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AP2-associated protein kinase 1 (EC 2.7.11.1) (Adaptor-associated kinase 1)
AAK1_PIG Reviewed; 968 AA.
F1SPM8;
19-OCT-2011, integrated into UniProtKB/Swiss-Prot.
19-OCT-2011, sequence version 2.
28-FEB-2018, entry version 40.
RecName: Full=AP2-associated protein kinase 1 {ECO:0000303|PubMed:11877457};
EC=2.7.11.1 {ECO:0000250|UniProtKB:P0C1X8};
AltName: Full=Adaptor-associated kinase 1 {ECO:0000303|PubMed:11877457};
Name=AAK1;
Sus scrofa (Pig).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Suina; Suidae;
Sus.
NCBI_TaxID=9823;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Porcine genome sequencing project;
Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-54.
Uenishi H., Morozumi T., Toki D., Eguchi-Ogawa T., Tanaka-Matsuda M.;
"Porcine ESTs using full-length-enriched cDNA libraries.";
Submitted (FEB-2010) to the EMBL/GenBank/DDBJ databases.
[3] {ECO:0000305}
FUNCTION.
PubMed=11877457; DOI=10.1083/jcb.200111068;
Ricotta D., Conner S.D., Schmid S.L., von Figura K., Honing S.;
"Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity
binding to membrane protein sorting signals.";
J. Cell Biol. 156:791-795(2002).
-!- 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.
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. {ECO:0000269|PubMed:11877457}.
-!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
{ECO:0000250|UniProtKB:P0C1X8}.
-!- ENZYME REGULATION: Stimulated by clathrin.
{ECO:0000250|UniProtKB:P0C1X8}.
-!- SUBUNIT: Interacts with alpha-adaptin, AP-2, clathrin, NUMB and
EPS15. 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 (By similarity). {ECO:0000250}.
-!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:F1MH24,
ECO:0000250|UniProtKB:P0C1X8}; Peripheral membrane protein
{ECO:0000250|UniProtKB:F1MH24, ECO:0000250|UniProtKB:P0C1X8}.
Membrane, clathrin-coated pit {ECO:0000250|UniProtKB:F1MH24,
ECO:0000250|UniProtKB:P0C1X8}. 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|UniProtKB:F1MH24, ECO:0000250|UniProtKB:P0C1X8}.
-!- PTM: Autophosphorylated. {ECO:0000250|UniProtKB:P0C1X8}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr
protein kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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EMBL; CU467585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; FS674854; -; NOT_ANNOTATED_CDS; mRNA.
SMR; F1SPM8; -.
STRING; 9823.ENSSSCP00000008900; -.
PaxDb; F1SPM8; -.
PeptideAtlas; F1SPM8; -.
PRIDE; F1SPM8; -.
Ensembl; ENSSSCT00000009130; ENSSSCP00000008900; ENSSSCG00000008337.
eggNOG; KOG1989; Eukaryota.
eggNOG; ENOG410Y515; LUCA.
GeneTree; ENSGT00880000137958; -.
InParanoid; F1SPM8; -.
Reactome; R-SSC-8856825; Cargo recognition for clathrin-mediated endocytosis.
Reactome; R-SSC-8856828; Clathrin-mediated endocytosis.
Proteomes; UP000008227; Chromosome 3.
GO; GO:0031252; C:cell leading edge; ISS:UniProtKB.
GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
GO; GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
GO; GO:0019897; C:extrinsic component of plasma membrane; ISS:UniProtKB.
GO; GO:0043195; C:terminal bouton; ISS:UniProtKB.
GO; GO:0035612; F:AP-2 adaptor complex binding; ISS:UniProtKB.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0005112; F:Notch binding; ISS:UniProtKB.
GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
GO; GO:0045747; P:positive regulation of Notch signaling pathway; ISS:UniProtKB.
GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; IDA:UniProtKB.
GO; GO:0032880; P:regulation of protein localization; ISS:UniProtKB.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00069; Pkinase; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
2: Evidence at transcript level;
Acetylation; ATP-binding; Cell membrane; Coated pit;
Complete proteome; Endocytosis; Kinase; Membrane; Methylation;
Nucleotide-binding; Phosphoprotein; Reference proteome;
Serine/threonine-protein kinase; Transferase.
CHAIN 1 968 AP2-associated protein kinase 1.
/FTId=PRO_0000413362.
DOMAIN 46 315 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
NP_BIND 52 60 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
COMPBIAS 397 621 Gln-rich.
COMPBIAS 665 670 Poly-Ala.
ACT_SITE 176 176 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 74 74 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 1 1 N-acetylmethionine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 14 14 Phosphoserine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 234 234 Phosphotyrosine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 235 235 Phosphoserine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 354 354 Phosphothreonine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 389 389 Phosphothreonine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 391 391 Omega-N-methylarginine.
{ECO:0000250|UniProtKB:Q3UHJ0}.
MOD_RES 613 613 Phosphothreonine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 625 625 Phosphoserine.
{ECO:0000250|UniProtKB:P0C1X8}.
MOD_RES 627 627 Phosphothreonine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 630 630 Phosphoserine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 631 631 Phosphoserine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 644 644 Phosphoserine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 657 657 Phosphoserine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 660 660 Phosphothreonine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 694 694 Phosphotyrosine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 738 738 Phosphoserine.
{ECO:0000250|UniProtKB:Q2M2I8}.
MOD_RES 853 853 Phosphoserine.
{ECO:0000250|UniProtKB:Q3UHJ0}.
MOD_RES 944 944 Phosphoserine.
{ECO:0000250|UniProtKB:Q3UHJ0}.
MOD_RES 945 945 Phosphoserine.
{ECO:0000250|UniProtKB:Q3UHJ0}.
SEQUENCE 968 AA; 104310 MW; 4F07200E056E047D CRC64;
MKKFFDSRRE QGGSGLGSGS SGGGGSTSGL GSGYIGRVFG IGRQQVTVDE VLAEGGFAIV
FLVRTSNGMK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH KNIVGYIDSS INNVSSGDVW
EVLILMDFCR GGQVVNLMNQ RLQTGFTESE VLQIFCDTCE AVARLHQCKT PIIHRDLKVE
NILLHDRGHY VLCDFGSATN KFQNPQTEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKIIT
TKADIWALGC LLYKLCYFTL PFGESQVAIC DGNFTIPDNS RYSQDMHCLI RYMLEPDPDK
RPDIYQVSFF SFKLLKKECP VPNVQNSPIP AKLPEPVKAS EAAAKKTQPK ARLTDPIPTT
ETSIAPRQRP KAGQTQPNPG ILPIQPALTP RKRAMVQPPP QVAGSSNQPG LLASVPQPKT
QAPPSQPLPQ SQAKQPQAPP APQQPPSAPA QGLPAQAQAT PQHQQQLFLK QQPQPPQPQP
QAQAPPVKSL KFYPFYPMCK GRQTVSSQFQ AVHPAAQQPA IAQFPAVSQG SSQQQLIQNF
YQQQQQQQQQ QQLATTLHQQ QLLTQQAALQ QKTTVAAIQP PQAQPATASQ PPPAQEPAQI
QAPVRQQPKV QTTPPPAIQG QKLGSLTPPS SPKAQRAGHR RILSDVTHSA VFGVPASKST
QLLQAAAAEA SLNKSKSATT TPSGSPRASQ QNVYNPSEGS TWNPFDDDNF SKLTAEELLN
KDFAKLGEGK HPEKLGGSAE SLIPGFQPTQ GDAFAASSFA AGTAEKRKGG QAVDSSLPLL
SVSDPFIPLQ VPDAPEKLIE GLKSPDTSLL LPDLLPMTDP FGSTSDAVIE KADVAVESLI
PGLEPPVPQR LPSQTESVAS NRTDSLTGED ALIDCSLLSN PTTDLLEEFA PIAISAPAHK
AAEDSNLISG FDVPEGSDKV AEDEFDPIPV LITKNPQGGH SRNSSGSSES SLPNLARSLL
LVDQLIDL
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Pathways :
WP1493: Carbon assimilation C4 pathway
WP1567: Glycolysis and Gluconeogenesis
WP1619: Amino sugar and nucleotide sugar metabolism
WP1653: Galactose metabolism
WP1681: Pantothenate and CoA biosynthesis
WP1701: Starch and sucrose metabolism
WP1703: Streptomycin biosynthesis
WP1844: MAP kinase cascade
WP1946: Cori Cycle
WP2340: Thiamine (vitamin B1) biosynthesis and salvage
WP2341: vitamin B1 (thiamin) biosynthesis and salvage pathway
WP253: Glycolysis
WP32: Translation Factors
WP1049: G Protein Signaling Pathways
WP1165: G Protein Signaling Pathways
WP1371: G Protein Signaling Pathways
WP1438: Influenza A virus infection
WP1502: Mitochondrial biogenesis
WP1531: Vitamin D synthesis
WP1566: Citrate cycle (TCA cycle)
WP1613: 1,4-Dichlorobenzene degradation
WP1616: ABC transporters
WP1624: Bacterial secretion system
WP1625: Base excision repair
WP1644: DNA replication
Related Genes :
[Ap2m1] AP-2 complex subunit mu (AP-2 mu chain) (Adaptor protein complex AP-2 subunit mu) (Adaptor-related protein complex 2 subunit mu) (Clathrin assembly protein complex 2 mu medium chain) (Clathrin coat assembly protein AP50) (Clathrin coat-associated protein AP50) (Mu2-adaptin) (Plasma membrane adaptor AP-2 50 kDa protein)
[AP2M1 CLAPM1 KIAA0109] AP-2 complex subunit mu (AP-2 mu chain) (Adaptin-mu2) (Adaptor protein complex AP-2 subunit mu) (Adaptor-related protein complex 2 subunit mu) (Clathrin assembly protein complex 2 mu medium chain) (Clathrin coat assembly protein AP50) (Clathrin coat-associated protein AP50) (HA2 50 kDa subunit) (Plasma membrane adaptor AP-2 50 kDa protein)
[Ap2m1 Clapm1] AP-2 complex subunit mu (AP-2 mu chain) (Adaptor protein complex AP-2 subunit mu) (Adaptor-related protein complex 2 subunit mu) (Clathrin assembly protein complex 2 mu medium chain) (Clathrin coat assembly protein AP50) (Clathrin coat-associated protein AP50) (Mu2-adaptin) (Plasma membrane adaptor AP-2 50 kDa protein)
[TFAP2A AP2TF TFAP2] Transcription factor AP-2-alpha (AP2-alpha) (AP-2 transcription factor) (Activating enhancer-binding protein 2-alpha) (Activator protein 2) (AP-2)
[Ap2a2 Adtab] AP-2 complex subunit alpha-2 (100 kDa coated vesicle protein C) (Adaptor protein complex AP-2 subunit alpha-2) (Adaptor-related protein complex 2 subunit alpha-2) (Alpha-adaptin C) (Alpha2-adaptin) (Clathrin assembly protein complex 2 alpha-C large chain) (Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit)
[AP2S1 AP17 CLAPS2] AP-2 complex subunit sigma (Adaptor protein complex AP-2 subunit sigma) (Adaptor-related protein complex 2 subunit sigma) (Clathrin assembly protein 2 sigma small chain) (Clathrin coat assembly protein AP17) (Clathrin coat-associated protein AP17) (HA2 17 kDa subunit) (Plasma membrane adaptor AP-2 17 kDa protein) (Sigma2-adaptin)
[AP2B1 ADTB2 CLAPB1] AP-2 complex subunit beta (AP105B) (Adaptor protein complex AP-2 subunit beta) (Adaptor-related protein complex 2 subunit beta) (Beta-2-adaptin) (Beta-adaptin) (Clathrin assembly protein complex 2 beta large chain) (Plasma membrane adaptor HA2/AP2 adaptin beta subunit)
[Ap2a2 Adtab] AP-2 complex subunit alpha-2 (100 kDa coated vesicle protein C) (Adaptor protein complex AP-2 subunit alpha-2) (Adaptor-related protein complex 2 subunit alpha-2) (Alpha-adaptin C) (Alpha2-adaptin) (Clathrin assembly protein complex 2 alpha-C large chain) (Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit)
[AP2A2 ADTAB CLAPA2 HIP9 HYPJ KIAA0899] AP-2 complex subunit alpha-2 (100 kDa coated vesicle protein C) (Adaptor protein complex AP-2 subunit alpha-2) (Adaptor-related protein complex 2 subunit alpha-2) (Alpha-adaptin C) (Alpha2-adaptin) (Clathrin assembly protein complex 2 alpha-C large chain) (Huntingtin yeast partner J) (Huntingtin-interacting protein 9) (HIP-9) (Huntingtin-interacting protein J) (Plasma membrane adaptor HA2/AP2 adaptin alpha C subunit)
[AP2A1 ADTAA CLAPA1] AP-2 complex subunit alpha-1 (100 kDa coated vesicle protein A) (Adaptor protein complex AP-2 subunit alpha-1) (Adaptor-related protein complex 2 subunit alpha-1) (Alpha-adaptin A) (Alpha1-adaptin) (Clathrin assembly protein complex 2 alpha-A large chain) (Plasma membrane adaptor HA2/AP2 adaptin alpha A subunit)
[Ap2a1 Adtaa Clapa1] AP-2 complex subunit alpha-1 (100 kDa coated vesicle protein A) (Adaptor protein complex AP-2 subunit alpha-1) (Adaptor-related protein complex 2 subunit alpha-1) (Alpha-adaptin A) (Alpha1-adaptin) (Clathrin assembly protein complex 2 alpha-A large chain) (Plasma membrane adaptor HA2/AP2 adaptin alpha A subunit)
[Ap2b1 Clapb1] AP-2 complex subunit beta (AP105B) (Adaptor protein complex AP-2 subunit beta) (Adaptor-related protein complex 2 subunit beta) (Beta-2-adaptin) (Beta-adaptin) (Clathrin assembly protein complex 2 beta large chain) (Plasma membrane adaptor HA2/AP2 adaptin beta subunit)
[Ap2s1 Ap17 Claps2] AP-2 complex subunit sigma (Adaptor protein complex AP-2 subunit sigma) (Adaptor-related protein complex 2 subunit sigma) (Clathrin assembly protein 2 sigma small chain) (Clathrin coat assembly protein AP17) (Clathrin coat-associated protein AP17) (Plasma membrane adaptor AP-2 17 kDa protein) (Sigma-adaptin 3b) (Sigma2-adaptin)
[Ap2b1 Clapb1] AP-2 complex subunit beta (AP105B) (Adaptor protein complex AP-2 subunit beta) (Adaptor-related protein complex 2 subunit beta) (Beta-2-adaptin) (Beta-adaptin) (Clathrin assembly protein complex 2 beta large chain) (Plasma membrane adaptor HA2/AP2 adaptin beta subunit)
[Tfap2a Ap2tf Tcfap2a] Transcription factor AP-2-alpha (AP2-alpha) (AP-2 transcription factor) (Activating enhancer-binding protein 2-alpha) (Activator protein 2) (AP-2)
[TFAP2A] Transcription factor AP-2-alpha (AP2-alpha) (AP-2 transcription factor) (Activating enhancer-binding protein 2-alpha) (Activator protein 2) (AP-2)
[Tfap2a Tcfap2a] Transcription factor AP-2-alpha (AP2-alpha) (AP-2 transcription factor) (Activating enhancer-binding protein 2-alpha) (Activator protein 2) (AP-2)
[TFAP2A] Transcription factor AP-2-alpha (AP2-alpha) (AP-2 transcription factor) (Activating enhancer-binding protein 2-alpha) (Activator protein 2) (AP-2)
[Tfap2c Tcfap2c] Transcription factor AP-2 gamma (AP2-gamma) (AP-2.2) (Activating enhancer-binding protein 2 gamma)
[TFAP2C] Transcription factor AP-2 gamma (AP2-gamma) (Activating enhancer-binding protein 2 gamma) (Transcription factor ERF-1)
[TFAP2B] Transcription factor AP-2-beta (AP2-beta) (Activating enhancer-binding protein 2-beta)
[Tfap2b Tcfap2b] Transcription factor AP-2-beta (AP2-beta) (Activating enhancer-binding protein 2-beta)
[TFAP2B] Transcription factor AP-2-beta (AP2-beta) (Activating enhancer-binding protein 2-beta)
[Tfap2d Tcfap2d] Transcription factor AP-2-delta (AP2-delta) (Activating enhancer-binding protein 2-delta)
[DREB1A CBF3 CRAP2 ERF072 At4g25480 M7J2.150] Dehydration-responsive element-binding protein 1A (Protein DREB1A) (C-repeat/dehydration-responsive element-binding factor 3) (C-repeat-binding factor 3) (CRT/DRE-binding factor 3) (Cold resistance-related AP2 transcription factor)
[Ap2s1 Ap17 Claps2] AP-2 complex subunit sigma (Adaptor protein complex AP-2 subunit sigma) (Adaptor-related protein complex 2 subunit sigma) (Clathrin assembly protein 2 sigma small chain) (Clathrin coat assembly protein AP17) (Clathrin coat-associated protein AP17) (Plasma membrane adaptor AP-2 17 kDa protein) (Sigma-adaptin 3b) (Sigma2-adaptin)
[AP2B1 CLAPB1] AP-2 complex subunit beta (AP105B) (Adaptor protein complex AP-2 subunit beta) (Adaptor-related protein complex 2 subunit beta) (Beta-2-adaptin) (Beta-adaptin) (Clathrin assembly protein complex 2 beta large chain) (Plasma membrane adaptor HA2/AP2 adaptin beta subunit)
[AP2M1] AP-2 complex subunit mu (AP-2 mu chain) (Adaptor protein complex AP-2 subunit mu) (Adaptor-related protein complex 2 subunit mu) (Clathrin assembly protein complex 2 mu medium chain) (Clathrin coat assembly protein AP50) (Clathrin coat-associated protein AP50) (HA2 50 kDa subunit) (Mu2-adaptin) (Plasma membrane adaptor AP-2 50 kDa protein)
[Tfap2e Tcfap2e] Transcription factor AP-2-epsilon (AP2-epsilon) (Activating enhancer-binding protein 2-epsilon)
[Ap2a1 Ap2a1_predicted rCG_54084] AP-2 complex subunit alpha
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