Reviewed, UniProtKB/Swiss-Prot Q9BZL6 (KPCD2_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase D2
    EC=2.7.11.13
Alternative name(s):
    nPKC-D2

Gene names

Name:	PRKD2
Synonyms:	PKD2
ORF Names:	HSPC187

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	878 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium By similarity.
Enzyme regulation	Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains bind DAG, mediating translocation to membranes. Autophosphorylation of Ser-710 and phosphorylation of Ser-706 by PKC relieves auto-inhibition by the PH domain By similarity.
Subcellular location	Cytoplasm By similarity. Membrane By similarity. Note: Translocation to the cell membrane is required for kinase activation By similarity.
Tissue specificity	Widely expressed.
Post-translational modification	Phosphorylation of Ser-876 correlates with the activation status of 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.
Sequence caution	The sequence AAF36107.1 differs from that shown. Reason: Frameshift at positions 604, 606, 738, 744, 755, 758, 833 and 854.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Polymorphism
Domain	Phorbol-ester binding Repeat Zinc-finger
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	intracellular signaling cascade Non-traceable author statement. Source: UniProtKB protein amino acid phosphorylation Ref.1 Non-traceable author statement. Source: UniProtKB
Cellular component	intracellular Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from electronic annotation. Source: EC zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 878

878

Serine/threonine-protein kinase D2

PRO_0000055716

Regions

Domain

397 – 509

113

PH

Domain

551 – 807

257

Protein kinase

Zinc finger

138 – 188

51

Phorbol-ester/DAG-type 1

Zinc finger

264 – 314

51

Phorbol-ester/DAG-type 2

Nucleotide binding

557 – 565

9

ATP By similarity

Sites

Active site

674

1

Proton acceptor By similarity

Binding site

580

1

ATP By similarity

Amino acid modifications

Modified residue

197

1

Phosphoserine Ref.4 Ref.5 Ref.6 Ref.8 Ref.10 Ref.11

Modified residue

198

1

Phosphoserine Ref.4

Modified residue

200

1

Phosphoserine Ref.11 Ref.9

Modified residue

203

1

Phosphoserine Ref.11

Modified residue

206

1

Phosphoserine Ref.11

Modified residue

212

1

Phosphoserine By similarity

Modified residue

214

1

Phosphoserine Ref.6 Ref.10 Ref.11

Modified residue

375

1

Phosphoserine Ref.10

Modified residue

396

1

Phosphoserine Ref.10

Modified residue

518

1

Phosphoserine Ref.10

Modified residue

706

1

Phosphoserine; by PKC By similarity

Modified residue

710

1

Phosphoserine; by autocatalysis By similarity

Modified residue

876

1

Phosphoserine; by autocatalysis Ref.10 Ref.1

Natural variations

Natural variant

324

1

V → M

VAR_042330

Natural variant

496

1

A → V

VAR_042331

Natural variant

604

1

S → G

VAR_042332

Natural variant

773

1

W → R

VAR_042333

Natural variant

848

1

G → E in a lung adenocarcinoma sample; somatic mutation. Ref.14

VAR_042334

Natural variant

870

1

G → E in a gastric adenocarcinoma sample; somatic mutation. Ref.14

VAR_042335

Experimental info

Mutagenesis

275

1

P → G: Increase in ability to bind phorbol ester, slight increase in ability to bind DAG. Ref.7

Sequence conflict

790

1

V → L in AAF36107. Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

878

Helix Strand Turn

Details...

Beta strand

399 – 406

8

Beta strand

409 – 411

3

Beta strand

415 – 421

7

Beta strand

423 – 433

11

Beta strand

438 – 442

5

Turn

443 – 445

3

Beta strand

448 – 452

5

Beta strand

456 – 458

3

Beta strand

465 – 470

6

Beta strand

486 – 488

3

Helix

495 – 507

13

Sequences

	Sequence		Length	Mass (Da)
	Q9BZL6-1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 8BAB45E8F99D23E7	FASTA	878	96,722
	10 20 30 40 50 60 MATAPSYPAG LPGSPGPGSP PPPGGLELQS PPPLLPQIPA PGSGVSFHIQ IGLTREFVLL 70 80 90 100 110 120 PAASELAHVK QLACSIVDQK FPECGFYGLY DKILLFKHDP TSANLLQLVR SSGDIQEGDL 130 140 150 160 170 180 VEVVLSASAT FEDFQIRPHA LTVHSYRAPA FCDHCGEMLF GLVRQGLKCD GCGLNYHKRC 190 200 210 220 230 240 AFSIPNNCSG ARKRRLSSTS LASGHSVRLG TSESLPCTAE ELSRSTTELL PRRPPSSSSS 250 260 270 280 290 300 SSASSYTGRP IELDKMLLSK VKVPHTFLIH SYTRPTVCQA CKKLLKGLFR QGLQCKDCKF 310 320 330 340 350 360 NCHKRCATRV PNDCLGEALI NGDVPMEEAT DFSEADKSAL MDESEDSGVI PGSHSENALH 370 380 390 400 410 420 ASEEEEGEGG KAQSSLGYIP LMRVVQSVRH TTRKSSTTLR EGWVVHYSNK DTLRKRHYWR 430 440 450 460 470 480 LDCKCITLFQ NNTTNRYYKE IPLSEILTVE SAQNFSLVPP GTNPHCFEIV TANATYFVGE 490 500 510 520 530 540 MPGGTPGGPS GQGAEAARGW ETAIRQALMP VILQDAPSAP GHAPHRQASL SISVSNSQIQ 550 560 570 580 590 600 ENVDIATVYQ IFPDEVLGSG QFGVVYGGKH RKTGRDVAVK VIDKLRFPTK QESQLRNEVA 610 620 630 640 650 660 ILQSLRHPGI VNLECMFETP EKVFVVMEKL HGDMLEMILS SEKGRLPERL TKFLITQILV 670 680 690 700 710 720 ALRHLHFKNI VHCDLKPENV LLASADPFPQ VKLCDFGFAR IIGEKSFRRS VVGTPAYLAP 730 740 750 760 770 780 EVLLNQGYNR SLDMWSVGVI MYVSLSGTFP FNEDEDINDQ IQNAAFMYPA SPWSHISAGA 790 800 810 820 830 840 IDLINNLLQV KMRKRYSVDK SLSHPWLQEY QTWLDLRELE GKMGERYITH ESDDARWEQF 850 860 870 AAEHPLPGSG LPTDRDLGGA CPPQDHDMQG LAERISVL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and characterization of the human protein kinase D2. A novel member of the protein kinase d family of serine threonine kinases." Sturany S., Van Lint J., Mueller F., Wilda M., Hameister H., Hoecker M., Brey A., Gern U., Vandenheede J., Gress T., Adler G., Seufferlein T. J. Biol. Chem. 276:3310-3318(2001) [PubMed: 11062248] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT SER-876. Tissue: Pancreas.
[2]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 337-878. Tissue: Uterus.
[3]	"Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells." Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., Tao J., Huang Q.-H., Zhou J., Hu G.-X. , Gu J., Chen S.-J., Chen Z. Genome Res. 10:1546-1560(2000) [PubMed: 11042152] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 574-878. Tissue: Umbilical cord blood.
[4]	"Global phosphoproteome of HT-29 human colon adenocarcinoma cells." Kim J.-E., Tannenbaum S.R., White F.M. J. Proteome Res. 4:1339-1346(2005) [PubMed: 16083285] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197 AND SER-198, MASS SPECTROMETRY.
[5]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197, MASS SPECTROMETRY. Tissue: Epithelium.
[6]	"Proteomics analysis of protein kinases by target class-selective prefractionation and tandem mass spectrometry." Wissing J., Jaensch L., Nimtz M., Dieterich G., Hornberger R., Keri G., Wehland J., Daub H. Mol. Cell. Proteomics 6:537-547(2007) [PubMed: 17192257] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197; SER-214 AND SER-710, MASS SPECTROMETRY.
[7]	"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: 18076381] [Abstract] Cited for: PHORBOL-ESTER BINDING, MUTAGENESIS OF PRO-275.
[8]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197, MASS SPECTROMETRY.
[9]	"Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment." Carrascal M., Ovelleiro D., Casas V., Gay M., Abian J. J. Proteome Res. 7:5167-5176(2008) [PubMed: 19367720] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-200, MASS SPECTROMETRY. Tissue: T-cell.
[10]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-197; SER-214; SER-375; SER-396; SER-518; SER-706; SER-710 AND SER-876, MASS SPECTROMETRY.
[11]	"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-197; SER-200; SER-203; SER-206; SER-214 AND SER-710, MASS SPECTROMETRY.
[12]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]	"Solution structure of the PH domain of protein kinase C, D2 type from human." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 395-509.
[14]	"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] MET-324; VAL-496; GLY-604; ARG-773; GLU-848 AND GLU-870.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF309082 mRNA. Translation: AAK01149.1.
AL050147 mRNA. Translation: CAB43292.1.
AF151021 mRNA. Translation: AAF36107.1. Frameshift.

IPI

IPI00941257.

PIR

T08777.

RefSeq

NP_001073349.1.
NP_001073350.1.
NP_001073351.1.
NP_057541.2.

UniGene

Hs.466987

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2COA	NMR	-	A	398-509	[»]
3BGM	X-ray	1.60	C	526-534	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q9BZL6.

PTM databases

PhosphoSite

Q9BZL6.

Proteomic databases

PRIDE

Q9BZL6.

Genome annotation databases

Ensembl

ENST00000291281; ENSP00000291281; ENSG00000105287; Homo sapiens. [Genome view]
ENST00000433867; ENSP00000393978; ENSG00000105287; Homo sapiens. [Genome view]
ENST00000449438; ENSP00000408285; ENSG00000105287; Homo sapiens. [Genome view]
ENST00000454760; ENSP00000414761; ENSG00000105287; Homo sapiens. [Genome view]

GeneID

25865.

KEGG

hsa:25865.

UCSC

uc002pfh.1. human.

Organism-specific databases

CTD

25865.

GeneCards

GC19M051869.

H-InvDB

HIX0015258.

HGNC

HGNC:17293. PRKD2.

HPA

HPA021490.

MIM

607074. gene.

PharmGKB

PA134903505.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9BZL6.

HOVERGEN

Q9BZL6.

Enzyme and pathway databases

BRENDA

2.7.11.13. 247.

Gene expression databases

ArrayExpress

Q9BZL6.

Bgee

Q9BZL6.

CleanEx

HS_PKD2.
HS_PRKD2.

Genevestigator

Q9BZL6.

GermOnline

ENSG00000105287. Homo sapiens.

Family and domain databases

InterPro

IPR020454. DAG/PE_bd.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR002219. Prot_Kinase_C-like_PE/DAG_bd.
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]

PRINTS

PR00008. DAGPEDOMAIN.

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

47239.

SOURCE

Search...

Entry information

Entry name

KPCD2_HUMAN

Accession

Primary (citable) accession number: Q9BZL6
Secondary accession number(s): Q8TB08, Q9P0T6, Q9Y3X8

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 27, 2002
Last sequence update:	June 1, 2001
Last modified:	October 13, 2009
This is version 98 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.