P63318 (KPCG_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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 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. Cytoplasm › perinuclear region By similarity. Cell membrane; Peripheral membrane protein. Cell junction › synapse › synaptosome. Cell projection › dendrite By similarity. Note: Translocates to synaptic membranes on stimulation. Ref.10 Ref.13
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.
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 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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	chemosensory 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: Compara 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: 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 electronic annotation. Source: Compara 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_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW 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.13. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium-dependent protein kinase C activity Inferred from electronic annotation. Source: Compara 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_0000055690
Regions
	Domain	170 – 260	91	C2
	Domain	351 – 614	264	Protein kinase
	Domain	615 – 685	71	AGC-kinase C-terminal
	Zinc finger	35 – 85	51	Phorbol-ester/DAG-type 1
	Zinc finger	100 – 150	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	357 – 365	9	ATP By similarity
Sites
	Active site	480	1	Proton acceptor By similarity
	Metal binding	186	1	Calcium 1; via carbonyl oxygen By similarity
	Metal binding	187	1	Calcium 1 By similarity
	Metal binding	187	1	Calcium 2 By similarity
	Metal binding	193	1	Calcium 2 By similarity
	Metal binding	246	1	Calcium 1 By similarity
	Metal binding	246	1	Calcium 2 By similarity
	Metal binding	247	1	Calcium 2; via carbonyl oxygen By similarity
	Metal binding	248	1	Calcium 1 By similarity
	Metal binding	248	1	Calcium 2 By similarity
	Metal binding	248	1	Calcium 3 By similarity
	Metal binding	251	1	Calcium 3 By similarity
	Metal binding	252	1	Calcium 3; via carbonyl oxygen By similarity
	Metal binding	254	1	Calcium 1 By similarity
	Metal binding	254	1	Calcium 3 By similarity
	Binding site	380	1	ATP By similarity
Amino acid modifications
	Modified residue	195	1	Phosphotyrosine Ref.11
	Modified residue	250	1	Phosphothreonine; by autocatalysis By similarity
	Modified residue	312	1	Phosphotyrosine Ref.11
	Modified residue	322	1	Phosphoserine Ref.12
	Modified residue	330	1	Phosphoserine Ref.12
	Modified residue	514	1	Phosphothreonine; by PDPK1 Probable
	Modified residue	518	1	Phosphothreonine Ref.12
	Modified residue	648	1	Phosphothreonine; by autocatalysis Potential
	Modified residue	655	1	Phosphothreonine; by autocatalysis Ref.10 Ref.12
	Modified residue	674	1	Phosphothreonine; by autocatalysis Ref.10
	Modified residue	675	1	Phosphotyrosine; by SYK By similarity
	Modified residue	687	1	Phosphoserine Ref.12

Sequences

	Sequence		Length	Mass (Da)
	P63318 [UniParc]. Last modified October 11, 2004. Version 1. Checksum: E6E2F7A3B93042FF	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

References

	« Hide 'large scale' referencesShow '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]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-195 AND TYR-312, MASS SPECTROMETRY. Tissue: Brain.
[12]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-322; SER-330; THR-514; THR-518; THR-655 AND SER-687, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MASS SPECTROMETRY. Tissue: Brain cortex.
[13]	"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.
IPI	IPI00122069.
PIR	JN0548.
RefSeq	NP_035232.1. NM_011102.3.
UniGene	Mm.7980.
3D structure databases
ProteinModelPortal	P63318.
SMR	P63318. Positions 36-683.
ModBase	Search...
Protein-protein interaction databases
IntAct	P63318. 8 interactions.
MINT	MINT-98016.
Proteomic databases
PaxDb	P63318.
PRIDE	P63318.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000100301; ENSMUSP00000097874; ENSMUSG00000078816. ENSMUST00000181455; ENSMUSP00000137923; ENSMUSG00000097449.
GeneID	18752.
KEGG	mmu:18752.
Organism-specific databases
CTD	5582.
MGI	MGI:97597. Prkcg.
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233022.
HOVERGEN	HBG108317.
InParanoid	P63318.
KO	K02677.
OMA	MDWERLE.
OrthoDB	EOG40CHGD.
Gene expression databases
ArrayExpress	P63318.
Bgee	P63318.
CleanEx	MM_PRKCC.
Genevestigator	P63318.
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	P63318.
ChEMBL	CHEMBL2956.
NextBio	294925.
SOURCE	Search...

Entry information

Entry name

KPCG_MOUSE

Accession

Primary (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:	April 3, 2013
This is version 93 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program