ID AAK1_RAT Reviewed; 962 AA.
AC P0C1X8;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 24-JAN-2024, entry version 108.
DE RecName: Full=AP2-associated protein kinase 1;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q2M2I8};
DE AltName: Full=Adaptor-associated kinase 1;
GN Name=Aak1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP FUNCTION, INTERACTION WITH ALPHA-ADAPTIN, AND SUBCELLULAR LOCATION.
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).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619; THR-621; SER-625;
RP SER-638 AND SER-939, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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:11877461). 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:11877461}.
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 (PubMed:11877461). 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:Q2M2I8, ECO:0000269|PubMed:11877461}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:F1MH24};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:F1MH24}. Membrane,
CC clathrin-coated pit {ECO:0000269|PubMed:11877461}. Presynapse
CC {ECO:0000269|PubMed:11877461}. 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: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; AABR03032075; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03032129; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; P0C1X8; -.
DR SMR; P0C1X8; -.
DR IntAct; P0C1X8; 1.
DR MINT; P0C1X8; -.
DR STRING; 10116.ENSRNOP00000044665; -.
DR iPTMnet; P0C1X8; -.
DR PhosphoSitePlus; P0C1X8; -.
DR jPOST; P0C1X8; -.
DR PaxDb; 10116-ENSRNOP00000044665; -.
DR UCSC; RGD:1305520; rat.
DR AGR; RGD:1305520; -.
DR RGD; 1305520; Aak1.
DR eggNOG; KOG1989; Eukaryota.
DR InParanoid; P0C1X8; -.
DR PhylomeDB; P0C1X8; -.
DR Reactome; R-RNO-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-RNO-8856828; Clathrin-mediated endocytosis.
DR PRO; PR:P0C1X8; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0044305; C:calyx of Held; IDA:SynGO.
DR GO; GO:0031252; C:cell leading edge; IDA:UniProtKB.
DR GO; GO:0071439; C:clathrin complex; IDA:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; ISS:UniProtKB.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0043195; C:terminal bouton; IDA:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IDA: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; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0140238; P:presynaptic endocytosis; IDA:SynGO.
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 CDD; cd14037; STKc_NAK_like; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR47907:SF3; AP2-ASSOCIATED PROTEIN KINASE 1; 1.
DR PANTHER; PTHR47907; PROTEIN KINASE DOMAIN-CONTAINING PROTEIN; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 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..962
FT /note="AP2-associated protein kinase 1"
FT /id="PRO_0000250580"
FT DOMAIN 46..314
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 325..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 576..633
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 664..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 824..961
FT /note="Clathrin-binding domain (CBD)"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT REGION 839..860
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 925..946
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 11..27
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..381
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 398..431
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 432..446
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 447..484
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 491..515
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 576..628
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 666..702
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 846..860
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 928..946
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 353
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 388
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 390
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 440
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 607
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 619
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 621
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 625
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 638
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 651
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 654
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 732
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q2M2I8"
FT MOD_RES 847
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 938
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 939
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
SQ SEQUENCE 962 AA; 103761 MW; 755E6F250C7A373E CRC64;
MKKFFDSRRE QGSSGLGSGS SGGGGSSSGL GSGYIGRVFG IGRQQVTVDE VLAEGGFALV
FLVRTSNGVK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH KNIVGYIDSS INNVSSGDVW
EVLILMDFCR GGQVVNLMNQ RLQTGFTENE VLQIFCDTCE AVARLHQCKT PIIHRDLKVE
NILLHDRGHY VLCDFGSATN KFQNPQAEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKIIT
TKADIWALGC LLYKLCYFTL PFGESQVAIC DGSFTIPDNS RYSQDMHCLI YMLEPDPDKR
PDIYQVSYFS FKLLKKECPV PNVQNSPIPT KLPEPVKASE AAVKKTQPKA RLTDPIPTTE
TSIAPRQRPK AGQTQPNPGI LPIQPALTPR KRATVQPLPQ ATGPSNQPSL LASVSQPKAQ
ATPSQPLQSS QPKQPQAPPT PQQTPAPQTQ GLPTQAQATP QHQQQLLLKQ QQQQQQQQQQ
QQPQQPTAPP QPSGTFYQQQ QPQQQQAQTQ QQFQAVHPAA QQSVTAQFPV VSQGGSQQQL
MQNFYQQQQQ QQQQQQQLMA QQAALQQKTA VVVPQPQAQP ATAPQAAAAQ EPQIQAPARQ
QPKVQTTPPP TIQGQKVGSL TPPSSPKTQR AGHRRILSDV THSAVFGVPA SKSTQLLHAA
AAEASLSKSK SATTTPSGSP RTSQQNVSNA SEGSTWNPFD DDNFSKLTAE ELLNKDFAKL
GEGKLPEKLG GSAESLIPGF QATQGDAFAT SSFSAGTAEK RKGGQAVDSG IPLLSVSDPF
IPLQVPDAPE KLIEGLKSPD TSLLLPDLLP MTDPFGSTSD AVIEKADAAV ESLIPGLEPP
VAQRLPSHTE SVTSNRTDSL TGEDSLLDCS LLSNPTADLL DEFAPIALSA STHKAAEDSN
LISGFGVAEG SEKVAEDEFD PIPVLITKNT QGGHSRNSSG SSESSLPNLA RSLLLVDQLI
DL
//
