Protein kinase C gamma type - Rattus norvegicus (Rat)

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P63319 (KPCG_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 95. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Protein kinase C gamma type
Short name=PKC-gamma
EC=2.7.11.13

Gene names

Name:	Prkcg
Synonyms:	Pkcc, Pkcg, Prkcc

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	697 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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 By similarity. Ref.5 Ref.6 Ref.7 Ref.9 Ref.10 Ref.11
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 By similarity. Interacts with GRIA4. Interacts with TP53INP1 and p53/TP53 By similarity. Ref.7
Subcellular location	Cytoplasm. Cytoplasm › perinuclear region. Cell membrane; Peripheral membrane protein. Cell junction › synapse › synaptosome. Cell projection › dendrite. Note: Translocates to synaptic membranes on stimulation. Ref.7 Ref.8 Ref.11
Post-translational modification	Autophosphorylation on Thr-674 appears to regulate motor functions of junctophilins, JPH3 and JPH4 By similarity.
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 component	Cell junction Cell membrane Cell projection Cytoplasm Membrane Synapse Synaptosome
Domain	Repeat Zinc-finger
Ligand	ATP-binding Calcium Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chemosensory behavior Inferred from electronic annotation. Source: Compara innervation Inferred from electronic annotation. Source: Compara intracellular signal transduction Non-traceable author statement PubMed 11507002. Source: RGD learning or memory Inferred from expression pattern PubMed 12000125. Source: RGD negative regulation of neuron apoptotic process Inferred from mutant phenotype Ref.10. Source: UniProtKB negative regulation of protein catabolic process Inferred from electronic annotation. Source: Compara negative regulation of protein ubiquitination Inferred from electronic annotation. Source: Compara positive regulation of mismatch repair Inferred from electronic annotation. Source: Compara protein autophosphorylation Inferred from direct assay PubMed 18972403. Source: RGD response to morphine Inferred from sequence or structural similarity. Source: UniProtKB response to pain Inferred from sequence or structural similarity. Source: UniProtKB synaptic transmission Non-traceable author statement Ref.8. Source: RGD
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytosol Inferred from direct assay Ref.7. Source: UniProtKB dendrite Inferred from direct assay Ref.7. Source: UniProtKB nucleus Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from direct assay Ref.7. Source: UniProtKB plasma membrane Inferred from direct assay Ref.7. Source: UniProtKB synaptic membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium-dependent protein kinase C activity Inferred from direct assay PubMed 18972403. Source: RGD zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 697

697

Protein kinase C gamma type

PRO_0000055692

Regions

Domain

170 – 260

Domain

351 – 614

264

Protein kinase

Domain

615 – 685

AGC-kinase C-terminal

Zinc finger

35 – 85

Phorbol-ester/DAG-type 1

Zinc finger

100 – 150

Phorbol-ester/DAG-type 2

Nucleotide binding

357 – 365

ATP By similarity

Sites

Active site

480

Proton acceptor By similarity

Metal binding

186

Calcium 1; via carbonyl oxygen By similarity

Metal binding

187

Calcium 1 By similarity

Metal binding

187

Calcium 2 By similarity

Metal binding

193

Calcium 2 By similarity

Metal binding

246

Calcium 1 By similarity

Metal binding

246

Calcium 2 By similarity

Metal binding

247

Calcium 2; via carbonyl oxygen By similarity

Metal binding

248

Calcium 1 By similarity

Metal binding

248

Calcium 2 By similarity

Metal binding

248

Calcium 3 By similarity

Metal binding

251

Calcium 3 By similarity

Metal binding

252

Calcium 3; via carbonyl oxygen By similarity

Metal binding

254

Calcium 1 By similarity

Metal binding

254

Calcium 3 By similarity

Binding site

380

ATP By similarity

Amino acid modifications

Modified residue

195

Phosphotyrosine By similarity

Modified residue

250

Phosphothreonine; by autocatalysis By similarity

Modified residue

312

Phosphotyrosine By similarity

Modified residue

322

Phosphoserine By similarity

Modified residue

330

Phosphoserine By similarity

Modified residue

514

Phosphothreonine; by PDPK1 By similarity

Modified residue

518

Phosphothreonine By similarity

Modified residue

648

Phosphothreonine; by autocatalysis By similarity

Modified residue

655

Phosphothreonine; by autocatalysis Potential

Modified residue

674

Phosphothreonine; by autocatalysis By similarity

Modified residue

675

Phosphotyrosine; by SYK By similarity

Modified residue

687

Phosphoserine By similarity

Secondary structure

697

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

P63319 [UniParc].

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

697

78,358

        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' referencesShow 'large scale' references »
[1]	"Nucleotide sequences of cDNAs for alpha and gamma subspecies of rat brain protein kinase C." Ono Y., Fujii T., Igarashi K., Kikkawa U., Ogita K., Nishizuka Y. Nucleic Acids Res. 16:5199-5200(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"Cloning and expression of multiple protein kinase C cDNAs." Knopf J.L., Lee M.-H., Sultzman L.A., Kriz R.W., Loomis C.R., Hewick R.M., Bell R.M. Cell 46:491-502(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Characterization of the 5'-flanking region of the rat protein kinase C gamma gene." Chen K.H., Widen S.G., Wilson S.H., Huang K.P. J. Biol. Chem. 265:19961-19965(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-56.
[5]	"Exposure to chronic psychosocial stress and corticosterone in the rat: effects on spatial discrimination learning and hippocampal protein kinase Cgamma immunoreactivity." Krugers H.J., Douma B.R., Andringa G., Bohus B., Korf J., Luiten P.G. Hippocampus 7:427-436(1997) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Inflammation-induced up-regulation of protein kinase Cgamma immunoreactivity in rat spinal cord correlates with enhanced nociceptive processing." Martin W.J., Liu H., Wang H., Malmberg A.B., Basbaum A.I. Neuroscience 88:1267-1274(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN INFLAMMATORY PAIN.
[7]	"Protein kinase C gamma associates directly with the GluR4 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit. Effect on receptor phosphorylation." Correia S.S., Duarte C.B., Faro C.J., Pires E.V., Carvalho A.L. J. Biol. Chem. 278:6307-6313(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF GRIA4/GLUR4, INTERACTION WITH GRIA4/GLUR4, SUBCELLULAR LOCATION.
[8]	"Protein kinase C-gamma and calcium/calmodulin-dependent protein kinase II-alpha are persistently translocated to cell membranes of the rat brain during and after middle cerebral artery occlusion." Matsumoto S., Shamloo M., Matsumoto E., Isshiki A., Wieloch T. J. Cereb. Blood Flow Metab. 24:54-61(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[9]	"Serines 890 and 896 of the NMDA receptor subunit NR1 are differentially phosphorylated by protein kinase C isoforms." Sanchez-Perez A.M., Felipo V. Neurochem. Int. 47:84-91(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF GRIN1/NMDAR1.
[10]	"Insulin receptor-protein kinase C-gamma signaling mediates inhibition of hypoxia-induced necrosis of cortical neurons." Hamabe W., Fujita R., Ueda H. J. Pharmacol. Exp. Ther. 313:1027-1034(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL SURVIVAL.
[11]	"NMR structure of a protein kinase C-gamma phorbol-binding domain and study of protein-lipid micelle interactions." Xu R.X., Pawelczyk T., Xia T.-H., Brown S.C. Biochemistry 36:10709-10717(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 91-172 IN COMPLEX WITH PHORBOL-12,13-DIBUTYRATE, FUNCTION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X07287 mRNA. Translation: CAA30267.1.
M13707 mRNA. Translation: AAA41874.1.
BC089226 mRNA. Translation: AAH89226.1.
M55417 Genomic DNA. Translation: AAA41873.1.

IPI

IPI00201797.

PIR

KIRTGC. A05105.

RefSeq

NP_036760.1. NM_012628.1.

UniGene

Rn.9747.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1TBN	NMR	-	A	91-172	[»]
1TBO	NMR	-	A	91-172	[»]

ProteinModelPortal

P63319.

SMR

P63319. Positions 36-683.

ModBase

Search...

Protein-protein interaction databases

STRING

10116.ENSRNOP00000019825.

PTM databases

PhosphoSite

P63319.

Proteomic databases

PaxDb

P63319.

PRIDE

P63319.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000019825; ENSRNOP00000019825; ENSRNOG00000014688.

GeneID

24681.

KEGG

rno:24681.

UCSC

RGD:3397. rat.

Organism-specific databases

CTD

5582.

RGD

3397. Prkcg.

Phylogenomic databases

eggNOG

COG0515.

GeneTree

ENSGT00640000091170.

HOGENOM

HOG000233022.

HOVERGEN

HBG108317.

InParanoid

P63319.

K02677.

OMA

MDWERLE.

OrthoDB

EOG40CHGD.

Gene expression databases

Genevestigator

P63319.

GermOnline

ENSRNOG00000014688. Rattus norvegicus.

Family and domain databases

InterPro

IPR000961. AGC-kinase_C.
IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR020477. C2_dom.
IPR018029. C2_membr_targeting.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR017892. Pkinase_C.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_cat_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]

Pfam

PF00130. C1_1. 2 hits.
PF00168. C2. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]

PIRSF

PIRSF000550. PKC_alpha. 1 hit.

PRINTS

PR00360. C2DOMAIN.
PR00008. DAGPEDOMAIN.

SMART

SM00109. C1. 2 hits.
SM00239. C2. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF56112. Kinase_like. 1 hit.

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.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P63319.

ChEMBL

CHEMBL3604.

EvolutionaryTrace

P63319.

NextBio

294925.

Entry information

Entry name

KPCG_RAT

Accession

Primary (citable) accession number: P63319
Secondary accession number(s): P05697, Q5FWS3

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 11, 2004
Last sequence update:	October 11, 2004
Last modified:	May 1, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents