AAK1

Protein identityUniProt · HPA

UniProt accession

Q2M2I8

Gene

AAK1

Ensembl

ENSG00000115977

Chromosome

2

Canonical length

961 aa

Protein class

Enzymes, Predicted intracellular proteins

Subcellular location

Vesicles,Plasma membrane,Cytosol

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

961 residues, UniProt reviewed canonical sequence.

>Q2M2I8|AAK1
     1  MKKFFDSRRE QGGSGLGSGS SGGGGSTSGL GSGYIGRVFG IGRQQVTVDE VLAEGGFAIV
    61  FLVRTSNGMK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH KNIVGYIDSS INNVSSGDVW
   121  EVLILMDFCR GGQVVNLMNQ RLQTGFTENE VLQIFCDTCE AVARLHQCKT PIIHRDLKVE
   181  NILLHDRGHY VLCDFGSATN KFQNPQTEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKIIT
   241  TKADIWALGC LLYKLCYFTL PFGESQVAIC DGNFTIPDNS RYSQDMHCLI RYMLEPDPDK
   301  RPDIYQVSYF SFKLLKKECP IPNVQNSPIP AKLPEPVKAS EAAAKKTQPK ARLTDPIPTT
   361  ETSIAPRQRP KAGQTQPNPG ILPIQPALTP RKRATVQPPP QAAGSSNQPG LLASVPQPKP
   421  QAPPSQPLPQ TQAKQPQAPP TPQQTPSTQA QGLPAQAQAT PQHQQQLFLK QQQQQQQPPP
   481  AQQQPAGTFY QQQQAQTQQF QAVHPATQKP AIAQFPVVSQ GGSQQQLMQN FYQQQQQQQQ
   541  QQQQQQLATA LHQQQLMTQQ AALQQKPTMA AGQQPQPQPA AAPQPAPAQE PAIQAPVRQQ
   601  PKVQTTPPPA VQGQKVGSLT PPSSPKTQRA GHRRILSDVT HSAVFGVPAS KSTQLLQAAA
   661  AEASLNKSKS ATTTPSGSPR TSQQNVYNPS EGSTWNPFDD DNFSKLTAEE LLNKDFAKLG
   721  EGKHPEKLGG SAESLIPGFQ STQGDAFATT SFSAGTAEKR KGGQTVDSGL PLLSVSDPFI
   781  PLQVPDAPEK LIEGLKSPDT SLLLPDLLPM TDPFGSTSDA VIEKADVAVE SLIPGLEPPV
   841  PQRLPSQTES VTSNRTDSLT GEDSLLDCSL LSNPTTDLLE EFAPTAISAP VHKAAEDSNL
   901  ISGFDVPEGS DKVAEDEFDP IPVLITKNPQ GGHSRNSSGS SESSLPNLAR SLLLVDQLID
   961  L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AAK1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.56

Highest tissue expression

84 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.13

gnomAD pLI

1

gnomAD missense Z

2.61

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• membrane organization
• positive regulation of Notch signaling pathway
• presynaptic endocytosis
• protein phosphorylation
• protein stabilization
• regulation of clathrin-dependent endocytosis
• regulation of protein localization

Molecular functions

• AP-2 adaptor complex binding
• ATP binding
• Notch binding
• protein serine kinase activity
• protein serine/threonine kinase activity

Cellular components

• cell leading edge
• clathrin-coated pit
• clathrin-coated vesicle
• cytosol
• plasma membrane
• presynapse
• terminal bouton

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• AP2-associated Ser/Thr protein kinase
• Protein kinase domain

KeywordsUniProt

• Acetylation
• ATP-binding
• Cell membrane
• Cell projection
• Coated pit
• Endocytosis
• Kinase
• Membrane
• Methylation
• Nucleotide-binding
• Pharmaceutical
• Phosphoprotein
• Serine/threonine-protein kinase
• Synapse
• Transferase

InteractionsUniProt · HPA

Protein binding partners of AAK1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NUMB
• AP2B1
• AP2S1
• ATP13A2
• RALBP1
• WNK1