Names & Taxonomy

Uniprot ID:
Q05513
Entry Name:
KPCZ_HUMAN
Status:
reviewed
Protein Names:
Protein kinase C zeta type (EC 2.7.11.13) (nPKC-zeta)
Gene Names:
PRKCZ PKC2
Gene Names Primary:
PRKCZ
Organism:
Homo sapiens (Human)

Structure

Length:
592
Sequence:
MPSRTGPKMEGSGGRVRLKAHYGGDIFITSVDAATTFEELCEEVRDMCRLHQQHPLTLKWVDSEGDPCTVSSQMELEEAFRLARQCRDEGLIIHVFPSTPEQPGLPCPGEDKSIYRRGARRWRKLYRANGHLFQAKRFNRRAYCGQCSERIWGLARQGYRCINCKLLVHKRCHGLVPLTCRKHMDSVMPSQEPPVDDKNEDADLPSEETDGIAYISSSRKHDSIKDDSEDLKPVIDGMDGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRFLSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQALPPFQPQITDDYGLDNFDTQFTSEPVQLTPDDEDAIKRIDQSEFEGFEYINPLLLSTEESV
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cytoplasm

Function

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. Phosphorylates VAMP2 in vitro (PubMed:17313651).
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.
Enzyme Regulation:
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).
Active Site:
ACT_SITE 376 376 Proton acceptor.
Cross Reference Drug Bank:
DB00675
Gene Ontology Go:
apical cortex
apical plasma membrane
axon hillock
bicellular tight junction
cell junction
cell leading edge
cell-cell junction
cytoplasm
cytosol
endosome
extracellular exosome
filamentous actin
membrane
membrane raft
microtubule organizing center
myelin sheath abaxonal region
nuclear envelope
nuclear matrix
perinuclear region of cytoplasm
plasma membrane
vesicle
ATP binding
insulin receptor substrate binding
metal ion binding
potassium channel regulator activity
protein kinase activity
protein kinase C activity
protein serine/threonine kinase activity
actin cytoskeleton reorganization
activation of phospholipase D activity
activation of protein kinase B activity
blood coagulation
cell migration
establishment of cell polarity
inflammatory response
insulin receptor signaling pathway
intracellular signal transduction
long-term memory
long-term synaptic potentiation
membrane depolarization
membrane hyperpolarization
microtubule cytoskeleton organization
negative regulation of apoptotic process
negative regulation of hydrolase activity
negative regulation of insulin receptor signaling pathway
negative regulation of peptidyl-tyrosine phosphorylation
negative regulation of protein complex assembly
neuron projection extension
peptidyl-serine phosphorylation
platelet activation
positive regulation of cell proliferation
positive regulation of cell-matrix adhesion
positive regulation of ERK1 and ERK2 cascade
positive regulation of excitatory postsynaptic potential
positive regulation of glucose import
positive regulation of insulin receptor signaling pathway
positive regulation of interleukin-10 secretion
positive regulation of interleukin-13 secretion
positive regulation of interleukin-4 production
positive regulation of interleukin-5 secretion
positive regulation of NF-kappaB transcription factor activity
positive regulation of T-helper 2 cell cytokine production
positive regulation of T-helper 2 cell differentiation
protein heterooligomerization
protein kinase C signaling
protein localization to plasma membrane
protein phosphorylation
signal transduction
transforming growth factor beta receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
vesicle transport along microtubule
Gene Ontology Biological Process:
actin cytoskeleton reorganization
activation of phospholipase D activity
activation of protein kinase B activity
blood coagulation
cell migration
establishment of cell polarity
inflammatory response
insulin receptor signaling pathway
intracellular signal transduction
long-term memory
long-term synaptic potentiation
membrane depolarization
membrane hyperpolarization
microtubule cytoskeleton organization
negative regulation of apoptotic process
negative regulation of hydrolase activity
negative regulation of insulin receptor signaling pathway
negative regulation of peptidyl-tyrosine phosphorylation
negative regulation of protein complex assembly
neuron projection extension
peptidyl-serine phosphorylation
platelet activation
positive regulation of cell-matrix adhesion
positive regulation of cell proliferation
positive regulation of ERK1 and ERK2 cascade
positive regulation of excitatory postsynaptic potential
positive regulation of glucose import
positive regulation of insulin receptor signaling pathway
positive regulation of interleukin-10 secretion
positive regulation of interleukin-13 secretion
positive regulation of interleukin-4 production
positive regulation of interleukin-5 secretion
positive regulation of NF-kappaB transcription factor activity
positive regulation of T-helper 2 cell cytokine production
positive regulation of T-helper 2 cell differentiation
protein heterooligomerization
protein kinase C signaling
protein localization to plasma membrane
protein phosphorylation
signal transduction
transforming growth factor beta receptor signaling pathway
vascular endothelial growth factor receptor signaling pathway
vesicle transport along microtubule
Gene Ontology Molecular Function:
ATP binding
insulin receptor substrate binding
metal ion binding
potassium channel regulator activity
protein kinase activity
protein kinase C activity
protein serine/threonine kinase activity
Gene Ontology Cellular Component:
apical cortex
apical plasma membrane
axon hillock
bicellular tight junction
cell-cell junction
cell junction
cell leading edge
cytoplasm
cytosol
endosome
extracellular exosome
filamentous actin
membrane
membrane raft
microtubule organizing center
myelin sheath abaxonal region
nuclear envelope
nuclear matrix
perinuclear region of cytoplasm
plasma membrane
vesicle
Keywords:
ATP-binding
Alternative splicing
Cell junction
Complete proteome
Cytoplasm
Endosome
Inflammatory response
Kinase
Metal-binding
Nucleotide-binding
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transferase
Zinc
Zinc-finger
Interacts With:
P31749; O95999; Q07021; Q9Y624; P08238; P49757-1; P16554; Q9NPB6; Q9BYG5; Q9BYG4; P41743; Q04759; P40337

Publication

PubMed ID:
8224878 14702039 16710414 15489334 8375396 7597083 9447975 9566925 9768361 10356400 11035106 11260256 11781095 12162751 11755531 12234671 12893243 12887891 15084291 15324659 15314172 16792529 17313651 18190796 18321849 18691976 18669648 20332120 12761192 16903823 16322752 21269460 24275569 16959974 17344846