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P63318 (KPCG_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein kinase C gamma type

Short name=PKC-gamma
EC=2.7.11.13
Gene names
Name:Prkcg
Synonyms:Pkcc, Pkcg, Prkcc
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length697 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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 By similarity. Ref.3 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Binds 3 calcium ions per subunit. The ions are bound to the C2 domain By similarity.

Enzyme regulation

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.

Subunit structure

Interacts with CDCP1 and GRIA4 By similarity. Interacts with TP53INP1 and p53/TP53 By similarity.

Subcellular location

Cytoplasm. Cytoplasmperinuclear region By similarity. Cell membrane; Peripheral membrane protein. Cell junctionsynapsesynaptosome. Cell projectiondendrite By similarity. Note: Translocates to synaptic membranes on stimulation. Ref.10 Ref.12

Tissue specificity

Expressed in brain cerebellum and cortex. Highly expressed in Purkinje cells. Ref.10

Post-translational modification

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

Ubiquitinated By similarity.

Disruption phenotype

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. Ref.4

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 C2 domain.

Contains 2 phorbol-ester/DAG-type zinc fingers.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Membrane
Synapse
Synaptosome
   DomainRepeat
Zinc-finger
   LigandATP-binding
Calcium
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processchemosensory behavior

Inferred from mutant phenotype PubMed 11606660. Source: MGI

innervation

Inferred from mutant phenotype Ref.4. Source: UniProtKB

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

learning or memory

Inferred from electronic annotation. Source: Ensembl

negative regulation of neuron apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of protein catabolic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein ubiquitination

Inferred from electronic annotation. Source: Ensembl

positive regulation of mismatch repair

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from electronic annotation. Source: Ensembl

response to morphine

Inferred from mutant phenotype Ref.8. Source: UniProtKB

response to pain

Inferred from mutant phenotype Ref.5. Source: UniProtKB

synaptic transmission

Inferred from mutant phenotype Ref.4. Source: UniProtKB

   Cellular_componentcell-cell junction

Inferred from direct assay PubMed 23793062. Source: MGI

cytoplasm

Inferred from direct assay Ref.10. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from direct assay PubMed 11549583. Source: MGI

nucleus

Inferred from direct assay PubMed 10882525PubMed 14613966. Source: MGI

perinuclear region of cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.10. Source: UniProtKB

synaptic membrane

Inferred from direct assay Ref.12. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

calcium-dependent protein kinase C activity

Inferred from electronic annotation. Source: Ensembl

protein serine/threonine/tyrosine kinase activity

Inferred from sequence orthology PubMed 22797923. Source: MGI

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 697697Protein kinase C gamma type
PRO_0000055690

Regions

Domain170 – 26091C2
Domain351 – 614264Protein kinase
Domain615 – 68571AGC-kinase C-terminal
Zinc finger35 – 8551Phorbol-ester/DAG-type 1
Zinc finger100 – 15051Phorbol-ester/DAG-type 2
Nucleotide binding357 – 3659ATP By similarity

Sites

Active site4801Proton acceptor By similarity
Metal binding1861Calcium 1; via carbonyl oxygen By similarity
Metal binding1871Calcium 1 By similarity
Metal binding1871Calcium 2 By similarity
Metal binding1931Calcium 2 By similarity
Metal binding2461Calcium 1 By similarity
Metal binding2461Calcium 2 By similarity
Metal binding2471Calcium 2; via carbonyl oxygen By similarity
Metal binding2481Calcium 1 By similarity
Metal binding2481Calcium 2 By similarity
Metal binding2481Calcium 3 By similarity
Metal binding2511Calcium 3 By similarity
Metal binding2521Calcium 3; via carbonyl oxygen By similarity
Metal binding2541Calcium 1 By similarity
Metal binding2541Calcium 3 By similarity
Binding site3801ATP By similarity

Amino acid modifications

Modified residue2501Phosphothreonine; by autocatalysis By similarity
Modified residue5141Phosphothreonine; by PDPK1 Probable
Modified residue6481Phosphothreonine; by autocatalysis Potential
Modified residue6551Phosphothreonine; by autocatalysis Ref.10
Modified residue6741Phosphothreonine; by autocatalysis Ref.10
Modified residue6751Phosphotyrosine; by SYK By similarity

Sequences

Sequence LengthMass (Da)Tools
P63318 [UniParc].

Last modified October 11, 2004. Version 1.
Checksum: E6E2F7A3B93042FF

FASTA69778,358
        10         20         30         40         50         60 
MAGLGPGGGD SEGGPRPLFC RKGALRQKVV HEVKSHKFTA RFFKQPTFCS HCTDFIWGIG 

        70         80         90        100        110        120 
KQGLQCQVCS FVVHRRCHEF VTFECPGAGK GPQTDDPRNK HKFRLHSYSS PTFCDHCGSL 

       130        140        150        160        170        180 
LYGLVHQGMK CSCCEMNVHR RCVRSVPSLC GVDHTERRGR LQLEIRAPTS DEIHITVGEA 

       190        200        210        220        230        240 
RNLIPMDPNG LSDPYVKLKL IPDPRNLTKQ KTKTVKATLN PVWNETFVFN LKPGDVERRL 

       250        260        270        280        290        300 
SVEVWDWDRT SRNDFMGAMS FGVSELLKAP VDGWYKLLNQ EEGEYYNVPV ADADNCSLLQ 

       310        320        330        340        350        360 
KFEACNYPLE LYERVRMGPS SSPIPSPSPS PTDSKRCFFG ASPGRLHISD FSFLMVLGKG 

       370        380        390        400        410        420 
SFGKVMLAER RGSDELYAIK ILKKDVIVQD DDVDCTLVEK RVLALGGRGP GGRPHFLTQL 

       430        440        450        460        470        480 
HSTFQTPDRL YFVMEYVTGG DLMYHIQQLG KFKEPHAAFY AAEIAIGLFF LHNQGIIYRD 

       490        500        510        520        530        540 
LKLDNVMLDA EGHIKITDFG MCKENVFPGS TTRTFCGTPD YIAPEIIAYQ PYGKSVDWWS 

       550        560        570        580        590        600 
FGVLLYEMLA GQPPFDGEDE EELFQAIMEQ TVTYPKSLSR EAVAICKGFL TKHPGKRLGS 

       610        620        630        640        650        660 
GPDGEPTIRA HGFFRWIDWE RLERLEIAPP FRPRPCGRSG ENFDKFFTRA APALTPPDRL 

       670        680        690 
VLASIDQADF QGFTYVNPDF VHPDARSPTS PVPVPVM 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and sequence of a mouse brain cDNA coding for protein kinase C-gamma isozyme."
Bowers B.J., Parham C.L., Sikela J.M., Wehner J.M.
Gene 123:263-265(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]Tseng C.P., Verma A.
Submitted (JAN-1994) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
Tissue: Brain.
[3]"Modified hippocampal long-term potentiation in PKC gamma-mutant mice."
Abeliovich A., Chen C., Goda Y., Silva A.J., Stevens C.F., Tonegawa S.
Cell 75:1253-1262(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN LONG-TERM POTENTIATION.
[4]"Impaired motor coordination correlates with persistent multiple climbing fiber innervation in PKC gamma mutant mice."
Chen C., Kano M., Abeliovich A., Chen L., Bao S., Kim J.J., Hashimoto K., Thompson R.F., Tonegawa S.
Cell 83:1233-1242(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: DISRUPTION PHENOTYPE.
[5]"Preserved acute pain and reduced neuropathic pain in mice lacking PKCgamma."
Malmberg A.B., Chen C., Tonegawa S., Basbaum A.I.
Science 278:279-283(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NEUROPATHIC PAIN.
[6]"Enhanced mu-opioid responses in the spinal cord of mice lacking protein kinase Cgamma isoform."
Narita M., Mizoguchi H., Suzuki T., Narita M., Dun N.J., Imai S., Yajima Y., Nagase H., Suzuki T., Tseng L.F.
J. Biol. Chem. 276:15409-15414(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OPIOID SIGNALING.
[7]"Involvement of spinal protein kinase Cgamma in the attenuation of opioid mu-receptor-mediated G-protein activation after chronic intrathecal administration of [D-Ala2,N-MePhe4,Gly-Ol(5)]enkephalin."
Narita M., Mizoguchi H., Narita M., Nagase H., Suzuki T., Tseng L.F.
J. Neurosci. 21:3715-3720(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OPIOID SIGNALING.
[8]"Involvement of protein kinase Cgamma isoform in morphine-induced reinforcing effects."
Narita M., Aoki T., Ozaki S., Yajima Y., Suzuki T.
Neuroscience 103:309-314(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OPIOID SIGNALING.
[9]"Reduced development of tolerance to the analgesic effects of morphine and clonidine in PKC gamma mutant mice."
Zeitz K.P., Malmberg A.B., Gilbert H., Basbaum A.I.
Pain 94:245-253(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN OPIOID SIGNALING.
[10]"Abnormal features in mutant cerebellar Purkinje cells lacking junctophilins."
Ikeda A., Miyazaki T., Kakizawa S., Okuno Y., Tsuchiya S., Myomoto A., Saito S.Y., Yamamoto T., Yamazaki T., Iino M., Tsujimoto G., Watanabe M., Takeshima H.
Biochem. Biophys. Res. Commun. 363:835-839(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-514; THR-655 AND THR-674, SUBCELLULAR LOCATION, FUNCTION, TISSUE SPECIFICITY.
[11]"Qualitative and quantitative analyses of protein phosphorylation in naive and stimulated mouse synaptosomal preparations."
Munton R.P., Tweedie-Cullen R., Livingstone-Zatchej M., Weinandy F., Waidelich M., Longo D., Gehrig P., Potthast F., Rutishauser D., Gerrits B., Panse C., Schlapbach R., Mansuy I.M.
Mol. Cell. Proteomics 6:283-293(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Brain cortex.
[12]"Isoflurane inhibits protein kinase Cgamma and calcium/calmodulin dependent protein kinase ii-alpha translocation to synaptic membranes in ischemic mice brains."
Matsumoto S., Murozono M., Nagaoka D., Matsuoka S., Takeda A., Narita H., Watanabe S., Isshiki A., Watanabe Y.
Neurochem. Res. 33:2302-2309(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X67129 mRNA. Translation: CAA47608.1.
L28035 mRNA. Translation: AAA39939.1.
CCDSCCDS57470.1.
PIRJN0548.
RefSeqNP_035232.1. NM_011102.4.
UniGeneMm.7980.

3D structure databases

ProteinModelPortalP63318.
SMRP63318. Positions 36-683.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid202196. 3 interactions.
IntActP63318. 10 interactions.
MINTMINT-98016.

Chemistry

BindingDBP63318.

Proteomic databases

MaxQBP63318.
PaxDbP63318.
PRIDEP63318.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000100301; ENSMUSP00000097874; ENSMUSG00000078816.
ENSMUST00000181455; ENSMUSP00000137923; ENSMUSG00000097449.
GeneID18752.
KEGGmmu:18752.
UCSCuc029wcz.1. mouse.

Organism-specific databases

CTD5582.
MGIMGI:97597. Prkcg.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233022.
HOVERGENHBG108317.
InParanoidP63318.
KOK02677.
OMAAIRAHGF.
OrthoDBEOG77M8QM.
PhylomeDBP63318.
TreeFamTF351133.

Gene expression databases

ArrayExpressP63318.
BgeeP63318.
CleanExMM_PRKCC.
GenevestigatorP63318.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR014375. Protein_kinase_C_a/b/g.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000550. PKC_alpha. 1 hit.
PRINTSPR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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]
ProtoNetSearch...

Other

NextBio294925.
PROP63318.
SOURCESearch...

Entry information

Entry nameKPCG_MOUSE
AccessionPrimary (citable) accession number: P63318
Secondary accession number(s): P05697
Entry history
Integrated into UniProtKB/Swiss-Prot: October 11, 2004
Last sequence update: October 11, 2004
Last modified: July 9, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot