AAK1_PIG
ID AAK1_PIG Reviewed; 968 AA.
AC F1SPM8;
DT 19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
DT 19-OCT-2011, sequence version 2.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=AP2-associated protein kinase 1 {ECO:0000303|PubMed:11877457};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q2M2I8};
DE AltName: Full=Adaptor-associated kinase 1 {ECO:0000303|PubMed:11877457};
GN Name=AAK1;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-54.
RA Uenishi H., Morozumi T., Toki D., Eguchi-Ogawa T., Tanaka-Matsuda M.;
RT "Porcine ESTs using full-length-enriched cDNA libraries.";
RL Submitted (FEB-2010) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0000305}
RP FUNCTION.
RX PubMed=11877457; DOI=10.1083/jcb.200111068;
RA Ricotta D., Conner S.D., Schmid S.L., von Figura K., Honing S.;
RT "Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity
RT binding to membrane protein sorting signals.";
RL J. Cell Biol. 156:791-795(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 (PubMed:11877457). Preferentially,
CC may phosphorylate substrates on threonine residues (By similarity).
CC Regulates phosphorylation of other AP-2 subunits as well as AP-2
CC localization and AP-2-mediated internalization of ligand complexes (By
CC similarity). Phosphorylates NUMB and regulates its cellular
CC localization, promoting NUMB localization to endosomes (By similarity).
CC Binds to and stabilizes the activated form of NOTCH1, increases its
CC localization in endosomes and regulates its transcriptional activity
CC (By similarity). {ECO:0000250|UniProtKB:Q2M2I8,
CC ECO:0000269|PubMed:11877457}.
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 (By similarity). Interacts with membrane-bound activated
CC NOTCH1 but not with the inactive full-length form of NOTCH1 (By
CC similarity). Preferentially interacts with monoubiquitinated activated
CC NOTCH1 compared to the non-ubiquitinated form (By similarity).
CC {ECO:0000250|UniProtKB:P0C1X8, ECO:0000250|UniProtKB:Q2M2I8}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:F1MH24};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:F1MH24}. 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. {ECO:0000250|UniProtKB:P0C1X8}.
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; CU467585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; FS674854; -; NOT_ANNOTATED_CDS; mRNA.
DR AlphaFoldDB; F1SPM8; -.
DR SMR; F1SPM8; -.
DR STRING; 9823.ENSSSCP00000008900; -.
DR PaxDb; F1SPM8; -.
DR PeptideAtlas; F1SPM8; -.
DR PRIDE; F1SPM8; -.
DR eggNOG; KOG1989; Eukaryota.
DR InParanoid; F1SPM8; -.
DR OMA; ASLNKSX; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; 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; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; ISS: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; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; IDA: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 2: Evidence at transcript 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..968
FT /note="AP2-associated protein kinase 1"
FT /id="PRO_0000413362"
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 327..485
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 578..640
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 671..708
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 830..967
FT /note="Clathrin-binding domain (CBD)"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT REGION 843..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 929..952
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 400..419
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..449
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 450..472
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 600..632
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 936..952
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 52..60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="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 613
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 625
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0C1X8"
FT MOD_RES 627
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 630
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 644
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 657
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 660
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 694
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 738
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 853
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 944
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 945
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
SQ SEQUENCE 968 AA; 104310 MW; 4F07200E056E047D CRC64;
MKKFFDSRRE QGGSGLGSGS SGGGGSTSGL GSGYIGRVFG IGRQQVTVDE VLAEGGFAIV
FLVRTSNGMK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH KNIVGYIDSS INNVSSGDVW
EVLILMDFCR GGQVVNLMNQ RLQTGFTESE VLQIFCDTCE AVARLHQCKT PIIHRDLKVE
NILLHDRGHY VLCDFGSATN KFQNPQTEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKIIT
TKADIWALGC LLYKLCYFTL PFGESQVAIC DGNFTIPDNS RYSQDMHCLI RYMLEPDPDK
RPDIYQVSFF SFKLLKKECP VPNVQNSPIP AKLPEPVKAS EAAAKKTQPK ARLTDPIPTT
ETSIAPRQRP KAGQTQPNPG ILPIQPALTP RKRAMVQPPP QVAGSSNQPG LLASVPQPKT
QAPPSQPLPQ SQAKQPQAPP APQQPPSAPA QGLPAQAQAT PQHQQQLFLK QQPQPPQPQP
QAQAPPVKSL KFYPFYPMCK GRQTVSSQFQ AVHPAAQQPA IAQFPAVSQG SSQQQLIQNF
YQQQQQQQQQ QQLATTLHQQ QLLTQQAALQ QKTTVAAIQP PQAQPATASQ PPPAQEPAQI
QAPVRQQPKV QTTPPPAIQG QKLGSLTPPS SPKAQRAGHR RILSDVTHSA VFGVPASKST
QLLQAAAAEA SLNKSKSATT TPSGSPRASQ QNVYNPSEGS TWNPFDDDNF SKLTAEELLN
KDFAKLGEGK HPEKLGGSAE SLIPGFQPTQ GDAFAASSFA AGTAEKRKGG QAVDSSLPLL
SVSDPFIPLQ VPDAPEKLIE GLKSPDTSLL LPDLLPMTDP FGSTSDAVIE KADVAVESLI
PGLEPPVPQR LPSQTESVAS NRTDSLTGED ALIDCSLLSN PTTDLLEEFA PIAISAPAHK
AAEDSNLISG FDVPEGSDKV AEDEFDPIPV LITKNPQGGH SRNSSGSSES SLPNLARSLL
LVDQLIDL
