KPCG_HUMAN
ID KPCG_HUMAN Reviewed; 697 AA.
AC P05129; B7Z8Q0;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 3.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=Protein kinase C gamma type;
DE Short=PKC-gamma;
DE EC=2.7.11.13;
GN Name=PRKCG; Synonyms=PKCG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Cui W.C., Yu L., Chu Y.Y., Wang J., Zheng L.H., Zhou G.J., Zhao S.Y.;
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-317 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=3755548; DOI=10.1126/science.3755548;
RA Coussens L., Parker P.J., Rhee L., Yang-Feng T.L., Chen E.,
RA Waterfield M.D., Francke U., Ullrich A.;
RT "Multiple, distinct forms of bovine and human protein kinase C suggest
RT diversity in cellular signaling pathways.";
RL Science 233:859-866(1986).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 162-697 (ISOFORM 1).
RC TISSUE=Hippocampus;
RX PubMed=8375396; DOI=10.1111/j.1432-1033.1993.tb18179.x;
RA Kochs G., Hummel R., Meyer D., Hug H., Marme D., Sarre T.F.;
RT "Activation and substrate specificity of the human protein kinase C alpha
RT and zeta isoenzymes.";
RL Eur. J. Biochem. 216:597-606(1993).
RN [7]
RP INTERACTION WITH CDCP1.
RX PubMed=15851033; DOI=10.1016/j.cell.2005.02.019;
RA Benes C.H., Wu N., Elia A.E.H., Dharia T., Cantley L.C., Soltoff S.P.;
RT "The C2 domain of PKCdelta is a phosphotyrosine binding domain.";
RL Cell 121:271-280(2005).
RN [8]
RP FUNCTION, AND INTERACTION WITH TP53INP1 AND P53/TP53.
RX PubMed=16377624; DOI=10.1074/jbc.m512074200;
RA Yoshida K., Liu H., Miki Y.;
RT "Protein kinase C delta regulates Ser46 phosphorylation of p53 tumor
RT suppressor in the apoptotic response to DNA damage.";
RL J. Biol. Chem. 281:5734-5740(2006).
RN [9]
RP REVIEW ON FUNCTION.
RX PubMed=12417016; DOI=10.1093/oxfordjournals.jbchem.a003274;
RA Saito N., Shirai Y.;
RT "Protein kinase C gamma (PKC gamma): function of neuron specific isotype.";
RL J. Biochem. 132:683-687(2002).
RN [10]
RP REVIEW ON FUNCTION.
RX PubMed=17629453; DOI=10.1016/j.cellsig.2007.05.014;
RA Barnett M.E., Madgwick D.K., Takemoto D.J.;
RT "Protein kinase C as a stress sensor.";
RL Cell. Signal. 19:1820-1829(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP UBIQUITINATION.
RX PubMed=20596523; DOI=10.1371/journal.pone.0011332;
RA Del Rincon S.V., Rogers J., Widschwendter M., Sun D., Sieburg H.B.,
RA Spruck C.;
RT "Development and validation of a method for profiling post-translational
RT modification activities using protein microarrays.";
RL PLoS ONE 5:E11332-E11332(2010).
RN [13]
RP STRUCTURE BY NMR OF 36-105.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the phorbol esters/diacylglycerol binding domain of
RT protein kinase C gamma.";
RL Submitted (DEC-2007) to the PDB data bank.
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 154-295 IN COMPLEX WITH CALCIUM
RP IONS, AND COFACTOR.
RA Pike A.C.W., Amos A., Johansson C., Sobott F., Savitsky P., Berridge G.,
RA Fedorov O., Umeano C., Gorrec F., Bunkoczi G., Debreczeni J., Von Delft F.,
RA Arrowsmith C.H., Edwards A., Weigelt J., Sundstrom M., Knapp S.;
RT "Crystal structure of C2 domain of protein kinase C gamma.";
RL Submitted (APR-2007) to the PDB data bank.
RN [15]
RP VARIANTS CYS-141; GLN-415; ASP-523 AND SER-659.
RX PubMed=9545390; DOI=10.1086/301819;
RA Al-Maghtheh M., Vithana E.N., Inglehearn C.F., Moore T., Bird A.C.,
RA Bhattacharya S.S.;
RT "Segregation of a PRKCG mutation in two RP11 families.";
RL Am. J. Hum. Genet. 62:1248-1252(1998).
RN [16]
RP SHOWS THAT THE VARIANTS ARE NOT A CAUSE OF RP11.
RX PubMed=10441600; DOI=10.1086/302554;
RA Dryja T.P., McEvoy J., McGee T.L., Berson E.L.;
RT "No mutations in the coding region of the PRKCG gene in three families with
RT retinitis pigmentosa linked to the RP11 locus on chromosome 19q.";
RL Am. J. Hum. Genet. 65:926-928(1999).
RN [17]
RP TISSUE SPECIFICITY, AND VARIANTS SCA14 TYR-101; PRO-119 AND ASP-128.
RX PubMed=12644968; DOI=10.1086/373883;
RA Chen D.-H., Brkanac Z., Verlinde C.L.M.J., Tan X.-J., Bylenok L.,
RA Nochlin D., Matsushita M., Lipe H., Wolff J., Fernandez M., Cimino P.J.,
RA Bird T.D., Raskind W.H.;
RT "Missense mutations in the regulatory domain of PKC gamma: a new mechanism
RT for dominant nonepisodic cerebellar ataxia.";
RL Am. J. Hum. Genet. 72:839-849(2003).
RN [18]
RP VARIANTS SCA14 VAL-63 AND ARG-63, AND SUBCELLULAR LOCATION.
RX PubMed=29053796; DOI=10.1093/brain/awx251;
RA Nibbeling E.A.R., Duarri A., Verschuuren-Bemelmans C.C., Fokkens M.R.,
RA Karjalainen J.M., Smeets C.J.L.M., de Boer-Bergsma J.J., van der Vries G.,
RA Dooijes D., Bampi G.B., van Diemen C., Brunt E., Ippel E., Kremer B.,
RA Vlak M., Adir N., Wijmenga C., van de Warrenburg B.P.C., Franke L.,
RA Sinke R.J., Verbeek D.S.;
RT "Exome sequencing and network analysis identifies shared mechanisms
RT underlying spinocerebellar ataxia.";
RL Brain 140:2860-2878(2017).
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. Is activated in
CC lens epithelial cells upon hydrogen peroxide treatment, and
CC 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 (By
CC similarity). Phosphorylates p53/TP53 and promotes p53/TP53-dependent
CC apoptosis in response to DNA damage. Involved in the phase resetting of
CC the cerebral cortex circadian clock during temporally restricted
CC feeding. Stabilizes the core clock component ARNTL/BMAL1 by interfering
CC with its ubiquitination, thus suppressing its degradation, resulting in
CC phase resetting of the cerebral cortex clock (By similarity).
CC {ECO:0000250|UniProtKB:P63318, ECO:0000250|UniProtKB:P63319,
CC ECO:0000269|PubMed:16377624}.
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, ECO:0000269|Ref.14};
CC Note=Binds 3 Ca(2+) ions per subunit. The ions are bound to the C2
CC domain. {ECO:0000269|Ref.14};
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 GRIA4 (By similarity). Interacts with CDCP1.
CC Interacts with TP53INP1 and p53/TP53. Interacts with ARNTL/BMAL1 (By
CC similarity). {ECO:0000250|UniProtKB:P63318,
CC ECO:0000269|PubMed:15851033, ECO:0000269|PubMed:16377624}.
CC -!- INTERACTION:
CC P05129; Q96KS9: FAM167A; NbExp=3; IntAct=EBI-949799, EBI-10290462;
CC P05129; P08238: HSP90AB1; NbExp=2; IntAct=EBI-949799, EBI-352572;
CC P05129; P08727: KRT19; NbExp=3; IntAct=EBI-949799, EBI-742756;
CC P05129; O75925: PIAS1; NbExp=3; IntAct=EBI-949799, EBI-629434;
CC P05129; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-949799, EBI-11528848;
CC P05129; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-949799, EBI-3923210;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P63318}.
CC Cytoplasm, perinuclear region {ECO:0000250}. Cell membrane
CC {ECO:0000269|PubMed:29053796}; 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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P05129-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P05129-2; Sequence=VSP_056467, VSP_056468, VSP_056469;
CC -!- TISSUE SPECIFICITY: Expressed in Purkinje cells of the cerebellar
CC cortex. {ECO:0000269|PubMed:12644968}.
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:0000269|PubMed:20596523}.
CC -!- DISEASE: Spinocerebellar ataxia 14 (SCA14) [MIM:605361]:
CC Spinocerebellar ataxia is a clinically and genetically heterogeneous
CC group of cerebellar disorders. Patients show progressive incoordination
CC of gait and often poor coordination of hands, speech and eye movements,
CC due to degeneration of the cerebellum with variable involvement of the
CC brainstem and spinal cord. SCA14 is an autosomal dominant cerebellar
CC ataxia (ADCA). {ECO:0000269|PubMed:12644968,
CC ECO:0000269|PubMed:29053796}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Mutations of the PRKCG gene; Note=Retina
CC International's Scientific Newsletter;
CC URL="https://www.retina-international.org/files/sci-news/prkcgmut.htm";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF345987; AAK13533.1; -; mRNA.
DR EMBL; AK303741; BAH14036.1; -; mRNA.
DR EMBL; AC008440; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC047876; AAH47876.1; -; mRNA.
DR EMBL; M13977; AAA60102.1; -; mRNA.
DR EMBL; Z15114; CAA78820.1; -; mRNA.
DR CCDS; CCDS12867.1; -. [P05129-1]
DR PIR; D24664; D24664.
DR RefSeq; NP_001303258.1; NM_001316329.1.
DR RefSeq; NP_002730.1; NM_002739.4. [P05129-1]
DR PDB; 2E73; NMR; -; A=36-105.
DR PDB; 2UZP; X-ray; 2.00 A; A/B/C=154-295.
DR PDBsum; 2E73; -.
DR PDBsum; 2UZP; -.
DR AlphaFoldDB; P05129; -.
DR SMR; P05129; -.
DR BioGRID; 111568; 67.
DR DIP; DIP-39795N; -.
DR IntAct; P05129; 42.
DR MINT; P05129; -.
DR STRING; 9606.ENSP00000263431; -.
DR BindingDB; P05129; -.
DR ChEMBL; CHEMBL2938; -.
DR DrugBank; DB09096; Benzoyl peroxide.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB00675; Tamoxifen.
DR DrugCentral; P05129; -.
DR GuidetoPHARMACOLOGY; 1484; -.
DR iPTMnet; P05129; -.
DR PhosphoSitePlus; P05129; -.
DR SwissPalm; P05129; -.
DR BioMuta; PRKCG; -.
DR DMDM; 462455; -.
DR EPD; P05129; -.
DR jPOST; P05129; -.
DR MassIVE; P05129; -.
DR MaxQB; P05129; -.
DR PaxDb; P05129; -.
DR PeptideAtlas; P05129; -.
DR PRIDE; P05129; -.
DR ProteomicsDB; 51803; -. [P05129-1]
DR ProteomicsDB; 6967; -.
DR Antibodypedia; 32756; 672 antibodies from 39 providers.
DR DNASU; 5582; -.
DR Ensembl; ENST00000263431.4; ENSP00000263431.3; ENSG00000126583.12. [P05129-1]
DR GeneID; 5582; -.
DR KEGG; hsa:5582; -.
DR MANE-Select; ENST00000263431.4; ENSP00000263431.3; NM_002739.5; NP_002730.1.
DR UCSC; uc002qcq.2; human. [P05129-1]
DR CTD; 5582; -.
DR DisGeNET; 5582; -.
DR GeneCards; PRKCG; -.
DR GeneReviews; PRKCG; -.
DR HGNC; HGNC:9402; PRKCG.
DR HPA; ENSG00000126583; Tissue enriched (brain).
DR MalaCards; PRKCG; -.
DR MIM; 176980; gene.
DR MIM; 605361; phenotype.
DR neXtProt; NX_P05129; -.
DR OpenTargets; ENSG00000126583; -.
DR Orphanet; 98763; Spinocerebellar ataxia type 14.
DR PharmGKB; PA33766; -.
DR VEuPathDB; HostDB:ENSG00000126583; -.
DR eggNOG; KOG0696; Eukaryota.
DR GeneTree; ENSGT00940000161219; -.
DR HOGENOM; CLU_000288_54_2_1; -.
DR InParanoid; P05129; -.
DR OMA; DLKSQHT; -.
DR OrthoDB; 614710at2759; -.
DR PhylomeDB; P05129; -.
DR TreeFam; TF351133; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; P05129; -.
DR Reactome; R-HSA-111933; Calmodulin induced events.
DR Reactome; R-HSA-114516; Disinhibition of SNARE formation.
DR Reactome; R-HSA-416993; Trafficking of GluR2-containing AMPA receptors.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR Reactome; R-HSA-5099900; WNT5A-dependent internalization of FZD4.
DR Reactome; R-HSA-76005; Response to elevated platelet cytosolic Ca2+.
DR SignaLink; P05129; -.
DR SIGNOR; P05129; -.
DR BioGRID-ORCS; 5582; 14 hits in 1104 CRISPR screens.
DR ChiTaRS; PRKCG; human.
DR EvolutionaryTrace; P05129; -.
DR GeneWiki; PRKCG; -.
DR GenomeRNAi; 5582; -.
DR Pharos; P05129; Tchem.
DR PRO; PR:P05129; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P05129; protein.
DR Bgee; ENSG00000126583; Expressed in right frontal lobe and 113 other tissues.
DR ExpressionAtlas; P05129; baseline and differential.
DR Genevisible; P05129; HS.
DR GO; GO:0044305; C:calyx of Held; IEA:Ensembl.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0030425; C:dendrite; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0099524; C:postsynaptic cytosol; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0099523; C:presynaptic cytosol; IEA:Ensembl.
DR GO; GO:0097060; C:synaptic membrane; IEA:Ensembl.
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:0004672; F:protein kinase activity; IDA:HGNC-UCL.
DR GO; GO:0004697; F:protein kinase C activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0007268; P:chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0007635; P:chemosensory behavior; IEA:Ensembl.
DR GO; GO:0060384; P:innervation; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007611; P:learning or memory; IEA:Ensembl.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
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:0042177; P:negative regulation of protein catabolic process; IDA:HGNC-UCL.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:HGNC-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IDA:HGNC-UCL.
DR GO; GO:0032425; P:positive regulation of mismatch repair; IDA:HGNC-UCL.
DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IEA:Ensembl.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; TAS:ProtInc.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0050764; P:regulation of phagocytosis; IEA:Ensembl.
DR GO; GO:0032095; P:regulation of response to food; ISS:UniProtKB.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0043278; P:response to morphine; ISS:UniProtKB.
DR GO; GO:0048265; P:response to pain; ISS:UniProtKB.
DR GO; GO:1990911; P:response to psychosocial stress; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
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 3D-structure; Alternative splicing; ATP-binding; Biological rhythms;
KW Calcium; Cell membrane; Cell projection; Cytoplasm; Disease variant;
KW Kinase; Membrane; Metal-binding; Neurodegeneration; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Spinocerebellar ataxia; Synapse;
KW Synaptosome; Transferase; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..697
FT /note="Protein kinase C gamma type"
FT /id="PRO_0000055689"
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:0000269|Ref.14"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 187
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 193
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 246
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 247
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 248
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 251
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|Ref.14"
FT BINDING 254
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000269|Ref.14"
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:0000255"
FT MOD_RES 655
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P63318"
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"
FT VAR_SEQ 1..20
FT /note="MAGLGPGVGDSEGGPRPLFC -> MPRICDLRVSRRWEGPPDGR (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056467"
FT VAR_SEQ 21..133
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056468"
FT VAR_SEQ 553..588
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056469"
FT VARIANT 63
FT /note="G -> R (in SCA14)"
FT /evidence="ECO:0000269|PubMed:29053796"
FT /id="VAR_080740"
FT VARIANT 63
FT /note="G -> V (in SCA14; dbSNP:rs386134159)"
FT /evidence="ECO:0000269|PubMed:29053796"
FT /id="VAR_080741"
FT VARIANT 101
FT /note="H -> Y (in SCA14; dbSNP:rs121918511)"
FT /evidence="ECO:0000269|PubMed:12644968"
FT /id="VAR_017060"
FT VARIANT 119
FT /note="S -> P (in SCA14; dbSNP:rs121918512)"
FT /evidence="ECO:0000269|PubMed:12644968"
FT /id="VAR_017061"
FT VARIANT 128
FT /note="G -> D (in SCA14; dbSNP:rs121918513)"
FT /evidence="ECO:0000269|PubMed:12644968"
FT /id="VAR_017062"
FT VARIANT 141
FT /note="R -> C"
FT /evidence="ECO:0000269|PubMed:9545390"
FT /id="VAR_008755"
FT VARIANT 415
FT /note="H -> Q"
FT /evidence="ECO:0000269|PubMed:9545390"
FT /id="VAR_008756"
FT VARIANT 523
FT /note="A -> D"
FT /evidence="ECO:0000269|PubMed:9545390"
FT /id="VAR_008757"
FT VARIANT 659
FT /note="R -> S (in dbSNP:rs752933837)"
FT /evidence="ECO:0000269|PubMed:9545390"
FT /id="VAR_008758"
FT CONFLICT 314..317
FT /note="RVRM -> VSRT (in Ref. 5; AAA60102)"
FT /evidence="ECO:0000305"
FT TURN 50..52
FT /evidence="ECO:0007829|PDB:2E73"
FT STRAND 57..59
FT /evidence="ECO:0007829|PDB:2E73"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:2E73"
FT HELIX 75..80
FT /evidence="ECO:0007829|PDB:2E73"
FT TURN 86..89
FT /evidence="ECO:0007829|PDB:2E73"
FT STRAND 160..169
FT /evidence="ECO:0007829|PDB:2UZP"
FT STRAND 172..182
FT /evidence="ECO:0007829|PDB:2UZP"
FT STRAND 194..201
FT /evidence="ECO:0007829|PDB:2UZP"
FT STRAND 222..230
FT /evidence="ECO:0007829|PDB:2UZP"
FT HELIX 233..237
FT /evidence="ECO:0007829|PDB:2UZP"
FT STRAND 239..246
FT /evidence="ECO:0007829|PDB:2UZP"
FT STRAND 249..251
FT /evidence="ECO:0007829|PDB:2UZP"
FT STRAND 254..262
FT /evidence="ECO:0007829|PDB:2UZP"
FT HELIX 263..268
FT /evidence="ECO:0007829|PDB:2UZP"
FT STRAND 271..276
FT /evidence="ECO:0007829|PDB:2UZP"
FT HELIX 280..283
FT /evidence="ECO:0007829|PDB:2UZP"
SQ SEQUENCE 697 AA; 78448 MW; 3F911B5BEF713C41 CRC64;
MAGLGPGVGD SEGGPRPLFC RKGALRQKVV HEVKSHKFTA RFFKQPTFCS HCTDFIWGIG
KQGLQCQVCS FVVHRRCHEF VTFECPGAGK GPQTDDPRNK HKFRLHSYSS PTFCDHCGSL
LYGLVHQGMK CSCCEMNVHR RCVRSVPSLC GVDHTERRGR LQLEIRAPTA DEIHVTVGEA
RNLIPMDPNG LSDPYVKLKL IPDPRNLTKQ KTRTVKATLN PVWNETFVFN LKPGDVERRL
SVEVWDWDRT SRNDFMGAMS FGVSELLKAP VDGWYKLLNQ EEGEYYNVPV ADADNCSLLQ
KFEACNYPLE LYERVRMGPS SSPIPSPSPS PTDPKRCFFG 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 RLERLEIPPP FRPRPCGRSG ENFDKFFTRA APALTPPDRL
VLASIDQADF QGFTYVNPDF VHPDARSPTS PVPVPVM
