, ECO:0000269PubMed:18657069, ECO:0000269PubMed:21464124}.

Subcellular Localization

Cell membrane {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Membrane, clathrin-coated pit {ECO:0000250}. 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 (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Detected in brain, heart and liver. Isoform 1 is the predominant isoform in brain. {ECO:0000269PubMed:17494869}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 4 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	4 [view]
Protein-Protein	4 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005112	Notch binding
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0035612	AP-2 adaptor complex binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006897	endocytosis
GO:0032880	regulation of protein localization
GO:0045747	positive regulation of Notch signaling pathway
GO:0046777	protein autophosphorylation
GO:0050821	protein stabilization
GO:2000369	regulation of clathrin-mediated endocytosis

Cellular Component

GO:0005905	coated pit
GO:0019897	extrinsic component of plasma membrane
GO:0030136	clathrin-coated vesicle
GO:0031252	cell leading edge
GO:0043195	terminal bouton

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt