P09217 (KPCZ_RAT) 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
Synonyms:	Pkcz

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	592 AA.
Sequence status	Complete.
Protein existence	Evidence at protein 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 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. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
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 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 By similarity. 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 PDK1 (via N-terminus region) By similarity. Ref.7 Ref.13 Ref.14
Subcellular location	Cytoplasm. 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. Ref.7 Ref.13
Domain	The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B By similarity. Ref.7 The C1 domain does not bind the diacylglycerol (DAG). Ref.7
Post-translational modification	CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDK1; phosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2 By similarity. Ref.15
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	actin cytoskeleton reorganization Inferred from mutant phenotype. Source: RGD activation of phospholipase D activity Inferred from mutant phenotype. Source: RGD activation of protein kinase B activity Inferred from mutant phenotype. Source: RGD cell migration Inferred from mutant phenotype. Source: RGD cellular protein localization Inferred from mutant phenotype. Source: RGD insulin receptor signaling pathway Inferred from mutant phenotype. Source: RGD long-term memory Inferred from mutant phenotype. Source: RGD membrane depolarization Inferred from mutant phenotype. Source: RGD membrane hyperpolarization Inferred from mutant phenotype. Source: RGD negative regulation of apoptotic process Inferred from direct assay. Source: RGD negative regulation of hydrolase activity Inferred from direct assay. Source: RGD peptidyl-serine phosphorylation Inferred from direct assay. Source: RGD positive regulation of cell proliferation Inferred from mutant phenotype. Source: RGD positive regulation of cell-matrix adhesion Inferred from mutant phenotype. Source: RGD positive regulation of glucose import Inferred from mutant phenotype. Source: RGD positive regulation of protein transport Inferred from mutant phenotype. Source: RGD positive regulation of synaptic transmission Inferred from mutant phenotype. Source: RGD protein kinase C signaling cascade Inferred from mutant phenotype. Source: RGD vesicle transport along microtubule Inferred from mutant phenotype. Source: RGD
Cellular component	cell leading edge Inferred from direct assay. Source: RGD cytosol Inferred from direct assay. Source: RGD endosome Inferred from electronic annotation. Source: UniProtKB-SubCell membrane raft Inferred from direct assay. Source: RGD microsome Inferred from direct assay. Source: RGD perinuclear region of cytoplasm Inferred from direct assay. Source: RGD protein complex Inferred from direct assay. Source: RGD
Molecular function	14-3-3 protein binding Inferred from physical interaction. Source: RGD ATP binding Inferred from direct assay. Source: RGD phospholipase binding Inferred from physical interaction. Source: RGD potassium channel regulator activity Inferred from mutant phenotype. Source: RGD protein domain specific binding Inferred from physical interaction. Source: RGD protein kinase C activity Inferred from direct assay. Source: RGD protein kinase binding Inferred from physical interaction. Source: RGD 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 – 592	592	Protein kinase C zeta type		PRO_0000055704
Regions
	Domain	15 – 98	84	OPR
	Domain	252 – 518	267	Protein kinase
	Domain	519 – 590	72	AGC-kinase C-terminal
	Zinc finger	130 – 180	51	Phorbol-ester/DAG-type
	Nucleotide binding	258 – 266	9	ATP By similarity
	Region	79 – 145	67	Interaction with SQSTM1
Sites
	Active site	376	1	Proton acceptor By similarity
	Binding site	281	1	ATP By similarity
Amino acid modifications
	Modified residue	410	1	Phosphothreonine; by PDPK1 By similarity
	Modified residue	560	1	Phosphothreonine Ref.15
Experimental info
	Mutagenesis	62	1	D → A: Loss of interaction with SQSTM1. Ref.14
	Sequence conflict	102 – 112	11	QPGMPCPGEDK → FRAEEAAEKAE in AAA41878. Ref.2
	Sequence conflict	102 – 112	11	QPGMPCPGEDK → FRAEEAAEKAE no nucleotide entry Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P09217 [UniParc]. Last modified February 1, 1991. Version 2. Checksum: 5A3021171C2FD7C7	FASTA	592	67,733
	10 20 30 40 50 60 MPSRTDPKMD RSGGRVRLKA HYGGDILITS VDPTTTFQDL CEEVRDMCGL HQQHPLTLKW 70 80 90 100 110 120 VDSEGDPCTV SSQMELEEAF RLACQGRDEV LIIHVFPSIP EQPGMPCPGE DKSIYRRGAR 130 140 150 160 170 180 RWRKLYRANG HLFQAKRFNR RAYCGQCSER IWGLARQGYR CINCKLLVHK RCHVLVPLTC 190 200 210 220 230 240 RRHMDSVMPS QEPPVDDKND GVDLPSEETD GIAYISSSRK HDNIKDDSED LKPVIDGVDG 250 260 270 280 290 300 IKISQGLGLQ DFDLIRVIGR GSYAKVLLVR LKKNDQIYAM KVVKKELVHD DEDIDWVQTE 310 320 330 340 350 360 KHVFEQASSN PFLVGLHSCF QTTSRLFLVI EYVNGGDLMF HMQRQRKLPE EHARFYAAEI 370 380 390 400 410 420 CIALNFLHER GIIYRDLKLD NVLLDADGHI KLTDYGMCKE GLGPGDTTST FCGTPNYIAP 430 440 450 460 470 480 EILRGEEYGF SVDWWALGVL MFEMMAGRSP FDIITDNPDM NTEDYLFQVI LEKPIRIPRF 490 500 510 520 530 540 LSVKASHVLK GFLNKDPKER LGCRPQTGFS DIKSHAFFRS IDWDLLEKKQ TLPPFQPQIT 550 560 570 580 590 DDYGLDNFDT QFTSEPVQLT PDDEDVIKRI DQSEFEGFEY INPLLLSAEE SV

References

[1]	"Protein kinase C zeta subspecies from rat brain: its structure, expression, and properties." Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. Proc. Natl. Acad. Sci. U.S.A. 86:3099-3103(1989) [PubMed: 2470089] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	"The structure, expression, and properties of additional members of the protein kinase C family." Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. J. Biol. Chem. 263:6927-6932(1988) [PubMed: 2834397] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 101-592. Tissue: Brain.
[3]	"Identification of three additional members of rat protein kinase C family: delta-, epsilon- and zeta-subspecies." Ono Y., Fujii T., Ogita K., Kikkawa U., Igarashi K., Nishizuka Y. FEBS Lett. 226:125-128(1987) [PubMed: 3691811] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 101-180.
[4]	"Persistent activation of the zeta isoform of protein kinase C in the maintenance of long-term potentiation." Sacktor T.C., Osten P., Valsamis H., Jiang X., Naik M.U., Sublette E. Proc. Natl. Acad. Sci. U.S.A. 90:8342-8346(1993) [PubMed: 8378304] [Abstract] Cited for: FUNCTION IN LONG-TERM POTENTIATION.
[5]	"Evidence for a role of MEK and MAPK during signal transduction by protein kinase C zeta." Berra E., Diaz-Meco M.T., Lozano J., Frutos S., Municio M.M., Sanchez P., Sanz L., Moscat J. EMBO J. 14:6157-6163(1995) [PubMed: 8557035] [Abstract] Cited for: FUNCTION IN ACTIVATION OF MAP2K1/MEK1 AND MAPK3/ERK1.
[6]	"Protein kinase C-zeta as a downstream effector of phosphatidylinositol 3-kinase during insulin stimulation in rat adipocytes. Potential role in glucose transport." Standaert M.L., Galloway L., Karnam P., Bandyopadhyay G., Moscat J., Farese R.V. J. Biol. Chem. 272:30075-30082(1997) [PubMed: 9374484] [Abstract] Cited for: FUNCTION.
[7]	"Interaction of protein kinase C zeta with ZIP, a novel protein kinase C-binding protein." Puls A., Schmidt S., Grawe F., Stabel S. Proc. Natl. Acad. Sci. U.S.A. 94:6191-6196(1997) [PubMed: 9177193] [Abstract] Cited for: FUNCTION, INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION, DOMAIN.
[8]	"Activation of IkappaB kinase beta by protein kinase C isoforms." Lallena M.J., Diaz-Meco M.T., Bren G., Paya C.V., Moscat J. Mol. Cell. Biol. 19:2180-2188(1999) [PubMed: 10022904] [Abstract] Cited for: FUNCTION IN NF-KAPPA-B ACTIVATION.
[9]	"The atypical PKC-interacting protein p62 channels NF-kappaB activation by the IL-1-TRAF6 pathway." Sanz L., Diaz-Meco M.T., Nakano H., Moscat J. EMBO J. 19:1576-1586(2000) [PubMed: 10747026] [Abstract] Cited for: FUNCTION IN NF-KAPPA-B ACTIVATION.
[10]	"Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta." Etienne-Manneville S., Hall A. Cell 106:489-498(2001) [PubMed: 11525734] [Abstract] Cited for: FUNCTION IN CELL POLARITY.
[11]	"MEK5, a new target of the atypical protein kinase C isoforms in mitogenic signaling." Diaz-Meco M.T., Moscat J. Mol. Cell. Biol. 21:1218-1227(2001) [PubMed: 11158308] [Abstract] Cited for: FUNCTION IN ACTIVATION OF MAP2K5/MEK5 AND MAPK7/ERK5.
[12]	"Protein kinase Mzeta is necessary and sufficient for LTP maintenance." Ling D.S., Benardo L.S., Serrano P.A., Blace N., Kelly M.T., Crary J.F., Sacktor T.C. Nat. Neurosci. 5:295-296(2002) [PubMed: 11914719] [Abstract] Cited for: FUNCTION IN LONG-TERM POTENTIATION.
[13]	"ZIP3, a new splice variant of the PKC-zeta-interacting protein family, binds to GABAC receptors, PKC-zeta, and Kv beta 2." Croci C., Brandstaetter J.H., Enz R. J. Biol. Chem. 278:6128-6135(2003) [PubMed: 12431995] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND GABRR3, SUBCELLULAR LOCATION.
[14]	"Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins." Lamark T., Perander M., Outzen H., Kristiansen K., Oevervatn A., Michaelsen E., Bjoerkoey G., Johansen T. J. Biol. Chem. 278:34568-34581(2003) [PubMed: 12813044] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND MAP2K5, MUTAGENESIS OF ASP-62.
[15]	"Molecular mechanisms regulating protein kinase Czeta turnover and cellular transformation." Le Good J.A., Brindley D.N. Biochem. J. 378:83-92(2004) [PubMed: 14580237] [Abstract] Cited for: PHOSPHORYLATION AT THR-410 AND THR-560.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	J04532 mRNA. Translation: AAA41934.1. M18332 mRNA. Translation: AAA41878.1.
IPI	IPI00212818.
PIR	A30314.
RefSeq	NP_071952.1. NM_022507.1.
UniGene	Rn.1109.
3D structure databases
ProteinModelPortal	P09217.
SMR	P09217. Positions 12-98, 247-584.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-40867N.
IntAct	P09217. 1 interaction.
MINT	MINT-125335.
STRING	P09217.
PTM databases
PhosphoSite	P09217.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	25522.
KEGG	rno:25522.
Organism-specific databases
CTD	5590.
RGD	3399. Prkcz.
Phylogenomic databases
eggNOG	maNOG15988.
GeneTree	ENSGT00590000082854.
HOVERGEN	HBG108317.
InParanoid	P09217.
OrthoDB	EOG4T782V.
PhylomeDB	P09217.
Enzyme and pathway databases
BRENDA	2.7.11.13. 5301.
Reactome	REACT_82403. Hemostasis.
Gene expression databases
ArrayExpress	P09217.
Genevestigator	P09217.
GermOnline	ENSRNOG00000015480. Rattus norvegicus.
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. IPR017442. Se/Thr_kinase-like_dom. IPR008271. Ser/Thr_kinase_AS. IPR002290. Ser/Thr_kinase_dom. [Graphical view]
KO	K06069.
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...
Other
NextBio	606991.

Entry information

Entry name

KPCZ_RAT

Accession

Primary (citable) accession number: P09217

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	February 1, 1991
Last modified:	January 25, 2012
This is version 125 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program