AAK1_HUMAN
ID AAK1_HUMAN Reviewed; 961 AA.
AC Q2M2I8; Q4ZFZ3; Q53RX6; Q9UPV4;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUL-2010, sequence version 3.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=AP2-associated protein kinase 1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:11877457, ECO:0000269|PubMed:11877461, ECO:0000269|PubMed:12952931, ECO:0000269|PubMed:14617351, ECO:0000269|PubMed:17494869, ECO:0000269|PubMed:18657069};
DE AltName: Full=Adaptor-associated kinase 1;
GN Name=AAK1; Synonyms=KIAA1048;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY,
RP ACTIVITY REGULATION, INTERACTION WITH CLATHRIN AND AP-2, TISSUE
RP SPECIFICITY, AND DOMAIN.
RC TISSUE=Brain;
RX PubMed=17494869; DOI=10.1091/mbc.e06-09-0831;
RA Henderson D.M., Conner S.D.;
RT "A novel AAK1 splice variant functions at multiple steps of the endocytic
RT pathway.";
RL Mol. Biol. Cell 18:2698-2706(2007).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-509.
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT GLN-509.
RC TISSUE=Cerebellum;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11877457; DOI=10.1083/jcb.200111068;
RA Ricotta D., Conner S.D., Schmid S.L., von Figura K., Honing S.;
RT "Phosphorylation of the AP2 mu subunit by AAK1 mediates high affinity
RT binding to membrane protein sorting signals.";
RL J. Cell Biol. 156:791-795(2002).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=11877461; DOI=10.1083/jcb.200108123;
RA Conner S.D., Schmid S.L.;
RT "Identification of an adaptor-associated kinase, AAK1, as a regulator of
RT clathrin-mediated endocytosis.";
RL J. Cell Biol. 156:921-929(2002).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH AP-2, AND MUTAGENESIS OF
RP LYS-74 AND ASP-176.
RX PubMed=12952931; DOI=10.1083/jcb.200304069;
RA Conner S.D., Schmid S.L.;
RT "Differential requirements for AP-2 in clathrin-mediated endocytosis.";
RL J. Cell Biol. 162:773-779(2003).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND INTERACTION WITH
RP CLATHRIN AND AP-2.
RX PubMed=14617351; DOI=10.1046/j.1398-9219.2003.0142.x;
RA Conner S.D., Schroter T., Schmid S.L.;
RT "AAK1-mediated micro2 phosphorylation is stimulated by assembled
RT clathrin.";
RL Traffic 4:885-890(2003).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389 AND THR-606, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-637, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=T-cell;
RX PubMed=19367720; DOI=10.1021/pr800500r;
RA Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J.;
RT "Phosphorylation analysis of primary human T lymphocytes using sequential
RT IMAC and titanium oxide enrichment.";
RL J. Proteome Res. 7:5167-5176(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389; THR-441; SER-637 AND
RP SER-731, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-234; SER-235; THR-389;
RP THR-606; THR-620; SER-623; SER-624 AND SER-637, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH NUMB, AND MUTAGENESIS OF
RP LYS-74 AND ASP-176.
RX PubMed=18657069; DOI=10.1111/j.1600-0854.2008.00790.x;
RA Sorensen E.B., Conner S.D.;
RT "AAK1 regulates Numb function at an early step in clathrin-mediated
RT endocytosis.";
RL Traffic 9:1791-1800(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; THR-354; THR-389;
RP SER-637; SER-650; TYR-687 AND SER-731, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-389; THR-606; SER-637 AND
RP THR-653, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-620; SER-623; SER-624 AND
RP SER-637, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [21]
RP FUNCTION, INTERACTION WITH EPS15 AND NOTCH1, AND MUTAGENESIS OF LYS-74 AND
RP 777-ASP--PHE-779.
RX PubMed=21464124; DOI=10.1074/jbc.m110.190769;
RA Gupta-Rossi N., Ortica S., Meas-Yedid V., Heuss S., Moretti J.,
RA Olivo-Marin J.C., Israel A.;
RT "The adaptor-associated kinase 1, AAK1, is a positive regulator of the
RT Notch pathway.";
RL J. Biol. Chem. 286:18720-18730(2011).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-606; THR-620; SER-624 AND
RP SER-637, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; THR-606; THR-620 AND
RP SER-637, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-620, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP FUNCTION (MICROBIAL INFECTION).
RX PubMed=25653444; DOI=10.1128/jvi.02705-14;
RA Neveu G., Ziv-Av A., Barouch-Bentov R., Berkerman E., Mulholland J.,
RA Einav S.;
RT "AP-2-associated protein kinase 1 and cyclin G-associated kinase regulate
RT hepatitis C virus entry and are potential drug targets.";
RL J. Virol. 89:4387-4404(2015).
RN [27] {ECO:0007744|PDB:4WSQ}
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 29-345 IN COMPLEX WITH INHIBITOR,
RP AND CATALYTIC ACTIVITY.
RX PubMed=26853940; DOI=10.1016/j.str.2015.12.015;
RA Sorrell F.J., Szklarz M., Abdul Azeez K.R., Elkins J.M., Knapp S.;
RT "Family-wide Structural Analysis of Human Numb-Associated Protein
RT Kinases.";
RL Structure 24:401-411(2016).
RN [28] {ECO:0007744|PDB:5TE0}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 27-365.
RA Counago R.M., Elkins J.M., Arrowsmith C.H., Bountra C., Arruda P.,
RA Edwards A.M., Gileadi O.;
RT "Crystal Structure of Adaptor Protein 2 Associated Kinase (AAK1) in complex
RT with BIBF 1120.";
RL Submitted (SEP-2016) to the PDB data bank.
RN [29] {ECO:0007744|PDB:5L4Q}
RP X-RAY CRYSTALLOGRAPHY (1.97 ANGSTROMS) OF 27-365, AND CATALYTIC ACTIVITY.
RX PubMed=31136173; DOI=10.1021/acs.jmedchem.9b00136;
RA Verdonck S., Pu S.Y., Sorrell F.J., Elkins J.M., Froeyen M., Gao L.J.,
RA Prugar L.I., Dorosky D.E., Brannan J.M., Barouch-Bentov R., Knapp S.,
RA Dye J.M., Herdewijn P., Einav S., De Jonghe S.;
RT "Synthesis and Structure-Activity Relationships of 3,5-Disubstituted-
RT pyrrolo[2,3- b]pyridines as Inhibitors of Adaptor-Associated Kinase 1 with
RT Antiviral Activity.";
RL J. Med. Chem. 62:5810-5831(2019).
RN [30]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-59; HIS-533; ALA-603; MET-694; THR-725;
RP ARG-771 AND ASP-835.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Regulates clathrin-mediated endocytosis by phosphorylating
CC the AP2M1/mu2 subunit of the adaptor protein complex 2 (AP-2) which
CC ensures high affinity binding of AP-2 to cargo membrane proteins during
CC the initial stages of endocytosis (PubMed:17494869, PubMed:11877457,
CC PubMed:11877461, PubMed:12952931, PubMed:14617351, PubMed:25653444).
CC Isoform 1 and isoform 2 display similar levels of kinase activity
CC towards AP2M1 (PubMed:17494869). Preferentially, may phosphorylate
CC substrates on threonine residues (PubMed:11877457, PubMed:18657069).
CC Regulates phosphorylation of other AP-2 subunits as well as AP-2
CC localization and AP-2-mediated internalization of ligand complexes
CC (PubMed:12952931). Phosphorylates NUMB and regulates its cellular
CC localization, promoting NUMB localization to endosomes
CC (PubMed:18657069). Binds to and stabilizes the activated form of
CC NOTCH1, increases its localization in endosomes and regulates its
CC transcriptional activity (PubMed:21464124).
CC {ECO:0000269|PubMed:11877457, ECO:0000269|PubMed:11877461,
CC ECO:0000269|PubMed:12952931, ECO:0000269|PubMed:14617351,
CC ECO:0000269|PubMed:17494869, ECO:0000269|PubMed:18657069,
CC ECO:0000269|PubMed:21464124, ECO:0000269|PubMed:25653444}.
CC -!- FUNCTION: (Microbial infection) By regulating clathrin-mediated
CC endocytosis, AAK1 plays a role in the entry of hepatitis C virus as
CC well as for the lifecycle of other viruses such as Ebola and Dengue.
CC {ECO:0000269|PubMed:25653444, ECO:0000305|PubMed:31136173}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000305};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:11877457,
CC ECO:0000269|PubMed:11877461, ECO:0000269|PubMed:12952931,
CC ECO:0000269|PubMed:14617351, ECO:0000269|PubMed:17494869,
CC ECO:0000269|PubMed:18657069, ECO:0000269|PubMed:26853940,
CC ECO:0000269|PubMed:31136173};
CC -!- ACTIVITY REGULATION: Stimulated by clathrin.
CC {ECO:0000269|PubMed:14617351, ECO:0000269|PubMed:17494869}.
CC -!- SUBUNIT: Interacts (via CBD domain) with clathrin (PubMed:17494869,
CC PubMed:14617351). Interacts with AP-2 complex (PubMed:17494869,
CC PubMed:12952931, PubMed:14617351). Interacts with NUMB
CC (PubMed:18657069). Interacts with alpha-adaptin (By similarity).
CC Interacts with EPS15 isoform 2 (PubMed:21464124). Interacts with
CC membrane-bound activated NOTCH1 but not with the inactive full-length
CC form of NOTCH1 (PubMed:21464124). Preferentially interacts with
CC monoubiquitinated activated NOTCH1 compared to the non-ubiquitinated
CC form (PubMed:21464124). {ECO:0000250|UniProtKB:P0C1X8,
CC ECO:0000269|PubMed:12952931, ECO:0000269|PubMed:14617351,
CC ECO:0000269|PubMed:17494869, ECO:0000269|PubMed:18657069,
CC ECO:0000269|PubMed:21464124}.
CC -!- INTERACTION:
CC Q2M2I8; Q9NQ11: ATP13A2; NbExp=2; IntAct=EBI-1383433, EBI-6308763;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:F1MH24};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:F1MH24}. Membrane,
CC clathrin-coated pit {ECO:0000269|PubMed:11877461}. Presynapse
CC {ECO:0000250|UniProtKB:P0C1X8}. Note=Active when found in clathrin-
CC coated pits at the plasma membrane. In neuronal cells, enriched at
CC presynaptic terminals. In non-neuronal cells, enriched at leading edge
CC of migrating cells. {ECO:0000250|UniProtKB:P0C1X8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=AAK1L {ECO:0000303|PubMed:17494869};
CC IsoId=Q2M2I8-1; Sequence=Displayed;
CC Name=2; Synonyms=AAK1S {ECO:0000303|PubMed:17494869};
CC IsoId=Q2M2I8-2; Sequence=VSP_039459;
CC -!- TISSUE SPECIFICITY: Detected in brain, heart and liver. Isoform 1 is
CC the predominant isoform in brain. {ECO:0000269|PubMed:17494869}.
CC -!- PTM: Autophosphorylated. {ECO:0000269|PubMed:17494869}.
CC -!- PHARMACEUTICAL: By regulating the entry of hepatitis C virus as well as
CC the lifecycle of other viruses such as Ebola and Dengue, AAK1 is a
CC potential drug target for developing antiviral therapies.
CC {ECO:0000305|PubMed:25653444, ECO:0000305|PubMed:31136173}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA83000.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AB028971; BAA83000.2; ALT_INIT; mRNA.
DR EMBL; AC092431; AAX88861.1; -; Genomic_DNA.
DR EMBL; AC079121; AAY14931.1; -; Genomic_DNA.
DR EMBL; AC136007; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC104842; AAI04843.1; -; mRNA.
DR EMBL; BC111965; AAI11966.1; -; mRNA.
DR CCDS; CCDS1893.2; -. [Q2M2I8-1]
DR RefSeq; NP_055726.3; NM_014911.3. [Q2M2I8-1]
DR PDB; 4WSQ; X-ray; 1.95 A; A/B=29-345.
DR PDB; 5L4Q; X-ray; 1.97 A; A/B=27-365.
DR PDB; 5TE0; X-ray; 1.90 A; A=27-365.
DR PDBsum; 4WSQ; -.
DR PDBsum; 5L4Q; -.
DR PDBsum; 5TE0; -.
DR AlphaFoldDB; Q2M2I8; -.
DR SMR; Q2M2I8; -.
DR BioGRID; 116520; 64.
DR IntAct; Q2M2I8; 47.
DR MINT; Q2M2I8; -.
DR STRING; 9606.ENSP00000386456; -.
DR BindingDB; Q2M2I8; -.
DR ChEMBL; CHEMBL3830; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q2M2I8; -.
DR GuidetoPHARMACOLOGY; 1921; -.
DR GlyGen; Q2M2I8; 7 sites, 2 O-linked glycans (7 sites).
DR iPTMnet; Q2M2I8; -.
DR MetOSite; Q2M2I8; -.
DR PhosphoSitePlus; Q2M2I8; -.
DR SwissPalm; Q2M2I8; -.
DR BioMuta; AAK1; -.
DR DMDM; 300669613; -.
DR EPD; Q2M2I8; -.
DR jPOST; Q2M2I8; -.
DR MassIVE; Q2M2I8; -.
DR MaxQB; Q2M2I8; -.
DR PaxDb; Q2M2I8; -.
DR PeptideAtlas; Q2M2I8; -.
DR PRIDE; Q2M2I8; -.
DR ProteomicsDB; 61355; -. [Q2M2I8-1]
DR ProteomicsDB; 61356; -. [Q2M2I8-2]
DR Antibodypedia; 7943; 369 antibodies from 39 providers.
DR DNASU; 22848; -.
DR Ensembl; ENST00000406297.7; ENSP00000385181.3; ENSG00000115977.21. [Q2M2I8-2]
DR Ensembl; ENST00000409085.9; ENSP00000386456.3; ENSG00000115977.21. [Q2M2I8-1]
DR GeneID; 22848; -.
DR KEGG; hsa:22848; -.
DR MANE-Select; ENST00000409085.9; ENSP00000386456.3; NM_014911.5; NP_055726.4.
DR UCSC; uc002sfp.3; human. [Q2M2I8-1]
DR CTD; 22848; -.
DR DisGeNET; 22848; -.
DR GeneCards; AAK1; -.
DR HGNC; HGNC:19679; AAK1.
DR HPA; ENSG00000115977; Tissue enhanced (parathyroid).
DR MIM; 616405; gene.
DR neXtProt; NX_Q2M2I8; -.
DR OpenTargets; ENSG00000115977; -.
DR PharmGKB; PA134990616; -.
DR VEuPathDB; HostDB:ENSG00000115977; -.
DR eggNOG; KOG1989; Eukaryota.
DR GeneTree; ENSGT00940000155968; -.
DR InParanoid; Q2M2I8; -.
DR OMA; ASLNKSX; -.
DR OrthoDB; 826336at2759; -.
DR PhylomeDB; Q2M2I8; -.
DR TreeFam; TF317300; -.
DR PathwayCommons; Q2M2I8; -.
DR Reactome; R-HSA-8856825; Cargo recognition for clathrin-mediated endocytosis.
DR Reactome; R-HSA-8856828; Clathrin-mediated endocytosis.
DR SignaLink; Q2M2I8; -.
DR SIGNOR; Q2M2I8; -.
DR BioGRID-ORCS; 22848; 19 hits in 1111 CRISPR screens.
DR ChiTaRS; AAK1; human.
DR GeneWiki; AAK1; -.
DR GenomeRNAi; 22848; -.
DR Pharos; Q2M2I8; Tchem.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q2M2I8; protein.
DR Bgee; ENSG00000115977; Expressed in lateral nuclear group of thalamus and 213 other tissues.
DR ExpressionAtlas; Q2M2I8; baseline and differential.
DR Genevisible; Q2M2I8; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0031252; C:cell leading edge; ISS:UniProtKB.
DR GO; GO:0005905; C:clathrin-coated pit; IEA:UniProtKB-SubCell.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0043195; C:terminal bouton; ISS:UniProtKB.
DR GO; GO:0035612; F:AP-2 adaptor complex binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005112; F:Notch binding; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0061024; P:membrane organization; TAS:Reactome.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050821; P:protein stabilization; IDA:UniProtKB.
DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; IDA:UniProtKB.
DR GO; GO:0032880; P:regulation of protein localization; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; ATP-binding;
KW Cell membrane; Cell projection; Coated pit; Endocytosis; Kinase; Membrane;
KW Methylation; Nucleotide-binding; Pharmaceutical; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Synapse; Transferase.
FT CHAIN 1..961
FT /note="AP2-associated protein kinase 1"
FT /id="PRO_0000250578"
FT DOMAIN 46..315
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 327..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 562..632
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 664..701
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 823..960
FT /note="Clathrin-binding domain (CBD)"
FT /evidence="ECO:0000269|PubMed:17494869"
FT REGION 836..860
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 921..945
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 353..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 399..414
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 416..443
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 444..493
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 562..577
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 598..627
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 843..860
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 929..945
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 52..60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 234
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 354
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 389
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 391
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 441
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 606
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 618
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P0C1X8"
FT MOD_RES 620
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 623
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 624
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692"
FT MOD_RES 637
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19367720,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 650
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 653
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 687
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 731
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 846
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 937
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT MOD_RES 938
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q3UHJ0"
FT VAR_SEQ 823..961
FT /note="EKADVAVESLIPGLEPPVPQRLPSQTESVTSNRTDSLTGEDSLLDCSLLSNP
FT TTDLLEEFAPTAISAPVHKAAEDSNLISGFDVPEGSDKVAEDEFDPIPVLITKNPQGGH
FT SRNSSGSSESSLPNLARSLLLVDQLIDL -> GKVIISVSSVMHDMCACFKNDKYLVNQ
FT SLGNSPATPEAKAI (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10470851,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_039459"
FT VARIANT 59
FT /note="I -> V (in dbSNP:rs34535244)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040348"
FT VARIANT 509
FT /note="K -> Q (in dbSNP:rs6715776)"
FT /evidence="ECO:0000269|PubMed:10470851,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_031129"
FT VARIANT 533
FT /note="Q -> H (in dbSNP:rs1263928487)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040349"
FT VARIANT 603
FT /note="V -> A (in dbSNP:rs56038532)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040350"
FT VARIANT 694
FT /note="T -> M (in dbSNP:rs55889248)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040351"
FT VARIANT 725
FT /note="P -> T (in dbSNP:rs35285785)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040352"
FT VARIANT 771
FT /note="P -> R (in dbSNP:rs34422616)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040353"
FT VARIANT 835
FT /note="G -> D"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040354"
FT MUTAGEN 74
FT /note="K->A: Inhibits autophosphorylation and
FT phosphorylation of AP2M1. Does not affect NUMB
FT localization. Does not interact with monoubiquitinated
FT NOTCH1."
FT /evidence="ECO:0000269|PubMed:12952931,
FT ECO:0000269|PubMed:18657069, ECO:0000269|PubMed:21464124"
FT MUTAGEN 176
FT /note="D->A: Inhibits autophosphorylation and
FT phosphorylation of AP2M1. Does not affect NUMB
FT localization."
FT /evidence="ECO:0000269|PubMed:12952931,
FT ECO:0000269|PubMed:18657069"
FT MUTAGEN 777..779
FT /note="DPF->AAA: Does not affect interaction with NOTCH1
FT but abolishes interaction with ESP15."
FT /evidence="ECO:0000269|PubMed:21464124"
FT HELIX 31..34
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 44..55
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 58..64
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 70..78
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 81..97
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 106..113
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 120..127
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 134..139
FT /evidence="ECO:0007829|PDB:5TE0"
FT TURN 142..144
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 148..167
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 168..170
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:5TE0"
FT STRAND 190..192
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 205..208
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 210..220
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 228..231
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 242..257
FT /evidence="ECO:0007829|PDB:5TE0"
FT TURN 261..264
FT /evidence="ECO:0007829|PDB:4WSQ"
FT HELIX 266..271
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:5TE0"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 304..315
FT /evidence="ECO:0007829|PDB:5TE0"
FT HELIX 339..344
FT /evidence="ECO:0007829|PDB:5TE0"
SQ SEQUENCE 961 AA; 103885 MW; 1FB44D0FDEF6CAD0 CRC64;
MKKFFDSRRE QGGSGLGSGS SGGGGSTSGL GSGYIGRVFG IGRQQVTVDE VLAEGGFAIV
FLVRTSNGMK CALKRMFVNN EHDLQVCKRE IQIMRDLSGH KNIVGYIDSS INNVSSGDVW
EVLILMDFCR GGQVVNLMNQ RLQTGFTENE VLQIFCDTCE AVARLHQCKT PIIHRDLKVE
NILLHDRGHY VLCDFGSATN KFQNPQTEGV NAVEDEIKKY TTLSYRAPEM VNLYSGKIIT
TKADIWALGC LLYKLCYFTL PFGESQVAIC DGNFTIPDNS RYSQDMHCLI RYMLEPDPDK
RPDIYQVSYF SFKLLKKECP IPNVQNSPIP AKLPEPVKAS EAAAKKTQPK ARLTDPIPTT
ETSIAPRQRP KAGQTQPNPG ILPIQPALTP RKRATVQPPP QAAGSSNQPG LLASVPQPKP
QAPPSQPLPQ TQAKQPQAPP TPQQTPSTQA QGLPAQAQAT PQHQQQLFLK QQQQQQQPPP
AQQQPAGTFY QQQQAQTQQF QAVHPATQKP AIAQFPVVSQ GGSQQQLMQN FYQQQQQQQQ
QQQQQQLATA LHQQQLMTQQ AALQQKPTMA AGQQPQPQPA AAPQPAPAQE PAIQAPVRQQ
PKVQTTPPPA VQGQKVGSLT PPSSPKTQRA GHRRILSDVT HSAVFGVPAS KSTQLLQAAA
AEASLNKSKS ATTTPSGSPR TSQQNVYNPS EGSTWNPFDD DNFSKLTAEE LLNKDFAKLG
EGKHPEKLGG SAESLIPGFQ STQGDAFATT SFSAGTAEKR KGGQTVDSGL PLLSVSDPFI
PLQVPDAPEK LIEGLKSPDT SLLLPDLLPM TDPFGSTSDA VIEKADVAVE SLIPGLEPPV
PQRLPSQTES VTSNRTDSLT GEDSLLDCSL LSNPTTDLLE EFAPTAISAP VHKAAEDSNL
ISGFDVPEGS DKVAEDEFDP IPVLITKNPQ GGHSRNSSGS SESSLPNLAR SLLLVDQLID
L
