Serine/threonine-protein kinase D2 - Rattus norvegicus (Rat)

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Q5XIS9 (KPCD2_RAT) Reviewed, UniProtKB/Swiss-Prot

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

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase D2
EC=2.7.11.13

Alternative name(s):
nPKC-D2

Gene names

Name:

Prkd2

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	875 AA.
Sequence status	Complete.
Protein existence	Evidence 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 apparatus › trans-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 process	Adaptive immunity Angiogenesis Cell adhesion Immunity
Cellular component	Cell membrane Cytoplasm Golgi apparatus Membrane
Domain	Repeat Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP 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: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 875

875

Serine/threonine-protein kinase D2

PRO_0000260437

Regions

Domain

398 – 510

113

Domain

552 – 808

257

Protein kinase

Zinc finger

138 – 188

Phorbol-ester/DAG-type 1

Zinc finger

265 – 315

Phorbol-ester/DAG-type 2

Nucleotide binding

558 – 566

ATP By similarity

Sites

Active site

675

Proton acceptor By similarity

Binding site

581

ATP By similarity

Amino acid modifications

Modified residue

189

Phosphoserine By similarity

Modified residue

197

Phosphoserine By similarity

Modified residue

198

Phosphoserine By similarity

Modified residue

199

Phosphothreonine By similarity

Modified residue

200

Phosphoserine By similarity

Modified residue

203

Phosphoserine By similarity

Modified residue

206

Phosphoserine By similarity

Modified residue

211

Phosphoserine Ref.2

Modified residue

212

Phosphoserine By similarity

Modified residue

214

Phosphoserine Ref.2

Modified residue

225

Phosphoserine By similarity

Modified residue

227

Phosphothreonine By similarity

Modified residue

236

Phosphoserine By similarity

Modified residue

237

Phosphoserine By similarity

Modified residue

238

Phosphoserine By similarity

Modified residue

244

Phosphoserine; by CSNK1D and CSNK1E By similarity

Modified residue

339

Phosphoserine By similarity

Modified residue

354

Phosphoserine By similarity

Modified residue

363

Phosphoserine By similarity

Modified residue

375

Phosphoserine By similarity

Modified residue

376

Phosphoserine By similarity

Modified residue

397

Phosphoserine By similarity

Modified residue

439

Phosphotyrosine; by ABL1 By similarity

Modified residue

519

Phosphoserine By similarity

Modified residue

707

Phosphoserine; by PKC By similarity

Modified residue

711

Phosphoserine; by autocatalysis By similarity

Modified residue

718

Phosphotyrosine By similarity

Modified residue

873

Phosphoserine; by autocatalysis By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q5XIS9 [UniParc].

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

875

96,497

        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

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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.
IPI	IPI00364038.
RefSeq	NP_001013917.1. NM_001013895.1.
UniGene	Rn.15035.
3D structure databases
HSSP	HSSP built from PDB template 2COA based on UniProtKB Q9BZL6.
ProteinModelPortal	Q5XIS9.
SMR	Q5XIS9. Positions 396-510.
ModBase	Search...
PTM databases
PhosphoSite	Q5XIS9.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000022360; ENSRNOP00000022360; ENSRNOG00000016434.
GeneID	292658.
KEGG	rno:292658.
NMPDR	fig\|10116.3.peg.1129.
UCSC	NM_001013895. rat.
Organism-specific databases
CTD	25865.
RGD	1308054. Prkd2.
Phylogenomic databases
eggNOG	maNOG12873.
GeneTree	ENSGT00600000084006.
HOVERGEN	HBG003564.
InParanoid	Q5XIS9.
OMA	LPQDHEM.
OrthoDB	EOG4548XW.
PhylomeDB	Q5XIS9.
Gene expression databases
ArrayExpress	Q5XIS9.
Genevestigator	Q5XIS9.
GermOnline	ENSRNOG00000016434. Rattus norvegicus.
Family and domain databases
InterPro	IPR020454. 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]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
KO	K06070.
PANTHER	PTHR22968. PKC_mu_like. 1 hit.
Pfam	PF00130. C1_1. 2 hits. PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF000552. PKC_mu_nu_D2. 1 hit.
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 2 hits. SM00233. PH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
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. [Graphical view]
ProtoNet	Search...
Other
NextBio	634460.

Entry information

Entry name

KPCD2_RAT

Accession

Primary (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 status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

PTM databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents