PEAK1_HUMAN
ID PEAK1_HUMAN Reviewed; 1746 AA.
AC Q9H792; Q6ZS78; Q8NAZ4; Q8NCM3; Q8TEG7;
DT 03-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2009, sequence version 4.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Inactive tyrosine-protein kinase PEAK1 {ECO:0000305};
DE AltName: Full=Pseudopodium-enriched atypical kinase 1 {ECO:0000303|PubMed:20534451};
DE AltName: Full=Sugen kinase 269 {ECO:0000303|PubMed:29212708};
DE AltName: Full=Tyrosine-protein kinase SgK269;
GN Name=PEAK1; Synonyms=KIAA2002;
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 537-1746.
RC TISSUE=Lung, Mesangial cell, and Smooth muscle;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 707-1120.
RC TISSUE=Spleen;
RA Jikuya H., Takano J., Nomura N., Kikuno R., Nagase T., Ohara O.;
RT "The nucleotide sequence of a long cDNA clone isolated from human spleen.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 983-1746.
RC TISSUE=Brain;
RX PubMed=12056414; DOI=10.1093/dnares/9.2.47;
RA Ohara O., Nagase T., Mitsui G., Kohga H., Kikuno R., Hiraoka S.,
RA Takahashi Y., Kitajima S., Saga Y., Koseki H.;
RT "Characterization of size-fractionated cDNA libraries generated by the in
RT vitro recombination-assisted method.";
RL DNA Res. 9:47-57(2002).
RN [5]
RP IDENTIFICATION.
RX PubMed=12471243; DOI=10.1126/science.1075762;
RA Manning G., Whyte D.B., Martinez R., Hunter T., Sudarsanam S.;
RT "The protein kinase complement of the human genome.";
RL Science 298:1912-1934(2002).
RN [6]
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 [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-540 AND SER-587, AND
RP IDENTIFICATION BY MASS 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 [8]
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 [9]
RP FUNCTION, INTERACTION WITH BCAR1 AND CRK, SUBCELLULAR LOCATION, AND
RP PHOSPHORYLATION BY CSK.
RX PubMed=20534451; DOI=10.1073/pnas.0914776107;
RA Wang Y., Kelber J.A., Tran Cao H.S., Cantin G.T., Lin R., Wang W.,
RA Kaushal S., Bristow J.M., Edgington T.S., Hoffman R.M., Bouvet M.,
RA Yates J.R. III, Klemke R.L.;
RT "Pseudopodium-enriched atypical kinase 1 regulates the cytoskeleton and
RT cancer progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:10920-10925(2010).
RN [10]
RP ERRATUM OF PUBMED:20534451.
RA Wang Y., Kelber J.A., Tran Cao H.S., Cantin G.T., Lin R., Wang W.,
RA Kaushal S., Bristow J.M., Edgington T.S., Hoffman R.M., Bouvet M.,
RA Yates J.R. III, Klemke R.L.;
RL Proc. Natl. Acad. Sci. U.S.A. 107:13556-13556(2010).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281 AND TYR-635, AND
RP 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 [12]
RP PHOSPHORYLATION AT TYR-665, MUTAGENESIS OF TYR-665, SUBCELLULAR LOCATION,
RP AND FUNCTION.
RX PubMed=23105102; DOI=10.1074/jbc.m112.410910;
RA Bristow J.M., Reno T.A., Jo M., Gonias S.L., Klemke R.L.;
RT "Dynamic phosphorylation of tyrosine 665 in pseudopodium-enriched atypical
RT kinase 1 (PEAK1) is essential for the regulation of cell migration and
RT focal adhesion turnover.";
RL J. Biol. Chem. 288:123-131(2013).
RN [13]
RP FUNCTION, INTERACTION WITH SHC1, PHOSPHORYLATION AT TYR-1188, MUTAGENESIS
RP OF TYR-1188, IN COMPLEX WITH PPP1CA, PPP1CC AND SHC1, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RX PubMed=23846654; DOI=10.1038/nature12308;
RA Zheng Y., Zhang C., Croucher D.R., Soliman M.A., St-Denis N.,
RA Pasculescu A., Taylor L., Tate S.A., Hardy W.R., Colwill K., Dai A.Y.,
RA Bagshaw R., Dennis J.W., Gingras A.C., Daly R.J., Pawson T.;
RT "Temporal regulation of EGF signalling networks by the scaffold protein
RT Shc1.";
RL Nature 499:166-171(2013).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-281; SER-572; SER-587;
RP SER-648; SER-854; SER-898; THR-1151 AND SER-1374, AND IDENTIFICATION BY
RP 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 [15]
RP LACK OF ATP-BINDING.
RX PubMed=24107129; DOI=10.1042/bj20131174;
RA Murphy J.M., Zhang Q., Young S.N., Reese M.L., Bailey F.P., Eyers P.A.,
RA Ungureanu D., Hammaren H., Silvennoinen O., Varghese L.N., Chen K.,
RA Tripaydonis A., Jura N., Fukuda K., Qin J., Nimchuk Z., Mudgett M.B.,
RA Elowe S., Gee C.L., Liu L., Daly R.J., Manning G., Babon J.J., Lucet I.S.;
RT "A robust methodology to subclassify pseudokinases based on their
RT nucleotide-binding properties.";
RL Biochem. J. 457:323-334(2014).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1151, 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 [17]
RP SUBUNIT, INTERACTION WITH PRAG1, AND MUTAGENESIS OF PHE-1609.
RX PubMed=29079850; DOI=10.1038/s41467-017-01279-9;
RA Patel O., Griffin M.D.W., Panjikar S., Dai W., Ma X., Chan H., Zheng C.,
RA Kropp A., Murphy J.M., Daly R.J., Lucet I.S.;
RT "Structure of SgK223 pseudokinase reveals novel mechanisms of homotypic and
RT heterotypic association.";
RL Nat. Commun. 8:1157-1157(2017).
RN [18]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-213; ILE-240; PRO-440; GLN-611;
RP ILE-792; GLU-836; PHE-1035; LYS-1071; PRO-1077; LEU-1145; GLN-1408;
RP THR-1542 AND GLY-1699.
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).
RN [19] {ECO:0007744|PDB:6BHC}
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 1272-1743, MUTAGENESIS OF
RP ALA-1707, SUBUNIT, AND DOMAIN.
RX PubMed=29212708; DOI=10.1074/jbc.ra117.000751;
RA Ha B.H., Boggon T.J.;
RT "The crystal structure of pseudokinase PEAK1 (Sugen kinase 269) reveals an
RT unusual catalytic cleft and a novel mode of kinase fold dimerization.";
RL J. Biol. Chem. 293:1642-1650(2018).
CC -!- FUNCTION: Probable catalytically inactive kinase. Scaffolding protein
CC that regulates the cytoskeleton to control cell spreading and migration
CC by modulating focal adhesion dynamics (PubMed:23105102,
CC PubMed:20534451). Acts as a scaffold for mediating EGFR signaling
CC (PubMed:23846654). {ECO:0000269|PubMed:20534451,
CC ECO:0000269|PubMed:23105102, ECO:0000269|PubMed:23846654}.
CC -!- SUBUNIT: Homodimer (PubMed:29212708). Interacts with BCAR1 and CRK
CC (PubMed:20534451). Interacts with PRAG1 (PubMed:29079850). Interacts
CC (when phosphorylated at Tyr-1188) with SHC1 (via PID domain)
CC (PubMed:23846654). Found in a complex with PPP1CA, PPP1CC, SHC1 and
CC PEAK1. {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23846654,
CC ECO:0000269|PubMed:29079850, ECO:0000269|PubMed:29212708}.
CC -!- INTERACTION:
CC Q9H792; P56945: BCAR1; NbExp=3; IntAct=EBI-2609701, EBI-702093;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23105102}. Cell
CC junction, focal adhesion {ECO:0000269|PubMed:20534451,
CC ECO:0000269|PubMed:23105102}. Note=Colocalizes with F-actin in serum-
CC rich medium (PubMed:20534451). Actin colocalization is reduced during
CC serum starvation (PubMed:20534451). {ECO:0000269|PubMed:20534451}.
CC -!- DOMAIN: The dimerization region encompasses helices both from the
CC N- and C-terminal of the protein kinase domain.
CC {ECO:0000269|PubMed:29212708}.
CC -!- PTM: Phosphorylated on tyrosine in a CSK-dependent manner in response
CC to adhesion to fibronectin and to EGF stimulation (PubMed:20534451).
CC Phosphorylation at Tyr-665 by a Src family kinase controls subcellular
CC localization to focal adhesion and focal adhesion dynamics
CC (PubMed:20534451). Phosphorylation at Tyr-1188 is essential for binding
CC to SHC1 (PubMed:23846654). {ECO:0000269|PubMed:20534451,
CC ECO:0000269|PubMed:23846654}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. {ECO:0000305}.
CC -!- CAUTION: Has been the subject of controversy surrounding its catalytic
CC capabilities. Early characterization of PEAK1 gave a weak in vitro
CC tyrosine kinase activity (PubMed:20534451). The crystal structure
CC indicates that the kinase-domain contains a closed nucleotide-binding
CC cleft that in this conformation may deleteriously affect nucleotide
CC binding (PubMed:29212708). Furthermore PEAK1 is devoid of nucleotide
CC binding activity, as detected by a thermal-shift assay
CC (PubMed:24107129). So it seems probable that PEAK1 is an inactive
CC kinase. {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:24107129,
CC ECO:0000269|PubMed:29212708}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15006.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC87076.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AC087465; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC107883; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK024793; BAB15006.1; ALT_INIT; mRNA.
DR EMBL; AK091802; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK127658; BAC87076.1; ALT_INIT; mRNA.
DR EMBL; AK074157; BAB84983.1; -; mRNA.
DR EMBL; AB082533; BAC02711.1; -; mRNA.
DR CCDS; CCDS42062.1; -.
DR RefSeq; NP_079052.2; NM_024776.3.
DR RefSeq; XP_005254727.1; XM_005254670.2.
DR RefSeq; XP_005254728.1; XM_005254671.2.
DR RefSeq; XP_005254730.1; XM_005254673.2.
DR RefSeq; XP_005254731.1; XM_005254674.2.
DR RefSeq; XP_005254732.1; XM_005254675.4.
DR RefSeq; XP_011520335.1; XM_011522033.2.
DR RefSeq; XP_011520336.1; XM_011522034.2.
DR RefSeq; XP_011520337.1; XM_011522035.2.
DR RefSeq; XP_011520338.1; XM_011522036.2.
DR RefSeq; XP_011520339.1; XM_011522037.2.
DR RefSeq; XP_011520340.1; XM_011522038.2.
DR RefSeq; XP_011520341.1; XM_011522039.2.
DR PDB; 6BHC; X-ray; 2.30 A; A=1272-1743.
DR PDBsum; 6BHC; -.
DR AlphaFoldDB; Q9H792; -.
DR SMR; Q9H792; -.
DR BioGRID; 122926; 116.
DR DIP; DIP-56276N; -.
DR IntAct; Q9H792; 64.
DR MINT; Q9H792; -.
DR STRING; 9606.ENSP00000452796; -.
DR BindingDB; Q9H792; -.
DR ChEMBL; CHEMBL3627585; -.
DR GlyConnect; 1692; 11 N-Linked glycans (1 site).
DR GlyGen; Q9H792; 2 sites, 11 N-linked glycans (1 site), 1 O-linked glycan (1 site).
DR iPTMnet; Q9H792; -.
DR PhosphoSitePlus; Q9H792; -.
DR BioMuta; PEAK1; -.
DR DMDM; 223634730; -.
DR EPD; Q9H792; -.
DR jPOST; Q9H792; -.
DR MassIVE; Q9H792; -.
DR MaxQB; Q9H792; -.
DR PaxDb; Q9H792; -.
DR PeptideAtlas; Q9H792; -.
DR PRIDE; Q9H792; -.
DR ProteomicsDB; 81090; -.
DR Antibodypedia; 7598; 218 antibodies from 29 providers.
DR DNASU; 79834; -.
DR Ensembl; ENST00000312493.5; ENSP00000309230.4; ENSG00000173517.11.
DR Ensembl; ENST00000560626.6; ENSP00000452796.2; ENSG00000173517.11.
DR Ensembl; ENST00000682557.1; ENSP00000507603.1; ENSG00000173517.11.
DR GeneID; 79834; -.
DR KEGG; hsa:79834; -.
DR MANE-Select; ENST00000682557.1; ENSP00000507603.1; NM_001385026.1; NP_001371955.1.
DR UCSC; uc059lyw.1; human.
DR CTD; 79834; -.
DR DisGeNET; 79834; -.
DR GeneCards; PEAK1; -.
DR HGNC; HGNC:29431; PEAK1.
DR HPA; ENSG00000173517; Low tissue specificity.
DR MIM; 614248; gene.
DR neXtProt; NX_Q9H792; -.
DR OpenTargets; ENSG00000173517; -.
DR VEuPathDB; HostDB:ENSG00000173517; -.
DR eggNOG; ENOG502QVUZ; Eukaryota.
DR GeneTree; ENSGT00940000157591; -.
DR HOGENOM; CLU_002882_0_0_1; -.
DR InParanoid; Q9H792; -.
DR OMA; MGWNRNR; -.
DR OrthoDB; 49921at2759; -.
DR PhylomeDB; Q9H792; -.
DR PathwayCommons; Q9H792; -.
DR Reactome; R-HSA-9013420; RHOU GTPase cycle.
DR Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR SignaLink; Q9H792; -.
DR BioGRID-ORCS; 79834; 9 hits in 1051 CRISPR screens.
DR ChiTaRS; PEAK1; human.
DR GenomeRNAi; 79834; -.
DR Pharos; Q9H792; Tchem.
DR PRO; PR:Q9H792; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9H792; protein.
DR Bgee; ENSG00000173517; Expressed in skin of hip and 187 other tissues.
DR ExpressionAtlas; Q9H792; baseline and differential.
DR Genevisible; Q9H792; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0048041; P:focal adhesion assembly; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0051893; P:regulation of focal adhesion assembly; IDA:UniProtKB.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IDA:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR008266; Tyr_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; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell junction; Cytoplasm; Cytoskeleton; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..1746
FT /note="Inactive tyrosine-protein kinase PEAK1"
FT /id="PRO_0000250589"
FT DOMAIN 1313..1675
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 44..66
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 334..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 489..517
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 551..577
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 671..700
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 713..764
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 802..920
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1052..1102
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1138..1158
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1285..1311
FT /note="Required for homodimerization"
FT /evidence="ECO:0000269|PubMed:29212708"
FT REGION 1402..1456
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1670..1743
FT /note="Required for homodimerization"
FT /evidence="ECO:0000269|PubMed:29212708"
FT COMPBIAS 44..58
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 334..368
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 386..408
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 493..517
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 675..700
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 812..859
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 860..876
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 877..907
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1052..1066
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1409..1424
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1436..1454
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 572
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 587
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 635
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 641
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q69Z38"
FT MOD_RES 648
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 665
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:23105102"
FT MOD_RES 826
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q69Z38"
FT MOD_RES 854
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 898
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1151
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 1188
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:23846654"
FT MOD_RES 1374
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 213
FT /note="G -> R (in dbSNP:rs35459975)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041817"
FT VARIANT 240
FT /note="V -> I (in dbSNP:rs56129428)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041818"
FT VARIANT 440
FT /note="S -> P (in dbSNP:rs35335169)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041819"
FT VARIANT 611
FT /note="H -> Q (in a bladder carcinoma NOS sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041820"
FT VARIANT 792
FT /note="S -> I (in dbSNP:rs34885462)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041821"
FT VARIANT 836
FT /note="D -> E (in dbSNP:rs56388121)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041822"
FT VARIANT 1035
FT /note="S -> F (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041823"
FT VARIANT 1071
FT /note="R -> K (in dbSNP:rs12909704)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041824"
FT VARIANT 1077
FT /note="T -> P (in dbSNP:rs56133554)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041825"
FT VARIANT 1145
FT /note="P -> L (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041826"
FT VARIANT 1408
FT /note="P -> Q (in dbSNP:rs56079860)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041827"
FT VARIANT 1542
FT /note="S -> T (in dbSNP:rs1867780)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041828"
FT VARIANT 1699
FT /note="R -> G (in dbSNP:rs34004337)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041829"
FT MUTAGEN 665
FT /note="Y->E: No effect on localization with actin.
FT Decreases localization in focal adhesion. Fails to regulate
FT focal adhesion dynamics. Decreases cell migration."
FT /evidence="ECO:0000269|PubMed:23105102"
FT MUTAGEN 665
FT /note="Y->F: No effect on focal adhesion subcellular
FT localization. Does not affect colocalization with F-actin."
FT /evidence="ECO:0000269|PubMed:23105102"
FT MUTAGEN 1188
FT /note="Y->F: Fails to bind SHC1."
FT /evidence="ECO:0000269|PubMed:23846654"
FT MUTAGEN 1609
FT /note="F->A: No effect on interaction with PRAG1."
FT /evidence="ECO:0000269|PubMed:29079850"
FT MUTAGEN 1707
FT /note="A->D: Disrupts homodimerization."
FT /evidence="ECO:0000269|PubMed:29212708"
FT CONFLICT 779
FT /note="S -> F (in Ref. 2; BAC87076)"
FT /evidence="ECO:0000305"
FT CONFLICT 1046..1049
FT /note="SHMT -> RYVK (in Ref. 2; AK091802)"
FT /evidence="ECO:0000305"
FT CONFLICT 1112..1120
FT /note="QSRAAMIPP -> KCKCPISSI (in Ref. 3; BAB84983)"
FT /evidence="ECO:0000305"
FT CONFLICT 1375..1378
FT /note="LAVR -> SQEF (in Ref. 2; BAC87076)"
FT /evidence="ECO:0000305"
FT HELIX 1286..1309
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1323..1326
FT /evidence="ECO:0007829|PDB:6BHC"
FT STRAND 1327..1330
FT /evidence="ECO:0007829|PDB:6BHC"
FT STRAND 1335..1337
FT /evidence="ECO:0007829|PDB:6BHC"
FT STRAND 1339..1348
FT /evidence="ECO:0007829|PDB:6BHC"
FT STRAND 1351..1361
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1374..1379
FT /evidence="ECO:0007829|PDB:6BHC"
FT STRAND 1393..1398
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1400..1402
FT /evidence="ECO:0007829|PDB:6BHC"
FT STRAND 1456..1465
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1471..1476
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1479..1484
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1486..1507
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1508..1510
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1519..1521
FT /evidence="ECO:0007829|PDB:6BHC"
FT STRAND 1522..1525
FT /evidence="ECO:0007829|PDB:6BHC"
FT STRAND 1550..1553
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1574..1576
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1579..1583
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1590..1602
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1608..1611
FT /evidence="ECO:0007829|PDB:6BHC"
FT TURN 1616..1619
FT /evidence="ECO:0007829|PDB:6BHC"
FT TURN 1622..1624
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1635..1645
FT /evidence="ECO:0007829|PDB:6BHC"
FT TURN 1650..1652
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1656..1667
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1672..1680
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1684..1709
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1719..1730
FT /evidence="ECO:0007829|PDB:6BHC"
FT HELIX 1733..1743
FT /evidence="ECO:0007829|PDB:6BHC"
SQ SEQUENCE 1746 AA; 193106 MW; 7C9A9F60BBCF6C61 CRC64;
MSACNTFTEH VWKPGECKNC FKPKSLHQLP PDPEKAPITH GNVKTNANHS NNHRIRNTGN
FRPPVAKKPT IAVKPTMIVA DGQSICGELS IQEHCENKPV IIGWNRNRAA LSQKPLNNNN
EDDEGISHVP KPYGNNDSAK KMSDNNNGLT EVLKEIAGLD TAPQIRGNET NSRETFLGRI
NDCYKRSLER KLPPSCMIGG IKETQGKHVI LSGSTEVISN EGGRFCYPEF SSGEESEEDV
LFSNMEEEHE SWDESDEELL AMEIRMRGQP RFANFRANTL SPVRFFVDKK WNTIPLRNKS
LQRICAVDYD DSYDEILNGY EENSVVSYGQ GSIQSMVSSD STSPDSSLTE ESRSETASSL
SQKICNGGLS PGNPGDSKDM KEIEPNYESP SSNNQDKDSS QASKSSIKVP ETHKAVLALR
LEEKDGKIAV QTEKEESKAS TDVAGQAVTI NLVPTEEQAK PYRVVNLEQP LCKPYTVVDV
SAAMASEHLE GPVNSPKTKS SSSTPNSPVT SSSLTPGQIS AHFQKSSAIR YQEVWTSSTS
PRQKIPKVEL ITSGTGPNVP PRKNCHKSAP TSPTATNISS KTIPVKSPNL SEIKFNSYNN
AGMPPFPIII HDEPTYARSS KNAIKVPIVI NPNAYDNLAI YKSFLGTSGE LSVKEKTTSV
ISHTYEEIET ESKVPDNTTS KTTDCLQTKG FSNSTEHKRG SVAQKVQEFN NCLNRGQSSP
QRSYSSSHSS PAKIQRATQE PVAKIEGTQE SQMVGSSSTR EKASTVLSQI VASIQPPQSP
PETPQSGPKA CSVEELYAIP PDADVAKSTP KSTPVRPKSL FTSQPSGEAE APQTTDSPTT
KVQKDPSIKP VTPSPSKLVT SPQSEPPAPF PPPRSTSSPY HAGNLLQRHF TNWTKPTSPT
RSTEAESVLH SEGSRRAADA KPKRWISFKS FFRRRKTDEE DDKEKEREKG KLVGLDGTVI
HMLPPPPVQR HHWFTEAKGE SSEKPAIVFM YRCDPAQGQL SVDQSKARTD QAAVMEKGRA
ENALLQDSEK KRSHSSPSQI PKKILSHMTH EVTEDFSPRD PRTVVGKQDG RGCTSVTTAL
SLPELEREDG KEDISDPMDP NPCSATYSNL GQSRAAMIPP KQPRQPKGAV DDAIAFGGKT
DQEAPNASQP TPPPLPKKMI IRANTEPISK DLQKSMESSL CVMANPTYDI DPNWDASSAG
SSISYELKGL DIESYDSLER PLRKERPVPS AANSISSLTT LSIKDRFSNS MESLSSRRGP
SCRQGRGIQK PQRQALYRGL ENREEVVGKI RSLHTDALKK LAVKCEDLFM AGQKDQLRFG
VDSWSDFRLT SDKPCCEAGD AVYYTASYAK DPLNNYAVKI CKSKAKESQQ YYHSLAVRQS
LAVHFNIQQD CGHFLAEVPN RLLPWEDPDD PEKDEDDMEE TEEDAKGETD GKNPKPCSEA
ASSQKENQGV MSKKQRSHVV VITREVPCLT VADFVRDSLA QHGKSPDLYE RQVCLLLLQL
CSGLEHLKPY HVTHCDLRLE NLLLVHYQPG GTAQGFGPAE PSPTSSYPTR LIVSNFSQAK
QKSHLVDPEI LRDQSRLAPE IITATQYKKC DEFQTGILIY EMLHLPNPFD ENPELKEREY
TRADLPRIPF RSPYSRGLQQ LASCLLNPNP SERILISDAK GILQCLLWGP REDLFQTFTA
CPSLVQRNTL LQNWLDIKRT LLMIKFAEKS LDREGGISLE DWLCAQYLAF ATTDSLSCIV
KILQHR
