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

    Gene ID: 22848, updated on 2-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
    mouse all
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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 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 variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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 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 Notch binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables histone H2AS1 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
    		  
    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.

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