ID KPCD2_RAT Reviewed; 875 AA. AC Q5XIS9; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 23-NOV-2004, sequence version 1. DT 27-MAR-2024, entry version 159. DE RecName: Full=Serine/threonine-protein kinase D2; DE EC=2.7.11.13 {ECO:0000250|UniProtKB:Q9BZL6}; DE AltName: Full=nPKC-D2; GN Name=Prkd2; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [2] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197; SER-203; SER-211; RP SER-214 AND SER-711, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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. May CC potentiate mitogenesis induced by the neuropeptide bombesin 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. In response to oxidative CC stress, is phosphorylated at Tyr-438 and Tyr-718 by ABL1, which leads CC to the activation of PRKD2 without increasing its catalytic activity, CC and mediates activation of NF-kappa-B. In response to the activation of CC the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CC CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to CC nuclear export of HDAC7 and inhibition of HDAC7 transcriptional CC repression of NR4A1/NUR77. Upon TCR stimulation, is activated CC independently of ZAP70, translocates from the cytoplasm to the nucleus CC and is required for interleukin-2 (IL2) promoter up-regulation. During CC adaptive immune responses, is required in peripheral T-lymphocytes for CC the production of the effector cytokines IL2 and IFNG after TCR CC engagement and for optimal induction of antibody responses to antigens. CC In epithelial cells stimulated with lysophosphatidic acid (LPA), is CC activated through a PKC-dependent pathway and mediates LPA-stimulated CC interleukin-8 (IL8) secretion via a NF-kappa-B-dependent pathway. CC During TCR-induced T-cell activation, interacts with and is activated CC by the tyrosine kinase LCK, which results in the activation of the NFAT CC transcription factors. 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. Plays an important CC role in endothelial cell proliferation and migration prior to CC angiogenesis, partly through modulation of the expression of KDR/VEGFR2 CC and FGFR1, two key growth factor receptors involved in angiogenesis. In CC secretory pathway, is required for the release of chromogranin-A CC (CHGA)-containing secretory granules from the TGN. Downstream of PRKCA, CC plays important roles in angiotensin-2-induced monocyte adhesion to CC endothelial cells. {ECO:0000250}. 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:0000250|UniProtKB:Q9BZL6}; 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:0000250|UniProtKB:Q9BZL6}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q9BZL6}; CC -!- ACTIVITY REGULATION: Activated by DAG and phorbol esters. Phorbol- CC ester/DAG-type domains bind DAG, mediating translocation to membranes. CC Autophosphorylation of Ser-711 and phosphorylation of Ser-707 by PKC CC relieves auto-inhibition by the PH domain. Catalytic activity is CC further increased by phosphorylation at Tyr-718 in response to CC oxidative stress. {ECO:0000250|UniProtKB:Q9BZL6}. CC -!- SUBUNIT: Interacts (via C-terminus) with LCK. Interacts (via N-terminus CC and zing-finger domain 1 and 2) with PRKCD in response to oxidative CC stress; the interaction is independent of PRKD2 tyrosine CC phosphorylation. {ECO:0000250|UniProtKB:Q9BZL6}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BZL6}. Cell CC membrane {ECO:0000250|UniProtKB:Q15139}. Golgi apparatus, trans-Golgi CC network {ECO:0000250|UniProtKB:Q9BZL6}. Note=Translocation to the cell CC membrane is required for kinase activation. Accumulates in the nucleus CC upon CK1-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:0000250|UniProtKB:Q9BZL6}. CC -!- PTM: Phosphorylation of Ser-873 correlates with the activation status CC of the kinase. Ser-707 is probably phosphorylated by PKC. CC Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear CC localization and substrate targeting. Phosphorylation at Ser-244, Ser- CC 707 and Ser-711 is required for nuclear localization. Phosphorylated at CC Tyr-438 by ABL1 in response to oxidative stress. Phosphorylated at Tyr- CC 718 by ABL1 specifically in response to oxidative stress; requires CC prior phosphorylation at Ser-707 or/and Ser-711. CC {ECO:0000250|UniProtKB:Q9BZL6}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr CC protein kinase family. PKD subfamily. {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; BC083592; AAH83592.1; -; mRNA. DR RefSeq; NP_001013917.1; NM_001013895.1. DR AlphaFoldDB; Q5XIS9; -. DR SMR; Q5XIS9; -. DR STRING; 10116.ENSRNOP00000022360; -. DR iPTMnet; Q5XIS9; -. DR PhosphoSitePlus; Q5XIS9; -. DR PaxDb; 10116-ENSRNOP00000022360; -. DR Ensembl; ENSRNOT00000022360.6; ENSRNOP00000022360.3; ENSRNOG00000016434.6. DR Ensembl; ENSRNOT00055054123; ENSRNOP00055044762; ENSRNOG00055031225. DR Ensembl; ENSRNOT00060038398; ENSRNOP00060031666; ENSRNOG00060022147. DR Ensembl; ENSRNOT00065055289; ENSRNOP00065045480; ENSRNOG00065032097. DR GeneID; 292658; -. DR KEGG; rno:292658; -. DR UCSC; RGD:1308054; rat. DR AGR; RGD:1308054; -. DR CTD; 25865; -. DR RGD; 1308054; Prkd2. DR eggNOG; KOG4236; Eukaryota. DR GeneTree; ENSGT00950000183024; -. DR HOGENOM; CLU_009772_1_0_1; -. DR InParanoid; Q5XIS9; -. DR OMA; WVVHYSS; -. DR OrthoDB; 2939922at2759; -. DR PhylomeDB; Q5XIS9; -. DR TreeFam; TF314320; -. DR PRO; PR:Q5XIS9; -. DR Proteomes; UP000002494; Chromosome 1. DR Bgee; ENSRNOG00000016434; Expressed in thymus and 19 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISO:RGD. 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; IEA:UniProtKB-EC. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004672; F:protein kinase activity; ISO:RGD. DR GO; GO:0005080; F:protein kinase C binding; ISO:RGD. DR GO; GO:0106310; F:protein serine kinase activity; ISO:RGD. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD. 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; ISO:RGD. DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB. DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD. DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS: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; ISS:UniProtKB. DR GO; GO:2001028; P:positive regulation of endothelial cell chemotaxis; ISO:RGD. DR GO; GO:0038033; P:positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway; ISO:RGD. DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISS:UniProtKB. DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISS: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; ISS: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; ISS:UniProtKB. DR GO; GO:1902533; P:positive regulation of intracellular signal transduction; ISO:RGD. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS: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; ISO:RGD. DR GO; GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0070232; P:regulation of T cell apoptotic process; ISO:RGD. DR GO; GO:0050852; P:T cell receptor signaling pathway; ISO:RGD. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; ISO:RGD. 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; Q5XIS9; RN. PE 1: Evidence at protein level; KW Adaptive immunity; Angiogenesis; ATP-binding; Cell adhesion; Cell membrane; KW Cytoplasm; Golgi apparatus; Immunity; Kinase; Magnesium; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Repeat; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. FT CHAIN 1..875 FT /note="Serine/threonine-protein kinase D2" FT /id="PRO_0000260437" FT DOMAIN 398..510 FT /note="PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145" FT DOMAIN 552..808 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 265..315 FT /note="Phorbol-ester/DAG-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226" FT REGION 1..33 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 MOTIF 725..727 FT /note="Important for ABL1-mediated Tyr-718 phosphorylation" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT COMPBIAS 10..33 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 675 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 558..566 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 581 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 26 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O94806" 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:22673903" FT MOD_RES 198 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT MOD_RES 200 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT MOD_RES 203 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 206 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT MOD_RES 211 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" 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:22673903" FT MOD_RES 244 FT /note="Phosphoserine; by CSNK1D and CSNK1E" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT MOD_RES 245 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT MOD_RES 408 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q15139" FT MOD_RES 439 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT MOD_RES 519 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT MOD_RES 707 FT /note="Phosphoserine; by PKC" FT /evidence="ECO:0000250|UniProtKB:Q15139" FT MOD_RES 711 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 718 FT /note="Phosphotyrosine; by ABL1" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" FT MOD_RES 873 FT /note="Phosphoserine; by autocatalysis" FT /evidence="ECO:0000250|UniProtKB:Q9BZL6" SQ SEQUENCE 875 AA; 96497 MW; 789FD9853EEDF6A1 CRC64; MAAAPSHPAG LPCSPGPGSP PPPGGSDLQS LPPLLPQIPA PGSGVSFHIQ IGLTREFVLL PAASELAHVK QLACSIVDQK FPECGFYGLY DKILLFKHDP TSANLLQLVR SAADIQEGDL VEVVLSASAT FEDFQIRPHA LTVHSYRAPA FCDHCGEMLF GLVRQGLKCD GCGLNYHKRC AFSIPNNCSG ARKRRLSSTS LASGHSVRLG SSESLPCTAE ELSRSTTDLL PRRPPSSSSS SSSSSFYTGR PIELDKMLMS KVKVPHTFLI HSYTRPTVCQ ACKKLLKGLF RQGLQCKDCK FNCHKRCATR VPNDCLGEAL INGDVPMEEA ADYSEADKSS LSDELEDSGV IPGSHAENAL HASEEEEGEG GKAQSSLGYI PLMRVVQSVR HTTRKSSTTL REGWVVHYSN KDTLRKRHYW RLDCKCITLF QNNTTNRYYK EIPLSEILAV EPAQNFSLVP PGTNPHCFEI ITANVTYFVG ETPGGAPGGP SGQGTEAARG WETAIRQALM PVILQDAPSA PGHTPHRQAS LSISVSNSQI QENVDIATVY QIFPDEVLGS GQFGVVYGGK HRKTGRDVAV KVIDKLRFPT KQESQLRNEV AILQSLRHPG IVNLECMFET PEKVFVVMEK LHGDMLEMIL SSEKGRLPER LTKFLITQIL VALRHLHFKN IVHCDLKPEN VLLASADPFP QVKLCDFGFA RIIGEKSFRR SVVGTPAYLA PEVLLNQGYN RSLDMWSVGV IMYVSLSGTF PFNEDEDIND QIQNAAFMYP ASPWSHISSG AIDLINNLLQ VKMRKRYSVD KSLSHPWLQE YQTWLDLREL EGKMGERYIT HESDDARWDQ FVSERHGTPA EGDLGGACLP QDHEMQGLAE RISIL //