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Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon)

 KPCE_RABIT              Reviewed;         736 AA.
P10830;
01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
01-JUL-1989, sequence version 1.
08-MAY-2019, entry version 148.
RecName: Full=Protein kinase C epsilon type;
EC=2.7.11.13;
AltName: Full=nPKC-epsilon;
Name=PRKCE;
Oryctolagus cuniculus (Rabbit).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae;
Oryctolagus.
NCBI_TaxID=9986;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=3370672; DOI=10.1016/0092-8674(88)90091-8;
Ohno S., Akita Y., Konno Y., Imajoh S., Suzuki K.;
"A novel phorbol ester receptor/protein kinase, nPKC, distantly
related to the protein kinase C family.";
Cell 53:731-741(1988).
-!- FUNCTION: Calcium-independent, phospholipid- and diacylglycerol
(DAG)-dependent serine/threonine-protein kinase that plays
essential roles in the regulation of multiple cellular processes
linked to cytoskeletal proteins, such as cell adhesion, motility,
migration and cell cycle, functions in neuron growth and ion
channel regulation, and is involved in immune response, cancer
cell invasion and regulation of apoptosis. Mediates cell adhesion
to the extracellular matrix via integrin-dependent signaling, by
mediating angiotensin-2-induced activation of integrin beta-1
(ITGB1) in cardiac fibroblasts. Phosphorylates MARCKS, which
phosphorylates and activates PTK2/FAK, leading to the spread of
cardiomyocytes. Involved in the control of the directional
transport of ITGB1 in mesenchymal cells by phosphorylating
vimentin (VIM), an intermediate filament (IF) protein. In
epithelial cells, associates with and phosphorylates keratin-8
(KRT8), which induces targeting of desmoplakin at desmosomes and
regulates cell-cell contact. Phosphorylates IQGAP1, which binds to
CDC42, mediating epithelial cell-cell detachment prior to
migration. During cytokinesis, forms a complex with YWHAB, which
is crucial for daughter cell separation, and facilitates
abscission by a mechanism which may implicate the regulation of
RHOA. In cardiac myocytes, regulates myofilament function and
excitation coupling at the Z-lines, where it is indirectly
associated with F-actin via interaction with COPB1. During
endothelin-induced cardiomyocyte hypertrophy, mediates activation
of PTK2/FAK, which is critical for cardiomyocyte survival and
regulation of sarcomere length. Plays a role in the pathogenesis
of dilated cardiomyopathy via persistent phosphorylation of
troponin I (TNNI3). Involved in nerve growth factor (NFG)-induced
neurite outgrowth and neuron morphological change independently of
its kinase activity, by inhibition of RHOA pathway, activation of
CDC42 and cytoskeletal rearrangement. May be involved in
presynaptic facilitation by mediating phorbol ester-induced
synaptic potentiation. Phosphorylates gamma-aminobutyric acid
receptor subunit gamma-2 (GABRG2), which reduces the response of
GABA receptors to ethanol and benzodiazepines and may mediate
acute tolerance to the intoxicating effects of ethanol. Upon PMA
treatment, phosphorylates the capsaicin- and heat-activated cation
channel TRPV1, which is required for bradykinin-induced
sensitization of the heat response in nociceptive neurons. Is able
to form a complex with PDLIM5 and N-type calcium channel, and may
enhance channel activities and potentiates fast synaptic
transmission by phosphorylating the pore-forming alpha subunit
CACNA1B (CaV2.2). Downstream of TLR4, plays an important role in
the lipopolysaccharide (LPS)-induced immune response by
phosphorylating and activating TICAM2/TRAM, which in turn
activates the transcription factor IRF3 and subsequent cytokines
production. In differentiating erythroid progenitors, is regulated
by EPO and controls the protection against the TNFSF10/TRAIL-
mediated apoptosis, via BCL2. May be involved in the regulation of
the insulin-induced phosphorylation and activation of AKT1 (By
similarity). {ECO:0000250}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
EC=2.7.11.13;
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
EC=2.7.11.13;
-!- ACTIVITY REGULATION: Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ)
are calcium-insensitive, but activated by diacylglycerol (DAG) and
phosphatidylserine. Three specific sites; Thr-565 (activation loop
of the kinase domain), Thr-709 (turn motif) and Ser-728
(hydrophobic region), need to be phosphorylated for its full
activation.
-!- SUBUNIT: Forms a ternary complex with TRIM63 and GN2BL1. Can form
a complex with PDLIM5 and N-type calcium channel. Interacts with
COPB1, DGKQ, STAT3 and YWHAB (By similarity). Interacts with
HSP90AB1; promotes functional activation in a heat shock-dependent
manner (By similarity). {ECO:0000250,
ECO:0000250|UniProtKB:Q02156}.
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm,
cytoskeleton {ECO:0000250}. Cell membrane {ECO:0000250}.
Cytoplasm, perinuclear region {ECO:0000250}. Nucleus
{ECO:0000250}. Note=Translocated to plasma membrane in epithelial
cells stimulated by HGF. Associated with the Golgi at the
perinuclear site in pre-passage fibroblasts. In passaging cells,
translocated to the cell periphery. Translocated to the nucleus in
PMA-treated cells (By similarity). {ECO:0000250}.
-!- DOMAIN: The C1 domain, containing the phorbol ester/DAG-type
region 1 (C1A) and 2 (C1B), is the diacylglycerol sensor and the
C2 domain is a non-calcium binding domain.
-!- PTM: Phosphorylation on Thr-565 by PDPK1 triggers
autophosphorylation on Ser-728. Phosphorylation in the hinge
domain at Ser-350 by MAPK11 or MAPK14, Ser-346 by GSK3B and Ser-
368 by autophosphorylation is required for interaction with YWHAB
(By similarity). {ECO:0000250}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
protein kinase family. PKC subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; M20014; AAA31426.1; -; mRNA.
PIR; A29880; KIRBCE.
RefSeq; NP_001075743.1; NM_001082274.1.
SMR; P10830; -.
STRING; 9986.ENSOCUP00000011861; -.
GeneID; 100009103; -.
KEGG; ocu:100009103; -.
CTD; 5581; -.
eggNOG; KOG0694; Eukaryota.
eggNOG; ENOG410XNPH; LUCA.
HOGENOM; HOG000233022; -.
InParanoid; P10830; -.
KO; K18050; -.
OrthoDB; 222529at2759; -.
BRENDA; 2.7.11.13; 1749.
Proteomes; UP000001811; Unplaced.
GO; GO:0071944; C:cell periphery; ISS:UniProtKB.
GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
GO; GO:0003785; F:actin monomer binding; ISS:UniProtKB.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0004699; F:calcium-independent protein kinase C activity; IEA:InterPro.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISS:UniProtKB.
GO; GO:0030838; P:positive regulation of actin filament polymerization; ISS:UniProtKB.
GO; GO:0032467; P:positive regulation of cytokinesis; ISS:UniProtKB.
GO; GO:0010634; P:positive regulation of epithelial cell migration; ISS:UniProtKB.
GO; GO:0010763; P:positive regulation of fibroblast migration; ISS:UniProtKB.
GO; GO:0090303; P:positive regulation of wound healing; ISS:UniProtKB.
GO; GO:0035669; P:TRAM-dependent toll-like receptor 4 signaling pathway; ISS:UniProtKB.
CDD; cd00029; C1; 2.
CDD; cd05591; STKc_nPKC_epsilon; 1.
Gene3D; 2.60.40.150; -; 1.
InterPro; IPR000961; AGC-kinase_C.
InterPro; IPR000008; C2_dom.
InterPro; IPR035892; C2_domain_sf.
InterPro; IPR020454; DAG/PE-bd.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR034669; nPKC_epsilon.
InterPro; IPR002219; PE/DAG-bd.
InterPro; IPR027274; PKC_epsilon.
InterPro; IPR017892; Pkinase_C.
InterPro; IPR014376; Prot_kin_PKC_delta.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR008271; Ser/Thr_kinase_AS.
Pfam; PF00130; C1_1; 2.
Pfam; PF00168; C2; 1.
Pfam; PF00069; Pkinase; 1.
Pfam; PF00433; Pkinase_C; 1.
PIRSF; PIRSF000551; PKC_delta; 1.
PIRSF; PIRSF501106; Protein_kin_C_epsilon; 1.
PRINTS; PR00008; DAGPEDOMAIN.
SMART; SM00109; C1; 2.
SMART; SM00239; C2; 1.
SMART; SM00133; S_TK_X; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS51285; AGC_KINASE_CTER; 1.
PROSITE; PS50004; C2; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PROSITE; PS00479; ZF_DAG_PE_1; 1.
PROSITE; PS50081; ZF_DAG_PE_2; 2.
2: Evidence at transcript level;
ATP-binding; Cell adhesion; Cell cycle; Cell division; Cell membrane;
Complete proteome; Cytoplasm; Cytoskeleton; Immunity; Kinase;
Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
Reference proteome; Repeat; Serine/threonine-protein kinase;
Transferase; Zinc; Zinc-finger.
CHAIN 1 736 Protein kinase C epsilon type.
/FTId=PRO_0000055699.
DOMAIN 1 99 C2. {ECO:0000255|PROSITE-
ProRule:PRU00041}.
DOMAIN 407 667 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
DOMAIN 668 736 AGC-kinase C-terminal.
ZN_FING 169 220 Phorbol-ester/DAG-type 1.
{ECO:0000255|PROSITE-ProRule:PRU00226}.
ZN_FING 242 292 Phorbol-ester/DAG-type 2.
{ECO:0000255|PROSITE-ProRule:PRU00226}.
NP_BIND 413 421 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ACT_SITE 531 531 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 436 436 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 62 62 Phosphoserine.
{ECO:0000250|UniProtKB:P16054}.
MOD_RES 228 228 Phosphothreonine.
{ECO:0000250|UniProtKB:Q02156}.
MOD_RES 234 234 Phosphoserine.
{ECO:0000250|UniProtKB:P16054}.
MOD_RES 309 309 Phosphothreonine.
{ECO:0000250|UniProtKB:Q02156}.
MOD_RES 316 316 Phosphoserine.
{ECO:0000250|UniProtKB:Q02156}.
MOD_RES 329 329 Phosphoserine.
{ECO:0000250|UniProtKB:Q02156}.
MOD_RES 337 337 Phosphoserine.
{ECO:0000250|UniProtKB:P16054}.
MOD_RES 346 346 Phosphoserine; by GSK3-beta.
{ECO:0000250|UniProtKB:Q02156}.
MOD_RES 349 349 Phosphothreonine.
{ECO:0000250|UniProtKB:P16054}.
MOD_RES 350 350 Phosphoserine; by MAPK11 and MAPK14.
{ECO:0000250|UniProtKB:P16054}.
MOD_RES 368 368 Phosphoserine; by autocatalysis.
{ECO:0000250|UniProtKB:Q02156}.
MOD_RES 388 388 Phosphoserine.
{ECO:0000250|UniProtKB:Q02156}.
MOD_RES 565 565 Phosphothreonine; by PDPK1.
{ECO:0000250|UniProtKB:Q02156}.
MOD_RES 702 702 Phosphothreonine; by autocatalysis.
{ECO:0000255}.
MOD_RES 709 709 Phosphothreonine; by autocatalysis.
{ECO:0000250|UniProtKB:Q02156,
ECO:0000255}.
MOD_RES 728 728 Phosphoserine; by autocatalysis.
{ECO:0000250|UniProtKB:Q02156}.
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


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Related Genes :
[PRKCE PKCE] Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon)
[PRKCE] Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon)
[Prkce Pkce Pkcea] Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon)
[Prkce Pkce] Protein kinase C epsilon type (EC 2.7.11.13) (nPKC-epsilon)
[PRKCD] Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)]
[PRKCQ PRKCT] Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta)
[Prkcd Pkcd] Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)]
[Prkcd Pkcd] Protein kinase C delta type (EC 2.7.11.13) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)]
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[Prkcz Pkcz] Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta)
[Ikbke Ikke Ikki] Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i)
[Prkcq Pkcq] Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta)
[Prkcq Pkcq] Protein kinase C theta type (EC 2.7.11.13) (nPKC-theta)
[Prkcz Pkcz] Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta)
[PRKD1 PKD PKD1 PRKCM] Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu)
[PRKCD] Protein kinase C delta type (EC 2.7.11.13) (Tyrosine-protein kinase PRKCD) (EC 2.7.10.2) (nPKC-delta) [Cleaved into: Protein kinase C delta type regulatory subunit; Protein kinase C delta type catalytic subunit (Sphingosine-dependent protein kinase-1) (SDK1)]
[Prkd1 Pkcm Pkd Prkcm] Serine/threonine-protein kinase D1 (EC 2.7.11.13) (Protein kinase C mu type) (Protein kinase D) (nPKC-D1) (nPKC-mu)
[PRKCI DXS1179E] Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (PRKC-lambda/iota) (aPKC-lambda/iota) (nPKC-iota)
[IKBKE IKKE IKKI KIAA0151] Inhibitor of nuclear factor kappa-B kinase subunit epsilon (I-kappa-B kinase epsilon) (IKK-E) (IKK-epsilon) (IkBKE) (EC 2.7.11.10) (Inducible I kappa-B kinase) (IKK-i)
[Prkci Pkcl] Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (aPKC-lambda/iota) (nPKC-iota)
[PRKCZ PKC2] Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta)
[PRKCZ] Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta)
[Prkci Pkcl] Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (aPKC-lambda/iota) (nPKC-iota)
[PRKCI] Protein kinase C iota type (EC 2.7.11.13) (nPKC-iota)
[Csnk1e] Casein kinase I isoform epsilon (CKI-epsilon) (CKIe) (EC 2.7.11.1)
[prkci hal] Protein kinase C iota type (EC 2.7.11.13) (Atypical protein kinase C-lambda/iota) (aPKC-lambda/iota) (Heart and soul protein) (nPKC-iota)
[hchA A8C65_13880 A9R57_25255 AKG99_20940 AMK83_16550 B7C53_22525 B9M99_11580 B9T59_01945 BJJ90_15205 BMT49_12710 BMT53_00170 BUE81_10670 BW690_17225 BZL69_29425 C2U48_24800 C5715_19445 C5N07_21380 C6669_19295 C7B06_02290 C7B07_03930 CDL37_00765 CG691_19145 CG705_13560 CG706_14580 CIJ94_05515 COD46_23180 CQP61_17160 CRD98_26150 CY655_12940 D5618_21870 D8K42_21280 D8Y29_11125 D9D20_21030 D9D43_06110 D9E22_21005 D9H68_20750 D9H70_25730 D9I87_15275 DL800_09215 DNQ41_14245 DQE83_22775 DTL43_21780 DTM25_06080 DU321_04440 E2855_02503 E2863_02392 EC95NR1_00961 ED648_25045 EFV01_02465 EFV04_09725 EOL36_23890 ERS085379_01273 ERS085386_05041 HMPREF3040_01583 HW43_13705 NCTC10082_04431 NCTC10418_03071 NCTC10767_03558 NCTC11022_01867 NCTC11126_04427 NCTC11181_05650 NCTC12950_02263 NCTC13462_05714 NCTC8985_00529 NCTC9111_05933 NCTC9112_02079 NCTC9703_00277 PU06_24500 SAMEA3472043_00447 SAMEA3472055_03589 SAMEA3472056_01268 SAMEA3472070_00654 SAMEA3472080_04213 SAMEA3472090_03376 SAMEA3472110_00060 SAMEA3472112_00448 SAMEA3752372_00752 UN91_23615 WQ89_10695] Protein/nucleic acid deglycase HchA (EC 3.1.2.-) (EC 3.5.1.-) (EC 3.5.1.124) (Maillard deglycase)
[CSNK1E] Casein kinase I isoform epsilon (CKI-epsilon) (CKIe) (EC 2.7.11.1)
[Ptpre Ptpe] Receptor-type tyrosine-protein phosphatase epsilon (Protein-tyrosine phosphatase epsilon) (R-PTP-epsilon) (EC 3.1.3.48)

Bibliography :
[19929130] Long-term pioglitazone treatment augments insulin sensitivity and PKC-epsilon and PKC-theta activation in skeletal muscles in sucrose fed rats.
[7512966] Human leukemia K562 cell mutant (K562/OA200) selected for resistance to okadaic acid (protein phosphatase inhibitor) lacks protein kinase C-epsilon, exhibits multidrug resistance phenotype, and expresses drug pump P-glycoprotein.
[1731907] Purification and characterization of protein kinase C epsilon from rabbit brain.