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Protein

AP2-associated protein kinase 1

Gene

Aak1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. 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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

Stimulated by clathrin.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei74ATPPROSITE-ProRule annotation1
Active sitei176Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi52 – 60ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processEndocytosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-8856825 Cargo recognition for clathrin-mediated endocytosis
R-MMU-8856828 Clathrin-mediated endocytosis

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
Synonyms:Kiaa1048
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1098687 Aak1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Coated pit, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002505791 – 959AP2-associated protein kinase 1Add BLAST959

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineBy similarity1
Modified residuei14PhosphoserineBy similarity1
Modified residuei234PhosphotyrosineBy similarity1
Modified residuei235PhosphoserineBy similarity1
Modified residuei354PhosphothreonineBy similarity1
Modified residuei389PhosphothreonineCombined sources1
Modified residuei391Omega-N-methylarginineCombined sources1
Modified residuei441PhosphothreonineBy similarity1
Modified residuei604PhosphothreonineCombined sources1
Modified residuei616PhosphoserineBy similarity1
Modified residuei618PhosphothreonineCombined sources1
Modified residuei621PhosphoserineBy similarity1
Modified residuei622PhosphoserineCombined sources1
Modified residuei635PhosphoserineCombined sources1
Modified residuei648PhosphoserineBy similarity1
Modified residuei651PhosphothreonineBy similarity1
Modified residuei729PhosphoserineBy similarity1
Modified residuei844PhosphoserineCombined sources1
Modified residuei935PhosphoserineCombined sources1
Modified residuei936PhosphoserineCombined sources1

Post-translational modificationi

Autophosphorylated.By similarity

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein

Proteomic databases

MaxQBiQ3UHJ0
PaxDbiQ3UHJ0
PeptideAtlasiQ3UHJ0
PRIDEiQ3UHJ0

PTM databases

iPTMnetiQ3UHJ0
PhosphoSitePlusiQ3UHJ0

Expressioni

Gene expression databases

BgeeiENSMUSG00000057230
ExpressionAtlasiQ3UHJ0 baseline and differential
GenevisibleiQ3UHJ0 MM

Interactioni

Subunit structurei

Interacts with alpha-adaptin, AP-2, clathrin, NUMB and EPS15 isoform 2 (By similarity). 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.By similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi234710, 4 interactors
IntActiQ3UHJ0, 4 interactors
STRINGi10090.ENSMUSP00000086948

Structurei

3D structure databases

ProteinModelPortaliQ3UHJ0
SMRiQ3UHJ0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini46 – 315Protein kinasePROSITE-ProRule annotationAdd BLAST270

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi22 – 25Poly-Gly4
Compositional biasi397 – 612Gln-richAdd BLAST216
Compositional biasi656 – 661Poly-Ala6

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG1989 Eukaryota
ENOG410Y515 LUCA
GeneTreeiENSGT00880000137958
HOGENOMiHOG000232173
HOVERGENiHBG080803
InParanoidiQ3UHJ0
KOiK08853
OMAiQLIQNFY
OrthoDBiEOG091G02KI
PhylomeDBiQ3UHJ0
TreeFamiTF317300

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q3UHJ0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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 RYMLEPDPDK
310 320 330 340 350
RPDIYQVSYF SFKLLKKECP VPNVQNSPIP AKLPEPVKAS EAAVKKTQPK
360 370 380 390 400
ARLTDPIPTT ETSIAPRQRP KAGQTQPNPG ILPIQPALTP RKRATVQPLP
410 420 430 440 450
QAAGPSNQPG LLPSVSQPKA QATPSQPLQS SQPKQPQAPP TPQQTPATQT
460 470 480 490 500
QGLPTQAQAT PQHQQQHLLK QQQQQQQQPQ QPTAPPQPAG TFYQQQQQQQ
510 520 530 540 550
QQQAQTQQFQ AVHPAAQQPV TAQFPVGSQG GAQQQLMQNF YHQQQQQQQQ
560 570 580 590 600
QQQLMAQQAA LQQKTAVVVP QSQAQPATAP QAAAAQEPGQ IQAPVRQQPK
610 620 630 640 650
VQTTPPPTIQ GQKVGSLTPP SSPKTQRAGH RRILSDVTHS AVFGVPASKS
660 670 680 690 700
TQLLQAAAAE ASLNKSKSAT TTPSGSPRTS QQNVSNASEG STWNPFDDDN
710 720 730 740 750
FSKLTAEELL NKDFAKLGEG KLPEKLGGSA ESLIPGFQPT QGDAFTTPSF
760 770 780 790 800
SAGTAEKRKG GQAVDSGIPL LSVSDPFIPL QVPDAPEKLI EGLKSPDTSL
810 820 830 840 850
LLPDLLPMTD PFGSTSDAVI DKADVAVESL IPGLEPPVAQ RLPSQTESVT
860 870 880 890 900
SNRTDSLTGE DSLLDCSLLS NPTAGLLEEF APIALSAPTH KAAEDSNLIS
910 920 930 940 950
GFGVAEGSEK VAEDEFDPIP VLITKNTQGG HSRNSSGSSE SSLPNLARSL

LLVDQLIDL
Length:959
Mass (Da):103,346
Last modified:October 3, 2006 - v2
Checksum:iB7D666EFD56D097A
GO
Isoform 2 (identifier: Q3UHJ0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     509-589: Missing.

Note: No experimental confirmation available.
Show »
Length:878
Mass (Da):94,661
Checksum:i3AE736423984C27D
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti79N → K in BAE27867 (PubMed:16141072).Curated1
Sequence conflicti686N → S in BAC98082 (PubMed:14621295).Curated1
Sequence conflicti733L → V in AAI41177 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_020670509 – 589Missing in isoform 2. 1 PublicationAdd BLAST81

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK147363 mRNA Translation: BAE27867.1
AK158879 mRNA Translation: BAE34710.1
BC043125 mRNA Translation: AAH43125.1
BC141176 mRNA Translation: AAI41177.1
AK129272 mRNA Translation: BAC98082.1
CCDSiCCDS20317.1 [Q3UHJ0-2]
CCDS39544.1 [Q3UHJ0-1]
RefSeqiNP_001035195.1, NM_001040106.2 [Q3UHJ0-1]
NP_808430.2, NM_177762.6 [Q3UHJ0-2]
UniGeneiMm.221038

Genome annotation databases

EnsembliENSMUST00000003710; ENSMUSP00000003710; ENSMUSG00000057230 [Q3UHJ0-2]
ENSMUST00000089519; ENSMUSP00000086948; ENSMUSG00000057230 [Q3UHJ0-1]
GeneIDi269774
KEGGimmu:269774
UCSCiuc009css.1 mouse [Q3UHJ0-1]
uc009cst.1 mouse [Q3UHJ0-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAAK1_MOUSE
AccessioniPrimary (citable) accession number: Q3UHJ0
Secondary accession number(s): B2RUJ0
, Q3TY53, Q6ZPZ6, Q80XP6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: October 3, 2006
Last modified: March 28, 2018
This is version 117 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

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