UniProtKB - P63319 (KPCG_RAT)
Protein
Protein kinase C gamma type
Gene
Prkcg
Organism
Rattus norvegicus (Rat)
Status
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
Cofactori
Ca2+PROSITE-ProRule annotationNote: Binds 3 Ca2+ ions per subunit. The ions are bound to the C2 domain.By similarity
Activity 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 186 | Calcium 1; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 187 | Calcium 1By similarity | 1 | |
Metal bindingi | 187 | Calcium 2By similarity | 1 | |
Metal bindingi | 193 | Calcium 2By similarity | 1 | |
Metal bindingi | 246 | Calcium 1By similarity | 1 | |
Metal bindingi | 246 | Calcium 2By similarity | 1 | |
Metal bindingi | 247 | Calcium 2; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 248 | Calcium 1By similarity | 1 | |
Metal bindingi | 248 | Calcium 2By similarity | 1 | |
Metal bindingi | 248 | Calcium 3By similarity | 1 | |
Metal bindingi | 251 | Calcium 3By similarity | 1 | |
Metal bindingi | 252 | Calcium 3; via carbonyl oxygenBy similarity | 1 | |
Metal bindingi | 254 | Calcium 1By similarity | 1 | |
Metal bindingi | 254 | Calcium 3By similarity | 1 | |
Binding sitei | 380 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 480 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 35 – 85 | Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST | 51 | |
Zinc fingeri | 100 – 150 | Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST | 51 | |
Nucleotide bindingi | 357 – 365 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- calcium-dependent protein kinase C activity Source: RGD
- protein kinase activity Source: RGD
- protein kinase C activity Source: RGD
- protein serine/threonine/tyrosine kinase activity Source: RGD
- protein serine/threonine kinase activity Source: GO_Central
- zinc ion binding Source: InterPro
GO - Biological processi
- chemical synaptic transmission Source: RGD
- chemosensory behavior Source: RGD
- innervation Source: RGD
- intracellular signal transduction Source: GO_Central
- learning or memory Source: RGD
- negative regulation of neuron apoptotic process Source: UniProtKB
- negative regulation of proteasomal protein catabolic process Source: UniProtKB
- negative regulation of protein catabolic process Source: RGD
- negative regulation of protein ubiquitination Source: UniProtKB
- peptidyl-serine phosphorylation Source: GO_Central
- phosphorylation Source: RGD
- positive regulation of mismatch repair Source: RGD
- presynaptic modulation of chemical synaptic transmission Source: RGD
- protein autophosphorylation Source: RGD
- regulation of circadian rhythm Source: UniProtKB
- regulation of phagocytosis Source: RGD
- regulation of response to food Source: UniProtKB
- regulation of synaptic vesicle exocytosis Source: RGD
- response to morphine Source: UniProtKB
- response to pain Source: UniProtKB
- response to psychosocial stress Source: UniProtKB
- rhythmic process Source: UniProtKB-KW
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Biological rhythms |
Ligand | ATP-binding, Calcium, Metal-binding, Nucleotide-binding, Zinc |
Enzyme and pathway databases
Reactomei | R-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 | |
Gene namesi | Name:Prkcg Synonyms:Pkcc, Pkcg, Prkcc |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 3397, Prkcg |
Subcellular locationi
Plasma membrane
- Cell membrane 2 Publications; Peripheral membrane protein
Other locations
- Cytoplasm By similarity
- perinuclear region
- synaptosome 1 Publication
- dendrite 1 Publication
Note: Translocates to synaptic membranes on stimulation.1 Publication
Cytosol
- cytosol Source: UniProtKB
- postsynaptic cytosol Source: SynGO
- presynaptic cytosol Source: RGD
Nucleus
- nucleus Source: RGD
Plasma Membrane
- plasma membrane Source: UniProtKB
- synaptic membrane Source: RGD
Other locations
- calyx of Held Source: RGD
- cell-cell junction Source: RGD
- cytoplasm Source: RGD
- dendrite Source: UniProtKB
- neuron projection Source: RGD
- perinuclear region of cytoplasm Source: UniProtKB
- postsynaptic density Source: RGD
Keywords - Cellular componenti
Cell junction, Cell membrane, Cell projection, Cytoplasm, Membrane, Synapse, SynaptosomePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000055692 | 1 – 697 | Protein kinase C gamma typeAdd BLAST | 697 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 250 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 320 | PhosphoserineBy similarity | 1 | |
Modified residuei | 322 | PhosphoserineBy similarity | 1 | |
Modified residuei | 326 | PhosphoserineCombined sources | 1 | |
Modified residuei | 328 | PhosphoserineCombined sources | 1 | |
Modified residuei | 330 | PhosphoserineCombined sources | 1 | |
Modified residuei | 332 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 373 | PhosphoserineBy similarity | 1 | |
Modified residuei | 514 | Phosphothreonine; by PDPK1By similarity | 1 | |
Modified residuei | 648 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 655 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 674 | Phosphothreonine; by autocatalysisBy similarity | 1 | |
Modified residuei | 675 | Phosphotyrosine; by SYKBy similarity | 1 | |
Modified residuei | 687 | PhosphoserineCombined sources | 1 |
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 conjugationProteomic databases
PaxDbi | P63319 |
PRIDEi | P63319 |
PTM databases
iPTMneti | P63319 |
PhosphoSitePlusi | P63319 |
Expressioni
Gene expression databases
Bgeei | ENSRNOG00000054371, Expressed in brain and 22 other tissues |
Genevisiblei | P63319, RN |
Interactioni
Subunit structurei
Interacts with GRIA4.
Interacts with CDCP1, TP53INP1 and p53/TP53 (By similarity).
Interacts with ARNTL/BMAL1 (By similarity).
By similarity1 PublicationBinary interactionsi
P63319
With | #Exp. | IntAct |
---|---|---|
LIMK1 [P53667] from Homo sapiens. | 3 | EBI-12598030,EBI-444403 |
Protein-protein interaction databases
BioGRIDi | 246813, 23 interactors |
IntActi | P63319, 1 interactor |
STRINGi | 10116.ENSRNOP00000019825 |
Chemistry databases
BindingDBi | P63319 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P63319 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P63319 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 157 – 275 | C2PROSITE-ProRule annotationAdd BLAST | 119 | |
Domaini | 351 – 614 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 264 | |
Domaini | 615 – 685 | AGC-kinase C-terminalPROSITE-ProRule annotationAdd BLAST | 71 |
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 35 – 85 | Phorbol-ester/DAG-type 1PROSITE-ProRule annotationAdd BLAST | 51 | |
Zinc fingeri | 100 – 150 | Phorbol-ester/DAG-type 2PROSITE-ProRule annotationAdd BLAST | 51 |
Keywords - Domaini
Repeat, Zinc-fingerPhylogenomic databases
eggNOGi | KOG0696, Eukaryota |
GeneTreei | ENSGT00940000161219 |
HOGENOMi | CLU_000288_54_2_1 |
InParanoidi | P63319 |
OMAi | KCTSCDM |
OrthoDBi | 614710at2759 |
PhylomeDBi | P63319 |
TreeFami | TF351133 |
Family and domain databases
CDDi | cd00029, C1, 2 hits |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00130, C1_1, 2 hits PF00168, C2, 1 hit PF00069, Pkinase, 1 hit PF00433, Pkinase_C, 1 hit |
PIRSFi | PIRSF000550, PKC_alpha, 1 hit |
PRINTSi | PR00360, C2DOMAIN PR00008, DAGPEDOMAIN |
SMARTi | View protein in SMART SM00109, C1, 2 hits SM00239, C2, 1 hit SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
i Sequence
Sequence statusi: Complete.
P63319-1 [UniParc]FASTAAdd to basket
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
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 |
PIRi | A05105, KIRTGC |
RefSeqi | NP_036760.1, NM_012628.1 |
Genome annotation databases
Ensembli | ENSRNOT00000080032; ENSRNOP00000071203; ENSRNOG00000054371 |
GeneIDi | 24681 |
KEGGi | rno:24681 |
UCSCi | RGD:3397, rat |
Similar proteinsi
Cross-referencesi
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 |
PIRi | A05105, KIRTGC |
RefSeqi | NP_036760.1, NM_012628.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1TBN | NMR | - | A | 91-172 | [»] | |
1TBO | NMR | - | A | 91-172 | [»] | |
SMRi | P63319 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 246813, 23 interactors |
IntActi | P63319, 1 interactor |
STRINGi | 10116.ENSRNOP00000019825 |
Chemistry databases
BindingDBi | P63319 |
ChEMBLi | CHEMBL3604 |
DrugCentrali | P63319 |
PTM databases
iPTMneti | P63319 |
PhosphoSitePlusi | P63319 |
Proteomic databases
PaxDbi | P63319 |
PRIDEi | P63319 |
Genome annotation databases
Ensembli | ENSRNOT00000080032; ENSRNOP00000071203; ENSRNOG00000054371 |
GeneIDi | 24681 |
KEGGi | rno:24681 |
UCSCi | RGD:3397, rat |
Organism-specific databases
CTDi | 5582 |
RGDi | 3397, Prkcg |
Phylogenomic databases
eggNOGi | KOG0696, Eukaryota |
GeneTreei | ENSGT00940000161219 |
HOGENOMi | CLU_000288_54_2_1 |
InParanoidi | P63319 |
OMAi | KCTSCDM |
OrthoDBi | 614710at2759 |
PhylomeDBi | P63319 |
TreeFami | TF351133 |
Enzyme and pathway databases
Reactomei | R-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+ |
Miscellaneous databases
EvolutionaryTracei | P63319 |
PROi | PR:P63319 |
Gene expression databases
Bgeei | ENSRNOG00000054371, Expressed in brain and 22 other tissues |
Genevisiblei | P63319, RN |
Family and domain databases
CDDi | cd00029, C1, 2 hits |
Gene3Di | 2.60.40.150, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00130, C1_1, 2 hits PF00168, C2, 1 hit PF00069, Pkinase, 1 hit PF00433, Pkinase_C, 1 hit |
PIRSFi | PIRSF000550, PKC_alpha, 1 hit |
PRINTSi | PR00360, C2DOMAIN PR00008, DAGPEDOMAIN |
SMARTi | View protein in SMART SM00109, C1, 2 hits SM00239, C2, 1 hit SM00133, S_TK_X, 1 hit SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View 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 |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | KPCG_RAT | |
Accessioni | P63319Primary (citable) accession number: P63319 Secondary accession number(s): P05697, Q5FWS3 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 11, 2004 |
Last sequence update: | October 11, 2004 | |
Last modified: | December 2, 2020 | |
This is version 156 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families