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Protein

Protein kinase C gamma type

Gene

Prkcg

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays diverse roles in neuronal cells and eye tissues, such as regulation of the neuronal receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and neuronal functions related to sensitivity to opiates, pain and alcohol, mediation of synaptic function and cell survival after ischemia, and inhibition of gap junction activity after oxidative stress. Binds and phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its function by increasing plasma membrane-associated GRIA4 expression. In primary cerebellar neurons treated with the agonist 3,5-dihyidroxyphenylglycine, functions downstream of the metabotropic glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor which plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. May be involved in the regulation of hippocampal long-term potentiation (LTP), but may be not necessary for the process of synaptic plasticity. May be involved in desensitization of mu-type opioid receptor-mediated G-protein activation in the spinal cord, and may be critical for the development and/or maintenance of morphine-induced reinforcing effects in the limbic forebrain. May modulate the functionality of mu-type-opioid receptors by participating in a signaling pathway which leads to the phosphorylation and degradation of opioid receptors. May also contribute to chronic morphine-induced changes in nociceptive processing. Plays a role in neuropathic pain mechanisms and contributes to the maintenance of the allodynia pain produced by peripheral inflammation. Plays an important role in initial sensitivity and tolerance to ethanol, by mediating the behavioral effects of ethanol as well as the effects of this drug on the GABA(A) receptors. During and after cerebral ischemia modulate neurotransmission and cell survival in synaptic membranes, and is involved in insulin-induced inhibition of necrosis, an important mechanism for minimizing ischemic injury. Required for the elimination of multiple climbing fibers during innervation of Purkinje cells in developing cerebellum. Is activated in lens epithelial cells upon hydrogen peroxide treatment, and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of GJA1 gap junction plaques and inhibition of gap junction activity which could provide a protective effect against oxidative stress. Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. Involved in the phase resetting of the cerebral cortex circadian clock during temporally restricted feeding. Stabilizes the core clock component ARNTL/BMAL1 by interfering with its ubiquitination, thus suppressing its degradation, resulting in phase resetting of the cerebral cortex clock (PubMed:23185022).8 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Ca2+By similarityNote: Binds 3 Ca2+ ions per subunit. The ions are bound to the C2 domain.By similarity

Enzyme regulationi

Classical (or conventional) PKCs (PRKCA, PRKCB and PRKCG) are activated by calcium and diacylglycerol (DAG) in the presence of phosphatidylserine. Three specific sites; Thr-514 (activation loop of the kinase domain), Thr-655 (turn motif) and Thr-674 (hydrophobic region), need to be phosphorylated for its full activation.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi186Calcium 1; via carbonyl oxygenBy similarity1
Metal bindingi187Calcium 1By similarity1
Metal bindingi187Calcium 2By similarity1
Metal bindingi193Calcium 2By similarity1
Metal bindingi246Calcium 1By similarity1
Metal bindingi246Calcium 2By similarity1
Metal bindingi247Calcium 2; via carbonyl oxygenBy similarity1
Metal bindingi248Calcium 1By similarity1
Metal bindingi248Calcium 2By similarity1
Metal bindingi248Calcium 3By similarity1
Metal bindingi251Calcium 3By similarity1
Metal bindingi252Calcium 3; via carbonyl oxygenBy similarity1
Metal bindingi254Calcium 1By similarity1
Metal bindingi254Calcium 3By similarity1
Binding sitei380ATPPROSITE-ProRule annotation1
Active sitei480Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri35 – 85Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri100 – 150Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi357 – 365ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

  • chemical synaptic transmission Source: UniProtKB
  • chemosensory behavior Source: MGI
  • innervation Source: UniProtKB
  • intracellular signal transduction Source: GO_Central
  • learning or memory Source: Ensembl
  • negative regulation of neuron apoptotic process Source: UniProtKB
  • negative regulation of proteasomal protein catabolic process Source: UniProtKB
  • negative regulation of protein catabolic process Source: MGI
  • negative regulation of protein ubiquitination Source: UniProtKB
  • peptidyl-serine phosphorylation Source: GO_Central
  • phosphorylation Source: MGI
  • positive regulation of mismatch repair Source: MGI
  • protein autophosphorylation Source: Ensembl
  • regulation of circadian rhythm Source: UniProtKB
  • regulation of phagocytosis Source: MGI
  • regulation of response to food Source: UniProtKB
  • response to morphine Source: UniProtKB
  • response to pain Source: UniProtKB
  • rhythmic process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Biological rhythms

Keywords - Ligandi

ATP-binding, Calcium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13. 3474.
ReactomeiR-MMU-111933. Calmodulin induced events.
R-MMU-114516. Disinhibition of SNARE formation.
R-MMU-416993. Trafficking of GluR2-containing AMPA receptors.
R-MMU-5099900. WNT5A-dependent internalization of FZD4.
R-MMU-76005. Response to elevated platelet cytosolic Ca2+.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C gamma type (EC:2.7.11.13)
Short name:
PKC-gamma
Gene namesi
Name:Prkcg
Synonyms:Pkcc, Pkcg, Prkcc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:97597. Prkcg.

Subcellular locationi

GO - Cellular componenti

  • cell-cell junction Source: MGI
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • dendrite Source: MGI
  • nucleus Source: MGI
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • postsynaptic density Source: MGI
  • synaptic membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Synapse, Synaptosome

Pathology & Biotechi

Disruption phenotypei

Mice exhibit impaired motor coordination due to the inability to eliminate multiple climbing fibers during innervation of Purkinje cells. 40% of Purkinje cells are still innervated by multiple climbing fibers. Exhibit food-anticipatory activity comparable to that of wild type mice but they do not reduce their late night activity or adapt their food intake amount to restricted feeding as efficiently as wild type mice.2 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000556901 – 697Protein kinase C gamma typeAdd BLAST697

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei250Phosphothreonine; by autocatalysisBy similarity1
Modified residuei320PhosphoserineCombined sources1
Modified residuei322PhosphoserineCombined sources1
Modified residuei326PhosphoserineCombined sources1
Modified residuei328PhosphoserineCombined sources1
Modified residuei330PhosphoserineCombined sources1
Modified residuei332PhosphothreonineCombined sources1
Modified residuei373PhosphoserineCombined sources1
Modified residuei514Phosphothreonine; by PDPK11 Publication1
Modified residuei648Phosphothreonine; by autocatalysisSequence analysis1
Modified residuei655Phosphothreonine; by autocatalysis2 Publications1
Modified residuei674Phosphothreonine; by autocatalysis1 Publication1
Modified residuei675Phosphotyrosine; by SYKBy similarity1
Modified residuei687PhosphoserineBy similarity1

Post-translational modificationi

Autophosphorylation on Thr-674 appears to regulate motor functions of junctophilins, JPH3 and JPH4.1 Publication
Ubiquitinated.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP63318.
PeptideAtlasiP63318.
PRIDEiP63318.

PTM databases

iPTMnetiP63318.
PhosphoSitePlusiP63318.
SwissPalmiP63318.

Expressioni

Tissue specificityi

Expressed in the cerebellum, cerebral cortex and hippocampus (at protein level). Highly expressed in Purkinje cells.2 Publications

Gene expression databases

BgeeiENSMUSG00000078816.
CleanExiMM_PRKCC.
ExpressionAtlasiP63318. baseline and differential.
GenevisibleiP63318. MM.

Interactioni

Subunit structurei

Interacts with CDCP1 and GRIA4 (By similarity). Interacts with TP53INP1 and p53/TP53 (By similarity). Interacts with ARNTL/BMAL1.By similarity1 Publication

Protein-protein interaction databases

BioGridi202196. 3 interactors.
IntActiP63318. 11 interactors.
MINTiMINT-98016.
STRINGi10090.ENSMUSP00000097874.

Structurei

3D structure databases

ProteinModelPortaliP63318.
SMRiP63318.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini170 – 260C2PROSITE-ProRule annotationAdd BLAST91
Domaini351 – 614Protein kinasePROSITE-ProRule annotationAdd BLAST264
Domaini615 – 685AGC-kinase C-terminalAdd BLAST71

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 C2 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 fingeri35 – 85Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST51
Zinc fingeri100 – 150Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiKOG0694. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiP63318.
KOiK19663.
OMAiRCFFGTS.
OrthoDBiEOG091G0QRS.
PhylomeDBiP63318.
TreeFamiTF351133.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014375. Protein_kinase_C_a/b/g.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000550. PKC_alpha. 1 hit.
PRINTSiPR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS50004. C2. 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]

Sequencei

Sequence statusi: Complete.

P63318-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGLGPGGGD SEGGPRPLFC RKGALRQKVV HEVKSHKFTA RFFKQPTFCS
60 70 80 90 100
HCTDFIWGIG KQGLQCQVCS FVVHRRCHEF VTFECPGAGK GPQTDDPRNK
110 120 130 140 150
HKFRLHSYSS PTFCDHCGSL LYGLVHQGMK CSCCEMNVHR RCVRSVPSLC
160 170 180 190 200
GVDHTERRGR LQLEIRAPTS DEIHITVGEA RNLIPMDPNG LSDPYVKLKL
210 220 230 240 250
IPDPRNLTKQ KTKTVKATLN PVWNETFVFN LKPGDVERRL SVEVWDWDRT
260 270 280 290 300
SRNDFMGAMS FGVSELLKAP VDGWYKLLNQ EEGEYYNVPV ADADNCSLLQ
310 320 330 340 350
KFEACNYPLE LYERVRMGPS SSPIPSPSPS PTDSKRCFFG ASPGRLHISD
360 370 380 390 400
FSFLMVLGKG SFGKVMLAER RGSDELYAIK ILKKDVIVQD DDVDCTLVEK
410 420 430 440 450
RVLALGGRGP GGRPHFLTQL HSTFQTPDRL YFVMEYVTGG DLMYHIQQLG
460 470 480 490 500
KFKEPHAAFY AAEIAIGLFF LHNQGIIYRD LKLDNVMLDA EGHIKITDFG
510 520 530 540 550
MCKENVFPGS TTRTFCGTPD YIAPEIIAYQ PYGKSVDWWS FGVLLYEMLA
560 570 580 590 600
GQPPFDGEDE EELFQAIMEQ TVTYPKSLSR EAVAICKGFL TKHPGKRLGS
610 620 630 640 650
GPDGEPTIRA HGFFRWIDWE RLERLEIAPP FRPRPCGRSG ENFDKFFTRA
660 670 680 690
APALTPPDRL VLASIDQADF QGFTYVNPDF VHPDARSPTS PVPVPVM
Length:697
Mass (Da):78,358
Last modified:October 11, 2004 - v1
Checksum:iE6E2F7A3B93042FF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67129 mRNA. Translation: CAA47608.1.
L28035 mRNA. Translation: AAA39939.1.
CCDSiCCDS57470.1.
PIRiJN0548.
RefSeqiNP_035232.1. NM_011102.4.
UniGeneiMm.7980.

Genome annotation databases

EnsembliENSMUST00000100301; ENSMUSP00000097874; ENSMUSG00000078816.
ENSMUST00000181455; ENSMUSP00000137923; ENSMUSG00000097449.
GeneIDi18752.
KEGGimmu:18752.
UCSCiuc029wcz.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X67129 mRNA. Translation: CAA47608.1.
L28035 mRNA. Translation: AAA39939.1.
CCDSiCCDS57470.1.
PIRiJN0548.
RefSeqiNP_035232.1. NM_011102.4.
UniGeneiMm.7980.

3D structure databases

ProteinModelPortaliP63318.
SMRiP63318.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202196. 3 interactors.
IntActiP63318. 11 interactors.
MINTiMINT-98016.
STRINGi10090.ENSMUSP00000097874.

PTM databases

iPTMnetiP63318.
PhosphoSitePlusiP63318.
SwissPalmiP63318.

Proteomic databases

PaxDbiP63318.
PeptideAtlasiP63318.
PRIDEiP63318.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000100301; ENSMUSP00000097874; ENSMUSG00000078816.
ENSMUST00000181455; ENSMUSP00000137923; ENSMUSG00000097449.
GeneIDi18752.
KEGGimmu:18752.
UCSCiuc029wcz.2. mouse.

Organism-specific databases

CTDi5582.
MGIiMGI:97597. Prkcg.

Phylogenomic databases

eggNOGiKOG0694. Eukaryota.
ENOG410XNPH. LUCA.
GeneTreeiENSGT00820000126964.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiP63318.
KOiK19663.
OMAiRCFFGTS.
OrthoDBiEOG091G0QRS.
PhylomeDBiP63318.
TreeFamiTF351133.

Enzyme and pathway databases

BRENDAi2.7.11.13. 3474.
ReactomeiR-MMU-111933. Calmodulin induced events.
R-MMU-114516. Disinhibition of SNARE formation.
R-MMU-416993. Trafficking of GluR2-containing AMPA receptors.
R-MMU-5099900. WNT5A-dependent internalization of FZD4.
R-MMU-76005. Response to elevated platelet cytosolic Ca2+.

Miscellaneous databases

PROiP63318.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000078816.
CleanExiMM_PRKCC.
ExpressionAtlasiP63318. baseline and differential.
GenevisibleiP63318. MM.

Family and domain databases

CDDicd00029. C1. 2 hits.
Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR017892. Pkinase_C.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014375. Protein_kinase_C_a/b/g.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFiPIRSF000550. PKC_alpha. 1 hit.
PRINTSiPR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS50004. C2. 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 nameiKPCG_MOUSE
AccessioniPrimary (citable) accession number: P63318
Secondary accession number(s): P05697
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: November 30, 2016
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. 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.