KPCZ_RABIT
ID KPCZ_RABIT Reviewed; 591 AA.
AC O19111;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Protein kinase C zeta type;
DE EC=2.7.11.13 {ECO:0000250|UniProtKB:Q05513};
DE AltName: Full=nPKC-zeta;
GN Name=PRKCZ;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=New Zealand white; TISSUE=Kidney;
RX PubMed=9186872; DOI=10.1038/ki.1997.250;
RA Hao C.-M., Breyer R.M., Davis L.S., Breyer M.D.;
RT "Intrarenal distribution of rabbit PKC zeta.";
RL Kidney Int. 51:1831-1837(1997).
CC -!- FUNCTION: Calcium- and diacylglycerol-independent serine/threonine-
CC protein kinase that functions in phosphatidylinositol 3-kinase (PI3K)
CC pathway and mitogen-activated protein (MAP) kinase cascade, and is
CC involved in NF-kappa-B activation, mitogenic signaling, cell
CC proliferation, cell polarity, inflammatory response and maintenance of
CC long-term potentiation (LTP). Upon lipopolysaccharide (LPS) treatment
CC in macrophages, or following mitogenic stimuli, functions downstream of
CC PI3K to activate MAP2K1/MEK1-MAPK1/ERK2 signaling cascade independently
CC of RAF1 activation. Required for insulin-dependent activation of AKT3,
CC but may function as an adapter rather than a direct activator. Upon
CC insulin treatment may act as a downstream effector of PI3K and
CC contribute to the activation of translocation of the glucose
CC transporter SLC2A4/GLUT4 and subsequent glucose transport in
CC adipocytes. In EGF-induced cells, binds and activates MAP2K5/MEK5-
CC MAPK7/ERK5 independently of its kinase activity and can activate JUN
CC promoter through MEF2C. Through binding with SQSTM1/p62, functions in
CC interleukin-1 signaling and activation of NF-kappa-B with the specific
CC adapters RIPK1 and TRAF6. Participates in TNF-dependent transactivation
CC of NF-kappa-B by phosphorylating and activating IKBKB kinase, which in
CC turn leads to the degradation of NF-kappa-B inhibitors. In migrating
CC astrocytes, forms a cytoplasmic complex with PARD6A and is recruited by
CC CDC42 to function in the establishment of cell polarity along with the
CC microtubule motor and dynein. In association with FEZ1, stimulates
CC neuronal differentiation in PC12 cells. In the inflammatory response,
CC is required for the T-helper 2 (Th2) differentiation process, including
CC interleukin production, efficient activation of JAK1 and the subsequent
CC phosphorylation and nuclear translocation of STAT6. May be involved in
CC development of allergic airway inflammation (asthma), a process
CC dependent on Th2 immune response. In the NF-kappa-B-mediated
CC inflammatory response, can relieve SETD6-dependent repression of NF-
CC kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'.
CC Phosphorylates VAMP2 in vitro (By similarity).
CC {ECO:0000250|UniProtKB:P09217, ECO:0000250|UniProtKB:Q05513}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.13;
CC Evidence={ECO:0000250|UniProtKB:Q05513};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.13; Evidence={ECO:0000250|UniProtKB:Q05513};
CC -!- ACTIVITY REGULATION: Atypical PKCs (PRKCI and PRKCZ) exhibit an
CC elevated basal enzymatic activity (that may be due to the interaction
CC with SMG1 or SQSTM1) and are not regulated by diacylglycerol,
CC phosphatidylserine, phorbol esters or calcium ions. Two specific sites,
CC Thr-409 (activation loop of the kinase domain) and Thr-559 (turn
CC motif), need to be phosphorylated for its full activation.
CC Phosphatidylinositol 3,4,5-trisphosphate might be a physiological
CC activator (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with PARD6A, PARD6B and PARD6G. Part of a complex
CC with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts
CC with ADAP1/CENTA1. Interacts directly with SQSTM1. Forms a ternary
CC complex with SQSTM1 and KCNAB2. Forms another ternary complex with
CC SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5. Interacts
CC (via the protein kinase domain) with WWC1. Forms a tripartite complex
CC with WWC1 and DDR1, but predominantly in the absence of collagen.
CC Component of the Par polarity complex, composed of at least
CC phosphorylated PRKCZ, PARD3 and TIAM1. Interacts with PDPK1 (via N-
CC terminal region). Interacts with WDFY2 (via WD repeats 1-3). Interacts
CC with VAMP2. Forms a complex with WDFY2 and VAMP2. Interacts with APPL1
CC (By similarity). {ECO:0000250|UniProtKB:P09217,
CC ECO:0000250|UniProtKB:Q05513}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q05513}.
CC Endosome {ECO:0000250|UniProtKB:Q05513}. Cell junction
CC {ECO:0000250|UniProtKB:Q05513}. Membrane
CC {ECO:0000250|UniProtKB:P09217}; Peripheral membrane protein
CC {ECO:0000305}. Note=In the retina, localizes in the terminals of the
CC rod bipolar cells (By similarity). Associated with endosomes (By
CC similarity). Presence of KRIT1, CDH5 and RAP1B is required for its
CC localization to the cell junction (By similarity). Colocalizes with
CC VAMP2 and WDFY2 in intracellular vesicles (By similarity). Transiently
CC translocates to the membrane of CA1 hippocampal cells in response to
CC the induction of long term potentiation (By similarity).
CC {ECO:0000250|UniProtKB:P09217, ECO:0000250|UniProtKB:Q05513}.
CC -!- DOMAIN: The PB1 domain mediate mutually exclusive interactions with
CC SQSTM1 and PARD6B. {ECO:0000250}.
CC -!- DOMAIN: The C1 domain does not bind the diacylglycerol (DAG).
CC -!- PTM: CDH5 is required for its phosphorylation at Thr-409.
CC Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by
CC the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at
CC Thr-409 by PI3K activates the kinase (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. AGC Ser/Thr
CC protein kinase family. PKC subfamily. {ECO:0000305}.
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DR EMBL; U78768; AAB67317.1; -; mRNA.
DR RefSeq; NP_001076227.1; NM_001082758.1.
DR AlphaFoldDB; O19111; -.
DR SMR; O19111; -.
DR PRIDE; O19111; -.
DR GeneID; 100009538; -.
DR KEGG; ocu:100009538; -.
DR CTD; 5590; -.
DR eggNOG; KOG0695; Eukaryota.
DR InParanoid; O19111; -.
DR OrthoDB; 614710at2759; -.
DR BRENDA; 2.7.11.13; 1749.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004698; F:calcium-dependent protein kinase C activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0030010; P:establishment of cell polarity; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:UniProtKB.
DR GO; GO:0046628; P:positive regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:UniProtKB.
DR GO; GO:0032736; P:positive regulation of interleukin-13 production; ISS:UniProtKB.
DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISS:UniProtKB.
DR GO; GO:0032754; P:positive regulation of interleukin-5 production; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:2000553; P:positive regulation of T-helper 2 cell cytokine production; ISS:UniProtKB.
DR GO; GO:0045630; P:positive regulation of T-helper 2 cell differentiation; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR CDD; cd00029; C1; 1.
DR CDD; cd06404; PB1_aPKC; 1.
DR InterPro; IPR000961; AGC-kinase_C.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR034877; PB1_aPKC.
DR InterPro; IPR000270; PB1_dom.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR012233; PKC.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF00564; PB1; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PIRSF; PIRSF000554; PKC_zeta; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00666; PB1; 1.
DR SMART; SM00133; S_TK_X; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS51285; AGC_KINASE_CTER; 1.
DR PROSITE; PS51745; PB1; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell junction; Cytoplasm; Endosome; Inflammatory response;
KW Kinase; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..591
FT /note="Protein kinase C zeta type"
FT /id="PRO_0000055703"
FT DOMAIN 15..98
FT /note="PB1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT DOMAIN 251..517
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 518..589
FT /note="AGC-kinase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00618"
FT ZN_FING 130..180
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 79..145
FT /note="Interaction with SQSTM1"
FT /evidence="ECO:0000250"
FT ACT_SITE 375
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 257..265
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 280
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 409
FT /note="Phosphothreonine; by PDPK1 and PI3K"
FT /evidence="ECO:0000250|UniProtKB:Q05513"
FT MOD_RES 559
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q05513"
FT MOD_RES 590
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09217"
SQ SEQUENCE 591 AA; 67095 MW; 83D32A8744CADDB6 CRC64;
MPSRAGPKMD GSGGRVRLKA HYSGDIFITS VDAATTFEEL CEEVRDMCGL HQHHPLTLKW
VDSEGDPRTV SSQMELGEAF RLAGQHRDDG LILHVFPSTP EQPGMPCPGE DKSIYRRGAR
RWRKLYRANG HLFQAKRFNR RAYCGQCSER IWGLARQGYR CINCKLLVHK RCHGLVPLTC
RRHMDSVMPS QEPPVADKSD DADLPSQETD GIAFISTRKQ DSGQEDAEDL KPVIDGVDGI
KISQGLGLQD FDLIRVIGRG SYAKVLLVRL KKNGQVYAMK VVKKELVHDD EDIDWVQTEK
HVFEQASGNP FLVGLHSCFQ TTSRLFLVIE YVNGGDLMFH MQRQRKLPEE HARFYAAEIC
IALNFLHERG IIYRDLKLDN VLLDADGHIK LTDYGMCKEG LGPGDTTSTF CGTPNYIAPE
ILRGEEYGFS VDWWALGVLM FEMMAGRSPF DIITDNPDMN TEDYLFQVIL EKPIRIPRFL
SVKASHVLKG FLNKDPKERL GCRPQTGFSD IKSHAFFRSI DWDLLEKKQA LPPFQPQITD
DYGLDNSDTQ FTSEPVQLTP DDEDVIKRID QSEFEGFEYI NPLLLSTEES V
