O19111 (KPCZ_RABIT) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 111. History...
Names and origin
|Protein names||Recommended name:|
Protein kinase C zeta type
|Organism||Oryctolagus cuniculus (Rabbit) [Reference proteome]|
|Taxonomic identifier||9986 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus|
|Sequence length||591 AA.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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 By similarity.
ATP + a protein = ADP + a phosphoprotein.
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-409 (activation loop of the kinase domain) and Thr-559 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator By similarity.
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. Interacts directly with SQSTM1. 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-terminus region) By similarity.
Cytoplasm By similarity. Endosome By similarity. Cell junction By similarity. 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.
The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B By similarity.
The C1 domain does not bind the diacylglycerol (DAG).
CDH5 is required for its phosphorylation at Thr-409. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2. Phosphorylation at Thr-409 by PI3K activates the kinase By similarity.
Contains 1 AGC-kinase C-terminal domain.
Contains 1 OPR domain.
Contains 1 phorbol-ester/DAG-type zinc finger.
Contains 1 protein kinase domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 591||591||Protein kinase C zeta type||PRO_0000055703|
|Domain||15 – 98||84||OPR|
|Domain||251 – 517||267||Protein kinase|
|Domain||518 – 589||72||AGC-kinase C-terminal|
|Zinc finger||130 – 180||51||Phorbol-ester/DAG-type|
|Nucleotide binding||257 – 265||9||ATP By similarity|
|Region||79 – 145||67||Interaction with SQSTM1 By similarity|
|Active site||375||1||Proton acceptor By similarity|
|Binding site||280||1||ATP By similarity|
Amino acid modifications
|Modified residue||409||1||Phosphothreonine; by PDPK1 and PI3K By similarity|
|Modified residue||559||1||Phosphothreonine By similarity|
|U78768 mRNA. Translation: AAB67317.1.|
|RefSeq||NP_001076227.1. NM_001082758.1. |
3D structure databases
|SMR||O19111. Positions 12-98, 246-583. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
Enzyme and pathway databases
|BRENDA||126.96.36.199. 1749. |
Family and domain databases
|InterPro||IPR000961. AGC-kinase_C. |
|Pfam||PF00130. C1_1. 1 hit. |
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
|PIRSF||PIRSF000554. PKC_zeta. 1 hit. |
|PRINTS||PR00008. DAGPEDOMAIN. |
|SMART||SM00109. C1. 1 hit. |
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
|SUPFAM||SSF56112. SSF56112. 1 hit. |
|PROSITE||PS51285. AGC_KINASE_CTER. 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. 1 hit.
|Accession||Primary (citable) accession number: O19111|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families