AAK1 Gene
protein-coding GIFtS: 54
GCID: GC02M069685
|
|
AP2 associated kinase 1
| |
Aliases
for AAK1 gene
(According to
1HGNC,
2Entrez Gene,
3UniProtKB/Swiss-Prot,
4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc,
7Ensembl,
8DME,
9miRBase,
and/or 10fRNAdb)
About This Section
|
| Aliases |
|---|
| AP2 Associated Kinase 11 2 | | KIAA10481 3 | | Adaptor-Associated Kinase 12 3 | | EC 2.7.11.13 8 | | DKFZp686K161321 | | AP2-Associated Protein Kinase 12 |
Export aliases for AAK1 gene to outside databasesPrevious GC identifers: GC02M069717 GC02M069899 GC02M069683 GC02M069619 GC02M069561 GC02M069421 |
Summaries
for AAK1 gene(According to Entrez Gene,
Tocris Bioscience,
Wikipedia's
Gene Wiki,
PharmGKB,
UniProtKB/Swiss-Prot,
and/or
UniProtKB/TrEMBL)
About This Section
|
Entrez Gene summary for AAK1:
Adaptor-related protein complex 2 (AP-2 complexes) functions during receptor-mediated endocytosis to trigger clathrinassembly, interact with membrane-bound receptors, and recruit encodytic accessory factors. This gene encodes a memberof the SNF1 subfamily of Ser/Thr protein kinases. The protein interacts with and phosphorylates a subunit of the AP-2complex, which promotes binding of AP-2 to sorting signals found in membrane-bound receptors and subsequent receptorendocytosis. Its kinase activity is stimulated by clathrin. Alternatively spliced transcript variants have beendescribed, but their biological validity has not been determined. (provided by RefSeq, Jul 2008)
UniProtKB/Swiss-Prot: AAK1_HUMAN, Q2M2I8Function: Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor proteincomplex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages ofendocytosis. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. Regulatesphosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligandcomplexes. 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 itstranscriptional activity
Gene Wiki entry for AAK1
|
Genomic Views
for AAK1 gene
(According to
GeneLoc and/or
HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to
UCSC (hg19) and
Ensembl (release 69),
Regulatory elements and Epigenetics data according to
QIAGEN,
SABiosciences, and/or
SwitchGear Genomics)
About This Section
| RefSeq DNA sequence:- NC_000002.11 NC_018913.1 NT_022184.15
Regulatory elements:
 SABiosciences Regulatory transcription factor binding sites in the AAK1 gene promoter:
NF-1 AML1a AP-2alpha isoform 3 Lmo2 AP-2alpha isoform 2 AP-2alpha isoform 4 AP-2alpha AP-2alphaA
Other transcription factors
Search SABiosciences Chromatin IP Primers for AAK1
Epigenetics:
| | QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat AAK1 |
Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track
Entrez Gene cytogenetic band: 2p14 Ensembl cytogenetic band: 2p13.3 HGNC cytogenetic band: 2p13.3AAK1 Gene in genomic location: bands according to Ensembl, locations according to
 (and/or Entrez Gene and/or Ensembl if different)
GeneLoc information about chromosome 2 GeneLoc Exon Structure GeneLoc location for GC02M069685: view genomic region
(about GC identifiers)
Start:
|
69,685,127 bp from pter |
End:
|
69,901,481 bp from pter |
Size:
|
216,355 bases |
Orientation:
|
minus strand |
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Proteins
for AAK1 gene
(According to
1UniProtKB,
HORDE,
neXtProt,
Ensembl,
and/or Reactome,
Modification sites according to 2PhosphoSitePlus,
Specific Peptides from DME,
Protein expression images according to data from SPIRE MOPED and PaxDb,
RefSeq according to NCBI,
PDB rendering according to OCA and/or Proteopedia,
Recombinant Proteins
from
EMD Millipore,
R&D Systems,
GenScript,
Enzo Life Sciences,
OriGene,
Novus Biologicals,
Sino Biological,
ProSpec, and/or
Uscn,
Biochemical Assays by
EMD Millipore,
R&D Systems,
OriGene,
GenScript,
Cell Signaling Technology,
Enzo Life Sciences, and/or
Uscn,
Ontologies according to Gene
Ontology Consortium 01 Mar 2013 and
Entrez Gene,
Antibodies by
EMD Millipore,
R&D Systems,
GenScript,
Cell Signaling Technology,
OriGene,
Novus Biologicals,
Thermo Fisher Scientific,
Abcam, and/or
Uscn)
About This Section
|
UniProtKB/Swiss-Prot: AAK1_HUMAN, Q2M2I8 (See
protein sequence)Recommended Name: AP2-associated protein kinase 1 Size: 961 amino acids; 103885 Da
Subunit: Interacts with alpha-adaptin, AP-2, clathrin, NUMB and EPS15 isoform 2. Interacts with membrane-boundactivated NOTCH1 but not with the inactive full-length form of NOTCH1. Preferentially interacts with monoubiquitinatedactivated NOTCH1 compared to the non-ubiquitinated form
Subcellular location: Cell membrane; Peripheral membrane protein (By similarity). Membrane, clathrin-coated pit (Bysimilarity). Note=Active when found in clathrin-coated pits at the plasma membrane. In neuronal cells, enriched atpresynaptic terminals. In non-neuronal cells, enriched at leading edge of migrating cells (By similarity)
Sequence caution: Sequence=BAA83000.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Secondary accessions: Q4ZFZ3 Q53RX6 Q9UPV4Alternative splicing: 2 isoforms: Q2M2I8-1 Q2M2I8-2 Explore the universe of human proteins at neXtProt for AAK1: NX_Q2M2I8
Post-translational modifications:
Autophosphorylated (By similarity)1
View modification sites using PhosphoSitePlus2View neXtProt modification sites for NX_Q2M2I8
4/11 DME Specific Peptides for AAK1 (Q2M2I8) (see all 11)
AAK1 Protein expression data from MOPED and PaxDb: About this image 
REFSEQ proteins: NP_055726.3
ENSEMBL proteins: ENSP00000386342 ENSP00000386456 ENSP00000385181
Human Recombinant Protein Products:
Gene Ontology (GO): 5/6 cellular component terms (GO ID links to tree view) (see all 6): About this table
AAK1 for ontologies About GeneDecksing
AAK1 Antibody Products:
Assay Products for AAK1: |
Protein
Domains /
Families
for AAK1 gene(According to InterPro, ProtoNet,
UniProtKB, and/or BLOCKS,
Sets of similar genes according to GeneDecks)
About This Section
|
AAK1 for domains About GeneDecksing
3 InterPro domains/families:Graphical View of Domain Structure for InterPro Entry Q2M2I8ProtoNet protein and cluster: Q2M2I8 UniProtKB/Swiss-Prot: AAK1_HUMAN, Q2M2I8Similarity: Belongs to the protein kinase superfamily. Ser/Thr protein kinase familySimilarity: Contains 1 protein kinase domain |
Function
for AAK1 gene
(According to 1UniProtKB,
Genatlas,
LifeMap Discovery™,
IUBMB, and/or
2DME,
Human phenotypes from GenomeRNAi,
Animal models from MGI Mar 06 2013,
bound targets from SABiosciences,
miRNA Gene Targets from miRTarBase
shRNA from
OriGene,
RNAi from
EMD Millipore,
siRNAs from
OriGene,
QIAGEN,
microRNA from QIAGEN,
Gene Editing from DNA2.0,
Clones from EMD Millipore,
OriGene,
SwitchGear Genomics,
GenScript,
Sino Biological,
DNA2.0,
and Vector BioLabs,
Cell Lines from GenScript,
LifeMap BioReagents,
In Situ Hybridization Assays from Advanced Cell Diagnostics,
Ontologies according to Gene Ontology Consortium 01 Mar 2013 via
Entrez Gene.)
About This Section
|
Function Summary:
UniProtKB/Swiss-Prot: AAK1_HUMAN, Q2M2I8Function: Regulates clathrin-mediated endocytosis by phosphorylating the AP2M1/mu2 subunit of the adaptor proteincomplex 2 (AP-2) which ensures high affinity binding of AP-2 to cargo membrane proteins during the initial stages ofendocytosis. Isoform 1 and isoform 2 display similar levels of kinase activity towards AP2M1. Regulatesphosphorylation of other AP-2 subunits as well as AP-2 localization and AP-2-mediated internalization of ligandcomplexes. 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 itstranscriptional activityCatalytic activity: ATP + a protein = ADP + a phosphoproteinEnzyme regulation: Stimulated by clathrin (By similarity)Enzyme Number (IUBMB): EC 2.7.11.11 2
Clone
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OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for AAK1 (see all 3)
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In Situ Assay
Products: |
 | Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for AAK1 |
Gene Ontology (GO): 5 molecular function terms (GO ID links to tree view): About this table
AAK1 for ontologies About GeneDecksing
1 GenomeRNAi human phenotype for AAK1:
|
Pathways & Interactions
for AAK1 gene
(Pathways according to
EMD Millipore,
R&D Systems,
Cell Signaling Technology,
KEGG,
PharmGKB,
BioSystems,
Reactome,
Tocris Bioscience,
GeneGo (Thomson Reuters),
QIAGEN,
and/or UniProtKB,
Sets of similar genes according to GeneDecks,
Interaction Networks according to
SABiosciences,
and/or STRING,
Interactions according to 1UniProtKB,
2MINT,
3I2D, and/or
4STRING,
with links to IntAct and
Ensembl,
Ontologies according to Gene Ontology Consortium 01 Mar 2013 via
Entrez Gene).
About This Section
|
Interactions:
Search SABiosciences Gene Network CentralTM Interacting Genes and Proteins Networks for AAK1
STRING Interaction
Network Preview (showing 1 interactants - click image to see more details)
4 Interacting proteins for AAK1 (Q2M2I81, 3 ENSP000003864564) via UniProtKB, MINT, STRING, and/or I2DAbout this table
Gene Ontology (GO): 5/7 biological process terms (GO ID links to tree view) (see all 7): About this table
AAK1 for ontologies About GeneDecksing
|
Drugs & Compounds
for AAK1 gene(Chemical Compounds according to UniProtKB, Enzo Life Sciences,
EMD Millipore, Tocris Bioscience
HMDB,
BitterDB, and/or
Novoseek, and Drugs according to
DrugBank,
Enzo Life Sciences, and/or
PharmGKB, with drugs/clinical trials/news
search links to CenterWatch)
About This Section
|
 Browse Tocris compounds for AAK1
2 HMDB Compounds for AAK1 About this table
Search CenterWatch for drugs/clinical trials and news about AAK1
|
Transcripts
for AAK1 gene(Secondary structures according to
fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene
(Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or
AceView,
transcript ids from Ensembl
with links to UCSC,
exon structure from GeneLoc,
alternative splicing isoforms according to ASD and/or
ECgene,
RNAi Products from
EMD Millipore,
siRNAs from
OriGene,
QIAGEN,
shRNA from
OriGene,
microRNA from QIAGEN,
Tagged/untagged cDNA clones from
OriGene,
SwitchGear Genomics,
GenScript,
DNA2.0,
Vector BioLabs,
Primers from
OriGene,
SABiosciences, and/or
QIAGEN
)
About This Section
|
REFSEQ mRNAs for AAK1 gene: NM_014911.3 Unigene Cluster for AAK1: AP2 associated kinase 1 Hs.468878 [show with all ESTs]Unigene Representative Sequence: NM_01491110 Ensembl transcripts including schematic representations, and UCSC links where relevant: ENST00000409068 ENST00000409085(uc002sfp.2) ENST00000489327 ENST00000406297(uc010fdk.2 uc010yqm.1)
ENST00000470281 ENST00000495836(uc010fdm.1) ENST00000495239 ENST00000471775
ENST00000461002 ENST00000492192
Clone
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OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for AAK1 (see all 3)
OriGene custom cloning services – gene synthesis, subcloning, mutagenesis,
variant library, vector shuttling
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Additional cDNA sequence: AF090100.1 AF090101.1 AK055622.1 AK056043.1 AK074292.1 AK098797.1 AK124229.1 AK124872.1 AK127187.1 AK310951.1 BC002695.2 BC073953.1 BC090950.1 BC104842.1 BC111965.1 BC132937.1 BC132939.1 BC143710.1 BX640963.1 BX641060.1 24/25 DOTS entries (see all 25): DT.40236651 DT.212178 DT.423892 DT.91770925 DT.97835469 DT.97840143 DT.406526 DT.120967885 DT.75100760 DT.120967810 DT.101955018 DT.91681853 DT.92048762 DT.40269460 DT.91657368 DT.91709840 DT.95157451 DT.120967884 DT.91874433 DT.95169277 DT.95370485 DT.99973978 DT.40316488 DT.75173194 24/158 AceView cDNA sequences (see all 158): BU616599 BX496298 BX643479 BM708925 AI417784 BG167887 CR624904 CB161647 BE673248 AW183814 BM683347 CR599899 AI940506 AA406326 AI092715 AA320178 AI393040 AW150262 AK127187 BE502816 AI561048 BQ448135 AW005687 BC073953
GeneLoc Exon Structure
|
Expression
for AAK1 gene
(RNA expression data according to
H-InvDB,
NONCODE,
miRBase, and
RNAdb,
Expression images according to data from
BioGPS,
Illumina Human BodyMap, and
CGAP
SAGE,
Sets of similar genes according to GeneDecks,
in vivo and in vitro expression data from LifeMap Discovery™,
plus additional links to
Genevestigator, and/or
SOURCE, and/or
BioGPS, and/or
UniProtKB,
PCR Arrays from
SABiosciences,
Primers from
OriGene,
SABiosciences, and/or
QIAGEN,
In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section
| AAK1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AAAGTCAATC
About this image
See AAK1 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for AAK1
SOURCE GeneReport for Unigene cluster: Hs.468878
UniProtKB/Swiss-Prot: AAK1_HUMAN, Q2M2I8Tissue specificity: Detected in brain, heart and liver. Isoform 1 is the predominant isoform in brain
SABiosciences Custom PCR Arrays for AAK1
Primer
Products: | | OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for AAK1
Browse OriGene validated miRNA SYBR primer pairs
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Assay Products: |
| Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for AAK1 |
Orthologs
for AAK1 gene
(Orthologs according to
1,2HomoloGene (2older version, for species not in 1newer version),
3euGenes,
4SGD
,
5MGI Mar 06 2013,
with possible further links to
Flybase
and/or
WormBase,
and/or
6Ensembl pan taxonomic compara ,
Gene Trees according to Ensembl and
TreeFam)
About This Section
|
This gene was present in the common ancestor of animals.
Orthologs for AAK1 gene from 6/22 species (see all 22) About this table
| Organism |
Taxonomic
classification |
Gene |
Description |
Human
Similarity |
Orthology
Type |
Details |
chicken
(Gallus gallus) |
Aves |
AAK16 |
Uncharacterized protein |
76(a) |
1 ↔ 1 |
22(31147-93233) |
lizard
(Anolis carolinensis) |
Reptilia |
AAK16 |
-- |
57(a) |
1 ↔ 1 |
GL344011.1(30262-92168) |
African clawed frog
(Xenopus laevis) |
Amphibia |
BQ385825.12 |
-- |
75.89(n) |
|
BQ385825.1 |
zebrafish
(Danio rerio) |
Actinopterygii |
AL923286.12 |
-- |
77.76(n) |
|
AL923286.1 |
fruit fly
(Drosophila melanogaster) |
Insecta |
Nak6 |
Numb-associated kinase |
17(a) |
1 → many |
2L(18957900-18968721) |
worm
(Caenorhabditis elegans) |
Secernentea |
sel-56 |
Suppressor/Enhancer of Lin-12 family member (sel-5... |
17(a) |
1 → many |
III(4571721-4578405) |
ENSEMBL Gene Tree for AAK1 (if available)
TreeFam Gene Tree for AAK1 (if available) |
Paralogs
for AAK1 gene(Paralogs according to
1HomoloGene,
2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
About This Section
| Paralogs for AAK1 gene
- BMP2K2
2 SIMAP similar genes for AAK1 using alignment to 6 protein entries: AAK1_HUMAN (see all proteins):BMP2K DKFZp564L2416
AAK1 for paralogs About GeneDecksing
|
Genomic Variants
for AAK1 gene(SNPs/Variants according to the
1NCBI SNP Database,
2Ensembl,
3PupaSUITE,
UniProtKB, and
DNA2.0,
Linkage Disequilibrium by HapMap,
Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene
Mutation Database (HGMD) and the Locus Specific Mutation
Databases (LSDB), Blood group antigen gene mutations by BGMUT,
Resequencing Primers from QIAGEN,
Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section
|
| Genomic Data | Transcription Related Data | Allele Frequencies | | SNP ID | Valid | Clinical
significance | Chr 2 pos | Sequence | # | AA
Chg | Type | More | # | Allele
freq | Pop | Total
sample | More |
|---|
HapMap Linkage Disequilibrium report for AAK1 (69685127 - 69901481 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 3 variations for AAK1
2 CNVs: 5986 7279
1 Indel: 59000 | SABiosciences Cancer Mutation PCR Assays |
| | QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing AAK1 |
|
Disorders
/ Diseases
for AAK1 gene
(in which this Gene is Involved, According to MalaCards,
OMIM, UniProtKB,
the University of Copenhagen DISEASES
database,
Genatlas, GeneTests,
GAD,
HuGE Navigator,
and/or TGDB.)
About This Section
|
AAK1 for disorders About GeneDecksing
4  diseases for AAK1: About MalaCardsnecrotizing fasciitis fasciitis malaria neuronitis
Human Genome Epidemiology (HuGE) Navigator: AAK1 (2 documents)
Export disorders for AAK1 gene to outside databases
|
Publications
for AAK1 gene (in
PubMed.
Associations of this gene to articles via
1Entrez Gene,
2UniProtKB/Swiss-Prot,
3HGNC,
4GAD,
5PharmGKB,
6HMDB,
7DrugBank,
8UniProtKB/TrEMBL,
9 Novoseek, and/or
10fRNAdb)
About This Section
|
PubMed articles for AAK1 gene, integrated from 9 sources (see all 38):
(articles sorted by number of sources associating them with AAK1) | |  | Utopia: connect your pdf to the dynamic
world of online information |
- AAK1 regulates Numb function at an early step in clathrin-mediated endocytosis. (PubMed id 18657069)1, 2, 9 Sorensen E.B. and Conner S.D. (2008)
- Differential requirements for AP-2 in clathrin-mediated endocytosis. (PubMed id 12952931)1, 2, 9 Conner S.D. and Schmid S.L. (2003)
- The adaptor-associated kinase 1, AAK1, is a positive regulator of the Notch pathway. (PubMed id 21464124)1, 2 Gupta-Rossi N.... Israel A. (2011)
- A novel AAK1 splice variant functions at multiple steps of the endocytic pathway. (PubMed id 17494869)1, 2 Henderson D.M. and Conner S.D. (2007)
- A probability-based approach for high-throughput protein phosphorylation analysis and site localization. (PubMed id 16964243)1, 2 Beausoleil S.A.... Gygi S.P. (2006)
- Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PubMed id 15815621)1, 2 Hillier L.W....Wilson R.K. (2005)
- The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
- Identification of an adaptor-associated kinase, AAK1, as a regulator of clathrin-mediated endocytosis. (PubMed id 11877461)1, 3 Conner S.D. and Schmid S.L. (2002)
- The protein kinase complement of the human genome. (PubMed id 12471243)1, 3 Manning G.... Sudarsanam S. (2002)
- Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. (PubMed id 10470851)1, 2 Kikuno R....Ohara O. (1999)
|
External Searches for AAK1 gene
(in PubMed,
OMIM, and NCBI Bookshelf)
About This Section
|
|
Genome Databases showing AAK1 gene
(According to
Entrez Gene,
HGNC,
AceView,
euGenes,
Ensembl,
miRBase,
ECgene,
Kegg,
and/or
H-InvDB)
About This Section
|
|
Other Databases showing AAK1 gene
(According to HUGE)
About This Section
| |
Specialized Databases showing AAK1 gene(According to PharmGKB,
ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section
|
| Name | Description |
| PharmGKB entry for AAK1 | Pharmacogenomics, SNPs, Pathways |
|
| | |
About This Section
| Patent Information for AAK1 gene:
Search GeneIP for patents involving AAK1
GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search
|
Products
for AAK1 gene(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or
Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
About This Section
|
 | |
 | |
 |
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