CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-002224
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein kinase C gamma type 
Protein Synonyms/Alias
 PKC-gamma 
Gene Name
 PRKCG 
Gene Synonyms/Alias
 PKCG 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
197GLSDPYVKLKLIPDPacetylation[1]
Reference
 [1] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 
Functional Description
 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 (By similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in response to DNA damage. 
Sequence Annotation
 DOMAIN 170 260 C2.
 DOMAIN 351 614 Protein kinase.
 DOMAIN 615 685 AGC-kinase C-terminal.
 ZN_FING 35 85 Phorbol-ester/DAG-type 1.
 ZN_FING 100 150 Phorbol-ester/DAG-type 2.
 NP_BIND 357 365 ATP (By similarity).
 ACT_SITE 480 480 Proton acceptor (By similarity).
 METAL 186 186 Calcium 1; via carbonyl oxygen.
 METAL 187 187 Calcium 1.
 METAL 187 187 Calcium 2.
 METAL 193 193 Calcium 2.
 METAL 246 246 Calcium 1.
 METAL 246 246 Calcium 2.
 METAL 247 247 Calcium 2; via carbonyl oxygen.
 METAL 248 248 Calcium 1.
 METAL 248 248 Calcium 2.
 METAL 248 248 Calcium 3.
 METAL 251 251 Calcium 3.
 METAL 252 252 Calcium 3; via carbonyl oxygen.
 METAL 254 254 Calcium 1.
 METAL 254 254 Calcium 3.
 BINDING 380 380 ATP (By similarity).
 MOD_RES 195 195 Phosphotyrosine (By similarity).
 MOD_RES 250 250 Phosphothreonine; by autocatalysis (By
 MOD_RES 312 312 Phosphotyrosine (By similarity).
 MOD_RES 322 322 Phosphoserine (By similarity).
 MOD_RES 330 330 Phosphoserine (By similarity).
 MOD_RES 514 514 Phosphothreonine; by PDPK1 (Probable).
 MOD_RES 518 518 Phosphothreonine (By similarity).
 MOD_RES 648 648 Phosphothreonine; by autocatalysis
 MOD_RES 655 655 Phosphothreonine; by autocatalysis (By
 MOD_RES 674 674 Phosphothreonine; by autocatalysis (By
 MOD_RES 675 675 Phosphotyrosine; by SYK (By similarity).
 MOD_RES 687 687 Phosphoserine (By similarity).  
Keyword
 3D-structure; ATP-binding; Calcium; Cell junction; Cell membrane; Cell projection; Complete proteome; Cytoplasm; Disease mutation; Kinase; Membrane; Metal-binding; Neurodegeneration; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Serine/threonine-protein kinase; Spinocerebellar ataxia; Synapse; Synaptosome; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 697 AA 
Protein Sequence
MAGLGPGVGD SEGGPRPLFC RKGALRQKVV HEVKSHKFTA RFFKQPTFCS HCTDFIWGIG 60
KQGLQCQVCS FVVHRRCHEF VTFECPGAGK GPQTDDPRNK HKFRLHSYSS PTFCDHCGSL 120
LYGLVHQGMK CSCCEMNVHR RCVRSVPSLC GVDHTERRGR LQLEIRAPTA DEIHVTVGEA 180
RNLIPMDPNG LSDPYVKLKL IPDPRNLTKQ KTRTVKATLN PVWNETFVFN LKPGDVERRL 240
SVEVWDWDRT SRNDFMGAMS FGVSELLKAP VDGWYKLLNQ EEGEYYNVPV ADADNCSLLQ 300
KFEACNYPLE LYERVRMGPS SSPIPSPSPS PTDPKRCFFG ASPGRLHISD FSFLMVLGKG 360
SFGKVMLAER RGSDELYAIK ILKKDVIVQD DDVDCTLVEK RVLALGGRGP GGRPHFLTQL 420
HSTFQTPDRL YFVMEYVTGG DLMYHIQQLG KFKEPHAAFY AAEIAIGLFF LHNQGIIYRD 480
LKLDNVMLDA EGHIKITDFG MCKENVFPGT TTRTFCGTPD YIAPEIIAYQ PYGKSVDWWS 540
FGVLLYEMLA GQPPFDGEDE EELFQAIMEQ TVTYPKSLSR EAVAICKGFL TKHPGKRLGS 600
GPDGEPTIRA HGFFRWIDWE RLERLEIPPP FRPRPCGRSG ENFDKFFTRA APALTPPDRL 660
VLASIDQADF QGFTYVNPDF VHPDARSPTS PVPVPVM 697 
Gene Ontology
 GO:0030054; C:cell junction; IEA:UniProtKB-KW.
 GO:0005829; C:cytosol; ISS:UniProtKB.
 GO:0030425; C:dendrite; ISS:UniProtKB.
 GO:0005634; C:nucleus; IEA:Compara.
 GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
 GO:0005886; C:plasma membrane; ISS:UniProtKB.
 GO:0097060; C:synaptic membrane; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0004698; F:calcium-dependent protein kinase C activity; IEA:Compara.
 GO:0004697; F:protein kinase C activity; TAS:ProtInc.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0007202; P:activation of phospholipase C activity; TAS:Reactome.
 GO:0008219; P:cell death; IEA:UniProtKB-KW.
 GO:0007635; P:chemosensory behavior; IEA:Compara.
 GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome.
 GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome.
 GO:0045087; P:innate immune response; TAS:Reactome.
 GO:0060384; P:innervation; IEA:Compara.
 GO:0035556; P:intracellular signal transduction; IEA:InterPro.
 GO:0007611; P:learning or memory; IEA:Compara.
 GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
 GO:0042177; P:negative regulation of protein catabolic process; IDA:HGNC.
 GO:0031397; P:negative regulation of protein ubiquitination; IDA:HGNC.
 GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0032425; P:positive regulation of mismatch repair; IDA:HGNC.
 GO:0046777; P:protein autophosphorylation; IEA:Compara.
 GO:0043278; P:response to morphine; ISS:UniProtKB.
 GO:0048265; P:response to pain; ISS:UniProtKB.
 GO:0007268; P:synaptic transmission; TAS:Reactome. 
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. 
Pfam
 PF00130; C1_1
 PF00168; C2
 PF00069; Pkinase
 PF00433; Pkinase_C 
SMART
 SM00109; C1
 SM00239; C2
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS50004; C2
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS00479; ZF_DAG_PE_1
 PS50081; ZF_DAG_PE_2 
PRINTS
 PR00360; C2DOMAIN.
 PR00008; DAGPEDOMAIN.