KPCL_MOUSE
ID KPCL_MOUSE Reviewed; 683 AA.
AC P23298; Q8K2K8;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Protein kinase C eta type;
DE EC=2.7.11.13;
DE AltName: Full=PKC-L;
DE AltName: Full=nPKC-eta;
GN Name=Prkch; Synonyms=Pkch;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Epidermis;
RX PubMed=2266135; DOI=10.1016/s0021-9258(18)45723-7;
RA Osada S., Mizuno K., Saido T.C., Akita Y., Suzuki K., Kuroki T., Ohno S.;
RT "A phorbol ester receptor/protein kinase, nPKC eta, a new member of the
RT protein kinase C family predominantly expressed in lung and skin.";
RL J. Biol. Chem. 265:22434-22440(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N-3; TISSUE=Mammary tumor;
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 [4]
RP FUNCTION, INTERACTION WITH FYN, AND SUBCELLULAR LOCATION.
RX PubMed=11106751; DOI=10.1016/s1097-2765(00)00110-6;
RA Cabodi S., Calautti E., Talora C., Kuroki T., Stein P.L., Dotto G.P.;
RT "A PKC-eta/Fyn-dependent pathway leading to keratinocyte growth arrest and
RT differentiation.";
RL Mol. Cell 6:1121-1129(2000).
RN [5]
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 [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [7]
RP FUNCTION, INTERACTION WITH RALA, AND SUBCELLULAR LOCATION.
RX PubMed=21346190; DOI=10.1091/mbc.e10-09-0754;
RA Shirai Y., Morioka S., Sakuma M., Yoshino K., Otsuji C., Sakai N.,
RA Kashiwagi K., Chida K., Shirakawa R., Horiuchi H., Nishigori C., Ueyama T.,
RA Saito N.;
RT "Direct binding of RalA to PKC? and its crucial role in morphological
RT change during keratinocyte differentiation.";
RL Mol. Biol. Cell 22:1340-1352(2011).
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:11106751,
CC ECO:0000269|PubMed:18780722, ECO:0000269|PubMed:21346190}.
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 -!- 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.
CC -!- SUBUNIT: Interacts with FYN (PubMed:11106751). Interacts with RALA
CC (PubMed:21346190). Interacts with DGKQ (By similarity).
CC {ECO:0000250|UniProtKB:P24723, ECO:0000269|PubMed:11106751,
CC ECO:0000269|PubMed:21346190}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:11106751,
CC ECO:0000269|PubMed:21346190}. Note=Associates with cell membrane during
CC keratinocytes differentiation.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in lung and skin.
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 -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; D90242; BAA14288.1; -; mRNA.
DR EMBL; AK164044; BAE37603.1; -; mRNA.
DR EMBL; BC031121; AAH31121.1; -; mRNA.
DR CCDS; CCDS25976.1; -.
DR PIR; A23690; A23690.
DR RefSeq; NP_001300906.1; NM_001313977.1.
DR RefSeq; NP_032882.2; NM_008856.4.
DR AlphaFoldDB; P23298; -.
DR SMR; P23298; -.
DR BioGRID; 202199; 1.
DR IntAct; P23298; 1.
DR STRING; 10090.ENSMUSP00000021527; -.
DR BindingDB; P23298; -.
DR ChEMBL; CHEMBL4992; -.
DR iPTMnet; P23298; -.
DR PhosphoSitePlus; P23298; -.
DR EPD; P23298; -.
DR jPOST; P23298; -.
DR MaxQB; P23298; -.
DR PaxDb; P23298; -.
DR PRIDE; P23298; -.
DR ProteomicsDB; 264863; -.
DR DNASU; 18755; -.
DR Ensembl; ENSMUST00000021527; ENSMUSP00000021527; ENSMUSG00000021108.
DR GeneID; 18755; -.
DR KEGG; mmu:18755; -.
DR UCSC; uc007nwn.1; mouse.
DR CTD; 5583; -.
DR MGI; MGI:97600; Prkch.
DR VEuPathDB; HostDB:ENSMUSG00000021108; -.
DR eggNOG; KOG0694; Eukaryota.
DR GeneTree; ENSGT00940000158220; -.
DR InParanoid; P23298; -.
DR OMA; EFRHFSF; -.
DR OrthoDB; 222529at2759; -.
DR PhylomeDB; P23298; -.
DR TreeFam; TF351133; -.
DR BRENDA; 2.7.11.13; 3474.
DR Reactome; R-MMU-114508; Effects of PIP2 hydrolysis.
DR BioGRID-ORCS; 18755; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Prkch; mouse.
DR PRO; PR:P23298; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; P23298; protein.
DR Bgee; ENSMUSG00000021108; Expressed in ectoplacental cone and 187 other tissues.
DR ExpressionAtlas; P23298; baseline and differential.
DR Genevisible; P23298; MM.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; ISO:MGI.
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; IPI:UniProtKB.
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; ISS: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; ISS:UniProtKB.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; ISS:UniProtKB.
DR GO; GO:0045618; P:positive regulation of keratinocyte differentiation; IMP:UniProtKB.
DR GO; GO:0010744; P:positive regulation of macrophage derived foam cell differentiation; IMP:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0070528; P:protein kinase C signaling; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:2000810; P:regulation of bicellular tight junction assembly; ISS:UniProtKB.
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 ATP-binding; Cytoplasm; Differentiation; Kinase; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; 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_0000055706"
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 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"
FT /evidence="ECO:0000250|UniProtKB:P24723"
FT MOD_RES 32
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P24723"
FT MOD_RES 317
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19144319"
FT MOD_RES 513
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250"
FT MOD_RES 656
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P24723"
FT MOD_RES 675
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q64617"
FT CONFLICT 582
FT /note="T -> R (in Ref. 1; BAA14288)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 683 AA; 77919 MW; 50454A6AE1900AD3 CRC64;
MSSGTMKFNG YLRVRIGEAV GLQPTRWSLR HSLFKKGHQL LDPYLTVSVD QVRVGQTSTK
QKTNKPTYNE EFCANVTDGG HLELAVFHET PLGYDHFVAN CTLQFQELLR TAGTSDTFEG
WVDLEPEGKV FVVITLTGSF TEATLQRDRI FKHFTRKRQR AMRRRVHQVN GHKFMATYLR
QPTYCSHCRE FIWGVFGKQG YQCQVCTCVV HKRCHHLIVT ACTCQNNINK VDAKIAEQRF
GINIPHKFNV HNYKVPTFCD HCGSLLWGIM RQGLQCKICK MNVHIRCQAN VAPNCGVNAV
ELAKTLAGMG LQPGNISPTS KLISRSTLRR QGKEGSKEGN GIGVNSSSRF GIDNFEFIRV
LGKGSFGKVM LARIKETGEL YAVKVLKKDV ILQDDDVECT MTEKRILSLA RNHPFLTQLF
CCFQTPDRLF FVMEFVNGGD LMFHIQKSRR FDEARARFYA AEIISALMFL HEKGIIYRDL
KLDNVLLDHE GHCKLADFGM CKEGICNGVT TATFCGTPDY IAPEILQEML YGPAVDWWAM
GVLLYEMLCG HAPFEAENED DLFEAILNDE VVYPTWLHED ATGILKSFMT KNPTMRLGSL
TQGGEHEILR HPFFKEIDWA QLNHRQLEPP FRPRIKSRED VSNFDPDFIK EEPVLTPIDE
GHLPMINQDE FRNFSYVSPE LQL
