Reviewed, UniProtKB/Swiss-Prot Q2M2I8 (AAK1_HUMAN)

Names and origin

Protein names

Recommended name:
    AP2-associated protein kinase 1
    EC=2.7.11.1
Alternative name(s):
    Adaptor-associated kinase 1

Gene names

Name:	AAK1
Synonyms:	KIAA1048

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	863 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphorylates the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2). May play a role in regulating aspects of clathrin-mediated endocytosis By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Stimulated by clathrin By similarity.
Subunit structure	Interacts with alpha-adaptin and AP-2 By similarity.
Subcellular location	Membrane; Peripheral membrane proteinBy similarity. Note= Active when found in clathrin-coated pits at the plasma membrane By similarity.
Post-translational modification	Autophosphorylated By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. Contains 1 protein kinase domain.

Ontologies

Keywords
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
None. [Check GOA]

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 863	863	AP2-associated protein kinase 1
Regions
	Domain	46 – 315	270	Protein kinase
	Nucleotide binding	52 – 60	9	ATP By similarity
	Compositional bias	12 – 42	31	Gly-rich
	Compositional bias	397 – 614	218	Gln-rich
	Compositional bias	658 – 663	6	Poly-Ala
Sites
	Active site	176	1	Proton acceptor By similarity
	Binding site	74	1	ATP By similarity
Amino acid modifications
	Modified residue	21	1	Phosphoserine By similarity
	Modified residue	389	1	Phosphothreonine
	Modified residue	606	1	Phosphothreonine
	Modified residue	620	1	Phosphothreonine
	Modified residue	623	1	Phosphoserine By similarity
	Modified residue	637	1	Phosphoserine By similarity
	Modified residue	640	1	Phosphothreonine By similarity
	Modified residue	652	1	Phosphoserine By similarity
	Modified residue	670	1	Phosphoserine
	Modified residue	676	1	Phosphoserine
	Modified residue	731	1	Phosphoserine By similarity
Natural variations
	Natural variant	59	1	I → V
	Natural variant	509	1	K → Q: dbSNP rs6715776.
	Natural variant	533	1	Q → H
	Natural variant	603	1	V → A
	Natural variant	694	1	T → M
	Natural variant	725	1	P → T
	Natural variant	771	1	P → R
	Natural variant	835	1	D → G

Sequences

	Sequence		Length	Mass (Da)
	Q2M2I8-1 [UniParc]. Last modified March 20, 2007. Version 2. Checksum: 012198AEE90CC0E7	FASTA	863	93,578
	10 20 30 40 50 60 MKKFFDSRRE QGGSGLGSGS SGGGGSTSGL GSGYIGRVFG IGRQQVTVDE VLAEGGFAIV 70 80 90 100 110 120 FLVRTSNGMK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH KNIVGYIDSS INNVSSGDVW 130 140 150 160 170 180 EVLILMDFCR GGQVVNLMNQ RLQTGFTENE VLQIFCDTCE AVARLHQCKT PIIHRDLKVE 190 200 210 220 230 240 NILLHDRGHY VLCDFGSATN KFQNPQTEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKIIT 250 260 270 280 290 300 TKADIWALGC LLYKLCYFTL PFGESQVAIC DGNFTIPDNS RYSQDMHCLI RYMLEPDPDK 310 320 330 340 350 360 RPDIYQVSYF SFKLLKKECP IPNVQNSPIP AKLPEPVKAS EAAAKKTQPK ARLTDPIPTT 370 380 390 400 410 420 ETSIAPRQRP KAGQTQPNPG ILPIQPALTP RKRATVQPPP QAAGSSNQPG LLASVPQPKP 430 440 450 460 470 480 QAPPSQPLPQ TQAKQPQAPP TPQQTPSTQA QGLPAQAQAT PQHQQQLFLK QQQQQQQPPP 490 500 510 520 530 540 AQQQPAGTFY QQQQAQTQQF QAVHPATQKP AIAQFPVVSQ GGSQQQLMQN FYQQQQQQQQ 550 560 570 580 590 600 QQQQQQLATA LHQQQLMTQQ AALQQKPTMA AGQQPQPQPA AAPQPAPAQE PAIQAPVRQQ 610 620 630 640 650 660 PKVQTTPPPA VQGQKVGSLT PPSSPKTQRA GHRRILSDVT HSAVFGVPAS KSTQLLQAAA 670 680 690 700 710 720 AEASLNKSKS ATTTPSGSPR TSQQNVYNPS EGSTWNPFDD DNFSKLTAEE LLNKDFAKLG 730 740 750 760 770 780 EGKHPEKLGG SAESLIPGFQ STQGDAFATT SFSAGTAEKR KGGQTVDSGL PLLSVSDPFI 790 800 810 820 830 840 PLQVPDAPEK LIEGLKSPDT SLLLPDLLPM TDPFGSTSDA VIGKVIISVS SVMHDMCACF 850 860 KNDKYLVNQS LGNSPATPEA KAI

References

[1]	"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." Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 6:197-205(1999) [PubMed: 10470851] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-509. Tissue: Brain.
[2]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed: 15815621] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLN-509. Tissue: Cerebellum.
[4]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-606; SER-670 AND SER-676, MASS SPECTROMETRY. Tissue: Epithelium.
[5]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-620, MASS SPECTROMETRY.
[6]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389 AND THR-606, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389, MASS SPECTROMETRY.
[8]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-59; HIS-533; ALA-603; MET-694; THR-725; ARG-771 AND GLY-835.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB028971 mRNA. Translation: BAA83000.2. Different initiation. AC092431 Genomic DNA. Translation: AAX88861.1. AC079121 Genomic DNA. Translation: AAY14931.1. BC104842 mRNA. Translation: AAI04843.1. BC111965 mRNA. Translation: AAI11966.1.
RefSeq	NP_055726.3.
UniGene	Hs.468878 Hs.695145
3D structure databases
ModBase	Search...
Protein-protein interaction databases
IntAct	Q2M2I8.
PTM databases
PhosphoSite	Q2M2I8.
Genome annotation databases
Ensembl	ENSG00000115977. Homo sapiens. [Contig view]
GeneID	22848.
KEGG	hsa:22848.
Organism-specific databases
HGNC	HGNC:19679. AAK1.
PharmGKB	PA134990616.
HUGE	Search...
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q2M2I8.
Gene expression databases
ArrayExpress	Q2M2I8.
CleanEx	HS_AAK1.
GermOnline	ENSG00000115977. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
PROSITE	PS00107. PROTEIN_KINASE_ATP. False negative. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. [Graphical view]
BLOCKS	Search...
Other Resources
ProtoNet	Search...

Entry information

Entry name

AAK1_HUMAN

Accession

Primary (citable) accession number: Q2M2I8
Secondary accession number(s): Q4ZFZ3, Q53RX6, Q9UPV4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 3, 2006
Last sequence update:	March 20, 2007
Last modified:	July 22, 2008
This is version 30 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)