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 27-MAR-2024, entry version 220. 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 (PubMed:10764790, PubMed:12505989, CC PubMed:12637538, PubMed:17442957, PubMed:18509061, PubMed:19135240, CC PubMed:19211839). Phosphorylates the epidermal growth factor receptor CC (EGFR) on dual threonine residues, which leads to the suppression of CC epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and CC subsequent JUN phosphorylation (PubMed:10523301). 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 (PubMed:12505989). Involved in cell migration by regulating CC integrin alpha-5/beta-3 recycling and promoting its recruitment in CC newly forming focal adhesion. In osteoblast differentiation, mediates CC the bone morphogenetic protein 2 (BMP2)-induced nuclear export of CC HDAC7, which results in the inhibition of HDAC7 transcriptional CC repression of RUNX2 (PubMed:18509061). In neurons, plays an important CC role in neuronal polarity by regulating the biogenesis of TGN-derived CC dendritic vesicles, and is involved in the maintenance of dendritic CC arborization and Golgi structure in hippocampal cells. May potentiate CC mitogenesis induced by the neuropeptide bombesin or vasopressin by CC mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, CC which leads to accumulation of immediate-early gene products including CC FOS that stimulate cell cycle progression. Plays an important role in CC the proliferative response induced by low calcium in keratinocytes, CC through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of CC novel PKC signaling, plays a role in cardiac hypertrophy by CC phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent CC nuclear export of HDAC5, MEF2A transcriptional activation and induction CC of downstream target genes that promote myocyte hypertrophy and CC pathological cardiac remodeling (PubMed:18332134). Mediates cardiac CC troponin I (TNNI3) phosphorylation at the PKA sites, which results in CC reduced myofilament calcium sensitivity, and accelerated crossbridge CC cycling kinetics. The PRKD1-HDAC5 pathway is also involved in CC angiogenesis by mediating VEGFA-induced specific subset of gene CC expression, cell migration, and tube formation (PubMed:19211839). 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 (PubMed:10764790). In CC epithelial cells, is required for transducing flagellin-stimulated CC inflammatory responses by binding and phosphorylating TLR5, which CC contributes to MAPK14/p38 activation and production of inflammatory CC cytokines (PubMed:17442957). Acts as an activator of NLRP3 inflammasome CC assembly by mediating phosphorylation of NLRP3 (By similarity). May CC play a role in inflammatory response by mediating activation of NF- CC kappa-B. May be involved in pain transmission by directly modulating CC TRPV1 receptor (PubMed:15471852). Plays a role in activated KRAS- CC mediated stabilization of ZNF304 in colorectal cancer (CRC) cells CC (PubMed:24623306). Regulates nuclear translocation of transcription CC factor TFEB in macrophages upon live S.enterica infection (By CC 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="https://atlasgeneticsoncology.org/gene/41860/PRKCM"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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; 179. DR DIP; DIP-38481N; -. DR IntAct; Q15139; 137. DR STRING; 9606.ENSP00000390535; -. 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 SwissPalm; Q15139; -. DR BioMuta; PRKD1; -. DR DMDM; 209572639; -. DR EPD; Q15139; -. DR jPOST; Q15139; -. DR MassIVE; Q15139; -. DR MaxQB; Q15139; -. DR PaxDb; 9606-ENSP00000333568; -. DR PeptideAtlas; Q15139; -. DR ProteomicsDB; 60458; -. DR Pumba; Q15139; -. DR Antibodypedia; 4337; 1137 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 AGR; HGNC:9407; -. 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; RGKAYKW; -. DR OrthoDB; 2939922at2759; -. 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; 13 hits in 1186 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 166 other cell types or tissues. DR ExpressionAtlas; Q15139; baseline and differential. 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:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0005802; C:trans-Golgi network; IDA:UniProtKB. DR GO; GO:0030018; C:Z disc; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; IDA:CACAO. DR GO; GO:0031072; F:heat shock protein binding; IEA:Ensembl. 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:0141038; F:phosphatidylinositol 3-kinase activator activity; IDA:ParkinsonsUK-UCL. DR GO; GO:0005080; F:protein kinase C binding; IEA:Ensembl. DR GO; GO:0106310; F:protein serine kinase activity; IGI:BHF-UCL. 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:1904385; P:cellular response to angiotensin; IEA:Ensembl. DR GO; GO:1990859; P:cellular response to endothelin; IEA:Ensembl. DR GO; GO:0071447; P:cellular response to hydroperoxide; IMP:ParkinsonsUK-UCL. DR GO; GO:0071874; P:cellular response to norepinephrine stimulus; IEA:Ensembl. DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB. DR GO; GO:1904628; P:cellular response to phorbol 13-acetate 12-myristate; IEA:Ensembl. 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: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; IMP:UniProtKB. 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:0043123; P:positive regulation of canonical NF-kappaB signal transduction; IMP:UniProtKB. DR GO; GO:0045793; P:positive regulation of cell size; IEA:Ensembl. 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:0010628; P:positive regulation of gene expression; IEA:Ensembl. 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:1900227; P:positive regulation of NLRP3 inflammasome complex assembly; ISS:UniProtKB. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; ISS:UniProtKB. DR GO; GO:0090277; P:positive regulation of peptide hormone secretion; IEA:Ensembl. DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IDA:ParkinsonsUK-UCL. DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IEA:Ensembl. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IEA:Ensembl. DR GO; GO:0060298; P:positive regulation of sarcomere organization; 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: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:0051279; P:regulation of release of sequestered calcium ion into cytosol; IEA:Ensembl. DR GO; GO:0014723; P:regulation of skeletal muscle contraction by modulation of calcium ion sensitivity of myofibril; 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; cd20839; C1_PKD1_rpt1; 1. DR CDD; cd20842; C1_PKD1_rpt2; 1. DR CDD; cd01239; PH_PKD; 1. DR CDD; cd14082; STKc_PKD; 1. DR Gene3D; 3.30.60.20; -; 2. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; PROTEIN KINASE C, MU; 1. DR PANTHER; PTHR22968:SF9; SERINE_THREONINE-PROTEIN KINASE D1; 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; SSF57889; Cysteine-rich domain; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. 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. DR Genevisible; Q15139; HS. 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 //