UniProt Accession

 AAK1_HUMAN; Q2M2I8; Q4ZFZ3; Q53RX6; Q9UPV4 

Genbank Protein ID

 AB028971; AC092431; AC079121; AC136007; BC104842; BC111965 

Genbank Nucleotide ID

 BAA83000.2; AAX88861.1; AAY14931.1; AAI04843.1; AAI11966.1 

Protein Name

 AP2-associated protein kinase 1 

Protein Synonyms/Alias

 Adaptor-associated kinase 1 

Gene Name

 AAK1 

Gene Synonyms/Alias

 KIAA1048 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
169	VARLHQCKTPIIHRD	ubiquitination	[1]
178	PIIHRDLKVENILLH	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 

Functional 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. 

Sequence Annotation

 DOMAIN 46 315 Protein kinase.
 NP_BIND 52 60 ATP (By similarity).
 ACT_SITE 176 176 Proton acceptor (By similarity).
 BINDING 74 74 ATP (By similarity).
 MOD_RES 14 14 Phosphoserine.
 MOD_RES 21 21 Phosphoserine (By similarity).
 MOD_RES 234 234 Phosphotyrosine.
 MOD_RES 235 235 Phosphoserine.
 MOD_RES 354 354 Phosphothreonine.
 MOD_RES 389 389 Phosphothreonine.
 MOD_RES 441 441 Phosphothreonine.
 MOD_RES 606 606 Phosphothreonine.
 MOD_RES 620 620 Phosphothreonine.
 MOD_RES 623 623 Phosphoserine.
 MOD_RES 624 624 Phosphoserine.
 MOD_RES 637 637 Phosphoserine.
 MOD_RES 640 640 Phosphothreonine (By similarity).
 MOD_RES 650 650 Phosphoserine.
 MOD_RES 652 652 Phosphoserine (By similarity).
 MOD_RES 653 653 Phosphothreonine.
 MOD_RES 687 687 Phosphotyrosine.
 MOD_RES 731 731 Phosphoserine.
 MOD_RES 937 937 Phosphoserine (By similarity).
 MOD_RES 938 938 Phosphoserine (By similarity).  

Keyword

 Alternative splicing; ATP-binding; Cell membrane; Coated pit; Complete proteome; Endocytosis; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 961 AA 

Protein Sequence

Gene Ontology

 GO:0031252; C:cell leading edge; ISS:UniProtKB.
 GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB.
 GO:0005905; C:coated pit; IEA:UniProtKB-SubCell.
 GO:0019897; C:extrinsic to plasma membrane; ISS:UniProtKB.
 GO:0043195; C:terminal bouton; ISS:UniProtKB.
 GO:0035612; F:AP-2 adaptor complex binding; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005112; F:Notch binding; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
 GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
 GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
 GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
 GO:0050821; P:protein stabilization; IDA:UniProtKB.
 GO:2000369; P:regulation of clathrin-mediated endocytosis; IDA:UniProtKB.
 GO:0032880; P:regulation of protein localization; IDA:UniProtKB. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

  

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS