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 02-SEP-2026, entry version 234. 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=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.13; CC 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}. 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; 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_006255.5. [P24723-1] DR RefSeq; XP_024305429.1; XM_024449661.2. [P24723-2] DR RefSeq; XP_024305430.1; XM_024449662.2. [P24723-2] DR RefSeq; XP_054232364.1; XM_054376389.1. [P24723-2] DR RefSeq; XP_054232365.1; XM_054376390.1. [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 PDB; 8FP1; X-ray; 1.85 A; A=333-683. DR PDB; 8FP3; X-ray; 2.30 A; A=333-683. DR AlphaFoldDB; P24723; -. DR MDRepo; P24723; -. DR SMR; P24723; -. DR BioGRID; 111569; 31. DR DIP; DIP-44588N; -. DR FunCoup; P24723; 864. DR IntAct; P24723; 14. DR MINT; P24723; -. DR NDEx; IQUERY-CP-PRKCH; 17 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000329127; -. DR BindingDB; P24723; -. DR ChEMBL; CHEMBL3616; -. DR DrugCentral; P24723; -. DR GuidetoPHARMACOLOGY; 1487; -. DR GlyGen; P24723; 3 sites, 3 N-linked glycans (2 sites), 1 O-linked glycan (1 site). DR iPTMnet; P24723; -. DR PhosphoSitePlus; P24723; -. DR BioMuta; PRKCH; -. DR DMDM; 281185512; -. DR CPTAC; CPTAC-3187; -. DR CPTAC; CPTAC-3188; -. DR jPOST; P24723; -. DR MassIVE; P24723; -. DR PaxDb; 9606-ENSP00000329127; -. DR PeptideAtlas; P24723; -. DR ProteomicsDB; 4395; -. DR ProteomicsDB; 54223; -. [P24723-1] DR Pumba; P24723; -. DR Antibodypedia; 24422; 316 antibodies from 36 providers. DR DNASU; 5583; -. DR Ensembl; ENST00000332981.11; ENSP00000329127.5; ENSG00000027075.18. [P24723-1] DR Ensembl; ENST00000555082.6; ENSP00000450981.1; ENSG00000027075.18. [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 AGR; HGNC:9403; -. DR ClinPGx; PA33767; -. 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 OpenTargets; ENSG00000027075; -. DR VEuPathDB; HostDB:ENSG00000027075; -. DR eggNOG; KOG0694; Eukaryota. DR GeneTree; ENSGT00940000158220; -. DR HOGENOM; CLU_000288_54_4_1; -. DR InParanoid; P24723; -. DR OMA; MTKNPNM; -. DR OrthoDB; 63267at2759; -. DR PAN-GO; P24723; 2 GO annotations based on evolutionary models. DR PhylomeDB; P24723; -. 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 Agora; ENSG00000027075; -. DR BioGRID-ORCS; 5583; 14 hits in 1196 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 189 other cell types or tissues. DR ExpressionAtlas; P24723; baseline and differential. 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:InterPro. DR GO; GO:0004697; F:diacylglycerol-dependent serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0004699; F:diacylglycerol-dependent, calcium-independent serine/threonine kinase activity; IEA:Ensembl. DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; EXP:UniProtKB. 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: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:0141212; P:phospholipase C/protein kinase C signal transduction; IEA:Ensembl. 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:1903078; P:positive regulation of protein localization to plasma membrane; TAS:ParkinsonsUK-UCL. DR GO; GO:0006468; P:protein phosphorylation; IMP: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; cd20835; C1_nPKC_epsilon-like_rpt1; 1. DR CDD; cd20838; C1_nPKC_epsilon-like_rpt2; 1. DR CDD; cd04014; C2_PKC_epsilon; 1. DR CDD; cd05590; STKc_nPKC_eta; 1. DR FunFam; 3.30.200.20:FF:000080; Protein kinase C; 1. DR FunFam; 3.30.60.20:FF:000003; Protein kinase C delta; 1. DR FunFam; 1.10.510.10:FF:000126; Protein kinase C epsilon; 1. DR FunFam; 2.60.40.150:FF:000056; Protein kinase C epsilon; 1. DR FunFam; 3.30.60.20:FF:000024; Protein kinase C epsilon; 1. DR Gene3D; 3.30.60.20; -; 2. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; PKC_DAG/PE. 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 PANTHER; PTHR24351; RIBOSOMAL PROTEIN S6 KINASE; 1. 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; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF57889; Cysteine-rich domain; 2. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. 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. DR PDBsum; 2FK9; -. DR PDBsum; 3TXO; -. DR PDBsum; 8FP1; -. DR PDBsum; 8FP3; -. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; KW Differentiation; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; KW Proteomics identification; Reference proteome; Repeat; KW Serine/threonine-protein kinase; Transferase; 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 (risk factor for ischemic stroke; increases FT autophosphorylation and kinase activity; 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 aLLTEL/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 HELIX 57..60 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..136 FT /evidence="ECO:0007829|PDB:2FK9" FT HELIX 352..354 FT /evidence="ECO:0007829|PDB:8FP1" FT STRAND 355..364 FT /evidence="ECO:0007829|PDB:8FP1" FT STRAND 367..374 FT /evidence="ECO:0007829|PDB:8FP1" FT TURN 375..377 FT /evidence="ECO:0007829|PDB:8FP1" FT STRAND 380..387 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 388..393 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 397..409 FT /evidence="ECO:0007829|PDB:8FP1" FT TURN 410..412 FT /evidence="ECO:0007829|PDB:8FP1" FT STRAND 419..424 FT /evidence="ECO:0007829|PDB:8FP1" FT STRAND 426..434 FT /evidence="ECO:0007829|PDB:8FP1" FT STRAND 438..440 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 441..448 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 453..472 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 482..484 FT /evidence="ECO:0007829|PDB:8FP1" FT STRAND 485..487 FT /evidence="ECO:0007829|PDB:8FP1" FT STRAND 493..495 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 518..520 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 523..526 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 534..549 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 559..568 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 569..574 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 579..588 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 593..595 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 600..602 FT /evidence="ECO:0007829|PDB:8FP1" FT TURN 603..605 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 606..609 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 612..614 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 619..623 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 646..648 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 655..658 FT /evidence="ECO:0007829|PDB:8FP1" FT TURN 660..662 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 663..665 FT /evidence="ECO:0007829|PDB:8FP1" FT HELIX 668..671 FT /evidence="ECO:0007829|PDB:8FP1" 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 //