ID KPCD2_HUMAN Reviewed; 878 AA. AC Q9BZL6; B4DTS2; M0QZW1; M0R2R2; Q8NCK8; Q8TB08; Q9P0T6; Q9Y3X8; DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot. DT 28-MAR-2018, sequence version 3. DT 27-MAR-2024, entry version 223. DE RecName: Full=Serine/threonine-protein kinase D2; DE EC=2.7.11.13 {ECO:0000269|PubMed:11062248, ECO:0000269|PubMed:12058027, ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:28428613}; DE AltName: Full=nPKC-D2; GN Name=PRKD2; Synonyms=PKD2; ORFNames=HSPC187; 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), CATALYTIC ACTIVITY, COFACTOR, RP TISSUE SPECIFICITY, AND PHOSPHORYLATION AT SER-876. RC TISSUE=Pancreas; RX PubMed=11062248; DOI=10.1074/jbc.m008719200; RA Sturany S., Van Lint J., Mueller F., Wilda M., Hameister H., Hoecker M., RA Brey A., Gern U., Vandenheede J., Gress T., Adler G., Seufferlein T.; RT "Molecular cloning and characterization of the human protein kinase D2. A RT novel member of the protein kinase d family of serine threonine kinases."; RL J. Biol. Chem. 276:3310-3318(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3). RC TISSUE=Mammary gland, and Placenta; 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=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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 337-878 (ISOFORM 1/2). RC TISSUE=Uterus; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 574-878 (ISOFORM 1/2). RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [6] RP CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, AND PHOSPHORYLATION AT RP SER-706; SER-710 AND SER-876. RX PubMed=12058027; DOI=10.1074/jbc.m200934200; RA Sturany S., Van Lint J., Gilchrist A., Vandenheede J.R., Adler G., RA Seufferlein T.; RT "Mechanism of activation of protein kinase D2(PKD2) by the CCK(B)/gastrin RT receptor."; RL J. Biol. Chem. 277:29431-29436(2002). RN [7] RP FUNCTION IN NF-KAPPA-B ACTIVATION, PHOSPHORYLATION AT TYR-438, AND RP MUTAGENESIS OF TYR-438. RX PubMed=15604256; DOI=10.1158/0008-5472.can-04-0981; RA Mihailovic T., Marx M., Auer A., Van Lint J., Schmid M., Weber C., RA Seufferlein T.; RT "Protein kinase D2 mediates activation of nuclear factor kappaB by Bcr-Abl RT in Bcr-Abl+ human myeloid leukemia cells."; RL Cancer Res. 64:8939-8944(2004). RN [8] RP FUNCTION IN TRAFFICKING. RX PubMed=14743217; DOI=10.1038/ncb1090; RA Yeaman C., Ayala M.I., Wright J.R., Bard F., Bossard C., Ang A., Maeda Y., RA Seufferlein T., Mellman I., Nelson W.J., Malhotra V.; RT "Protein kinase D regulates basolateral membrane protein exit from trans- RT Golgi network."; RL Nat. Cell Biol. 6:106-112(2004). RN [9] RP FUNCTION IN ADAPTIVE IMMUNE RESPONSE. RX PubMed=17077180; DOI=10.1093/intimm/dxl108; RA Irie A., Harada K., Tsukamoto H., Kim J.R., Araki N., Nishimura Y.; RT "Protein kinase D2 contributes to either IL-2 promoter regulation or RT induction of cell death upon TCR stimulation depending on its activity in RT Jurkat cells."; RL Int. Immunol. 18:1737-1747(2006). RN [10] RP FUNCTION. RX PubMed=16928771; DOI=10.1152/ajpcell.00308.2006; RA Chiu T.T., Leung W.Y., Moyer M.P., Strieter R.M., Rozengurt E.; RT "Protein kinase D2 mediates lysophosphatidic acid-induced interleukin 8 RT production in nontransformed human colonic epithelial cells through NF- RT kappaB."; RL Am. J. Physiol. 292:C767-C777(2007). RN [11] RP FUNCTION IN PHOSPHORYLATION OF HDAC7, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-244. RX PubMed=17962809; DOI=10.1038/sj.emboj.7601891; RA von Blume J., Knippschild U., Dequiedt F., Giamas G., Beck A., Auer A., RA Van Lint J., Adler G., Seufferlein T.; RT "Phosphorylation at Ser244 by CK1 determines nuclear localization and RT substrate targeting of PKD2."; RL EMBO J. 26:4619-4633(2007). RN [12] RP FUNCTION IN CELL ADHESION. RX PubMed=17951978; DOI=10.1254/jphs.fp0070858; RA Ge X., Low B., Liang M., Fu J.; RT "Angiotensin II directly triggers endothelial exocytosis via protein kinase RT C-dependent protein kinase D2 activation."; RL J. Pharmacol. Sci. 105:168-176(2007). RN [13] RP PHORBOL-ESTER BINDING, AND MUTAGENESIS OF PRO-275. 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 [14] RP FUNCTION IN SECRETORY PATHWAY, AND SUBCELLULAR LOCATION. RX PubMed=18262756; DOI=10.1016/j.cellsig.2008.01.003; RA von Wichert G., Edenfeld T., von Blume J., Krisp H., Krndija D., Schmid H., RA Oswald F., Lother U., Walther P., Adler G., Seufferlein T.; RT "Protein kinase D2 regulates chromogranin A secretion in human BON RT neuroendocrine tumour cells."; RL Cell. Signal. 20:925-934(2008). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-710 AND SER-876, 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 [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200; SER-203; SER-206; RP SER-214 AND SER-710, 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 [17] 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 [18] RP FUNCTION, AND INTERACTION WITH LCK. RX PubMed=19192391; DOI=10.5483/bmbrep.2009.42.1.035; RA Li Q., Sun X., Wu J., Lin Z., Luo Y.; RT "PKD2 interacts with Lck and regulates NFAT activity in T cells."; RL BMB Rep. 42:35-40(2009). RN [19] RP FUNCTION IN ANGIOGENESIS. RX PubMed=19001381; DOI=10.1074/jbc.m807546200; RA Hao Q., Wang L., Zhao Z.J., Tang H.; RT "Identification of protein kinase D2 as a pivotal regulator of endothelial RT cell proliferation, migration, and angiogenesis."; RL J. Biol. Chem. 284:799-806(2009). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-206; SER-518; SER-710; RP TYR-717 AND SER-876, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [22] 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 [23] 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 [24] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, 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 [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197; SER-198; SER-200; RP SER-203; SER-206 AND SER-710, AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [26] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214, 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 [27] RP FUNCTION, INTERACTION WITH CIB1 ISOFORM 2, AND MUTAGENESIS OF SER-244; RP ASP-695; SER-706 AND SER-710. RX PubMed=23503467; DOI=10.1038/onc.2013.43; RA Armacki M., Joodi G., Nimmagadda S.C., de Kimpe L., Pusapati G.V., RA Vandoninck S., Van Lint J., Illing A., Seufferlein T.; RT "A novel splice variant of calcium and integrin-binding protein 1 mediates RT protein kinase D2-stimulated tumour growth by regulating angiogenesis."; RL Oncogene 33:1167-1180(2014). RN [28] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION, INTERACTION RP WITH PRKCD, MOTIF, PHOSPHORYLATION AT SER-706; SER-710 AND TYR-717, AND RP MUTAGENESIS OF TYR-87; TYR-438; SER-706; SER-710; TYR-717 AND RP 724-LEU--GLN-726. RX PubMed=28428613; DOI=10.1038/s41598-017-00800-w; RA Cobbaut M., Derua R., Doeppler H., Lou H.J., Vandoninck S., Storz P., RA Turk B.E., Seufferlein T., Waelkens E., Janssens V., Van Lint J.; RT "Differential regulation of PKD isoforms in oxidative stress conditions RT through phosphorylation of a conserved Tyr in the P+1 loop."; RL Sci. Rep. 7:887-887(2017). RN [29] RP STRUCTURE BY NMR OF 395-509. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the PH domain of protein kinase C, D2 type from RT human."; RL Submitted (NOV-2005) to the PDB data bank. RN [30] RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 526-534. RX PubMed=18836451; DOI=10.1038/ni.1660; RA Mohammed F., Cobbold M., Zarling A.L., Salim M., Barrett-Wilt G.A., RA Shabanowitz J., Hunt D.F., Engelhard V.H., Willcox B.E.; RT "Phosphorylation-dependent interaction between antigenic peptides and MHC RT class I: a molecular basis for the presentation of transformed self."; RL Nat. Immunol. 9:1236-1243(2008). RN [31] RP VARIANTS [LARGE SCALE ANALYSIS] MET-324; VAL-496; GLY-604; ARG-773; GLU-848 RP AND GLU-870. 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: 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 cell CC proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress-induced CC NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, CC signaling downstream of T-cell antigen receptor (TCR) and cytokine CC production, and plays a role in Golgi membrane trafficking, CC angiogenesis, secretory granule release and cell adhesion CC (PubMed:15604256, PubMed:14743217, PubMed:17077180, PubMed:16928771, CC PubMed:17962809, PubMed:17951978, PubMed:18262756, PubMed:19192391, CC PubMed:19001381, PubMed:23503467, PubMed:28428613). May potentiate CC mitogenesis induced by the neuropeptide bombesin by mediating an CC increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to CC accumulation of immediate-early gene products including FOS that CC stimulate cell cycle progression (By similarity). In response to CC oxidative stress, is phosphorylated at Tyr-438 and Tyr-717 by ABL1, CC which leads to the activation of PRKD2 without increasing its catalytic CC activity, and mediates activation of NF-kappa-B (PubMed:15604256, CC PubMed:28428613). In response to the activation of the gastrin receptor CC CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates CC to the nucleus, phosphorylates HDAC7, leading to nuclear export of CC HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77 CC (PubMed:17962809). Upon TCR stimulation, is activated independently of CC ZAP70, translocates from the cytoplasm to the nucleus and is required CC for interleukin-2 (IL2) promoter up-regulation (PubMed:17077180). CC During adaptive immune responses, is required in peripheral T- CC lymphocytes for the production of the effector cytokines IL2 and IFNG CC after TCR engagement and for optimal induction of antibody responses to CC antigens (By similarity). In epithelial cells stimulated with CC lysophosphatidic acid (LPA), is activated through a PKC-dependent CC pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a CC NF-kappa-B-dependent pathway (PubMed:16928771). During TCR-induced T- CC cell activation, interacts with and is activated by the tyrosine kinase CC LCK, which results in the activation of the NFAT transcription factors CC (PubMed:19192391). In the trans-Golgi network (TGN), regulates the CC fission of transport vesicles that are on their way to the plasma CC membrane and in polarized cells is involved in the transport of CC proteins from the TGN to the basolateral membrane (PubMed:14743217). CC Plays an important role in endothelial cell proliferation and migration CC prior to angiogenesis, partly through modulation of the expression of CC KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in CC angiogenesis (PubMed:19001381). In secretory pathway, is required for CC the release of chromogranin-A (CHGA)-containing secretory granules from CC the TGN (PubMed:18262756). Downstream of PRKCA, plays important roles CC in angiotensin-2-induced monocyte adhesion to endothelial cells CC (PubMed:17951978). Plays a regulatory role in angiogenesis and tumor CC growth by phosphorylating a downstream mediator CIB1 isoform 2, CC resulting in vascular endothelial growth factor A (VEGFA) secretion CC (PubMed:23503467). {ECO:0000250|UniProtKB:Q8BZ03, CC ECO:0000269|PubMed:14743217, ECO:0000269|PubMed:15604256, CC ECO:0000269|PubMed:16928771, ECO:0000269|PubMed:17077180, CC ECO:0000269|PubMed:17951978, ECO:0000269|PubMed:17962809, CC ECO:0000269|PubMed:18262756, ECO:0000269|PubMed:19001381, CC ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, CC ECO:0000269|PubMed:28428613}. 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:11062248, ECO:0000269|PubMed:12058027, CC ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:28428613}; 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:11062248, CC ECO:0000269|PubMed:12058027, ECO:0000269|PubMed:17962809, CC ECO:0000269|PubMed:28428613}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000269|PubMed:11062248, ECO:0000269|PubMed:12058027, CC ECO:0000269|PubMed:28428613}; CC -!- ACTIVITY REGULATION: Activated by DAG and phorbol esters CC (PubMed:12058027, PubMed:17962809, PubMed:28428613). Phorbol-ester/DAG- CC type domains bind DAG, mediating translocation to membranes CC (PubMed:17962809). Autophosphorylation of Ser-710 and phosphorylation CC of Ser-706 by PKC relieves auto-inhibition by the PH domain CC (PubMed:17962809). Catalytic activity is further increased by CC phosphorylation at Tyr-717 in response to oxidative stress CC (PubMed:28428613). {ECO:0000269|PubMed:12058027, CC ECO:0000269|PubMed:17962809, ECO:0000269|PubMed:28428613}. CC -!- SUBUNIT: Interacts (via C-terminus) with LCK (PubMed:19192391). CC Interacts (via N-terminal AP-rich region) with CIB1 isoform 2 CC (PubMed:23503467). Interacts (via N-terminus and zing-finger domain 1 CC and 2) with PRKCD in response to oxidative stress; the interaction is CC independent of PRKD2 tyrosine phosphorylation (PubMed:28428613). CC {ECO:0000269|PubMed:19192391, ECO:0000269|PubMed:23503467, CC ECO:0000269|PubMed:28428613}. CC -!- INTERACTION: CC Q9BZL6; Q8WUI4: HDAC7; NbExp=6; IntAct=EBI-1384325, EBI-1048378; CC Q9BZL6; Q04917: YWHAH; NbExp=2; IntAct=EBI-1384325, EBI-306940; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17962809}. Cell CC membrane {ECO:0000250|UniProtKB:Q15139}. Nucleus CC {ECO:0000269|PubMed:17962809}. Golgi apparatus, trans-Golgi network CC {ECO:0000269|PubMed:18262756}. Note=Translocation to the cell membrane CC is required for kinase activation. Accumulates in the nucleus upon CK1- CC mediated phosphorylation after activation of G-protein-coupled CC receptors. Nuclear accumulation is regulated by blocking nuclear export CC of active PRKD2 rather than by increasing import. CC {ECO:0000269|PubMed:17962809}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q9BZL6-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9BZL6-2; Sequence=VSP_057279; CC Name=3; CC IsoId=Q9BZL6-3; Sequence=VSP_059398; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:11062248}. CC -!- PTM: Phosphorylation of Ser-876 correlates with the activation status CC of the kinase (PubMed:11062248). Ser-706 or/and Ser-710 are probably CC phosphorylated by PKC (PubMed:12058027, PubMed:28428613). CC Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear CC localization and substrate targeting (PubMed:17962809). Phosphorylation CC at Ser-244, Ser-706 and Ser-710 is required for nuclear localization CC (PubMed:17962809). Phosphorylated at Tyr-438 by ABL1 in response to CC oxidative stress (PubMed:15604256). Phosphorylated at Tyr-717 by ABL1 CC specifically in response to oxidative stress; requires prior CC phosphorylation at Ser-706 or/and Ser-710 (PubMed:28428613). CC {ECO:0000269|PubMed:11062248, ECO:0000269|PubMed:12058027, CC ECO:0000269|PubMed:15604256, ECO:0000269|PubMed:17962809, CC ECO:0000269|PubMed:28428613}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. PKD subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF36107.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF309082; AAK01149.1; -; mRNA. DR EMBL; AK074673; BAC11127.1; -; mRNA. DR EMBL; AK095884; BAG53158.1; -; mRNA. DR EMBL; AK300339; BAG62084.1; -; mRNA. DR EMBL; AC008635; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC093503; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; KC877745; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL050147; CAB43292.1; -; mRNA. DR EMBL; AF151021; AAF36107.1; ALT_FRAME; mRNA. DR CCDS; CCDS12689.1; -. [Q9BZL6-1] DR CCDS; CCDS59401.1; -. [Q9BZL6-2] DR PIR; T08777; T08777. DR RefSeq; NP_001073349.1; NM_001079880.1. [Q9BZL6-1] DR RefSeq; NP_001073350.1; NM_001079881.1. [Q9BZL6-1] DR RefSeq; NP_001073351.1; NM_001079882.1. [Q9BZL6-2] DR RefSeq; NP_057541.2; NM_016457.4. [Q9BZL6-1] DR RefSeq; XP_005258773.2; XM_005258716.2. [Q9BZL6-2] DR PDB; 2COA; NMR; -; A=398-509. DR PDB; 3BGM; X-ray; 1.60 A; C=526-534. DR PDB; 4NNX; X-ray; 2.10 A; C=526-534. DR PDB; 4NNY; X-ray; 1.90 A; C=526-534. DR PDBsum; 2COA; -. DR PDBsum; 3BGM; -. DR PDBsum; 4NNX; -. DR PDBsum; 4NNY; -. DR AlphaFoldDB; Q9BZL6; -. DR BMRB; Q9BZL6; -. DR SMR; Q9BZL6; -. DR BioGRID; 117384; 310. DR IntAct; Q9BZL6; 86. DR MINT; Q9BZL6; -. DR STRING; 9606.ENSP00000393978; -. DR BindingDB; Q9BZL6; -. DR ChEMBL; CHEMBL4900; -. DR DrugCentral; Q9BZL6; -. DR GuidetoPHARMACOLOGY; 2173; -. DR GlyGen; Q9BZL6; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9BZL6; -. DR PhosphoSitePlus; Q9BZL6; -. DR BioMuta; PRKD2; -. DR DMDM; 296434570; -. DR CPTAC; CPTAC-1364; -. DR EPD; Q9BZL6; -. DR jPOST; Q9BZL6; -. DR MassIVE; Q9BZL6; -. DR MaxQB; Q9BZL6; -. DR PaxDb; 9606-ENSP00000393978; -. DR PeptideAtlas; Q9BZL6; -. DR ProteomicsDB; 79872; -. [Q9BZL6-1] DR Pumba; Q9BZL6; -. DR Antibodypedia; 18122; 675 antibodies from 41 providers. DR DNASU; 25865; -. DR Ensembl; ENST00000291281.9; ENSP00000291281.3; ENSG00000105287.13. [Q9BZL6-1] DR Ensembl; ENST00000433867.5; ENSP00000393978.1; ENSG00000105287.13. [Q9BZL6-1] DR Ensembl; ENST00000595515.5; ENSP00000470804.1; ENSG00000105287.13. [Q9BZL6-3] DR Ensembl; ENST00000600194.5; ENSP00000472744.1; ENSG00000105287.13. [Q9BZL6-2] DR Ensembl; ENST00000601806.5; ENSP00000469106.1; ENSG00000105287.13. [Q9BZL6-2] DR GeneID; 25865; -. DR KEGG; hsa:25865; -. DR MANE-Select; ENST00000291281.9; ENSP00000291281.3; NM_016457.5; NP_057541.2. DR UCSC; uc002pfi.4; human. [Q9BZL6-1] DR UCSC; uc010xye.3; human. DR AGR; HGNC:17293; -. DR CTD; 25865; -. DR DisGeNET; 25865; -. DR GeneCards; PRKD2; -. DR HGNC; HGNC:17293; PRKD2. DR HPA; ENSG00000105287; Low tissue specificity. DR MIM; 607074; gene. DR neXtProt; NX_Q9BZL6; -. DR OpenTargets; ENSG00000105287; -. DR PharmGKB; PA134903505; -. DR VEuPathDB; HostDB:ENSG00000105287; -. DR eggNOG; KOG4236; Eukaryota. DR GeneTree; ENSGT00950000183024; -. DR HOGENOM; CLU_009772_1_0_1; -. DR InParanoid; Q9BZL6; -. DR OMA; KSPPWDI; -. DR OrthoDB; 2939922at2759; -. DR PhylomeDB; Q9BZL6; -. DR TreeFam; TF314320; -. DR BRENDA; 2.7.11.13; 2681. DR PathwayCommons; Q9BZL6; -. DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis. DR SignaLink; Q9BZL6; -. DR SIGNOR; Q9BZL6; -. DR BioGRID-ORCS; 25865; 31 hits in 1202 CRISPR screens. DR ChiTaRS; PRKD2; human. DR EvolutionaryTrace; Q9BZL6; -. DR GeneWiki; PRKD2; -. DR GenomeRNAi; 25865; -. DR Pharos; Q9BZL6; Tchem. DR PRO; PR:Q9BZL6; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9BZL6; Protein. DR Bgee; ENSG00000105287; Expressed in vena cava and 201 other cell types or tissues. DR ExpressionAtlas; Q9BZL6; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; TAS:Reactome. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; IDA:BHF-UCL. DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB. 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:0002250; P:adaptive immune response; IEA:UniProtKB-KW. DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW. DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW. DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL. DR GO; GO:0061154; P:endothelial tube morphogenesis; TAS:BHF-UCL. DR GO; GO:0035556; P:intracellular signal transduction; IMP:BHF-UCL. 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:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL. DR GO; GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISS:UniProtKB. DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:UniProtKB. 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; IMP:UniProtKB. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB. DR GO; GO:0045743; P:positive regulation of fibroblast growth factor receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISS:UniProtKB. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB. DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; IMP:BHF-UCL. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL. DR GO; GO:0006468; P:protein phosphorylation; IDA:CACAO. DR GO; GO:0070232; P:regulation of T cell apoptotic process; IMP:BHF-UCL. DR GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome. DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:BHF-UCL. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL. DR CDD; cd20840; C1_PKD2_rpt1; 1. DR CDD; cd20843; C1_PKD2_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:SF12; SERINE_THREONINE-PROTEIN KINASE D2; 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; Q9BZL6; HS. PE 1: Evidence at protein level; KW 3D-structure; Adaptive immunity; Alternative splicing; Angiogenesis; KW ATP-binding; Cell adhesion; Cell membrane; Cytoplasm; Golgi apparatus; KW Immunity; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. FT CHAIN 1..878 FT /note="Serine/threonine-protein kinase D2" FT /id="PRO_0000055716" FT DOMAIN 397..509 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 551..807 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT ZN_FING 138..188 FT /note="Phorbol-ester/DAG-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT ZN_FING 264..314 FT /note="Phorbol-ester/DAG-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT REGION 1..35 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 224..247 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 343..373 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 844..869 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 724..726 FT /note="Important for ABL1-mediated Tyr-717 phosphorylation" FT /evidence="ECO:0000269|PubMed:28428613" FT COMPBIAS 10..35 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 674 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 557..565 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 580 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 30 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O94806" FT MOD_RES 87 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q15139" FT MOD_RES 197 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 198 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 200 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 203 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163" FT MOD_RES 206 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:23186163" FT MOD_RES 212 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8BZ03" FT MOD_RES 214 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:24275569" FT MOD_RES 244 FT /note="Phosphoserine; by CSNK1D and CSNK1E" FT /evidence="ECO:0000269|PubMed:17962809" FT MOD_RES 407 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q15139" FT MOD_RES 438 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:15604256, FT ECO:0000305|PubMed:28428613" FT MOD_RES 518 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES 706 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000269|PubMed:12058027, FT ECO:0000269|PubMed:28428613" FT MOD_RES 710 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:12058027, FT ECO:0000269|PubMed:28428613, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19369195, FT ECO:0007744|PubMed:23186163" FT MOD_RES 717 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000269|PubMed:28428613, FT ECO:0007744|PubMed:19369195" FT MOD_RES 876 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000269|PubMed:11062248, FT ECO:0000269|PubMed:12058027, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:19369195" FT VAR_SEQ 1..157 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_057279" FT VAR_SEQ 779 FT /note="G -> GGAWGPPTPWA (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_059398" FT VARIANT 324 FT /note="V -> M (in dbSNP:rs45455991)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042330" FT VARIANT 496 FT /note="A -> V (in dbSNP:rs55716765)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042331" FT VARIANT 604 FT /note="S -> G (in dbSNP:rs34325043)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042332" FT VARIANT 773 FT /note="W -> R (in dbSNP:rs55933311)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042333" FT VARIANT 835 FT /note="A -> V (in dbSNP:rs314665)" FT /id="VAR_061531" FT VARIANT 848 FT /note="G -> E (in a lung adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042334" FT VARIANT 870 FT /note="G -> E (in a gastric adenocarcinoma sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042335" FT MUTAGEN 87 FT /note="Y->F: Loss of phosphorylation. No effect on the FT interaction with PRKCD. No effect on Ser-706 or/and Ser-710 FT phosphorylation." FT /evidence="ECO:0000269|PubMed:28428613" FT MUTAGEN 244 FT /note="S->E: Constitutive kinase activity; when associated FT with E-706 and E-710." FT /evidence="ECO:0000269|PubMed:23503467" FT MUTAGEN 275 FT /note="P->G: Increase in ability to bind phorbol ester, FT slight increase in ability to bind DAG." FT /evidence="ECO:0000269|PubMed:18076381" FT MUTAGEN 438 FT /note="Y->D: Slight increase in Tyr-717 phosphorylation. No FT effect on Ser-706 or/and Ser-710 phosphorylation. Increase FT in Tyr-717 phosphorylation; when associated with E-706 and FT E-710." FT /evidence="ECO:0000269|PubMed:28428613" FT MUTAGEN 438 FT /note="Y->F: Loss of phosphorylation. No effect on FT phosphorylation of Tyr-717 and on Ser-706 or/and Ser-710 FT phosphorylation." FT /evidence="ECO:0000269|PubMed:15604256, FT ECO:0000269|PubMed:28428613" FT MUTAGEN 695 FT /note="D->A: Loss of kinase activity." FT /evidence="ECO:0000269|PubMed:23503467" FT MUTAGEN 706 FT /note="S->A: Abolishes phosphorylation. Loss of Tyr-717 FT phosphorylation and any other tyrosine phosphorylation, and FT increases NF-kappa-B activation in response to oxidative FT stress; when associated with A-710." FT /evidence="ECO:0000269|PubMed:28428613" FT MUTAGEN 706 FT /note="S->E: Constitutive kinase activity; when associated FT with E-710 or with E-244 and E-710. Increases Tyr-717 FT phosphorylation; when associated with E-710 or with E-710 FT and D-438." FT /evidence="ECO:0000269|PubMed:23503467, FT ECO:0000269|PubMed:28428613" FT MUTAGEN 710 FT /note="S->A: Abolishes phosphorylation. Loss of Tyr-717 FT phosphorylation and any other tyrosine phosphorylation, and FT increases NF-kappa-B activation in response to oxidative FT stress; when associated with A-706." FT /evidence="ECO:0000269|PubMed:28428613" FT MUTAGEN 710 FT /note="S->E: Constitutive kinase activity; when associated FT with E-706 or with E-244 and E-706. when associated with FT E-710 or with E-244 and E-710. Increases Tyr-717 FT phosphorylation; when associated with E-710 or with E-710 FT and D-438." FT /evidence="ECO:0000269|PubMed:23503467, FT ECO:0000269|PubMed:28428613" FT MUTAGEN 717 FT /note="Y->F: Abolishes phosphorylation. Decreases substrate FT affinity and increases catalytic efficiency. Increases FT Ser-706 or/and Ser-710 phosphorylation. Increases FT NF-kappa-B activation in response to oxidative stress." FT /evidence="ECO:0000269|PubMed:28428613" FT MUTAGEN 724..726 FT /note="LNQ->RNK: Reduced catalytic activity. Severe FT reduction in Tyr-717 phosphorylation by ABL1 in response to FT oxidative stress. No effect on Ser-706 or/and Ser-710 FT phosphorylation and on NF-kappa-B activation in response to FT oxidative stress." FT /evidence="ECO:0000269|PubMed:28428613" FT CONFLICT 790 FT /note="V -> L (in Ref. 5; AAF36107)" FT /evidence="ECO:0000305" FT STRAND 399..406 FT /evidence="ECO:0007829|PDB:2COA" FT STRAND 409..411 FT /evidence="ECO:0007829|PDB:2COA" FT STRAND 415..421 FT /evidence="ECO:0007829|PDB:2COA" FT STRAND 423..433 FT /evidence="ECO:0007829|PDB:2COA" FT STRAND 438..442 FT /evidence="ECO:0007829|PDB:2COA" FT TURN 443..445 FT /evidence="ECO:0007829|PDB:2COA" FT STRAND 448..452 FT /evidence="ECO:0007829|PDB:2COA" FT STRAND 456..458 FT /evidence="ECO:0007829|PDB:2COA" FT STRAND 465..470 FT /evidence="ECO:0007829|PDB:2COA" FT STRAND 486..488 FT /evidence="ECO:0007829|PDB:2COA" FT HELIX 495..507 FT /evidence="ECO:0007829|PDB:2COA" SQ SEQUENCE 878 AA; 96722 MW; 8BAB45E8F99D23E7 CRC64; MATAPSYPAG LPGSPGPGSP PPPGGLELQS PPPLLPQIPA PGSGVSFHIQ IGLTREFVLL PAASELAHVK QLACSIVDQK FPECGFYGLY DKILLFKHDP TSANLLQLVR SSGDIQEGDL VEVVLSASAT FEDFQIRPHA LTVHSYRAPA FCDHCGEMLF GLVRQGLKCD GCGLNYHKRC AFSIPNNCSG ARKRRLSSTS LASGHSVRLG TSESLPCTAE ELSRSTTELL PRRPPSSSSS SSASSYTGRP IELDKMLLSK VKVPHTFLIH SYTRPTVCQA CKKLLKGLFR QGLQCKDCKF NCHKRCATRV PNDCLGEALI NGDVPMEEAT DFSEADKSAL MDESEDSGVI PGSHSENALH ASEEEEGEGG KAQSSLGYIP LMRVVQSVRH TTRKSSTTLR EGWVVHYSNK DTLRKRHYWR LDCKCITLFQ NNTTNRYYKE IPLSEILTVE SAQNFSLVPP GTNPHCFEIV TANATYFVGE MPGGTPGGPS GQGAEAARGW ETAIRQALMP VILQDAPSAP GHAPHRQASL SISVSNSQIQ ENVDIATVYQ IFPDEVLGSG QFGVVYGGKH RKTGRDVAVK VIDKLRFPTK QESQLRNEVA ILQSLRHPGI VNLECMFETP EKVFVVMEKL HGDMLEMILS SEKGRLPERL TKFLITQILV ALRHLHFKNI VHCDLKPENV LLASADPFPQ VKLCDFGFAR IIGEKSFRRS VVGTPAYLAP EVLLNQGYNR SLDMWSVGVI MYVSLSGTFP FNEDEDINDQ IQNAAFMYPA SPWSHISAGA IDLINNLLQV KMRKRYSVDK SLSHPWLQEY QTWLDLRELE GKMGERYITH ESDDARWEQF AAEHPLPGSG LPTDRDLGGA CPPQDHDMQG LAERISVL //