Reviewed, UniProtKB/Swiss-Prot P09217 (KPCZ_RAT)

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.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This is a calcium-independent, phospholipid-dependent, serine- and threonine-specific enzyme. Phosphorylates KCNAB2. Ref.4 PKC is activated by diacylglycerol which in turn phosphorylates a range of cellular proteins. PKC also serves as the receptor for phorbol esters, a class of tumor promoters. Subunit of a quaternary complex that plays a central role in epithelial cell polarization By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Enzyme regulation	Phosphatidylinositol 3,4,5-trisphosphate might be a physiological activator. Two specific sites, Thr-410 (activation loop of the kinase domain) and Thr-560 (turn motif), need to be phosphorylated for its full activation.
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.
Subcellular location	Cytoplasm. Note: In the retina, localizes in the terminals of the rod bipolar cells. Ref.4 Ref.5
Domain	The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B By similarity. The C1 domain does not bind the diacylglycerol (DAG). Ref.4
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
Cellular component	Cytoplasm
Domain	Phorbol-ester binding Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
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 insulin receptor signaling pathway Inferred from mutant phenotype. Source: RGD intracellular signaling cascade Inferred from direct assay. 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 apoptosis 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 heterooligomerization Inferred from physical interaction. Source: RGD vesicle transport along microtubule Inferred from mutant phenotype. Source: RGD
Cellular component	cytosol Inferred from direct assay. Source: RGD 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
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipase binding Inferred from physical interaction. Source: RGD potassium channel regulator activity Inferred from mutant phenotype. Source: RGD protein kinase C activity Inferred from electronic annotation. Source: EC protein kinase binding Inferred from physical interaction. Source: RGD zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
TRIM41	Q8WV44-2	1	EBI-1551121,EBI-726015	From a different organism.

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.7
Experimental info
	Mutagenesis	62	1	D → A: Loss of interaction with SQSTM1. Ref.6
	Sequence conflict	102 – 112	11	QPGMPCPGEDK → FRAEEAAEKAE Ref.2
	Sequence conflict	102 – 112	11	QPGMPCPGEDK → FRAEEAAEKAE Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P09217-1 [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]	"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: INTERACTION WITH SQSTM1 AND KCNAB2, DOMAIN, SUBCELLULAR LOCATION, FUNCTION.
[5]	"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.
[6]	"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.
[7]	"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
EMBLGenBankDDBJ	J04532 mRNA. Translation: AAA41934.1. M18332 mRNA. Translation: AAA41878.1.
IPI	IPI00212818.
PIR	A30314.
RefSeq	NP_071952.1.
UniGene	Rn.1109
3D structure databases
HSSP	HSSP built from PDB template 1GZK based on UniProtKB P31751.
ModBase	Search...
Protein-protein interaction databases
IntAct	P09217. 1 interaction.
STRING	P09217.
PTM databases
PhosphoSite	P09217.
Genome annotation databases
Ensembl	ENSRNOT00000021285; ENSRNOP00000021285; ENSRNOG00000015480; Rattus norvegicus. [Genome view]
GeneID	25522.
KEGG	rno:25522.
Organism-specific databases
CTD	25522.
RGD	3399. Prkcz.
Phylogenomic databases
HOVERGEN	P09217.
Enzyme and pathway databases
BRENDA	2.7.11.13. 248.
Gene expression databases
ArrayExpress	P09217.
Genevestigator	P09217.
GermOnline	ENSRNOG00000015480. Rattus norvegicus.
Family and domain databases
InterPro	IPR000961. AGC-kinase_C. IPR020454. DAG/PE_bd. IPR000270. OPR_PB1. IPR015745. PKC. IPR012233. PKC_zeta. IPR017892. Pkinase_C. IPR002219. Prot_Kinase_C-like_PE/DAG_bd. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. [Graphical view]
PANTHER	PTHR22985:SF86. PKC. 1 hit.
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.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00109. C1. 1 hit. SM00666. PB1. 1 hit. SM00133. S_TK_X. 1 hit. SM00220. S_TKc. 1 hit. [Graphical view]
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 Resources
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:	October 13, 2009
This is version 103 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)