Reviewed, UniProtKB/Swiss-Prot O94806 (KPCD3_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase D3
    EC=2.7.11.13
Alternative name(s):
    Protein kinase C nu type
    nPKC-nu
    Protein kinase EPK2

Gene names

Name:	PRKD3
Synonyms:	EPK2, PRKCN

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	890 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. Upon diacylglycerol-activation, phosphorylates a range of cellular proteins. Also serves as the receptor for phorbol esters, a class of tumor promoters.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Tissue specificity	Ubiquitous.
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	Alternative splicing 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
Technical term	3D-structure
Gene Ontology (GO)
Biological process	activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway 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
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein kinase C activity Ref.1 Traceable author statement. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VAMP2	P63027	2	EBI-1255366,EBI-520113

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O94806-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O94806-2)

The sequence of this isoform differs from the canonical sequence as follows:
     595-611: HRKTGRDVAIKVIDKMR → QLQPFAYCTHYFKNWKM
     612-890: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 890	890	Serine/threonine-protein kinase D3		PRO_0000055717
Regions
	Domain	416 – 532	117	PH
	Domain	576 – 832	257	Protein kinase
	Zinc finger	154 – 204	51	Phorbol-ester/DAG-type 1
	Zinc finger	271 – 321	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	582 – 590	9	ATP By similarity
Sites
	Active site	699	1	Proton acceptor By similarity
	Binding site	605	1	ATP By similarity
Amino acid modifications
	Modified residue	6	1	Phosphoserine Ref.6
	Modified residue	27	1	Phosphoserine Ref.6 Ref.7
	Modified residue	30	1	Phosphoserine Ref.7
	Modified residue	31	1	Phosphoserine Ref.6
	Modified residue	37	1	Phosphoserine Ref.6
	Modified residue	41	1	Phosphoserine Ref.6 Ref.7 Ref.3
	Modified residue	44	1	Phosphoserine Ref.6 Ref.7 Ref.3
	Modified residue	213	1	Phosphoserine Ref.6
	Modified residue	216	1	Phosphoserine Ref.6
	Modified residue	252	1	Phosphoserine Ref.6
	Modified residue	364	1	Phosphoserine Ref.6 Ref.7 Ref.4
	Modified residue	391	1	Phosphoserine Ref.6 Ref.5
	Modified residue	395	1	Phosphoserine Ref.6
	Modified residue	535	1	Phosphothreonine Ref.6
	Modified residue	543	1	Phosphoserine Ref.6
	Modified residue	731	1	Phosphoserine Ref.6
	Modified residue	735	1	Phosphoserine Ref.6 Ref.5
Natural variations
	Alternative sequence	595 – 611	17	HRKTG…IDKMR → QLQPFAYCTHYFKNWKM in isoform 2.		VSP_029405
	Alternative sequence	612 – 890	279	Missing in isoform 2.		VSP_029406
	Natural variant	42	1	N → D: dbSNP rs11896614.		VAR_037147
	Natural variant	128	1	A → T: dbSNP rs17852819. Ref.2		VAR_037148
	Natural variant	225	1	P → S: dbSNP rs34280934.		VAR_050561
	Natural variant	546	1	Q → R: dbSNP rs17856887. Ref.2		VAR_037149
	Natural variant	716	1	V → M in a glioblastoma multiforme sample; somatic mutation. Ref.9		VAR_042336

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 66D5E7E7235064F5	FASTA	890	100,471
	10 20 30 40 50 60 MSANNSPPSA QKSVLPTAIP AVLPAASPCS SPKTGLSARL SNGSFSAPSL TNSRGSVHTV 70 80 90 100 110 120 SFLLQIGLTR ESVTIEAQEL SLSAVKDLVC SIVYQKFPEC GFFGMYDKIL LFRHDMNSEN 130 140 150 160 170 180 ILQLITSADE IHEGDLVEVV LSALATVEDF QIRPHTLYVH SYKAPTFCDY CGEMLWGLVR 190 200 210 220 230 240 QGLKCEGCGL NYHKRCAFKI PNNCSGVRKR RLSNVSLPGP GLSVPRPLQP EYVALPSEES 250 260 270 280 290 300 HVHQEPSKRI PSWSGRPIWM EKMVMCRVKV PHTFAVHSYT RPTICQYCKR LLKGLFRQGM 310 320 330 340 350 360 QCKDCKFNCH KRCASKVPRD CLGEVTFNGE PSSLGTDTDI PMDIDNNDIN SDSSRGLDDT 370 380 390 400 410 420 EEPSPPEDKM FFLDPSDLDV ERDEEAVKTI SPSTSNNIPL MRVVQSIKHT KRKSSTMVKE 430 440 450 460 470 480 GWMVHYTSRD NLRKRHYWRL DSKCLTLFQN ESGSKYYKEI PLSEILRISS PRDFTNISQG 490 500 510 520 530 540 SNPHCFEIIT DTMVYFVGEN NGDSSHNPVL AATGVGLDVA QSWEKAIRQA LMPVTPQASV 550 560 570 580 590 600 CTSPGQGKDH KDLSTSISVS NCQIQENVDI STVYQIFADE VLGSGQFGIV YGGKHRKTGR 610 620 630 640 650 660 DVAIKVIDKM RFPTKQESQL RNEVAILQNL HHPGIVNLEC MFETPERVFV VMEKLHGDML 670 680 690 700 710 720 EMILSSEKSR LPERITKFMV TQILVALRNL HFKNIVHCDL KPENVLLASA EPFPQVKLCD 730 740 750 760 770 780 FGFARIIGEK SFRRSVVGTP AYLAPEVLRS KGYNRSLDMW SVGVIIYVSL SGTFPFNEDE 790 800 810 820 830 840 DINDQIQNAA FMYPPNPWRE ISGEAIDLIN NLLQVKMRKR YSVDKSLSHP WLQDYQTWLD 850 860 870 880 890 LREFETRIGE RYITHESDDA RWEIHAYTHN LVYPKHFIMA PNPDDMEEDP
	Isoform 2. Checksum: 1714FAD7DA82C942	FASTA	611	68,123
	10 20 30 40 50 60 MSANNSPPSA QKSVLPTAIP AVLPAASPCS SPKTGLSARL SNGSFSAPSL TNSRGSVHTV 70 80 90 100 110 120 SFLLQIGLTR ESVTIEAQEL SLSAVKDLVC SIVYQKFPEC GFFGMYDKIL LFRHDMNSEN 130 140 150 160 170 180 ILQLITSADE IHEGDLVEVV LSALATVEDF QIRPHTLYVH SYKAPTFCDY CGEMLWGLVR 190 200 210 220 230 240 QGLKCEGCGL NYHKRCAFKI PNNCSGVRKR RLSNVSLPGP GLSVPRPLQP EYVALPSEES 250 260 270 280 290 300 HVHQEPSKRI PSWSGRPIWM EKMVMCRVKV PHTFAVHSYT RPTICQYCKR LLKGLFRQGM 310 320 330 340 350 360 QCKDCKFNCH KRCASKVPRD CLGEVTFNGE PSSLGTDTDI PMDIDNNDIN SDSSRGLDDT 370 380 390 400 410 420 EEPSPPEDKM FFLDPSDLDV ERDEEAVKTI SPSTSNNIPL MRVVQSIKHT KRKSSTMVKE 430 440 450 460 470 480 GWMVHYTSRD NLRKRHYWRL DSKCLTLFQN ESGSKYYKEI PLSEILRISS PRDFTNISQG 490 500 510 520 530 540 SNPHCFEIIT DTMVYFVGEN NGDSSHNPVL AATGVGLDVA QSWEKAIRQA LMPVTPQASV 550 560 570 580 590 600 CTSPGQGKDH KDLSTSISVS NCQIQENVDI STVYQIFADE VLGSGQFGIV YGGKQLQPFA 610 YCTHYFKNWK M

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"PKCnu, a new member of the protein kinase C family, composes a fourth subfamily with PKCmu." Hayashi A., Seki N., Hattori A., Kozuma S., Saito T. Biochim. Biophys. Acta 1450:99-106(1999) [PubMed: 10231560] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Embryo.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANTS THR-128 AND ARG-546. Tissue: Testis.
[3]	"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-41 AND SER-44, MASS SPECTROMETRY. Tissue: Epithelium.
[4]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364, MASS SPECTROMETRY. Tissue: Epithelium.
[5]	"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-391 AND SER-735, MASS SPECTROMETRY.
[6]	"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-6; SER-27; SER-31; SER-37; SER-41; SER-44; SER-213; SER-216; SER-252; SER-364; SER-391; SER-395; THR-535; SER-543; SER-731 AND SER-735, MASS SPECTROMETRY.
[7]	"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-27; SER-30; SER-41; SER-44 AND SER-364, MASS SPECTROMETRY.
[8]	"Solution structure of the PH domain of protein kinase C, nu type from human." RIKEN structural genomics initiative (RSGI) Submitted (JAN-2007) to the PDB data bank Cited for: STRUCTURE BY NMR OF 414-532.
[9]	"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: VARIANT [LARGE SCALE ANALYSIS] MET-716.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

AB015982 mRNA. Translation: BAA36514.1.
BC030706 mRNA. Translation: AAH30706.1.

IPI

IPI00015538.
IPI00871931.

RefSeq

NP_005804.1.

UniGene

Hs.660757
Hs.696257

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D9Z	NMR	-	A	417-532	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

O94806. 1 interaction.

PTM databases

PhosphoSite

O94806.

Proteomic databases

PRIDE

O94806.

Genome annotation databases

Ensembl

ENSG00000115825. Homo sapiens. [Contig view]

GeneID

23683.

KEGG

hsa:23683.

Organism-specific databases

GeneCards

GC02M037389.

H-InvDB

HIX0001974.

HGNC

HGNC:9408. PRKD3.

MIM

607077. gene.

PharmGKB

PA33772.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O94806.

HOVERGEN

O94806.

OMA

O94806. ISSPQDF.

Enzyme and pathway databases

BRENDA

2.7.11.13. 247.

Gene expression databases

ArrayExpress

O94806.

Bgee

O94806.

CleanEx

HS_PRKD3.

GermOnline

ENSG00000115825. 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

46561.

SOURCE

Search...

Entry information

Entry name

KPCD3_HUMAN

Accession

Primary (citable) accession number: O94806
Secondary accession number(s): Q8NEL8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	May 1, 1999
Last modified:	June 16, 2009
This is version 81 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)