AAK1

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[5][6][7] and is involved in clathrin mediated endocytosis. Alternatively spliced transcript variants have been described, but their biological validity has not been determined.[7]

AAK1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4WSQ, 5L4Q
Identifiers
Aliases	AAK1, AP2 associated kinase 1
External IDs	OMIM: 616405 MGI: 1098687 HomoloGene: 128746 GeneCards: AAK1
EC number	2.7.11.1
Gene location (Human) Chr. Chromosome 2 (human)[1] Band 2p13.3 Start 69,457,997 bp[1] End 69,674,349 bp[1]
Gene location (Mouse) Chr. Chromosome 6 (mouse)[2] Band 6 D1|6 37.75 cM Start 86,849,517 bp[2] End 87,003,223 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • AP-2 adaptor complex binding • nucleotide binding • protein kinase activity • Notch binding • kinase activity • GO:0001948 protein binding • ATP binding • protein serine/threonine kinase activity Cellular component • membrane • cell membrane • terminal bouton • cell leading edge • clathrin-coated pit • extrinsic component of plasma membrane • clathrin-coated vesicle • cytoplasm • cytosol • cell nucleus Biological process • endocytosis • phosphorylation • protein stabilization • regulation of protein localization • autophosphorylation • positive regulation of Notch signaling pathway • protein phosphorylation • regulation of clathrin-dependent endocytosis • membrane organization • regulation of endocytosis Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	22848	269774
Ensembl	ENSG00000115977	ENSMUSG00000057230
UniProt	Q2M2I8	Q3UHJ0
RefSeq (mRNA)	NM_014911 NM_001371575 NM_001371577	NM_001040106 NM_177762
RefSeq (protein)	NP_055726 NP_001358504 NP_001358506	NP_001035195 NP_808430 NP_001365581 NP_001365583 NP_001365584
Location (UCSC)	Chr 2: 69.46 – 69.67 Mb	Chr 6: 86.85 – 87 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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 endocytic 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.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000115977 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000057230 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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. S2CID 26554314.
7. "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. S2CID 84066885.
• 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. S2CID 14294292.
• 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.