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P63318

- KPCG_MOUSE

UniProt

P63318 - KPCG_MOUSE

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Protein

Protein kinase C gamma type

Gene
Prkcg, Pkcc, Pkcg, Prkcc
Organism
Mus musculus (Mouse)
Status
Reviewed - 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 By similarity.7 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Binds 3 calcium 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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi186 – 1861Calcium 1; via carbonyl oxygen By similarity
Metal bindingi187 – 1871Calcium 1 By similarity
Metal bindingi187 – 1871Calcium 2 By similarity
Metal bindingi193 – 1931Calcium 2 By similarity
Metal bindingi246 – 2461Calcium 1 By similarity
Metal bindingi246 – 2461Calcium 2 By similarity
Metal bindingi247 – 2471Calcium 2; via carbonyl oxygen By similarity
Metal bindingi248 – 2481Calcium 1 By similarity
Metal bindingi248 – 2481Calcium 2 By similarity
Metal bindingi248 – 2481Calcium 3 By similarity
Metal bindingi251 – 2511Calcium 3 By similarity
Metal bindingi252 – 2521Calcium 3; via carbonyl oxygen By similarity
Metal bindingi254 – 2541Calcium 1 By similarity
Metal bindingi254 – 2541Calcium 3 By similarity
Binding sitei380 – 3801ATP By similarity
Active sitei480 – 4801Proton acceptor By similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri35 – 8551Phorbol-ester/DAG-type 1Add
BLAST
Zinc fingeri100 – 15051Phorbol-ester/DAG-type 2Add
BLAST
Nucleotide bindingi357 – 3659ATP By similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. calcium-dependent protein kinase C activity Source: Ensembl
  3. protein serine/threonine/tyrosine kinase activity Source: MGI
  4. zinc ion binding Source: InterPro

GO - Biological processi

  1. chemosensory behavior Source: MGI
  2. innervation Source: UniProtKB
  3. intracellular signal transduction Source: InterPro
  4. learning or memory Source: Ensembl
  5. negative regulation of neuron apoptotic process Source: UniProtKB
  6. negative regulation of protein catabolic process Source: Ensembl
  7. negative regulation of protein ubiquitination Source: Ensembl
  8. positive regulation of mismatch repair Source: Ensembl
  9. protein autophosphorylation Source: Ensembl
  10. response to morphine Source: UniProtKB
  11. response to pain Source: UniProtKB
  12. synaptic transmission Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

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

Enzyme and pathway databases

ReactomeiREACT_206166. Response to elevated platelet cytosolic Ca2+.
REACT_215302. Disinhibition of SNARE formation.
REACT_215587. Calmodulin induced events.
REACT_222404. WNT5A-dependent internalization of FZD4.

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
ProteomesiUP000000589: Chromosome 7

Organism-specific databases

MGIiMGI:97597. Prkcg.

Subcellular locationi

Cytoplasm. Cytoplasmperinuclear region By similarity. Cell membrane; Peripheral membrane protein. Cell junctionsynapsesynaptosome. Cell projectiondendrite By similarity
Note: Translocates to synaptic membranes on stimulation.2 Publications

GO - Cellular componenti

  1. cell-cell junction Source: MGI
  2. cytoplasm Source: UniProtKB
  3. cytosol Source: UniProtKB
  4. dendrite Source: MGI
  5. nucleus Source: MGI
  6. perinuclear region of cytoplasm Source: UniProtKB
  7. plasma membrane Source: UniProtKB
  8. 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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 697697Protein kinase C gamma typePRO_0000055690Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei250 – 2501Phosphothreonine; by autocatalysis By similarity
Modified residuei514 – 5141Phosphothreonine; by PDPK1 Inferred
Modified residuei648 – 6481Phosphothreonine; by autocatalysis Reviewed prediction
Modified residuei655 – 6551Phosphothreonine; by autocatalysis1 Publication
Modified residuei674 – 6741Phosphothreonine; by autocatalysis1 Publication
Modified residuei675 – 6751Phosphotyrosine; by SYK By similarity

Post-translational modificationi

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

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP63318.
PaxDbiP63318.
PRIDEiP63318.

Expressioni

Tissue specificityi

Expressed in brain cerebellum and cortex. Highly expressed in Purkinje cells.1 Publication

Gene expression databases

ArrayExpressiP63318.
BgeeiP63318.
CleanExiMM_PRKCC.
GenevestigatoriP63318.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi202196. 3 interactions.
IntActiP63318. 10 interactions.
MINTiMINT-98016.

Structurei

3D structure databases

ProteinModelPortaliP63318.
SMRiP63318. Positions 36-683.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini170 – 26091C2Add
BLAST
Domaini351 – 614264Protein kinaseAdd
BLAST
Domaini615 – 68571AGC-kinase C-terminalAdd
BLAST

Sequence similaritiesi

Contains 1 C2 domain.

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri35 – 8551Phorbol-ester/DAG-type 1Add
BLAST
Zinc fingeri100 – 15051Phorbol-ester/DAG-type 2Add
BLAST

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233022.
HOVERGENiHBG108317.
InParanoidiP63318.
KOiK02677.
OMAiAIRAHGF.
OrthoDBiEOG77M8QM.
PhylomeDBiP63318.
TreeFamiTF351133.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000961. 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]
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

MAGLGPGGGD SEGGPRPLFC RKGALRQKVV HEVKSHKFTA RFFKQPTFCS    50
HCTDFIWGIG KQGLQCQVCS FVVHRRCHEF VTFECPGAGK GPQTDDPRNK 100
HKFRLHSYSS PTFCDHCGSL LYGLVHQGMK CSCCEMNVHR RCVRSVPSLC 150
GVDHTERRGR LQLEIRAPTS DEIHITVGEA RNLIPMDPNG LSDPYVKLKL 200
IPDPRNLTKQ KTKTVKATLN PVWNETFVFN LKPGDVERRL SVEVWDWDRT 250
SRNDFMGAMS FGVSELLKAP VDGWYKLLNQ EEGEYYNVPV ADADNCSLLQ 300
KFEACNYPLE LYERVRMGPS SSPIPSPSPS PTDSKRCFFG ASPGRLHISD 350
FSFLMVLGKG SFGKVMLAER RGSDELYAIK ILKKDVIVQD DDVDCTLVEK 400
RVLALGGRGP GGRPHFLTQL HSTFQTPDRL YFVMEYVTGG DLMYHIQQLG 450
KFKEPHAAFY AAEIAIGLFF LHNQGIIYRD LKLDNVMLDA EGHIKITDFG 500
MCKENVFPGS TTRTFCGTPD YIAPEIIAYQ PYGKSVDWWS FGVLLYEMLA 550
GQPPFDGEDE EELFQAIMEQ TVTYPKSLSR EAVAICKGFL TKHPGKRLGS 600
GPDGEPTIRA HGFFRWIDWE RLERLEIAPP FRPRPCGRSG ENFDKFFTRA 650
APALTPPDRL VLASIDQADF QGFTYVNPDF VHPDARSPTS PVPVPVM 697
Length:697
Mass (Da):78,358
Last modified:October 11, 2004 - v1
Checksum:iE6E2F7A3B93042FF
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
X67129 mRNA. Translation: CAA47608.1 .
L28035 mRNA. Translation: AAA39939.1 .
CCDSi CCDS57470.1.
PIRi JN0548.
RefSeqi NP_035232.1. NM_011102.4.
UniGenei Mm.7980.

3D structure databases

ProteinModelPortali P63318.
SMRi P63318. Positions 36-683.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 202196. 3 interactions.
IntActi P63318. 10 interactions.
MINTi MINT-98016.

Chemistry

BindingDBi P63318.

Proteomic databases

MaxQBi P63318.
PaxDbi P63318.
PRIDEi P63318.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000100301 ; ENSMUSP00000097874 ; ENSMUSG00000078816 .
ENSMUST00000181455 ; ENSMUSP00000137923 ; ENSMUSG00000097449 .
GeneIDi 18752.
KEGGi mmu:18752.
UCSCi uc029wcz.1. mouse.

Organism-specific databases

CTDi 5582.
MGIi MGI:97597. Prkcg.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233022.
HOVERGENi HBG108317.
InParanoidi P63318.
KOi K02677.
OMAi AIRAHGF.
OrthoDBi EOG77M8QM.
PhylomeDBi P63318.
TreeFami TF351133.

Enzyme and pathway databases

Reactomei REACT_206166. Response to elevated platelet cytosolic Ca2+.
REACT_215302. Disinhibition of SNARE formation.
REACT_215587. Calmodulin induced events.
REACT_222404. WNT5A-dependent internalization of FZD4.

Miscellaneous databases

NextBioi 294925.
PROi P63318.
SOURCEi Search...

Gene expression databases

ArrayExpressi P63318.
Bgeei P63318.
CleanExi MM_PRKCC.
Genevestigatori P63318.

Family and domain databases

Gene3Di 2.60.40.150. 1 hit.
InterProi IPR000961. 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 ]
Pfami PF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view ]
PIRSFi PIRSF000550. PKC_alpha. 1 hit.
PRINTSi PR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.
SMARTi SM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEi 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.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

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: September 3, 2014
This is version 105 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

External Data

Dasty 3

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