P10830 (KPCE_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein kinase C epsilon type
EC=2.7.11.13

Alternative name(s):
nPKC-epsilon

Gene names

Name:

PRKCE

Organism

Oryctolagus cuniculus (Rabbit) [Complete proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	736 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

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.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme 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 structure	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.
Subcellular location	Cytoplasm By similarity. Cytoplasm › cytoskeleton By similarity. Cell membrane By similarity. Cytoplasm › perinuclear region By similarity. Nucleus By similarity. 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.
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.
Post-translational modification	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.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 C2 domain. Contains 2 phorbol-ester/DAG-type zinc fingers. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell adhesion Cell cycle Cell division Immunity
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Nucleus
Domain	Repeat Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 736	736	Protein kinase C epsilon type		PRO_0000055699
Regions
	Domain	1 – 99	99	C2
	Domain	407 – 667	261	Protein kinase
	Domain	668 – 736	69	AGC-kinase C-terminal
	Zinc finger	169 – 220	52	Phorbol-ester/DAG-type 1
	Zinc finger	242 – 292	51	Phorbol-ester/DAG-type 2
	Nucleotide binding	413 – 421	9	ATP By similarity
Sites
	Active site	531	1	Proton acceptor By similarity
	Binding site	436	1	ATP By similarity
Amino acid modifications
	Modified residue	228	1	Phosphothreonine By similarity
	Modified residue	234	1	Phosphoserine By similarity
	Modified residue	309	1	Phosphothreonine By similarity
	Modified residue	316	1	Phosphoserine By similarity
	Modified residue	329	1	Phosphoserine By similarity
	Modified residue	337	1	Phosphoserine By similarity
	Modified residue	339	1	Phosphoserine By similarity
	Modified residue	346	1	Phosphoserine; by GSK3-beta By similarity
	Modified residue	349	1	Phosphothreonine By similarity
	Modified residue	350	1	Phosphoserine; by MAPK11 and MAPK14 By similarity
	Modified residue	368	1	Phosphoserine; by autocatalysis By similarity
	Modified residue	565	1	Phosphothreonine; by PDPK1 By similarity
	Modified residue	702	1	Phosphothreonine; by autocatalysis Potential
	Modified residue	709	1	Phosphothreonine; by autocatalysis Potential
	Modified residue	728	1	Phosphoserine; by autocatalysis By similarity

Sequences

	Sequence		Length	Mass (Da)
	P10830 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 261C4FEE59E9BFEB	FASTA	736	83,516
	10 20 30 40 50 60 MVVFNGLLKI KICEAVSLKP TAWSLRHAVG PRPQTFLLDP YIALNVDDSR IGQTATKQKT 70 80 90 100 110 120 NSPAWHDEFV TDVCNGRKIE LAVFHDAPIG YDDFVANCTI QFEELLQNGS RHFEDWIDLE 130 140 150 160 170 180 PEGKVYVIID LSGSSGEAPK DNEERVFRER MRPRKRQGAV RRRVHQVNGH KFMATYLRQP 190 200 210 220 230 240 TYCSHCRDFI WGVIGKQGYQ CQVCTCVVHK RCHELIITKV AGLKKQETPD EVGSQRFSVN 250 260 270 280 290 300 MPHKFGIHNY KVPTFCDHCG SLLWGLLRQG LQCKVCKMNV HRRCETNVAP NCGVDARGIA 310 320 330 340 350 360 KVLADLGVTP DKITNSGQRR KKLIGGAESP QPTSGSSPSE EDRSKSAPTS PCDQELKELE 370 380 390 400 410 420 NNIRKALSFD NRGEEHRAAS STDGQLGSPE NGEVRQGQAK RLGLDEFNFI KVLGKGSFGK 430 440 450 460 470 480 VMLAELKGKD EVYAVKVLKK DVILQDDDVD CTMTEKRILA LARKHPYLTQ LYCCFQTKDR 490 500 510 520 530 540 LFFVMEYVNG GDLMFQIQRS RKFDEPRSRF YAAEVTSALM FLHQHGVIYR DLKLDNILLD 550 560 570 580 590 600 AEGHCKLADF GMCKEGILNG VTTTTFCGTP DYIAPEILQE LEYGPSVDWW ALGVLMYEMM 610 620 630 640 650 660 AGQPPFEADN EDDLFESILH DDVLYPVWLS KEAVSILKAF MTKNPHKRLG CVAAQNGEDA 670 680 690 700 710 720 IKQHPFFKEI DWVLLEQKKI KPPFKPRIKT KRDVNNFDQD FTREEPVLTL VDEAIVKQIN 730 QEEFKGFSYF GEDLMP

References

[1]	"A novel phorbol ester receptor/protein kinase, nPKC, distantly related to the protein kinase C family." Ohno S., Akita Y., Konno Y., Imajoh S., Suzuki K. Cell 53:731-741(1988) [PubMed: 3370672] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M20014 mRNA. Translation: AAA31426.1.
PIR	KIRBCE. A29880.
RefSeq	NP_001075743.1. NM_001082274.1.
UniGene	Ocu.1940.
3D structure databases
ProteinModelPortal	P10830.
SMR	P10830. Positions 1-136, 239-295, 404-735.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100009103.
Organism-specific databases
CTD	5581.
Phylogenomic databases
eggNOG	maNOG14735.
GeneTree	ENSGT00590000082973.
HOVERGEN	HBG108317.
OrthoDB	EOG40P467.
Enzyme and pathway databases
BRENDA	2.7.11.13. 1749.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR018029. C2_membr_targeting. IPR020454. DAG/PE-bd. IPR011009. Kinase-like_dom. IPR017892. Pkinase_C. IPR014376. Prot_kin_PKC_delta. IPR002219. Prot_Kinase_C-like_PE/DAG-bd. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
Pfam	PF00130. C1_1. 2 hits. PF00168. C2. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000551. PKC_delta. 1 hit.
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 2 hits. SM00239. C2. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF49562. C2_CaLB. 1 hit. SSF56112. Kinase_like. 1 hit.
PROSITE	PS51285. AGC_KINASE_CTER. 1 hit. PS50004. C2. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS00479. ZF_DAG_PE_1. 1 hit. PS50081. ZF_DAG_PE_2. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

KPCE_RABIT

Accession

Primary (citable) accession number: P10830

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	January 25, 2012
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program