PKN2_HUMAN
ID PKN2_HUMAN Reviewed; 984 AA.
AC Q16513; B4DQ21; B4DTP5; B4DVG1; D3DT24; Q08AF4; Q9H1W4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Serine/threonine-protein kinase N2;
DE EC=2.7.11.13;
DE AltName: Full=PKN gamma;
DE AltName: Full=Protein kinase C-like 2;
DE AltName: Full=Protein-kinase C-related kinase 2;
GN Name=PKN2; Synonyms=PRK2, PRKCL2;
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).
RX PubMed=7988719; DOI=10.1016/0014-5793(94)01202-4;
RA Palmer R.H., Ridden J., Parker P.J.;
RT "Identification of multiple, novel, protein kinase C-related gene
RT products.";
RL FEBS Lett. 356:5-8(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=B-cell, and Spleen;
RX PubMed=7851406; DOI=10.1111/j.1432-1033.1995.tb20395.x;
RA Palmer R.H., Ridden J., Parker P.J.;
RT "Cloning and expression patterns of two members of a novel protein-kinase-
RT C-related kinase family.";
RL Eur. J. Biochem. 227:344-351(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2; 4 AND 5).
RC TISSUE=Placenta, and Spleen;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
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 FUNCTION, AND INTERACTION WITH CD44.
RX PubMed=15123640; DOI=10.1074/jbc.m403608200;
RA Bourguignon L.Y., Singleton P.A., Diedrich F.;
RT "Hyaluronan-CD44 interaction with Rac1-dependent protein kinase N-gamma
RT promotes phospholipase Cgamma1 activation, Ca(2+) signaling, and cortactin-
RT cytoskeleton function leading to keratinocyte adhesion and
RT differentiation.";
RL J. Biol. Chem. 279:29654-29669(2004).
RN [8]
RP ACTIVITY REGULATION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF ASP-117 AND
RP ASP-700.
RX PubMed=9368003; DOI=10.1074/jbc.272.47.29449;
RA Cryns V.L., Byun Y., Rana A., Mellor H., Lustig K.D., Ghanem L.,
RA Parker P.J., Kirschner M.W., Yuan J.;
RT "Specific proteolysis of the kinase protein kinase C-related kinase 2 by
RT caspase-3 during apoptosis. Identification by a novel, small pool
RT expression cloning strategy.";
RL J. Biol. Chem. 272:29449-29453(1997).
RN [9]
RP FUNCTION, INTERACTION WITH RAC1 AND RHOA, AND AUTOPHOSPHORYLATION.
RX PubMed=9121475; DOI=10.1128/mcb.17.4.2247;
RA Vincent S., Settleman J.;
RT "The PRK2 kinase is a potential effector target of both Rho and Rac GTPases
RT and regulates actin cytoskeletal organization.";
RL Mol. Cell. Biol. 17:2247-2256(1997).
RN [10]
RP FUNCTION, INTERACTION WITH PDPK1, AND MUTAGENESIS OF PHE-974; PHE-977;
RP ASP-978 AND TYR-979.
RX PubMed=10226025; DOI=10.1016/s0960-9822(99)80186-9;
RA Balendran A., Casamayor A., Deak M., Paterson A., Gaffney P., Currie R.,
RA Downes C.P., Alessi D.R.;
RT "PDK1 acquires PDK2 activity in the presence of a synthetic peptide derived
RT from the carboxyl terminus of PRK2.";
RL Curr. Biol. 9:393-404(1999).
RN [11]
RP INTERACTION WITH NCK1 AND NCK2, AND TISSUE SPECIFICITY.
RX PubMed=10026169; DOI=10.1074/jbc.274.9.5542;
RA Braverman L.E., Quilliam L.A.;
RT "Identification of Grb4/Nckbeta, a src homology 2 and 3 domain-containing
RT adapter protein having similar binding and biological properties to Nck.";
RL J. Biol. Chem. 274:5542-5549(1999).
RN [12]
RP INTERACTION WITH MAP3K2.
RX PubMed=10818102; DOI=10.1074/jbc.m003148200;
RA Sun W., Vincent S., Settleman J., Johnson G.L.;
RT "MEK kinase 2 binds and activates protein kinase C-related kinase 2.
RT Bifurcation of kinase regulatory pathways at the level of an MAPK kinase
RT kinase.";
RL J. Biol. Chem. 275:24421-24428(2000).
RN [13]
RP FUNCTION IN APOPTOSIS, FUNCTION IN AKT1 ACTIVITY INHIBITION, ACTIVITY
RP REGULATION, INTERACTION WITH AKT1, AND MUTAGENESIS OF ASP-117 AND ASP-700.
RX PubMed=10926925; DOI=10.1074/jbc.m001753200;
RA Koh H., Lee K.H., Kim D., Kim S., Kim J.W., Chung J.;
RT "Inhibition of Akt and its anti-apoptotic activities by tumor necrosis
RT factor-induced protein kinase C-related kinase 2 (PRK2) cleavage.";
RL J. Biol. Chem. 275:34451-34458(2000).
RN [14]
RP PHOSPHORYLATION AT THR-816 BY PDPK1, AND INTERACTION WITH PDPK1.
RX PubMed=10792047; DOI=10.1073/pnas.090491897;
RA Dong L.Q., Landa L.R., Wick M.J., Zhu L., Mukai H., Ono Y., Liu F.;
RT "Phosphorylation of protein kinase N by phosphoinositide-dependent protein
RT kinase-1 mediates insulin signals to the actin cytoskeleton.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:5089-5094(2000).
RN [15]
RP INTERACTION WITH PTPN13, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-686
RP AND CYS-984.
RX PubMed=11356191; DOI=10.1016/s0014-5793(01)02401-2;
RA Gross C., Heumann R., Erdmann K.S.;
RT "The protein kinase C-related kinase PRK2 interacts with the protein
RT tyrosine phosphatase PTP-BL via a novel PDZ domain binding motif.";
RL FEBS Lett. 496:101-104(2001).
RN [16]
RP FUNCTION IN KINASE ACTIVITY INHIBITION, AND INTERACTION WITH PDPK1.
RX PubMed=11781095; DOI=10.1021/bi010719z;
RA Hodgkinson C.P., Sale G.J.;
RT "Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by
RT a C-terminal PRK2 fragment.";
RL Biochemistry 41:561-569(2002).
RN [17]
RP FUNCTION IN CELL ADHESION, AND INDUCTION.
RX PubMed=11777936; DOI=10.1083/jcb.200105140;
RA Calautti E., Grossi M., Mammucari C., Aoyama Y., Pirro M., Ono Y., Li J.,
RA Dotto G.P.;
RT "Fyn tyrosine kinase is a downstream mediator of Rho/PRK2 function in
RT keratinocyte cell-cell adhesion.";
RL J. Cell Biol. 156:137-148(2002).
RN [18]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HCV NS5B (MICROBIAL
RP INFECTION).
RX PubMed=15364941; DOI=10.1074/jbc.m408617200;
RA Kim S.J., Kim J.H., Kim Y.G., Lim H.S., Oh J.W.;
RT "Protein kinase C-related kinase 2 regulates hepatitis C virus RNA
RT polymerase function by phosphorylation.";
RL J. Biol. Chem. 279:50031-50041(2004).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-958, AND IDENTIFICATION BY
RP 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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-302; SER-306 AND SER-360, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [21]
RP FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=17332740; DOI=10.1038/sj.emboj.7601637;
RA Schmidt A., Durgan J., Magalhaes A., Hall A.;
RT "Rho GTPases regulate PRK2/PKN2 to control entry into mitosis and exit from
RT cytokinesis.";
RL EMBO J. 26:1624-1636(2007).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17924679; DOI=10.1021/pr070152u;
RA Yu L.R., Zhu Z., Chan K.C., Issaq H.J., Dimitrov D.S., Veenstra T.D.;
RT "Improved titanium dioxide enrichment of phosphopeptides from HeLa cells
RT and high confident phosphopeptide identification by cross-validation of
RT MS/MS and MS/MS/MS spectra.";
RL J. Proteome Res. 6:4150-4162(2007).
RN [23]
RP ACTIVITY REGULATION, INTERACTION WITH PDPK1, AND MUTAGENESIS OF THR-816;
RP THR-958; PHE-977; ASP-978 AND TYR-979.
RX PubMed=18835241; DOI=10.1016/j.abb.2008.09.008;
RA Lim W.G., Chen X., Liu J.P., Tan B.J., Zhou S., Smith A., Lees N., Hou L.,
RA Gu F., Yu X.Y., Du Y., Smith D., Verma C., Liu K., Duan W.;
RT "The C-terminus of PRK2/PKNgamma is required for optimal activation by RhoA
RT in a GTP-dependent manner.";
RL Arch. Biochem. Biophys. 479:170-178(2008).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-958, 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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-110; THR-121; THR-124;
RP SER-302; SER-306; SER-360; SER-362; SER-535; THR-628; SER-631 AND THR-958,
RP AND 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 [27]
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 [28]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [29]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [30]
RP FUNCTION IN PHOSPHORYLATION OF HDAC5, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=20188095; DOI=10.1016/j.febslet.2010.02.057;
RA Harrison B.C., Huynh K., Lundgaard G.L., Helmke S.M., Perryman M.B.,
RA McKinsey T.A.;
RT "Protein kinase C-related kinase targets nuclear localization signals in a
RT subset of class IIa histone deacetylases.";
RL FEBS Lett. 584:1103-1110(2010).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-302; SER-306; SER-360;
RP SER-583 AND THR-958, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [32]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [33]
RP FUNCTION, INTERACTION WITH RAC1; RHOA AND RHOC, AND SUBCELLULAR LOCATION.
RX PubMed=20974804; DOI=10.1128/mcb.01001-10;
RA Wallace S.W., Magalhaes A., Hall A.;
RT "The Rho target PRK2 regulates apical junction formation in human bronchial
RT epithelial cells.";
RL Mol. Cell. Biol. 31:81-91(2011).
RN [34]
RP FUNCTION IN CELL MIGRATION, AND TISSUE SPECIFICITY.
RX PubMed=21754995; DOI=10.1371/journal.pone.0021732;
RA Lachmann S., Jevons A., De Rycker M., Casamassima A., Radtke S.,
RA Collazos A., Parker P.J.;
RT "Regulatory domain selectivity in the cell-type specific PKN-dependence of
RT cell migration.";
RL PLoS ONE 6:E21732-E21732(2011).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-21; SER-360; SER-583; THR-628
RP AND THR-958, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-952 AND THR-958, AND
RP IDENTIFICATION BY 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 [37]
RP FUNCTION, INTERACTION WITH CDK10, PHOSPHORYLATION AT THR-121 AND THR-124 BY
RP CDK10, AND MUTAGENESIS OF THR-121 AND THR-124.
RX PubMed=27104747; DOI=10.1080/15384101.2016.1147632;
RA Guen V.J., Gamble C., Perez D.E., Bourassa S., Zappel H., Gaertner J.,
RA Lees J.A., Colas P.;
RT "STAR syndrome-associated CDK10/Cyclin M regulates actin network
RT architecture and ciliogenesis.";
RL Cell Cycle 15:678-688(2016).
CC -!- FUNCTION: PKC-related serine/threonine-protein kinase and Rho/Rac
CC effector protein that participates in specific signal transduction
CC responses in the cell. Plays a role in the regulation of cell cycle
CC progression, actin cytoskeleton assembly, cell migration, cell
CC adhesion, tumor cell invasion and transcription activation signaling
CC processes. Phosphorylates CTTN in hyaluronan-induced astrocytes and
CC hence decreases CTTN ability to associate with filamentous actin.
CC Phosphorylates HDAC5, therefore lead to impair HDAC5 import. Direct
CC RhoA target required for the regulation of the maturation of primordial
CC junctions into apical junction formation in bronchial epithelial cells.
CC Required for G2/M phases of the cell cycle progression and abscission
CC during cytokinesis in a ECT2-dependent manner. Stimulates FYN kinase
CC activity that is required for establishment of skin cell-cell adhesion
CC during keratinocytes differentiation. Regulates epithelial bladder
CC cells speed and direction of movement during cell migration and tumor
CC cell invasion. Inhibits Akt pro-survival-induced kinase activity.
CC Mediates Rho protein-induced transcriptional activation via the c-fos
CC serum response factor (SRF). Involved in the negative regulation of
CC ciliogenesis (PubMed:27104747). {ECO:0000269|PubMed:10226025,
CC ECO:0000269|PubMed:10926925, ECO:0000269|PubMed:11777936,
CC ECO:0000269|PubMed:11781095, ECO:0000269|PubMed:15123640,
CC ECO:0000269|PubMed:15364941, ECO:0000269|PubMed:17332740,
CC ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:20974804,
CC ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:27104747,
CC ECO:0000269|PubMed:9121475}.
CC -!- FUNCTION: (Microbial infection) Phosphorylates HCV NS5B leading to
CC stimulation of HCV RNA replication. {ECO:0000269|PubMed:15364941}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13;
CC -!- ACTIVITY REGULATION: Kinase activity is activated upon binding to GTP-
CC bound Rhoa/Rac1 GTPases. Activated by caspase-3 (CASP3) cleavage during
CC apoptosis. Activated by lipids, particularly cardiolipin and to a
CC lesser extent by other acidic phospholipids and unsaturated fatty
CC acids. Two specific sites, Thr-816 (activation loop of the kinase
CC domain) and Thr-958 (turn motif), need to be phosphorylated for its
CC full activation. {ECO:0000269|PubMed:10926925,
CC ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:9368003}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=15.83 uM for HDAC5 {ECO:0000269|PubMed:20188095};
CC -!- SUBUNIT: Interacts (via the REM repeats) with RHOA (GTP-bound form
CC preferentially) and interacts (via the REM repeats) with RAC1 (GTP-
CC bound form preferentially); the interactions induce its
CC autophosphorylation (PubMed:9121475, PubMed:20974804). Interacts with
CC RHOC (PubMed:20974804). Interacts with NCK1 and NCK2 (PubMed:10026169).
CC Interacts with NCK1 (via SH3 domains) (By similarity). Interacts with
CC CD44 (PubMed:15123640). Interacts (via C-terminal kinase domain) with
CC PDPK1; the interaction stimulates PDPK1 kinase activity
CC (PubMed:10226025, PubMed:10792047, PubMed:11781095, PubMed:18835241).
CC Interacts with MAP3K2; the interaction activates PRK2 kinase activity
CC in a MAP3K2-independent kinase activity (PubMed:10818102). Interacts
CC (via C-terminal domain) with AKT1; the interaction occurs with the C-
CC terminal cleavage product of PRK2 in apoptotic cells (PubMed:10926925).
CC Interacts (via C-terminus) with PTPN13 (via PDZ 3 domain)
CC (PubMed:11356191). Interacts with CDK10 (PubMed:27104747).
CC {ECO:0000250|UniProtKB:Q8BWW9, ECO:0000269|PubMed:10026169,
CC ECO:0000269|PubMed:10226025, ECO:0000269|PubMed:10792047,
CC ECO:0000269|PubMed:10818102, ECO:0000269|PubMed:10926925,
CC ECO:0000269|PubMed:11356191, ECO:0000269|PubMed:11781095,
CC ECO:0000269|PubMed:15123640, ECO:0000269|PubMed:15364941,
CC ECO:0000269|PubMed:18835241, ECO:0000269|PubMed:20974804,
CC ECO:0000269|PubMed:27104747, ECO:0000269|PubMed:9121475}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HCV NS5B (via N-terminal
CC finger domain). {ECO:0000269|PubMed:15364941}.
CC -!- INTERACTION:
CC Q16513; Q15118: PDK1; NbExp=6; IntAct=EBI-2511350, EBI-7016221;
CC Q16513; PRO_0000278753 [O92972]; Xeno; NbExp=7; IntAct=EBI-2511350, EBI-10006231;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11356191,
CC ECO:0000269|PubMed:17332740}. Nucleus {ECO:0000269|PubMed:11356191}.
CC Membrane {ECO:0000250|UniProtKB:Q8BWW9}. Cell projection, lamellipodium
CC {ECO:0000269|PubMed:11356191}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:11356191}. Cleavage furrow
CC {ECO:0000269|PubMed:17332740}. Midbody {ECO:0000269|PubMed:17332740}.
CC Cell junction {ECO:0000269|PubMed:20974804}. Note=Colocalizes with
CC PTPN13 in lamellipodia-like structures, regions of large actin
CC turnover. Accumulates during telophase at the cleavage furrow and
CC concentrates finally around the midbody in cytokinesis. Recruited to
CC nascent cell-cell contacts at the apical surface of cells. In the
CC course of viral infection, colocalizes with HCV NS5B at perinuclear
CC region in the cytoplasm. {ECO:0000269|PubMed:11356191,
CC ECO:0000269|PubMed:17332740}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q16513-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16513-2; Sequence=VSP_042183;
CC Name=3;
CC IsoId=Q16513-3; Sequence=VSP_042184;
CC Name=4;
CC IsoId=Q16513-4; Sequence=VSP_042181;
CC Name=5;
CC IsoId=Q16513-5; Sequence=VSP_042180, VSP_042182;
CC -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in numerous tumor cell lines,
CC especially in bladder tumor cells. {ECO:0000269|PubMed:10026169,
CC ECO:0000269|PubMed:21754995}.
CC -!- INDUCTION: Up-regulated during keratinocyte differentiation.
CC {ECO:0000269|PubMed:11777936}.
CC -!- DOMAIN: The N-terminal regioninterferes with the interaction between
CC AKT1 and the C-terminal regionof PKN2.
CC -!- DOMAIN: The C1 domain does not bind the diacylglycerol (DAG).
CC -!- DOMAIN: The apoptotic C-terminal cleavage product inhibits EGF-induced
CC kinase activity of AKT1 phosphorylation at 'Thr-308' and 'Ser-473'
CC sites, PDPK1 autophosphorylation and kinases PRKCD and PRKCZ
CC phosphorylations.
CC -!- PTM: Autophosphorylated. Phosphorylated during mitosis. Phosphorylated
CC by CDK10 (PubMed:27104747). {ECO:0000269|PubMed:10792047,
CC ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:27104747}.
CC -!- PTM: Activated by limited proteolysis with trypsin (By similarity).
CC Proteolytically cleaved by caspase-3 during the induction of apoptotic
CC cell death. {ECO:0000250, ECO:0000269|PubMed:9368003}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; U33052; AAC50208.1; -; mRNA.
DR EMBL; S75548; AAB33346.1; -; mRNA.
DR EMBL; AK298595; BAG60783.1; -; mRNA.
DR EMBL; AK300304; BAG62057.1; -; mRNA.
DR EMBL; AK301066; BAG62673.1; -; mRNA.
DR EMBL; AC119426; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL136381; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471097; EAW73161.1; -; Genomic_DNA.
DR EMBL; CH471097; EAW73164.1; -; Genomic_DNA.
DR EMBL; BC125199; AAI25200.1; -; mRNA.
DR CCDS; CCDS714.1; -. [Q16513-1]
DR CCDS; CCDS81350.1; -. [Q16513-3]
DR PIR; S67527; S67527.
DR RefSeq; NP_001307636.1; NM_001320707.1. [Q16513-3]
DR RefSeq; NP_001307637.1; NM_001320708.1. [Q16513-4]
DR RefSeq; NP_001307638.1; NM_001320709.1. [Q16513-2]
DR RefSeq; NP_006247.1; NM_006256.3. [Q16513-1]
DR RefSeq; XP_011540074.1; XM_011541772.2. [Q16513-5]
DR PDB; 4CRS; X-ray; 2.75 A; A=646-984.
DR PDB; 4RRV; X-ray; 1.41 A; B=969-983.
DR PDB; 6CCY; X-ray; 2.18 A; A=969-983.
DR PDB; 6GBE; NMR; -; B=973-984.
DR PDBsum; 4CRS; -.
DR PDBsum; 4RRV; -.
DR PDBsum; 6CCY; -.
DR PDBsum; 6GBE; -.
DR AlphaFoldDB; Q16513; -.
DR SMR; Q16513; -.
DR BioGRID; 111572; 174.
DR ELM; Q16513; -.
DR IntAct; Q16513; 80.
DR MINT; Q16513; -.
DR STRING; 9606.ENSP00000359552; -.
DR BindingDB; Q16513; -.
DR ChEMBL; CHEMBL3032; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q16513; -.
DR GuidetoPHARMACOLOGY; 1521; -.
DR GlyGen; Q16513; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q16513; -.
DR MetOSite; Q16513; -.
DR PhosphoSitePlus; Q16513; -.
DR BioMuta; PKN2; -.
DR DMDM; 6225859; -.
DR EPD; Q16513; -.
DR jPOST; Q16513; -.
DR MassIVE; Q16513; -.
DR MaxQB; Q16513; -.
DR PaxDb; Q16513; -.
DR PeptideAtlas; Q16513; -.
DR PRIDE; Q16513; -.
DR ProteomicsDB; 60880; -. [Q16513-1]
DR ProteomicsDB; 60881; -. [Q16513-2]
DR ProteomicsDB; 60882; -. [Q16513-3]
DR ProteomicsDB; 60883; -. [Q16513-4]
DR ProteomicsDB; 60884; -. [Q16513-5]
DR Antibodypedia; 33594; 256 antibodies from 34 providers.
DR DNASU; 5586; -.
DR Ensembl; ENST00000370513.9; ENSP00000359544.5; ENSG00000065243.20. [Q16513-3]
DR Ensembl; ENST00000370521.8; ENSP00000359552.3; ENSG00000065243.20. [Q16513-1]
DR GeneID; 5586; -.
DR KEGG; hsa:5586; -.
DR MANE-Select; ENST00000370521.8; ENSP00000359552.3; NM_006256.4; NP_006247.1.
DR UCSC; uc001dmn.4; human. [Q16513-1]
DR CTD; 5586; -.
DR DisGeNET; 5586; -.
DR GeneCards; PKN2; -.
DR HGNC; HGNC:9406; PKN2.
DR HPA; ENSG00000065243; Low tissue specificity.
DR MIM; 602549; gene.
DR neXtProt; NX_Q16513; -.
DR OpenTargets; ENSG00000065243; -.
DR PharmGKB; PA33770; -.
DR VEuPathDB; HostDB:ENSG00000065243; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000154339; -.
DR HOGENOM; CLU_000288_132_1_1; -.
DR InParanoid; Q16513; -.
DR OMA; TECIPEI; -.
DR OrthoDB; 520651at2759; -.
DR PhylomeDB; Q16513; -.
DR TreeFam; TF102005; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; Q16513; -.
DR Reactome; R-HSA-5625740; RHO GTPases activate PKNs.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013026; RHOB GTPase cycle.
DR Reactome; R-HSA-9013106; RHOC GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR SABIO-RK; Q16513; -.
DR SignaLink; Q16513; -.
DR SIGNOR; Q16513; -.
DR BioGRID-ORCS; 5586; 163 hits in 1111 CRISPR screens.
DR ChiTaRS; PKN2; human.
DR GeneWiki; PKN2; -.
DR GenomeRNAi; 5586; -.
DR Pharos; Q16513; Tchem.
DR PRO; PR:Q16513; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q16513; protein.
DR Bgee; ENSG00000065243; Expressed in tongue squamous epithelium and 213 other tissues.
DR ExpressionAtlas; Q16513; baseline and differential.
DR Genevisible; Q16513; HS.
DR GO; GO:0043296; C:apical junction complex; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:HPA.
DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
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:0048471; C:perinuclear region of cytoplasm; IDA:AgBase.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0042826; F:histone deacetylase binding; IDA:UniProtKB.
DR GO; GO:0016301; F:kinase activity; IDA:AgBase.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0070063; F:RNA polymerase binding; IPI:AgBase.
DR GO; GO:0031267; F:small GTPase binding; IEA:InterPro.
DR GO; GO:0043297; P:apical junction assembly; IMP:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0030030; P:cell projection organization; IEA:UniProtKB-KW.
DR GO; GO:0010631; P:epithelial cell migration; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0032467; P:positive regulation of cytokinesis; IMP:UniProtKB.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; IMP:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:AgBase.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:2000145; P:regulation of cell motility; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd08687; C2_PKN-like; 1.
DR CDD; cd11622; HR1_PKN_1; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR037784; C2_PKN.
DR InterPro; IPR011072; HR1_rho-bd.
DR InterPro; IPR036274; HR1_rpt_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR037313; PKN_HR1_1.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF02185; HR1; 3.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR SMART; SM00239; C2; 1.
DR SMART; SM00742; Hr1; 3.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF46585; SSF46585; 3.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS51860; REM_1; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding;
KW Cell adhesion; Cell cycle; Cell division; Cell junction; Cell projection;
KW Cilium biogenesis/degradation; Coiled coil; Cytoplasm; Cytoskeleton;
KW Host-virus interaction; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..984
FT /note="Serine/threonine-protein kinase N2"
FT /id="PRO_0000055722"
FT DOMAIN 33..109
FT /note="REM-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 121..203
FT /note="REM-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 204..284
FT /note="REM-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 353..473
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 657..916
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 917..984
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 114..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 351..383
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 382..463
FT /note="Necessary to rescue apical junction formation"
FT /evidence="ECO:0000250"
FT REGION 558..584
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 917..977
FT /note="Necessary for the catalytic activity"
FT REGION 978..984
FT /note="Negatively regulates the responsiveness of the
FT catalytic activity by cardiolipin and is required for
FT optimal activation by the GTP-bound RhoA"
FT COMPBIAS 355..383
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 782
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 663..671
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 686
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 117..118
FT /note="Cleavage; by caspase-3"
FT SITE 700..701
FT /note="Cleavage; by caspase-3"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 77
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWW9"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 121
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:27104747,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 124
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:27104747,
FT ECO:0007744|PubMed:18669648"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"
FT MOD_RES 306
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 362
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 535
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 583
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 620
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BWW9"
FT MOD_RES 628
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 631
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 816
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:10792047"
FT MOD_RES 952
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 958
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..326
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042180"
FT VAR_SEQ 1..157
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042181"
FT VAR_SEQ 327..329
FT /note="LTG -> MNS (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042182"
FT VAR_SEQ 375..390
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042183"
FT VAR_SEQ 428..475
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042184"
FT VARIANT 94
FT /note="E -> D (in dbSNP:rs12039846)"
FT /id="VAR_050562"
FT VARIANT 197
FT /note="A -> E (in dbSNP:rs35207128)"
FT /id="VAR_050563"
FT VARIANT 655
FT /note="Q -> R (in dbSNP:rs12085658)"
FT /id="VAR_050564"
FT MUTAGEN 117
FT /note="D->A: Prevents proteolytic processing by caspase-3
FT during apoptosis. Diminishes pro-apoptotic function; when
FT associated with E-700."
FT /evidence="ECO:0000269|PubMed:10926925,
FT ECO:0000269|PubMed:9368003"
FT MUTAGEN 121
FT /note="T->A: Does not suppress ciliogenesis; when
FT associated with A-124."
FT /evidence="ECO:0000269|PubMed:27104747"
FT MUTAGEN 124
FT /note="T->A: Does not suppress ciliogenesis; when
FT associated with A-121."
FT /evidence="ECO:0000269|PubMed:27104747"
FT MUTAGEN 686
FT /note="K->R: Does not inhibit interaction with PTPN13."
FT /evidence="ECO:0000269|PubMed:11356191"
FT MUTAGEN 700
FT /note="D->E: Prevents proteolytic processing by caspase-3
FT during apoptosis. Diminishes pro-apoptotic function; when
FT associated with A-117."
FT /evidence="ECO:0000269|PubMed:10926925,
FT ECO:0000269|PubMed:9368003"
FT MUTAGEN 816
FT /note="T->A: Reduces catalytic activity."
FT /evidence="ECO:0000269|PubMed:18835241"
FT MUTAGEN 958
FT /note="T->A: Abolishes catalytic activity."
FT /evidence="ECO:0000269|PubMed:18835241"
FT MUTAGEN 974
FT /note="F->A: Abolishes interaction with PDPK1 and prevents
FT the phosphorylation of AKT1 at 'Ser-473'."
FT /evidence="ECO:0000269|PubMed:10226025"
FT MUTAGEN 977
FT /note="F->A,L: Abolishes interaction with PDPK1 and
FT prevents the phosphorylation of AKT1 at 'Ser-473'. Reduces
FT catalytic activity by 90%."
FT /evidence="ECO:0000269|PubMed:10226025,
FT ECO:0000269|PubMed:18835241"
FT MUTAGEN 977
FT /note="F->W,Y: Reduces catalytic activity by 50%."
FT /evidence="ECO:0000269|PubMed:10226025,
FT ECO:0000269|PubMed:18835241"
FT MUTAGEN 978
FT /note="D->A,S: Abolishes interaction with PDPK1 and
FT prevents the phosphorylation of AKT1 at 'Ser-473'."
FT /evidence="ECO:0000269|PubMed:10226025,
FT ECO:0000269|PubMed:18835241"
FT MUTAGEN 978
FT /note="D->A: Does not inhibit catalytic activity."
FT /evidence="ECO:0000269|PubMed:10226025,
FT ECO:0000269|PubMed:18835241"
FT MUTAGEN 979
FT /note="Y->A: Abolishes interaction with PDPK1 and prevents
FT the phosphorylation of AKT1 at 'Ser-473'."
FT /evidence="ECO:0000269|PubMed:10226025,
FT ECO:0000269|PubMed:18835241"
FT MUTAGEN 979
FT /note="Y->A: Reduces catalytic activity by 50%."
FT /evidence="ECO:0000269|PubMed:10226025,
FT ECO:0000269|PubMed:18835241"
FT MUTAGEN 979
FT /note="Y->F,L,W: Reduces catalytic activity by 25%."
FT /evidence="ECO:0000269|PubMed:10226025,
FT ECO:0000269|PubMed:18835241"
FT MUTAGEN 984
FT /note="C->S: Inhibits interaction with PTPN13."
FT /evidence="ECO:0000269|PubMed:11356191"
FT CONFLICT 483
FT /note="I -> V (in Ref. 3; BAG62673)"
FT /evidence="ECO:0000305"
FT CONFLICT 565
FT /note="K -> R (in Ref. 3; BAG60783)"
FT /evidence="ECO:0000305"
FT CONFLICT 625
FT /note="K -> R (in Ref. 3; BAG62673)"
FT /evidence="ECO:0000305"
FT CONFLICT 795
FT /note="F -> L (in Ref. 6; AAI25200)"
FT /evidence="ECO:0000305"
FT HELIX 647..649
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 652..654
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 657..665
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 670..676
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 682..689
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 690..695
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 699..714
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 723..729
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 732..738
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 745..749
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 756..774
FT /evidence="ECO:0007829|PDB:4CRS"
FT TURN 775..777
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 785..787
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 788..790
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 796..798
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 805..807
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 821..823
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 826..830
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 838..852
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 862..871
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 882..891
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 896..898
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 903..905
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 907..911
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 914..916
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 921..925
FT /evidence="ECO:0007829|PDB:4CRS"
FT STRAND 944..946
FT /evidence="ECO:0007829|PDB:4CRS"
FT HELIX 948..951
FT /evidence="ECO:0007829|PDB:4CRS"
FT TURN 973..976
FT /evidence="ECO:0007829|PDB:6CCY"
SQ SEQUENCE 984 AA; 112035 MW; 687EC417A0F51C1D CRC64;
MASNPERGEI LLTELQGDSR SLPFSENVSA VQKLDFSDTM VQQKLDDIKD RIKREIRKEL
KIKEGAENLR KVTTDKKSLA YVDNILKKSN KKLEELHHKL QELNAHIVVS DPEDITDCPR
TPDTPNNDPR CSTSNNRLKA LQKQLDIELK VKQGAENMIQ MYSNGSSKDR KLHGTAQQLL
QDSKTKIEVI RMQILQAVQT NELAFDNAKP VISPLELRME ELRHHFRIEF AVAEGAKNVM
KLLGSGKVTD RKALSEAQAR FNESSQKLDL LKYSLEQRLN EVPKNHPKSR IIIEELSLVA
ASPTLSPRQS MISTQNQYST LSKPAALTGT LEVRLMGCQD ILENVPGRSK ATSVALPGWS
PSETRSSFMS RTSKSKSGSS RNLLKTDDLS NDVCAVLKLD NTVVGQTSWK PISNQSWDQK
FTLELDRSRE LEISVYWRDW RSLCAVKFLR LEDFLDNQRH GMCLYLEPQG TLFAEVTFFN
PVIERRPKLQ RQKKIFSKQQ GKTFLRAPQM NINIATWGRL VRRAIPTVNH SGTFSPQAPV
PTTVPVVDVR IPQLAPPASD STVTKLDFDL EPEPPPAPPR ASSLGEIDES SELRVLDIPG
QDSETVFDIQ NDRNSILPKS QSEYKPDTPQ SGLEYSGIQE LEDRRSQQRF QFNLQDFRCC
AVLGRGHFGK VLLAEYKNTN EMFAIKALKK GDIVARDEVD SLMCEKRIFE TVNSVRHPFL
VNLFACFQTK EHVCFVMEYA AGGDLMMHIH TDVFSEPRAV FYAACVVLGL QYLHEHKIVY
RDLKLDNLLL DTEGFVKIAD FGLCKEGMGY GDRTSTFCGT PEFLAPEVLT ETSYTRAVDW
WGLGVLIYEM LVGESPFPGD DEEEVFDSIV NDEVRYPRFL STEAISIMRR LLRRNPERRL
GASEKDAEDV KKHPFFRLID WSALMDKKVK PPFIPTIRGR EDVSNFDDEF TSEAPILTPP
REPRILSEEE QEMFRDFDYI ADWC
