Gene/Proteome Database (LMPD)

LMPD ID
LMP002054
Gene ID
5590
Species
Homo sapiens (Human)
Gene Name
protein kinase C, zeta
Gene Symbol
PRKCZ
Synonyms
PKC-ZETA; PKC2
Alternate Names
protein kinase C zeta type; nPKC-zeta
Chromosome
1
Map Location
1p36.33-p36.2
EC Number
2.7.11.13
Summary
Protein kinase C (PKC) zeta is a member of the PKC family of serine/threonine kinases which are involved in a variety of cellular processes such as proliferation, differentiation and secretion. Unlike the classical PKC isoenzymes which are calcium-dependent, PKC zeta exhibits a kinase activity which is independent of calcium and diacylglycerol but not of phosphatidylserine. Furthermore, it is insensitive to typical PKC inhibitors and cannot be activated by phorbol ester. Unlike the classical PKC isoenzymes, it has only a single zinc finger module. These structural and biochemical properties indicate that the zeta subspecies is related to, but distinct from other isoenzymes of PKC. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Orthologs
View orthologs and multiple alignments for PRKCZ

Proteins

protein kinase C zeta type isoform 1
Refseq ID NP_002735
Protein GI 52486327
UniProt ID Q05513
mRNA ID NM_002744
Length 592
RefSeq Status REVIEWED
MPSRTGPKMEGSGGRVRLKAHYGGDIFITSVDAATTFEELCEEVRDMCRLHQQHPLTLKWVDSEGDPCTVSSQMELEEAFRLARQCRDEGLIIHVFPSTPEQPGLPCPGEDKSIYRRGARRWRKLYRANGHLFQAKRFNRRAYCGQCSERIWGLARQGYRCINCKLLVHKRCHGLVPLTCRKHMDSVMPSQEPPVDDKNEDADLPSEETDGIAYISSSRKHDSIKDDSEDLKPVIDGMDGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRFLSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQALPPFQPQITDDYGLDNFDTQFTSEPVQLTPDDEDAIKRIDQSEFEGFEYINPLLLSTEESV
protein kinase C zeta type isoform 2
Refseq ID NP_001028753
Protein GI 75709226
UniProt ID Q05513
mRNA ID NM_001033581
Length 409
RefSeq Status REVIEWED
MDSVMPSQEPPVDDKNEDADLPSEETDGIAYISSSRKHDSIKDDSEDLKPVIDGMDGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRFLSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQALPPFQPQITDDYGLDNFDTQFTSEPVQLTPDDEDAIKRIDQSEFEGFEYINPLLLSTEESV
protein kinase C zeta type isoform 2
Refseq ID NP_001028754
Protein GI 75709228
UniProt ID Q05513
mRNA ID NM_001033582
Length 409
RefSeq Status REVIEWED
Protein sequence is identical to GI:75709226 (mRNA isoform)
protein kinase C zeta type isoform 3
Refseq ID NP_001229803
Protein GI 338968874
UniProt ID Q05513
mRNA ID NM_001242874
Length 488
RefSeq Status REVIEWED
MLTPRTDESIYRRGARRWRKLYRANGHLFQAKRFNRRAYCGQCSERIWGLARQGYRCINCKLLVHKRCHGLVPLTCRKHMDSVMPSQEPPVDDKNEDADLPSEETDGIAYISSSRKHDSIKDDSEDLKPVIDGMDGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRFLSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQALPPFQPQITDDYGLDNFDTQFTSEPVQLTPDDEDAIKRIDQSEFEGFEYINPLLLSTEESV

Gene Information

Entrez Gene ID
5590
Gene Name
protein kinase C, zeta
Gene Symbol
PRKCZ
Species
Homo sapiens

Gene Ontology (GO Annotations)

GO ID Source Type Description
GO:0045179 IEA:Ensembl C apical cortex
GO:0016324 IEA:Ensembl C apical plasma membrane
GO:0043203 IEA:Ensembl C axon hillock
GO:0005911 IDA:UniProtKB C cell-cell junction
GO:0030054 TAS:Reactome C cell junction
GO:0031252 IEA:Ensembl C cell leading edge
GO:0005737 TAS:ProtInc C cytoplasm
GO:0005829 IEA:Ensembl C cytosol
GO:0005768 IEA:UniProtKB-KW C endosome
GO:0070062 IDA:UniProt C extracellular vesicular exosome
GO:0016020 TAS:ProtInc C membrane
GO:0045121 IEA:Ensembl C membrane raft
GO:0005815 IEA:Ensembl C microtubule organizing center
GO:0035748 IEA:Ensembl C myelin sheath abaxonal region
GO:0005635 IEA:Ensembl C nuclear envelope
GO:0016363 IEA:Ensembl C nuclear matrix
GO:0048471 IEA:Ensembl C perinuclear region of cytoplasm
GO:0005886 TAS:ProtInc C plasma membrane
GO:0043234 IEA:Ensembl C protein complex
GO:0005923 IEA:Ensembl C tight junction
GO:0005524 IEA:UniProtKB-KW F ATP binding
GO:0043560 IC:BHF-UCL F insulin receptor substrate binding
GO:0015459 IEA:Ensembl F potassium channel regulator activity
GO:0004672 IDA:UniProtKB F protein kinase activity
GO:0004697 IEA:UniProtKB-EC F protein kinase C activity
GO:0004674 IDA:BHF-UCL F protein serine/threonine kinase activity
GO:0008270 IEA:InterPro F zinc ion binding
GO:0031532 IEA:Ensembl P actin cytoskeleton reorganization
GO:0031584 IEA:Ensembl P activation of phospholipase D activity
GO:0032148 IEA:Ensembl P activation of protein kinase B activity
GO:0007596 TAS:Reactome P blood coagulation
GO:0016477 IEA:Ensembl P cell migration
GO:0030010 ISS:UniProtKB P establishment of cell polarity
GO:0006954 IEA:UniProtKB-KW P inflammatory response
GO:0008286 IEA:Ensembl P insulin receptor signaling pathway
GO:0007616 IEA:Ensembl P long-term memory
GO:0060291 ISS:UniProtKB P long-term synaptic potentiation
GO:0060081 IEA:Ensembl P membrane hyperpolarization
GO:0000226 IEA:Ensembl P microtubule cytoskeleton organization
GO:0043066 TAS:ProtInc P negative regulation of apoptotic process
GO:0051346 IEA:Ensembl P negative regulation of hydrolase activity
GO:0046627 IMP:BHF-UCL P negative regulation of insulin receptor signaling pathway
GO:0050732 IMP:BHF-UCL P negative regulation of peptidyl-tyrosine phosphorylation
GO:0031333 IMP:BHF-UCL P negative regulation of protein complex assembly
GO:1990138 IEA:Ensembl P neuron projection extension
GO:0018105 IDA:BHF-UCL P peptidyl-serine phosphorylation
GO:0030168 TAS:Reactome P platelet activation
GO:0001954 IEA:Ensembl P positive regulation of cell-matrix adhesion
GO:0008284 IEA:Ensembl P positive regulation of cell proliferation
GO:0070374 IMP:UniProtKB P positive regulation of ERK1 and ERK2 cascade
GO:2000463 ISS:UniProtKB P positive regulation of excitatory postsynaptic membrane potential
GO:0046326 IEA:Ensembl P positive regulation of glucose import
GO:0046628 ISS:UniProtKB P positive regulation of insulin receptor signaling pathway
GO:2001181 ISS:UniProtKB P positive regulation of interleukin-10 secretion
GO:2000667 ISS:UniProtKB P positive regulation of interleukin-13 secretion
GO:0032753 ISS:UniProtKB P positive regulation of interleukin-4 production
GO:2000664 ISS:UniProtKB P positive regulation of interleukin-5 secretion
GO:0051092 ISS:UniProtKB P positive regulation of NF-kappaB transcription factor activity
GO:2000553 ISS:UniProtKB P positive regulation of T-helper 2 cell cytokine production
GO:0045630 ISS:UniProtKB P positive regulation of T-helper 2 cell differentiation
GO:0051291 IEA:Ensembl P protein heterooligomerization
GO:0070528 IEA:Ensembl P protein kinase C signaling
GO:0072659 IEA:Ensembl P protein localization to plasma membrane
GO:0006468 IDA:UniProtKB P protein phosphorylation
GO:0007165 TAS:ProtInc P signal transduction
GO:0007179 TAS:Reactome P transforming growth factor beta receptor signaling pathway
GO:0047496 IEA:Ensembl P vesicle transport along microtubule

KEGG Pathway Links

KEGG Pathway ID Description
hsa04390 Hippo signaling pathway
hsa04611 Platelet activation
hsa04015 Rap1 signaling pathway

Domain Information

InterPro Annotations

Accession Description
IPR000961 AGC-kinase, C-terminal
IPR020454 Diacylglycerol/phorbol-ester binding
IPR000270 Phox/Bem1p
IPR017441 Protein kinase, ATP binding site
IPR012233 Protein kinase C
IPR002219 Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
IPR017892 Protein kinase, C-terminal
IPR000719 Protein kinase domain
IPR011009 Protein kinase-like domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR008271 Serine/threonine-protein kinase, active site

UniProt Annotations

Entry Information

Gene Name
protein kinase C, zeta
Protein Entry
KPCZ_HUMAN
UniProt ID
Q05513
Species
Human

Comments

Comment Type Description
Alternative Products Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=Q05513-1; Sequence=Displayed; Name=2; IsoId=Q05513-2; Sequence=VSP_041904; Name=3; IsoId=Q05513-3; Sequence=VSP_046347; Note=No experimental confirmation available.;
Catalytic Activity ATP + a protein = ADP + a phosphoprotein.
Domain The C1 domain does not bind the diacylglycerol (DAG).
Domain The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B.
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).
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. {ECO
Interaction P31749:AKT1; NbExp=2; IntAct=EBI-295351, EBI-296087; Q9Y624:F11R; NbExp=2; IntAct=EBI-295351, EBI-742600; P08238:HSP90AB1; NbExp=2; IntAct=EBI-295351, EBI-352572; P49757-1:NUMB; NbExp=4; IntAct=EBI-295351, EBI-7199607; P16554:numb (xeno); NbExp=2; IntAct=EBI-295351, EBI-429581; Q9NPB6:PARD6A; NbExp=6; IntAct=EBI-295351, EBI-81876; Q9BYG5:PARD6B; NbExp=4; IntAct=EBI-295351, EBI-295391; Q9BYG4:PARD6G; NbExp=2; IntAct=EBI-295351, EBI-295417; P41743:PRKCI; NbExp=2; IntAct=EBI-295351, EBI-286199; Q04759:PRKCQ; NbExp=3; IntAct=EBI-295351, EBI-374762; P40337:VHL; NbExp=3; IntAct=EBI-295351, EBI-301246;
Ptm 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. {ECO
Sequence Caution Sequence=CAA78813.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence= ;
Similarity Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily.
Similarity Contains 1 AGC-kinase C-terminal domain.
Similarity Contains 1 OPR domain.
Similarity Contains 1 phorbol-ester/DAG-type zinc finger.
Similarity Contains 1 protein kinase domain.
Subcellular Location Cytoplasm. Endosome. Cell junction. Note=In the retina, localizes in the terminals of the rod bipolar cells (By similarity). Associates with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction.
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). {ECO
Tissue Specificity Expressed in brain, and to a lesser extent in lung, kidney and testis.

Identical and Related Proteins

Unique RefSeq proteins for LMP002054 (as displayed in Record Overview)

Protein GI Database Accession Length Protein Name
52486327 RefSeq NP_002735 592 protein kinase C zeta type isoform 1
75709226 RefSeq NP_001028753 409 protein kinase C zeta type isoform 2
338968874 RefSeq NP_001229803 488 protein kinase C zeta type isoform 3

Identical Sequences to LMP002054 proteins

Reference Database Accession Length Protein Name
GI:52486327 DBBJ BAG73606.1 592 protein kinase C zeta, partial [synthetic construct]
GI:52486327 GenBank ABM84848.1 592 protein kinase C, zeta, partial [synthetic construct]
GI:52486327 GenBank ABM87177.1 592 protein kinase C, zeta, partial [synthetic construct]
GI:52486327 GenBank ADS38995.1 592 Sequence 11 from patent US 7790854
GI:52486327 GenBank AIC49477.1 592 PRKCZ, partial [synthetic construct]
GI:52486327 GenBank AIC62579.1 592 PRKCZ, partial [synthetic construct]
GI:75709226 RefSeq XP_004024552.1 409 PREDICTED: protein kinase C zeta type-like isoform 1 [Gorilla gorilla gorilla]
GI:75709226 RefSeq XP_006710830.1 409 PREDICTED: protein kinase C zeta type isoform X4 [Homo sapiens]
GI:338968874 RefSeq XP_007979125.1 488 PREDICTED: protein kinase C zeta type isoform X2 [Chlorocebus sabaeus]
GI:75709226 RefSeq XP_007979127.1 409 PREDICTED: protein kinase C zeta type isoform X4 [Chlorocebus sabaeus]
GI:75709226 RefSeq XP_007979128.1 409 PREDICTED: protein kinase C zeta type isoform X4 [Chlorocebus sabaeus]
GI:75709226 RefSeq XP_007979129.1 409 PREDICTED: protein kinase C zeta type isoform X4 [Chlorocebus sabaeus]
GI:75709226 RefSeq XP_007979130.1 409 PREDICTED: protein kinase C zeta type isoform X4 [Chlorocebus sabaeus]

Related Sequences to LMP002054 proteins

Reference Database Accession Length Protein Name
GI:75709226 DBBJ BAG73606.1 592 protein kinase C zeta, partial [synthetic construct]
GI:338968874 DBBJ BAH11883.1 488 unnamed protein product [Homo sapiens]
GI:338968874 EMBL CAI45373.1 592 unnamed protein product [Homo sapiens]
GI:52486327 EMBL CAI45373.1 592 unnamed protein product [Homo sapiens]
GI:75709226 EMBL CAI45373.1 592 unnamed protein product [Homo sapiens]
GI:52486327 GenBank AAA36488.1 592 protein kinase C zeta [Homo sapiens]
GI:52486327 GenBank AAP36798.1 593 Homo sapiens protein kinase C, zeta, partial [synthetic construct]
GI:52486327 GenBank AAQ02396.1 593 protein kinase C, zeta, partial [synthetic construct]
GI:52486327 GenBank AAX29131.1 593 protein kinase C zeta, partial [synthetic construct]
GI:75709226 GenBank AAX32544.1 592 protein kinase C zeta [synthetic construct]
GI:338968874 GenBank AAX32544.1 592 protein kinase C zeta [synthetic construct]
GI:75709226 GenBank AAX32545.1 592 protein kinase C zeta [synthetic construct]
GI:52486327 GenBank ADC21463.1 592 Sequence 2 from patent US 7638482
GI:75709226 GenBank ADC21463.1 592 Sequence 2 from patent US 7638482
GI:338968874 GenBank ADC21463.1 592 Sequence 2 from patent US 7638482
GI:338968874 RefSeq XP_003939694.1 488 PREDICTED: protein kinase C zeta type isoform X2 [Saimiri boliviensis boliviensis]
GI:75709226 RefSeq XP_006710827.1 546 PREDICTED: protein kinase C zeta type isoform X1 [Homo sapiens]
GI:338968874 RefSeq XP_006710827.1 546 PREDICTED: protein kinase C zeta type isoform X1 [Homo sapiens]