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Protein

Protein kinase C zeta type

Gene

PRKCZ

Organism
Oryctolagus cuniculus (Rabbit)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

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. Phosphorylates VAMP2 in vitro (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Enzyme regulationi

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-409 (activation loop of the kinase domain) and Thr-559 (turn motif), need to be phosphorylated for its full activation. Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei280ATPPROSITE-ProRule annotation1
Active sitei375Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri130 – 180Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51
Nucleotide bindingi257 – 265ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processInflammatory response
LigandATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.11.13. 1749.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein kinase C zeta type (EC:2.7.11.13)
Alternative name(s):
nPKC-zeta
Gene namesi
Name:PRKCZ
OrganismiOryctolagus cuniculus (Rabbit)
Taxonomic identifieri9986 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresLagomorphaLeporidaeOryctolagus
Proteomesi
  • UP000001811 Componenti: Unplaced

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell junction, Cytoplasm, Endosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000557031 – 591Protein kinase C zeta typeAdd BLAST591

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei409Phosphothreonine; by PDPK1 and PI3KBy similarity1
Modified residuei559PhosphothreonineBy similarity1
Modified residuei590PhosphoserineBy similarity1

Post-translational modificationi

CDH5 is required for its phosphorylation at Thr-409. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminal cleavage product of PKN2. Phosphorylation at Thr-409 by PI3K activates the kinase (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Interactioni

Subunit structurei

Interacts with PARD6A, PARD6B and PARD6G. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with ADAP1/CENTA1. Interacts directly with SQSTM1. Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5. 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). Interacts with VAMP2. Forms a complex with WDFY2 and VAMP2.By similarity

Protein-protein interaction databases

STRINGi9986.ENSOCUP00000006125.

Structurei

3D structure databases

ProteinModelPortaliO19111.
SMRiO19111.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 98PB1PROSITE-ProRule annotationAdd BLAST84
Domaini251 – 517Protein kinasePROSITE-ProRule annotationAdd BLAST267
Domaini518 – 589AGC-kinase C-terminalAdd BLAST72

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni79 – 145Interaction with SQSTM1By similarityAdd BLAST67

Domaini

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

Sequence similaritiesi

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri130 – 180Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST51

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0695. Eukaryota.
ENOG410ZMG2. LUCA.
HOVERGENiHBG108317.
InParanoidiO19111.
KOiK18952.

Family and domain databases

CDDicd00029. C1. 1 hit.
cd06404. PB1_aPKC. 1 hit.
InterProiView protein in InterPro
IPR000961. AGC-kinase_C.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom_sf.
IPR034877. PB1_aPKC.
IPR000270. PB1_dom.
IPR002219. PE/DAG-bd.
IPR012233. PKC.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00130. C1_1. 1 hit.
PF00564. PB1. 1 hit.
PF00069. Pkinase. 1 hit.
PIRSFiPIRSF000554. PKC_zeta. 1 hit.
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiView protein in SMART
SM00109. C1. 1 hit.
SM00666. PB1. 1 hit.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS51285. AGC_KINASE_CTER. 1 hit.
PS51745. PB1. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.

Sequencei

Sequence statusi: Complete.

O19111-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPSRAGPKMD GSGGRVRLKA HYSGDIFITS VDAATTFEEL CEEVRDMCGL
60 70 80 90 100
HQHHPLTLKW VDSEGDPRTV SSQMELGEAF RLAGQHRDDG LILHVFPSTP
110 120 130 140 150
EQPGMPCPGE DKSIYRRGAR RWRKLYRANG HLFQAKRFNR RAYCGQCSER
160 170 180 190 200
IWGLARQGYR CINCKLLVHK RCHGLVPLTC RRHMDSVMPS QEPPVADKSD
210 220 230 240 250
DADLPSQETD GIAFISTRKQ DSGQEDAEDL KPVIDGVDGI KISQGLGLQD
260 270 280 290 300
FDLIRVIGRG SYAKVLLVRL KKNGQVYAMK VVKKELVHDD EDIDWVQTEK
310 320 330 340 350
HVFEQASGNP FLVGLHSCFQ TTSRLFLVIE YVNGGDLMFH MQRQRKLPEE
360 370 380 390 400
HARFYAAEIC IALNFLHERG IIYRDLKLDN VLLDADGHIK LTDYGMCKEG
410 420 430 440 450
LGPGDTTSTF CGTPNYIAPE ILRGEEYGFS VDWWALGVLM FEMMAGRSPF
460 470 480 490 500
DIITDNPDMN TEDYLFQVIL EKPIRIPRFL SVKASHVLKG FLNKDPKERL
510 520 530 540 550
GCRPQTGFSD IKSHAFFRSI DWDLLEKKQA LPPFQPQITD DYGLDNSDTQ
560 570 580 590
FTSEPVQLTP DDEDVIKRID QSEFEGFEYI NPLLLSTEES V
Length:591
Mass (Da):67,095
Last modified:January 1, 1998 - v1
Checksum:i83D32A8744CADDB6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U78768 mRNA. Translation: AAB67317.1.
RefSeqiNP_001076227.1. NM_001082758.1.
UniGeneiOcu.2166.

Genome annotation databases

GeneIDi100009538.
KEGGiocu:100009538.

Similar proteinsi

Entry informationi

Entry nameiKPCZ_RABIT
AccessioniPrimary (citable) accession number: O19111
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: January 1, 1998
Last modified: November 22, 2017
This is version 133 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families