Reviewed, UniProtKB/Swiss-Prot Q15139 (KPCD1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase D1
    EC=2.7.11.13
Alternative name(s):
    nPKC-D1
    Protein kinase D
    Protein kinase C mu type
    nPKC-mu

Gene names

Name:	PRKD1
Synonyms:	PKD, PKD1, PRKCM

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	912 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Calcium-independent, phospholipid-dependent, serine- and threonine-specific kinase involved in resistance to oxidative stress.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Activated by diacylglycerol and phorbol esters.
Subunit structure	Interacts (via N-terminus) with ADAP1/CENTA1. Interacts with Src. Ref.5
Post-translational modification	Phosphorylation of Ser-738 and/or Ser-742 in activated PKD is mediated by transphosphorylation By similarity. Phosphorylation of Tyr-463 mediated by the Src/Abl pathway in response to oxidative stress activates the kinase.
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
Coding sequence diversity	Polymorphism
Domain	Phorbol-ester binding Repeat Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell proliferation Ref.1 Traceable author statement. Source: ProtInc intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Ref.1 Traceable author statement. Source: ProtInc
Cellular component	cytosol Traceable author statement. Source: ProtInc integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.5 Inferred from physical interaction. Source: UniProtKB protein kinase C activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDH1	P12830	3	EBI-1181072,EBI-727477
MAPK13	O15264	2	EBI-1181072,EBI-2116951
MT2A	P02795	4	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 By similarity
Amino acid modifications
	Modified residue	95	1	Phosphotyrosine Ref.8
	Modified residue	205	1	Phosphoserine Ref.7
	Modified residue	210	1	Phosphothreonine Ref.7
	Modified residue	432	1	Phosphotyrosine Ref.6
	Modified residue	463	1	Phosphotyrosine Ref.6
	Modified residue	502	1	Phosphotyrosine Ref.6
	Modified residue	738	1	Phosphoserine By similarity
	Modified residue	742	1	Phosphoserine Ref.9
	Modified residue	910	1	Phosphoserine; by autocatalysis By similarity
Natural variations
	Natural variant	152	1	H → Y in a colorectal cancer sample; somatic mutation. Ref.10		VAR_035468
	Natural variant	225	1	S → P Ref.11		VAR_042324
	Natural variant	478	1	K → Q: dbSNP rs55852813. Ref.11		VAR_042325
	Natural variant	585	1	P → S in a metastatic melanoma sample; somatic mutation. Ref.11		VAR_042326
	Natural variant	677	1	R → M in a lung bronchoalveolar carcinoma sample; somatic mutation. Ref.11		VAR_042327
	Natural variant	679	1	P → L: dbSNP rs34588699. Ref.11		VAR_042328
	Natural variant	825	1	R → K: dbSNP rs11161065.		VAR_046988
	Natural variant	857	1	E → K in a colorectal cancer sample; somatic mutation. Ref.10		VAR_035469
	Natural variant	891	1	H → R: dbSNP rs45582934. Ref.11		VAR_042329
Experimental info
	Mutagenesis	432	1	Y → E: Decreased phosphorylation level when coexpressed with SRC in HeLa cells. Unchanged phosphorylation level when coexpressed with ABL. Ref.6
	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.6
	Mutagenesis	463	1	Y → E: Constitutive activation and constitutive phosphorylation of S-738 and S-742. Ref.6
	Mutagenesis	463	1	Y → F: Decreased phosphorylation level when coexpressed with either SRC or ABL in HeLa cells. Decreased kinase activity. Ref.6
	Mutagenesis	502	1	Y → E: Loss of activation. Ref.6
	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.6
	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)
	Q15139-1 [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: 8119958] [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: 14702039] [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: 12508121] [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]	"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: 12893243] [Abstract] Cited for: INTERACTION WITH ADAP1.
[6]	"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: 12637538] [Abstract] Cited for: PHOSPHORYLATION AT TYR-432; TYR-463 AND TYR-502, MUTAGENESIS OF TYR-432; TYR-463 AND TYR-502.
[7]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed: 17487921] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205 AND THR-210, MASS SPECTROMETRY.
[8]	"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: 17804414] [Abstract] Cited for: PHOSPHORYLATION AT TYR-95.
[9]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-742, MASS SPECTROMETRY.
[10]	"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: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] TYR-152 AND LYS-857.
[11]	"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: 17344846] [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
EMBLGenBankDDBJ	X75756 mRNA. Translation: CAA53384.1. AK314170 mRNA. Translation: BAG36853.1. AL135858 Genomic DNA. No translation available. CH471078 Genomic DNA. Translation: EAW65971.1.
IPI	IPI00924658.
PIR	A53215.
RefSeq	NP_002733.2.
UniGene	Hs.508999
3D structure databases
HSSP	HSSP built from PDB template 1PTQ based on UniProtKB P28867.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15139. 6 interactions.
PTM databases
PhosphoSite	Q15139.
Proteomic databases
PRIDE	Q15139.
Genome annotation databases
Ensembl	ENSG00000184304. Homo sapiens. [Contig view]
GeneID	5587.
KEGG	hsa:5587.
Organism-specific databases
GeneCards	GC14M029115.
H-InvDB	HIX0037727.
HGNC	HGNC:9407. PRKD1.
HPA	CAB018367.
MIM	605435. gene.
PharmGKB	PA33771.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q15139.
OMA	Q15139. REMACSI.
Enzyme and pathway databases
BRENDA	2.7.11.13. 247.
Pathway_Interaction_DB	igf1_pathway. IGF1 pathway. lysophospholipid_pathway. LPA receptor mediated events.
Gene expression databases
ArrayExpress	Q15139.
Bgee	Q15139.
CleanEx	HS_PKD1. HS_PRKD1.
GermOnline	ENSG00000184304. Homo sapiens.
Family and domain databases
InterPro	IPR002219. DAG_PE_bd. IPR011993. PH_type. IPR001849. Pleckstrin_homology. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR015727. Protein_Kinase_C_mu-related. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 1 hit.
PANTHER	PTHR22968. PKC_mu_like. 1 hit.
Pfam	PF00130. C1_1. 2 hits. PF00169. PH. 1 hit. PF00069. Pkinase. 1 hit. [Graphical view]
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00109. C1. 2 hits. SM00233. PH. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
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 Resources
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:	June 16, 2009
This is version 91 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)