Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person UniProt:Q2M2I8-1 AAK1

Class:IdReferenceIsoform:8968638
_chainChangeLogchain:1-961 added on Fri February 17 2017
_displayNameUniProt:Q2M2I8-1 AAK1
_timestamp2025-02-21 18:53:50
chainchain:1-961
checksum1FB44D0FDEF6CAD0
commentFUNCTION 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
descriptionrecommendedName: AP2-associated protein kinase 1 ecNumber evidence="8 9 10 11 14 15"2.7.11.1 alternativeName: Adaptor-associated kinase 1
geneNameAAK1
KIAA1048
identifierQ2M2I8
isoformParent
isSequenceChangedFALSE
keyword3D-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
nameAAK1
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8987665] ENSEMBL:ENSG00000115977 AAK1 [Homo sapiens]
secondaryIdentifierAAK1_HUMAN
Q4ZFZ3
Q53RX6
Q9UPV4
sequenceLength961
species[Species:48887] Homo sapiens
variantIdentifierQ2M2I8-1
[Change default viewing format]
No pathways have been reviewed or authored by UniProt:Q2M2I8-1 AAK1 (8968638)