PTK6_HUMAN
ID PTK6_HUMAN Reviewed; 451 AA.
AC Q13882; B2RCR3; B4DW46; Q58F01;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Protein-tyrosine kinase 6;
DE EC=2.7.10.2 {ECO:0000269|PubMed:12121988, ECO:0000269|PubMed:27480927, ECO:0000269|PubMed:27993680};
DE AltName: Full=Breast tumor kinase;
DE AltName: Full=Tyrosine-protein kinase BRK;
GN Name=PTK6; Synonyms=BRK;
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).
RC TISSUE=Mammary tumor;
RX PubMed=8036022;
RA Mitchell P.J., Barker K.T., Martindale J.E., Kamalati T., Lowe P.N.,
RA Page M.J., Gusterson B.A., Crompton M.R.;
RT "Cloning and characterisation of cDNAs encoding a novel non-receptor
RT tyrosine kinase, brk, expressed in human breast tumours.";
RL Oncogene 9:2383-2390(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RX PubMed=9333026; DOI=10.1038/sj.onc.1201292;
RA Mitchell P.J., Barker K.T., Shipley J., Crompton M.R.;
RT "Characterisation and chromosome mapping of the human non receptor tyrosine
RT kinase gene, brk.";
RL Oncogene 15:1497-1502(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Melanocyte;
RX PubMed=9749526;
RA Lee H.-Y., Kim M., Lee K.-H., Kang K.-N., Lee S.-T.;
RT "Exon-intron structure of the human PTK6 gene demonstrates that PTK6
RT constitutes a distinct family of non-receptor tyrosine kinase.";
RL Mol. Cells 8:401-407(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Urinary bladder;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Blood;
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 [7]
RP CHARACTERIZATION, INTERACTION WITH EGFR, AND MUTAGENESIS OF LYS-219 AND
RP TYR-447.
RX PubMed=8940083; DOI=10.1074/jbc.271.48.30956;
RA Kamalati T., Jolin H.E., Mitchell P.J., Barker K.T., Jackson L.E.,
RA Dean C.J., Page M.J., Gusterson B.A., Crompton M.R.;
RT "Brk, a breast tumor-derived non-receptor protein-tyrosine kinase,
RT sensitizes mammary epithelial cells to epidermal growth factor.";
RL J. Biol. Chem. 271:30956-30963(1996).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=9185712;
RX DOI=10.1002/(sici)1097-0215(19970611)71:6<1061::aid-ijc24>3.0.co;2-f;
RA Easty D.J., Mitchell P.J., Patel K., Florenes V.A., Spritz R.A.,
RA Bennett D.C.;
RT "Loss of expression of receptor tyrosine kinase family genes PTK7 and SEK
RT in metastatic melanoma.";
RL Int. J. Cancer 71:1061-1065(1997).
RN [9]
RP FUNCTION, INTERACTION WITH STAP2, AND MUTAGENESIS OF TRP-44; TYR-66;
RP ARG-105 AND LYS-219.
RX PubMed=10980601; DOI=10.1038/sj.onc.1203775;
RA Mitchell P.J., Sara E.A., Crompton M.R.;
RT "A novel adaptor-like protein which is a substrate for the non-receptor
RT tyrosine kinase, BRK.";
RL Oncogene 19:4273-4282(2000).
RN [10]
RP SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-447, AND INTERACTION WITH
RP KHDRBS1.
RX PubMed=10913193; DOI=10.1128/mcb.20.16.6114-6126.2000;
RA Derry J.J., Richard S., Valderrama Carvajal H., Ye X., Vasioukhin V.,
RA Cochrane A.W., Chen T., Tyner A.L.;
RT "Sik (BRK) phosphorylates Sam68 in the nucleus and negatively regulates its
RT RNA binding ability.";
RL Mol. Cell. Biol. 20:6114-6126(2000).
RN [11]
RP PHOSPHORYLATION AT TYR-13; TYR-61; TYR-66; TYR-114; TYR-342 AND TYR-351,
RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF TYR-342
RP AND TYR-447, ACTIVITY REGULATION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12121988; DOI=10.1074/jbc.m203877200;
RA Qiu H., Miller W.T.;
RT "Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation
RT and by autoinhibition.";
RL J. Biol. Chem. 277:34634-34641(2002).
RN [12]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12833144; DOI=10.1038/sj.onc.1206465;
RA Derry J.J., Prins G.S., Ray V., Tyner A.L.;
RT "Altered localization and activity of the intracellular tyrosine kinase
RT BRK/Sik in prostate tumor cells.";
RL Oncogene 22:4212-4220(2003).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-219 AND TYR-447, AND
RP PHOSPHORYLATION.
RX PubMed=15471878; DOI=10.1074/jbc.m409579200;
RA Haegebarth A., Heap D., Bie W., Derry J.J., Richard S., Tyner A.L.;
RT "The nuclear tyrosine kinase BRK/Sik phosphorylates and inhibits the RNA-
RT binding activities of the Sam68-like mammalian proteins SLM-1 and SLM-2.";
RL J. Biol. Chem. 279:54398-54404(2004).
RN [14]
RP FUNCTION IN CELL MIGRATION, FUNCTION IN PHOSPHORYLATION OF PXN, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH PXN.
RX PubMed=15572663; DOI=10.1128/mcb.24.24.10558-10572.2004;
RA Chen H.Y., Shen C.H., Tsai Y.T., Lin F.C., Huang Y.P., Chen R.H.;
RT "Brk activates rac1 and promotes cell migration and invasion by
RT phosphorylating paxillin.";
RL Mol. Cell. Biol. 24:10558-10572(2004).
RN [15]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15509496; DOI=10.1016/j.oraloncology.2004.05.010;
RA Petro B.J., Tan R.C., Tyner A.L., Lingen M.W., Watanabe K.;
RT "Differential expression of the non-receptor tyrosine kinase BRK in oral
RT squamous cell carcinoma and normal oral epithelium.";
RL Oral Oncol. 40:1040-1047(2004).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF BTK, AND INTERACTION WITH BTK.
RX PubMed=15539407; DOI=10.1074/jbc.m412038200;
RA Zhang P., Ostrander J.H., Faivre E.J., Olsen A., Fitzsimmons D.,
RA Lange C.A.;
RT "Regulated association of protein kinase B/Akt with breast tumor kinase.";
RL J. Biol. Chem. 280:1982-1991(2005).
RN [17]
RP MUTAGENESIS OF TRP-184, AND ACTIVITY REGULATION.
RX PubMed=15961400; DOI=10.1074/jbc.m504568200;
RA Kim H.I.E., Lee S.T.;
RT "An intramolecular interaction between SH2-kinase linker and kinase domain
RT is essential for the catalytic activity of protein-tyrosine kinase-6.";
RL J. Biol. Chem. 280:28973-28980(2005).
RN [18]
RP FUNCTION IN PHOSPHORYLATION OF KHDRBS1.
RX PubMed=16179349; DOI=10.1074/jbc.m505802200;
RA Lukong K.E., Larocque D., Tyner A.L., Richard S.;
RT "Tyrosine phosphorylation of sam68 by breast tumor kinase regulates
RT intranuclear localization and cell cycle progression.";
RL J. Biol. Chem. 280:38639-38647(2005).
RN [19]
RP INTERACTION WITH IRS4, AND ACTIVITY REGULATION.
RX PubMed=15870689; DOI=10.1038/sj.onc.1208721;
RA Qiu H., Zappacosta F., Su W., Annan R.S., Miller W.T.;
RT "Interaction between Brk kinase and insulin receptor substrate-4.";
RL Oncogene 24:5656-5664(2005).
RN [20]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=16651629; DOI=10.2353/ajpath.2006.050521;
RA Kasprzycka M., Majewski M., Wang Z.J., Ptasznik A., Wysocka M., Zhang Q.,
RA Marzec M., Gimotty P., Crompton M.R., Wasik M.A.;
RT "Expression and oncogenic role of Brk (PTK6/Sik) protein tyrosine kinase in
RT lymphocytes.";
RL Am. J. Pathol. 168:1631-1641(2006).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF STAT3, AND ACTIVITY REGULATION.
RX PubMed=16568091; DOI=10.1038/sj.onc.1209501;
RA Liu L., Gao Y., Qiu H., Miller W.T., Poli V., Reich N.C.;
RT "Identification of STAT3 as a specific substrate of breast tumor kinase.";
RL Oncogene 25:4904-4912(2006).
RN [22]
RP ACTIVITY REGULATION, AND MUTAGENESIS OF TRP-44.
RX PubMed=17822667; DOI=10.1016/j.bbrc.2007.08.055;
RA Kim H.I.E., Jung J., Lee E.S., Kim Y.C., Lee W., Lee S.T.;
RT "Molecular dissection of the interaction between the SH3 domain and the
RT SH2-Kinase Linker region in PTK6.";
RL Biochem. Biophys. Res. Commun. 362:829-834(2007).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF STAT5B.
RX PubMed=17997837; DOI=10.1186/bcr1794;
RA Weaver A.M., Silva C.M.;
RT "Signal transducer and activator of transcription 5b: a new target of
RT breast tumor kinase/protein tyrosine kinase 6.";
RL Breast Cancer Res. 9:R79-R79(2007).
RN [24]
RP FUNCTION IN PHOSPHORYLATION OF ARHGAP35.
RX PubMed=18829532; DOI=10.1158/0008-5472.can-08-0997;
RA Shen C.H., Chen H.Y., Lin M.S., Li F.Y., Chang C.C., Kuo M.L.,
RA Settleman J., Chen R.H.;
RT "Breast tumor kinase phosphorylates p190RhoGAP to regulate rho and ras and
RT promote breast carcinoma growth, migration, and invasion.";
RL Cancer Res. 68:7779-7787(2008).
RN [25]
RP INTERACTION WITH ADAM15.
RX PubMed=18296648; DOI=10.1158/1541-7786.mcr-07-2028;
RA Zhong J.L., Poghosyan Z., Pennington C.J., Scott X., Handsley M.M.,
RA Warn A., Gavrilovic J., Honert K., Kruger A., Span P.N., Sweep F.C.,
RA Edwards D.R.;
RT "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human
RT mammary carcinoma.";
RL Mol. Cancer Res. 6:383-394(2008).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-114, AND IDENTIFICATION BY
RP 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 [27]
RP INTERACTION WITH ERBB2.
RX PubMed=18719096; DOI=10.1073/pnas.0805009105;
RA Xiang B., Chatti K., Qiu H., Lakshmi B., Krasnitz A., Hicks J., Yu M.,
RA Miller W.T., Muthuswamy S.K.;
RT "Brk is coamplified with ErbB2 to promote proliferation in breast cancer.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12463-12468(2008).
RN [28]
RP INTERACTION WITH SFPQ.
RX PubMed=19439179; DOI=10.1016/j.cellsig.2009.04.008;
RA Lukong K.E., Huot M.E., Richard S.;
RT "BRK phosphorylates PSF promoting its cytoplasmic localization and cell
RT cycle arrest.";
RL Cell. Signal. 21:1415-1422(2009).
RN [29]
RP REVIEW ON FUNCTION.
RX PubMed=20193745; DOI=10.1016/j.bbcan.2010.02.003;
RA Brauer P.M., Tyner A.L.;
RT "Building a better understanding of the intracellular tyrosine kinase PTK6
RT - BRK by BRK.";
RL Biochim. Biophys. Acta 1806:66-73(2010).
RN [30]
RP PHOSPHORYLATION OF CTNNB1, AND INTERACTION WITH CTNNB1.
RX PubMed=20026641; DOI=10.1242/jcs.053264;
RA Palka-Hamblin H.L., Gierut J.J., Bie W., Brauer P.M., Zheng Y., Asara J.M.,
RA Tyner A.L.;
RT "Identification of beta-catenin as a target of the intracellular tyrosine
RT kinase PTK6.";
RL J. Cell Sci. 123:236-245(2010).
RN [31]
RP FUNCTION (ISOFORM 2), AND INTERACTION (ISOFORM 2) WITH KHDRBS1 AND CTNNB1.
RX PubMed=21479203; DOI=10.1371/journal.pone.0014789;
RA Brauer P.M., Zheng Y., Evans M.D., Dominguez-Brauer C., Peehl D.M.,
RA Tyner A.L.;
RT "The alternative splice variant of protein tyrosine kinase 6 negatively
RT regulates growth and enhances PTK6-mediated inhibition of beta-catenin.";
RL PLoS ONE 6:E14789-E14789(2011).
RN [32]
RP STRUCTURE BY NMR OF 75-174.
RX PubMed=15056653; DOI=10.1074/jbc.m313185200;
RA Hong E., Shin J., Kim H.I., Lee S.T., Lee W.;
RT "Solution structure and backbone dynamics of the non-receptor protein-
RT tyrosine kinase-6 Src homology 2 domain.";
RL J. Biol. Chem. 279:29700-29708(2004).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.33 ANGSTROMS) OF 185-446, CATALYTIC ACTIVITY, AND
RP MUTAGENESIS OF LYS-219.
RX PubMed=27480927; DOI=10.1016/j.bbrc.2016.07.121;
RA Thakur M.K., Kumar A., Birudukota S., Swaminathan S., Tyagi R., Gosu R.;
RT "Crystal structure of the kinase domain of human protein tyrosine kinase 6
RT (PTK6) at 2.33 A resolution.";
RL Biochem. Biophys. Res. Commun. 478:637-642(2016).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 185-446 IN COMPLEXES WITH
RP INHIBITORS, AND CATALYTIC ACTIVITY.
RX PubMed=27993680; DOI=10.1016/j.bbrc.2016.12.030;
RA Thakur M.K., Birudukota S., Swaminathan S., Battula S.K., Vadivelu S.,
RA Tyagi R., Gosu R.;
RT "Co-crystal structures of PTK6: With Dasatinib at 2.24 A, with novel
RT imidazo[1,2-a]pyrazin-8-amine derivative inhibitor at 1.70 A resolution.";
RL Biochem. Biophys. Res. Commun. 482:1289-1295(2017).
RN [35]
RP VARIANTS [LARGE SCALE ANALYSIS] PHE-16 AND THR-436.
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: Non-receptor tyrosine-protein kinase implicated in the
CC regulation of a variety of signaling pathways that control the
CC differentiation and maintenance of normal epithelia, as well as tumor
CC growth. Function seems to be context dependent and differ depending on
CC cell type, as well as its intracellular localization. A number of
CC potential nuclear and cytoplasmic substrates have been identified.
CC These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1,
CC KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B
CC and a variety of signaling molecules: ARHGAP35/p190RhoGAP,
CC PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of
CC proteins that are likely upstream of PTK6 in various signaling
CC pathways, or for which PTK6 may play an adapter-like role. These
CC proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-
CC tumorigenic tissues, PTK6 promotes cellular differentiation and
CC apoptosis. In tumors PTK6 contributes to cancer progression by
CC sensitizing cells to mitogenic signals and enhancing proliferation,
CC anchorage-independent survival and migration/invasion. Association with
CC EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and
CC growth through enhancement of EGF-induced signaling via BTK/AKT and PI3
CC kinase. Contributes to migration and proliferation by contributing to
CC EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes
CC association with RASA1/p120RasGAP, inactivating RhoA while activating
CC RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by
CC PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration
CC and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation.
CC Nuclear PTK6 may be important for regulating growth in normal
CC epithelia, while cytoplasmic PTK6 might activate oncogenic signaling
CC pathways.
CC -!- FUNCTION: Isoform 2 inhibits PTK6 phosphorylation and PTK6 association
CC with other tyrosine-phosphorylated proteins.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028,
CC ECO:0000269|PubMed:12121988, ECO:0000269|PubMed:27480927,
CC ECO:0000269|PubMed:27993680};
CC -!- ACTIVITY REGULATION: Activated by EGF, NRG1 and IGF1. Inhibited by
CC SOCS3 to phosphorylate STAT3. Stabilized in the inactive form by an
CC association between the SH3 domain and the SH2-TK linker region.
CC Interaction between Trp-184 within SH2-TK linker region and the
CC catalytic domain appears essential for positive regulation of kinase
CC activity. {ECO:0000269|PubMed:12121988, ECO:0000269|PubMed:15870689,
CC ECO:0000269|PubMed:15961400, ECO:0000269|PubMed:16568091,
CC ECO:0000269|PubMed:17822667}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=83 uM for ATP {ECO:0000269|PubMed:12121988};
CC Vmax=37 nmol/min/mg enzyme {ECO:0000269|PubMed:12121988};
CC -!- SUBUNIT: Interacts with GAP-A.p65 (By similarity). Interacts (via SH3
CC and SH2 domains) with KHDRBS1. Interacts (via SH3 and SH2 domains) with
CC phosphorylated IRS4. Interacts with ADAM15. Interacts (via SH3 domain)
CC with SFPQ. Interacts with EGFR and ERBB2. Interacts with STAP2.
CC Interacts with PNX. Interacts with SFPQ. Interacts with PTK/ATK.
CC Interacts with CTNNB1. {ECO:0000250, ECO:0000269|PubMed:10913193,
CC ECO:0000269|PubMed:10980601, ECO:0000269|PubMed:15539407,
CC ECO:0000269|PubMed:15572663, ECO:0000269|PubMed:15870689,
CC ECO:0000269|PubMed:18296648, ECO:0000269|PubMed:18719096,
CC ECO:0000269|PubMed:19439179, ECO:0000269|PubMed:20026641,
CC ECO:0000269|PubMed:8940083}.
CC -!- INTERACTION:
CC Q13882; Q08043: ACTN3; NbExp=3; IntAct=EBI-1383632, EBI-2880652;
CC Q13882; Q3KP44: ANKRD55; NbExp=3; IntAct=EBI-1383632, EBI-14493093;
CC Q13882; Q13191: CBLB; NbExp=3; IntAct=EBI-1383632, EBI-744027;
CC Q13882; Q16543: CDC37; NbExp=4; IntAct=EBI-1383632, EBI-295634;
CC Q13882; Q92841: DDX17; NbExp=4; IntAct=EBI-1383632, EBI-746012;
CC Q13882; Q8N9I9: DTX3; NbExp=3; IntAct=EBI-1383632, EBI-2340258;
CC Q13882; Q5JST6: EFHC2; NbExp=7; IntAct=EBI-1383632, EBI-2349927;
CC Q13882; P04626: ERBB2; NbExp=4; IntAct=EBI-1383632, EBI-641062;
CC Q13882; O00471: EXOC5; NbExp=6; IntAct=EBI-1383632, EBI-949824;
CC Q13882; O14526: FCHO1; NbExp=4; IntAct=EBI-1383632, EBI-719823;
CC Q13882; Q13480: GAB1; NbExp=6; IntAct=EBI-1383632, EBI-517684;
CC Q13882; P08238: HSP90AB1; NbExp=3; IntAct=EBI-1383632, EBI-352572;
CC Q13882; P42858: HTT; NbExp=4; IntAct=EBI-1383632, EBI-466029;
CC Q13882; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-1383632, EBI-747204;
CC Q13882; Q5VWX1: KHDRBS2; NbExp=4; IntAct=EBI-1383632, EBI-742808;
CC Q13882; Q5T5P2-6: KIAA1217; NbExp=3; IntAct=EBI-1383632, EBI-10188326;
CC Q13882; P10721: KIT; NbExp=4; IntAct=EBI-1383632, EBI-1379503;
CC Q13882; O14770-4: MEIS2; NbExp=3; IntAct=EBI-1383632, EBI-8025850;
CC Q13882; Q13064: MKRN3; NbExp=3; IntAct=EBI-1383632, EBI-2340269;
CC Q13882; Q8TDC0: MYOZ3; NbExp=3; IntAct=EBI-1383632, EBI-5662487;
CC Q13882; P78337: PITX1; NbExp=3; IntAct=EBI-1383632, EBI-748265;
CC Q13882; Q9NQX0: PRDM6; NbExp=3; IntAct=EBI-1383632, EBI-11320284;
CC Q13882; Q13882: PTK6; NbExp=3; IntAct=EBI-1383632, EBI-1383632;
CC Q13882; Q04864: REL; NbExp=3; IntAct=EBI-1383632, EBI-307352;
CC Q13882; P23246: SFPQ; NbExp=5; IntAct=EBI-1383632, EBI-355453;
CC Q13882; Q13239-3: SLA; NbExp=3; IntAct=EBI-1383632, EBI-17630587;
CC Q13882; O00401: WASL; NbExp=3; IntAct=EBI-1383632, EBI-957615;
CC Q13882; Q9BYN7: ZNF341; NbExp=3; IntAct=EBI-1383632, EBI-9089622;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Cell projection, ruffle.
CC Membrane {ECO:0000250}. Note=Colocalizes with KHDRBS1, KHDRBS2 or
CC KHDRBS3, within the nucleus. Nuclear localization in epithelial cells
CC of normal prostate but cytoplasmic localization in cancer prostate.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13882-1; Sequence=Displayed;
CC Name=2; Synonyms=ALT-PTK6, LambdaM5;
CC IsoId=Q13882-2; Sequence=VSP_042066, VSP_042067;
CC -!- TISSUE SPECIFICITY: Epithelia-specific. Very high level in colon and
CC high levels in small intestine and prostate, and low levels in some
CC fetal tissues. Not expressed in breast or ovarian tissue but expressed
CC in high percentage of breast and ovarian cancers. Also overexpressed in
CC some metastatic melanomas, lymphomas, colon cancers, squamous cell
CC carcinomas and prostate cancers. Also found in melanocytes. Not
CC expressed in heart, brain, placenta, lung, liver, skeletal muscle,
CC kidney and pancreas. Isoform 2 is present in prostate epithelial cell
CC lines derived from normal prostate and prostate adenocarcinomas, as
CC well as in a variety of cell lines. {ECO:0000269|PubMed:12833144,
CC ECO:0000269|PubMed:15509496, ECO:0000269|PubMed:16651629,
CC ECO:0000269|PubMed:9185712}.
CC -!- DOMAIN: The SH3 domain plays a major role in substrate interactions.
CC The SH2 domain of PTK6 plays a role in protein-protein interactions,
CC but is likely more important for the regulation of catalytic activity.
CC -!- PTM: Autophosphorylated. Autophosphorylation of Tyr-342 leads to an
CC increase of kinase activity. Tyr-447 binds to the SH2 domain when
CC phosphorylated and negatively regulates kinase activity.
CC {ECO:0000269|PubMed:10913193, ECO:0000269|PubMed:12121988,
CC ECO:0000269|PubMed:15471878, ECO:0000269|PubMed:20026641}.
CC -!- MISCELLANEOUS: The inhibitors bind to the ATP-binding pocket.
CC {ECO:0000269|PubMed:27993680}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. BRK/PTK6/SIK subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAG62908.1; Type=Erroneous translation; Note=Wrong choice of CDS.; 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; X78549; CAA55295.1; -; mRNA.
DR EMBL; U61412; AAC34935.1; -; Genomic_DNA.
DR EMBL; U61406; AAC34935.1; JOINED; Genomic_DNA.
DR EMBL; U61407; AAC34935.1; JOINED; Genomic_DNA.
DR EMBL; U61408; AAC34935.1; JOINED; Genomic_DNA.
DR EMBL; U61409; AAC34935.1; JOINED; Genomic_DNA.
DR EMBL; U61410; AAC34935.1; JOINED; Genomic_DNA.
DR EMBL; U61411; AAC34935.1; JOINED; Genomic_DNA.
DR EMBL; AK315232; BAG37660.1; -; mRNA.
DR EMBL; AK301364; BAG62908.1; ALT_SEQ; mRNA.
DR EMBL; AL121829; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC035843; AAH35843.1; -; mRNA.
DR CCDS; CCDS13524.1; -. [Q13882-1]
DR CCDS; CCDS74750.1; -. [Q13882-2]
DR PIR; S49016; S49016.
DR RefSeq; NP_001243287.1; NM_001256358.1. [Q13882-2]
DR RefSeq; NP_005966.1; NM_005975.3. [Q13882-1]
DR PDB; 1RJA; NMR; -; A=75-174.
DR PDB; 2KGT; NMR; -; A=1-72.
DR PDB; 5D7V; X-ray; 2.33 A; A/B/C/D=185-446.
DR PDB; 5DA3; X-ray; 1.70 A; A=185-446.
DR PDB; 5H2U; X-ray; 2.24 A; A/B/C/D=185-446.
DR PDB; 6CZ2; X-ray; 2.50 A; A=182-443.
DR PDB; 6CZ3; X-ray; 1.80 A; A=182-443.
DR PDB; 6CZ4; X-ray; 1.50 A; A=182-443.
DR PDBsum; 1RJA; -.
DR PDBsum; 2KGT; -.
DR PDBsum; 5D7V; -.
DR PDBsum; 5DA3; -.
DR PDBsum; 5H2U; -.
DR PDBsum; 6CZ2; -.
DR PDBsum; 6CZ3; -.
DR PDBsum; 6CZ4; -.
DR AlphaFoldDB; Q13882; -.
DR BMRB; Q13882; -.
DR SMR; Q13882; -.
DR BioGRID; 111720; 94.
DR DIP; DIP-39785N; -.
DR IntAct; Q13882; 74.
DR MINT; Q13882; -.
DR STRING; 9606.ENSP00000442460; -.
DR BindingDB; Q13882; -.
DR ChEMBL; CHEMBL4601; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB11800; Tivozanib.
DR DrugBank; DB05294; Vandetanib.
DR DrugBank; DB15035; Zanubrutinib.
DR DrugCentral; Q13882; -.
DR GuidetoPHARMACOLOGY; 2182; -.
DR iPTMnet; Q13882; -.
DR PhosphoSitePlus; Q13882; -.
DR BioMuta; PTK6; -.
DR DMDM; 8928302; -.
DR EPD; Q13882; -.
DR jPOST; Q13882; -.
DR MassIVE; Q13882; -.
DR MaxQB; Q13882; -.
DR PaxDb; Q13882; -.
DR PeptideAtlas; Q13882; -.
DR PRIDE; Q13882; -.
DR ProteomicsDB; 59709; -. [Q13882-1]
DR ProteomicsDB; 59710; -. [Q13882-2]
DR Antibodypedia; 29774; 547 antibodies from 38 providers.
DR DNASU; 5753; -.
DR Ensembl; ENST00000217185.3; ENSP00000217185.3; ENSG00000101213.7. [Q13882-2]
DR Ensembl; ENST00000542869.3; ENSP00000442460.2; ENSG00000101213.7. [Q13882-1]
DR GeneID; 5753; -.
DR KEGG; hsa:5753; -.
DR MANE-Select; ENST00000542869.3; ENSP00000442460.2; NM_005975.4; NP_005966.1.
DR UCSC; uc002yfg.5; human. [Q13882-1]
DR CTD; 5753; -.
DR DisGeNET; 5753; -.
DR GeneCards; PTK6; -.
DR HGNC; HGNC:9617; PTK6.
DR HPA; ENSG00000101213; Tissue enhanced (esophagus, skin, vagina).
DR MIM; 602004; gene.
DR neXtProt; NX_Q13882; -.
DR OpenTargets; ENSG00000101213; -.
DR PharmGKB; PA33960; -.
DR VEuPathDB; HostDB:ENSG00000101213; -.
DR eggNOG; KOG0197; Eukaryota.
DR GeneTree; ENSGT00940000161218; -.
DR HOGENOM; CLU_000288_7_2_1; -.
DR InParanoid; Q13882; -.
DR OMA; VRHYRIW; -.
DR OrthoDB; 539311at2759; -.
DR PhylomeDB; Q13882; -.
DR TreeFam; TF351634; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; Q13882; -.
DR Reactome; R-HSA-187577; SCF(Skp2)-mediated degradation of p27/p21.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-8847993; ERBB2 Activates PTK6 Signaling.
DR Reactome; R-HSA-8849468; PTK6 Regulates Proteins Involved in RNA Processing.
DR Reactome; R-HSA-8849469; PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1.
DR Reactome; R-HSA-8849470; PTK6 Regulates Cell Cycle.
DR Reactome; R-HSA-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR Reactome; R-HSA-8849472; PTK6 Down-Regulation.
DR Reactome; R-HSA-8849473; PTK6 Expression.
DR Reactome; R-HSA-8849474; PTK6 Activates STAT3.
DR Reactome; R-HSA-8857538; PTK6 promotes HIF1A stabilization.
DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1.
DR SABIO-RK; Q13882; -.
DR SignaLink; Q13882; -.
DR SIGNOR; Q13882; -.
DR BioGRID-ORCS; 5753; 16 hits in 1102 CRISPR screens.
DR EvolutionaryTrace; Q13882; -.
DR GeneWiki; PTK6; -.
DR GenomeRNAi; 5753; -.
DR Pharos; Q13882; Tchem.
DR PRO; PR:Q13882; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q13882; protein.
DR Bgee; ENSG00000101213; Expressed in esophagus squamous epithelium and 125 other tissues.
DR Genevisible; Q13882; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0001726; C:ruffle; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0004713; F:protein tyrosine kinase activity; EXP:Reactome.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:BHF-UCL.
DR GO; GO:0038128; P:ERBB2 signaling pathway; TAS:Reactome.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; IEA:Ensembl.
DR GO; GO:0045926; P:negative regulation of growth; IEA:Ensembl.
DR GO; GO:0061099; P:negative regulation of protein tyrosine kinase activity; IDA:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; TAS:Reactome.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; TAS:Reactome.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; TAS:Reactome.
DR GO; GO:0046777; P:protein autophosphorylation; IMP:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0007260; P:tyrosine phosphorylation of STAT protein; IDA:UniProtKB.
DR CDD; cd10358; SH2_PTK6_Brk; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR035846; PTK6_SH2.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell projection;
KW Cytoplasm; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; SH2 domain; SH3 domain; Transferase;
KW Tyrosine-protein kinase.
FT CHAIN 1..451
FT /note="Protein-tyrosine kinase 6"
FT /id="PRO_0000088133"
FT DOMAIN 8..72
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 78..170
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 191..445
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 171..190
FT /note="Linker"
FT ACT_SITE 312
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 197..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 219
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000305|PubMed:27480927, ECO:0000305|PubMed:27993680"
FT MOD_RES 13
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12121988"
FT MOD_RES 61
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12121988"
FT MOD_RES 66
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12121988"
FT MOD_RES 114
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12121988,
FT ECO:0007744|PubMed:18691976"
FT MOD_RES 342
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12121988"
FT MOD_RES 351
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:12121988"
FT MOD_RES 447
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:10913193"
FT VAR_SEQ 78..134
FT /note="WFFGCISRSEAVRRLQAEGNATGAFLIRVSEKPSADYVLSVRDTQAVRHYKI
FT WRRAG -> AGHAGCAALQDLAACRGPAAPERGGVLPQPARACELPQGPEPVPRPAAGR
FT ALPEARA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:9333026"
FT /id="VSP_042066"
FT VAR_SEQ 135..451
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:9333026"
FT /id="VSP_042067"
FT VARIANT 16
FT /note="L -> F (in a renal papillary sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041760"
FT VARIANT 436
FT /note="A -> T (in dbSNP:rs56145017)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041761"
FT MUTAGEN 44
FT /note="W->A: Strong decrease in STAP2 phosphorylation.
FT Markedly decreased interaction between SH3 domain the
FT linker region."
FT /evidence="ECO:0000269|PubMed:10980601,
FT ECO:0000269|PubMed:17822667"
FT MUTAGEN 66
FT /note="Y->A: Decrease in STAP2 phosphorylation."
FT /evidence="ECO:0000269|PubMed:10980601"
FT MUTAGEN 105
FT /note="R->L: Decrease in STAP2 phosphorylation."
FT /evidence="ECO:0000269|PubMed:10980601"
FT MUTAGEN 184
FT /note="W->A: Abrogates interaction between PTK6-domain
FT kinase and PTK6-linker. Abrogates autophosphorylation and
FT phosphorylation of KHDRBS1."
FT /evidence="ECO:0000269|PubMed:15961400"
FT MUTAGEN 219
FT /note="K->M: Abolishes kinase activity and cell
FT transformation, and phosphorylation of STAP2."
FT /evidence="ECO:0000269|PubMed:10980601,
FT ECO:0000269|PubMed:15471878, ECO:0000269|PubMed:8940083"
FT MUTAGEN 219
FT /note="K->R: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:27480927"
FT MUTAGEN 342
FT /note="Y->A: 3-fold lower specific kinase activity.
FT Decreased, but still significant, autophosphorylation.
FT Decreased, but still significant, autophosphorylation; when
FT associated with A-447."
FT /evidence="ECO:0000269|PubMed:12121988"
FT MUTAGEN 447
FT /note="Y->F: Decrease in transforming potential and
FT increase in the kinase activity level. Decreased, but still
FT significant, autophosphorylation; when associated with A-
FT 342."
FT /evidence="ECO:0000269|PubMed:12121988,
FT ECO:0000269|PubMed:15471878, ECO:0000269|PubMed:8940083"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:2KGT"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:2KGT"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:2KGT"
FT STRAND 56..62
FT /evidence="ECO:0007829|PDB:2KGT"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:2KGT"
FT STRAND 67..70
FT /evidence="ECO:0007829|PDB:2KGT"
FT HELIX 85..92
FT /evidence="ECO:0007829|PDB:1RJA"
FT STRAND 102..106
FT /evidence="ECO:0007829|PDB:1RJA"
FT STRAND 108..112
FT /evidence="ECO:0007829|PDB:1RJA"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:1RJA"
FT STRAND 125..131
FT /evidence="ECO:0007829|PDB:1RJA"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:1RJA"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:1RJA"
FT STRAND 143..147
FT /evidence="ECO:0007829|PDB:1RJA"
FT HELIX 148..157
FT /evidence="ECO:0007829|PDB:1RJA"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:1RJA"
FT HELIX 188..190
FT /evidence="ECO:0007829|PDB:6CZ4"
FT STRAND 191..200
FT /evidence="ECO:0007829|PDB:6CZ4"
FT STRAND 203..210
FT /evidence="ECO:0007829|PDB:6CZ4"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:6CZ4"
FT STRAND 214..221
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 229..240
FT /evidence="ECO:0007829|PDB:6CZ4"
FT STRAND 250..254
FT /evidence="ECO:0007829|PDB:6CZ4"
FT STRAND 256..264
FT /evidence="ECO:0007829|PDB:6CZ4"
FT STRAND 268..271
FT /evidence="ECO:0007829|PDB:6CZ2"
FT HELIX 272..278
FT /evidence="ECO:0007829|PDB:6CZ4"
FT TURN 281..283
FT /evidence="ECO:0007829|PDB:5DA3"
FT HELIX 286..305
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 315..317
FT /evidence="ECO:0007829|PDB:6CZ4"
FT STRAND 318..320
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 322..324
FT /evidence="ECO:0007829|PDB:5DA3"
FT STRAND 326..328
FT /evidence="ECO:0007829|PDB:6CZ4"
FT TURN 334..336
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 339..342
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 345..348
FT /evidence="ECO:0007829|PDB:5DA3"
FT HELIX 351..353
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 356..361
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 366..380
FT /evidence="ECO:0007829|PDB:6CZ4"
FT TURN 381..384
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 393..402
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 414..423
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 428..430
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 434..441
FT /evidence="ECO:0007829|PDB:6CZ4"
FT HELIX 442..444
FT /evidence="ECO:0007829|PDB:5D7V"
SQ SEQUENCE 451 AA; 51834 MW; CDCAC0EE242E1BD7 CRC64;
MVSRDQAHLG PKYVGLWDFK SRTDEELSFR AGDVFHVARK EEQWWWATLL DEAGGAVAQG
YVPHNYLAER ETVESEPWFF GCISRSEAVR RLQAEGNATG AFLIRVSEKP SADYVLSVRD
TQAVRHYKIW RRAGGRLHLN EAVSFLSLPE LVNYHRAQSL SHGLRLAAPC RKHEPEPLPH
WDDWERPREE FTLCRKLGSG YFGEVFEGLW KDRVQVAIKV ISRDNLLHQQ MLQSEIQAMK
KLRHKHILAL YAVVSVGDPV YIITELMAKG SLLELLRDSD EKVLPVSELL DIAWQVAEGM
CYLESQNYIH RDLAARNILV GENTLCKVGD FGLARLIKED VYLSHDHNIP YKWTAPEALS
RGHYSTKSDV WSFGILLHEM FSRGQVPYPG MSNHEAFLRV DAGYRMPCPL ECPPSVHKLM
LTCWCRDPEQ RPCFKALRER LSSFTSYENP T
