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Q15139 (KPCD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase D1

EC=2.7.11.13
Alternative name(s):
Protein kinase C mu type
Protein kinase D
nPKC-D1
nPKC-mu
Gene names
Name:PRKD1
Synonyms:PKD, PKD1, PRKCM
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length912 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 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-463 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.5 Ref.6 Ref.8 Ref.9 Ref.10 Ref.14 Ref.16 Ref.17 Ref.19 Ref.20

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

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-742 and phosphorylation of Ser-738 by PKC relieves auto-inhibition by the PH domain. Phosphorylation on Tyr-463 by the SRC-ABL1 pathway in response to oxidative stress, is also required for activation. Activated by DAPK1 under oxidative stress. Ref.9 Ref.12 Ref.15

Subunit structure

Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with MAPK13 and SRC. Interacts with DAPK1 in an oxidative stress-regulated manner. Ref.7 Ref.12 Ref.19

Subcellular location

Cytoplasm. Cell membrane. Golgi apparatustrans-Golgi network By similarity. Note: Translocation to the cell membrane is required for kinase activation. Ref.15

Post-translational modification

Phosphorylated at Ser-397 and Ser-401 by MAPK13 during regulation of insulin secretion in pancreatic beta cells. Phosphorylated by DAPK1. Phosphorylated by ABL at Tyr-463, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-738/Ser-742 by PKRD. Ref.9 Ref.11 Ref.12 Ref.13 Ref.19

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 processAngiogenesis
Apoptosis
Differentiation
Immunity
Inflammatory response
Innate immunity
Neurogenesis
   Cellular componentCell membrane
Cytoplasm
Golgi apparatus
Membrane
   Coding sequence diversityPolymorphism
   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_processGolgi organization

Inferred from mutant phenotype Ref.20. Source: UniProtKB

Golgi vesicle transport

Inferred from sequence or structural similarity. Source: UniProtKB

angiogenesis

Inferred from electronic annotation. Source: UniProtKB-KW

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Traceable author statement Ref.1. Source: ProtInc

cellular response to oxidative stress

Inferred from direct assay Ref.8. Source: UniProtKB

cellular response to vascular endothelial growth factor stimulus

Inferred from mutant phenotype Ref.16. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

integrin-mediated signaling pathway

Traceable author statement PubMed 21488147. Source: BHF-UCL

intracellular signal transduction

Inferred from mutant phenotype PubMed 18059339PubMed 18440775. Source: BHF-UCL

negative regulation of cell death

Inferred from mutant phenotype Ref.8. Source: UniProtKB

negative regulation of endocytosis

Traceable author statement PubMed 21488147. Source: BHF-UCL

peptidyl-serine phosphorylation

Inferred from direct assay PubMed 18440775. Source: BHF-UCL

positive regulation of CREB transcription factor activity

Inferred from genetic interaction PubMed 20497126. Source: BHF-UCL

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of angiogenesis

Inferred from mutant phenotype Ref.16. Source: UniProtKB

positive regulation of blood vessel endothelial cell migration

Inferred from mutant phenotype PubMed 18440775. Source: BHF-UCL

positive regulation of endothelial cell chemotaxis

Inferred from mutant phenotype PubMed 18440775. Source: BHF-UCL

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

Inferred from mutant phenotype PubMed 18440775. Source: BHF-UCL

positive regulation of endothelial cell migration

Inferred from mutant phenotype Ref.16. Source: UniProtKB

positive regulation of endothelial cell proliferation

Inferred from genetic interaction PubMed 20497126. Source: BHF-UCL

positive regulation of histone deacetylase activity

Inferred from genetic interaction PubMed 20497126. Source: BHF-UCL

positive regulation of neuron projection development

Inferred from mutant phenotype Ref.20. Source: UniProtKB

positive regulation of osteoblast differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of peptidyl-serine phosphorylation

Inferred from genetic interaction PubMed 20497126. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 18059339. Source: BHF-UCL

protein autophosphorylation

Traceable author statement PubMed 21488147. Source: BHF-UCL

regulation of integrin-mediated signaling pathway

Traceable author statement PubMed 21488147. Source: BHF-UCL

regulation of keratinocyte proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

signal transduction

Traceable author statement Ref.1. Source: ProtInc

small molecule metabolic process

Traceable author statement. Source: Reactome

sphingolipid biosynthetic process

Traceable author statement. Source: Reactome

sphingolipid metabolic process

Traceable author statement. Source: Reactome

vascular endothelial growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 18059339. Source: BHF-UCL

   Cellular_componentcell cortex

Inferred from electronic annotation. Source: Ensembl

cell-cell junction

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from direct assay. Source: HPA

trans-Golgi network

Inferred from direct assay Ref.20. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

identical protein binding

Inferred from physical interaction PubMed 10831594. Source: IntAct

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

protein kinase C activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein serine/threonine kinase activity

Traceable author statement Ref.1. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 912912Serine/threonine-protein kinase D1
PRO_0000055714

Regions

Domain422 – 541120PH
Domain583 – 839257Protein kinase
Zinc finger146 – 19651Phorbol-ester/DAG-type 1
Zinc finger270 – 32051Phorbol-ester/DAG-type 2
Nucleotide binding589 – 5979ATP By similarity
Compositional bias17 – 2610Poly-Ala
Compositional bias200 – 2034Poly-Arg

Sites

Active site7061Proton acceptor By similarity
Binding site6121ATP

Amino acid modifications

Modified residue951Phosphotyrosine Ref.13
Modified residue2051Phosphoserine Ref.24 Ref.27
Modified residue2081Phosphoserine Ref.27
Modified residue3451Phosphoserine Ref.24
Modified residue3971Phosphoserine; by MAPK13 Ref.19
Modified residue4011Phosphoserine; by MAPK13 Ref.19
Modified residue4321Phosphotyrosine Ref.9
Modified residue4481Phosphoserine Ref.24
Modified residue4631Phosphotyrosine; by ABL Ref.9 Ref.11
Modified residue4731Phosphoserine Ref.24
Modified residue5021Phosphotyrosine Ref.9
Modified residue7381Phosphoserine; by PKC/PRKCD Ref.11
Modified residue7421Phosphoserine; by autocatalysis and PKC/PRKCD Ref.11
Modified residue9101Phosphoserine; by autocatalysis Ref.12

Natural variations

Natural variant1521H → Y in a colorectal cancer sample; somatic mutation. Ref.28
VAR_035468
Natural variant2251S → P. Ref.29
VAR_042324
Natural variant4781K → Q. Ref.29
Corresponds to variant rs55852813 [ dbSNP | Ensembl ].
VAR_042325
Natural variant5851P → S in a metastatic melanoma sample; somatic mutation. Ref.29
VAR_042326
Natural variant6771R → M in a lung bronchoalveolar carcinoma sample; somatic mutation. Ref.29
VAR_042327
Natural variant6791P → L. Ref.29
Corresponds to variant rs34588699 [ dbSNP | Ensembl ].
VAR_042328
Natural variant8251R → K.
Corresponds to variant rs11161065 [ dbSNP | Ensembl ].
VAR_046988
Natural variant8571E → K in a colorectal cancer sample; somatic mutation. Ref.28
VAR_035469
Natural variant8911H → R. Ref.29
Corresponds to variant rs45582934 [ dbSNP | Ensembl ].
VAR_042329

Experimental info

Mutagenesis1571P → G: Increase in ability to bind phorbol ester, loss of ability to bind DAG. Ref.15
Mutagenesis2811P → G: No effect on ability to bind phorbol ester, slight increase in ability to bind DAG. Ref.15
Mutagenesis4321Y → E: Decreased phosphorylation level when coexpressed with SRC in HeLa cells. Unchanged phosphorylation level when coexpressed with ABL. Ref.9
Mutagenesis4321Y → F: Decreased phosphorylation level when coexpressed with SRC in HeLa cells. Unchanged phosphorylation level when coexpressed with ABL. Unaltered kinase activity. Decreased kinase activity; when associated with F-463 and F-502. Ref.9
Mutagenesis4631Y → E: Constitutive activation and constitutive phosphorylation of S-738 and S-742. Ref.9
Mutagenesis4631Y → F: Decreased phosphorylation level when coexpressed with either SRC or ABL in HeLa cells. Decreased kinase activity. Ref.9
Mutagenesis5021Y → E: Loss of activation. Ref.9
Mutagenesis5021Y → F: Decreased phosphorylation level when coexpressed with SRC in HeLa cells. Unchanged phosphorylation level when coexpressed with ABL. Unaltered kinase activity. Decreased kinase activity; when associated with F-432 and F-502. Ref.9
Mutagenesis6121K → W: Loss of kinase activity. Ref.9
Sequence conflict1351A → R in CAA53384. Ref.1
Sequence conflict8771G → R in CAA53384. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q15139 [UniParc].

Last modified October 14, 2008. Version 2.
Checksum: 0BC9414C335D2DBB

FASTA912101,704
        10         20         30         40         50         60 
MSAPPVLRPP SPLLPVAAAA AAAAAALVPG SGPGPAPFLA PVAAPVGGIS FHLQIGLSRE 

        70         80         90        100        110        120 
PVLLLQDSSG DYSLAHVREM ACSIVDQKFP ECGFYGMYDK ILLFRHDPTS ENILQLVKAA 

       130        140        150        160        170        180 
SDIQEGDLIE VVLSASATFE DFQIRPHALF VHSYRAPAFC DHCGEMLWGL VRQGLKCEGC 

       190        200        210        220        230        240 
GLNYHKRCAF KIPNNCSGVR RRRLSNVSLT GVSTIRTSSA ELSTSAPDEP LLQKSPSESF 

       250        260        270        280        290        300 
IGREKRSNSQ SYIGRPIHLD KILMSKVKVP HTFVIHSYTR PTVCQYCKKL LKGLFRQGLQ 

       310        320        330        340        350        360 
CKDCRFNCHK RCAPKVPNNC LGEVTINGDL LSPGAESDVV MEEGSDDNDS ERNSGLMDDM 

       370        380        390        400        410        420 
EEAMVQDAEM AMAECQNDSG EMQDPDPDHE DANRTISPST SNNIPLMRVV QSVKHTKRKS 

       430        440        450        460        470        480 
STVMKEGWMV HYTSKDTLRK RHYWRLDSKC ITLFQNDTGS RYYKEIPLSE ILSLEPVKTS 

       490        500        510        520        530        540 
ALIPNGANPH CFEITTANVV YYVGENVVNP SSPSPNNSVL TSGVGADVAR MWEIAIQHAL 

       550        560        570        580        590        600 
MPVIPKGSSV GTGTNLHRDI SVSISVSNCQ IQENVDISTV YQIFPDEVLG SGQFGIVYGG 

       610        620        630        640        650        660 
KHRKTGRDVA IKIIDKLRFP TKQESQLRNE VAILQNLHHP GVVNLECMFE TPERVFVVME 

       670        680        690        700        710        720 
KLHGDMLEMI LSSEKGRLPE HITKFLITQI LVALRHLHFK NIVHCDLKPE NVLLASADPF 

       730        740        750        760        770        780 
PQVKLCDFGF ARIIGEKSFR RSVVGTPAYL APEVLRNKGY NRSLDMWSVG VIIYVSLSGT 

       790        800        810        820        830        840 
FPFNEDEDIH DQIQNAAFMY PPNPWKEISH EAIDLINNLL QVKMRKRYSV DKTLSHPWLQ 

       850        860        870        880        890        900 
DYQTWLDLRE LECKIGERYI THESDDLRWE KYAGEQGLQY PTHLINPSAS HSDTPETEET 

       910 
EMKALGERVS IL 

« Hide

References

« Hide 'large scale' references
[1]"PKCmu is a novel, atypical member of the protein kinase C family."
Johannes F.-J., Prestle J., Eis S., Oberhagemann P., Pfizenmaier K.
J. Biol. Chem. 269:6140-6148(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Placenta.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[3]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"Cell-type specific phosphorylation of threonines T654 and T669 by PKD defines the signal capacity of the EGF receptor."
Bagowski C.P., Stein-Gerlach M., Choidas A., Ullrich A.
EMBO J. 18:5567-5576(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN EGFR PHOSPHORYLATION.
[6]"Proteolytic cleavage and activation of protein kinase C [micro] by caspase-3 in the apoptotic response of cells to 1-beta -D-arabinofuranosylcytosine and other genotoxic agents."
Endo K., Oki E., Biedermann V., Kojima H., Yoshida K., Johannes F.J., Kufe D., Datta R.
J. Biol. Chem. 275:18476-18481(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS.
[7]"Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C."
Zemlickova E., Dubois T., Kerai P., Clokie S., Cronshaw A.D., Wakefield R.I.D., Johannes F.-J., Aitken A.
Biochem. Biophys. Res. Commun. 307:459-465(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ADAP1.
[8]"Protein kinase D mediates a stress-induced NF-kappaB activation and survival pathway."
Storz P., Toker A.
EMBO J. 22:109-120(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL SURVIVAL.
[9]"Tyrosine phosphorylation of protein kinase D in the pleckstrin homology domain leads to activation."
Storz P., Doppler H., Johannes F.J., Toker A.
J. Biol. Chem. 278:17969-17976(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT TYR-432; TYR-463 AND TYR-502, MUTAGENESIS OF TYR-432; TYR-463; TYR-502 AND LYS-612.
[10]"Interaction between protein kinase Cmu and the vanilloid receptor type 1."
Wang Y., Kedei N., Wang M., Wang Q.J., Huppler A.R., Toth A., Tran R., Blumberg P.M.
J. Biol. Chem. 279:53674-53682(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF TRPV1.
[11]"Protein kinase Cdelta selectively regulates protein kinase D-dependent activation of NF-kappaB in oxidative stress signaling."
Storz P., Doppler H., Toker A.
Mol. Cell. Biol. 24:2614-2626(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-463; SER-738 AND SER-742.
[12]"DAP kinase regulates JNK signaling by binding and activating protein kinase D under oxidative stress."
Eisenberg-Lerner A., Kimchi A.
Cell Death Differ. 14:1908-1915(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY DAPK1, INTERACTION WITH DAPK1, AUTOPHOSPHORYLATION AT SER-910, ENZYME REGULATION.
[13]"A novel tyrosine phosphorylation site in protein kinase D contributes to oxidative stress-mediated activation."
Doppler H., Storz P.
J. Biol. Chem. 282:31873-31881(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT TYR-95.
[14]"Protein kinase D interaction with TLR5 is required for inflammatory signaling in response to bacterial flagellin."
Ivison S.M., Graham N.R., Bernales C.Q., Kifayet A., Ng N., Shobab L.A., Steiner T.S.
J. Immunol. 178:5735-5743(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INNATE IMMUNITY.
[15]"Selective binding of phorbol esters and diacylglycerol by individual C1 domains of the PKD family."
Chen J., Deng F., Li J., Wang Q.J.
Biochem. J. 411:333-342(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHORBOL-ESTER BINDING, SUBCELLULAR LOCATION, MUTAGENESIS OF PRO-157 AND PRO-281.
[16]"Protein kinase D-dependent phosphorylation and nuclear export of histone deacetylase 5 mediates vascular endothelial growth factor-induced gene expression and angiogenesis."
Ha C.H., Wang W., Jhun B.S., Wong C., Hausser A., Pfizenmaier K., McKinsey T.A., Olson E.N., Jin Z.G.
J. Biol. Chem. 283:14590-14599(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC5, FUNCTION IN ANGIOGENESIS.
[17]"Control of endothelial cell proliferation and migration by VEGF signaling to histone deacetylase 7."
Wang S., Li X., Parra M., Verdin E., Bassel-Duby R., Olson E.N.
Proc. Natl. Acad. Sci. U.S.A. 105:7738-7743(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF HDAC7.
[18]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Regulation of PKD by the MAPK p38delta in insulin secretion and glucose homeostasis."
Sumara G., Formentini I., Collins S., Sumara I., Windak R., Bodenmiller B., Ramracheya R., Caille D., Jiang H., Platt K.A., Meda P., Aebersold R., Rorsman P., Ricci R.
Cell 136:235-248(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-397 AND SER-401, INTERACTION WITH MAPK13, FUNCTION.
[20]"Protein kinase D controls the integrity of Golgi apparatus and the maintenance of dendritic arborization in hippocampal neurons."
Czoendoer K., Ellwanger K., Fuchs Y.F., Lutz S., Gulyas M., Mansuy I.M., Hausser A., Pfizenmaier K., Schlett K.
Mol. Biol. Cell 20:2108-2120(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN ANGIOGENESIS.
[21]"Protein kinase D: an intracellular traffic regulator on the move."
Van Lint J., Rykx A., Maeda Y., Vantus T., Sturany S., Malhotra V., Vandenheede J.R., Seufferlein T.
Trends Cell Biol. 12:193-200(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION IN TRAFFICKING.
[22]"Protein kinase D signaling."
Rozengurt E., Rey O., Waldron R.T.
J. Biol. Chem. 280:13205-13208(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[23]"Protein kinase d in the cardiovascular system: emerging roles in health and disease."
Avkiran M., Rowland A.J., Cuello F., Haworth R.S.
Circ. Res. 102:157-163(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[24]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205; SER-345; SER-448 AND SER-473, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Protein kinase D1, a new molecular player in VEGF signaling and angiogenesis."
Ha C.H., Jin Z.G.
Mol. Cells 28:1-5(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION IN ANGIOGENESIS.
[26]"Protein kinase D signaling: multiple biological functions in health and disease."
Rozengurt E.
Physiology (Bethesda) 26:23-33(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[27]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205 AND SER-208, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[28]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] TYR-152 AND LYS-857.
[29]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] PRO-225; GLN-478; SER-585; MET-677; LEU-679 AND ARG-891.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X75756 mRNA. Translation: CAA53384.1.
AK314170 mRNA. Translation: BAG36853.1.
AL135858 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW65971.1.
CCDSCCDS9637.1.
PIRA53215.
RefSeqNP_002733.2. NM_002742.2.
UniGeneHs.508999.

3D structure databases

ProteinModelPortalQ15139.
SMRQ15139. Positions 147-196, 271-320, 420-541, 550-867.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111573. 26 interactions.
DIPDIP-38481N.
IntActQ15139. 5 interactions.
MINTMINT-88491.
STRING9606.ENSP00000333568.

Chemistry

BindingDBQ15139.
ChEMBLCHEMBL2096620.
GuidetoPHARMACOLOGY1489.

PTM databases

PhosphoSiteQ15139.

Polymorphism databases

DMDM209572639.

Proteomic databases

MaxQBQ15139.
PaxDbQ15139.
PRIDEQ15139.

Protocols and materials databases

DNASU5587.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000331968; ENSP00000333568; ENSG00000184304.
GeneID5587.
KEGGhsa:5587.
UCSCuc001wqh.3. human.

Organism-specific databases

CTD5587.
GeneCardsGC14M030045.
H-InvDBHIX0037727.
HGNCHGNC:9407. PRKD1.
HPACAB018367.
HPA029834.
MIM605435. gene.
neXtProtNX_Q15139.
PharmGKBPA33771.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG003564.
InParanoidQ15139.
KOK06070.
OrthoDBEOG75B84N.
PhylomeDBQ15139.
TreeFamTF314320.

Enzyme and pathway databases

BRENDA2.7.11.13. 2681.
ReactomeREACT_111217. Metabolism.
SignaLinkQ15139.

Gene expression databases

ArrayExpressQ15139.
BgeeQ15139.
CleanExHS_PKD1.
HS_PRKD1.
GenevestigatorQ15139.

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

GeneWikiProtein_kinase_D1.
GenomeRNAi5587.
NextBio21670.
PROQ15139.
SOURCESearch...

Entry information

Entry nameKPCD1_HUMAN
AccessionPrimary (citable) accession number: Q15139
Secondary accession number(s): A6NL64, B2RAF6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 14, 2008
Last modified: July 9, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM