CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011291
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Protein kinase C zeta type 
Protein Synonyms/Alias
 nPKC-zeta 
Gene Name
 PRKCZ 
Gene Synonyms/Alias
 PKC2 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
273VLLVRLKKNDQIYAMubiquitination[1]
Reference
 [1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 15 98 OPR.
 DOMAIN 252 518 Protein kinase.
 DOMAIN 519 590 AGC-kinase C-terminal.
 ZN_FING 130 180 Phorbol-ester/DAG-type.
 NP_BIND 258 266 ATP (By similarity).
 REGION 79 145 Interaction with SQSTM1 (By similarity).
 ACT_SITE 376 376 Proton acceptor (By similarity).
 BINDING 281 281 ATP (By similarity).
 MOD_RES 410 410 Phosphothreonine; by PDPK1 and PI3K.
 MOD_RES 560 560 Phosphothreonine.  
Keyword
 Alternative splicing; ATP-binding; Cell junction; Complete proteome; Cytoplasm; Endosome; Inflammatory response; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 592 AA 
Protein Sequence
MPSRTGPKME GSGGRVRLKA HYGGDIFITS VDAATTFEEL CEEVRDMCRL HQQHPLTLKW 60
VDSEGDPCTV SSQMELEEAF RLARQCRDEG LIIHVFPSTP EQPGLPCPGE DKSIYRRGAR 120
RWRKLYRANG HLFQAKRFNR RAYCGQCSER IWGLARQGYR CINCKLLVHK RCHGLVPLTC 180
RKHMDSVMPS QEPPVDDKNE DADLPSEETD GIAYISSSRK HDSIKDDSED LKPVIDGMDG 240
IKISQGLGLQ DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE 300
KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE EHARFYAAEI 360
CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE GLGPGDTTST FCGTPNYIAP 420
EILRGEEYGF SVDWWALGVL MFEMMAGRSP FDIITDNPDM NTEDYLFQVI LEKPIRIPRF 480
LSVKASHVLK GFLNKDPKER LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ ALPPFQPQIT 540
DDYGLDNFDT QFTSEPVQLT PDDEDAIKRI DQSEFEGFEY INPLLLSTEE SV 592 
Gene Ontology
 GO:0045179; C:apical cortex; IEA:Compara.
 GO:0016324; C:apical plasma membrane; IEA:Compara.
 GO:0031252; C:cell leading edge; IEA:Compara.
 GO:0005911; C:cell-cell junction; IDA:UniProtKB.
 GO:0005737; C:cytoplasm; TAS:ProtInc.
 GO:0005829; C:cytosol; IEA:Compara.
 GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
 GO:0045121; C:membrane raft; IEA:Compara.
 GO:0035748; C:myelin sheath abaxonal region; IEA:Compara.
 GO:0005635; C:nuclear envelope; IEA:Compara.
 GO:0016363; C:nuclear matrix; IEA:Compara.
 GO:0048471; C:perinuclear region of cytoplasm; IEA:Compara.
 GO:0005886; C:plasma membrane; TAS:ProtInc.
 GO:0043234; C:protein complex; IEA:Compara.
 GO:0005923; C:tight junction; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0043560; F:insulin receptor substrate binding; IC:BHF-UCL.
 GO:0015459; F:potassium channel regulator activity; IEA:Compara.
 GO:0004697; F:protein kinase C activity; IEA:EC.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0031532; P:actin cytoskeleton reorganization; IEA:Compara.
 GO:0031584; P:activation of phospholipase D activity; IEA:Compara.
 GO:0032148; P:activation of protein kinase B activity; IEA:Compara.
 GO:0016477; P:cell migration; IEA:Compara.
 GO:0030010; P:establishment of cell polarity; ISS:UniProtKB.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0008286; P:insulin receptor signaling pathway; IEA:Compara.
 GO:0007616; P:long-term memory; IEA:Compara.
 GO:0060291; P:long-term synaptic potentiation; ISS:UniProtKB.
 GO:0060081; P:membrane hyperpolarization; IEA:Compara.
 GO:0000226; P:microtubule cytoskeleton organization; IEA:Compara.
 GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
 GO:0051346; P:negative regulation of hydrolase activity; IEA:Compara.
 GO:0046627; P:negative regulation of insulin receptor signaling pathway; IMP:BHF-UCL.
 GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL.
 GO:0031333; P:negative regulation of protein complex assembly; IMP:BHF-UCL.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
 GO:0030168; P:platelet activation; TAS:Reactome.
 GO:0008284; P:positive regulation of cell proliferation; IEA:Compara.
 GO:0001954; P:positive regulation of cell-matrix adhesion; IEA:Compara.
 GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:UniProtKB.
 GO:2000463; P:positive regulation of excitatory postsynaptic membrane potential; ISS:UniProtKB.
 GO:0046326; P:positive regulation of glucose import; IEA:Compara.
 GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISS:UniProtKB.
 GO:2001181; P:positive regulation of interleukin-10 secretion; ISS:UniProtKB.
 GO:2000667; P:positive regulation of interleukin-13 secretion; ISS:UniProtKB.
 GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
 GO:2000664; P:positive regulation of interleukin-5 secretion; ISS:UniProtKB.
 GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
 GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISS:UniProtKB.
 GO:0045630; P:positive regulation of T-helper 2 cell differentiation; ISS:UniProtKB.
 GO:0051291; P:protein heterooligomerization; IEA:Compara.
 GO:0070528; P:protein kinase C signaling cascade; IEA:Compara.
 GO:0072659; P:protein localization to plasma membrane; IEA:Compara.
 GO:0007179; P:transforming growth factor beta receptor signaling pathway; TAS:Reactome.
 GO:0047496; P:vesicle transport along microtubule; IEA:Compara. 
Interpro
 IPR000961; 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_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 
Pfam
 PF00130; C1_1
 PF00564; PB1
 PF00069; Pkinase
 PF00433; Pkinase_C 
SMART
 SM00109; C1
 SM00666; PB1
 SM00133; S_TK_X
 SM00220; S_TKc 
PROSITE
 PS51285; AGC_KINASE_CTER
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS00479; ZF_DAG_PE_1
 PS50081; ZF_DAG_PE_2 
PRINTS
 PR00008; DAGPEDOMAIN.