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Protein

AP2-associated protein kinase 1

Gene

Aak1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. 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.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Stimulated by clathrin.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei74 – 741ATPPROSITE-ProRule annotation
Active sitei176 – 1761Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi52 – 609ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • AP-2 adaptor complex binding Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • Notch binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • endocytosis Source: UniProtKB-KW
  • positive regulation of Notch signaling pathway Source: UniProtKB
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • protein stabilization Source: UniProtKB
  • regulation of clathrin-mediated endocytosis Source: UniProtKB
  • regulation of protein localization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Endocytosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
AP2-associated protein kinase 1 (EC:2.7.11.1)
Alternative name(s):
Adaptor-associated kinase 1
Gene namesi
Name:Aak1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1305520. Aak1.

Subcellular locationi

GO - Cellular componenti

  • cell leading edge Source: UniProtKB
  • clathrin complex Source: UniProtKB
  • coated pit Source: UniProtKB-SubCell
  • extrinsic component of plasma membrane Source: UniProtKB
  • terminal bouton Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Coated pit, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 962962AP2-associated protein kinase 1PRO_0000250580Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei14 – 141PhosphoserineBy similarity
Modified residuei234 – 2341PhosphotyrosineBy similarity
Modified residuei235 – 2351PhosphoserineBy similarity
Modified residuei353 – 3531PhosphothreonineBy similarity
Modified residuei388 – 3881PhosphothreonineBy similarity
Modified residuei440 – 4401PhosphothreonineBy similarity
Modified residuei607 – 6071PhosphothreonineBy similarity
Modified residuei619 – 6191PhosphoserineCombined sources
Modified residuei621 – 6211PhosphothreonineCombined sources
Modified residuei624 – 6241PhosphoserineBy similarity
Modified residuei625 – 6251PhosphoserineCombined sources
Modified residuei638 – 6381PhosphoserineCombined sources
Modified residuei651 – 6511PhosphoserineBy similarity
Modified residuei654 – 6541PhosphothreonineBy similarity
Modified residuei732 – 7321PhosphoserineBy similarity
Modified residuei847 – 8471PhosphoserineBy similarity
Modified residuei938 – 9381PhosphoserineBy similarity
Modified residuei939 – 9391PhosphoserineCombined sources

Post-translational modificationi

Autophosphorylated.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiP0C1X8.
PRIDEiP0C1X8.

PTM databases

iPTMnetiP0C1X8.
PhosphoSiteiP0C1X8.

Interactioni

Subunit structurei

Interacts with alpha-adaptin, AP-2, clathrin, NUMB and EPS15. Interacts with membrane-bound activated NOTCH1 but not with the inactive full-length form of NOTCH1. Preferentially interacts with monoubiquitinated activated NOTCH1 compared to the non-ubiquitinated form.1 Publication

GO - Molecular functioni

  • AP-2 adaptor complex binding Source: UniProtKB
  • Notch binding Source: UniProtKB

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000044665.

Structurei

3D structure databases

ProteinModelPortaliP0C1X8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini46 – 314269Protein kinasePROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi22 – 254Poly-Gly
Compositional biasi396 – 615220Gln-richAdd
BLAST
Compositional biasi659 – 6646Poly-Ala

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1989. Eukaryota.
ENOG410Y515. LUCA.
HOGENOMiHOG000232173.
HOVERGENiHBG080803.
InParanoidiP0C1X8.
PhylomeDBiP0C1X8.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P0C1X8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKKFFDSRRE QGSSGLGSGS SGGGGSSSGL GSGYIGRVFG IGRQQVTVDE
60 70 80 90 100
VLAEGGFALV FLVRTSNGVK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH
110 120 130 140 150
KNIVGYIDSS INNVSSGDVW EVLILMDFCR GGQVVNLMNQ RLQTGFTENE
160 170 180 190 200
VLQIFCDTCE AVARLHQCKT PIIHRDLKVE NILLHDRGHY VLCDFGSATN
210 220 230 240 250
KFQNPQAEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKIIT TKADIWALGC
260 270 280 290 300
LLYKLCYFTL PFGESQVAIC DGSFTIPDNS RYSQDMHCLI YMLEPDPDKR
310 320 330 340 350
PDIYQVSYFS FKLLKKECPV PNVQNSPIPT KLPEPVKASE AAVKKTQPKA
360 370 380 390 400
RLTDPIPTTE TSIAPRQRPK AGQTQPNPGI LPIQPALTPR KRATVQPLPQ
410 420 430 440 450
ATGPSNQPSL LASVSQPKAQ ATPSQPLQSS QPKQPQAPPT PQQTPAPQTQ
460 470 480 490 500
GLPTQAQATP QHQQQLLLKQ QQQQQQQQQQ QQPQQPTAPP QPSGTFYQQQ
510 520 530 540 550
QPQQQQAQTQ QQFQAVHPAA QQSVTAQFPV VSQGGSQQQL MQNFYQQQQQ
560 570 580 590 600
QQQQQQQLMA QQAALQQKTA VVVPQPQAQP ATAPQAAAAQ EPQIQAPARQ
610 620 630 640 650
QPKVQTTPPP TIQGQKVGSL TPPSSPKTQR AGHRRILSDV THSAVFGVPA
660 670 680 690 700
SKSTQLLHAA AAEASLSKSK SATTTPSGSP RTSQQNVSNA SEGSTWNPFD
710 720 730 740 750
DDNFSKLTAE ELLNKDFAKL GEGKLPEKLG GSAESLIPGF QATQGDAFAT
760 770 780 790 800
SSFSAGTAEK RKGGQAVDSG IPLLSVSDPF IPLQVPDAPE KLIEGLKSPD
810 820 830 840 850
TSLLLPDLLP MTDPFGSTSD AVIEKADAAV ESLIPGLEPP VAQRLPSHTE
860 870 880 890 900
SVTSNRTDSL TGEDSLLDCS LLSNPTADLL DEFAPIALSA STHKAAEDSN
910 920 930 940 950
LISGFGVAEG SEKVAEDEFD PIPVLITKNT QGGHSRNSSG SSESSLPNLA
960
RSLLLVDQLI DL
Length:962
Mass (Da):103,761
Last modified:October 3, 2006 - v1
Checksum:i755E6F250C7A373E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03032075 Genomic DNA. No translation available.
AABR03032129 Genomic DNA. No translation available.
UniGeneiRn.203307.

Genome annotation databases

UCSCiRGD:1305520. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AABR03032075 Genomic DNA. No translation available.
AABR03032129 Genomic DNA. No translation available.
UniGeneiRn.203307.

3D structure databases

ProteinModelPortaliP0C1X8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000044665.

PTM databases

iPTMnetiP0C1X8.
PhosphoSiteiP0C1X8.

Proteomic databases

PaxDbiP0C1X8.
PRIDEiP0C1X8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:1305520. rat.

Organism-specific databases

RGDi1305520. Aak1.

Phylogenomic databases

eggNOGiKOG1989. Eukaryota.
ENOG410Y515. LUCA.
HOGENOMiHOG000232173.
HOVERGENiHBG080803.
InParanoidiP0C1X8.
PhylomeDBiP0C1X8.

Miscellaneous databases

PROiP0C1X8.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
    Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M.
    , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
    Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Brown Norway.
  2. "Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis."
    Conner S.D., Schmid S.L.
    J. Cell Biol. 156:921-929(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH ALPHA-ADAPTIN.
  3. "AAK1-mediated micro2 phosphorylation is stimulated by assembled clathrin."
    Conner S.D., Schroter T., Schmid S.L.
    Traffic 4:885-890(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION.
  4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-619; THR-621; SER-625; SER-638 AND SER-939, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiAAK1_RAT
AccessioniPrimary (citable) accession number: P0C1X8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: October 3, 2006
Last modified: May 11, 2016
This is version 76 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.