Description: Homo sapiens protein kinase C, zeta (PRKCZ), transcript variant 1, mRNA. RefSeq Summary (NM_002744): 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]. Transcript (Including UTRs) Position: hg19 chr1:1,981,909-2,116,834 Size: 134,926 Total Exon Count: 18 Strand: + Coding Region Position: hg19 chr1:1,982,070-2,116,448 Size: 134,379 Coding Exon Count: 18
ID:KPCZ_HUMAN DESCRIPTION: RecName: Full=Protein kinase C zeta type; EC=2.7.11.13; AltName: Full=nPKC-zeta; 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 interleukines 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. 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-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). 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-terminus region). INTERACTION: Q9NPB6:PARD6A; NbExp=3; IntAct=EBI-295351, EBI-81876; Q9BYG5:PARD6B; NbExp=3; IntAct=EBI-295351, EBI-295391; Q04759:PRKCQ; NbExp=3; IntAct=EBI-295351, EBI-374762; 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. TISSUE SPECIFICITY: Expressed in brain, and to a lesser extent in lung, kidney and testis. DOMAIN: The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B. DOMAIN: The C1 domain does not bind the diacylglycerol (DAG). PTM: CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2. 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. SEQUENCE CAUTION: Sequence=CAA78813.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
Body Height Hana Lango Allen et al. Nature 2010, Hundreds of variants clustered in genomic loci and biological pathways affect human height., Nature.
[PubMed 20881960]
diabetes, type 2 Sun, H. X. et al. 2002, [Linkage disequilibrium analysis of the single nucleotide polymorphisms in the PRKCZ gene], Zhongguo yi xue ke xue yuan xue bao Acta Academiae Medicinae Sinicae. 2002 Oct;24(5):474-80.
[PubMed 12905768]
The haplotype formed by 5 SNPs in the PRKCZ gene may be associated with type 2 diabetes in Han population of China, which is confirmed from statistics to be a susceptibility gene for the disease.
diabetes, type 2 Sun, H. X. et al. 2002, [The association of two single nucleotide polymorphisms in PRKCZ and UTS2 respectively with type 2 diabetes in Han people of northern China], Zhongguo yi xue ke xue yuan xue bao Acta Academiae Medicinae Sinicae. 2002 Jun;24(3):223-7.
[PubMed 12905622]
The two SNP may be associated with type 2 diabetes in Han people of China, which makes base for further study of the relation between the genes they located with type 2 diabetes.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q05513
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
BC014270 - Homo sapiens protein kinase C, zeta, mRNA (cDNA clone MGC:10512 IMAGE:3835020), complete cds. BC008058 - Homo sapiens protein kinase C, zeta, mRNA (cDNA clone MGC:1669 IMAGE:2987996), complete cds. AB464093 - Synthetic construct DNA, clone: pF1KB6135, Homo sapiens PRKCZ gene for protein kinase C zeta, without stop codon, in Flexi system. DQ892929 - Synthetic construct clone IMAGE:100005559; FLH190935.01X; RZPDo839F0776D protein kinase C, zeta (PRKCZ) gene, encodes complete protein. DQ893922 - Synthetic construct Homo sapiens clone IMAGE:100008382; FLH165717.01L; RZPDo839F11159D protein kinase C, zeta (PRKCZ) gene, encodes complete protein. DQ896178 - Synthetic construct Homo sapiens clone IMAGE:100010638; FLH190932.01L; RZPDo839F0766D protein kinase C, zeta (PRKCZ) gene, encodes complete protein. KJ891890 - Synthetic construct Homo sapiens clone ccsbBroadEn_01284 PRKCZ gene, encodes complete protein. KJ905291 - Synthetic construct Homo sapiens clone ccsbBroadEn_14796 PRKCZ gene, encodes complete protein. BT007082 - Homo sapiens protein kinase C, zeta mRNA, complete cds. L14283 - Human protein kinase C zeta mRNA, complete cds. AK290995 - Homo sapiens cDNA FLJ76797 complete cds, highly similar to Homo sapiens protein kinase C, zeta (PRKCZ), mRNA. Z15108 - H.sapiens mRNA for protein kinase C zeta. DD327949 - ATYPICAL PROTEIN KINASE C ISOFORMS IN DISORDERS OF THE NERVOUS SYSTEM AND CANCER. AK294649 - Homo sapiens cDNA FLJ53316 complete cds, highly similar to Protein kinase C zeta type (EC 2.7.11.13). AK294782 - Homo sapiens cDNA FLJ54715 complete cds, highly similar to Protein kinase C zeta type (EC 2.7.11.13). AK097627 - Homo sapiens cDNA FLJ40308 fis, clone TESTI2029264, highly similar to Protein kinase C zeta type (EC 2.7.11.13). AK302160 - Homo sapiens cDNA FLJ60366 complete cds, highly similar to Protein kinase C zeta type (EC 2.7.11.13). JD143343 - Sequence 124367 from Patent EP1572962. JD190608 - Sequence 171632 from Patent EP1572962. CU675909 - Synthetic construct Homo sapiens gateway clone IMAGE:100017725 5' read PRKCZ mRNA. AK310372 - Homo sapiens cDNA, FLJ17414. DQ577590 - Homo sapiens piRNA piR-45702, complete sequence. AK131526 - Homo sapiens cDNA FLJ16754 fis, clone BRACE2047573, highly similar to Protein kinase C, zeta type (EC 2.7.1.-). JD259739 - Sequence 240763 from Patent EP1572962. JD351314 - Sequence 332338 from Patent EP1572962. JD404916 - Sequence 385940 from Patent EP1572962. JD140870 - Sequence 121894 from Patent EP1572962. JD216698 - Sequence 197722 from Patent EP1572962. JD276286 - Sequence 257310 from Patent EP1572962. JD445000 - Sequence 426024 from Patent EP1572962. JD470605 - Sequence 451629 from Patent EP1572962. JD161141 - Sequence 142165 from Patent EP1572962.
Biochemical and Signaling Pathways
KEGG - Kyoto Encyclopedia of Genes and Genomes hsa04062 - Chemokine signaling pathway hsa04144 - Endocytosis hsa04530 - Tight junction hsa04910 - Insulin signaling pathway hsa04930 - Type II diabetes mellitus
BioCarta from NCI Cancer Genome Anatomy Project h_ptdinsPathway - Phosphoinositides and their downstream targets.
Reactome (by CSHL, EBI, and GO)
Protein Q05513 (Reactome details) participates in the following event(s):
R-HSA-437192 PDK1 binds PKC zeta R-HSA-437195 PDK1 activates PKC zeta R-HSA-5218821 PDK1 phosphorylates PKC R-HSA-5218805 PKC autophosphorylates R-HSA-5218813 DAG and Ca+2 bind to PKC and tether it to membrane R-HSA-2134506 TGFBR1 is recruited to tight junctions by PARD6A R-NUL-2161147 TGFBR1 is recruited to tight junction by binding Pard6a R-HSA-2134519 TGFBR2 is recruited to tight junctions after TGF-beta stimulation R-HSA-2134532 TGFBR2 phosphorylates TGFBR1 and PARD6A R-HSA-2160932 SMURF1 binds phosphorylated PARD6A R-NUL-2161165 TGFBR2 phosphorylates Pard6a R-NUL-2161160 TGFBR2 is recruited to tight junctions-associated, Pard6a-bound, TGFBR1 after TGF-beta stimulation R-HSA-5218823 PKC phosphorylates sphingosine kinase 1 R-HSA-2160935 SMURF1 ubiquitinates RHOA R-HSA-114604 GPVI-mediated activation cascade R-HSA-5218921 VEGFR2 mediated cell proliferation R-HSA-76002 Platelet activation, signaling and aggregation R-HSA-4420097 VEGFA-VEGFR2 Pathway R-HSA-109582 Hemostasis R-HSA-2173791 TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) R-HSA-194138 Signaling by VEGF R-HSA-170834 Signaling by TGF-beta Receptor Complex R-HSA-9006934 Signaling by Receptor Tyrosine Kinases R-HSA-9006936 Signaling by TGF-beta family members R-HSA-162582 Signal Transduction
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