KPCL_HUMAN
ID KPCL_HUMAN Reviewed; 683 AA.
AC P24723; B4DJN5; Q16246; Q8NE03;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-2009, sequence version 4.
DT 03-AUG-2022, entry version 215.
DE RecName: Full=Protein kinase C eta type;
DE EC=2.7.11.13 {ECO:0000269|PubMed:34593629};
DE AltName: Full=PKC-L;
DE AltName: Full=nPKC-eta;
GN Name=PRKCH; Synonyms=PKCL, PRKCL;
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), AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=1986216; DOI=10.1128/mcb.11.1.126-133.1991;
RA Bacher N., Zisman Y., Berent E., Livneh E.;
RT "Isolation and characterization of PKC-L, a new member of the protein
RT kinase C-related gene family specifically expressed in lung, skin, and
RT heart.";
RL Mol. Cell. Biol. 11:126-133(1991).
RN [2]
RP ERRATUM OF PUBMED:1986216, AND SEQUENCE REVISION.
RX PubMed=1545821; DOI=10.1128/mcb.12.3.1404-.1992;
RA Bacher N., Zisman Y., Berent E., Livneh E.;
RL Mol. Cell. Biol. 12:1404-1404(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Thalamus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 438-539 (ISOFORM 1).
RX PubMed=7988719; DOI=10.1016/0014-5793(94)01202-4;
RA Palmer R.H., Ridden J., Parker P.J.;
RT "Identification of multiple, novel, protein kinase C-related gene
RT products.";
RL FEBS Lett. 356:5-8(1994).
RN [8]
RP FUNCTION.
RX PubMed=11112424; DOI=10.1006/bbrc.2000.3903;
RA Akkaraju G.R., Basu A.;
RT "Overexpression of protein kinase C-eta attenuates caspase activation and
RT tumor necrosis factor-alpha-induced cell death.";
RL Biochem. Biophys. Res. Commun. 279:103-107(2000).
RN [9]
RP FUNCTION IN CELL PROLIFERATION.
RX PubMed=10806212; DOI=10.1074/jbc.m003203200;
RA Hussaini I.M., Karns L.R., Vinton G., Carpenter J.E., Redpath G.T.,
RA Sando J.J., VandenBerg S.R.;
RT "Phorbol 12-myristate 13-acetate induces protein kinase ceta-specific
RT proliferative response in astrocytic tumor cells.";
RL J. Biol. Chem. 275:22348-22354(2000).
RN [10]
RP FUNCTION.
RX PubMed=11772428; DOI=10.1093/neuonc/4.1.9;
RA Hussaini I.M., Carpenter J.E., Redpath G.T., Sando J.J., Shaffrey M.E.,
RA Vandenberg S.R.;
RT "Protein kinase C-eta regulates resistance to UV- and gamma-irradiation-
RT induced apoptosis in glioblastoma cells by preventing caspase-9
RT activation.";
RL Neuro-oncol. 4:9-21(2002).
RN [11]
RP FUNCTION IN CELL PROLIFERATION.
RX PubMed=15489897; DOI=10.1038/sj.onc.1208093;
RA Aeder S.E., Martin P.M., Soh J.W., Hussaini I.M.;
RT "PKC-eta mediates glioblastoma cell proliferation through the Akt and mTOR
RT signaling pathways.";
RL Oncogene 23:9062-9069(2004).
RN [12]
RP INTERACTION WITH DGKQ.
RX PubMed=15632189; DOI=10.1074/jbc.m409301200;
RA van Baal J., de Widt J., Divecha N., van Blitterswijk W.J.;
RT "Translocation of diacylglycerol kinase theta from cytosol to plasma
RT membrane in response to activation of G protein-coupled receptors and
RT protein kinase C.";
RL J. Biol. Chem. 280:9870-9878(2005).
RN [13]
RP FUNCTION.
RX PubMed=17146445; DOI=10.1038/sj.onc.1210090;
RA Uht R.M., Amos S., Martin P.M., Riggan A.E., Hussaini I.M.;
RT "The protein kinase C-eta isoform induces proliferation in glioblastoma
RT cell lines through an ERK/Elk-1 pathway.";
RL Oncogene 26:2885-2893(2007).
RN [14]
RP FUNCTION IN B-CELL SIGNALING.
RX PubMed=18780722; DOI=10.1093/intimm/dxn101;
RA Oda A., Ono T., Yamamoto M., Goitsuka R., Kitamura D.;
RT "PKC eta directs induction of IRF-4 expression and Ig kappa gene
RT rearrangement in pre-BCR signaling pathway.";
RL Int. Immunol. 20:1417-1426(2008).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
RP INDUCTION.
RX PubMed=19797084; DOI=10.1128/mcb.01044-09;
RA Raveh-Amit H., Maissel A., Poller J., Marom L., Elroy-Stein O., Shapira M.,
RA Livneh E.;
RT "Translational control of protein kinase Ceta by two upstream open reading
RT frames.";
RL Mol. Cell. Biol. 29:6140-6148(2009).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF OCLN.
RX PubMed=19114660; DOI=10.1073/pnas.0802741106;
RA Suzuki T., Elias B.C., Seth A., Shen L., Turner J.R., Giorgianni F.,
RA Desiderio D., Guntaka R., Rao R.;
RT "PKC eta regulates occludin phosphorylation and epithelial tight junction
RT integrity.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:61-66(2009).
RN [18]
RP FUNCTION.
RX PubMed=20558593; DOI=10.1124/mol.110.064394;
RA Lee H.K., Yeo S., Kim J.S., Lee J.G., Bae Y.S., Lee C., Baek S.H.;
RT "Protein kinase C-eta and phospholipase D2 pathway regulates foam cell
RT formation via regulator of G protein signaling 2.";
RL Mol. Pharmacol. 78:478-485(2010).
RN [19]
RP FUNCTION.
RX PubMed=21820409; DOI=10.1016/j.bbrc.2011.07.090;
RA Raveh-Amit H., Hai N., Rotem-Dai N., Shahaf G., Gopas J., Livneh E.;
RT "Protein kinase C? activates NF-?B in response to camptothecin-induced DNA
RT damage.";
RL Biochem. Biophys. Res. Commun. 412:313-317(2011).
RN [20]
RP REVIEW.
RX PubMed=12473186; DOI=10.1093/oxfordjournals.jbchem.a003297;
RA Kashiwagi M., Ohba M., Chida K., Kuroki T.;
RT "Protein kinase C eta (PKC eta): its involvement in keratinocyte
RT differentiation.";
RL J. Biochem. 132:853-857(2002).
RN [21]
RP FUNCTION.
RX PubMed=22304920; DOI=10.1016/j.cell.2012.01.016;
RA Lau E., Kluger H., Varsano T., Lee K., Scheffler I., Rimm D.L., Ideker T.,
RA Ronai Z.A.;
RT "PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while
RT blocking its apoptotic function at mitochondria.";
RL Cell 148:543-555(2012).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-28, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-656, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [24]
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, INTERACTION WITH PRKCH UPSTREAM
RP OPEN READING FRAME 2, AND PHOSPHORYLATION AT THR-656 AND SER-675.
RX PubMed=34593629; DOI=10.1073/pnas.2018899118;
RA Jayaram D.R., Frost S., Argov C., Liju V.B., Anto N.P., Muraleedharan A.,
RA Ben-Ari A., Sinay R., Smoly I., Novoplansky O., Isakov N., Toiber D.,
RA Keasar C., Elkabets M., Yeger-Lotem E., Livneh E.;
RT "Unraveling the hidden role of a uORF-encoded peptide as a kinase inhibitor
RT of PKCs.";
RL Proc. Natl. Acad. Sci. U.S.A. 118:0-0(2021).
RN [25]
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1-138, PHOSPHORYLATION AT SER-28
RP AND SER-32, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=16973127; DOI=10.1016/j.bbrc.2006.08.160;
RA Littler D.R., Walker J.R., She Y.-M., Finerty P.J. Jr., Newman E.M.,
RA Dhe-Paganon S.;
RT "Structure of human protein kinase C eta (PKCeta) C2 domain and
RT identification of phosphorylation sites.";
RL Biochem. Biophys. Res. Commun. 349:1182-1189(2006).
RN [26]
RP ASSOCIATION OF VARIANT ILE-374 WITH ISCHSTR, AND CHARACTERIZATION OF
RP VARIANT ILE-374.
RX PubMed=17206144; DOI=10.1038/ng1945;
RA Kubo M., Hata J., Ninomiya T., Matsuda K., Yonemoto K., Nakano T.,
RA Matsushita T., Yamazaki K., Ohnishi Y., Saito S., Kitazono T., Ibayashi S.,
RA Sueishi K., Iida M., Nakamura Y., Kiyohara Y.;
RT "A nonsynonymous SNP in PRKCH (protein kinase C eta) increases the risk of
RT cerebral infarction.";
RL Nat. Genet. 39:212-217(2007).
RN [27]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-19; ARG-65; GLN-149; GLN-359; ILE-374;
RP ALA-575; ILE-594 AND SER-612.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that is involved in the
CC regulation of cell differentiation in keratinocytes and pre-B cell
CC receptor, mediates regulation of epithelial tight junction integrity
CC and foam cell formation, and is required for glioblastoma proliferation
CC and apoptosis prevention in MCF-7 cells. In keratinocytes, binds and
CC activates the tyrosine kinase FYN, which in turn blocks epidermal
CC growth factor receptor (EGFR) signaling and leads to keratinocyte
CC growth arrest and differentiation. Associates with the cyclin CCNE1-
CC CDK2-CDKN1B complex and inhibits CDK2 kinase activity, leading to RB1
CC dephosphorylation and thereby G1 arrest in keratinocytes. In
CC association with RALA activates actin depolymerization, which is
CC necessary for keratinocyte differentiation. In the pre-B cell receptor
CC signaling, functions downstream of BLNK by up-regulating IRF4, which in
CC turn activates L chain gene rearrangement. Regulates epithelial tight
CC junctions (TJs) by phosphorylating occludin (OCLN) on threonine
CC residues, which is necessary for the assembly and maintenance of TJs.
CC In association with PLD2 and via TLR4 signaling, is involved in
CC lipopolysaccharide (LPS)-induced RGS2 down-regulation and foam cell
CC formation. Upon PMA stimulation, mediates glioblastoma cell
CC proliferation by activating the mTOR pathway, the PI3K/AKT pathway and
CC the ERK1-dependent phosphorylation of ELK1. Involved in the protection
CC of glioblastoma cells from irradiation-induced apoptosis by preventing
CC caspase-9 activation. In camptothecin-treated MCF-7 cells, regulates
CC NF-kappa-B upstream signaling by activating IKBKB, and confers
CC protection against DNA damage-induced apoptosis. Promotes oncogenic
CC functions of ATF2 in the nucleus while blocking its apoptotic function
CC at mitochondria. Phosphorylates ATF2 which promotes its nuclear
CC retention and transcriptional activity and negatively regulates its
CC mitochondrial localization. {ECO:0000269|PubMed:10806212,
CC ECO:0000269|PubMed:11112424, ECO:0000269|PubMed:11772428,
CC ECO:0000269|PubMed:15489897, ECO:0000269|PubMed:17146445,
CC ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:19114660,
CC ECO:0000269|PubMed:20558593, ECO:0000269|PubMed:21820409,
CC ECO:0000269|PubMed:22304920}.
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 Evidence={ECO:0000269|PubMed:34593629};
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; Evidence={ECO:0000269|PubMed:34593629};
CC -!- ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are
CC calcium-insensitive, but activated by diacylglycerol (DAG) and
CC phosphatidylserine. Three specific sites; Thr-513 (activation loop of
CC the kinase domain), Thr-656 (turn motif) and Ser-675 (hydrophobic
CC region), need to be phosphorylated for its full activation. Inhibited
CC by PRKCH upstream open reading frame 2 (PubMed:34593629).
CC {ECO:0000269|PubMed:34593629}.
CC -!- SUBUNIT: Interacts with FYN (By similarity). Interacts with RALA (By
CC similarity). Interacts with DGKQ (PubMed:15632189). Interacts with
CC PRKCH upstream open reading frame 2; the interaction leads to
CC inhibition of kinase activity (PubMed:34593629).
CC {ECO:0000250|UniProtKB:P23298, ECO:0000269|PubMed:15632189,
CC ECO:0000269|PubMed:34593629}.
CC -!- INTERACTION:
CC P24723; Q16625-1: OCLN; NbExp=2; IntAct=EBI-2865850, EBI-16115673;
CC P24723; Q28269: OCLN; Xeno; NbExp=2; IntAct=EBI-2865850, EBI-16222162;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P24723-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P24723-2; Sequence=VSP_056572;
CC -!- TISSUE SPECIFICITY: Most abundant in lung, less in heart and skin.
CC {ECO:0000269|PubMed:1986216}.
CC -!- INDUCTION: By stress conditions caused by amino acid starvation (at
CC protein level). {ECO:0000269|PubMed:19797084}.
CC -!- DOMAIN: The C1 domain, containing the phorbol ester/DAG-type region 1
CC (C1A) and 2 (C1B), is the diacylglycerol sensor and the C2 domain is a
CC non-calcium binding domain.
CC -!- DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute
CC neurologic event leading to death of neural tissue of the brain and
CC resulting in loss of motor, sensory and/or cognitive function. Ischemic
CC strokes, resulting from vascular occlusion, is considered to be a
CC highly complex disease consisting of a group of heterogeneous disorders
CC with multiple genetic and environmental risk factors.
CC {ECO:0000269|PubMed:17206144}. Note=Disease susceptibility is
CC associated with variants 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}.
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DR EMBL; M55284; AAA60100.1; -; mRNA.
DR EMBL; AK290183; BAF82872.1; -; mRNA.
DR EMBL; AK296158; BAG58897.1; -; mRNA.
DR EMBL; AL138996; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL355916; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359220; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471061; EAW80800.1; -; Genomic_DNA.
DR EMBL; CH471061; EAW80801.1; -; Genomic_DNA.
DR EMBL; BC037268; AAH37268.1; -; mRNA.
DR EMBL; S74620; AAB32724.1; -; mRNA.
DR CCDS; CCDS9752.1; -. [P24723-1]
DR PIR; A39666; A39666.
DR RefSeq; NP_006246.2; NM_006255.4. [P24723-1]
DR RefSeq; XP_016876947.1; XM_017021458.1. [P24723-2]
DR PDB; 2FK9; X-ray; 1.75 A; A=1-138.
DR PDB; 3TXO; X-ray; 2.05 A; A=333-683.
DR PDBsum; 2FK9; -.
DR PDBsum; 3TXO; -.
DR AlphaFoldDB; P24723; -.
DR SMR; P24723; -.
DR BioGRID; 111569; 24.
DR DIP; DIP-44588N; -.
DR IntAct; P24723; 12.
DR MINT; P24723; -.
DR STRING; 9606.ENSP00000329127; -.
DR BindingDB; P24723; -.
DR ChEMBL; CHEMBL3616; -.
DR DrugCentral; P24723; -.
DR GuidetoPHARMACOLOGY; 1487; -.
DR iPTMnet; P24723; -.
DR PhosphoSitePlus; P24723; -.
DR BioMuta; PRKCH; -.
DR DMDM; 281185512; -.
DR EPD; P24723; -.
DR jPOST; P24723; -.
DR MassIVE; P24723; -.
DR MaxQB; P24723; -.
DR PaxDb; P24723; -.
DR PeptideAtlas; P24723; -.
DR PRIDE; P24723; -.
DR ProteomicsDB; 4395; -.
DR ProteomicsDB; 54223; -. [P24723-1]
DR Antibodypedia; 24422; 284 antibodies from 33 providers.
DR DNASU; 5583; -.
DR Ensembl; ENST00000332981.11; ENSP00000329127.5; ENSG00000027075.17. [P24723-1]
DR Ensembl; ENST00000555082.5; ENSP00000450981.1; ENSG00000027075.17. [P24723-2]
DR GeneID; 5583; -.
DR KEGG; hsa:5583; -.
DR MANE-Select; ENST00000332981.11; ENSP00000329127.5; NM_006255.5; NP_006246.2.
DR UCSC; uc001xfn.4; human. [P24723-1]
DR CTD; 5583; -.
DR DisGeNET; 5583; -.
DR GeneCards; PRKCH; -.
DR HGNC; HGNC:9403; PRKCH.
DR HPA; ENSG00000027075; Low tissue specificity.
DR MalaCards; PRKCH; -.
DR MIM; 601367; phenotype.
DR MIM; 605437; gene.
DR neXtProt; NX_P24723; -.
DR OpenTargets; ENSG00000027075; -.
DR PharmGKB; PA33767; -.
DR VEuPathDB; HostDB:ENSG00000027075; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000158220; -.
DR HOGENOM; CLU_000288_54_4_1; -.
DR InParanoid; P24723; -.
DR OMA; EFRHFSF; -.
DR OrthoDB; 222529at2759; -.
DR PhylomeDB; P24723; -.
DR TreeFam; TF351133; -.
DR BRENDA; 2.7.11.13; 2681.
DR PathwayCommons; P24723; -.
DR Reactome; R-HSA-114508; Effects of PIP2 hydrolysis.
DR Reactome; R-HSA-418597; G alpha (z) signalling events.
DR SABIO-RK; P24723; -.
DR SignaLink; P24723; -.
DR SIGNOR; P24723; -.
DR BioGRID-ORCS; 5583; 12 hits in 1115 CRISPR screens.
DR ChiTaRS; PRKCH; human.
DR EvolutionaryTrace; P24723; -.
DR GeneWiki; PRKCH; -.
DR GenomeRNAi; 5583; -.
DR Pharos; P24723; Tchem.
DR PRO; PR:P24723; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; P24723; protein.
DR Bgee; ENSG00000027075; Expressed in parotid gland and 187 other tissues.
DR ExpressionAtlas; P24723; baseline and differential.
DR Genevisible; P24723; HS.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
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:0004699; F:calcium-independent protein kinase C activity; IEA:Ensembl.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
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:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0034351; P:negative regulation of glial cell apoptotic process; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IBA:GO_Central.
DR GO; GO:0050861; P:positive regulation of B cell receptor signaling pathway; IMP:UniProtKB.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IMP:UniProtKB.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; ISS:UniProtKB.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IMP:UniProtKB.
DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; TAS:ParkinsonsUK-UCL.
DR GO; GO:0070528; P:protein kinase C signaling; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR CDD; cd00029; C1; 2.
DR CDD; cd05590; STKc_nPKC_eta; 1.
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; IPR034665; nPKC_eta.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027431; PKC_eta.
DR InterPro; IPR017892; Pkinase_C.
DR InterPro; IPR014376; Prot_kin_PKC_delta.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
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; PIRSF000551; PKC_delta; 1.
DR PIRSF; PIRSF501107; Protein_kin_C_eta; 1.
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; Cytoplasm;
KW Differentiation; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Repeat; Serine/threonine-protein kinase; Transferase;
KW Zinc; Zinc-finger.
FT CHAIN 1..683
FT /note="Protein kinase C eta type"
FT /id="PRO_0000055705"
FT DOMAIN 1..118
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 355..614
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 615..683
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 171..222
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 245..295
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 320..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 479
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 361..369
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 384
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 28
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:16973127,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 32
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000305|PubMed:16973127"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23298"
FT MOD_RES 513
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000305"
FT MOD_RES 656
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:34593629,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:34593629"
FT VAR_SEQ 1..161
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056572"
FT VARIANT 19
FT /note="A -> V (in dbSNP:rs55645551)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042312"
FT VARIANT 65
FT /note="K -> R (in dbSNP:rs55737090)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042313"
FT VARIANT 149
FT /note="R -> Q (in dbSNP:rs55848048)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042314"
FT VARIANT 359
FT /note="R -> Q (in dbSNP:rs55818778)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042315"
FT VARIANT 374
FT /note="V -> I (associated with susceptibility to ischemic
FT stroke; increases autophosphorylation and kinase activity;
FT dbSNP:rs2230500)"
FT /evidence="ECO:0000269|PubMed:17206144,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_034604"
FT VARIANT 497
FT /note="D -> Y (in dbSNP:rs11846991)"
FT /id="VAR_060736"
FT VARIANT 575
FT /note="T -> A (in a aLL TEL/AML1+ sample; somatic mutation;
FT dbSNP:rs1378993559)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042316"
FT VARIANT 594
FT /note="T -> I (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042317"
FT VARIANT 612
FT /note="P -> S (in dbSNP:rs34159231)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042318"
FT VARIANT 645
FT /note="D -> V (in dbSNP:rs35561533)"
FT /id="VAR_042438"
FT CONFLICT 96
FT /note="Missing (in Ref. 1; AAA60100)"
FT /evidence="ECO:0000305"
FT CONFLICT 109
FT /note="L -> R (in Ref. 1; AAA60100)"
FT /evidence="ECO:0000305"
FT CONFLICT 110
FT /note="R -> G (in Ref. 1; AAA60100)"
FT /evidence="ECO:0000305"
FT CONFLICT 393
FT /note="Q -> L (in Ref. 1; AAA60100)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="D -> E (in Ref. 7; AAB32724)"
FT /evidence="ECO:0000305"
FT STRAND 8..20
FT /evidence="ECO:0007829|PDB:2FK9"
FT HELIX 26..30
FT /evidence="ECO:0007829|PDB:2FK9"
FT TURN 31..33
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 34..37
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 43..49
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 67..79
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 81..88
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 91..94
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 96..104
FT /evidence="ECO:0007829|PDB:2FK9"
FT HELIX 105..112
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 129..137
FT /evidence="ECO:0007829|PDB:2FK9"
FT STRAND 355..364
FT /evidence="ECO:0007829|PDB:3TXO"
FT STRAND 367..374
FT /evidence="ECO:0007829|PDB:3TXO"
FT TURN 375..377
FT /evidence="ECO:0007829|PDB:3TXO"
FT STRAND 380..387
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 388..394
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 397..409
FT /evidence="ECO:0007829|PDB:3TXO"
FT TURN 410..412
FT /evidence="ECO:0007829|PDB:3TXO"
FT STRAND 419..424
FT /evidence="ECO:0007829|PDB:3TXO"
FT STRAND 426..434
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 441..448
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 453..472
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:3TXO"
FT STRAND 485..487
FT /evidence="ECO:0007829|PDB:3TXO"
FT STRAND 493..495
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 518..520
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 523..530
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 534..549
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 559..568
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 579..588
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 593..595
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 600..602
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 606..609
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 612..614
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 619..623
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 646..649
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 663..665
FT /evidence="ECO:0007829|PDB:3TXO"
FT HELIX 668..671
FT /evidence="ECO:0007829|PDB:3TXO"
SQ SEQUENCE 683 AA; 77828 MW; 0A29806CE31912F2 CRC64;
MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD QVRVGQTSTK
QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN CTLQFQELLR TTGASDTFEG
WVDLEPEGKV FVVITLTGSF TEATLQRDRI FKHFTRKRQR AMRRRVHQIN GHKFMATYLR
QPTYCSHCRE FIWGVFGKQG YQCQVCTCVV HKRCHHLIVT ACTCQNNINK VDSKIAEQRF
GINIPHKFSI HNYKVPTFCD HCGSLLWGIM RQGLQCKICK MNVHIRCQAN VAPNCGVNAV
ELAKTLAGMG LQPGNISPTS KLVSRSTLRR QGKESSKEGN GIGVNSSNRL GIDNFEFIRV
LGKGSFGKVM LARVKETGDL YAVKVLKKDV ILQDDDVECT MTEKRILSLA RNHPFLTQLF
CCFQTPDRLF FVMEFVNGGD LMFHIQKSRR FDEARARFYA AEIISALMFL HDKGIIYRDL
KLDNVLLDHE GHCKLADFGM CKEGICNGVT TATFCGTPDY IAPEILQEML YGPAVDWWAM
GVLLYEMLCG HAPFEAENED DLFEAILNDE VVYPTWLHED ATGILKSFMT KNPTMRLGSL
TQGGEHAILR HPFFKEIDWA QLNHRQIEPP FRPRIKSRED VSNFDPDFIK EEPVLTPIDE
GHLPMINQDE FRNFSYVSPE LQP
