KPCG_RABIT
ID KPCG_RABIT Reviewed; 697 AA.
AC P10829;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Protein kinase C gamma type;
DE Short=PKC-gamma;
DE EC=2.7.11.13;
DE AltName: Full=PKC-delta;
GN Name=PRKCG;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=2837282; DOI=10.1021/bi00406a040;
RA Ohno S., Kawasaki H., Konno Y., Inagaki M., Hidaka H., Suzuki K.;
RT "A fourth type of rabbit protein kinase C.";
RL Biochemistry 27:2083-2087(1988).
RN [2]
RP FUNCTION IN PHOSPHORYLATION OF GJA1/CX43, AND INDUCTION BY HYDROGEN
RP PEROXIDE.
RX PubMed=15642736; DOI=10.1074/jbc.m407762200;
RA Lin D., Takemoto D.J.;
RT "Oxidative activation of protein kinase Cgamma through the C1 domain.
RT Effects on gap junctions.";
RL J. Biol. Chem. 280:13682-13693(2005).
CC -!- FUNCTION: Calcium-activated, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that plays diverse roles in
CC neuronal cells and eye tissues, such as regulation of the neuronal
CC receptors GRIA4/GLUR4 and GRIN1/NMDAR1, modulation of receptors and
CC neuronal functions related to sensitivity to opiates, pain and alcohol,
CC mediation of synaptic function and cell survival after ischemia, and
CC inhibition of gap junction activity after oxidative stress. Binds and
CC phosphorylates GRIA4/GLUR4 glutamate receptor and regulates its
CC function by increasing plasma membrane-associated GRIA4 expression. In
CC primary cerebellar neurons treated with the agonist 3,5-
CC dihyidroxyphenylglycine, functions downstream of the metabotropic
CC glutamate receptor GRM5/MGLUR5 and phosphorylates GRIN1/NMDAR1 receptor
CC which plays a key role in synaptic plasticity, synaptogenesis,
CC excitotoxicity, memory acquisition and learning. May be involved in the
CC regulation of hippocampal long-term potentiation (LTP), but may be not
CC necessary for the process of synaptic plasticity. May be involved in
CC desensitization of mu-type opioid receptor-mediated G-protein
CC activation in the spinal cord, and may be critical for the development
CC and/or maintenance of morphine-induced reinforcing effects in the
CC limbic forebrain. May modulate the functionality of mu-type-opioid
CC receptors by participating in a signaling pathway which leads to the
CC phosphorylation and degradation of opioid receptors. May also
CC contributes to chronic morphine-induced changes in nociceptive
CC processing. Plays a role in neuropathic pain mechanisms and contributes
CC to the maintenance of the allodynia pain produced by peripheral
CC inflammation. Plays an important role in initial sensitivity and
CC tolerance to ethanol, by mediating the behavioral effects of ethanol as
CC well as the effects of this drug on the GABA(A) receptors. During and
CC after cerebral ischemia modulate neurotransmission and cell survival in
CC synaptic membranes, and is involved in insulin-induced inhibition of
CC necrosis, an important mechanism for minimizing ischemic injury.
CC Required for the elimination of multiple climbing fibers during
CC innervation of Purkinje cells in developing cerebellum (By similarity).
CC Is activated in lens epithelial cells upon hydrogen peroxide treatment,
CC and phosphorylates connexin-43 (GJA1/CX43), resulting in disassembly of
CC GJA1 gap junction plaques and inhibition of gap junction activity which
CC could provide a protective effect against oxidative stress.
CC Phosphorylates p53/TP53 and promotes p53/TP53-dependent apoptosis in
CC response to DNA damage. Involved in the phase resetting of the cerebral
CC cortex circadian clock during temporally restricted feeding. Stabilizes
CC the core clock component ARNTL/BMAL1 by interfering with its
CC ubiquitination, thus suppressing its degradation, resulting in phase
CC resetting of the cerebral cortex clock. {ECO:0000250|UniProtKB:P05129,
CC ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319,
CC ECO:0000269|PubMed:15642736}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13;
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00041};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domain. {ECO:0000250|UniProtKB:P05129};
CC -!- ACTIVITY REGULATION: Classical (or conventional) PKCs (PRKCA, PRKCB and
CC PRKCG) are activated by calcium and diacylglycerol (DAG) in the
CC presence of phosphatidylserine. Three specific sites; Thr-514
CC (activation loop of the kinase domain), Thr-655 (turn motif) and Thr-
CC 674 (hydrophobic region), need to be phosphorylated for its full
CC activation.
CC -!- SUBUNIT: Interacts with CDCP1 and GRIA4. Interacts with TP53INP1 and
CC p53/TP53. Interacts with ARNTL/BMAL1. {ECO:0000250|UniProtKB:P05129,
CC ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P63318}.
CC Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane
CC {ECO:0000250|UniProtKB:P63318}; Peripheral membrane protein
CC {ECO:0000250}. Synapse, synaptosome {ECO:0000250|UniProtKB:P63318}.
CC Cell projection, dendrite {ECO:0000250|UniProtKB:P63319}.
CC Note=Translocates to synaptic membranes on stimulation.
CC {ECO:0000250|UniProtKB:P63318}.
CC -!- TISSUE SPECIFICITY: Expressed specifically in brain.
CC {ECO:0000269|PubMed:2837282}.
CC -!- INDUCTION: Activated by hydrogen peroxide.
CC {ECO:0000269|PubMed:15642736}.
CC -!- PTM: Autophosphorylation on Thr-674 appears to regulate motor functions
CC of junctophilins, JPH3 and JPH4. {ECO:0000250|UniProtKB:P63318}.
CC -!- PTM: Ubiquitinated. {ECO:0000250|UniProtKB:P05129}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; M19338; AAA31449.1; -; mRNA.
DR PIR; A28708; KIRBGC.
DR RefSeq; NP_001075742.1; NM_001082273.1.
DR AlphaFoldDB; P10829; -.
DR SMR; P10829; -.
DR BioGRID; 1172125; 1.
DR MINT; P10829; -.
DR STRING; 9986.ENSOCUP00000023280; -.
DR GeneID; 100009102; -.
DR KEGG; ocu:100009102; -.
DR CTD; 5582; -.
DR eggNOG; KOG0696; Eukaryota.
DR InParanoid; P10829; -.
DR OrthoDB; 614710at2759; -.
DR BRENDA; 2.7.11.13; 1749.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISS:UniProtKB.
DR GO; GO:1901799; P:negative regulation of proteasomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0032095; P:regulation of response to food; ISS:UniProtKB.
DR GO; GO:0043278; P:response to morphine; ISS:UniProtKB.
DR GO; GO:0048265; P:response to pain; ISS:UniProtKB.
DR GO; GO:0048511; P:rhythmic process; IEA:UniProtKB-KW.
DR CDD; cd00029; C1; 2.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR014375; Protein_kinase_C_a/b/g.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 2.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF00433; Pkinase_C; 1.
DR PIRSF; PIRSF000550; PKC_alpha; 1.
DR PRINTS; PR00360; C2DOMAIN.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 2.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 2.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 1: Evidence at protein level;
KW ATP-binding; Biological rhythms; Calcium; Cell membrane; Cell projection;
KW Cytoplasm; Kinase; Membrane; Metal-binding; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Synapse; Synaptosome; Transferase;
KW Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..697
FT /note="Protein kinase C gamma type"
FT /id="PRO_0000055691"
FT DOMAIN 157..275
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 351..614
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 615..685
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 35..85
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 100..150
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ACT_SITE 480
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 186
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 251
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:P05129"
FT BINDING 357..365
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 380
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 250
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 322
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 332
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 514
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 648
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 655
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P63318, ECO:0000255"
FT MOD_RES 674
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P63318"
FT MOD_RES 675
FT /note="Phosphotyrosine; by SYK"
FT /evidence="ECO:0000250"
FT MOD_RES 687
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P63319"
SQ SEQUENCE 697 AA; 78372 MW; 925D22221F78E5BF CRC64;
MAGLGPGGGD SEGGPRPLFC RKGALRQKVV HEVKSHKFTA RFFKQPTFCS HCTDFIWGIG
KQGLQCQVCS FVVHRRCHEF VTFECPGAGK GPQTDDPRNK HKFRLHSYSS PTFCDHCGSL
LYGLVHQGMK CSCCEMNVHR RCVRTVPSLC GVDHTERRGR LQLEIRAPTS DEIHVTVGEA
RNLIPMDPNG LSDPYVKLKL IPDPRNLTKQ KTRTVKATLN PVWNETFVFN LKPGDVERRL
SVEVWDWDRT SRNDFMGAMS FGVSELLKAP VDGWYKLLNQ EEGEYYNVPV ADADNCSLLQ
KFEACNYPLE LYERVRMGPS SSPIPSPSPS PTDSKRCFFG ASPGRLHISD FSFLMVLGKG
SFGKVMLAER RGSDELYAIK ILKKDVIVQD DDVDCTLVEK RVLALGGRGP GGRPHFLTQL
HSTFQTPDRL YFVMEYVTGG DLMYHIQQLG KFKEPHAAFY AAEIAIGLFF LHNQGIIYRD
LKLDNVMLDA EGHIKITDFG MCKENVFPGT TTRTFCGTPD YIAPEIIAYQ PYGKSVDWWS
FGVLLYEMLA GQPPFDGEDE EELFQAIMEQ TVTYPKSLSR EAVAICKGFL TKHPGKRLGS
GPDGEPTIRA HGFFRWIDWE RLERLEIAPP FRPRPCGRSG ENFDKFFTRA APAVTPPDRL
VLASIDQADF QGFTYVNPDF VHPDARSPSS PVPVPVM
