Free for academic non-profit institutions. Other users need a Commercial license

Aliases for AAK1 Gene

Aliases for AAK1 Gene

  • AP2 Associated Kinase 1 2 3 5
  • Adaptor-Associated Kinase 1 3 4
  • AP2-Associated Protein Kinase 1 3
  • EC 2.7.11.1 4
  • KIAA1048 4

External Ids for AAK1 Gene

Previous GeneCards Identifiers for AAK1 Gene

  • GC02M069717
  • GC02M069899
  • GC02M069683
  • GC02M069619
  • GC02M069561
  • GC02M069685

Summaries for AAK1 Gene

Entrez Gene Summary for AAK1 Gene

  • Adaptor-related protein complex 2 (AP-2 complexes) functions during receptor-mediated endocytosis to trigger clathrin assembly, interact with membrane-bound receptors, and recruit encodytic accessory factors. This gene encodes a member of the SNF1 subfamily of Ser/Thr protein kinases. The protein interacts with and phosphorylates a subunit of the AP-2 complex, which promotes binding of AP-2 to sorting signals found in membrane-bound receptors and subsequent receptor endocytosis. Its kinase activity is stimulated by clathrin. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

GeneCards Summary for AAK1 Gene

AAK1 (AP2 Associated Kinase 1) is a Protein Coding gene. Among its related pathways are Clathrin-mediated endocytosis and Vesicle-mediated transport. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is BMP2K.

UniProtKB/Swiss-Prot for AAK1 Gene

  • 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.

Gene Wiki entry for AAK1 Gene

Additional gene information for AAK1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for AAK1 Gene

Genomics for AAK1 Gene

GeneHancer (GH) Regulatory Elements for AAK1 Gene

Promoters and enhancers for AAK1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J069641 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 667.2 +30.2 30174 6.3 HDGF PKNOX1 SMAD1 ARNT ZFP64 ARID4B SIN3A DMAP1 ZNF2 YY1 AAK1 ANXA4 TIA1 PCBP1-AS1 MXD1 SNRNP27 GFPT1 GC02P069577
GH02J069673 Enhancer 1.1 Ensembl ENCODE 650.7 -0.8 -800 2.6 ATF1 PKNOX1 FOXA2 MLX ARID4B SIN3A DMAP1 ZFP91 FOS JUNB AAK1 GMCL1 ANXA4 PCBP1-AS1 TIA1 ENSG00000231024
GH02J069647 Enhancer 1.3 Ensembl ENCODE dbSUPER 12.9 +24.7 24708 3.8 IRF4 POLR2B ZNF143 ATF7 RUNX3 NCOA1 ZNF592 ATF4 SMARCA4 ZNF184 GFPT1 AAK1 SNRNP27 MXD1 ANXA4 GC02P069577
GH02J069624 Enhancer 1.2 Ensembl ENCODE dbSUPER 11.7 +49.0 49002 1.4 HDGF HDAC1 PKNOX1 TAF9B ARNT FEZF1 ZBTB40 CHAMP1 RBM34 ZNF366 TIA1 AAK1 GFPT1 ANXA4 B3GALNT1P1 GC02P069577
GH02J069714 Enhancer 1.1 Ensembl ENCODE 11.7 -40.5 -40481 0.5 ATF1 ARID4B ZNF2 ARID2 ZNF143 ATF7 RUNX3 NFKBIZ NCOA1 REST ENSG00000231024 AAK1 ANXA4 GC02P069822
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around AAK1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the AAK1 gene promoter:
  • AP-2alphaA
  • AP-2alpha isoform 4
  • AP-2alpha isoform 3
  • AP-2alpha isoform 2
  • AP-2alpha
  • Lmo2
  • AML1a
  • NF-1

Genomic Locations for AAK1 Gene

Genomic Locations for AAK1 Gene
chr2:69,457,995-69,674,349
(GRCh38/hg38)
Size:
216,355 bases
Orientation:
Minus strand
chr2:69,685,127-69,901,481
(GRCh37/hg19)
Size:
216,355 bases
Orientation:
Minus strand

Genomic View for AAK1 Gene

Genes around AAK1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
AAK1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for AAK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for AAK1 Gene

Proteins for AAK1 Gene

  • Protein details for AAK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q2M2I8-AAK1_HUMAN
    Recommended name:
    AP2-associated protein kinase 1
    Protein Accession:
    Q2M2I8
    Secondary Accessions:
    • Q4ZFZ3
    • Q53RX6
    • Q9UPV4

    Protein attributes for AAK1 Gene

    Size:
    961 amino acids
    Molecular mass:
    103885 Da
    Quaternary structure:
    • Interacts with alpha-adaptin, AP-2, clathrin, NUMB and EPS15 isoform 2. 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.
    SequenceCaution:
    • Sequence=BAA83000.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for AAK1 Gene

    Alternative splice isoforms for AAK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for AAK1 Gene

Post-translational modifications for AAK1 Gene

Other Protein References for AAK1 Gene

No data available for DME Specific Peptides for AAK1 Gene

Domains & Families for AAK1 Gene

Gene Families for AAK1 Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for AAK1 Gene

Suggested Antigen Peptide Sequences for AAK1 Gene

Graphical View of Domain Structure for InterPro Entry

Q2M2I8

UniProtKB/Swiss-Prot:

AAK1_HUMAN :
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
Family:
  • Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
genes like me logo Genes that share domains with AAK1: view

Function for AAK1 Gene

Molecular function for AAK1 Gene

UniProtKB/Swiss-Prot 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. 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.
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Stimulated by clathrin.

Enzyme Numbers (IUBMB) for AAK1 Gene

Phenotypes From GWAS Catalog for AAK1 Gene

Gene Ontology (GO) - Molecular Function for AAK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA --
GO:0004674 protein serine/threonine kinase activity TAS --
GO:0005112 Notch binding IDA 21464124
GO:0005515 protein binding IPI 22645275
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with AAK1: view
genes like me logo Genes that share phenotypes with AAK1: view

Animal Models for AAK1 Gene

MGI Knock Outs for AAK1:
  • Aak1 Aak1<tm1b(EUCOMM)Hmgu>

Animal Model Products

miRNA for AAK1 Gene

miRTarBase miRNAs that target AAK1

Clone Products

  • Addgene plasmids for AAK1

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for AAK1 Gene

Localization for AAK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for AAK1 Gene

Cell membrane; Peripheral membrane protein. 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 (By similarity). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for AAK1 gene
Compartment Confidence
plasma membrane 5
cytosol 5
mitochondrion 2
nucleus 2
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Plasma membrane (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for AAK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA --
GO:0005737 cytoplasm IBA --
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane IEA --
GO:0005905 clathrin-coated pit IEA --
genes like me logo Genes that share ontologies with AAK1: view

Pathways & Interactions for AAK1 Gene

genes like me logo Genes that share pathways with AAK1: view

SIGNOR curated interactions for AAK1 Gene

Activates:
Other effect:

Gene Ontology (GO) - Biological Process for AAK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006468 protein phosphorylation IDA 17494869
GO:0006897 endocytosis IEA --
GO:0016310 phosphorylation IEA --
GO:0030100 regulation of endocytosis IBA --
GO:0032880 regulation of protein localization IDA 18657069
genes like me logo Genes that share ontologies with AAK1: view

Drugs & Compounds for AAK1 Gene

(2) Drugs for AAK1 Gene - From: DrugBank and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
ATP Investigational Nutra Agonist, Activator, Full agonist, Antagonist, Potentiation, Pore Blocker 0

(1) Additional Compounds for AAK1 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0
genes like me logo Genes that share compounds with AAK1: view

Transcripts for AAK1 Gene

mRNA/cDNA for AAK1 Gene

(1) REFSEQ mRNAs :
(20) Additional mRNA sequences :
(57) Selected AceView cDNA sequences:
(13) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for AAK1 Gene

AP2 associated kinase 1:
Representative Sequences:

Clone Products

  • Addgene plasmids for AAK1

Alternative Splicing Database (ASD) splice patterns (SP) for AAK1 Gene

No ASD Table

Relevant External Links for AAK1 Gene

GeneLoc Exon Structure for
AAK1
ECgene alternative splicing isoforms for
AAK1

Expression for AAK1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for AAK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for AAK1 Gene

This gene is overexpressed in Brain - Frontal Cortex (BA9) (x5.7), Brain - Cortex (x5.0), Brain - Anterior cingulate cortex (BA24) (x4.8), Brain - Cerebellar Hemisphere (x4.4), and Brain - Cerebellum (x4.4).

Protein differential expression in normal tissues from HIPED for AAK1 Gene

This gene is overexpressed in Lung (20.1), Frontal cortex (8.4), and Brain (8.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for AAK1 Gene



Protein tissue co-expression partners for AAK1 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of AAK1 Gene:

AAK1

SOURCE GeneReport for Unigene cluster for AAK1 Gene:

Hs.468878

mRNA Expression by UniProt/SwissProt for AAK1 Gene:

Q2M2I8-AAK1_HUMAN
Tissue specificity: Detected in brain, heart and liver. Isoform 1 is the predominant isoform in brain.

Evidence on tissue expression from TISSUES for AAK1 Gene

  • Nervous system(4.9)
  • Liver(4.2)
  • Blood(4.1)
genes like me logo Genes that share expression patterns with AAK1: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for AAK1 Gene

Orthologs for AAK1 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for AAK1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia AAK1 34 33
  • 99.55 (n)
OneToOne
cow
(Bos Taurus)
Mammalia AAK1 34
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia AAK1 34 33
  • 90.18 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Aak1 16 34 33
  • 88.63 (n)
rat
(Rattus norvegicus)
Mammalia Aak1 33
  • 88.21 (n)
oppossum
(Monodelphis domestica)
Mammalia AAK1 34
  • 77 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia AAK1 34
  • 58 (a)
OneToOne
chicken
(Gallus gallus)
Aves AAK1 34 33
  • 76.02 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia AAK1 34
  • 60 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii AAK1 (1 of 2) 34
  • 76 (a)
OneToMany
aak1 34
  • 50 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Nak 34
  • 17 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea tag-257 34
  • 24 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes ARK1 34
  • 24 (a)
ManyToMany
PRK1 34
  • 21 (a)
ManyToMany
AKL1 34
  • 17 (a)
ManyToMany
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 39 (a)
OneToMany
Cin.9763 33
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.9763 33
Species where no ortholog for AAK1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)

Evolution for AAK1 Gene

ENSEMBL:
Gene Tree for AAK1 (if available)
TreeFam:
Gene Tree for AAK1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for AAK1: view image

Paralogs for AAK1 Gene

Paralogs for AAK1 Gene

(2) SIMAP similar genes for AAK1 Gene using alignment to 6 proteins:

  • AAK1_HUMAN
  • B7ZLC4_HUMAN
  • D6W5G0_HUMAN
  • E9PG46_HUMAN
  • L0R804_HUMAN
  • Q9BUD9_HUMAN
genes like me logo Genes that share paralogs with AAK1: view

Variants for AAK1 Gene

Sequence variations from dbSNP and Humsavar for AAK1 Gene

SNP ID Clin Chr 02 pos Variation AA Info Type
rs1000014394 -- 69,470,603(-) G/T 3_prime_UTR_variant
rs1000031983 -- 69,572,817(-) T/C intron_variant
rs1000045646 -- 69,467,528(-) G/A 3_prime_UTR_variant
rs1000049146 -- 69,517,044(-) T/C intron_variant
rs1000073201 -- 69,520,526(-) T/C intron_variant

Structural Variations from Database of Genomic Variants (DGV) for AAK1 Gene

Variant ID Type Subtype PubMed ID
esv2668895 CNV deletion 23128226
esv2674177 CNV deletion 23128226
esv33940 CNV loss 17666407
esv3396390 CNV insertion 20981092
esv3591183 CNV loss 21293372
esv3591184 CNV loss 21293372
nsv214841 CNV deletion 16902084
nsv527716 CNV loss 19592680
nsv819601 CNV loss 19587683
nsv834252 CNV loss 17160897
nsv834253 CNV loss 17160897
nsv954240 CNV deletion 24416366
nsv961413 CNV duplication 23825009
nsv961414 CNV duplication 23825009

Variation tolerance for AAK1 Gene

Residual Variation Intolerance Score: 25.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.51; 94.39% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for AAK1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
AAK1

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for AAK1 Gene

Disorders for AAK1 Gene

Additional Disease Information for AAK1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for AAK1 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for AAK1 Gene

Publications for AAK1 Gene

  1. AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis. (PMID: 18657069) Sorensen EB … Conner SD (Traffic (Copenhagen, Denmark) 2008) 3 4 22 58
  2. Differential requirements for AP-2 in clathrin-mediated endocytosis. (PMID: 12952931) Conner SD … Schmid SL (The Journal of cell biology 2003) 3 4 22 58
  3. The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway. (PMID: 21464124) Gupta-Rossi N … Israël A (The Journal of biological chemistry 2011) 3 4 58
  4. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. (PMID: 20379614) Rose JE … Uhl GR (Molecular medicine (Cambridge, Mass.) 2010) 3 44 58
  5. Genomewide association study for onset age in Parkinson disease. (PMID: 19772629) Latourelle JC … GenePD Investigators, Coordinators and Molecular Genetic Laboratories (BMC medical genetics 2009) 3 44 58

Products for AAK1 Gene

  • Addgene plasmids for AAK1

Sources for AAK1 Gene

Content
Loading form....