Reviewed, UniProtKB/Swiss-Prot Q05513 (KPCZ_HUMAN)

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:	PKC2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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. 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.
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	Forms a ternary complex with SQSTM1 and KCNAB2. Forms another ternary complex with SQSTM1 and GABRR3. Forms a complex with SQSTM1 and MAP2K5 By similarity. Interacts with PARD6A, PARD6B, PARD6G and SQSTM1. Part of a complex with PARD3, PARD6A or PARD6B or PARD6G and CDC42 or RAC1. Interacts with CENTA1. Forms a ternary complex composed of SQSTM1 and PAWR. Interacts directly with SQSTM1 Probable. Interacts with IKBKB.
Subcellular location	Cytoplasm. Endosome. Note= In the retina, localizes in the terminals of the rod bipolar cells By similarity. Associates with endosomes.
Tissue specificity	Expressed in brain, and to a lesser extent in lung, kidney and testis.
Domain	The OPR domain mediates mutually exclusive interactions with SQSTM1 and PARD6B. The C1 domain does not bind the diacylglycerol (DAG).
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 Endosome
Coding sequence diversity	Polymorphism
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	anti-apoptosis Traceable author statement. Source: ProtInc intracellular signaling cascade Inferred from electronic annotation. Source: InterPro protein amino acid phosphorylation Traceable author statement. Source: ProtInc
Cellular component	endosome Inferred from electronic annotation. Source: UniProtKB-KW membrane fraction Traceable author statement. Source: ProtInc
Molecular function	ATP binding Inferred from electronic annotation. Source: InterPro atypical protein kinase C activity Ref.2 Traceable author statement. Source: ProtInc diacylglycerol binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.9 Ref.10 Ref.12 Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PARD6B	Q9BYG5	1	EBI-295351,EBI-295391
PRKCQ	Q04759	2	EBI-295351,EBI-374762

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_0000055701
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 By similarity
Sites
	Active site	376	1	Proton acceptor By similarity
	Binding site	281	1	ATP By similarity
Amino acid modifications
	Modified residue	223	1	Phosphoserine
	Modified residue	410	1	Phosphothreonine; by PDPK1
	Modified residue	560	1	Phosphothreonine
Natural variations
	Natural variant	84	1	R → H		VAR_042310
	Natural variant	514	1	S → F in a colorectal cancer sample; somatic mutation.		VAR_035467
	Natural variant	519	1	R → C in a colorectal adenocarcinoma sample; somatic mutation.		VAR_042311
Experimental info
	Mutagenesis	19	1	K → A: No effect on interaction with SQSTM1 and PARD6B
	Mutagenesis	62	1	D → A: Loss of interaction with SQSTM1 and PARD6B
	Mutagenesis	66	1	D → A: Loss of interaction with SQSTM1 and PARD6B
	Sequence conflict	6	1	G → D in AAA36488. Ref.2
	Sequence conflict	262	1	S → T in AAA36488. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q05513-1 [UniParc]. Last modified June 21, 2005. Version 4. Checksum: 88CCD0577E6A596C	FASTA	592	67,660
	10 20 30 40 50 60 MPSRTGPKME GSGGRVRLKA HYGGDIFITS VDAATTFEEL CEEVRDMCRL HQQHPLTLKW 70 80 90 100 110 120 VDSEGDPCTV SSQMELEEAF RLARQCRDEG LIIHVFPSTP EQPGLPCPGE DKSIYRRGAR 130 140 150 160 170 180 RWRKLYRANG HLFQAKRFNR RAYCGQCSER IWGLARQGYR CINCKLLVHK RCHGLVPLTC 190 200 210 220 230 240 RKHMDSVMPS QEPPVDDKNE DADLPSEETD GIAYISSSRK HDSIKDDSED LKPVIDGMDG 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 ALPPFQPQIT 550 560 570 580 590 DDYGLDNFDT QFTSEPVQLT PDDEDAIKRI DQSEFEGFEY INPLLLSTEE SV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Activation and substrate specificity of the human protein kinase C alpha and zeta isoenzymes." Kochs G., Hummel R., Meyer D., Hug H., Marme D., Sarre T.F. Eur. J. Biochem. 216:597-606(1993) [PubMed: 8375396] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-592. Tissue: Hippocampus.
[2]	"The cDNA sequence encoding human protein kinase C-zeta." Barbee J.L., Loomis C.R., Deutscher S.L., Burns D.J. Gene 132:305-306(1993) [PubMed: 8224878] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Frontal cortex.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon and Ovary.
[6]	"Localization of atypical protein kinase C isoforms into lysosome-targeted endosomes through interaction with p62." Sanchez P., De Carcer G., Sandoval I.V., Moscat J., Diaz-Meco M.T. Mol. Cell. Biol. 18:3069-3080(1998) [PubMed: 9566925] [Abstract] Cited for: INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION.
[7]	"Regulation of protein kinase C zeta by PI 3-kinase and PDK-1." Chou M.M., Hou W., Johnson J., Graham L.K., Lee M.H., Chen C.S., Newton A.C., Schaffhausen B.S., Toker A. Curr. Biol. 8:1069-1077(1998) [PubMed: 9768361] [Abstract] Cited for: PHOSPHORYLATION AT THR-410 BY PDPK1.
[8]	"The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation." Sanz L., Sanchez P., Lallena M.-J., Diaz-Meco M.T., Moscat J. EMBO J. 18:3044-3053(1999) [PubMed: 10356400] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND IKBKB.
[9]	"Human homologues of the Caenorhabditis elegans cell polarity protein PAR6 as an adaptor that links the small GTPases Rac and Cdc42 to atypical protein kinase C." Noda Y., Takeya R., Ohno S., Naito S., Ito T., Sumimoto H. Genes Cells 6:107-119(2001) [PubMed: 11260256] [Abstract] Cited for: INTERACTION WITH PARD6A; PARD6B AND PARD6G. Tissue: Neuroblastoma.
[10]	"p62 forms a ternary complex with PKCzeta and PAR-4 and antagonizes PAR-4-induced PKCzeta inhibition." Chang S., Kim J.H., Shin J. FEBS Lett. 510:57-61(2002) [PubMed: 11755531] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND PAWR.
[11]	"Multiple splice variants of Par3 and of a novel related gene, Par3L, produce proteins with different binding properties." Gao L., Macara I.G., Joberty G. Gene 294:99-99(2002) [PubMed: 12234671] [Abstract] Cited for: INTERACTION WITH PARD3.
[12]	"Centaurin-alpha(1) associates with and is phosphorylated by isoforms of protein kinase C." Zemlickova E., Dubois T., Kerai P., Clokie S., Cronshaw A.D., Wakefield R.I.D., Johannes F.-J., Aitken A. Biochem. Biophys. Res. Commun. 307:459-465(2003) [PubMed: 12893243] [Abstract] Cited for: INTERACTION WITH CENTA1.
[13]	"PB1 domain-mediated heterodimerization in NADPH oxidase and signaling complexes of atypical protein kinase C with Par6 and p62." Wilson M.I., Gill D.J., Perisic O., Quinn M.T., Williams R.L. Mol. Cell 12:39-50(2003) [PubMed: 12887891] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND PARD6B, DOMAIN, MUTAGENESIS OF LYS-19; ASP-62 AND ASP-66.
[14]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, MASS SPECTROMETRY. Tissue: Epithelium.
[15]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-560, MASS SPECTROMETRY.
[16]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-514.
[17]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-84 AND CYS-519.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z15108 mRNA. Translation: CAA78813.1. Different initiation. L14283 mRNA. Translation: AAA36488.1. BT007082 mRNA. Translation: AAP35745.1. AL590822, AL391845, AL645703 Genomic DNA. Translation: CAI12484.1. AL391845, AL590822, AL645703 Genomic DNA. Translation: CAI15438.1. AL645703, AL391845, AL590822 Genomic DNA. Translation: CAI21535.1. BC008058 mRNA. Translation: AAH08058.1. BC014270 mRNA. Translation: AAH14270.1.
PIR	JN0877.
RefSeq	NP_001028753.1. NP_001028754.1. NP_002735.3.
UniGene	Hs.496255
3D structure databases
HSSP	HSSP built from PDB template 1GZK based on UniProtKB P31751.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q05513.
PTM databases
PhosphoSite	Q05513.
Genome annotation databases
Ensembl	ENSG00000067606. Homo sapiens. [Contig view]
GeneID	5590.
KEGG	hsa:5590.
Organism-specific databases
H-InvDB	HIX0000046.
HGNC	HGNC:9412. PRKCZ.
HPA	CAB004533.
MIM	176982. gene.
PharmGKB	PA33775.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q05513.
HOVERGEN	Q05513.
Gene expression databases
ArrayExpress	Q05513.
CleanEx	HS_PRKCZ.
GermOnline	ENSG00000067606. Homo sapiens.
Family and domain databases
InterPro	IPR002219. DAG_PE_bd. IPR000270. OPR_PB1. IPR015745. PKC. IPR012233. PKC_zeta. IPR000961. Pkinase_C. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_bd_CS. 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
BindingDB	Q05513.
NextBio	21684.
SOURCE	Search...

Entry information

Entry name

KPCZ_HUMAN

Accession

Primary (citable) accession number: Q05513
Secondary accession number(s): Q15207, Q5SYT5, Q969S4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	June 21, 2005