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Protein

Serine/threonine-protein kinase D3

Gene

PRKD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Converts transient diacylglycerol (DAG) signals into prolonged physiological effects, downstream of PKC. Involved in resistance to oxidative stress (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

Activated by DAG and phorbol esters. Phorbol-ester/DAG-type domains 1 and 2 bind both DAG and phorbol ester with high affinity and mediate translocation to the cell membrane. Autophosphorylation of Ser-735 and phosphorylation of Ser-731 by PKC relieves auto-inhibition by the PH domain.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei605ATPPROSITE-ProRule annotation1
Active sitei699Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri154 – 204Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri271 – 321Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi582 – 590ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: CACAO
  • metal ion binding Source: UniProtKB-KW
  • protein kinase C activity Source: ProtInc

GO - Biological processi

  • peptidyl-serine phosphorylation Source: GO_Central
  • protein kinase C-activating G-protein coupled receptor signaling pathway Source: ProtInc
  • protein kinase D signaling Source: GO_Central
  • protein phosphorylation Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS03940-MONOMER.
BRENDAi2.7.11.13. 2681.
ReactomeiR-HSA-1660661. Sphingolipid de novo biosynthesis.
SignaLinkiO94806.
SIGNORiO94806.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase D3 (EC:2.7.11.13)
Alternative name(s):
Protein kinase C nu type
Protein kinase EPK2
nPKC-nu
Gene namesi
Name:PRKD3
Synonyms:EPK2, PRKCN
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:9408. PRKD3.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Membrane 1 Publication

  • Note: Translocation to the cell membrane is required for kinase activation.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi156T → A: Slight loss in ability to bind DAG and phorbol-ester; when associated with F-158. 1 Publication1
Mutagenesisi158Y → F: Slight loss in ability to bind DAG and phorbol-ester; when associated with A-156. 1 Publication1
Mutagenesisi165P → G: No effect on ability to bind phorbol ester, loss of ability to bind DAG, reduced DAG-induced membrane translocation. 1 Publication1
Mutagenesisi166T → A: Slight loss in ability to bind DAG and phorbol-ester. 1 Publication1
Mutagenesisi170Y → F: Slight loss in ability to bind DAG and phorbol-ester. 1 Publication1
Mutagenesisi282P → G: No effect on ability to bind phorbol ester, increase in ability to bind DAG. 1 Publication1
Mutagenesisi284I → V: Slight increase in ability to bind DAG, no effect on phorbol-ester binding. 1
Mutagenesisi293K → W: Increased ability to bind DAG, no effect on phorbol-ester binding. 1 Publication1

Organism-specific databases

DisGeNETi23683.
OpenTargetsiENSG00000115825.
PharmGKBiPA33772.

Chemistry databases

ChEMBLiCHEMBL2595.
GuidetoPHARMACOLOGYi2174.

Polymorphism and mutation databases

BioMutaiPRKD3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557171 – 890Serine/threonine-protein kinase D3Add BLAST890

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei6PhosphoserineCombined sources1
Modified residuei27PhosphoserineCombined sources1
Modified residuei37PhosphoserineCombined sources1
Modified residuei41PhosphoserineCombined sources1
Modified residuei44PhosphoserineCombined sources1
Modified residuei213PhosphoserineCombined sources1
Modified residuei216PhosphoserineCombined sources1
Modified residuei364PhosphoserineCombined sources1
Modified residuei535PhosphothreonineCombined sources1
Modified residuei539PhosphoserineBy similarity1
Modified residuei731Phosphoserine; by PKCBy similarity1
Modified residuei735Phosphoserine; by autocatalysisBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO94806.
MaxQBiO94806.
PaxDbiO94806.
PeptideAtlasiO94806.
PRIDEiO94806.

PTM databases

iPTMnetiO94806.
PhosphoSitePlusiO94806.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000115825.
CleanExiHS_PRKD3.
ExpressionAtlasiO94806. baseline and differential.
GenevisibleiO94806. HS.

Organism-specific databases

HPAiHPA029529.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
VAMP2P630277EBI-1255366,EBI-520113

Protein-protein interaction databases

BioGridi117199. 9 interactors.
IntActiO94806. 12 interactors.
MINTiMINT-5003932.
STRINGi9606.ENSP00000234179.

Chemistry databases

BindingDBiO94806.

Structurei

Secondary structure

1890
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi417 – 429Combined sources13
Beta strandi434 – 443Combined sources10
Beta strandi445 – 449Combined sources5
Turni462 – 464Combined sources3
Beta strandi477 – 479Combined sources3
Beta strandi485 – 489Combined sources5
Beta strandi494 – 497Combined sources4
Turni508 – 514Combined sources7
Helixi517 – 532Combined sources16

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D9ZNMR-A417-532[»]
ProteinModelPortaliO94806.
SMRiO94806.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO94806.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini416 – 532PHPROSITE-ProRule annotationAdd BLAST117
Domaini576 – 832Protein kinasePROSITE-ProRule annotationAdd BLAST257

Sequence similaritiesi

Contains 1 PH domain.PROSITE-ProRule annotation
Contains 2 phorbol-ester/DAG-type zinc fingers.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri154 – 204Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri271 – 321Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG4236. Eukaryota.
ENOG410XQZ3. LUCA.
GeneTreeiENSGT00840000129794.
HOGENOMiHOG000015135.
HOVERGENiHBG003564.
InParanoidiO94806.
KOiK06070.
OMAiYTSRDTL.
OrthoDBiEOG091G02RG.
PhylomeDBiO94806.
TreeFamiTF314320.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.30.29.30. 1 hit.
InterProiIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR015727. Protein_Kinase_C_mu-related.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR22968. PTHR22968. 1 hit.
PfamiPF00130. C1_1. 2 hits.
PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF000552. PKC_mu_nu_D2. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00233. PH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50003. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O94806-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSANNSPPSA QKSVLPTAIP AVLPAASPCS SPKTGLSARL SNGSFSAPSL
60 70 80 90 100
TNSRGSVHTV SFLLQIGLTR ESVTIEAQEL SLSAVKDLVC SIVYQKFPEC
110 120 130 140 150
GFFGMYDKIL LFRHDMNSEN ILQLITSADE IHEGDLVEVV LSALATVEDF
160 170 180 190 200
QIRPHTLYVH SYKAPTFCDY CGEMLWGLVR QGLKCEGCGL NYHKRCAFKI
210 220 230 240 250
PNNCSGVRKR RLSNVSLPGP GLSVPRPLQP EYVALPSEES HVHQEPSKRI
260 270 280 290 300
PSWSGRPIWM EKMVMCRVKV PHTFAVHSYT RPTICQYCKR LLKGLFRQGM
310 320 330 340 350
QCKDCKFNCH KRCASKVPRD CLGEVTFNGE PSSLGTDTDI PMDIDNNDIN
360 370 380 390 400
SDSSRGLDDT EEPSPPEDKM FFLDPSDLDV ERDEEAVKTI SPSTSNNIPL
410 420 430 440 450
MRVVQSIKHT KRKSSTMVKE GWMVHYTSRD NLRKRHYWRL DSKCLTLFQN
460 470 480 490 500
ESGSKYYKEI PLSEILRISS PRDFTNISQG SNPHCFEIIT DTMVYFVGEN
510 520 530 540 550
NGDSSHNPVL AATGVGLDVA QSWEKAIRQA LMPVTPQASV CTSPGQGKDH
560 570 580 590 600
KDLSTSISVS NCQIQENVDI STVYQIFADE VLGSGQFGIV YGGKHRKTGR
610 620 630 640 650
DVAIKVIDKM RFPTKQESQL RNEVAILQNL HHPGIVNLEC MFETPERVFV
660 670 680 690 700
VMEKLHGDML EMILSSEKSR LPERITKFMV TQILVALRNL HFKNIVHCDL
710 720 730 740 750
KPENVLLASA EPFPQVKLCD FGFARIIGEK SFRRSVVGTP AYLAPEVLRS
760 770 780 790 800
KGYNRSLDMW SVGVIIYVSL SGTFPFNEDE DINDQIQNAA FMYPPNPWRE
810 820 830 840 850
ISGEAIDLIN NLLQVKMRKR YSVDKSLSHP WLQDYQTWLD LREFETRIGE
860 870 880 890
RYITHESDDA RWEIHAYTHN LVYPKHFIMA PNPDDMEEDP
Length:890
Mass (Da):100,471
Last modified:May 1, 1999 - v1
Checksum:i66D5E7E7235064F5
GO
Isoform 2 (identifier: O94806-2) [UniParc]FASTAAdd to basket

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

Show »
Length:611
Mass (Da):68,123
Checksum:i1714FAD7DA82C942
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03714742N → D.Corresponds to variant rs11896614dbSNPEnsembl.1
Natural variantiVAR_037148128A → T.1 PublicationCorresponds to variant rs17852819dbSNPEnsembl.1
Natural variantiVAR_050561225P → S.Corresponds to variant rs34280934dbSNPEnsembl.1
Natural variantiVAR_061532445L → I.Corresponds to variant rs55912911dbSNPEnsembl.1
Natural variantiVAR_037149546Q → R.1 PublicationCorresponds to variant rs17856887dbSNPEnsembl.1
Natural variantiVAR_042336716V → M in a glioblastoma multiforme sample; somatic mutation. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_029405595 – 611HRKTG…IDKMR → QLQPFAYCTHYFKNWKM in isoform 2. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_029406612 – 890Missing in isoform 2. 1 PublicationAdd BLAST279

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB015982 mRNA. Translation: BAA36514.1.
AC007390 Genomic DNA. Translation: AAY14817.1.
CH471053 Genomic DNA. Translation: EAX00398.1.
CH471053 Genomic DNA. Translation: EAX00399.1.
BC030706 mRNA. Translation: AAH30706.1.
CCDSiCCDS1789.1. [O94806-1]
RefSeqiNP_005804.1. NM_005813.4. [O94806-1]
XP_005264294.1. XM_005264237.3. [O94806-1]
UniGeneiHs.660757.
Hs.716034.

Genome annotation databases

EnsembliENST00000234179; ENSP00000234179; ENSG00000115825. [O94806-1]
ENST00000379066; ENSP00000368356; ENSG00000115825. [O94806-1]
GeneIDi23683.
KEGGihsa:23683.
UCSCiuc002rqd.4. human. [O94806-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB015982 mRNA. Translation: BAA36514.1.
AC007390 Genomic DNA. Translation: AAY14817.1.
CH471053 Genomic DNA. Translation: EAX00398.1.
CH471053 Genomic DNA. Translation: EAX00399.1.
BC030706 mRNA. Translation: AAH30706.1.
CCDSiCCDS1789.1. [O94806-1]
RefSeqiNP_005804.1. NM_005813.4. [O94806-1]
XP_005264294.1. XM_005264237.3. [O94806-1]
UniGeneiHs.660757.
Hs.716034.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2D9ZNMR-A417-532[»]
ProteinModelPortaliO94806.
SMRiO94806.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117199. 9 interactors.
IntActiO94806. 12 interactors.
MINTiMINT-5003932.
STRINGi9606.ENSP00000234179.

Chemistry databases

BindingDBiO94806.
ChEMBLiCHEMBL2595.
GuidetoPHARMACOLOGYi2174.

PTM databases

iPTMnetiO94806.
PhosphoSitePlusiO94806.

Polymorphism and mutation databases

BioMutaiPRKD3.

Proteomic databases

EPDiO94806.
MaxQBiO94806.
PaxDbiO94806.
PeptideAtlasiO94806.
PRIDEiO94806.

Protocols and materials databases

DNASUi23683.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000234179; ENSP00000234179; ENSG00000115825. [O94806-1]
ENST00000379066; ENSP00000368356; ENSG00000115825. [O94806-1]
GeneIDi23683.
KEGGihsa:23683.
UCSCiuc002rqd.4. human. [O94806-1]

Organism-specific databases

CTDi23683.
DisGeNETi23683.
GeneCardsiPRKD3.
H-InvDBHIX0030377.
HGNCiHGNC:9408. PRKD3.
HPAiHPA029529.
MIMi607077. gene.
neXtProtiNX_O94806.
OpenTargetsiENSG00000115825.
PharmGKBiPA33772.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4236. Eukaryota.
ENOG410XQZ3. LUCA.
GeneTreeiENSGT00840000129794.
HOGENOMiHOG000015135.
HOVERGENiHBG003564.
InParanoidiO94806.
KOiK06070.
OMAiYTSRDTL.
OrthoDBiEOG091G02RG.
PhylomeDBiO94806.
TreeFamiTF314320.

Enzyme and pathway databases

BioCyciZFISH:HS03940-MONOMER.
BRENDAi2.7.11.13. 2681.
ReactomeiR-HSA-1660661. Sphingolipid de novo biosynthesis.
SignaLinkiO94806.
SIGNORiO94806.

Miscellaneous databases

ChiTaRSiPRKD3. human.
EvolutionaryTraceiO94806.
GeneWikiiPRKD3.
GenomeRNAii23683.
PROiO94806.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000115825.
CleanExiHS_PRKD3.
ExpressionAtlasiO94806. baseline and differential.
GenevisibleiO94806. HS.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.30.29.30. 1 hit.
InterProiIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR015727. Protein_Kinase_C_mu-related.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PANTHERiPTHR22968. PTHR22968. 1 hit.
PfamiPF00130. C1_1. 2 hits.
PF00169. PH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF000552. PKC_mu_nu_D2. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00233. PH. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50003. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiKPCD3_HUMAN
AccessioniPrimary (citable) accession number: O94806
Secondary accession number(s): D6W587, Q53TR7, Q8NEL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: May 1, 1999
Last modified: November 30, 2016
This is version 163 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.