AAK1

AP2 associated kinase 1
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4WSQ​
Identifiers
Symbols	AAK1 ; DKFZp686F03202; DKFZp686K16132; FLJ23712; FLJ25931; FLJ31060; FLJ42882; FLJ45252; KIAA1048; MGC138170; MGC164568; MGC164570
External IDs	OMIM: 616405 MGI: 1098687 HomoloGene: 128746 ChEMBL: 3830 GeneCards: AAK1 Gene
EC number	2.7.11.1
Gene ontology Molecular function • protein serine/threonine kinase activity • Notch binding • protein binding • ATP binding • AP-2 adaptor complex binding Cellular component • coated pit • extrinsic component of plasma membrane • clathrin-coated vesicle • cell leading edge • terminal bouton Biological process • protein phosphorylation • endocytosis • regulation of protein localization • positive regulation of Notch signaling pathway • protein autophosphorylation • protein stabilization • regulation of clathrin-mediated endocytosis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	22848	269774
Ensembl	ENSG00000115977	ENSMUSG00000057230
UniProt	Q2M2I8	Q3UHJ0
RefSeq (mRNA)	NM_014911	NM_001040106
RefSeq (protein)	NP_055726	NP_001035195
Location (UCSC)	Chr 2: 69.46 – 69.67 Mb	Chr 6: 86.85 – 86.99 Mb
PubMed search

Adaptor-associated protein kinase 1 also known as AP2-associated protein kinase 1 is an enzyme that in humans is encoded by the AAK1 gene.^[1][2][3] Alternatively spliced transcript variants have been described, but their biological validity has not been determined.^[3]

Function

Adaptor-related protein complex 2 (AP-2 complexes) functions during receptor-mediated endocytosis to trigger clathrin assembly, interact with membrane-bound receptors, and recruit encodytic accessory factors. This gene encodes a member of the SNF1 subfamily of Ser/Thr protein kinases. The protein interacts with and phosphorylates a subunit of the AP-2 complex, which promotes binding of AP-2 to sorting signals found in membrane-bound receptors and subsequent receptor endocytosis. Its kinase activity is stimulated by clathrin.^[3]

References

1. Conner SD, Schmid SL (Mar 2002). "Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis". The Journal of Cell Biology 156 (5): 921–9. doi:10.1083/jcb.200108123. PMC 2173317. PMID 11877461.
2. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (Dec 2002). "The protein kinase complement of the human genome". Science 298 (5600): 1912–34. doi:10.1126/science.1075762. PMID 12471243.
3. "Entrez Gene: AAK1 AP2 associated kinase 1".

Further reading

• Kikuno R, Nagase T, Ishikawa K, Hirosawa M, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Jun 1999). "Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Research 6 (3): 197–205. doi:10.1093/dnares/6.3.197. PMID 10470851.
• Ricotta D, Conner SD, Schmid SL, von Figura K, Honing S (Mar 2002). "Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity binding to membrane protein sorting signals". The Journal of Cell Biology 156 (5): 791–5. doi:10.1083/jcb.200111068. PMC 2173304. PMID 11877457.
• Conner SD, Schmid SL (Sep 2003). "Differential requirements for AP-2 in clathrin-mediated endocytosis". The Journal of Cell Biology 162 (5): 773–9. doi:10.1083/jcb.200304069. PMC 2172816. PMID 12952931.
• Conner SD, Schröter T, Schmid SL (Dec 2003). "AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin". Traffic 4 (12): 885–90. doi:10.1046/j.1398-9219.2003.0142.x. PMID 14617351.
• Mishra SK, Hawryluk MJ, Brett TJ, Keyel PA, Dupin AL, Jha A, Heuser JE, Fremont DH, Traub LM (Oct 2004). "Dual engagement regulation of protein interactions with the AP-2 adaptor alpha appendage". The Journal of Biological Chemistry 279 (44): 46191–203. doi:10.1074/jbc.M408095200. PMID 15292237.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America 101 (33): 12130–5. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
• Kim JE, Tannenbaum SR, White FM (2005). "Global phosphoproteome of HT-29 human colon adenocarcinoma cells". Journal of Proteome Research 4 (4): 1339–46. doi:10.1021/pr050048h. PMID 16083285.
• Collawn JF (Jul 2006). "Unlocking the mysteries of Na+-K+-ATPase endocytosis: phosphorylation is the key". American Journal of Respiratory Cell and Molecular Biology 35 (1): 1–2. doi:10.1165/rcmb.f317. PMC 2658690. PMID 16782842.
• Schmid EM, Ford MG, Burtey A, Praefcke GJ, Peak-Chew SY, Mills IG, Benmerah A, McMahon HT (Sep 2006). "Role of the AP2 beta-appendage hub in recruiting partners for clathrin-coated vesicle assembly". PLoS Biology 4 (9): e262. doi:10.1371/journal.pbio.0040262. PMC 1540706. PMID 16903783.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (Oct 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243.
• Takahashi T, Furuchi T, Naganuma A (Dec 2006). "Endocytic Ark/Prk kinases play a critical role in adriamycin resistance in both yeast and mammalian cells". Cancer Research 66 (24): 11932–7. doi:10.1158/0008-5472.CAN-06-3220. PMID 17178891.
• Henderson DM, Conner SD (Jul 2007). "A novel AAK1 splice variant functions at multiple steps of the endocytic pathway". Molecular Biology of the Cell 18 (7): 2698–706. doi:10.1091/mbc.E06-09-0831. PMC 1924820. PMID 17494869.

External links

• AAK1 human gene location in the UCSC Genome Browser.
• AAK1 human gene details in the UCSC Genome Browser.