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AAK1 AP2 associated kinase 1 [ Homo sapiens (human) ]

Gene ID: 22848, updated on 14-Nov-2024

Summary

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Official Symbol
AAK1provided by HGNC
Official Full Name
AP2 associated kinase 1provided by HGNC
Primary source
HGNC:HGNC:19679
See related
Ensembl:ENSG00000115977 MIM:616405; AllianceGenome:HGNC:19679
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary
This gene encodes a member of the SNF1 subfamily of serine/threonine protein kinases. 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. The encoded 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. This kinase has been shown to play an important role in regulating the clathrin-mediated endocytosis of the rabies virus, facilitating infection. Inhibitors of this kinase are being studied as candidate therapeutics to disrupt the entry of viruses, including SARS-CoV-2, into target cells. It is also involved in positive regulation of Notch pathway signaling in mammals. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Aug 2020]
Annotation information
Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in SARS-CoV-2 infection.
Expression
Ubiquitous expression in brain (RPKM 7.8), thyroid (RPKM 4.9) and 24 other tissues See more
Orthologs
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Genomic context

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See AAK1 in Genome Data Viewer
Location:
2p13.3
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (69457997..69643739, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (69470304..69656050, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (69685129..69870871, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15971 Neighboring gene NFU1 iron-sulfur cluster scaffold Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr2:69671824-69672380 Neighboring gene uncharacterized LOC124906020 Neighboring gene Sharpr-MPRA regulatory region 9634 Neighboring gene RNA, 7SL, cytoplasmic 604, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15972 Neighboring gene small nucleolar RNA, H/ACA box 36C Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15973 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15974 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:69804675-69805175 Neighboring gene Sharpr-MPRA regulatory region 3088 Neighboring gene beta-1,3-N-acetylgalactosaminyltransferase 1 pseudogene 1 Neighboring gene ribosomal protein L36a pseudogene 16 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11597 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15975 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr2:69872055-69872657 Neighboring gene small nucleolar RNA U13 Neighboring gene annexin A4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15976 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11598 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11599 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15977 Neighboring gene SMARCA4 interacting SWI/SNF chromatin remodeling complex scaffold lncRNA

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The Serine/Threonine Kinase AP2-Associated Kinase 1 Plays an Important Role in Rabies Virus Entry. Wang C, et al. Viruses, 2019 Dec 30. PMID 31905947, Free PMC Article
  2. Baricitinib as potential treatment for 2019-nCoV acute respiratory disease. Richardson P, et al. Lancet, 2020 Feb 15. PMID 32032529, Free PMC Article
  3. Differential requirements for AP-2 in clathrin-mediated endocytosis. Conner SD, et al. J Cell Biol, 2003 Sep 1. PMID 12952931, Free PMC Article
  4. Therapeutic options for the treatment of 2019-novel coronavirus: An evidence-based approach. Sarma P, et al. Indian J Pharmacol, 2020 Jan-Feb. PMID 32201439, Free PMC Article
  5. Potential Treatments for COVID-19; a Narrative Literature Review. Rismanbaf A. Arch Acad Emerg Med, 2020. PMID 32232214, Free PMC Article

See all (85) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Extracellular vesicle-transmitted miR-671-5p alleviates lung inflammation and injury by regulating the AAK1/NF-kappaB axis.
    Title: Extracellular vesicle-transmitted miR-671-5p alleviates lung inflammation and injury by regulating the AAK1/NF-κB axis.
  2. The Serine/Threonine Kinase AP2-Associated Kinase 1 Plays an Important Role in Rabies Virus Entry.
    Title: The Serine/Threonine Kinase AP2-Associated Kinase 1 Plays an Important Role in Rabies Virus Entry.
  3. Author show that AAK1 promotes clearance of LRP6 from the plasma membrane to suppress the WNT pathway.
    Title: WNT Activates the AAK1 Kinase to Promote Clathrin-Mediated Endocytosis of LRP6 and Establish a Negative Feedback Loop.
  4. Results present the first structures of AAK1 and BIKE which reveal that all members of the Numb-associated kinase family share unusual activation segment architecture.
    Title: Family-wide Structural Analysis of Human Numb-Associated Protein Kinases.
  5. Two of these kinases that were classified as resistors were PX domain-containing serine/threonine kinase (PXK) and AP2-associated kinase 1 (AAK1), which promote receptor endocytosis and may enable cells to resist TRAIL-induced apoptosis
    Title: Integrative analysis of kinase networks in TRAIL-induced apoptosis provides a source of potential targets for combination therapy.
  6. AAK1 and GAK are critical regulators of HCV entry that function in part by activating EGFR, AP2M1, and NUMB, and as the molecular targets underlying the antiviral effect of sunitinib and erlotinib, respectively.
    Title: AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate hepatitis C virus entry and are potential drug targets.
  7. AAK1 increases the localization of activated Notch to Rab5-positive endocytic vesicles, while AAK1 depletion or overexpression of Numb, an inhibitor of the pathway, interferes with this localization.
    Title: The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway.
  8. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
  9. Observational study, meta-analysis, and genome-wide association study of gene-disease association. (HuGE Navigator)
    Title: Genomewide association study for onset age in Parkinson disease.
  10. These observations suggest that AAK1 functions at multiple steps of the endosomal pathway by regulating transferrin internalization and its rapid recycling back to the plasma membrane from early/sorting endosome.
    Title: A novel AAK1 splice variant functions at multiple steps of the endocytic pathway.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic Variants Associated with Serum Thyroid Stimulating Hormone (TSH) Levels in European Americans and African Americans from the eMERGE Network.
EBI GWAS Catalog
Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study.
EBI GWAS Catalog
Genomewide association study for onset age in Parkinson disease.
EBI GWAS Catalog

Variation

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See Variation Viewer (GRCh37.p13)

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of AP2 associated kinase 1 (AAK1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Nef nef Genome-wide shRNA screening identifies AAK1, which is required for HIV-1 Nef-induced downregulation of CD4 in HeLa CD4+ cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ23712, FLJ25931, FLJ31060, FLJ42882, FLJ45252, KIAA1048, MGC138170, MGC164568, MGC164570, DKFZp686F03202, DKFZp686K16132

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 3-phosphoinositide-dependent protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables AMP-activated protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables AP-2 adaptor complex binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables AP-2 adaptor complex binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables DNA-dependent protein kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables Notch binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables Rho-dependent protein serine/threonine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables eukaryotic translation initiation factor 2alpha kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AS1 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AS121 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AT120 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2AXS139 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2BS14 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H2BS36 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S10 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S28 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3S57 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T11 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T3 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T45 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H3T6 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables histone H4S1 kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables protein serine/threonine kinase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
  
enables ribosomal protein S6 kinase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in chromatin remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in membrane organization TAS
Traceable Author Statement
more info
  
involved_in positive regulation of Notch signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in presynaptic endocytosis IEA
Inferred from Electronic Annotation
more info
  
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein stabilization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of clathrin-dependent endocytosis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of clathrin-dependent endocytosis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of clathrin-dependent endocytosis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of protein localization IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in cell leading edge ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in clathrin-coated pit ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in clathrin-coated vesicle ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
  
is_active_in presynapse IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in terminal bouton ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
AP2-associated protein kinase 1
Names
adaptor-associated kinase 1
alternative protein AAK1
NP_001358504.1
NP_001358506.1
NP_001413674.1
NP_001413675.1
NP_055726.4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001371575.1 → NP_001358504.1  AP2-associated protein kinase 1 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AC079121, AC092431, AC114772, AC136007
    UniProtKB/TrEMBL
    B7ZLC4
    Related
    ENSP00000385181.3, ENST00000406297.7
    Conserved Domains (2) summary
    PHA03378
    Location:296 → 461
    PHA03378; EBNA-3B; Provisional
    cd14037
    Location:42 → 316
    STKc_NAK_like; Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases

  2. NM_001371577.1 → NP_001358506.1  AP2-associated protein kinase 1 isoform 3

    Status: REVIEWED

    Source sequence(s)
    AC079121, AC092431, AC114772
    UniProtKB/TrEMBL
    E9PG46
    Related
    ENSP00000386342.1, ENST00000409068.5
    Conserved Domains (2) summary
    PHA03378
    Location:296 → 461
    PHA03378; EBNA-3B; Provisional
    cd14037
    Location:42 → 316
    STKc_NAK_like; Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases

  3. NM_001426745.1 → NP_001413674.1  AP2-associated protein kinase 1 isoform 4

    Status: REVIEWED

    Source sequence(s)
    AC079121, AC092431, AC114772

  4. NM_001426746.1 → NP_001413675.1  AP2-associated protein kinase 1 isoform 5

    Status: REVIEWED

    Source sequence(s)
    AC079121, AC092431, AC114772
    Related
    ENSP00000485350.2, ENST00000606389.8

  5. NM_014911.5 → NP_055726.4  AP2-associated protein kinase 1 isoform 1

    Status: REVIEWED

    Source sequence(s)
    AC079121, AC114772, AC136007, AW451954, AW969393, BC111965, CA436375, DA121999, DB285703
    Consensus CDS
    CCDS1893.2
    UniProtKB/Swiss-Prot
    Q2M2I8, Q4ZFZ3, Q53RX6, Q9UPV4
    UniProtKB/TrEMBL
    B7ZLC4
    Related
    ENSP00000386456.3, ENST00000409085.9
    Conserved Domains (2) summary
    PHA03378
    Location:296 → 461
    PHA03378; EBNA-3B; Provisional
    cd14037
    Location:42 → 316
    STKc_NAK_like; Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    69457997..69643739 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    69470304..69656050 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q2M2I8.3 GenPept UniProtKB/Swiss-Prot:Q2M2I8

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

Chemical Information
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Research Materials
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