Q05513 · KPCZ_HUMAN

  • Protein
    Protein kinase C zeta type
  • Gene
    PRKCZ
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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'. Phosphorylates VAMP2 in vitro (PubMed:17313651).
Phosphorylates and activates LRRK1, which phosphorylates RAB proteins involved in intracellular trafficking (PubMed:36040231).

Isoform 2

Involved in late synaptic long term potention phase in CA1 hippocampal cells and long term memory maintenance.

Caution

Reported to phosphorylate STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis in vein endothelial cells treated with the oxidant peroxynitrite (PubMed:18321849).
However this paper was withdrawn by the authors due to concerns of image duplication in the figures. Its role in protein phosphorylation has been confirmed in other studies (PubMed:15084291, PubMed:15324659).

Catalytic activity

Activity 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).
Isoform 2: Constitutively active (By similarity).

Features

Showing features for binding site, active site.

Type
IDPosition(s)Description
Binding site258-266ATP (UniProtKB | ChEBI)
Binding site281ATP (UniProtKB | ChEBI)
Active site376Proton acceptor

GO annotations

AspectTerm
Cellular Componentapical cortex
Cellular Componentapical plasma membrane
Cellular Componentaxon hillock
Cellular Componentbicellular tight junction
Cellular Componentcell junction
Cellular Componentcell leading edge
Cellular Componentcell-cell junction
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentendosome
Cellular Componentextracellular exosome
Cellular Componentglutamatergic synapse
Cellular Componentmembrane
Cellular Componentmicrotubule organizing center
Cellular Componentmyelin sheath abaxonal region
Cellular Componentnuclear envelope
Cellular Componentnuclear matrix
Cellular ComponentPAR polarity complex
Cellular Componentperinuclear region of cytoplasm
Cellular Componentplasma membrane
Cellular Componentpostsynaptic density
Cellular ComponentSchaffer collateral - CA1 synapse
Cellular Componentstress fiber
Cellular Componenttight junction
Cellular Componentvesicle
Molecular Function14-3-3 protein binding
Molecular FunctionATP binding
Molecular Functioncalcium,diacylglycerol-dependent serine/threonine kinase activity
Molecular Functiondiacylglycerol-dependent serine/threonine kinase activity
Molecular Functiondiacylglycerol-dependent, calcium-independent serine/threonine kinase activity
Molecular Functioninsulin receptor substrate binding
Molecular Functionmetal ion binding
Molecular Functionphospholipase binding
Molecular Functionpotassium channel regulator activity
Molecular Functionprotein kinase activity
Molecular Functionprotein kinase binding
Molecular Functionprotein serine kinase activity
Molecular Functionprotein serine/threonine kinase activity
Molecular Functionprotein-containing complex binding
Biological Processcell migration
Biological Processcell surface receptor signaling pathway
Biological Processcellular response to insulin stimulus
Biological Processestablishment of cell polarity
Biological Processestablishment or maintenance of epithelial cell apical/basal polarity
Biological Processinflammatory response
Biological Processintracellular signal transduction
Biological Processlong-term memory
Biological Processlong-term synaptic potentiation
Biological Processmembrane depolarization
Biological Processmembrane hyperpolarization
Biological Processmicrotubule cytoskeleton organization
Biological Processnegative regulation of apoptotic process
Biological Processnegative regulation of insulin receptor signaling pathway
Biological Processnegative regulation of peptidyl-tyrosine phosphorylation
Biological Processnegative regulation of protein-containing complex assembly
Biological Processneuron projection extension
Biological Processpeptidyl-serine phosphorylation
Biological Processpositive regulation of cell population proliferation
Biological Processpositive regulation of cell-matrix adhesion
Biological Processpositive regulation of ERK1 and ERK2 cascade
Biological Processpositive regulation of excitatory postsynaptic potential
Biological Processpositive regulation of insulin receptor signaling pathway
Biological Processpositive regulation of interleukin-10 production
Biological Processpositive regulation of interleukin-13 production
Biological Processpositive regulation of interleukin-4 production
Biological Processpositive regulation of interleukin-5 production
Biological Processpositive regulation of NF-kappaB transcription factor activity
Biological Processpositive regulation of protein transport
Biological Processpositive regulation of T-helper 2 cell cytokine production
Biological Processpositive regulation of T-helper 2 cell differentiation
Biological Processprotein kinase C signaling
Biological Processprotein localization to plasma membrane
Biological Processprotein phosphorylation
Biological Processregulation of neurotransmitter receptor localization to postsynaptic specialization membrane
Biological Processsignal transduction
Biological Processvesicle transport along microtubule

Keywords

Enzyme and pathway databases

Protein family/group databases

Names & Taxonomy

Protein names

  • Recommended name
    Protein kinase C zeta type
  • EC number
  • Alternative names
    • nPKC-zeta

Gene names

    • Name
      PRKCZ
    • Synonyms
      PKC2

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q05513
  • Secondary accessions
    • A8K4N0
    • A8MU64
    • B7Z2J7
    • E9PCW2
    • Q15207

Proteomes

Organism-specific databases

Subcellular Location

Cytoplasm
Endosome
Cell junction
Membrane
; Peripheral membrane protein
Note: In the retina, localizes in the terminals of the rod bipolar cells (By similarity).
Associates with endosomes (PubMed:9566925).
Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction (PubMed:7597083).
Colocalizes with VAMP2 and WDFY2 in intracellular vesicles (PubMed:17313651).
Transiently translocates to the membrane of CA1 hippocampal cells in response to the induction of long term potentiation (By similarity).

Isoform 2

Cytoplasm

Keywords

Disease & Variants

Features

Showing features for mutagenesis, natural variant.

Type
IDPosition(s)Description
Mutagenesis19No effect on interaction with SQSTM1 and PARD6B.
Natural variantVAR_05056049in dbSNP:rs35271800
Mutagenesis62Loss of interaction with SQSTM1 and PARD6B.
Mutagenesis66Loss of interaction with SQSTM1 and PARD6B.
Natural variantVAR_04231084in dbSNP:rs56017162
Natural variantVAR_035467514in a colorectal cancer sample; somatic mutation
Natural variantVAR_042311519in a colorectal adenocarcinoma sample; somatic mutation; dbSNP:rs376894109

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 537 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for chain, modified residue (large scale data), modified residue.

Type
IDPosition(s)Source
Description
ChainPRO_00000557011-592UniProtProtein kinase C zeta type
Modified residue (large scale data)190PRIDEPhosphoserine
Modified residue (large scale data)223PRIDEPhosphoserine
Modified residue410UniProtPhosphothreonine; by PDPK1 and PI3K
Modified residue560UniProtPhosphothreonine
Modified residue (large scale data)560PRIDEPhosphothreonine
Modified residue591UniProtPhosphoserine
Modified residue (large scale data)591PRIDEPhosphoserine

Post-translational modification

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.

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Expressed in brain, and to a lesser extent in lung, kidney and testis.

Gene expression databases

Organism-specific databases

Interaction

Subunit

Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 (By similarity).
Interacts with PARD6A, PARD6B, PARD6G and SQSTM1. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Forms a ternary complex composed of SQSTM1 and PAWR. Interacts directly with SQSTM1 (Probable). Interacts with IKBKB. 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). Interacts with WDFY2 (via WD repeats 1-3) (PubMed:16792529).
Interacts with VAMP2 (PubMed:17313651).
Forms a complex with WDFY2 and VAMP2 (PubMed:17313651).
Interacts with APPL1 (PubMed:26583432).
Interacts with WWC1, WWC2 and WWC3 (PubMed:24682284).

Binary interactions

Complex viewer

View interactors in UniProtKB
View CPX-6195 in Complex Portal

Protein-protein interaction databases

Chemistry

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain, region, zinc finger.

Type
IDPosition(s)Description
Domain15-98PB1
Region79-145Interaction with SQSTM1
Zinc finger130-180Phorbol-ester/DAG-type
Domain252-518Protein kinase
Domain519-590AGC-kinase C-terminal

Domain

The PB1 domain mediate mutually exclusive interactions with SQSTM1 and PARD6B.
The C1 domain does not bind the diacylglycerol (DAG).

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete

This entry describes 3 isoforms produced by Alternative promoter usage & Alternative splicing.

Q05513-1

This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

  • Length
    592
  • Mass (Da)
    67,660
  • Last updated
    2005-06-21 v4
  • MD5 Checksum
    B70CA5932565C6B507515B708FA01636
MPSRTGPKMEGSGGRVRLKAHYGGDIFITSVDAATTFEELCEEVRDMCRLHQQHPLTLKWVDSEGDPCTVSSQMELEEAFRLARQCRDEGLIIHVFPSTPEQPGLPCPGEDKSIYRRGARRWRKLYRANGHLFQAKRFNRRAYCGQCSERIWGLARQGYRCINCKLLVHKRCHGLVPLTCRKHMDSVMPSQEPPVDDKNEDADLPSEETDGIAYISSSRKHDSIKDDSEDLKPVIDGMDGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRFLSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQALPPFQPQITDDYGLDNFDTQFTSEPVQLTPDDEDAIKRIDQSEFEGFEYINPLLLSTEESV

Q05513-2

  • Name
    2
  • Synonyms
    PKMzeta
  • Note
    Produced by alternative promoter usage.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q05513-3

  • Name
    3
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-112: MPSRTGPKMEGSGGRVRLKAHYGGDIFITSVDAATTFEELCEEVRDMCRLHQQHPLTLKWVDSEGDPCTVSSQMELEEAFRLARQCRDEGLIIHVFPSTPEQPGLPCPGEDK → MLTPRTDE

Computationally mapped potential isoform sequences

There are 15 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
J3KRP7J3KRP7_HUMANPRKCZ61
E9PBE1E9PBE1_HUMANPRKCZ347
D6RJG4D6RJG4_HUMANPRKCZ73
D6RG01D6RG01_HUMANPRKCZ82
D6REZ8D6REZ8_HUMANPRKCZ65
D6RGG1D6RGG1_HUMANPRKCZ109
D6RBD4D6RBD4_HUMANPRKCZ98
D6RAU1D6RAU1_HUMANPRKCZ136
D6RAN5D6RAN5_HUMANPRKCZ70
D6RDM0D6RDM0_HUMANPRKCZ73
D6RCN4D6RCN4_HUMANPRKCZ25
D6RD31D6RD31_HUMANPRKCZ21
D6RC84D6RC84_HUMANPRKCZ46
F2Z3C5F2Z3C5_HUMANPRKCZ181
F2Z2H9F2Z2H9_HUMANPRKCZ105

Sequence caution

The sequence CAA78813.1 differs from that shown. Reason: Erroneous initiation Truncated N-terminus.

Features

Showing features for alternative sequence, sequence conflict.

Type
IDPosition(s)Description
Alternative sequenceVSP_0463471-112in isoform 3
Alternative sequenceVSP_0419041-183in isoform 2
Sequence conflict6in Ref. 1; AAA36488
Sequence conflict198in Ref. 3; BAF83684
Sequence conflict262in Ref. 1; AAA36488
Sequence conflict281in Ref. 3; BAH11883
Sequence conflict366in Ref. 3; BAF83684
Sequence conflict500in Ref. 3; BAF83684
Sequence conflict522in Ref. 3; BAF83684

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
L14283
EMBL· GenBank· DDBJ
AAA36488.1
EMBL· GenBank· DDBJ
mRNA
BT007082
EMBL· GenBank· DDBJ
AAP35745.1
EMBL· GenBank· DDBJ
mRNA
AK290995
EMBL· GenBank· DDBJ
BAF83684.1
EMBL· GenBank· DDBJ
mRNA
AK294649
EMBL· GenBank· DDBJ
BAH11833.1
EMBL· GenBank· DDBJ
mRNA
AK294782
EMBL· GenBank· DDBJ
BAH11883.1
EMBL· GenBank· DDBJ
mRNA
AL162271
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL391845
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL590822
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
AL645703
EMBL· GenBank· DDBJ
-Genomic DNA No translation available.
BC008058
EMBL· GenBank· DDBJ
AAH08058.1
EMBL· GenBank· DDBJ
mRNA
BC014270
EMBL· GenBank· DDBJ
AAH14270.1
EMBL· GenBank· DDBJ
mRNA
Z15108
EMBL· GenBank· DDBJ
CAA78813.1
EMBL· GenBank· DDBJ
mRNA Different initiation

Genome annotation databases

Similar Proteins

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice.
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