Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q5XIS9 (KPCD2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase D2

EC=2.7.11.13
Alternative name(s):
nPKC-D2
Gene names
Name:Prkd2
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length875 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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-439 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 By similarity.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

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 By similarity.

Subunit structure

Interacts (via C-terminus) with LCK By similarity.

Subcellular location

Cytoplasm By similarity. Cell membrane By similarity. Golgi apparatustrans-Golgi network By similarity. Note: Translocation to the cell membrane is required for kinase activation. Accumulates in the nucleus upon CK1-mediated phosphorylation after activation of G-protein-coupled receptors. Nuclear accumulation is regulated by blocking nuclear export of active PRKD2 rather than by increasing import By similarity.

Post-translational modification

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 By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. PKD subfamily.

Contains 1 PH domain.

Contains 2 phorbol-ester/DAG-type zinc fingers.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processAdaptive immunity
Angiogenesis
Cell adhesion
Immunity
   Cellular componentCell membrane
Cytoplasm
Golgi apparatus
Membrane
   DomainRepeat
Zinc-finger
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cell death

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of CREB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of DNA biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T cell receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of angiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of blood vessel endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell adhesion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of endothelial cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of endothelial cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of fibroblast growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of histone deacetylase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-2 production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-8 production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

positive regulation of vascular endothelial growth factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase C activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 875875Serine/threonine-protein kinase D2
PRO_0000260437

Regions

Domain398 – 510113PH
Domain552 – 808257Protein kinase
Zinc finger138 – 18851Phorbol-ester/DAG-type 1
Zinc finger265 – 31551Phorbol-ester/DAG-type 2
Nucleotide binding558 – 5669ATP By similarity

Sites

Active site6751Proton acceptor By similarity
Binding site5811ATP By similarity

Amino acid modifications

Modified residue2001Phosphoserine By similarity
Modified residue2031Phosphoserine By similarity
Modified residue2061Phosphoserine By similarity
Modified residue2141Phosphoserine By similarity
Modified residue2441Phosphoserine; by CSNK1D and CSNK1E By similarity
Modified residue4391Phosphotyrosine; by ABL1 By similarity
Modified residue5191Phosphoserine By similarity
Modified residue7071Phosphoserine; by PKC By similarity
Modified residue7111Phosphoserine; by autocatalysis By similarity
Modified residue7181Phosphotyrosine By similarity
Modified residue8731Phosphoserine; by autocatalysis By similarity

Sequences

Sequence LengthMass (Da)Tools
Q5XIS9 [UniParc].

Last modified November 23, 2004. Version 1.
Checksum: 789FD9853EEDF6A1

FASTA87596,497
        10         20         30         40         50         60 
MAAAPSHPAG LPCSPGPGSP PPPGGSDLQS LPPLLPQIPA PGSGVSFHIQ IGLTREFVLL 

        70         80         90        100        110        120 
PAASELAHVK QLACSIVDQK FPECGFYGLY DKILLFKHDP TSANLLQLVR SAADIQEGDL 

       130        140        150        160        170        180 
VEVVLSASAT FEDFQIRPHA LTVHSYRAPA FCDHCGEMLF GLVRQGLKCD GCGLNYHKRC 

       190        200        210        220        230        240 
AFSIPNNCSG ARKRRLSSTS LASGHSVRLG SSESLPCTAE ELSRSTTDLL PRRPPSSSSS 

       250        260        270        280        290        300 
SSSSSFYTGR PIELDKMLMS KVKVPHTFLI HSYTRPTVCQ ACKKLLKGLF RQGLQCKDCK 

       310        320        330        340        350        360 
FNCHKRCATR VPNDCLGEAL INGDVPMEEA ADYSEADKSS LSDELEDSGV IPGSHAENAL 

       370        380        390        400        410        420 
HASEEEEGEG GKAQSSLGYI PLMRVVQSVR HTTRKSSTTL REGWVVHYSN KDTLRKRHYW 

       430        440        450        460        470        480 
RLDCKCITLF QNNTTNRYYK EIPLSEILAV EPAQNFSLVP PGTNPHCFEI ITANVTYFVG 

       490        500        510        520        530        540 
ETPGGAPGGP SGQGTEAARG WETAIRQALM PVILQDAPSA PGHTPHRQAS LSISVSNSQI 

       550        560        570        580        590        600 
QENVDIATVY QIFPDEVLGS GQFGVVYGGK HRKTGRDVAV KVIDKLRFPT KQESQLRNEV 

       610        620        630        640        650        660 
AILQSLRHPG IVNLECMFET PEKVFVVMEK LHGDMLEMIL SSEKGRLPER LTKFLITQIL 

       670        680        690        700        710        720 
VALRHLHFKN IVHCDLKPEN VLLASADPFP QVKLCDFGFA RIIGEKSFRR SVVGTPAYLA 

       730        740        750        760        770        780 
PEVLLNQGYN RSLDMWSVGV IMYVSLSGTF PFNEDEDIND QIQNAAFMYP ASPWSHISSG 

       790        800        810        820        830        840 
AIDLINNLLQ VKMRKRYSVD KSLSHPWLQE YQTWLDLREL EGKMGERYIT HESDDARWDQ 

       850        860        870 
FVSERHGTPA EGDLGGACLP QDHEMQGLAE RISIL 

« Hide

References

[1]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC083592 mRNA. Translation: AAH83592.1.
RefSeqNP_001013917.1. NM_001013895.1.
UniGeneRn.15035.

3D structure databases

ProteinModelPortalQ5XIS9.
SMRQ5XIS9. Positions 396-510.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000022360.

PTM databases

PhosphoSiteQ5XIS9.

Proteomic databases

PaxDbQ5XIS9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000022360; ENSRNOP00000022360; ENSRNOG00000016434.
GeneID292658.
KEGGrno:292658.
UCSCRGD:1308054. rat.

Organism-specific databases

CTD25865.
RGD1308054. Prkd2.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00750000117523.
HOGENOMHOG000015135.
HOVERGENHBG003564.
InParanoidQ5XIS9.
KOK06070.
OMALPQDHEM.
OrthoDBEOG75B84N.
PhylomeDBQ5XIS9.
TreeFamTF314320.

Gene expression databases

GenevestigatorQ5XIS9.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
InterProIPR020454. 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_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR015727. Protein_Kinase_C_mu-related.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERPTHR22968. PTHR22968. 1 hit.
PfamPF00130. C1_1. 2 hits.
PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF000552. PKC_mu_nu_D2. 1 hit.
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 2 hits.
SM00233. PH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS50003. 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.
[Graphical view]
ProtoNetSearch...

Other

NextBio634460.
PROQ5XIS9.

Entry information

Entry nameKPCD2_RAT
AccessionPrimary (citable) accession number: Q5XIS9
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: November 23, 2004
Last modified: April 16, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families