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 27-MAR-2024, entry version 176. 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 FUNCTION, INTERACTION WITH TNS3; SHC1; RASAL2 AND GRB2, SUBCELLULAR RP LOCATION, PHOSPHORYLATION AT TYR-635, AND MUTAGENESIS OF TYR-635 AND RP TYR-1188. RX PubMed=35687021; DOI=10.1083/jcb.202108027; RA Zuidema A., Atherton P., Kreft M., Hoekman L., Bleijerveld O.B., RA Nagaraj N., Chen N., Faessler R., Sonnenberg A.; RT "PEAK1 Y635 phosphorylation regulates cell migration through association RT with Tensin3 and integrins."; RL J. Cell Biol. 221:0-0(2022). RN [19] 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 [20] {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, PubMed:35687021). Acts as a scaffold for mediating CC EGFR signaling (PubMed:23846654). {ECO:0000269|PubMed:20534451, CC ECO:0000269|PubMed:23105102, ECO:0000269|PubMed:23846654, CC ECO:0000269|PubMed:35687021}. 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, PubMed:35687021). Found in a complex with PPP1CA, CC PPP1CC, SHC1 and PEAK1. Interacts (when phosphorylated at Tyr-635) with CC tensin TNS3 (when phosphorylated on the SH2 domain); TNS3 also CC interacts with integrins ITGB1, ITGB3 and ITGB5 and mediates their CC association with PEAK1 (PubMed:35687021). Interacts with RASAL2 and CC GRB2 (PubMed:35687021). {ECO:0000269|PubMed:20534451, CC ECO:0000269|PubMed:23846654, ECO:0000269|PubMed:29079850, CC ECO:0000269|PubMed:29212708, ECO:0000269|PubMed:35687021}. 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, ECO:0000269|PubMed:35687021}. CC Note=Colocalizes with F-actin in serum-rich medium (PubMed:20534451). CC Actin colocalization is reduced during serum starvation CC (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). Phosphorylation at Tyr-635 promotes CC interaction with tensin TNS3 (PubMed:35687021). CC {ECO:0000269|PubMed:20534451, ECO:0000269|PubMed:23846654, CC ECO:0000269|PubMed:35687021}. 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 PDB; 8DGM; X-ray; 3.20 A; B=1152-1171. DR PDBsum; 6BHC; -. DR PDBsum; 8DGM; -. DR AlphaFoldDB; Q9H792; -. DR SMR; Q9H792; -. DR BioGRID; 122926; 147. DR DIP; DIP-56276N; -. DR IntAct; Q9H792; 85. DR MINT; Q9H792; -. DR STRING; 9606.ENSP00000452796; -. DR BindingDB; Q9H792; -. DR ChEMBL; CHEMBL3627585; -. DR GlyConnect; 1692; 11 N-Linked glycans (1 site). DR GlyCosmos; Q9H792; 1 site, 11 glycans. DR GlyGen; Q9H792; 7 sites, 11 N-linked glycans (1 site), 1 O-linked glycan (6 sites). 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; 9606-ENSP00000452796; -. DR PeptideAtlas; Q9H792; -. DR ProteomicsDB; 81090; -. DR Pumba; Q9H792; -. DR Antibodypedia; 7598; 238 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 AGR; HGNC:29431; -. 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; RESWDES; -. DR OrthoDB; 2914135at2759; -. 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 1130 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 189 other cell types or tissues. DR ExpressionAtlas; Q9H792; baseline and differential. DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. 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:0051893; P:regulation of focal adhesion assembly; IDA:UniProtKB. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IDA:UniProtKB. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR008266; Tyr_kinase_AS. DR PANTHER; PTHR22972:SF5; INACTIVE TYROSINE-PROTEIN KINASE PEAK1; 1. DR PANTHER; PTHR22972; SERINE/THREONINE PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR Genevisible; Q9H792; HS. 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:0000269|PubMed:35687021, FT 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 635 FT /note="Y->E: 50% reduction in interaction with GRB2. No FT effect on interaction with SHC1." FT MUTAGEN 635 FT /note="Y->F: Impairs interaction with tensin TNS3 and FT association with integrin ITGB1. 50% reduction in FT interaction with GRB2. No effect on interaction with FT unphosphorylated SHC1 but reduces interaction with FT tyrosine-phosphorylated SHC1. Reduces focal adhesion FT localization. Reduces cell migration." FT /evidence="ECO:0000269|PubMed:35687021" 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. Reduced recruitment of FT SHC1 to focal adhesions. Slightly reduces interaction with FT GRB2. Does not affect interaction with RASAL2. Does not FT affect association with integrin ITGB1." FT /evidence="ECO:0000269|PubMed:23846654, FT ECO:0000269|PubMed:35687021" 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 //