AP2-associated protein kinase 1

Details

Name
AP2-associated protein kinase 1
Synonyms
  • 2.7.11.1
  • Adaptor-associated kinase 1
  • KIAA1048
Gene Name
AAK1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051696|AP2-associated protein kinase 1
MKKFFDSRREQGGSGLGSGSSGGGGSTSGLGSGYIGRVFGIGRQQVTVDEVLAEGGFAIV
FLVRTSNGMKCALKRMFVNNEHDLQVCKREIQIMRDLSGHKNIVGYIDSSINNVSSGDVW
EVLILMDFCRGGQVVNLMNQRLQTGFTENEVLQIFCDTCEAVARLHQCKTPIIHRDLKVE
NILLHDRGHYVLCDFGSATNKFQNPQTEGVNAVEDEIKKYTTLSYRAPEMVNLYSGKIIT
TKADIWALGCLLYKLCYFTLPFGESQVAICDGNFTIPDNSRYSQDMHCLIRYMLEPDPDK
RPDIYQVSYFSFKLLKKECPIPNVQNSPIPAKLPEPVKASEAAAKKTQPKARLTDPIPTT
ETSIAPRQRPKAGQTQPNPGILPIQPALTPRKRATVQPPPQAAGSSNQPGLLASVPQPKP
QAPPSQPLPQTQAKQPQAPPTPQQTPSTQAQGLPAQAQATPQHQQQLFLKQQQQQQQPPP
AQQQPAGTFYQQQQAQTQQFQAVHPATQKPAIAQFPVVSQGGSQQQLMQNFYQQQQQQQQ
QQQQQQLATALHQQQLMTQQAALQQKPTMAAGQQPQPQPAAAPQPAPAQEPAIQAPVRQQ
PKVQTTPPPAVQGQKVGSLTPPSSPKTQRAGHRRILSDVTHSAVFGVPASKSTQLLQAAA
AEASLNKSKSATTTPSGSPRTSQQNVYNPSEGSTWNPFDDDNFSKLTAEELLNKDFAKLG
EGKHPEKLGGSAESLIPGFQSTQGDAFATTSFSAGTAEKRKGGQTVDSGLPLLSVSDPFI
PLQVPDAPEKLIEGLKSPDTSLLLPDLLPMTDPFGSTSDAVIEKADVAVESLIPGLEPPV
PQRLPSQTESVTSNRTDSLTGEDSLLDCSLLSNPTTDLLEEFAPTAISAPVHKAAEDSNL
ISGFDVPEGSDKVAEDEFDPIPVLITKNPQGGHSRNSSGSSESSLPNLARSLLLVDQLID
L
Number of residues
961
Molecular Weight
103884.3
Theoretical pI
Not Available
GO Classification
Functions
AP-2 adaptor complex binding / ATP binding / Notch binding / protein serine/threonine kinase activity
Processes
endocytosis / membrane organization / positive regulation of Notch signaling pathway / protein autophosphorylation / protein phosphorylation / protein stabilization / regulation of clathrin-dependent endocytosis / regulation of protein localization
Components
cell leading edge / clathrin-coated pit / clathrin-coated vesicle / cytoplasm / cytosol / extrinsic component of plasma membrane / terminal bouton
General 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.
Specific Function
Ap-2 adaptor complex binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0051697|AP2-associated protein kinase 1 (AAK1)
ATGAAGAAGTTTTTCGACTCCCGGCGAGAGCAGGGCGGCTCTGGCCTGGGCTCCGGCTCC
AGCGGAGGAGGGGGCAGCACCTCGGGCCTGGGCAGTGGCTACATCGGAAGAGTCTTCGGC
ATCGGGCGACAGCAGGTCACAGTGGACGAGGTGTTGGCGGAAGGTGGATTTGCTATTGTA
TTTCTGGTGAGGACAAGCAATGGGATGAAATGTGCCTTGAAACGCATGTTTGTCAACAAT
GAGCATGATCTCCAGGTGTGCAAGAGAGAAATCCAGATAATGAGGGATCTTTCAGGGCAC
AAGAATATTGTGGGTTACATTGATTCTAGTATCAACAACGTGAGTAGCGGTGATGTATGG
GAAGTGCTCATTCTGATGGACTTTTGTAGAGGTGGCCAGGTGGTAAACCTGATGAACCAG
CGCCTGCAAACAGGCTTTACAGAGAATGAAGTGCTCCAGATATTTTGTGATACCTGTGAA
GCTGTTGCCCGCCTGCATCAGTGCAAAACTCCTATTATCCACCGGGACCTGAAGGTTGAA
AACATCCTCTTGCATGACCGAGGCCACTATGTCCTGTGTGACTTTGGAAGCGCCACCAAC
AAATTCCAGAATCCACAAACTGAGGGAGTCAATGCAGTAGAAGATGAGATTAAGAAATAC
ACAACGCTGTCCTATCGAGCACCAGAAATGGTCAACCTGTACAGTGGCAAAATCATCACT
ACGAAGGCAGACATTTGGGCTCTTGGATGTTTGTTGTATAAATTATGCTACTTCACTTTG
CCATTTGGGGAAAGTCAGGTGGCAATTTGTGATGGAAACTTCACAATTCCTGATAATTCT
CGATATTCTCAAGACATGCACTGCCTAATTAGGTATATGTTGGAACCAGACCCTGACAAA
AGGCCGGATATTTACCAGGTGTCCTACTTCTCATTTAAGCTACTCAAGAAAGAGTGCCCA
ATTCCAAATGTACAGAACTCTCCCATTCCTGCAAAGCTTCCTGAACCAGTGAAAGCCAGT
GAGGCAGCTGCAAAAAAGACCCAGCCAAAGGCCAGACTGACAGATCCCATTCCCACCACA
GAGACTTCAATTGCACCCCGCCAGAGGCCTAAAGCTGGGCAGACTCAGCCGAACCCAGGA
ATCCTTCCCATCCAGCCAGCGCTGACACCCCGGAAGAGGGCCACTGTTCAGCCCCCACCT
CAGGCTGCAGGATCCAGCAATCAGCCTGGCCTTTTAGCCAGTGTTCCCCAACCAAAACCC
CAAGCCCCACCCAGCCAGCCTCTGCCGCAAACTCAGGCCAAGCAGCCACAGGCTCCTCCC
ACTCCACAGCAGACGCCTTCTACTCAGGCCCAGGGTCTGCCCGCTCAGGCCCAGGCCACA
CCCCAGCACCAGCAGCAACTCTTCCTCAAGCAGCAACAGCAGCAGCAACAGCCACCGCCA
GCACAGCAGCAGCCGGCAGGCACGTTTTACCAGCAGCAGCAGGCCCAGACTCAGCAGTTT
CAGGCAGTACATCCAGCAACCCAGCAACCAGCAATTGCTCAGTTCCCTGTGGTGTCCCAA
GGAGGCTCTCAACAGCAGCTAATGCAGAATTTCTACCAGCAGCAGCAGCAGCAGCAACAA
CAACAGCAACAGCAACAGCTGGCCACAGCCCTGCATCAACAACAGCTGATGACTCAGCAG
GCTGCCTTGCAGCAAAAGCCCACTATGGCAGCAGGACAGCAGCCCCAGCCACAGCCAGCT
GCAGCCCCACAGCCAGCCCCTGCCCAGGAGCCAGCGATTCAAGCCCCAGTAAGACAACAG
CCAAAGGTTCAGACAACCCCACCTCCTGCCGTCCAGGGGCAGAAAGTTGGATCTCTCACT
CCACCCTCATCCCCCAAAACCCAACGTGCTGGGCACAGGCGTATTCTCAGTGACGTAACC
CACAGTGCAGTCTTTGGGGTCCCTGCCAGCAAATCAACCCAGCTGCTCCAGGCAGCTGCA
GCTGAGGCCAGTCTCAATAAGTCCAAGTCTGCAACCACCACTCCATCAGGCTCTCCTCGG
ACCTCTCAACAAAACGTTTATAATCCTTCAGAAGGGTCTACGTGGAATCCCTTTGATGAC
GATAATTTCTCCAAACTCACAGCTGAAGAACTGCTAAACAAGGACTTTGCCAAGCTTGGG
GAAGGCAAACATCCCGAGAAGCTTGGAGGCTCAGCTGAGAGTTTGATCCCAGGCTTTCAA
TCAACCCAAGGTGATGCTTTTGCTACGACCTCATTTTCTGCTGGAACTGCTGAAAAAAGG
AAGGGTGGGCAGACTGTGGACTCTGGCCTCCCGCTTCTAAGCGTGTCTGATCCTTTCATT
CCTCTTCAAGTACCTGATGCACCAGAAAAACTAATTGAGGGACTCAAATCTCCTGACACT
TCTCTTCTGCTCCCTGACCTCTTGCCTATGACAGATCCTTTTGGTAGCACTTCTGATGCT
GTAATTGAAAAAGCTGATGTTGCTGTTGAGAGTCTCATACCAGGACTGGAGCCCCCAGTT
CCCCAGCGCCTCCCATCTCAGACGGAATCTGTGACCTCGAATCGCACAGATTCTCTCACC
GGGGAAGATTCCCTGCTTGATTGCTCTCTGCTCTCTAACCCTACTACTGACCTTCTGGAA
GAGTTTGCCCCCACAGCAATCTCTGCTCCAGTCCATAAAGCTGCAGAAGATAGTAATCTC
ATCTCAGGTTTTGATGTCCCTGAGGGCTCGGACAAGGTGGCTGAAGATGAGTTTGACCCT
ATTCCTGTATTGATAACCAAAAACCCACAAGGTGGGCACTCTAGAAACAGCAGTGGGAGC
TCTGAGTCCAGTCTTCCCAACCTAGCCAGGTCTTTACTGCTGGTGGATCAGCTCATAGAC
CTGTAG
Chromosome Location
2
Locus
2p13.3
External Identifiers
ResourceLink
UniProtKB IDQ2M2I8
UniProtKB Entry NameAAK1_HUMAN
HGNC IDHGNC:19679
General References
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  8. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [Article]
  9. Carrascal M, Ovelleiro D, Casas V, Gay M, Abian J: Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment. J Proteome Res. 2008 Dec;7(12):5167-76. [Article]
  10. Daub H, Olsen JV, Bairlein M, Gnad F, Oppermann FS, Korner R, Greff Z, Keri G, Stemmann O, Mann M: Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle. Mol Cell. 2008 Aug 8;31(3):438-48. doi: 10.1016/j.molcel.2008.07.007. [Article]
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  12. Sorensen EB, Conner SD: AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis. Traffic. 2008 Sep;9(10):1791-800. doi: 10.1111/j.1600-0854.2008.00790.x. Epub 2008 Jul 24. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails