KPCD1_HUMAN
ID KPCD1_HUMAN Reviewed; 912 AA.
AC Q15139; A6NL64; B2RAF6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 14-OCT-2008, sequence version 2.
DT 03-AUG-2022, entry version 211.
DE RecName: Full=Serine/threonine-protein kinase D1;
DE EC=2.7.11.13;
DE AltName: Full=Protein kinase C mu type;
DE AltName: Full=Protein kinase D;
DE AltName: Full=nPKC-D1;
DE AltName: Full=nPKC-mu;
GN Name=PRKD1; Synonyms=PKD, PKD1, PRKCM;
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].
RC TISSUE=Placenta;
RX PubMed=8119958; DOI=10.1016/s0021-9258(17)37580-4;
RA Johannes F.-J., Prestle J., Eis S., Oberhagemann P., Pfizenmaier K.;
RT "PKCmu is a novel, atypical member of the protein kinase C family.";
RL J. Biol. Chem. 269:6140-6148(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
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 [5]
RP FUNCTION IN EGFR PHOSPHORYLATION.
RX PubMed=10523301; DOI=10.1093/emboj/18.20.5567;
RA Bagowski C.P., Stein-Gerlach M., Choidas A., Ullrich A.;
RT "Cell-type specific phosphorylation of threonines T654 and T669 by PKD
RT defines the signal capacity of the EGF receptor.";
RL EMBO J. 18:5567-5576(1999).
RN [6]
RP FUNCTION IN APOPTOSIS.
RX PubMed=10764790; DOI=10.1074/jbc.m002266200;
RA Endo K., Oki E., Biedermann V., Kojima H., Yoshida K., Johannes F.J.,
RA Kufe D., Datta R.;
RT "Proteolytic cleavage and activation of protein kinase C [micro] by
RT caspase-3 in the apoptotic response of cells to 1-beta -D-
RT arabinofuranosylcytosine and other genotoxic agents.";
RL J. Biol. Chem. 275:18476-18481(2000).
RN [7]
RP INTERACTION WITH ADAP1.
RX PubMed=12893243; DOI=10.1016/s0006-291x(03)01187-2;
RA Zemlickova E., Dubois T., Kerai P., Clokie S., Cronshaw A.D.,
RA Wakefield R.I.D., Johannes F.-J., Aitken A.;
RT "Centaurin-alpha(1) associates with and is phosphorylated by isoforms of
RT protein kinase C.";
RL Biochem. Biophys. Res. Commun. 307:459-465(2003).
RN [8]
RP FUNCTION IN CELL SURVIVAL.
RX PubMed=12505989; DOI=10.1093/emboj/cdg009;
RA Storz P., Toker A.;
RT "Protein kinase D mediates a stress-induced NF-kappaB activation and
RT survival pathway.";
RL EMBO J. 22:109-120(2003).
RN [9]
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT TYR-432; TYR-463 AND
RP TYR-502, AND MUTAGENESIS OF TYR-432; TYR-463; TYR-502 AND LYS-612.
RX PubMed=12637538; DOI=10.1074/jbc.m213224200;
RA Storz P., Doppler H., Johannes F.J., Toker A.;
RT "Tyrosine phosphorylation of protein kinase D in the pleckstrin homology
RT domain leads to activation.";
RL J. Biol. Chem. 278:17969-17976(2003).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF TRPV1.
RX PubMed=15471852; DOI=10.1074/jbc.m410331200;
RA Wang Y., Kedei N., Wang M., Wang Q.J., Huppler A.R., Toth A., Tran R.,
RA Blumberg P.M.;
RT "Interaction between protein kinase Cmu and the vanilloid receptor type
RT 1.";
RL J. Biol. Chem. 279:53674-53682(2004).
RN [11]
RP PHOSPHORYLATION AT TYR-463; SER-738 AND SER-742.
RX PubMed=15024053; DOI=10.1128/mcb.24.7.2614-2626.2004;
RA Storz P., Doppler H., Toker A.;
RT "Protein kinase Cdelta selectively regulates protein kinase D-dependent
RT activation of NF-kappaB in oxidative stress signaling.";
RL Mol. Cell. Biol. 24:2614-2626(2004).
RN [12]
RP PHOSPHORYLATION BY DAPK1, INTERACTION WITH DAPK1, PHOSPHORYLATION AT
RP SER-910, AND ACTIVITY REGULATION.
RX PubMed=17703233; DOI=10.1038/sj.cdd.4402212;
RA Eisenberg-Lerner A., Kimchi A.;
RT "DAP kinase regulates JNK signaling by binding and activating protein
RT kinase D under oxidative stress.";
RL Cell Death Differ. 14:1908-1915(2007).
RN [13]
RP PHOSPHORYLATION AT TYR-95.
RX PubMed=17804414; DOI=10.1074/jbc.m703584200;
RA Doppler H., Storz P.;
RT "A novel tyrosine phosphorylation site in protein kinase D contributes to
RT oxidative stress-mediated activation.";
RL J. Biol. Chem. 282:31873-31881(2007).
RN [14]
RP FUNCTION IN INNATE IMMUNITY.
RX PubMed=17442957; DOI=10.4049/jimmunol.178.9.5735;
RA Ivison S.M., Graham N.R., Bernales C.Q., Kifayet A., Ng N., Shobab L.A.,
RA Steiner T.S.;
RT "Protein kinase D interaction with TLR5 is required for inflammatory
RT signaling in response to bacterial flagellin.";
RL J. Immunol. 178:5735-5743(2007).
RN [15]
RP ACTIVITY REGULATION, PHORBOL-ESTER BINDING, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF PRO-157 AND PRO-281.
RX PubMed=18076381; DOI=10.1042/bj20071334;
RA Chen J., Deng F., Li J., Wang Q.J.;
RT "Selective binding of phorbol esters and diacylglycerol by individual C1
RT domains of the PKD family.";
RL Biochem. J. 411:333-342(2008).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF HDAC5, AND FUNCTION IN ANGIOGENESIS.
RX PubMed=18332134; DOI=10.1074/jbc.m800264200;
RA Ha C.H., Wang W., Jhun B.S., Wong C., Hausser A., Pfizenmaier K.,
RA McKinsey T.A., Olson E.N., Jin Z.G.;
RT "Protein kinase D-dependent phosphorylation and nuclear export of histone
RT deacetylase 5 mediates vascular endothelial growth factor-induced gene
RT expression and angiogenesis.";
RL J. Biol. Chem. 283:14590-14599(2008).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF HDAC7.
RX PubMed=18509061; DOI=10.1073/pnas.0802857105;
RA Wang S., Li X., Parra M., Verdin E., Bassel-Duby R., Olson E.N.;
RT "Control of endothelial cell proliferation and migration by VEGF signaling
RT to histone deacetylase 7.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:7738-7743(2008).
RN [18]
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 [19]
RP PHOSPHORYLATION AT SER-397 AND SER-401, INTERACTION WITH MAPK13, AND
RP FUNCTION.
RX PubMed=19135240; DOI=10.1016/j.cell.2008.11.018;
RA Sumara G., Formentini I., Collins S., Sumara I., Windak R., Bodenmiller B.,
RA Ramracheya R., Caille D., Jiang H., Platt K.A., Meda P., Aebersold R.,
RA Rorsman P., Ricci R.;
RT "Regulation of PKD by the MAPK p38delta in insulin secretion and glucose
RT homeostasis.";
RL Cell 136:235-248(2009).
RN [20]
RP FUNCTION IN ANGIOGENESIS.
RX PubMed=19211839; DOI=10.1091/mbc.e08-09-0957;
RA Czoendoer K., Ellwanger K., Fuchs Y.F., Lutz S., Gulyas M., Mansuy I.M.,
RA Hausser A., Pfizenmaier K., Schlett K.;
RT "Protein kinase D controls the integrity of Golgi apparatus and the
RT maintenance of dendritic arborization in hippocampal neurons.";
RL Mol. Biol. Cell 20:2108-2120(2009).
RN [21]
RP REVIEW ON FUNCTION IN TRAFFICKING.
RX PubMed=11978539; DOI=10.1016/s0962-8924(02)02262-6;
RA Van Lint J., Rykx A., Maeda Y., Vantus T., Sturany S., Malhotra V.,
RA Vandenheede J.R., Seufferlein T.;
RT "Protein kinase D: an intracellular traffic regulator on the move.";
RL Trends Cell Biol. 12:193-200(2002).
RN [22]
RP REVIEW ON FUNCTION.
RX PubMed=15701647; DOI=10.1074/jbc.r500002200;
RA Rozengurt E., Rey O., Waldron R.T.;
RT "Protein kinase D signaling.";
RL J. Biol. Chem. 280:13205-13208(2005).
RN [23]
RP REVIEW ON FUNCTION.
RX PubMed=18239146; DOI=10.1161/circresaha.107.168211;
RA Avkiran M., Rowland A.J., Cuello F., Haworth R.S.;
RT "Protein kinase d in the cardiovascular system: emerging roles in health
RT and disease.";
RL Circ. Res. 102:157-163(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205; SER-345; SER-448 AND
RP SER-473, AND 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 [25]
RP REVIEW ON FUNCTION IN ANGIOGENESIS.
RX PubMed=19655095; DOI=10.1007/s10059-009-0109-9;
RA Ha C.H., Jin Z.G.;
RT "Protein kinase D1, a new molecular player in VEGF signaling and
RT angiogenesis.";
RL Mol. Cells 28:1-5(2009).
RN [26]
RP REVIEW ON FUNCTION.
RX PubMed=21357900; DOI=10.1152/physiol.00037.2010;
RA Rozengurt E.;
RT "Protein kinase D signaling: multiple biological functions in health and
RT disease.";
RL Physiology (Bethesda) 26:23-33(2011).
RN [27]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205 AND SER-208, AND
RP IDENTIFICATION BY 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 [28]
RP FUNCTION, INTERACTION WITH USP28, AND INDUCTION.
RX PubMed=24623306; DOI=10.7554/elife.02313;
RA Serra R.W., Fang M., Park S.M., Hutchinson L., Green M.R.;
RT "A KRAS-directed transcriptional silencing pathway that mediates the CpG
RT island methylator phenotype.";
RL Elife 3:E02313-E02313(2014).
RN [29]
RP VARIANTS [LARGE SCALE ANALYSIS] TYR-152 AND LYS-857.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [30]
RP VARIANTS [LARGE SCALE ANALYSIS] PRO-225; GLN-478; SER-585; MET-677; LEU-679
RP AND ARG-891.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [31]
RP INVOLVEMENT IN CHDED, AND VARIANTS CHDED TRP-299 AND ARG-592.
RX PubMed=27479907; DOI=10.1038/ng.3627;
RG INTERVAL Study;
RG UK10K Consortium;
RG Deciphering Developmental Disorders Study;
RA Sifrim A., Hitz M.P., Wilsdon A., Breckpot J., Turki S.H., Thienpont B.,
RA McRae J., Fitzgerald T.W., Singh T., Swaminathan G.J., Prigmore E.,
RA Rajan D., Abdul-Khaliq H., Banka S., Bauer U.M., Bentham J., Berger F.,
RA Bhattacharya S., Bu'Lock F., Canham N., Colgiu I.G., Cosgrove C., Cox H.,
RA Daehnert I., Daly A., Danesh J., Fryer A., Gewillig M., Hobson E., Hoff K.,
RA Homfray T., Kahlert A.K., Ketley A., Kramer H.H., Lachlan K., Lampe A.K.,
RA Louw J.J., Manickara A.K., Manase D., McCarthy K.P., Metcalfe K., Moore C.,
RA Newbury-Ecob R., Omer S.O., Ouwehand W.H., Park S.M., Parker M.J.,
RA Pickardt T., Pollard M.O., Robert L., Roberts D.J., Sambrook J.,
RA Setchfield K., Stiller B., Thornborough C., Toka O., Watkins H.,
RA Williams D., Wright M., Mital S., Daubeney P.E., Keavney B., Goodship J.,
RA Abu-Sulaiman R.M., Klaassen S., Wright C.F., Firth H.V., Barrett J.C.,
RA Devriendt K., FitzPatrick D.R., Brook J.D., Hurles M.E.;
RT "Distinct genetic architectures for syndromic and nonsyndromic congenital
RT heart defects identified by exome sequencing.";
RL Nat. Genet. 48:1060-1065(2016).
CC -!- FUNCTION: Serine/threonine-protein kinase that converts transient
CC diacylglycerol (DAG) signals into prolonged physiological effects
CC downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and
CC Ras signaling, Golgi membrane integrity and trafficking, cell survival
CC through NF-kappa-B activation, cell migration, cell differentiation by
CC mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2)
CC signaling, and plays a role in cardiac hypertrophy, VEGFA-induced
CC angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated
CC inflammatory response. Phosphorylates the epidermal growth factor
CC receptor (EGFR) on dual threonine residues, which leads to the
CC suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1
CC activation and subsequent JUN phosphorylation. Phosphorylates RIN1,
CC inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and
CC increased competition with RAF1 for binding to GTP-bound form of Ras
CC proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric
CC G-protein beta/gamma-subunit complex to maintain the structural
CC integrity of the Golgi membranes, and is required for protein transport
CC along the secretory pathway. In the trans-Golgi network (TGN),
CC regulates the fission of transport vesicles that are on their way to
CC the plasma membrane. May act by activating the lipid kinase
CC phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local
CC synthesis of phosphorylated inositol lipids, which induces a sequential
CC production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are
CC necessary for membrane fission and generation of specific transport
CC carriers to the cell surface. Under oxidative stress, is phosphorylated
CC at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating
CC IKK complex and subsequent nuclear translocation and activation of
CC NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3
CC recycling and promoting its recruitment in newly forming focal
CC adhesion. In osteoblast differentiation, mediates the bone
CC morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which
CC results in the inhibition of HDAC7 transcriptional repression of RUNX2.
CC In neurons, plays an important role in neuronal polarity by regulating
CC the biogenesis of TGN-derived dendritic vesicles, and is involved in
CC the maintenance of dendritic arborization and Golgi structure in
CC hippocampal cells. May potentiate mitogenesis induced by the
CC neuropeptide bombesin or vasopressin by mediating an increase in the
CC duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of
CC immediate-early gene products including FOS that stimulate cell cycle
CC progression. Plays an important role in the proliferative response
CC induced by low calcium in keratinocytes, through sustained activation
CC of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a
CC role in cardiac hypertrophy by phosphorylating HDAC5, which in turn
CC triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A
CC transcriptional activation and induction of downstream target genes
CC that promote myocyte hypertrophy and pathological cardiac remodeling.
CC Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites,
CC which results in reduced myofilament calcium sensitivity, and
CC accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is
CC also involved in angiogenesis by mediating VEGFA-induced specific
CC subset of gene expression, cell migration, and tube formation. In
CC response to VEGFA, is necessary and required for HDAC7 phosphorylation
CC which induces HDAC7 nuclear export and endothelial cell proliferation
CC and migration. During apoptosis induced by cytarabine and other
CC genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting
CC in activation of its kinase function and increased sensitivity of cells
CC to the cytotoxic effects of genotoxic agents. In epithelial cells, is
CC required for transducing flagellin-stimulated inflammatory responses by
CC binding and phosphorylating TLR5, which contributes to MAPK14/p38
CC activation and production of inflammatory cytokines. May play a role in
CC inflammatory response by mediating activation of NF-kappa-B. May be
CC involved in pain transmission by directly modulating TRPV1 receptor.
CC Plays a role in activated KRAS-mediated stabilization of ZNF304 in
CC colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear
CC translocation of transcription factor TFEB in macrophages upon live
CC S.enterica infection (By similarity). {ECO:0000250|UniProtKB:Q62101,
CC ECO:0000269|PubMed:10523301, ECO:0000269|PubMed:10764790,
CC ECO:0000269|PubMed:12505989, ECO:0000269|PubMed:12637538,
CC ECO:0000269|PubMed:15471852, ECO:0000269|PubMed:17442957,
CC ECO:0000269|PubMed:18332134, ECO:0000269|PubMed:18509061,
CC ECO:0000269|PubMed:19135240, ECO:0000269|PubMed:19211839,
CC ECO:0000269|PubMed:24623306}.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by DAG and phorbol esters. Phorbol-
CC ester/DAG-type domain 1 binds DAG with high affinity and appears to
CC play the dominant role in mediating translocation to the cell membrane
CC and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol
CC ester with higher affinity. Autophosphorylation of Ser-742 and
CC phosphorylation of Ser-738 by PKC relieves auto-inhibition by the PH
CC domain. Phosphorylation on Tyr-463 by the SRC-ABL1 pathway in response
CC to oxidative stress, is also required for activation. Activated by
CC DAPK1 under oxidative stress. {ECO:0000269|PubMed:12637538,
CC ECO:0000269|PubMed:17703233, ECO:0000269|PubMed:18076381}.
CC -!- SUBUNIT: Interacts (via N-terminus) with ADAP1/CENTA1
CC (PubMed:12893243). Interacts with MAPK13 (PubMed:19135240). Interacts
CC with DAPK1 in an oxidative stress-regulated manner (PubMed:17703233).
CC Interacts with USP28; the interaction induces phosphorylation of USP28
CC and activated KRAS-mediated stabilization of ZNF304 (PubMed:24623306).
CC Interacts with AKAP13 (via C-terminal domain) (By similarity).
CC {ECO:0000250|UniProtKB:Q62101, ECO:0000269|PubMed:12893243,
CC ECO:0000269|PubMed:17703233, ECO:0000269|PubMed:19135240,
CC ECO:0000269|PubMed:24623306}.
CC -!- INTERACTION:
CC Q15139; P53367: ARFIP1; NbExp=2; IntAct=EBI-1181072, EBI-2808808;
CC Q15139; Q07021: C1QBP; NbExp=9; IntAct=EBI-1181072, EBI-347528;
CC Q15139; P12830: CDH1; NbExp=7; IntAct=EBI-1181072, EBI-727477;
CC Q15139; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1181072, EBI-352572;
CC Q15139; O15264: MAPK13; NbExp=6; IntAct=EBI-1181072, EBI-2116951;
CC Q15139; P02795: MT2A; NbExp=7; IntAct=EBI-1181072, EBI-996616;
CC Q15139; Q15139: PRKD1; NbExp=2; IntAct=EBI-1181072, EBI-1181072;
CC Q15139; Q8C2B3-1: Hdac7; Xeno; NbExp=3; IntAct=EBI-1181072, EBI-15705168;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18076381}. Cell
CC membrane {ECO:0000269|PubMed:18076381}. Golgi apparatus, trans-Golgi
CC network {ECO:0000250|UniProtKB:Q62101}. Note=Translocation to the cell
CC membrane is required for kinase activation.
CC -!- INDUCTION: Up-regulated by the intestine-specific transcription factor
CC CDX1 in an activated KRAS-dependent manner in colorectal cancer (CRC)
CC cells (PubMed:24623306). {ECO:0000269|PubMed:24623306}.
CC -!- PTM: Phosphorylated at Ser-397 and Ser-401 by MAPK13 during regulation
CC of insulin secretion in pancreatic beta cells (PubMed:19135240).
CC Phosphorylated by DAPK1 (PubMed:17703233). Phosphorylated at Tyr-95 and
CC by ABL at Tyr-463, which primes the kinase in response to oxidative
CC stress, and promotes a second step activating phosphorylation at Ser-
CC 738/Ser-742 by PKRD (PubMed:12637538, PubMed:15024053,
CC PubMed:17804414). Phosphorylated on Ser-910 upon S.enterica infection
CC in macrophages (By similarity). {ECO:0000250|UniProtKB:Q62101,
CC ECO:0000269|PubMed:12637538, ECO:0000269|PubMed:15024053,
CC ECO:0000269|PubMed:17703233, ECO:0000269|PubMed:17804414,
CC ECO:0000269|PubMed:19135240}.
CC -!- DISEASE: Congenital heart defects and ectodermal dysplasia (CHDED)
CC [MIM:617364]: An autosomal dominant syndrome characterized by atrial
CC and/or ventricular septal congenital heart defects and variable
CC features of ectodermal dysplasia, including sparse hair, dry skin, thin
CC skin, fragile nails, premature loss of primary teeth, and small widely
CC spaced teeth. Patients manifest developmental disabilities ranging from
CC motor delay and delayed speech to global developmental retardation.
CC {ECO:0000269|PubMed:27479907}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. PKD subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/PRKCMID41860ch14q11.html";
CC ---------------------------------------------------------------------------
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DR EMBL; X75756; CAA53384.1; -; mRNA.
DR EMBL; AK314170; BAG36853.1; -; mRNA.
DR EMBL; AL135858; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65971.1; -; Genomic_DNA.
DR CCDS; CCDS9637.1; -.
DR PIR; A53215; A53215.
DR RefSeq; NP_002733.2; NM_002742.2.
DR AlphaFoldDB; Q15139; -.
DR SMR; Q15139; -.
DR BioGRID; 111573; 176.
DR DIP; DIP-38481N; -.
DR IntAct; Q15139; 135.
DR STRING; 9606.ENSP00000333568; -.
DR BindingDB; Q15139; -.
DR ChEMBL; CHEMBL3863; -.
DR DrugBank; DB11752; Bryostatin 1.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q15139; -.
DR GuidetoPHARMACOLOGY; 1489; -.
DR iPTMnet; Q15139; -.
DR PhosphoSitePlus; Q15139; -.
DR BioMuta; PRKD1; -.
DR DMDM; 209572639; -.
DR EPD; Q15139; -.
DR jPOST; Q15139; -.
DR MassIVE; Q15139; -.
DR MaxQB; Q15139; -.
DR PaxDb; Q15139; -.
DR PeptideAtlas; Q15139; -.
DR PRIDE; Q15139; -.
DR ProteomicsDB; 60458; -.
DR Antibodypedia; 4337; 985 antibodies from 40 providers.
DR DNASU; 5587; -.
DR Ensembl; ENST00000331968.11; ENSP00000333568.6; ENSG00000184304.17.
DR GeneID; 5587; -.
DR KEGG; hsa:5587; -.
DR MANE-Select; ENST00000331968.11; ENSP00000333568.6; NM_002742.3; NP_002733.2.
DR UCSC; uc001wqh.4; human.
DR CTD; 5587; -.
DR DisGeNET; 5587; -.
DR GeneCards; PRKD1; -.
DR HGNC; HGNC:9407; PRKD1.
DR HPA; ENSG00000184304; Low tissue specificity.
DR MalaCards; PRKD1; -.
DR MIM; 605435; gene.
DR MIM; 617364; phenotype.
DR neXtProt; NX_Q15139; -.
DR OpenTargets; ENSG00000184304; -.
DR Orphanet; 500481; Squamous cell carcinoma of salivary glands.
DR PharmGKB; PA33771; -.
DR VEuPathDB; HostDB:ENSG00000184304; -.
DR eggNOG; KOG4236; Eukaryota.
DR GeneTree; ENSGT00950000183024; -.
DR HOGENOM; CLU_009772_1_0_1; -.
DR InParanoid; Q15139; -.
DR OMA; RHDQASE; -.
DR OrthoDB; 1444458at2759; -.
DR PhylomeDB; Q15139; -.
DR TreeFam; TF314320; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; Q15139; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR SignaLink; Q15139; -.
DR SIGNOR; Q15139; -.
DR BioGRID-ORCS; 5587; 11 hits in 1107 CRISPR screens.
DR ChiTaRS; PRKD1; human.
DR GeneWiki; Protein_kinase_D1; -.
DR GenomeRNAi; 5587; -.
DR Pharos; Q15139; Tchem.
DR PRO; PR:Q15139; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q15139; protein.
DR Bgee; ENSG00000184304; Expressed in ventricular zone and 164 other tissues.
DR ExpressionAtlas; Q15139; baseline and differential.
DR Genevisible; Q15139; HS.
DR GO; GO:0000421; C:autophagosome membrane; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005938; C:cell cortex; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005794; C:Golgi apparatus; IDA:CACAO.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB.
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:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004697; F:protein kinase C activity; IDA:CACAO.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071447; P:cellular response to hydroperoxide; IMP:ParkinsonsUK-UCL.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl.
DR GO; GO:0007030; P:Golgi organization; IMP:UniProtKB.
DR GO; GO:0048193; P:Golgi vesicle transport; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; TAS:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IMP:BHF-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:UniProtKB.
DR GO; GO:0045806; P:negative regulation of endocytosis; TAS:BHF-UCL.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:ParkinsonsUK-UCL.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:0032793; P:positive regulation of CREB transcription factor activity; IGI:BHF-UCL.
DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; IMP:BHF-UCL.
DR GO; GO:0038033; P:positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; IMP:UniProtKB.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IGI:BHF-UCL.
DR GO; GO:1901727; P:positive regulation of histone deacetylase activity; IGI:BHF-UCL.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:BHF-UCL.
DR GO; GO:0043552; P:positive regulation of phosphatidylinositol 3-kinase activity; IC:ParkinsonsUK-UCL.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
DR GO; GO:0089700; P:protein kinase D signaling; IGI:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:UniProtKB.
DR GO; GO:2001044; P:regulation of integrin-mediated signaling pathway; TAS:BHF-UCL.
DR GO; GO:0010837; P:regulation of keratinocyte proliferation; ISS:UniProtKB.
DR GO; GO:0031647; P:regulation of protein stability; IMP:UniProtKB.
DR GO; GO:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL.
DR CDD; cd00029; C1; 2.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR015727; Protein_Kinase_C_mu-related.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR22968; PTHR22968; 1.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF000552; PKC_mu_nu_D2; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00233; PH; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW Angiogenesis; Apoptosis; ATP-binding; Cell membrane; Cytoplasm;
KW Differentiation; Disease variant; Ectodermal dysplasia; Golgi apparatus;
KW Immunity; Inflammatory response; Innate immunity; Kinase; Magnesium;
KW Membrane; Metal-binding; Neurogenesis; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase;
KW Zinc; Zinc-finger.
FT CHAIN 1..912
FT /note="Serine/threonine-protein kinase D1"
FT /id="PRO_0000055714"
FT DOMAIN 422..541
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 583..839
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 146..196
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 270..320
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 377..402
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 706
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 589..597
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 612
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 95
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:17804414"
FT MOD_RES 205
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 219
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8BZ03"
FT MOD_RES 223
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZL6"
FT MOD_RES 345
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 397
FT /note="Phosphoserine; by MAPK13"
FT /evidence="ECO:0000269|PubMed:19135240"
FT MOD_RES 401
FT /note="Phosphoserine; by MAPK13"
FT /evidence="ECO:0000269|PubMed:19135240"
FT MOD_RES 432
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12637538"
FT MOD_RES 448
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 463
FT /note="Phosphotyrosine; by ABL"
FT /evidence="ECO:0000269|PubMed:12637538,
FT ECO:0000269|PubMed:15024053"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 502
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:12637538"
FT MOD_RES 548
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K1Y2"
FT MOD_RES 738
FT /note="Phosphoserine; by PKC/PRKCD"
FT /evidence="ECO:0000269|PubMed:15024053"
FT MOD_RES 742
FT /note="Phosphoserine; by autocatalysis and PKC/PRKCD"
FT /evidence="ECO:0000269|PubMed:15024053"
FT MOD_RES 749
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9BZL6"
FT MOD_RES 910
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:17703233"
FT VARIANT 152
FT /note="H -> Y (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1383618278)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035468"
FT VARIANT 225
FT /note="S -> P"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042324"
FT VARIANT 299
FT /note="L -> W (in CHDED; dbSNP:rs1057519636)"
FT /evidence="ECO:0000269|PubMed:27479907"
FT /id="VAR_078602"
FT VARIANT 478
FT /note="K -> Q (in dbSNP:rs55852813)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042325"
FT VARIANT 585
FT /note="P -> S (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042326"
FT VARIANT 592
FT /note="G -> R (in CHDED; dbSNP:rs1057519635)"
FT /evidence="ECO:0000269|PubMed:27479907"
FT /id="VAR_078603"
FT VARIANT 677
FT /note="R -> M (in a lung bronchoalveolar carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042327"
FT VARIANT 679
FT /note="P -> L (in dbSNP:rs34588699)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042328"
FT VARIANT 825
FT /note="R -> K (in dbSNP:rs11161065)"
FT /id="VAR_046988"
FT VARIANT 857
FT /note="E -> K (in a colorectal cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035469"
FT VARIANT 891
FT /note="H -> R (in dbSNP:rs45582934)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042329"
FT MUTAGEN 157
FT /note="P->G: Increase in ability to bind phorbol ester,
FT loss of ability to bind DAG."
FT /evidence="ECO:0000269|PubMed:18076381"
FT MUTAGEN 281
FT /note="P->G: No effect on ability to bind phorbol ester,
FT slight increase in ability to bind DAG."
FT /evidence="ECO:0000269|PubMed:18076381"
FT MUTAGEN 432
FT /note="Y->E: Decreased phosphorylation level when
FT coexpressed with SRC in HeLa cells. Unchanged
FT phosphorylation level when coexpressed with ABL."
FT /evidence="ECO:0000269|PubMed:12637538"
FT MUTAGEN 432
FT /note="Y->F: Decreased phosphorylation level when
FT coexpressed with SRC in HeLa cells. Unchanged
FT phosphorylation level when coexpressed with ABL. Unaltered
FT kinase activity. Decreased kinase activity; when associated
FT with F-463 and F-502."
FT /evidence="ECO:0000269|PubMed:12637538"
FT MUTAGEN 463
FT /note="Y->E: Constitutive activation and constitutive
FT phosphorylation of S-738 and S-742."
FT /evidence="ECO:0000269|PubMed:12637538"
FT MUTAGEN 463
FT /note="Y->F: Decreased phosphorylation level when
FT coexpressed with either SRC or ABL in HeLa cells. Decreased
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:12637538"
FT MUTAGEN 502
FT /note="Y->E: Loss of activation."
FT /evidence="ECO:0000269|PubMed:12637538"
FT MUTAGEN 502
FT /note="Y->F: Decreased phosphorylation level when
FT coexpressed with SRC in HeLa cells. Unchanged
FT phosphorylation level when coexpressed with ABL. Unaltered
FT kinase activity. Decreased kinase activity; when associated
FT with F-432 and F-502."
FT /evidence="ECO:0000269|PubMed:12637538"
FT MUTAGEN 612
FT /note="K->W: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:12637538"
FT CONFLICT 135
FT /note="A -> R (in Ref. 1; CAA53384)"
FT /evidence="ECO:0000305"
FT CONFLICT 877
FT /note="G -> R (in Ref. 1; CAA53384)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 912 AA; 101704 MW; 0BC9414C335D2DBB CRC64;
MSAPPVLRPP SPLLPVAAAA AAAAAALVPG SGPGPAPFLA PVAAPVGGIS FHLQIGLSRE
PVLLLQDSSG DYSLAHVREM ACSIVDQKFP ECGFYGMYDK ILLFRHDPTS ENILQLVKAA
SDIQEGDLIE VVLSASATFE DFQIRPHALF VHSYRAPAFC DHCGEMLWGL VRQGLKCEGC
GLNYHKRCAF KIPNNCSGVR RRRLSNVSLT GVSTIRTSSA ELSTSAPDEP LLQKSPSESF
IGREKRSNSQ SYIGRPIHLD KILMSKVKVP HTFVIHSYTR PTVCQYCKKL LKGLFRQGLQ
CKDCRFNCHK RCAPKVPNNC LGEVTINGDL LSPGAESDVV MEEGSDDNDS ERNSGLMDDM
EEAMVQDAEM AMAECQNDSG EMQDPDPDHE DANRTISPST SNNIPLMRVV QSVKHTKRKS
STVMKEGWMV HYTSKDTLRK RHYWRLDSKC ITLFQNDTGS RYYKEIPLSE ILSLEPVKTS
ALIPNGANPH CFEITTANVV YYVGENVVNP SSPSPNNSVL TSGVGADVAR MWEIAIQHAL
MPVIPKGSSV GTGTNLHRDI SVSISVSNCQ IQENVDISTV YQIFPDEVLG SGQFGIVYGG
KHRKTGRDVA IKIIDKLRFP TKQESQLRNE VAILQNLHHP GVVNLECMFE TPERVFVVME
KLHGDMLEMI LSSEKGRLPE HITKFLITQI LVALRHLHFK NIVHCDLKPE NVLLASADPF
PQVKLCDFGF ARIIGEKSFR RSVVGTPAYL APEVLRNKGY NRSLDMWSVG VIIYVSLSGT
FPFNEDEDIH DQIQNAAFMY PPNPWKEISH EAIDLINNLL QVKMRKRYSV DKTLSHPWLQ
DYQTWLDLRE LECKIGERYI THESDDLRWE KYAGEQGLQY PTHLINPSAS HSDTPETEET
EMKALGERVS IL
