AAK1_BOVIN
ID AAK1_BOVIN Reviewed; 957 AA.
AC F1MH24;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 2.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=AP2-associated protein kinase 1 {ECO:0000303|PubMed:11877461};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q2M2I8};
DE AltName: Full=Adaptor-associated kinase 1 {ECO:0000303|PubMed:11877461};
GN Name=AAK1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19390049; DOI=10.1126/science.1169588;
RG The bovine genome sequencing and analysis consortium;
RT "The genome sequence of taurine cattle: a window to ruminant biology and
RT evolution.";
RL Science 324:522-528(2009).
RN [2] {ECO:0000305}
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=11877461; DOI=10.1083/jcb.200108123;
RA Conner S.D., Schmid S.L.;
RT "Identification of an adaptor-associated kinase, AAK1, as a regulator of
RT clathrin-mediated endocytosis.";
RL J. Cell Biol. 156:921-929(2002).
CC -!- FUNCTION: Regulates clathrin-mediated endocytosis by phosphorylating
CC the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which
CC ensures high affinity binding of AP-2 to cargo membrane proteins during
CC the initial stages of endocytosis. Preferentially, may phosphorylate
CC substrates on threonine residues. Regulates phosphorylation of other
CC AP-2 subunits as well as AP-2 localization and AP-2-mediated
CC internalization of ligand complexes. Phosphorylates NUMB and regulates
CC its cellular localization, promoting NUMB localization to endosomes.
CC Binds to and stabilizes the activated form of NOTCH1, increases its
CC localization in endosomes and regulates its transcriptional activity.
CC {ECO:0000250|UniProtKB:Q2M2I8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:Q2M2I8};
CC -!- ACTIVITY REGULATION: Stimulated by clathrin.
CC {ECO:0000250|UniProtKB:Q2M2I8}.
CC -!- SUBUNIT: Interacts (via CBD domain) with clathrin (By similarity).
CC Interacts with AP-2 complex (By similarity). Interacts with NUMB (By
CC similarity). Interacts with alpha-adaptin (By similarity). Interacts
CC with EPS15 isoform 2 (By similarity). Interacts with membrane-bound
CC activated NOTCH1 but not with the inactive full-length form of NOTCH1
CC (By similarity). Preferentially interacts with monoubiquitinated
CC activated NOTCH1 compared to the non-ubiquitinated form (By
CC similarity). {ECO:0000250|UniProtKB:P0C1X8,
CC ECO:0000250|UniProtKB:Q2M2I8}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:11877461};
CC Peripheral membrane protein {ECO:0000269|PubMed:11877461}. Membrane,
CC clathrin-coated pit {ECO:0000250|UniProtKB:P0C1X8}. Presynapse
CC {ECO:0000250|UniProtKB:P0C1X8}. Note=Active when found in clathrin-
CC coated pits at the plasma membrane. In neuronal cells, enriched at
CC presynaptic terminals. In non-neuronal cells, enriched at leading edge
CC of migrating cells (By similarity). {ECO:0000250|UniProtKB:P0C1X8}.
CC -!- TISSUE SPECIFICITY: Detected in brain (at protein level).
CC {ECO:0000269|PubMed:11877461}.
CC -!- PTM: Autophosphorylated. {ECO:0000250|UniProtKB:Q2M2I8}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AAFC03047227; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAFC03072429; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; F1MH24; -.
DR SMR; F1MH24; -.
DR STRING; 9913.ENSBTAP00000012302; -.
DR iPTMnet; F1MH24; -.
DR PaxDb; F1MH24; -.
DR PRIDE; F1MH24; -.
DR eggNOG; KOG1989; Eukaryota.
DR HOGENOM; CLU_000288_109_5_1; -.
DR InParanoid; F1MH24; -.
DR OrthoDB; 826336at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0043195; C:terminal bouton; ISS:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005112; F:Notch binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; ISS:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Acetylation; ATP-binding; Cell membrane; Cell projection; Coated pit;
KW Endocytosis; Kinase; Membrane; Methylation; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Synapse; Transferase.
FT CHAIN 1..957
FT /note="AP2-associated protein kinase 1"
FT /id="PRO_0000413361"
FT DOMAIN 46..315
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 326..506
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 563..629
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 660..697
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 819..956
FT /note="Clathrin-binding domain (CBD)"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT REGION 832..855
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 919..941
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 399..415
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..447
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 448..504
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 589..621
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 839..855
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 925..941
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 52..60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P28523,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 234
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 354
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 389
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 391
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 441
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 602
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 614
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0C1X8"
FT MOD_RES 616
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 620
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 633
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 646
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 649
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 683
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 727
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 842
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 933
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 934
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
SQ SEQUENCE 957 AA; 103089 MW; ECB0D8B9B792CE82 CRC64;
MKKFFDSRRE QGGSGLGSGS SGGGGSTSGL GSGYIGRVFG IGRQQVTVDE VLAEGGFAIV
FLVRTSNGMK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH KNIVGYIDSS INSVSSGDVW
EVLILMDFCR GGQVVNLMNQ RLQTGFTENE VLQIFCDTCE AVARLHQCKT PIIHRDLKVE
NILLHDRGHY VLCDFGSATN KFQNPQTEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKVIT
TKADIWALGC LLYKLCYFTL PFGESQVAIC DGNFTIPDNS RYSQDMHCLI RYMLEPDPDK
RPDIYQVSYF SFKLLKKECP IPNVQNSPIP TKLPEPVKAS EAAAKKTQPK ARLTDPIPTT
ETSIAPRQRP KAGQTQPNPG ILPIQPALTP RKRATVQPPP QAAGSSNQPG LLASVPQPKT
QPPPSQPLPQ SQPKQPQAPP TSQQPPSAPA QALPTQAQAT PQHQQQLFLK QQQQQQTAPP
AQQPAGTFYQ QPQQQAQAPQ FQAVHPAAQQ PVIAQFPVVS QGSSQQQLIQ NFYQQQQQQQ
QLATALHQQQ LLTQQAALQQ KTTAAAAPQP QAQPAAAASP APAQEPAQIQ APVRQQPKVQ
TTPPPTIQGQ KLGSLTPPSS PKAQRAGHRR ILSDVTHSAV FGVPASKSTQ LLQAAAAEAS
LNKSKSATTT PSGSPRASQQ NVYNPSEGST WNPFDDDNFS KLTAEELLNK DFAKLGEGKY
PEKLGGSAES LIPGFQPTQG DAFAASSFSA GTAEKRKGGQ TMDSSLPLLS VSDPFIPLQV
PDAPEKLIEG LKSPDTSLLL PDLLPMTDPF GSTSDAVIEK ADVAVESLIP GLEPPVPQRL
PSQTESVTSN RTDSLTGEDS LIDCSLLSNP TTDLLEEFAP IAISAPAHKA AEDSNLISGF
DVPEGSDKVA EDEFDPIPVL ITKNPQGGHS RNSSGSSESS LPNLARSLLL VDQLIDL
