Q15139 (KPCD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	912 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 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.18 Ref.19
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.18
Subcellular location	Cytoplasm. Cell membrane. Golgi apparatus › trans-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.18
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	Angiogenesis Apoptosis Differentiation Immunity Inflammatory response Innate immunity Neurogenesis
Cellular component	Cell membrane Cytoplasm Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
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	Golgi organization Inferred from mutant phenotype Ref.19. 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 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 protein kinase cascade 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 phospholipid metabolic process Traceable author statement. Source: Reactome positive regulation of CREB transcription factor activity Inferred from genetic interaction PubMed 20497126. Source: BHF-UCL positive regulation of I-kappaB kinase/NF-kappaB cascade 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 by VEGF-activated vascular endothelial growth factor receptor signaling pathway Inferred from mutant phenotype PubMed 18440775. Source: BHF-UCL 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.19. 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 small molecule metabolic process Traceable author statement. Source: Reactome sphingolipid biosynthetic process Traceable author statement. Source: Reactome
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell cell cortex Inferred from electronic annotation. Source: Compara cell-cell junction Inferred from electronic annotation. Source: Compara cytosol Inferred from sequence or structural similarity. Source: UniProtKB integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc nucleus Inferred from electronic annotation. Source: Compara trans-Golgi network Inferred from direct assay Ref.19. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipid binding Inferred from electronic annotation. Source: InterPro protein kinase C activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-1181072,EBI-1181072
C1QBP	Q07021	9	EBI-1181072,EBI-347528
CDH1	P12830	7	EBI-1181072,EBI-727477
HSP90AB1	P08238	2	EBI-1181072,EBI-352572
MAPK13	O15264	6	EBI-1181072,EBI-2116951
MT2A	P02795	7	EBI-1181072,EBI-996616

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 912	912	Serine/threonine-protein kinase D1		PRO_0000055714
Regions
	Domain	422 – 541	120	PH
	Domain	583 – 839	257	Protein kinase
	Zinc finger	146 – 196	51	Phorbol-ester/DAG-type 1
	Zinc finger	270 – 320	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	589 – 597	9	ATP By similarity
	Compositional bias	17 – 26	10	Poly-Ala
	Compositional bias	200 – 203	4	Poly-Arg
Sites
	Active site	706	1	Proton acceptor By similarity
	Binding site	612	1	ATP
Amino acid modifications
	Modified residue	95	1	Phosphotyrosine Ref.13
	Modified residue	205	1	Phosphoserine Ref.23 Ref.26
	Modified residue	208	1	Phosphoserine Ref.26
	Modified residue	247	1	Phosphoserine By similarity
	Modified residue	345	1	Phosphoserine Ref.23
	Modified residue	397	1	Phosphoserine; by MAPK13 Ref.18
	Modified residue	401	1	Phosphoserine; by MAPK13 Ref.18
	Modified residue	432	1	Phosphotyrosine Ref.9
	Modified residue	448	1	Phosphoserine Ref.23
	Modified residue	463	1	Phosphotyrosine; by ABL Ref.9 Ref.11
	Modified residue	473	1	Phosphoserine Ref.23
	Modified residue	502	1	Phosphotyrosine Ref.9
	Modified residue	738	1	Phosphoserine; by PKC/PRKCD Ref.11
	Modified residue	742	1	Phosphoserine; by autocatalysis and PKC/PRKCD Ref.11
	Modified residue	910	1	Phosphoserine; by autocatalysis Ref.12
Natural variations
	Natural variant	152	1	H → Y in a colorectal cancer sample; somatic mutation. Ref.27		VAR_035468
	Natural variant	225	1	S → P. Ref.28		VAR_042324
	Natural variant	478	1	K → Q. Ref.28 Corresponds to variant rs55852813 [ dbSNP | Ensembl ].		VAR_042325
	Natural variant	585	1	P → S in a metastatic melanoma sample; somatic mutation. Ref.28		VAR_042326
	Natural variant	677	1	R → M in a lung bronchoalveolar carcinoma sample; somatic mutation. Ref.28		VAR_042327
	Natural variant	679	1	P → L. Ref.28 Corresponds to variant rs34588699 [ dbSNP | Ensembl ].		VAR_042328
	Natural variant	825	1	R → K. Corresponds to variant rs11161065 [ dbSNP | Ensembl ].		VAR_046988
	Natural variant	857	1	E → K in a colorectal cancer sample; somatic mutation. Ref.27		VAR_035469
	Natural variant	891	1	H → R. Ref.28 Corresponds to variant rs45582934 [ dbSNP | Ensembl ].		VAR_042329
Experimental info
	Mutagenesis	157	1	P → G: Increase in ability to bind phorbol ester, loss of ability to bind DAG. Ref.15
	Mutagenesis	281	1	P → G: No effect on ability to bind phorbol ester, slight increase in ability to bind DAG. Ref.15
	Mutagenesis	432	1	Y → E: Decreased phosphorylation level when coexpressed with SRC in HeLa cells. Unchanged phosphorylation level when coexpressed with ABL. Ref.9
	Mutagenesis	432	1	Y → 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
	Mutagenesis	463	1	Y → E: Constitutive activation and constitutive phosphorylation of S-738 and S-742. Ref.9
	Mutagenesis	463	1	Y → F: Decreased phosphorylation level when coexpressed with either SRC or ABL in HeLa cells. Decreased kinase activity. Ref.9
	Mutagenesis	502	1	Y → E: Loss of activation. Ref.9
	Mutagenesis	502	1	Y → 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
	Mutagenesis	612	1	K → W: Loss of kinase activity. Ref.9
	Sequence conflict	135	1	A → R in CAA53384. Ref.1
	Sequence conflict	877	1	G → R in CAA53384. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q15139 [UniParc]. Last modified October 14, 2008. Version 2. Checksum: 0BC9414C335D2DBB	FASTA	912	101,704
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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]	"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.
[19]	"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.
[20]	"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.
[21]	"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.
[22]	"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.
[23]	"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, MASS SPECTROMETRY.
[24]	"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 REVIEW ON FUNCTION IN ANGIOGENESIS.
[25]	"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.
[26]	"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, MASS SPECTROMETRY.
[27]	"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. , 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.
[28]	"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. , 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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.
IPI	IPI00782950.
PIR	A53215.
RefSeq	NP_002733.2. NM_002742.2.
UniGene	Hs.508999.
3D structure databases
ProteinModelPortal	Q15139.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-38481N.
IntAct	Q15139. 5 interactions.
STRING	9606.ENSP00000333568.
PTM databases
PhosphoSite	Q15139.
Polymorphism databases
DMDM	209572639.
Proteomic databases
PaxDb	Q15139.
PRIDE	Q15139.
Protocols and materials databases
DNASU	5587.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000331968; ENSP00000333568; ENSG00000184304.
GeneID	5587.
KEGG	hsa:5587.
UCSC	uc001wqh.3. human.
Organism-specific databases
CTD	5587.
GeneCards	GC14M030045.
H-InvDB	HIX0037727.
HGNC	HGNC:9407. PRKD1.
HPA	CAB018367. HPA029834.
MIM	605435. gene.
neXtProt	NX_Q15139.
PharmGKB	PA33771.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOVERGEN	HBG003564.
InParanoid	Q15139.
KO	K06070.
OrthoDB	EOG4548XW.
PhylomeDB	Q15139.
Enzyme and pathway databases
BRENDA	2.7.11.13. 2681.
Pathway_Interaction_DB	igf1_pathway. IGF1 pathway. lysophospholipid_pathway. LPA receptor mediated events.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q15139.
Bgee	Q15139.
CleanEx	HS_PKD1. HS_PRKD1.
Genevestigator	Q15139.
GermOnline	ENSG00000184304. Homo sapiens.
Family and domain databases
Gene3D	2.30.29.30. 1 hit.
InterPro	IPR020454. 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_cat_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]
PANTHER	PTHR22968. PTHR22968. 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
BindingDB	Q15139.
ChEMBL	CHEMBL3863.
GenomeRNAi	5587.
NextBio	21670.
SOURCE	Search...

Entry information

Entry name

KPCD1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 135 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.