ID KPCE_RABIT Reviewed; 736 AA.
AC P10830;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 24-JAN-2024, entry version 166.
DE RecName: Full=Protein kinase C epsilon type;
DE EC=2.7.11.13;
DE AltName: Full=nPKC-epsilon;
GN Name=PRKCE;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3370672; DOI=10.1016/0092-8674(88)90091-8;
RA Ohno S., Akita Y., Konno Y., Imajoh S., Suzuki K.;
RT "A novel phorbol ester receptor/protein kinase, nPKC, distantly related to
RT the protein kinase C family.";
RL Cell 53:731-741(1988).
CC -!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol (DAG)-
CC dependent serine/threonine-protein kinase that plays essential roles in
CC the regulation of multiple cellular processes linked to cytoskeletal
CC proteins, such as cell adhesion, motility, migration and cell cycle,
CC functions in neuron growth and ion channel regulation, and is involved
CC in immune response, cancer cell invasion and regulation of apoptosis.
CC Mediates cell adhesion to the extracellular matrix via integrin-
CC dependent signaling, by mediating angiotensin-2-induced activation of
CC integrin beta-1 (ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS,
CC which phosphorylates and activates PTK2/FAK, leading to the spread of
CC cardiomyocytes. Involved in the control of the directional transport of
CC ITGB1 in mesenchymal cells by phosphorylating vimentin (VIM), an
CC intermediate filament (IF) protein. In epithelial cells, associates
CC with and phosphorylates keratin-8 (KRT8), which induces targeting of
CC desmoplakin at desmosomes and regulates cell-cell contact.
CC Phosphorylates IQGAP1, which binds to CDC42, mediating epithelial cell-
CC cell detachment prior to migration. During cytokinesis, forms a complex
CC with YWHAB, which is crucial for daughter cell separation, and
CC facilitates abscission by a mechanism which may implicate the
CC regulation of RHOA. In cardiac myocytes, regulates myofilament function
CC and excitation coupling at the Z-lines, where it is indirectly
CC associated with F-actin via interaction with COPB1. During endothelin-
CC induced cardiomyocyte hypertrophy, mediates activation of PTK2/FAK,
CC which is critical for cardiomyocyte survival and regulation of
CC sarcomere length. Plays a role in the pathogenesis of dilated
CC cardiomyopathy via persistent phosphorylation of troponin I (TNNI3).
CC Involved in nerve growth factor (NFG)-induced neurite outgrowth and
CC neuron morphological change independently of its kinase activity, by
CC inhibition of RHOA pathway, activation of CDC42 and cytoskeletal
CC rearrangement. May be involved in presynaptic facilitation by mediating
CC phorbol ester-induced synaptic potentiation. Phosphorylates gamma-
CC aminobutyric acid receptor subunit gamma-2 (GABRG2), which reduces the
CC response of GABA receptors to ethanol and benzodiazepines and may
CC mediate acute tolerance to the intoxicating effects of ethanol. Upon
CC PMA treatment, phosphorylates the capsaicin- and heat-activated cation
CC channel TRPV1, which is required for bradykinin-induced sensitization
CC of the heat response in nociceptive neurons. Is able to form a complex
CC with PDLIM5 and N-type calcium channel, and may enhance channel
CC activities and potentiates fast synaptic transmission by
CC phosphorylating the pore-forming alpha subunit CACNA1B (CaV2.2).
CC Downstream of TLR4, plays an important role in the lipopolysaccharide
CC (LPS)-induced immune response by phosphorylating and activating
CC TICAM2/TRAM, which in turn activates the transcription factor IRF3 and
CC subsequent cytokines production. In differentiating erythroid
CC progenitors, is regulated by EPO and controls the protection against
CC the TNFSF10/TRAIL-mediated apoptosis, via BCL2. May be involved in the
CC regulation of the insulin-induced phosphorylation and activation of
CC AKT1 (By similarity). Phosphorylates NLRP5/MATER and may thereby
CC modulate AKT pathway activation in cumulus cells (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:Q02156}.
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-565 (activation loop of
CC the kinase domain), Thr-709 (turn motif) and Ser-728 (hydrophobic
CC region), need to be phosphorylated for its full activation.
CC -!- SUBUNIT: Forms a ternary complex with TRIM63 and RACK1/GN2BL1 (By
CC similarity). Can form a complex with PDLIM5 and N-type calcium channel
CC (By similarity). Interacts with COPB1 (By similarity). Interacts with
CC DGKQ (By similarity). Interacts with STAT3 (By similarity). Interacts
CC with YWHAB (By similarity). Interacts with HSP90AB1; promotes
CC functional activation in a heat shock-dependent manner (By similarity).
CC Interacts (via phorbol-ester/DAG-type 2 domain) with PRPH and VIM (By
CC similarity). Interacts with NLRP5/MATER (By similarity).
CC {ECO:0000250|UniProtKB:P09216, ECO:0000250|UniProtKB:P16054,
CC ECO:0000250|UniProtKB:Q02156}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q02156}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q02156}. Cell membrane
CC {ECO:0000250|UniProtKB:Q02156}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P16054}. Nucleus {ECO:0000250|UniProtKB:P16054}.
CC Note=Translocated to plasma membrane in epithelial cells stimulated by
CC HGF (By similarity). Associated with the Golgi at the perinuclear site
CC in pre-passage fibroblasts (By similarity). In passaging cells,
CC translocated to the cell periphery (By similarity). Translocated to the
CC nucleus in PMA-treated cells (By similarity).
CC {ECO:0000250|UniProtKB:P16054, ECO:0000250|UniProtKB:Q02156}.
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 -!- PTM: Phosphorylation on Thr-565 by PDPK1 triggers autophosphorylation
CC on Ser-728. Phosphorylation in the hinge domain at Ser-350 by MAPK11 or
CC MAPK14, Ser-346 by GSK3B and Ser-368 by autophosphorylation is required
CC for interaction with YWHAB (By similarity). {ECO:0000250}.
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; M20014; AAA31426.1; -; mRNA.
DR PIR; A29880; KIRBCE.
DR RefSeq; NP_001075743.1; NM_001082274.1.
DR AlphaFoldDB; P10830; -.
DR SMR; P10830; -.
DR STRING; 9986.ENSOCUP00000011861; -.
DR PaxDb; 9986-ENSOCUP00000011861; -.
DR GeneID; 100009103; -.
DR KEGG; ocu:100009103; -.
DR CTD; 5581; -.
DR eggNOG; KOG0694; Eukaryota.
DR InParanoid; P10830; -.
DR OrthoDB; 841660at2759; -.
DR BRENDA; 2.7.11.13; 1749.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0071944; C:cell periphery; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0003785; F:actin monomer binding; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004699; F:diacylglycerol-dependent, calcium-independent serine/threonine kinase activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
DR GO; GO:0032467; P:positive regulation of cytokinesis; ISS:UniProtKB.
DR GO; GO:0010634; P:positive regulation of epithelial cell migration; ISS:UniProtKB.
DR GO; GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB.
DR GO; GO:0090303; P:positive regulation of wound healing; ISS:UniProtKB.
DR GO; GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; ISS:UniProtKB.
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; cd05591; STKc_nPKC_epsilon; 1.
DR Gene3D; 3.30.60.20; -; 2.
DR Gene3D; 2.60.40.150; C2 domain; 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; IPR034669; nPKC_epsilon.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR027274; PKC_epsilon.
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:SF182; PROTEIN KINASE C EPSILON TYPE; 1.
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; PIRSF501106; Protein_kin_C_epsilon; 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; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 2.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell adhesion; Cell cycle; Cell division; Cell membrane;
KW Cytoplasm; Cytoskeleton; Immunity; Kinase; Membrane; Metal-binding;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..736
FT /note="Protein kinase C epsilon type"
FT /id="PRO_0000055699"
FT DOMAIN 1..117
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 407..667
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 668..736
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 169..220
FT /note="Phorbol-ester/DAG-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT ZN_FING 242..292
FT /note="Phorbol-ester/DAG-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 310..356
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..397
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 329..351
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 531
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 413..421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 436
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 228
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
FT MOD_RES 234
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 309
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
FT MOD_RES 316
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
FT MOD_RES 337
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 346
FT /note="Phosphoserine; by GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
FT MOD_RES 349
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 350
FT /note="Phosphoserine; by MAPK11 and MAPK14"
FT /evidence="ECO:0000250|UniProtKB:P16054"
FT MOD_RES 368
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
FT MOD_RES 388
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
FT MOD_RES 565
FT /note="Phosphothreonine; by PDPK1"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
FT MOD_RES 702
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000255"
FT MOD_RES 709
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q02156, ECO:0000255"
FT MOD_RES 728
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q02156"
SQ SEQUENCE 736 AA; 83516 MW; 261C4FEE59E9BFEB CRC64;
MVVFNGLLKI KICEAVSLKP TAWSLRHAVG PRPQTFLLDP YIALNVDDSR IGQTATKQKT
NSPAWHDEFV TDVCNGRKIE LAVFHDAPIG YDDFVANCTI QFEELLQNGS RHFEDWIDLE
PEGKVYVIID LSGSSGEAPK DNEERVFRER MRPRKRQGAV RRRVHQVNGH KFMATYLRQP
TYCSHCRDFI WGVIGKQGYQ CQVCTCVVHK RCHELIITKV AGLKKQETPD EVGSQRFSVN
MPHKFGIHNY KVPTFCDHCG SLLWGLLRQG LQCKVCKMNV HRRCETNVAP NCGVDARGIA
KVLADLGVTP DKITNSGQRR KKLIGGAESP QPTSGSSPSE EDRSKSAPTS PCDQELKELE
NNIRKALSFD NRGEEHRAAS STDGQLGSPE NGEVRQGQAK RLGLDEFNFI KVLGKGSFGK
VMLAELKGKD EVYAVKVLKK DVILQDDDVD CTMTEKRILA LARKHPYLTQ LYCCFQTKDR
LFFVMEYVNG GDLMFQIQRS RKFDEPRSRF YAAEVTSALM FLHQHGVIYR DLKLDNILLD
AEGHCKLADF GMCKEGILNG VTTTTFCGTP DYIAPEILQE LEYGPSVDWW ALGVLMYEMM
AGQPPFEADN EDDLFESILH DDVLYPVWLS KEAVSILKAF MTKNPHKRLG CVAAQNGEDA
IKQHPFFKEI DWVLLEQKKI KPPFKPRIKT KRDVNNFDQD FTREEPVLTL VDEAIVKQIN
QEEFKGFSYF GEDLMP
//
