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
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
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] |