KPCD2_RAT
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 03-AUG-2022, entry version 150.
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}.
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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; Q5XIS9; -.
DR PRIDE; Q5XIS9; -.
DR Ensembl; ENSRNOT00000022360; ENSRNOP00000022360; ENSRNOG00000016434.
DR GeneID; 292658; -.
DR KEGG; rno:292658; -.
DR UCSC; RGD:1308054; rat.
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; GKERDNF; -.
DR OrthoDB; 367841at2759; -.
DR PhylomeDB; Q5XIS9; -.
DR TreeFam; TF314320; -.
DR Reactome; R-RNO-1660661; Sphingolipid de novo biosynthesis.
DR PRO; PR:Q5XIS9; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000016434; Expressed in thymus and 19 other tissues.
DR Genevisible; Q5XIS9; RN.
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: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; ISO:RGD.
DR GO; GO:0005080; F:protein kinase C binding; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
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:0008219; P:cell death; ISO:RGD.
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:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
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:0032793; P:positive regulation of CREB transcription factor activity; ISO:RGD.
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:1901727; P:positive regulation of histone deacetylase activity; ISO:RGD.
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:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
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:0046777; P:protein autophosphorylation; ISO:RGD.
DR GO; GO:0089700; P:protein kinase D signaling; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; ISO:RGD.
DR GO; GO:0070232; P:regulation of T cell apoptotic process; IEA:Ensembl.
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; 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 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
