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Q5XIS9 (KPCD2_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 79. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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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)
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length875 AA.
Sequence statusComplete.
Protein existenceEvidence at protein 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.

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 residue1891Phosphoserine By similarity
Modified residue1971Phosphoserine By similarity
Modified residue1981Phosphoserine By similarity
Modified residue1991Phosphothreonine By similarity
Modified residue2001Phosphoserine By similarity
Modified residue2031Phosphoserine By similarity
Modified residue2061Phosphoserine By similarity
Modified residue2111Phosphoserine Ref.2
Modified residue2121Phosphoserine By similarity
Modified residue2141Phosphoserine Ref.2
Modified residue2251Phosphoserine By similarity
Modified residue2271Phosphothreonine By similarity
Modified residue2361Phosphoserine By similarity
Modified residue2371Phosphoserine By similarity
Modified residue2381Phosphoserine By similarity
Modified residue2441Phosphoserine; by CSNK1D and CSNK1E By similarity
Modified residue3391Phosphoserine By similarity
Modified residue3541Phosphoserine By similarity
Modified residue3631Phosphoserine By similarity
Modified residue3751Phosphoserine By similarity
Modified residue3761Phosphoserine By similarity
Modified residue3971Phosphoserine 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: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[2]"Quantitative phosphoproteomics of vasopressin-sensitive renal cells: regulation of aquaporin-2 phosphorylation at two sites."
Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.
Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006) [PubMed: 16641100] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-211 AND SER-214, MASS SPECTROMETRY.
Tissue: Renal collecting duct.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC083592 mRNA. Translation: AAH83592.1.
IPIIPI00364038.
RefSeqNP_001013917.1. NM_001013895.1.
UniGeneRn.15035.

3D structure databases

HSSPHSSP built from PDB template 2COA based on UniProtKB Q9BZL6.
ProteinModelPortalQ5XIS9.
SMRQ5XIS9. Positions 396-510.
ModBaseSearch...

PTM databases

PhosphoSiteQ5XIS9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000022360; ENSRNOP00000022360; ENSRNOG00000016434.
GeneID292658.
KEGGrno:292658.
NMPDRfig|10116.3.peg.1129.
UCSCNM_001013895. rat.

Organism-specific databases

CTD25865.
RGD1308054. Prkd2.

Phylogenomic databases

eggNOGmaNOG12873.
GeneTreeENSGT00600000084006.
HOVERGENHBG003564.
InParanoidQ5XIS9.
OMALPQDHEM.
OrthoDBEOG4548XW.
PhylomeDBQ5XIS9.

Gene expression databases

ArrayExpressQ5XIS9.
GenevestigatorQ5XIS9.
GermOnlineENSRNOG00000016434. Rattus norvegicus.

Family and domain databases

InterProIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR011993. PH_type.
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.
IPR017442. Se/Thr_kinase-like_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR002290. Ser/Thr_kinase_dom.
[Graphical view]
Gene3DG3DSA:2.30.29.30. PH_type. 1 hit.
KOK06070.
PANTHERPTHR22968. PKC_mu_like. 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. Kinase_like. 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.

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: January 25, 2012
This is version 79 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