O19111 (KPCZ_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Protein kinase C zeta type
EC=2.7.11.13

Alternative name(s):
nPKC-zeta

Gene names

Name:

PRKCZ

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	591 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

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 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 By similarity.
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-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.
Subunit structure	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-terminus region) By similarity.
Subcellular location	Cytoplasm By similarity. Endosome By similarity. Cell junction By similarity. Note: In the retina, localizes in the terminals of the rod bipolar cells. Associated with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction By similarity.
Domain	The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B By similarity. The C1 domain does not bind the diacylglycerol (DAG).
Post-translational modification	CDH5 is required for its phosphorylation at Thr-409. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2. Phosphorylation at Thr-409 by PI3K activates the kinase By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. Contains 1 AGC-kinase C-terminal domain. Contains 1 OPR domain. Contains 1 phorbol-ester/DAG-type zinc finger. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Inflammatory response
Cellular component	Cell junction Cytoplasm Endosome
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	establishment of cell polarity Inferred from sequence or structural similarity. Source: UniProtKB inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW intracellular signal transduction Inferred from electronic annotation. Source: InterPro long-term synaptic potentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of ERK1 and ERK2 cascade Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of T-helper 2 cell cytokine production Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of T-helper 2 cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of excitatory postsynaptic membrane potential Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-10 secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-13 secretion Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-4 production Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of interleukin-5 secretion Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cell-cell junction Inferred from sequence or structural similarity. Source: UniProtKB endosome Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase C activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 591	591	Protein kinase C zeta type		PRO_0000055703
Regions
	Domain	15 – 98	84	OPR
	Domain	251 – 517	267	Protein kinase
	Domain	518 – 589	72	AGC-kinase C-terminal
	Zinc finger	130 – 180	51	Phorbol-ester/DAG-type
	Nucleotide binding	257 – 265	9	ATP By similarity
	Region	79 – 145	67	Interaction with SQSTM1 By similarity
Sites
	Active site	375	1	Proton acceptor By similarity
	Binding site	280	1	ATP By similarity
Amino acid modifications
	Modified residue	409	1	Phosphothreonine; by PDPK1 and PI3K By similarity
	Modified residue	559	1	Phosphothreonine By similarity

Sequences

	Sequence		Length	Mass (Da)
	O19111 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 83D32A8744CADDB6	FASTA	591	67,095
	10 20 30 40 50 60 MPSRAGPKMD GSGGRVRLKA HYSGDIFITS VDAATTFEEL CEEVRDMCGL HQHHPLTLKW 70 80 90 100 110 120 VDSEGDPRTV SSQMELGEAF RLAGQHRDDG LILHVFPSTP EQPGMPCPGE DKSIYRRGAR 130 140 150 160 170 180 RWRKLYRANG HLFQAKRFNR RAYCGQCSER IWGLARQGYR CINCKLLVHK RCHGLVPLTC 190 200 210 220 230 240 RRHMDSVMPS QEPPVADKSD DADLPSQETD GIAFISTRKQ DSGQEDAEDL KPVIDGVDGI 250 260 270 280 290 300 KISQGLGLQD FDLIRVIGRG SYAKVLLVRL KKNGQVYAMK VVKKELVHDD EDIDWVQTEK 310 320 330 340 350 360 HVFEQASGNP FLVGLHSCFQ TTSRLFLVIE YVNGGDLMFH MQRQRKLPEE HARFYAAEIC 370 380 390 400 410 420 IALNFLHERG IIYRDLKLDN VLLDADGHIK LTDYGMCKEG LGPGDTTSTF CGTPNYIAPE 430 440 450 460 470 480 ILRGEEYGFS VDWWALGVLM FEMMAGRSPF DIITDNPDMN TEDYLFQVIL EKPIRIPRFL 490 500 510 520 530 540 SVKASHVLKG FLNKDPKERL GCRPQTGFSD IKSHAFFRSI DWDLLEKKQA LPPFQPQITD 550 560 570 580 590 DYGLDNSDTQ FTSEPVQLTP DDEDVIKRID QSEFEGFEYI NPLLLSTEES V

References

[1]	"Intrarenal distribution of rabbit PKC zeta." Hao C.-M., Breyer R.M., Davis L.S., Breyer M.D. Kidney Int. 51:1831-1837(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: New Zealand white. Tissue: Kidney.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U78768 mRNA. Translation: AAB67317.1.
RefSeq	NP_001076227.1. NM_001082758.1.
UniGene	Ocu.2166.
3D structure databases
ProteinModelPortal	O19111.
SMR	O19111. Positions 12-98, 246-583.
ModBase	Search...
Protein-protein interaction databases
STRING	9986.ENSOCUP00000006125.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	100009538.
Organism-specific databases
CTD	5590.
Phylogenomic databases
eggNOG	COG0515.
HOVERGEN	HBG108317.
Enzyme and pathway databases
BRENDA	2.7.11.13. 1749.
Family and domain databases
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. [Graphical view]
Pfam	PF00130. C1_1. 1 hit. PF00564. PB1. 1 hit. PF00069. Pkinase. 1 hit. PF00433. Pkinase_C. 1 hit. [Graphical view]
PIRSF	PIRSF000554. PKC_zeta. 1 hit.
PRINTS	PR00008. DAGPEDOMAIN.
SMART	SM00109. C1. 1 hit. SM00666. PB1. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS51285. AGC_KINASE_CTER. 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. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

KPCZ_RABIT

Accession

Primary (citable) accession number: O19111

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 1, 1998
Last modified:	April 3, 2013
This is version 109 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program