KPCD2_HUMAN
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 03-AUG-2022, entry version 214.
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 ---------------------------------------------------------------------------
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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; 262.
DR IntAct; Q9BZL6; 84.
DR MINT; Q9BZL6; -.
DR STRING; 9606.ENSP00000393978; -.
DR BindingDB; Q9BZL6; -.
DR ChEMBL; CHEMBL4900; -.
DR DrugCentral; Q9BZL6; -.
DR GuidetoPHARMACOLOGY; 2173; -.
DR GlyGen; Q9BZL6; 1 site, 1 O-linked glycan (1 site).
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; Q9BZL6; -.
DR PeptideAtlas; Q9BZL6; -.
DR PRIDE; Q9BZL6; -.
DR ProteomicsDB; 79872; -. [Q9BZL6-1]
DR Antibodypedia; 18122; 602 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 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; 367841at2759; -.
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; 25 hits in 1119 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 199 other tissues.
DR ExpressionAtlas; Q9BZL6; baseline and differential.
DR Genevisible; Q9BZL6; HS.
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:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
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:0004697; F:protein kinase C activity; TAS:Reactome.
DR GO; GO:0005080; F:protein kinase C binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA: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:0032793; P:positive regulation of CREB transcription factor activity; IGI:BHF-UCL.
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:1901727; P:positive regulation of histone deacetylase activity; IGI:BHF-UCL.
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:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:BHF-UCL.
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:0089700; P:protein kinase D signaling; IGI: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; 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; 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 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 E-
FT 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 Ser-
FT 706 or/and Ser-710 phosphorylation. Increases NF-kappa-B
FT 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
