PKN1_HUMAN
ID PKN1_HUMAN Reviewed; 942 AA.
AC Q16512; A8K7W5; B2R9R4; B3KVN3; Q15143; Q504U4; Q8IUV5; Q9UD44;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 234.
DE RecName: Full=Serine/threonine-protein kinase N1;
DE EC=2.7.11.13 {ECO:0000269|PubMed:18066052};
DE AltName: Full=Protease-activated kinase 1;
DE Short=PAK-1;
DE AltName: Full=Protein kinase C-like 1;
DE AltName: Full=Protein kinase C-like PKN;
DE AltName: Full=Protein kinase PKN-alpha;
DE AltName: Full=Protein-kinase C-related kinase 1;
DE AltName: Full=Serine-threonine protein kinase N;
GN Name=PKN1; Synonyms=PAK1, PKN, PRK1, PRKCL1;
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), AND MUTAGENESIS OF LYS-644.
RC TISSUE=Hippocampus;
RX PubMed=8135837; DOI=10.1006/bbrc.1994.1313;
RA Mukai H., Ono Y.;
RT "A novel protein kinase with leucine zipper-like sequences: its catalytic
RT domain is highly homologous to that of protein kinase C.";
RL Biochem. Biophys. Res. Commun. 199:897-904(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fetal brain;
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 1 AND 2), AND VARIANTS
RP ILE-555 AND ILE-901.
RC TISSUE=Kidney, Synovium, and Thymus;
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=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP ILE-901.
RC TISSUE=Brain, and Placenta;
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 [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 700-800 (ISOFORMS 1/2), AND VARIANT VAL-718.
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 [7]
RP FUNCTION.
RX PubMed=8557118; DOI=10.1016/0014-5793(95)01454-3;
RA Palmer R.H., Schonwasser D.C., Rahman D., Pappin D.J., Herget T.,
RA Parker P.J.;
RT "PRK1 phosphorylates MARCKS at the PKC sites: serine 152, serine 156 and
RT serine 163.";
RL FEBS Lett. 378:281-285(1996).
RN [8]
RP FUNCTION.
RX PubMed=8621664; DOI=10.1074/jbc.271.16.9816;
RA Mukai H., Toshimori M., Shibata H., Kitagawa M., Shimakawa M., Miyahara M.,
RA Sunakawa H., Ono Y.;
RT "PKN associates and phosphorylates the head-rod domain of neurofilament
RT protein.";
RL J. Biol. Chem. 271:9816-9822(1996).
RN [9]
RP ACTIVITY REGULATION, AND INTERACTION WITH RHOA.
RX PubMed=8571126; DOI=10.1126/science.271.5249.645;
RA Watanabe G., Saito Y., Madaule P., Ishizaki T., Fujisawa K., Morii N.,
RA Mukai H., Ono Y., Kakizuka A., Narumiya S.;
RT "Protein kinase N (PKN) and PKN-related protein rhophilin as targets of
RT small GTPase Rho.";
RL Science 271:645-648(1996).
RN [10]
RP FUNCTION.
RX PubMed=9175763; DOI=10.1006/bbrc.1997.6669;
RA Matsuzawa K., Kosako H., Inagaki N., Shibata H., Mukai H., Ono Y.,
RA Amano M., Kaibuchi K., Matsuura Y., Azuma I., Inagaki M.;
RT "Domain-specific phosphorylation of vimentin and glial fibrillary acidic
RT protein by PKN.";
RL Biochem. Biophys. Res. Commun. 234:621-625(1997).
RN [11]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH RHOB.
RX PubMed=9478917; DOI=10.1074/jbc.273.9.4811;
RA Mellor H., Flynn P., Nobes C.D., Hall A., Parker P.J.;
RT "PRK1 is targeted to endosomes by the small GTPase, RhoB.";
RL J. Biol. Chem. 273:4811-4814(1998).
RN [12]
RP ACTIVITY REGULATION, PROTEOLYTIC PROCESSING, AND MUTAGENESIS OF ASP-108;
RP ASP-451; ASP-454; ASP-558 AND ASP-560.
RX PubMed=9751706; DOI=10.1073/pnas.95.20.11566;
RA Takahashi M., Mukai H., Toshimori M., Miyamoto M., Ono Y.;
RT "Proteolytic activation of PKN by caspase-3 or related protease during
RT apoptosis.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:11566-11571(1998).
RN [13]
RP PHOSPHORYLATION AT THR-774 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 [14]
RP FUNCTION.
RX PubMed=11104762; DOI=10.1074/jbc.m007427200;
RA Taniguchi T., Kawamata T., Mukai H., Hasegawa H., Isagawa T., Yasuda M.,
RA Hashimoto T., Terashima A., Nakai M., Mori H., Ono Y., Tanaka C.;
RT "Phosphorylation of tau is regulated by PKN.";
RL J. Biol. Chem. 276:10025-10031(2001).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH AR.
RX PubMed=12514133; DOI=10.1093/emboj/cdg023;
RA Metzger E., Muller J.M., Ferrari S., Buettner R., Schule R.;
RT "A novel inducible transactivation domain in the androgen receptor:
RT implications for PRK in prostate cancer.";
RL EMBO J. 22:270-280(2003).
RN [16]
RP INTERACTION WITH S.TYPHIMURIUM SSPH1 (MICROBIAL INFECTION).
RX PubMed=16611232; DOI=10.1111/j.1462-5822.2005.00670.x;
RA Haraga A., Miller S.I.;
RT "A Salmonella type III secretion effector interacts with the mammalian
RT serine/threonine protein kinase PKN1.";
RL Cell. Microbiol. 8:837-846(2006).
RN [17]
RP INTERACTION WITH CCNT2.
RX PubMed=16331689; DOI=10.1002/jcp.20566;
RA Cottone G., Baldi A., Palescandolo E., Manente L., Penta R., Paggi M.G.,
RA De Luca A.;
RT "Pkn is a novel partner of cyclin T2a in muscle differentiation.";
RL J. Cell. Physiol. 207:232-237(2006).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-533 AND SER-562, 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 [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-778, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205 AND SER-537, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF LYS-644.
RX PubMed=18066052; DOI=10.1038/ncb1668;
RA Metzger E., Yin N., Wissmann M., Kunowska N., Fischer K., Friedrichs N.,
RA Patnaik D., Higgins J.M., Potier N., Scheidtmann K.H., Buettner R.,
RA Schule R.;
RT "Phosphorylation of histone H3 at threonine 11 establishes a novel
RT chromatin mark for transcriptional regulation.";
RL Nat. Cell Biol. 10:53-60(2008).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-533; SER-537; SER-559;
RP SER-562 AND SER-916, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP 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 [24]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [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 [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205; SER-533; SER-537;
RP SER-559; SER-562; THR-914 AND SER-916, AND IDENTIFICATION BY MASS
RP 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 [26]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-448, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [27]
RP FUNCTION, 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 [28]
RP INTERACTION WITH PRKCB.
RX PubMed=20228790; DOI=10.1038/nature08839;
RA Metzger E., Imhof A., Patel D., Kahl P., Hoffmeyer K., Friedrichs N.,
RA Muller J.M., Greschik H., Kirfel J., Ji S., Kunowska N.,
RA Beisenherz-Huss C., Gunther T., Buettner R., Schule R.;
RT "Phosphorylation of histone H3T6 by PKCbeta(I) controls demethylation at
RT histone H3K4.";
RL Nature 464:792-796(2010).
RN [29]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-533; SER-537 AND SER-562, 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 [30]
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 [31]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH AKAP13; MAPK14; ZAK AND
RP MAP2K3.
RX PubMed=21224381; DOI=10.1074/jbc.m110.185645;
RA Cariolato L., Cavin S., Diviani D.;
RT "A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling
RT complex involved in alpha1-adrenergic receptor-induced p38 activation.";
RL J. Biol. Chem. 286:7925-7937(2011).
RN [32]
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 [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-562, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [34]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-69; SER-533; SER-537;
RP SER-540; SER-562; SER-608 AND SER-916, AND IDENTIFICATION BY MASS
RP 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 [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-916, 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 [37]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 13-98 IN COMPLEX WITH RHOA.
RX PubMed=10619026; DOI=10.1016/s1097-2765(00)80389-5;
RA Maesaki R., Ihara K., Shimizu T., Kuroda S., Kaibuchi K., Hakoshima T.;
RT "The structural basis of Rho effector recognition revealed by the crystal
RT structure of human RhoA complexed with the effector domain of PKN/PRK1.";
RL Mol. Cell 4:793-803(1999).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 13-98.
RX PubMed=10388627; DOI=10.1006/jsbi.1999.4114;
RA Maesaki R., Shimizu T., Ihara K., Kuroda S., Kaibuchi K., Hakoshima T.;
RT "Biochemical and crystallographic characterization of a Rho effector domain
RT of the protein serine/threonine kinase N in a complex with RhoA.";
RL J. Struct. Biol. 126:166-170(1999).
RN [39]
RP STRUCTURE BY NMR OF 116-199 IN COMPLEX WITH RAC1.
RX PubMed=14514689; DOI=10.1074/jbc.m304313200;
RA Owen D., Lowe P.N., Nietlispach D., Brosnan C.E., Chirgadze D.Y.,
RA Parker P.J., Blundell T.L., Mott H.R.;
RT "Molecular dissection of the interaction between the small G proteins Rac1
RT and RhoA and protein kinase C-related kinase 1 (PRK1).";
RL J. Biol. Chem. 278:50578-50587(2003).
RN [40]
RP STRUCTURE BY NMR OF 122-199 IN COMPLEX WITH RAC1.
RX PubMed=18006505; DOI=10.1074/jbc.m706760200;
RA Modha R., Campbell L.J., Nietlispach D., Buhecha H.R., Owen D., Mott H.R.;
RT "The Rac1 polybasic region is required for interaction with its effector
RT PRK1.";
RL J. Biol. Chem. 283:1492-1500(2008).
RN [41]
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 122-199 IN COMPLEX WITH
RP SALMONELLA SSPH1, UBIQUITINATION (MICROBIAL INFECTION), MUTAGENESIS OF
RP ARG-181 AND ARG-185, FUNCTION AS ANDROGEN RECEPTOR COACTIVATOR, AND
RP INTERACTION WITH SALMONELLA SSPH1 (MICROBIAL INFECTION).
RX PubMed=24248594; DOI=10.1128/mcb.01360-13;
RA Keszei A.F., Tang X., McCormick C., Zeqiraj E., Rohde J.R., Tyers M.,
RA Sicheri F.;
RT "Structure of an SspH1-PKN1 complex reveals the basis for host substrate
RT recognition and mechanism of activation for a bacterial E3 ubiquitin
RT ligase.";
RL Mol. Cell. Biol. 34:362-373(2014).
RN [42]
RP VARIANTS [LARGE SCALE ANALYSIS] CYS-185; GLU-197; TRP-436; GLN-520;
RP ILE-555; GLN-635; VAL-718; LEU-873; ILE-901 AND VAL-921.
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: PKC-related serine/threonine-protein kinase involved in
CC various processes such as regulation of the intermediate filaments of
CC the actin cytoskeleton, cell migration, tumor cell invasion and
CC transcription regulation. Part of a signaling cascade that begins with
CC the activation of the adrenergic receptor ADRA1B and leads to the
CC activation of MAPK14. Regulates the cytoskeletal network by
CC phosphorylating proteins such as VIM and neurofilament proteins NEFH,
CC NEFL and NEFM, leading to inhibit their polymerization. Phosphorylates
CC 'Ser-575', 'Ser-637' and 'Ser-669' of MAPT/Tau, lowering its ability to
CC bind to microtubules, resulting in disruption of tubulin assembly. Acts
CC as a key coactivator of androgen receptor (AR)-dependent transcription,
CC by being recruited to AR target genes and specifically mediating
CC phosphorylation of 'Thr-11' of histone H3 (H3T11ph), a specific tag for
CC epigenetic transcriptional activation that promotes demethylation of
CC histone H3 'Lys-9' (H3K9me) by KDM4C/JMJD2C. Phosphorylates HDAC5,
CC HDAC7 and HDAC9, leading to impair their import in the nucleus.
CC Phosphorylates 'Thr-38' of PPP1R14A, 'Ser-159', 'Ser-163' and 'Ser-170'
CC of MARCKS, and GFAP. Able to phosphorylate RPS6 in vitro.
CC {ECO:0000269|PubMed:11104762, ECO:0000269|PubMed:12514133,
CC ECO:0000269|PubMed:17332740, ECO:0000269|PubMed:18066052,
CC ECO:0000269|PubMed:20188095, ECO:0000269|PubMed:21224381,
CC ECO:0000269|PubMed:21754995, ECO:0000269|PubMed:24248594,
CC ECO:0000269|PubMed:8557118, ECO:0000269|PubMed:8621664,
CC ECO:0000269|PubMed:9175763}.
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 Evidence={ECO:0000269|PubMed:18066052};
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; Evidence={ECO:0000269|PubMed:18066052};
CC -!- ACTIVITY REGULATION: Kinase activity is activated upon binding to Rho
CC proteins (RHOA, RHOB and RAC1). Activated by lipids, particularly
CC cardiolipin and to a lesser extent by other acidic phospholipids.
CC Activated by caspase-3 (CASP3) cleavage during apoptosis. Two specific
CC sites, Thr-774 (activation loop of the kinase domain) and Ser-916 (turn
CC motif), need to be phosphorylated for its full activation.
CC {ECO:0000269|PubMed:8571126, ECO:0000269|PubMed:9751706}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20.6 uM for HDAC5 {ECO:0000269|PubMed:20188095};
CC -!- SUBUNIT: Interacts with ZFAND6 (By similarity). Interacts with AR
CC (PubMed:12514133). Interacts with PRKCB (PubMed:20228790). Interacts
CC (via REM 1 and REM 2 repeats) with RAC1 (PubMed:14514689,
CC PubMed:18006505). Interacts (via REM 1 repeat) with RHOA
CC (PubMed:10619026, PubMed:8571126). Interacts with RHOB
CC (PubMed:9478917). Interacts (via C-terminus) with PDPK1
CC (PubMed:10792047). Interacts with CCNT2; enhances MYOD1-dependent
CC transcription (PubMed:16331689). Component of a signaling complex
CC containing at least AKAP13, PKN1, MAPK14, ZAK and MAP2K3. Within this
CC complex, AKAP13 interacts directly with PKN1, which in turn recruits
CC MAPK14, MAP2K3 and ZAK (PubMed:21224381).
CC {ECO:0000250|UniProtKB:P70268, ECO:0000269|PubMed:10619026,
CC ECO:0000269|PubMed:10792047, ECO:0000269|PubMed:12514133,
CC ECO:0000269|PubMed:14514689, ECO:0000269|PubMed:16331689,
CC ECO:0000269|PubMed:18006505, ECO:0000269|PubMed:20228790,
CC ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:8571126,
CC ECO:0000269|PubMed:9478917}.
CC -!- SUBUNIT: (Microbial infection) Interacts (via the second REM repeat)
CC with S.typhimurium E3 ubiquitin-protein ligase SspH1 (via the leucine-
CC rich repeat region) (PubMed:16611232, PubMed:24248594).
CC {ECO:0000269|PubMed:16611232, ECO:0000269|PubMed:24248594}.
CC -!- INTERACTION:
CC Q16512; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-602382, EBI-10173507;
CC Q16512; Q9ULX6: AKAP8L; NbExp=3; IntAct=EBI-602382, EBI-357530;
CC Q16512; Q6PJH3: AKAP9; NbExp=3; IntAct=EBI-602382, EBI-11745576;
CC Q16512; P05067: APP; NbExp=3; IntAct=EBI-602382, EBI-77613;
CC Q16512; P15289: ARSA; NbExp=3; IntAct=EBI-602382, EBI-2117357;
CC Q16512; Q14457: BECN1; NbExp=3; IntAct=EBI-602382, EBI-949378;
CC Q16512; Q9H2G9: BLZF1; NbExp=3; IntAct=EBI-602382, EBI-2548012;
CC Q16512; Q8WU43: C2orf15; NbExp=3; IntAct=EBI-602382, EBI-12904676;
CC Q16512; Q8IW40: CCDC103; NbExp=3; IntAct=EBI-602382, EBI-10261970;
CC Q16512; Q96M89-2: CCDC138; NbExp=3; IntAct=EBI-602382, EBI-10972887;
CC Q16512; Q15834: CCDC85B; NbExp=2; IntAct=EBI-602382, EBI-739674;
CC Q16512; Q8IV13: CCNJL; NbExp=3; IntAct=EBI-602382, EBI-21668062;
CC Q16512; Q01850: CDR2; NbExp=6; IntAct=EBI-602382, EBI-1181367;
CC Q16512; Q86XR8-3: CEP57; NbExp=3; IntAct=EBI-602382, EBI-11752486;
CC Q16512; Q8IYX8-2: CEP57L1; NbExp=3; IntAct=EBI-602382, EBI-10181988;
CC Q16512; Q8NHQ1: CEP70; NbExp=3; IntAct=EBI-602382, EBI-739624;
CC Q16512; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-602382, EBI-3867333;
CC Q16512; Q9NRI5-2: DISC1; NbExp=3; IntAct=EBI-602382, EBI-11988027;
CC Q16512; Q8WWB3: DYDC1; NbExp=3; IntAct=EBI-602382, EBI-740680;
CC Q16512; P26641: EEF1G; NbExp=3; IntAct=EBI-602382, EBI-351467;
CC Q16512; O00303: EIF3F; NbExp=3; IntAct=EBI-602382, EBI-711990;
CC Q16512; Q06547-2: GABPB1; NbExp=3; IntAct=EBI-602382, EBI-618189;
CC Q16512; Q08379: GOLGA2; NbExp=6; IntAct=EBI-602382, EBI-618309;
CC Q16512; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-602382, EBI-5916454;
CC Q16512; P54257: HAP1; NbExp=3; IntAct=EBI-602382, EBI-712814;
CC Q16512; Q96CS2: HAUS1; NbExp=3; IntAct=EBI-602382, EBI-2514791;
CC Q16512; Q9NSC5: HOMER3; NbExp=7; IntAct=EBI-602382, EBI-748420;
CC Q16512; O75031: HSF2BP; NbExp=3; IntAct=EBI-602382, EBI-7116203;
CC Q16512; Q9UKT9: IKZF3; NbExp=3; IntAct=EBI-602382, EBI-747204;
CC Q16512; Q5TA45: INTS11; NbExp=3; IntAct=EBI-602382, EBI-748258;
CC Q16512; Q8N5Z5: KCTD17; NbExp=3; IntAct=EBI-602382, EBI-743960;
CC Q16512; Q86T90: KIAA1328; NbExp=3; IntAct=EBI-602382, EBI-3437878;
CC Q16512; P19012: KRT15; NbExp=3; IntAct=EBI-602382, EBI-739566;
CC Q16512; P08779: KRT16; NbExp=3; IntAct=EBI-602382, EBI-356410;
CC Q16512; P08727: KRT19; NbExp=3; IntAct=EBI-602382, EBI-742756;
CC Q16512; Q15323: KRT31; NbExp=6; IntAct=EBI-602382, EBI-948001;
CC Q16512; O76011: KRT34; NbExp=5; IntAct=EBI-602382, EBI-1047093;
CC Q16512; Q92764: KRT35; NbExp=3; IntAct=EBI-602382, EBI-1058674;
CC Q16512; O76013-2: KRT36; NbExp=3; IntAct=EBI-602382, EBI-11958506;
CC Q16512; O76014: KRT37; NbExp=3; IntAct=EBI-602382, EBI-1045716;
CC Q16512; Q9BV99: LRRC61; NbExp=3; IntAct=EBI-602382, EBI-2350424;
CC Q16512; Q9NYL2-1: MAP3K20; NbExp=2; IntAct=EBI-602382, EBI-687346;
CC Q16512; P53778: MAPK12; NbExp=2; IntAct=EBI-602382, EBI-602406;
CC Q16512; O15344: MID1; NbExp=3; IntAct=EBI-602382, EBI-2340316;
CC Q16512; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-602382, EBI-10172526;
CC Q16512; Q8N108-16: MIER1; NbExp=3; IntAct=EBI-602382, EBI-25830642;
CC Q16512; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-602382, EBI-2548751;
CC Q16512; Q13064: MKRN3; NbExp=3; IntAct=EBI-602382, EBI-2340269;
CC Q16512; Q5JR59-3: MTUS2; NbExp=3; IntAct=EBI-602382, EBI-11522433;
CC Q16512; P07196: NEFL; NbExp=3; IntAct=EBI-602382, EBI-475646;
CC Q16512; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-602382, EBI-79165;
CC Q16512; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-602382, EBI-302345;
CC Q16512; P78424: POU6F2; NbExp=3; IntAct=EBI-602382, EBI-12029004;
CC Q16512; P28070: PSMB4; NbExp=3; IntAct=EBI-602382, EBI-603350;
CC Q16512; Q96QF0-7: RAB3IP; NbExp=3; IntAct=EBI-602382, EBI-11984839;
CC Q16512; Q9UJW9: SERTAD3; NbExp=3; IntAct=EBI-602382, EBI-748621;
CC Q16512; Q9H7B4: SMYD3; NbExp=3; IntAct=EBI-602382, EBI-347919;
CC Q16512; Q96R06: SPAG5; NbExp=3; IntAct=EBI-602382, EBI-413317;
CC Q16512; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-602382, EBI-2212028;
CC Q16512; Q9NZ72: STMN3; NbExp=3; IntAct=EBI-602382, EBI-725557;
CC Q16512; O75558: STX11; NbExp=3; IntAct=EBI-602382, EBI-714135;
CC Q16512; A1L190: SYCE3; NbExp=3; IntAct=EBI-602382, EBI-10283466;
CC Q16512; Q8WTV1: THAP3; NbExp=3; IntAct=EBI-602382, EBI-17438286;
CC Q16512; Q13077: TRAF1; NbExp=3; IntAct=EBI-602382, EBI-359224;
CC Q16512; Q12933: TRAF2; NbExp=3; IntAct=EBI-602382, EBI-355744;
CC Q16512; P14373: TRIM27; NbExp=3; IntAct=EBI-602382, EBI-719493;
CC Q16512; Q9BZW7: TSGA10; NbExp=3; IntAct=EBI-602382, EBI-744794;
CC Q16512; Q8IWV8-2: UBR2; NbExp=3; IntAct=EBI-602382, EBI-17923957;
CC Q16512; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-602382, EBI-739895;
CC Q16512; P08670: VIM; NbExp=3; IntAct=EBI-602382, EBI-353844;
CC Q16512; Q8TF47: ZFP90; NbExp=3; IntAct=EBI-602382, EBI-11419867;
CC Q16512; Q9UNY5: ZNF232; NbExp=3; IntAct=EBI-602382, EBI-749023;
CC Q16512; Q96MN9-2: ZNF488; NbExp=3; IntAct=EBI-602382, EBI-25831733;
CC Q16512; Q9P0T4: ZNF581; NbExp=3; IntAct=EBI-602382, EBI-745520;
CC Q16512; Q9UGI0: ZRANB1; NbExp=3; IntAct=EBI-602382, EBI-527853;
CC Q16512; A1JU68: yopM; Xeno; NbExp=2; IntAct=EBI-602382, EBI-26365850;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17332740,
CC ECO:0000269|PubMed:9478917}. Nucleus {ECO:0000269|PubMed:12514133}.
CC Endosome {ECO:0000269|PubMed:9478917}. Cell membrane
CC {ECO:0000250|UniProtKB:Q63433}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q63433}. Cleavage furrow
CC {ECO:0000269|PubMed:17332740}. Midbody {ECO:0000269|PubMed:17332740}.
CC Note=Associates with chromatin in a ligand-dependent manner.
CC Localization to endosomes is mediated via its interaction with RHOB.
CC Association to the cell membrane is dependent on Ser-377
CC phosphorylation. Accumulates during telophase at the cleavage furrow
CC and finally concentrates around the midbody in cytokinesis.
CC {ECO:0000250|UniProtKB:Q63433, ECO:0000269|PubMed:17332740}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q16512-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16512-2; Sequence=VSP_038143;
CC Name=3;
CC IsoId=Q16512-3; Sequence=VSP_039213, VSP_039214;
CC -!- TISSUE SPECIFICITY: Found ubiquitously. Expressed in heart, brain,
CC placenta, lung, skeletal muscle, kidney and pancreas. Expressed in
CC numerous tumor cell lines, especially in breast tumor cells.
CC {ECO:0000269|PubMed:21754995}.
CC -!- DOMAIN: The C1 domain does not bind the diacylglycerol (DAG).
CC -!- PTM: Autophosphorylated; preferably on serine. Phosphorylated during
CC mitosis. {ECO:0000269|PubMed:10792047, ECO:0000269|PubMed:17332740}.
CC -!- PTM: Activated by limited proteolysis with trypsin. {ECO:0000250}.
CC -!- PTM: (Microbial infection) In case of infection, polyubiquitinated by
CC the bacterial E3 ubiquitin-protein ligase SspH1, leading to its
CC proteasomal degradation. {ECO:0000269|PubMed:24248594}.
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; D26181; BAA05169.1; -; mRNA.
DR EMBL; S75546; AAB33345.1; -; mRNA.
DR EMBL; U33053; AAC50209.1; -; mRNA.
DR EMBL; AK123007; BAG53845.1; -; mRNA.
DR EMBL; AK292130; BAF84819.1; -; mRNA.
DR EMBL; AK313886; BAG36611.1; -; mRNA.
DR EMBL; AC008569; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC040061; AAH40061.1; -; mRNA.
DR EMBL; BC094766; AAH94766.1; -; mRNA.
DR CCDS; CCDS42513.1; -. [Q16512-1]
DR CCDS; CCDS42514.1; -. [Q16512-2]
DR PIR; JC2129; JC2129.
DR PIR; S51162; S51162.
DR RefSeq; NP_002732.3; NM_002741.3. [Q16512-1]
DR RefSeq; NP_998725.1; NM_213560.1. [Q16512-2]
DR PDB; 1CXZ; X-ray; 2.20 A; B=13-98.
DR PDB; 1URF; NMR; -; A=122-199.
DR PDB; 2RMK; NMR; -; B=122-199.
DR PDB; 4NKG; X-ray; 2.90 A; B/D=122-199.
DR PDB; 4OTD; X-ray; 2.00 A; A=605-942.
DR PDB; 4OTG; X-ray; 2.60 A; A=605-942.
DR PDB; 4OTH; X-ray; 1.80 A; A=605-942.
DR PDB; 4OTI; X-ray; 1.93 A; A=605-942.
DR PDBsum; 1CXZ; -.
DR PDBsum; 1URF; -.
DR PDBsum; 2RMK; -.
DR PDBsum; 4NKG; -.
DR PDBsum; 4OTD; -.
DR PDBsum; 4OTG; -.
DR PDBsum; 4OTH; -.
DR PDBsum; 4OTI; -.
DR AlphaFoldDB; Q16512; -.
DR SMR; Q16512; -.
DR BioGRID; 111571; 125.
DR CORUM; Q16512; -.
DR DIP; DIP-34240N; -.
DR ELM; Q16512; -.
DR IntAct; Q16512; 96.
DR MINT; Q16512; -.
DR STRING; 9606.ENSP00000343325; -.
DR BindingDB; Q16512; -.
DR ChEMBL; CHEMBL3384; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q16512; -.
DR GuidetoPHARMACOLOGY; 1520; -.
DR GlyConnect; 1737; 1 N-Linked glycan (1 site).
DR GlyGen; Q16512; 3 sites, 1 N-linked glycan (1 site), 1 O-linked glycan (2 sites).
DR iPTMnet; Q16512; -.
DR MetOSite; Q16512; -.
DR PhosphoSitePlus; Q16512; -.
DR BioMuta; PKN1; -.
DR DMDM; 259016304; -.
DR EPD; Q16512; -.
DR jPOST; Q16512; -.
DR MassIVE; Q16512; -.
DR MaxQB; Q16512; -.
DR PaxDb; Q16512; -.
DR PeptideAtlas; Q16512; -.
DR PRIDE; Q16512; -.
DR ProteomicsDB; 60877; -. [Q16512-1]
DR ProteomicsDB; 60878; -. [Q16512-2]
DR ProteomicsDB; 60879; -. [Q16512-3]
DR Antibodypedia; 1296; 252 antibodies from 34 providers.
DR DNASU; 5585; -.
DR Ensembl; ENST00000242783.11; ENSP00000242783.7; ENSG00000123143.13. [Q16512-1]
DR Ensembl; ENST00000342216.8; ENSP00000343325.4; ENSG00000123143.13. [Q16512-2]
DR GeneID; 5585; -.
DR KEGG; hsa:5585; -.
DR MANE-Select; ENST00000242783.11; ENSP00000242783.7; NM_002741.5; NP_002732.3.
DR UCSC; uc002myp.4; human. [Q16512-1]
DR CTD; 5585; -.
DR DisGeNET; 5585; -.
DR GeneCards; PKN1; -.
DR HGNC; HGNC:9405; PKN1.
DR HPA; ENSG00000123143; Low tissue specificity.
DR MIM; 601032; gene.
DR neXtProt; NX_Q16512; -.
DR OpenTargets; ENSG00000123143; -.
DR PharmGKB; PA33769; -.
DR VEuPathDB; HostDB:ENSG00000123143; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000154990; -.
DR HOGENOM; CLU_000288_132_1_1; -.
DR InParanoid; Q16512; -.
DR OMA; CTELRIE; -.
DR OrthoDB; 520651at2759; -.
DR PhylomeDB; Q16512; -.
DR TreeFam; TF102005; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; Q16512; -.
DR Reactome; R-HSA-5625740; RHO GTPases activate PKNs.
DR Reactome; R-HSA-5625886; Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3.
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; Q16512; -.
DR SignaLink; Q16512; -.
DR SIGNOR; Q16512; -.
DR BioGRID-ORCS; 5585; 15 hits in 1115 CRISPR screens.
DR ChiTaRS; PKN1; human.
DR EvolutionaryTrace; Q16512; -.
DR GeneWiki; Protein_kinase_N1; -.
DR GenomeRNAi; 5585; -.
DR Pharos; Q16512; Tchem.
DR PRO; PR:Q16512; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q16512; protein.
DR Bgee; ENSG00000123143; Expressed in apex of heart and 140 other tissues.
DR ExpressionAtlas; Q16512; baseline and differential.
DR Genevisible; Q16512; HS.
DR GO; GO:0032154; C:cleavage furrow; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0030496; C:midbody; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IDA:UniProtKB.
DR GO; GO:0042826; F:histone deacetylase binding; IDA:UniProtKB.
DR GO; GO:0035402; F:histone kinase activity (H3-T11 specific); IDA:UniProtKB.
DR GO; GO:0050681; F:nuclear androgen receptor binding; IDA:UniProtKB.
DR GO; GO:0030374; F:nuclear receptor coactivator activity; IDA:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0004697; F:protein kinase C activity; EXP:Reactome.
DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB.
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:0031267; F:small GTPase binding; IDA:UniProtKB.
DR GO; GO:0001783; P:B cell apoptotic process; IEA:Ensembl.
DR GO; GO:0001782; P:B cell homeostasis; IEA:Ensembl.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0010631; P:epithelial cell migration; IMP:UniProtKB.
DR GO; GO:0006972; P:hyperosmotic response; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IEA:Ensembl.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0043687; P:post-translational protein modification; IDA:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0060765; P:regulation of androgen receptor signaling pathway; TAS:Reactome.
DR GO; GO:2000145; P:regulation of cell motility; IMP:UniProtKB.
DR GO; GO:0002634; P:regulation of germinal center formation; IEA:Ensembl.
DR GO; GO:0002637; P:regulation of immunoglobulin production; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0003014; P:renal system process; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0048536; P:spleen development; IEA:Ensembl.
DR CDD; cd08687; C2_PKN-like; 1.
DR CDD; cd11630; HR1_PKN1_2; 1.
DR CDD; cd11622; HR1_PKN_1; 1.
DR IDEAL; IID00416; -.
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; IPR037317; PKN1_HR1_2.
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; 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; ATP-binding;
KW Cell membrane; Chromatin regulator; Coiled coil; Cytoplasm; Endosome;
KW Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transcription;
KW Transcription regulation; Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..942
FT /note="Serine/threonine-protein kinase N1"
FT /id="PRO_0000055719"
FT DOMAIN 25..100
FT /note="REM-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 112..193
FT /note="REM-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 201..280
FT /note="REM-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01207"
FT DOMAIN 307..470
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 615..874
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 875..942
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT REGION 102..121
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 181..185
FT /note="Important for interaction with bacterial SspH1 and
FT SspH1-mediated polyubiquitination"
FT /evidence="ECO:0000269|PubMed:24248594"
FT REGION 341..363
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 553..603
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 553..598
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 740
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 621..629
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 644
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 108..109
FT /note="Cleavage; by caspase-3"
FT SITE 454..455
FT /note="Cleavage; by caspase-3"
FT SITE 558..559
FT /note="Cleavage; by caspase-3"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 69
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 374
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q63433"
FT MOD_RES 448
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 533
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 537
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 540
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 559
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332"
FT MOD_RES 562
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 608
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 774
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000269|PubMed:10792047"
FT MOD_RES 778
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18220336"
FT MOD_RES 914
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT MOD_RES 916
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VAR_SEQ 1..7
FT /note="MASDAVQ -> MAEANNPSEQELE (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_038143"
FT VAR_SEQ 603
FT /note="S -> R (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039213"
FT VAR_SEQ 604..942
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_039214"
FT VARIANT 185
FT /note="R -> C (in a metastatic melanoma sample; somatic
FT mutation; dbSNP:rs267605306)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042337"
FT VARIANT 197
FT /note="A -> E (in dbSNP:rs1287763348)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042338"
FT VARIANT 436
FT /note="R -> W (in dbSNP:rs35132656)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042339"
FT VARIANT 520
FT /note="R -> Q (in dbSNP:rs56273055)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042340"
FT VARIANT 555
FT /note="L -> I (in dbSNP:rs34309238)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_042341"
FT VARIANT 635
FT /note="R -> Q (in dbSNP:rs35416389)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042342"
FT VARIANT 718
FT /note="I -> V (in dbSNP:rs2230539)"
FT /evidence="ECO:0000269|PubMed:17344846,
FT ECO:0000269|PubMed:7988719"
FT /id="VAR_042343"
FT VARIANT 873
FT /note="F -> L (in a breast infiltrating ductal carcinoma
FT sample; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042344"
FT VARIANT 901
FT /note="V -> I (in dbSNP:rs10846)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17344846"
FT /id="VAR_014937"
FT VARIANT 921
FT /note="A -> V (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042345"
FT MUTAGEN 108
FT /note="D->A: Abolishes cleavage by caspase-3 and formation
FT of AF1 fragment."
FT /evidence="ECO:0000269|PubMed:9751706"
FT MUTAGEN 181
FT /note="R->A: Abolishes interaction with bacterial SspH1."
FT /evidence="ECO:0000269|PubMed:24248594"
FT MUTAGEN 181
FT /note="R->K: Decreases interaction with bacterial SspH1."
FT /evidence="ECO:0000269|PubMed:24248594"
FT MUTAGEN 185
FT /note="R->A: Abolishes interaction with bacterial SspH1."
FT /evidence="ECO:0000269|PubMed:24248594"
FT MUTAGEN 451
FT /note="D->A: Abolishes cleavage by caspase-3 and formation
FT of 70 kDa fragment."
FT /evidence="ECO:0000269|PubMed:9751706"
FT MUTAGEN 454
FT /note="D->A: Abolishes cleavage by caspase-3 and formation
FT of 70 kDa fragment."
FT /evidence="ECO:0000269|PubMed:9751706"
FT MUTAGEN 558
FT /note="D->A: Abolishes cleavage by caspase-3 and formation
FT of AF3 fragment."
FT /evidence="ECO:0000269|PubMed:9751706"
FT MUTAGEN 560
FT /note="D->A: Abolishes cleavage by caspase-3 and formation
FT of AF3 fragment."
FT /evidence="ECO:0000269|PubMed:9751706"
FT MUTAGEN 644
FT /note="K->E: Abolishes Serine/threonine-protein kinase
FT activity."
FT /evidence="ECO:0000269|PubMed:18066052,
FT ECO:0000269|PubMed:8135837"
FT MUTAGEN 644
FT /note="K->R: Substantial reduction of autophosphorylation."
FT /evidence="ECO:0000269|PubMed:18066052,
FT ECO:0000269|PubMed:8135837"
FT CONFLICT 191
FT /note="G -> D (in Ref. 2; AAB33345/AAC50209)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="S -> P (in Ref. 3; BAG36611)"
FT /evidence="ECO:0000305"
FT CONFLICT 736
FT /note="I -> T (in Ref. 6; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 750
FT /note="T -> A (in Ref. 6; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 800
FT /note="G -> A (in Ref. 6; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 812
FT /note="E -> G (in Ref. 3; BAG36611)"
FT /evidence="ECO:0000305"
FT CONFLICT 887
FT /note="L -> P (in Ref. 3; BAG53845)"
FT /evidence="ECO:0000305"
FT HELIX 15..18
FT /evidence="ECO:0007829|PDB:1CXZ"
FT HELIX 29..66
FT /evidence="ECO:0007829|PDB:1CXZ"
FT HELIX 71..95
FT /evidence="ECO:0007829|PDB:1CXZ"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:1URF"
FT HELIX 126..151
FT /evidence="ECO:0007829|PDB:4NKG"
FT TURN 157..159
FT /evidence="ECO:0007829|PDB:4NKG"
FT HELIX 160..187
FT /evidence="ECO:0007829|PDB:4NKG"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:2RMK"
FT HELIX 612..614
FT /evidence="ECO:0007829|PDB:4OTH"
FT STRAND 615..624
FT /evidence="ECO:0007829|PDB:4OTH"
FT STRAND 627..634
FT /evidence="ECO:0007829|PDB:4OTH"
FT TURN 635..637
FT /evidence="ECO:0007829|PDB:4OTH"
FT STRAND 640..647
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 648..653
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 657..671
FT /evidence="ECO:0007829|PDB:4OTH"
FT TURN 672..674
FT /evidence="ECO:0007829|PDB:4OTG"
FT STRAND 681..686
FT /evidence="ECO:0007829|PDB:4OTH"
FT STRAND 688..696
FT /evidence="ECO:0007829|PDB:4OTH"
FT STRAND 700..702
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 703..706
FT /evidence="ECO:0007829|PDB:4OTH"
FT TURN 707..709
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 714..733
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 743..745
FT /evidence="ECO:0007829|PDB:4OTH"
FT STRAND 746..748
FT /evidence="ECO:0007829|PDB:4OTH"
FT STRAND 750..752
FT /evidence="ECO:0007829|PDB:4OTG"
FT STRAND 754..756
FT /evidence="ECO:0007829|PDB:4OTH"
FT STRAND 763..765
FT /evidence="ECO:0007829|PDB:4OTD"
FT HELIX 779..781
FT /evidence="ECO:0007829|PDB:4OTD"
FT HELIX 784..788
FT /evidence="ECO:0007829|PDB:4OTD"
FT HELIX 794..810
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 820..829
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 840..849
FT /evidence="ECO:0007829|PDB:4OTH"
FT TURN 854..856
FT /evidence="ECO:0007829|PDB:4OTH"
FT TURN 862..864
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 865..869
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 872..874
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 879..883
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 906..909
FT /evidence="ECO:0007829|PDB:4OTH"
FT HELIX 926..930
FT /evidence="ECO:0007829|PDB:4OTH"
FT TURN 931..934
FT /evidence="ECO:0007829|PDB:4OTH"
SQ SEQUENCE 942 AA; 103932 MW; 61360295EC70BB8E CRC64;
MASDAVQSEP RSWSLLEQLG LAGADLAAPG VQQQLELERE RLRREIRKEL KLKEGAENLR
RATTDLGRSL GPVELLLRGS SRRLDLLHQQ LQELHAHVVL PDPAATHDGP QSPGAGGPTC
SATNLSRVAG LEKQLAIELK VKQGAENMIQ TYSNGSTKDR KLLLTAQQML QDSKTKIDII
RMQLRRALQA GQLENQAAPD DTQGSPDLGA VELRIEELRH HFRVEHAVAE GAKNVLRLLS
AAKAPDRKAV SEAQEKLTES NQKLGLLREA LERRLGELPA DHPKGRLLRE ELAAASSAAF
STRLAGPFPA THYSTLCKPA PLTGTLEVRV VGCRDLPETI PWNPTPSMGG PGTPDSRPPF
LSRPARGLYS RSGSLSGRSS LKAEAENTSE VSTVLKLDNT VVGQTSWKPC GPNAWDQSFT
LELERARELE LAVFWRDQRG LCALKFLKLE DFLDNERHEV QLDMEPQGCL VAEVTFRNPV
IERIPRLRRQ KKIFSKQQGK AFQRARQMNI DVATWVRLLR RLIPNATGTG TFSPGASPGS
EARTTGDISV EKLNLGTDSD SSPQKSSRDP PSSPSSLSSP IQESTAPELP SETQETPGPA
LCSPLRKSPL TLEDFKFLAV LGRGHFGKVL LSEFRPSGEL FAIKALKKGD IVARDEVESL
MCEKRILAAV TSAGHPFLVN LFGCFQTPEH VCFVMEYSAG GDLMLHIHSD VFSEPRAIFY
SACVVLGLQF LHEHKIVYRD LKLDNLLLDT EGYVKIADFG LCKEGMGYGD RTSTFCGTPE
FLAPEVLTDT SYTRAVDWWG LGVLLYEMLV GESPFPGDDE EEVFDSIVND EVRYPRFLSA
EAIGIMRRLL RRNPERRLGS SERDAEDVKK QPFFRTLGWE ALLARRLPPP FVPTLSGRTD
VSNFDEEFTG EAPTLSPPRD ARPLTAAEQA AFLDFDFVAG GC
