PRKCZ - Protein kinase C zeta type - human protein (Function)
 
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PRKCZ »  Protein kinase C zeta type   [ EC 2.7.11.13 ]
 
Protein also known as:  nPKC-zeta.
Gene name:  PRKCZ
Entry whose protein(s) existence is based on evidence at protein level
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1 184 3
GENE REF ISO

Function

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Overview 
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 inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukins 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 NF-kappa-B-mediated inflammatory response, can relieve the SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Is necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells.  
5
  • CuratedUniProtKB
GO molecular function 
14-3-3 protein bindingdefinition[GO:0071889] silver  
  • IEAOrtholog Compara
ATP bindingdefinition[GO:0005524] silver  
  • IEAOrtholog Compara
Insulin receptor substrate bindingdefinition[GO:0043560]  
1
  • ICBHF-UCL
Phospholipase bindingdefinition[GO:0043274] silver  
  • IEAOrtholog Compara
Potassium channel regulator activitydefinition[GO:0015459] silver  
  • IEAOrtholog Compara
Protein bindingdefinition[GO:0005515]  
13
  • IPIIntAct
  • IPIUniProtKB
Protein domain specific bindingdefinition[GO:0019904] silver  
  • IEAOrtholog Compara
Protein kinase activitydefinition[GO:0004672]  
1
  • IDAUniProtKB
Protein kinase bindingdefinition[GO:0019901] silver  
  • IEAOrtholog Compara
Protein kinase C activitydefinition[GO:0004697]  
  • IEAEC 2 GO
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDABHF-UCL
Zinc ion bindingdefinition[GO:0008270] silver  
  • IEAInterPro 2 GO
GO biological process 
Actin cytoskeleton reorganizationdefinition[GO:0031532] silver  
  • IEAOrtholog Compara
Activation of phospholipase D activitydefinition[GO:0031584] silver  
  • IEAOrtholog Compara
Activation of protein kinase B activitydefinition[GO:0032148] silver  
  • IEAOrtholog Compara
Cell migrationdefinition[GO:0016477] silver  
  • IEAOrtholog Compara
Establishment of cell polaritydefinition[GO:0030010]  
  • ISSOrtholog Curator
Inflammatory responsedefinition[GO:0006954]  
  • IEAUniProtKB KW
Insulin receptor signaling pathwaydefinition[GO:0008286] silver  
  • IEAOrtholog Compara
Long-term memorydefinition[GO:0007616] silver  
  • IEAOrtholog Compara
Long-term synaptic potentiationdefinition[GO:0060291]  
  • ISSOrtholog Curator
Membrane hyperpolarizationdefinition[GO:0060081] silver  
  • IEAOrtholog Compara
Microtubule cytoskeleton organizationdefinition[GO:0000226] silver  
  • IEAOrtholog Compara
Negative regulation of apoptotic processdefinition[GO:0043066] silver  
  • IEAOrtholog Compara
Negative regulation of hydrolase activitydefinition[GO:0051346] silver  
  • IEAOrtholog Compara
Negative regulation of insulin receptor signaling pathwaydefinition[GO:0046627]  
1
  • IMPBHF-UCL
Negative regulation of peptidyl-tyrosine phosphorylationdefinition[GO:0050732]  
1
  • IMPBHF-UCL
Negative regulation of protein complex assemblydefinition[GO:0031333]  
1
  • IMPBHF-UCL
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDABHF-UCL
Positive regulation of cell proliferationdefinition[GO:0008284] silver  
  • IEAOrtholog Compara
Positive regulation of cell-matrix adhesiondefinition[GO:0001954] silver  
  • IEAOrtholog Compara
Positive regulation of ERK1 and ERK2 cascadedefinition[GO:0070374]  
1
  • IMPUniProtKB
Positive regulation of excitatory postsynaptic membrane potentialdefinition[GO:2000463]  
  • ISSOrtholog Curator
Positive regulation of glucose importdefinition[GO:0046326] silver  
  • IEAOrtholog Compara
Positive regulation of insulin receptor signaling pathwaydefinition[GO:0046628]  
  • ISSOrtholog Curator
Positive regulation of interleukin-10 secretiondefinition[GO:2001181]  
  • ISSOrtholog Curator
Positive regulation of interleukin-13 secretiondefinition[GO:2000667]  
  • ISSOrtholog Curator
Positive regulation of interleukin-4 productiondefinition[GO:0032753]  
  • ISSOrtholog Curator
Positive regulation of interleukin-5 secretiondefinition[GO:2000664]  
  • ISSOrtholog Curator
Positive regulation of NF-kappaB transcription factor activitydefinition[GO:0051092]  
  • ISSOrtholog Curator
Positive regulation of T-helper 2 cell cytokine productiondefinition[GO:2000553]  
  • ISSOrtholog Curator
Positive regulation of T-helper 2 cell differentiationdefinition[GO:0045630]  
  • ISSOrtholog Curator
Protein heterooligomerizationdefinition[GO:0051291] silver  
  • IEAOrtholog Compara
Protein kinase C signalingdefinition[GO:0070528] silver  
  • IEAOrtholog Compara
Protein localization to plasma membranedefinition[GO:0072659] silver  
  • IEAOrtholog Compara
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Vesicle transport along microtubuledefinition[GO:0047496] silver  
  • IEAOrtholog Compara
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.13: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
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).  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Chemokine signaling pathway  hsa04062+5590  
Endocytosis  hsa04144+5590  
Insulin signaling pathway  hsa04910+5590  
Tight junction  hsa04530+5590  
Type II diabetes mellitus  hsa04930+5590  
According to Reactome, this protein belongs to the following pathways:
Disease  REACT_116125  
Hemostasis  REACT_604  
Signal Transduction  REACT_111102  
 

Keywords

Biological process 
Inflammatory response  definition   [KW-0395]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Protein_kinase_M_zeta/Protein_kinase_C_zeta
GenomeRNAi: 5590
PRO: PR:Q05513
Chemistry
GuidetoPHARMACOLOGY: 1491