Q9WTQ1 (KPCD1_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified May 1, 2013. Version 78. History...
Names and origin
|Protein names||Recommended name:|
Serine/threonine-protein kinase D1
Protein kinase C mu type
Protein kinase D
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||918 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-469 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin 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. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor. Ref.3 Ref.4 Ref.6 Ref.7
ATP + a protein = ADP + a phosphoprotein.
Magnesium By similarity.
Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domain 1 binds DAG with high affinity and appears to play the dominant role in mediating translocation to the cell membrane and trans-Golgi network. Phorbol-ester/DAG-type domain 2 binds phorbol ester with higher affinity. Autophosphorylation of Ser-748 and phosphorylation of Ser-744 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-469 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress By similarity.
Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with MAPK13 and SRC By similarity. Interacts with DAPK1 in an oxidative stress-regulated manner By similarity.
Phosphorylated at Ser-403 and Ser-407 by MAPK13 during regulation of insulin secretion in pancreatic beta cells. Phosphorylated by DAPK1. Phosphorylated by ABL at Tyr-469, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-744/Ser-748 by PKRD By similarity. Ref.5
Contains 1 PH domain.
Contains 2 phorbol-ester/DAG-type zinc fingers.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 918||918||Serine/threonine-protein kinase D1||PRO_0000333881|
|Domain||428 – 547||120||PH|
|Domain||589 – 845||257||Protein kinase|
|Zinc finger||144 – 194||51||Phorbol-ester/DAG-type 1|
|Zinc finger||276 – 326||51||Phorbol-ester/DAG-type 2|
|Nucleotide binding||595 – 603||9||ATP By similarity|
|Compositional bias||16 – 26||11||Poly-Ala|
|Compositional bias||198 – 201||4||Poly-Arg|
|Active site||712||1||Proton acceptor By similarity|
|Binding site||618||1||ATP By similarity|
Amino acid modifications
|Modified residue||93||1||Phosphotyrosine By similarity|
|Modified residue||203||1||Phosphoserine By similarity|
|Modified residue||206||1||Phosphoserine By similarity|
|Modified residue||253||1||Phosphoserine By similarity|
|Modified residue||351||1||Phosphoserine By similarity|
|Modified residue||403||1||Phosphoserine; by MAPK13 By similarity|
|Modified residue||407||1||Phosphoserine; by MAPK13 By similarity|
|Modified residue||438||1||Phosphotyrosine By similarity|
|Modified residue||454||1||Phosphoserine By similarity|
|Modified residue||469||1||Phosphotyrosine; by ABL By similarity|
|Modified residue||508||1||Phosphotyrosine By similarity|
|Modified residue||744||1||Phosphoserine; by PKC/PRKCD By similarity|
|Modified residue||748||1||Phosphoserine; by autocatalysis and PKC/PRKCD By similarity|
|Modified residue||916||1||Phosphoserine; by autocatalysis Ref.5|
|Sequence conflict||718||1||V → G in BAA78373. Ref.2|
|||"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."|
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway.
|||"Rat PKC mu mRNA partial cds."|
Minami H., Owada Y., Kondo H.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 718-864.
|||"Gbetagamma-mediated regulation of Golgi organization is through the direct activation of protein kinase D."|
Jamora C., Yamanouye N., Van Lint J., Laudenslager J., Vandenheede J.R., Faulkner D.J., Malhotra V.
Cell 98:59-68(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN GOLGI REGULATION.
|||"Protein kinase D is a novel mediator of cardiac troponin I phosphorylation and regulates myofilament function."|
Haworth R.S., Cuello F., Herron T.J., Franzen G., Kentish J.C., Gautel M., Avkiran M.
Circ. Res. 95:1091-1099(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CARDIOMYOCYTE.
|||"Hepatocyte resistance to oxidative stress is dependent on protein kinase C-mediated down-regulation of c-Jun/AP-1."|
Wang Y., Schattenberg J.M., Rigoli R.M., Storz P., Czaja M.J.
J. Biol. Chem. 279:31089-31097(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-744; SER-748 AND SER-916.
|||"Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5."|
Vega R.B., Harrison B.C., Meadows E., Roberts C.R., Papst P.J., Olson E.N., McKinsey T.A.
Mol. Cell. Biol. 24:8374-8385(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CARDIAC HYPERTROPHY.
|||"Protein kinase d regulates trafficking of dendritic membrane proteins in developing neurons."|
Bisbal M., Conde C., Donoso M., Bollati F., Sesma J., Quiroga S., Diaz Anel A., Malhotra V., Marzolo M.P., Caceres A.
J. Neurosci. 28:9297-9308(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEURONAL POLARITY.
|+||Additional computationally mapped references.|
|AABR03048549 Genomic DNA. No translation available.|
AABR03048623 Genomic DNA. No translation available.
AABR03048825 Genomic DNA. No translation available.
AABR03049215 Genomic DNA. No translation available.
AABR03049278 Genomic DNA. No translation available.
AABR03050321 Genomic DNA. No translation available.
AABR03052344 Genomic DNA. No translation available.
AB020616 mRNA. Translation: BAA78373.1.
|RefSeq||NP_001263644.1. NM_001276715.1. |
3D structure databases
|SMR||Q9WTQ1. Positions 425-552. |
Protein-protein interaction databases
|IntAct||Q9WTQ1. 1 interaction.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000068077; ENSRNOP00000063159; ENSRNOG00000004165. |
|UCSC||RGD:620964. rat. |
|RGD||620964. Prkd1. |
Gene expression databases
Family and domain databases
|Gene3D||18.104.22.168. 1 hit. |
|InterPro||IPR020454. DAG/PE-bd. |
|PANTHER||PTHR22968. PTHR22968. 1 hit. |
|Pfam||PF00130. C1_1. 2 hits. |
PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
|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.
|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.
|Accession||Primary (citable) accession number: Q9WTQ1|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families