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Protein

Serine/threonine-protein kinase D2

Gene

Prkd2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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 (PubMed:17226786, PubMed:20819079). 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 (PubMed:17226786). In response to oxidative stress, is phosphorylated at Tyr-438 and Tyr-718 by ABL1, which leads to the activation of PRKD2 without increasing its catalytic activity, and mediates activation of NF-kappa-B (By similarity). 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 (By similarity). 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 (PubMed:20819079). 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 (By similarity). 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 (By similarity). 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 (By similarity). 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 (By similarity). In secretory pathway, is required for the release of chromogranin-A (CHGA)-containing secretory granules from the TGN (By similarity). Downstream of PRKCA, plays important roles in angiotensin-2-induced monocyte adhesion to endothelial cells (By similarity).By similarity2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Mg2+By similarity

Activity regulationi

Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes. Autophosphorylation of Ser-711 and phosphorylation of Ser-707 by PKC relieves auto-inhibition by the PH domain. Catalytic activity is further increased by phosphorylation at Tyr-718 in response to oxidative stress.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei581ATPPROSITE-ProRule annotation1
Active sitei675Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri138 – 188Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri265 – 315Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi558 – 566ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processAdaptive immunity, Angiogenesis, Cell adhesion, Immunity
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-1660661 Sphingolipid de novo biosynthesis

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase D2 (EC:2.7.11.131 Publication)
Alternative name(s):
nPKC-D2
Gene namesi
Name:Prkd2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:2141917 Prkd2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi707S → A: Strong decrease in catalytic activity; when associated with A-711. 1 Publication1
Mutagenesisi711S → A: Strong decrease in catalytic activity; when associated with A-707. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002604361 – 875Serine/threonine-protein kinase D2Add BLAST875

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei30PhosphoserineBy similarity1
Modified residuei87PhosphotyrosineBy similarity1
Modified residuei197PhosphoserineCombined sources1
Modified residuei198PhosphoserineBy similarity1
Modified residuei200PhosphoserineCombined sources1
Modified residuei203PhosphoserineBy similarity1
Modified residuei206PhosphoserineCombined sources1
Modified residuei211PhosphoserineCombined sources1
Modified residuei212PhosphoserineCombined sources1
Modified residuei214PhosphoserineCombined sources1
Modified residuei244Phosphoserine; by CSNK1D and CSNK1EBy similarity1
Modified residuei245PhosphoserineBy similarity1
Modified residuei408PhosphotyrosineBy similarity1
Modified residuei439Phosphotyrosine; by ABL1By similarity1
Modified residuei519PhosphoserineBy similarity1
Modified residuei707Phosphoserine; by PKC1 Publication1
Modified residuei711Phosphoserine; by autocatalysisCombined sources1 Publication1
Modified residuei718Phosphotyrosine; by ABL1By similarity1
Modified residuei873Phosphoserine; by autocatalysis1 Publication1

Post-translational modificationi

Phosphorylation of Ser-873 correlates with the activation status of the kinase. Ser-707 is probably phosphorylated by PKC. Phosphorylation at Ser-244 by CSNK1D and CSNK1E promotes nuclear localization and substrate targeting. Phosphorylation at Ser-244, Ser-707 and Ser-711 is required for nuclear localization. Phosphorylated at Tyr-438 by ABL1 in response to oxidative stress. Phosphorylated at Tyr-718 by ABL1 specifically in response to oxidative stress; requires prior phosphorylation at Ser-707 or/and Ser-711.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8BZ03
MaxQBiQ8BZ03
PaxDbiQ8BZ03
PeptideAtlasiQ8BZ03
PRIDEiQ8BZ03

PTM databases

iPTMnetiQ8BZ03
PhosphoSitePlusiQ8BZ03

Expressioni

Gene expression databases

BgeeiENSMUSG00000041187 Expressed in 229 organ(s), highest expression level in spleen
CleanExiMM_PRKD2
GenevisibleiQ8BZ03 MM

Interactioni

Subunit structurei

Interacts (via C-terminus) with LCK. Interacts (via N-terminus and zing-finger domain 1 and 2) with PRKCD in response to oxidative stress; the interaction is independent of PRKD2 tyrosine phosphorylation.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi221683, 1 interactor
IntActiQ8BZ03, 1 interactor
MINTiQ8BZ03
STRINGi10090.ENSMUSP00000083273

Structurei

3D structure databases

ProteinModelPortaliQ8BZ03
SMRiQ8BZ03
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini398 – 510PHPROSITE-ProRule annotationAdd BLAST113
Domaini552 – 808Protein kinasePROSITE-ProRule annotationAdd BLAST257

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi725 – 727Important for ABL1-mediated Tyr-718 phosphorylationBy similarity3

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri138 – 188Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri265 – 315Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG4236 Eukaryota
ENOG410XQZ3 LUCA
GeneTreeiENSGT00910000144054
HOGENOMiHOG000015135
HOVERGENiHBG003564
InParanoidiQ8BZ03
KOiK06070
OMAiCIILFQN
OrthoDBiEOG091G02RG
PhylomeDBiQ8BZ03
TreeFamiTF314320

Family and domain databases

CDDicd00029 C1, 2 hits
Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
IPR002219 PE/DAG-bd
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR015727 Protein_Kinase_C_mu-related
IPR008271 Ser/Thr_kinase_AS
PANTHERiPTHR22968 PTHR22968, 1 hit
PfamiView protein in Pfam
PF00130 C1_1, 2 hits
PF00069 Pkinase, 1 hit
PIRSFiPIRSF000552 PKC_mu_nu_D2, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 2 hits
SM00233 PH, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
PS00479 ZF_DAG_PE_1, 2 hits
PS50081 ZF_DAG_PE_2, 2 hits

Sequencei

Sequence statusi: Complete.

Q8BZ03-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MAAAPSHPAG LPGSPGPGSP PPPGGLDLQS PPPLLPQIPA PGSGVSFHIQ
60 70 80 90 100
IGLTREFVLL PAASELAHVK QLACSIVDQK FPECGFYGLY DKILLFKHDP
110 120 130 140 150
TSANLLQLVR SAADIQEGDL VEVVLSASAT FEDFQIRPHA LTVHSYRAPA
160 170 180 190 200
FCDHCGEMLF GLVRQGLKCD GCGLNYHKRC AFSIPNNCSG ARKRRLSSTS
210 220 230 240 250
LASGHSVRLG SSESLPCTAE ELSRSTTDLL PRRPPSSSSS SSSSSFYTGR
260 270 280 290 300
PIELDKMLMS KVKVPHTFLI HSYTRPTVCQ ACKKLLKGLF RQGLQCKDCK
310 320 330 340 350
FNCHKRCATR VPNDCLGEAL INGDVPMEEA ADYSEADKSS ISDELEDSGV
360 370 380 390 400
IPGSHSESAL HASEEEEGEG HKAQSSLGYI PLMRVVQSVR HTTRKSSTTL
410 420 430 440 450
REGWVVHYSN KDTLRKRHYW RLDCKCITLF QNNTTNRYYK EIPLSEILAV
460 470 480 490 500
EPAQNFSLVP PGTNPHCFEI ITANVTYFVG ETPGGAPGGP SGQGTEAVRG
510 520 530 540 550
WETAIRQALM PVILQDAPSA PGHTPHRQAS LSISVSNSQI QENVDIATVY
560 570 580 590 600
QIFPDEVLGS GQFGVVYGGK HRKTGRDVAV KVIDKLRFPT KQESQLRNEV
610 620 630 640 650
AILQSLRHPG IVNLECMFET PEKVFVVMEK LHGDMLEMIL SSEKGRLPER
660 670 680 690 700
LTKFLITQIL VALRHLHFKN IVHCDLKPEN VLLASADPFP QVKLCDFGFA
710 720 730 740 750
RIIGEKSFRR SVVGTPAYLA PEVLLNQGYN RSLDMWSVGV IMYVSLSGTF
760 770 780 790 800
PFNEDEDIND QIQNAAFMYP ASPWSHISSG AIDLINNLLQ VKMRKRYSVD
810 820 830 840 850
KSLSHPWLQE YQTWLDLREL EGKMGERYIT HESDDARWDQ FVAERHGTPA
860 870
EGDLGGACLP QDHEMQGLAE RISIL
Length:875
Mass (Da):96,542
Last modified:March 1, 2003 - v1
Checksum:iC7173546FA1E6DB1
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti213E → G in BAE42012 (PubMed:16141072).Curated1
Sequence conflicti220E → G in BAE41652 (PubMed:16141072).Curated1
Sequence conflicti310R → H in BAE32326 (PubMed:16141072).Curated1
Sequence conflicti310R → H in BAE41652 (PubMed:16141072).Curated1
Sequence conflicti630K → N in BAE42012 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK037030 mRNA Translation: BAC29677.1
AK154029 mRNA Translation: BAE32326.1
AK170236 mRNA Translation: BAE41652.1
AK170761 mRNA Translation: BAE42012.1
BC095949 mRNA Translation: AAH95949.1
BC096444 mRNA Translation: AAH96444.1
CCDSiCCDS20855.1
RefSeqiNP_001239387.1, NM_001252458.1
NP_849231.1, NM_178900.4
UniGeneiMm.1881
Mm.488710

Genome annotation databases

EnsembliENSMUST00000086104; ENSMUSP00000083273; ENSMUSG00000041187
ENSMUST00000168093; ENSMUSP00000131192; ENSMUSG00000041187
GeneIDi101540
KEGGimmu:101540
UCSCiuc009fig.2 mouse

Similar proteinsi

Entry informationi

Entry nameiKPCD2_MOUSE
AccessioniPrimary (citable) accession number: Q8BZ03
Secondary accession number(s): Q3TCE5, Q3TDF0, Q3U4V4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: March 1, 2003
Last modified: September 12, 2018
This is version 149 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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