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P0C1X8 (AAK1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified December 14, 2011. Version 47. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
AP2-associated protein kinase 1
EC=2.7.11.1
Alternative name(s):
Adaptor-associated kinase 1
Gene names
Name:Aak1
OrganismRattus norvegicus (Rat)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length962 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. 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. Ref.2

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulation

Stimulated by clathrin.

Subunit structure

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. Ref.2

Subcellular location

Cell membrane; Peripheral membrane protein By similarity. Membrane › clathrin-coated pit. Note: Active when found in clathrin-coated pits at the plasma membrane. In neuronal cells, enriched at presynaptic terminals. In non-neuronal cells, enriched at leading edge of migrating cells.

Post-translational modification

Autophosphorylated.

Sequence similarities

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processEndocytosis
   Cellular componentCell membrane
Coated pit
Membrane
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological processendocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of Notch signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.2. Source: UniProtKB

protein stabilization

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of clathrin-mediated endocytosis

Inferred from direct assay Ref.2. Source: UniProtKB

regulation of protein localization

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular componentcell leading edge

Inferred from direct assay Ref.2. Source: UniProtKB

clathrin complex

Inferred from direct assay Ref.2. Source: UniProtKB

coated pit

Inferred from electronic annotation. Source: UniProtKB-SubCell

extrinsic to plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

terminal button

Inferred from direct assay Ref.2. Source: UniProtKB

   Molecular functionAP-2 adaptor complex binding

Inferred from direct assay Ref.2. Source: UniProtKB

ATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

Notch binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.2. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 962962AP2-associated protein kinase 1
PRO_0000250580

Regions

Domain46 – 314269Protein kinase
Nucleotide binding52 – 609ATP By similarity
Compositional bias22 – 254Poly-Gly
Compositional bias396 – 615220Gln-rich
Compositional bias659 – 6646Poly-Ala

Sites

Active site1761Proton acceptor By similarity
Binding site741ATP By similarity

Amino acid modifications

Modified residue141Phosphoserine By similarity
Modified residue181Phosphoserine By similarity
Modified residue201Phosphoserine By similarity
Modified residue211Phosphoserine By similarity
Modified residue2211Phosphothreonine By similarity
Modified residue2221Phosphothreonine By similarity
Modified residue2341Phosphotyrosine By similarity
Modified residue2351Phosphoserine By similarity
Modified residue3261Phosphoserine By similarity
Modified residue3531Phosphothreonine By similarity
Modified residue3881Phosphothreonine By similarity
Modified residue4401Phosphothreonine By similarity
Modified residue6071Phosphothreonine By similarity
Modified residue6191Phosphoserine By similarity
Modified residue6211Phosphothreonine By similarity
Modified residue6241Phosphoserine By similarity
Modified residue6251Phosphoserine By similarity
Modified residue6381Phosphoserine By similarity
Modified residue6411Phosphothreonine By similarity
Modified residue6431Phosphoserine By similarity
Modified residue6511Phosphoserine By similarity
Modified residue6531Phosphoserine By similarity
Modified residue6541Phosphothreonine By similarity
Modified residue6691Phosphoserine By similarity
Modified residue6711Phosphoserine By similarity
Modified residue6731Phosphothreonine By similarity
Modified residue6751Phosphothreonine By similarity
Modified residue6771Phosphoserine By similarity
Modified residue6791Phosphoserine By similarity
Modified residue6821Phosphothreonine By similarity
Modified residue6831Phosphoserine By similarity
Modified residue6911Phosphoserine By similarity
Modified residue7321Phosphoserine By similarity
Modified residue9381Phosphoserine By similarity
Modified residue9391Phosphoserine By similarity

Sequences

Sequence LengthMass (Da)Tools
P0C1X8 [UniParc].

Last modified October 3, 2006. Version 1.
Checksum: 755E6F250C7A373E

FASTA962103,761
        10         20         30         40         50         60 
MKKFFDSRRE QGSSGLGSGS SGGGGSSSGL GSGYIGRVFG IGRQQVTVDE VLAEGGFALV 

        70         80         90        100        110        120 
FLVRTSNGVK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH KNIVGYIDSS INNVSSGDVW 

       130        140        150        160        170        180 
EVLILMDFCR GGQVVNLMNQ RLQTGFTENE VLQIFCDTCE AVARLHQCKT PIIHRDLKVE 

       190        200        210        220        230        240 
NILLHDRGHY VLCDFGSATN KFQNPQAEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKIIT 

       250        260        270        280        290        300 
TKADIWALGC LLYKLCYFTL PFGESQVAIC DGSFTIPDNS RYSQDMHCLI YMLEPDPDKR 

       310        320        330        340        350        360 
PDIYQVSYFS FKLLKKECPV PNVQNSPIPT KLPEPVKASE AAVKKTQPKA RLTDPIPTTE 

       370        380        390        400        410        420 
TSIAPRQRPK AGQTQPNPGI LPIQPALTPR KRATVQPLPQ ATGPSNQPSL LASVSQPKAQ 

       430        440        450        460        470        480 
ATPSQPLQSS QPKQPQAPPT PQQTPAPQTQ GLPTQAQATP QHQQQLLLKQ QQQQQQQQQQ 

       490        500        510        520        530        540 
QQPQQPTAPP QPSGTFYQQQ QPQQQQAQTQ QQFQAVHPAA QQSVTAQFPV VSQGGSQQQL 

       550        560        570        580        590        600 
MQNFYQQQQQ QQQQQQQLMA QQAALQQKTA VVVPQPQAQP ATAPQAAAAQ EPQIQAPARQ 

       610        620        630        640        650        660 
QPKVQTTPPP TIQGQKVGSL TPPSSPKTQR AGHRRILSDV THSAVFGVPA SKSTQLLHAA 

       670        680        690        700        710        720 
AAEASLSKSK SATTTPSGSP RTSQQNVSNA SEGSTWNPFD DDNFSKLTAE ELLNKDFAKL 

       730        740        750        760        770        780 
GEGKLPEKLG GSAESLIPGF QATQGDAFAT SSFSAGTAEK RKGGQAVDSG IPLLSVSDPF 

       790        800        810        820        830        840 
IPLQVPDAPE KLIEGLKSPD TSLLLPDLLP MTDPFGSTSD AVIEKADAAV ESLIPGLEPP 

       850        860        870        880        890        900 
VAQRLPSHTE SVTSNRTDSL TGEDSLLDCS LLSNPTADLL DEFAPIALSA STHKAAEDSN 

       910        920        930        940        950        960 
LISGFGVAEG SEKVAEDEFD PIPVLITKNT QGGHSRNSSG SSESSLPNLA RSLLLVDQLI 


DL

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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: 15057822] [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: 11877461] [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: 14617351] [Abstract]
Cited for: CHARACTERIZATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AABR03032075 Genomic DNA. No translation available.
AABR03032129 Genomic DNA. No translation available.
IPIIPI00786812.
UniGeneRn.203307.

3D structure databases

ProteinModelPortalP0C1X8.
ModBaseSearch...

Protein-protein interaction databases

STRINGP0C1X8.

PTM databases

PhosphoSiteP0C1X8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Organism-specific databases

RGD1305520. Aak1.

Phylogenomic databases

eggNOGroNOG15358.
GeneTreeENSGT00510000046552.
HOVERGENHBG080803.
InParanoidP0C1X8.
OrthoDBEOG4Q2DF0.
PhylomeDBP0C1X8.

Gene expression databases

ArrayExpressP0C1X8.
GenevestigatorP0C1X8.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameAAK1_RAT
AccessionPrimary (citable) accession number: P0C1X8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: October 3, 2006
Last modified: December 14, 2011
This is version 47 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents