Gene/Proteome Database (LMPD)

LMPD ID
LMP012518
Gene ID
Species
Rattus norvegicus (Rat)
Gene Name
protein kinase C, zeta
Gene Symbol
Synonyms
Pkcz; r14-3-3; 14-3-3-zetaisoform;
Alternate Names
protein kinase C zeta type; nPKC-zeta; 14 - 3 - 3 - zeta isoform;
Chromosome
5
Map Location
5q36
EC Number
2.7.11.13
Summary
may play an important role in insulin resistance in skeletal muscle and adipose tissue; mediates matrix metalloproteinase-9 (MMP-9) expression in glioma cells, key process in tumor invasion, through NF-kappaB [RGD, Feb 2006]
Orthologs

Proteins

protein kinase C zeta type
Refseq ID NP_071952
Protein GI 11968080
UniProt ID P09217
mRNA ID NM_022507
Length 592
MPSRTDPKMDRSGGRVRLKAHYGGDILITSVDPTTTFQDLCEEVRDMCGLHQQHPLTLKWVDSEGDPCTVSSQMELEEAFRLACQGRDEVLIIHVFPSIPEQPGMPCPGEDKSIYRRGARRWRKLYRANGHLFQAKRFNRRAYCGQCSERIWGLARQGYRCINCKLLVHKRCHVLVPLTCRRHMDSVMPSQEPPVDDKNDGVDLPSEETDGIAYISSSRKHDNIKDDSEDLKPVIDGVDGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRFLSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQTLPPFQPQITDDYGLDNFDTQFTSEPVQLTPDDEDVIKRIDQSEFEGFEYINPLLLSAEESV

Gene Information

Entrez Gene ID
Gene Name
protein kinase C, zeta
Gene Symbol
Species
Rattus norvegicus

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0045179 IEA:Ensembl C apical cortex
GO:0016324 IEA:Ensembl C apical plasma membrane
GO:0043203 IEA:Ensembl C axon hillock
GO:0031252 IDA:RGD C cell leading edge
GO:0005911 ISS:UniProtKB C cell-cell junction
GO:0005737 IDA:RGD C cytoplasm
GO:0005829 IDA:RGD C cytosol
GO:0005768 IEA:UniProtKB-KW C endosome
GO:0070062 IEA:Ensembl C extracellular vesicular exosome
GO:0043231 IDA:RGD C intracellular membrane-bounded organelle
GO:0045121 IDA:RGD C membrane raft
GO:0005815 IEA:Ensembl C microtubule organizing center
GO:0035748 IEA:Ensembl C myelin sheath abaxonal region
GO:0005635 IEA:Ensembl C nuclear envelope
GO:0016363 IEA:Ensembl C nuclear matrix
GO:0048471 IDA:RGD C perinuclear region of cytoplasm
GO:0005886 IDA:UniProtKB C plasma membrane
GO:0043234 IDA:RGD C protein complex
GO:0005923 IEA:Ensembl C tight junction
GO:0071889 IPI:RGD F 14-3-3 protein binding
GO:0005524 IDA:RGD F ATP binding
GO:0043274 IPI:RGD F phospholipase binding
GO:0015459 IMP:RGD F potassium channel regulator activity
GO:0019904 IPI:RGD F protein domain specific binding
GO:0004697 IDA:RGD F protein kinase C activity
GO:0004672 TAS:RGD F protein kinase activity
GO:0019901 IPI:RGD F protein kinase binding
GO:0004674 IDA:RGD F protein serine/threonine kinase activity
GO:0008270 IEA:InterPro F zinc ion binding
GO:0031532 IMP:RGD P actin cytoskeleton reorganization
GO:0031584 IMP:RGD P activation of phospholipase D activity
GO:0032148 IMP:RGD P activation of protein kinase B activity
GO:0016477 IMP:RGD P cell migration
GO:0007166 IMP:RGD P cell surface receptor signaling pathway
GO:0034613 IMP:RGD P cellular protein localization
GO:0032869 IMP:RGD P cellular response to insulin stimulus
GO:0030010 IMP:UniProtKB P establishment of cell polarity
GO:0006954 IEA:UniProtKB-KW P inflammatory response
GO:0008286 IMP:RGD P insulin receptor signaling pathway
GO:0035556 IDA:RGD P intracellular signal transduction
GO:0007616 IMP:RGD P long-term memory
GO:0060291 IMP:UniProtKB P long-term synaptic potentiation
GO:0051899 IMP:RGD P membrane depolarization
GO:0060081 IMP:RGD P membrane hyperpolarization
GO:0000226 IEA:Ensembl P microtubule cytoskeleton organization
GO:0043066 IDA:RGD P negative regulation of apoptotic process
GO:0051346 IDA:RGD P negative regulation of hydrolase activity
GO:0046627 IEA:Ensembl P negative regulation of insulin receptor signaling pathway
GO:0050732 IEA:Ensembl P negative regulation of peptidyl-tyrosine phosphorylation
GO:0031333 IEA:Ensembl P negative regulation of protein complex assembly
GO:1990138 IEA:Ensembl P neuron projection extension
GO:0018105 IDA:RGD P peptidyl-serine phosphorylation
GO:0070374 IMP:UniProtKB P positive regulation of ERK1 and ERK2 cascade
GO:0051092 IMP:UniProtKB P positive regulation of NF-kappaB transcription factor activity
GO:2000553 ISS:UniProtKB P positive regulation of T-helper 2 cell cytokine production
GO:0045630 ISS:UniProtKB P positive regulation of T-helper 2 cell differentiation
GO:0008284 IMP:RGD P positive regulation of cell proliferation
GO:0001954 IMP:RGD P positive regulation of cell-matrix adhesion
GO:2000463 IDA:UniProtKB P positive regulation of excitatory postsynaptic membrane potential
GO:0046326 IMP:RGD P positive regulation of glucose import
GO:0046628 IMP:UniProtKB P positive regulation of insulin receptor signaling pathway
GO:2001181 ISS:UniProtKB P positive regulation of interleukin-10 secretion
GO:2000667 ISS:UniProtKB P positive regulation of interleukin-13 secretion
GO:0032753 ISS:UniProtKB P positive regulation of interleukin-4 production
GO:2000664 ISS:UniProtKB P positive regulation of interleukin-5 secretion
GO:0051222 IMP:RGD P positive regulation of protein transport
GO:0050806 IMP:RGD P positive regulation of synaptic transmission
GO:0051291 IPI:RGD P protein heterooligomerization
GO:0070528 IMP:RGD P protein kinase C signaling
GO:0072659 IEA:Ensembl P protein localization to plasma membrane
GO:0006468 IDA:RGD P protein phosphorylation
GO:0007165 IDA:RGD P signal transduction
GO:0047496 IMP:RGD P vesicle transport along microtubule

KEGG Pathway Links

KEGG Pathway ID Description
ko04062 Chemokine signaling pathway
rno04062 Chemokine signaling pathway
ko04144 Endocytosis
rno04144 Endocytosis
ko04390 Hippo signaling pathway
rno04390 Hippo signaling pathway
ko04910 Insulin signaling pathway
rno04910 Insulin signaling pathway
ko04151 PI3K-Akt signaling pathway
rno04151 PI3K-Akt signaling pathway
rno04611 Platelet activation
ko04015 Rap1 signaling pathway
rno04015 Rap1 signaling pathway
ko04530 Tight junction
rno04530 Tight junction
ko04930 Type II diabetes mellitus
rno04930 Type II diabetes mellitus

REACTOME Pathway Links

REACTOME Pathway ID Description
5953253 Disease
5953651 GPVI-mediated activation cascade
5953645 Hemostasis
5953818 Loss of Function of SMAD2/3 in Cancer
5953821 Loss of Function of SMAD4 in Cancer
5953827 Loss of Function of TGFBR1 in Cancer
5953824 Loss of Function of TGFBR2 in Cancer
5953644 Platelet activation, signaling and aggregation
5953822 SMAD2/3 MH2 Domain Mutants in Cancer
5953817 SMAD2/3 Phosphorylation Motif Mutants in Cancer
5953820 SMAD4 MH2 Domain Mutants in Cancer
5953381 Signal Transduction
5953816 Signaling by TGF-beta Receptor Complex
5953819 Signaling by TGF-beta Receptor Complex in Cancer
5953420 Signaling by VEGF
5954545 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition)
5953826 TGFBR1 KD Mutants in Cancer
5953828 TGFBR1 LBD Mutants in Cancer
5953825 TGFBR2 Kinase Domain Mutants in Cancer
5953823 TGFBR2 MSI Frameshift Mutants in Cancer
5953419 VEGFA-VEGFR2 Pathway
5953418 VEGFR2 mediated cell proliferation

Domain Information

InterPro Annotations

Accession Description
IPR000961 AGC-kinase, C-terminal
IPR020454 Diacylglycerol/phorbol-ester binding
IPR000270 Phox/Bem1p
IPR012233 Protein kinase C
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR000719 Protein kinase domain
IPR017441 Protein kinase, ATP binding site
IPR017892 Protein kinase, C-terminal
IPR011009 Protein kinase-like domain
IPR008271 Serine/threonine-protein kinase, active site
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain

UniProt Annotations

Entry Information

Gene Name
protein kinase C, zeta
Protein Entry
KPCZ_RAT
UniProt ID
Species
Rat

Comments

Comment Type Description
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Domain The C1 domain does not bind the diacylglycerol (DAG)
Domain The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B
Enzyme Regulation Atypical PKCs (PRKCI and PRKCZ) exhibit an elevated basal enzymatic activity (that may be due to the interaction with SMG1 or SQSTM1) and are not regulated by diacylglycerol, phosphatidylserine, phorbol esters or calcium ions. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator (By similarity)
Function Calcium- and diacylglycerol-independent serine/threonine-protein kinase that functions in phosphatidylinositol 3-kinase (PI3K) pathway and mitogen-activated protein (MAP) kinase cascade, and is involved in NF-kappa-B activation, mitogenic signaling, cell proliferation, cell polarity, inflammatory response and maintenance of long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment in macrophages, or following mitogenic stimuli, functions downstream of PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently of RAF1 activation. Required for insulin-dependent activation of AKT3, but may function as an adapter rather than a direct activator. Upon insulin treatment may act as a downstream effector of PI3K and contribute to the activation of translocation of the glucose transporter SLC2A4/GLUT4 and subsequent glucose transport in adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-MAPK7/ERK5 independently of its kinase activity and can activate JUN promoter through MEF2C. Through binding with SQSTM1/p62, functions in interleukin-1 signaling and activation of NF-kappa-B with the specific adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in turn leads to the degradation of NF-kappa-B inhibitors. In migrating astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by CDC42 to function in the establishment of cell polarity along with the microtubule motor and dynein. In association with FEZ1, stimulates neuronal differentiation in PC12 cells. In the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin production, efficient activation of JAK1 and the subsequent phosphorylation and nuclear translocation of STAT6. May be involved in development of allergic airway inflammation (asthma), a process dependent on Th2 immune response. In the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. {ECO:0000269|PubMed:10022904, ECO:0000269|PubMed:10747026, ECO:0000269|PubMed:11158308, ECO:0000269|PubMed:11525734, ECO:0000269|PubMed:11914719, ECO:0000269|PubMed:8378304, ECO:0000269|PubMed:8557035, ECO:0000269|PubMed:9177193, ECO:0000269|PubMed:9374484}.
Ptm CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase (By similarity)
Similarity Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily
Similarity Contains 1 AGC-kinase C-terminal domain
Similarity Contains 1 OPR domain
Similarity Contains 1 phorbol-ester/DAG-type zinc finger
Similarity Contains 1 protein kinase domain
Subcellular Location Cytoplasm {ECO:0000269|PubMed:12431995, ECO:0000269|PubMed:9177193}. Endosome . Cell junction . Note=In the retina, localizes in the terminals of the rod bipolar cells. Associated with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction (By similarity)
Subunit Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1 (By similarity). Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5. Interacts (via the protein kinase domain) with WWC1. Forms a tripartite complex with WWC1 and DDR1, but predominantly in the absence of collagen. Component of the Par polarity complex, composed of at least phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with PDPK1 (via N-terminal region) (By similarity)

Identical and Related Proteins

Unique RefSeq proteins for LMP012518 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
11968080 RefSeq NP_071952 592 protein kinase C zeta type

Identical Sequences to LMP012518 proteins

Reference Database Accession Length Protein Name
GI:11968080 GenBank AAA41934.1 592 protein kinase C, zeta subspecies [Rattus norvegicus]
GI:11968080 GenBank EDL81295.1 592 protein kinase C, zeta, isoform CRA_c [Rattus norvegicus]
GI:11968080 SwissProt P09217.2 592 RecName: Full=Protein kinase C zeta type; AltName: Full=nPKC-zeta [Rattus norvegicus]

Related Sequences to LMP012518 proteins

Reference Database Accession Length Protein Name
GI:11968080 GenBank AAA41934.1 592 protein kinase C, zeta subspecies [Rattus norvegicus]
GI:11968080 GenBank EDL81295.1 592 protein kinase C, zeta, isoform CRA_c [Rattus norvegicus]
GI:11968080 SwissProt P09217.2 592 RecName: Full=Protein kinase C zeta type; AltName: Full=nPKC-zeta [Rattus norvegicus]