CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-020412
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase D2 
Protein Synonyms/Alias
 nPKC-D2 
Gene Name
 PRKD2 
Gene Synonyms/Alias
 PKD2; HSPC187 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
97YDKILLFKHDPTSANubiquitination[1]
260LDKMLLSKVKVPHTFubiquitination[1]
286QACKKLLKGLFRQGLubiquitination[2]
424HYWRLDCKCITLFQNubiquitination[1]
Reference
 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473] 
Functional Description
 Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of cell proliferation via MAPK1/3 (ERK1/2) signaling, oxidative stress- induced NF-kappa-B activation, inhibition of HDAC7 transcriptional repression, signaling downstream of T-cell antigen receptor (TCR) and cytokine production, and plays a role in Golgi membrane trafficking, angiogenesis, secretory granule release and cell adhesion. May potentiate mitogenesis induced by the neuropeptide bombesin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. In response to oxidative stress, is phosphorylated at Tyr-438 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B. In response to the activation of the gastrin receptor CCKBR, is phosphorylated at Ser-244 by CSNK1D and CSNK1E, translocates to the nucleus, phosphorylates HDAC7, leading to nuclear export of HDAC7 and inhibition of HDAC7 transcriptional repression of NR4A1/NUR77. Upon TCR stimulation, is activated independently of ZAP70, translocates from the cytoplasm to the nucleus and is required for interleukin-2 (IL2) promoter up-regulation. During adaptive immune responses, is required in peripheral T-lymphocytes for the production of the effector cytokines IL2 and IFNG after TCR engagement and for optimal induction of antibody responses to antigens. In epithelial cells stimulated with lysophosphatidic acid (LPA), is activated through a PKC-dependent pathway and mediates LPA-stimulated interleukin-8 (IL8) secretion via a NF- kappa-B-dependent pathway. During TCR-induced T-cell activation, interacts with and is activated by the tyrosine kinase LCK, which results in the activation of the NFAT transcription factors. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane and in polarized cells is involved in the transport of proteins from the TGN to the basolateral membrane. Plays an important role in endothelial cell proliferation and migration prior to angiogenesis, partly through modulation of the expression of KDR/VEGFR2 and FGFR1, two key growth factor receptors involved in angiogenesis. In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN. Downstream of PRKCA, plays important roles in angiotensin-2- induced monocyte adhesion to endothelial cells. 
Sequence Annotation
 DOMAIN 397 509 PH.
 DOMAIN 551 807 Protein kinase.
 ZN_FING 138 188 Phorbol-ester/DAG-type 1.
 ZN_FING 264 314 Phorbol-ester/DAG-type 2.
 NP_BIND 557 565 ATP (By similarity).
 ACT_SITE 674 674 Proton acceptor (By similarity).
 BINDING 580 580 ATP (By similarity).
 MOD_RES 200 200 Phosphoserine.
 MOD_RES 203 203 Phosphoserine.
 MOD_RES 206 206 Phosphoserine.
 MOD_RES 212 212 Phosphoserine (By similarity).
 MOD_RES 214 214 Phosphoserine.
 MOD_RES 244 244 Phosphoserine; by CSNK1D and CSNK1E.
 MOD_RES 438 438 Phosphotyrosine; by ABL1.
 MOD_RES 518 518 Phosphoserine.
 MOD_RES 706 706 Phosphoserine; by PKC.
 MOD_RES 710 710 Phosphoserine.
 MOD_RES 717 717 Phosphotyrosine.
 MOD_RES 876 876 Phosphoserine; by autocatalysis.  
Keyword
 3D-structure; Adaptive immunity; Angiogenesis; ATP-binding; Cell adhesion; Cell membrane; Complete proteome; Cytoplasm; Golgi apparatus; Immunity; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 878 AA 
Protein Sequence
MATAPSYPAG LPGSPGPGSP PPPGGLELQS PPPLLPQIPA PGSGVSFHIQ IGLTREFVLL 60
PAASELAHVK QLACSIVDQK FPECGFYGLY DKILLFKHDP TSANLLQLVR SSGDIQEGDL 120
VEVVLSASAT FEDFQIRPHA LTVHSYRAPA FCDHCGEMLF GLVRQGLKCD GCGLNYHKRC 180
AFSIPNNCSG ARKRRLSSTS LASGHSVRLG TSESLPCTAE ELSRSTTELL PRRPPSSSSS 240
SSASSYTGRP IELDKMLLSK VKVPHTFLIH SYTRPTVCQA CKKLLKGLFR QGLQCKDCKF 300
NCHKRCATRV PNDCLGEALI NGDVPMEEAT DFSEADKSAL MDESEDSGVI PGSHSENALH 360
ASEEEEGEGG KAQSSLGYIP LMRVVQSVRH TTRKSSTTLR EGWVVHYSNK DTLRKRHYWR 420
LDCKCITLFQ NNTTNRYYKE IPLSEILTVE SAQNFSLVPP GTNPHCFEIV TANATYFVGE 480
MPGGTPGGPS GQGAEAARGW ETAIRQALMP VILQDAPSAP GHAPHRQASL SISVSNSQIQ 540
ENVDIATVYQ IFPDEVLGSG QFGVVYGGKH RKTGRDVAVK VIDKLRFPTK QESQLRNEVA 600
ILQSLRHPGI VNLECMFETP EKVFVVMEKL HGDMLEMILS SEKGRLPERL TKFLITQILV 660
ALRHLHFKNI VHCDLKPENV LLASADPFPQ VKLCDFGFAR IIGEKSFRRS VVGTPAYLAP 720
EVLLNQGYNR SLDMWSVGVI MYVSLSGTFP FNEDEDINDQ IQNAAFMYPA SPWSHISAGA 780
IDLINNLLQV KMRKRYSVDK SLSHPWLQEY QTWLDLRELE GKMGERYITH ESDDVRWEQF 840
AAEHPLPGSG LPTDRDLGGA CPPQDHDMQG LAERISVL 878 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:BHF-UCL.
 GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IDA:BHF-UCL.
 GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; NAS:UniProtKB.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0005543; F:phospholipid binding; IEA:InterPro.
 GO:0004697; F:protein kinase C activity; IEA:EC.
 GO:0004674; F:protein serine/threonine kinase activity; NAS:UniProtKB.
 GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
 GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
 GO:0008219; P:cell death; IMP:BHF-UCL.
 GO:0061154; P:endothelial tube morphogenesis; TAS:BHF-UCL.
 GO:0007243; P:intracellular protein kinase cascade; IMP:BHF-UCL.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0045766; P:positive regulation of angiogenesis; IMP:UniProtKB.
 GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL.
 GO:0045785; P:positive regulation of cell adhesion; IMP:UniProtKB.
 GO:0032793; P:positive regulation of CREB transcription factor activity; IGI:BHF-UCL.
 GO:2000573; P:positive regulation of DNA biosynthetic process; ISS:UniProtKB.
 GO:0038033; P:positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway; IMP:BHF-UCL.
 GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:UniProtKB.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
 GO:0045743; P:positive regulation of fibroblast growth factor receptor signaling pathway; IMP:UniProtKB.
 GO:1901727; P:positive regulation of histone deacetylase activity; IGI:BHF-UCL.
 GO:0032743; P:positive regulation of interleukin-2 production; ISS:UniProtKB.
 GO:0032757; P:positive regulation of interleukin-8 production; IMP:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
 GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IGI:BHF-UCL.
 GO:0050862; P:positive regulation of T cell receptor signaling pathway; ISS:UniProtKB.
 GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
 GO:0030949; P:positive regulation of vascular endothelial growth factor receptor signaling pathway; IMP:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:BHF-UCL.
 GO:0050852; P:T cell receptor signaling pathway; IDA:BHF-UCL. 
Interpro
 IPR020454; DAG/PE-bd.
 IPR011009; Kinase-like_dom.
 IPR011993; PH_like_dom.
 IPR001849; Pleckstrin_homology.
 IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR015727; Protein_Kinase_C_mu-related.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00130; C1_1
 PF00169; PH
 PF00069; Pkinase 
SMART
 SM00109; C1
 SM00233; PH
 SM00220; S_TKc 
PROSITE
 PS50003; PH_DOMAIN
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS00479; ZF_DAG_PE_1
 PS50081; ZF_DAG_PE_2 
PRINTS
 PR00008; DAGPEDOMAIN.