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Protein

Protein kinase C gamma type

Gene

Prkcg

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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 contributes 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 (By similarity).By similarity6 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

  • ATP binding Source: UniProtKB-KW
  • calcium-dependent protein kinase C activity Source: RGD
  • protein kinase C activity Source: RGD
  • protein serine/threonine/tyrosine kinase activity Source: Ensembl
  • zinc ion binding Source: InterPro

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms
LigandATP-binding, Calcium, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

ReactomeiR-RNO-111933 Calmodulin induced events
R-RNO-114516 Disinhibition of SNARE formation
R-RNO-416993 Trafficking of GluR2-containing AMPA receptors
R-RNO-5099900 WNT5A-dependent internalization of FZD4
R-RNO-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
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi3397 Prkcg

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL3604

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000556921 – 697Protein kinase C gamma typeAdd BLAST697

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei250Phosphothreonine; by autocatalysisBy similarity1
Modified residuei320PhosphoserineBy similarity1
Modified residuei322PhosphoserineBy similarity1
Modified residuei326PhosphoserineCombined sources1
Modified residuei328PhosphoserineCombined sources1
Modified residuei330PhosphoserineCombined sources1
Modified residuei332PhosphothreonineBy similarity1
Modified residuei373PhosphoserineBy similarity1
Modified residuei514Phosphothreonine; by PDPK1By similarity1
Modified residuei648Phosphothreonine; by autocatalysisBy similarity1
Modified residuei655PhosphothreonineCombined sources1
Modified residuei674Phosphothreonine; by autocatalysisBy similarity1
Modified residuei675Phosphotyrosine; by SYKBy similarity1
Modified residuei687PhosphoserineCombined sources1

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiP63319
PRIDEiP63319

PTM databases

iPTMnetiP63319
PhosphoSitePlusiP63319

Expressioni

Gene expression databases

BgeeiENSRNOG00000054371
GenevisibleiP63319 RN

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
LIMK1P536673EBI-12598030,EBI-444403From Homo sapiens.

Protein-protein interaction databases

BioGridi246813, 20 interactors
IntActiP63319, 1 interactor
STRINGi10116.ENSRNOP00000019825

Chemistry databases

BindingDBiP63319

Structurei

Secondary structure

1697
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi103 – 105Combined sources3
Beta strandi108 – 110Combined sources3
Beta strandi115 – 117Combined sources3
Beta strandi125 – 127Combined sources3
Beta strandi129 – 131Combined sources3
Turni132 – 134Combined sources3
Turni140 – 145Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1TBNNMR-A91-172[»]
1TBONMR-A91-172[»]
ProteinModelPortaliP63319
SMRiP63319
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP63319

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

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
InParanoidiP63319
KOiK19663
OMAiHQFTARF
OrthoDBiEOG091G0QRS
PhylomeDBiP63319
TreeFamiTF351133

Family and domain databases

CDDicd00029 C1, 2 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000961 AGC-kinase_C
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
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
PfamiView protein in Pfam
PF00130 C1_1, 2 hits
PF00168 C2, 1 hit
PF00069 Pkinase, 1 hit
PF00433 Pkinase_C, 1 hit
PIRSFiPIRSF000550 PKC_alpha, 1 hit
PRINTSiPR00360 C2DOMAIN
PR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 2 hits
SM00239 C2, 1 hit
SM00133 S_TK_X, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS51285 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

Sequencei

Sequence statusi: Complete.

P63319-1 [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
X07287 mRNA Translation: CAA30267.1
M13707 mRNA Translation: AAA41874.1
BC089226 mRNA Translation: AAH89226.1
M55417 Genomic DNA Translation: AAA41873.1
PIRiA05105 KIRTGC
RefSeqiNP_036760.1, NM_012628.1
UniGeneiRn.9747

Genome annotation databases

EnsembliENSRNOT00000080032; ENSRNOP00000071203; ENSRNOG00000054371
GeneIDi24681
KEGGirno:24681
UCSCiRGD:3397 rat

Similar proteinsi

Entry informationi

Entry nameiKPCG_RAT
AccessioniPrimary (citable) accession number: P63319
Secondary accession number(s): P05697, Q5FWS3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: May 23, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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