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O19111 (KPCZ_RABIT) Reviewed, UniProtKB/Swiss-Prot

Last modified October 16, 2013. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein kinase C zeta type

EC=2.7.11.13
Alternative name(s):
nPKC-zeta
Gene names
Name:PRKCZ
OrganismOryctolagus cuniculus (Rabbit) [Reference proteome]
Taxonomic identifier9986 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus

Protein attributes

Sequence length591 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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 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.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

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-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.

Subunit structure

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.

Subcellular location

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.

Domain

The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B By similarity.

The C1 domain does not bind the diacylglycerol (DAG).

Post-translational modification

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.

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.

Contains 1 AGC-kinase C-terminal domain.

Contains 1 OPR domain.

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processInflammatory response
   Cellular componentCell junction
Cytoplasm
Endosome
   DomainZinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processestablishment of cell polarity

Inferred from sequence or structural similarity. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

long-term synaptic potentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T-helper 2 cell cytokine production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of T-helper 2 cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of excitatory postsynaptic membrane potential

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-10 secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-13 secretion

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-4 production

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-5 secretion

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell-cell junction

Inferred from sequence or structural similarity. Source: UniProtKB

endosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase C activity

Inferred from electronic annotation. Source: UniProtKB-EC

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 591591Protein kinase C zeta type
PRO_0000055703

Regions

Domain15 – 9884OPR
Domain251 – 517267Protein kinase
Domain518 – 58972AGC-kinase C-terminal
Zinc finger130 – 18051Phorbol-ester/DAG-type
Nucleotide binding257 – 2659ATP By similarity
Region79 – 14567Interaction with SQSTM1 By similarity

Sites

Active site3751Proton acceptor By similarity
Binding site2801ATP By similarity

Amino acid modifications

Modified residue4091Phosphothreonine; by PDPK1 and PI3K By similarity
Modified residue5591Phosphothreonine By similarity

Sequences

Sequence LengthMass (Da)Tools
O19111 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 83D32A8744CADDB6

FASTA59167,095
        10         20         30         40         50         60 
MPSRAGPKMD GSGGRVRLKA HYSGDIFITS VDAATTFEEL CEEVRDMCGL HQHHPLTLKW 

        70         80         90        100        110        120 
VDSEGDPRTV SSQMELGEAF RLAGQHRDDG LILHVFPSTP EQPGMPCPGE DKSIYRRGAR 

       130        140        150        160        170        180 
RWRKLYRANG HLFQAKRFNR RAYCGQCSER IWGLARQGYR CINCKLLVHK RCHGLVPLTC 

       190        200        210        220        230        240 
RRHMDSVMPS QEPPVADKSD DADLPSQETD GIAFISTRKQ DSGQEDAEDL KPVIDGVDGI 

       250        260        270        280        290        300 
KISQGLGLQD FDLIRVIGRG SYAKVLLVRL KKNGQVYAMK VVKKELVHDD EDIDWVQTEK 

       310        320        330        340        350        360 
HVFEQASGNP FLVGLHSCFQ TTSRLFLVIE YVNGGDLMFH MQRQRKLPEE HARFYAAEIC 

       370        380        390        400        410        420 
IALNFLHERG IIYRDLKLDN VLLDADGHIK LTDYGMCKEG LGPGDTTSTF CGTPNYIAPE 

       430        440        450        460        470        480 
ILRGEEYGFS VDWWALGVLM FEMMAGRSPF DIITDNPDMN TEDYLFQVIL EKPIRIPRFL 

       490        500        510        520        530        540 
SVKASHVLKG FLNKDPKERL GCRPQTGFSD IKSHAFFRSI DWDLLEKKQA LPPFQPQITD 

       550        560        570        580        590 
DYGLDNSDTQ FTSEPVQLTP DDEDVIKRID QSEFEGFEYI NPLLLSTEES V 

« Hide

References

[1]"Intrarenal distribution of rabbit PKC zeta."
Hao C.-M., Breyer R.M., Davis L.S., Breyer M.D.
Kidney Int. 51:1831-1837(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: New Zealand white.
Tissue: Kidney.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U78768 mRNA. Translation: AAB67317.1.
RefSeqNP_001076227.1. NM_001082758.1.
UniGeneOcu.2166.

3D structure databases

ProteinModelPortalO19111.
SMRO19111. Positions 12-98, 246-583.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9986.ENSOCUP00000006125.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID100009538.

Organism-specific databases

CTD5590.

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG108317.

Enzyme and pathway databases

BRENDA2.7.11.13. 1749.

Family and domain databases

InterProIPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR000270. OPR_PB1.
IPR012233. PKC_zeta.
IPR017892. Pkinase_C.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000554. PKC_zeta. 1 hit.
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS51285. 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.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameKPCZ_RABIT
AccessionPrimary (citable) accession number: O19111
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: October 16, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families