Q05513 (KPCZ_HUMAN) 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:	PKC2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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 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. Ref.7 Ref.11 Ref.14 Ref.19 Ref.20
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	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 ADAP1/CENTA1. Forms a ternary complex composed of SQSTM1 and PAWR. Interacts directly with SQSTM1 Probable. Interacts with IKBKB. 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). Ref.8 Ref.10 Ref.12 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.22 Ref.25
Subcellular location	Cytoplasm. Endosome. Cell junction. Note: In the retina, localizes in the terminals of the rod bipolar cells By similarity. Associates with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction. Ref.8 Ref.25
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. Ref.18 The C1 domain does not bind the diacylglycerol (DAG). Ref.18
Post-translational modification	CDH5 is required for its phosphorylation at Thr-410. Phosphorylated by protein kinase PDPK1; phosphorylation is inhibited by the apoptotic C-terminus cleavage product of PKN2. Phosphorylation at Thr-410 by PI3K activates the kinase. Ref.9 Ref.13 Ref.21 Ref.25
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.
Sequence caution	The sequence CAA78813.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Inflammatory response
Cellular component	Cell junction Cytoplasm Endosome
Coding sequence diversity	Alternative splicing Polymorphism
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 electronic annotation. Source: Compara activation of phospholipase D activity Inferred from electronic annotation. Source: Compara activation of protein kinase B activity Inferred from electronic annotation. Source: Compara cell migration Inferred from electronic annotation. Source: Compara establishment of cell polarity Inferred from sequence or structural similarity. Source: UniProtKB inflammatory response Inferred from electronic annotation. Source: UniProtKB-KW insulin receptor signaling pathway Inferred from electronic annotation. Source: Compara long-term memory Inferred from electronic annotation. Source: Compara long-term synaptic potentiation Inferred from sequence or structural similarity. Source: UniProtKB membrane hyperpolarization Inferred from electronic annotation. Source: Compara microtubule cytoskeleton organization Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Traceable author statement PubMed 10770953. Source: ProtInc negative regulation of hydrolase activity Inferred from electronic annotation. Source: Compara negative regulation of insulin receptor signaling pathway Inferred from mutant phenotype PubMed 15069075. Source: BHF-UCL negative regulation of peptidyl-tyrosine phosphorylation Inferred from mutant phenotype PubMed 15069075. Source: BHF-UCL negative regulation of protein complex assembly Inferred from mutant phenotype PubMed 15069075. Source: BHF-UCL peptidyl-serine phosphorylation Inferred from direct assay PubMed 15069075. Source: BHF-UCL platelet activation Traceable author statement. Source: Reactome positive regulation of ERK1 and ERK2 cascade Inferred from mutant phenotype Ref.11. 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 cell proliferation Inferred from electronic annotation. Source: Compara positive regulation of cell-matrix adhesion Inferred from electronic annotation. Source: Compara positive regulation of excitatory postsynaptic membrane potential Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of glucose import Inferred from electronic annotation. Source: Compara 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 protein heterooligomerization Inferred from electronic annotation. Source: Compara protein kinase C signaling cascade Inferred from electronic annotation. Source: Compara protein localization to plasma membrane Inferred from electronic annotation. Source: Compara transforming growth factor beta receptor signaling pathway Traceable author statement. Source: Reactome vesicle transport along microtubule Inferred from electronic annotation. Source: Compara
Cellular_component	apical cortex Inferred from electronic annotation. Source: Compara apical plasma membrane Inferred from electronic annotation. Source: Compara cell leading edge Inferred from electronic annotation. Source: Compara cell-cell junction Inferred from direct assay Ref.25. Source: UniProtKB cytoplasm Traceable author statement PubMed 7925449. Source: ProtInc cytosol Inferred from electronic annotation. Source: Compara endosome Inferred from electronic annotation. Source: UniProtKB-SubCell membrane raft Inferred from electronic annotation. Source: Compara myelin sheath abaxonal region Inferred from electronic annotation. Source: Compara nuclear envelope Inferred from electronic annotation. Source: Compara nuclear matrix Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement PubMed 7925449. Source: ProtInc protein complex Inferred from electronic annotation. Source: Compara tight junction Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW insulin receptor substrate binding Inferred by curator PubMed 15069075. Source: BHF-UCL potassium channel regulator activity Inferred from electronic annotation. Source: Compara protein kinase C activity Inferred from electronic annotation. Source: EC protein serine/threonine kinase activity Inferred from direct assay PubMed 15069075. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HSP90AB1	P08238	2	EBI-295351,EBI-352572
PARD6A	Q9NPB6	3	EBI-295351,EBI-81876
PARD6B	Q9BYG5	3	EBI-295351,EBI-295391
PRKCQ	Q04759	3	EBI-295351,EBI-374762

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q05513-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q05513-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-183: Missing.

Isoform 3 (identifier: Q05513-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-112: MPSRTGPKME...PGLPCPGEDK → MLTPRTDE

Note: No experimental confirmation available.

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	410	1	Phosphothreonine; by PDPK1 and PI3K Ref.9 Ref.21 Ref.25
	Modified residue	560	1	Phosphothreonine Ref.24
Natural variations
	Alternative sequence	1 – 183	183	Missing in isoform 2.		VSP_041904
	Alternative sequence	1 – 112	112	MPSRT…PGEDK → MLTPRTDE in isoform 3.		VSP_046347
	Natural variant	49	1	R → H. Corresponds to variant rs35271800 [ dbSNP | Ensembl ].		VAR_050560
	Natural variant	84	1	R → H. Ref.31 Corresponds to variant rs56017162 [ dbSNP | Ensembl ].		VAR_042310
	Natural variant	514	1	S → F in a colorectal cancer sample; somatic mutation. Ref.30		VAR_035467
	Natural variant	519	1	R → C in a colorectal adenocarcinoma sample; somatic mutation. Ref.31		VAR_042311
Experimental info
	Mutagenesis	19	1	K → A: No effect on interaction with SQSTM1 and PARD6B. Ref.18
	Mutagenesis	62	1	D → A: Loss of interaction with SQSTM1 and PARD6B. Ref.18
	Mutagenesis	66	1	D → A: Loss of interaction with SQSTM1 and PARD6B. Ref.18
	Sequence conflict	6	1	G → D in AAA36488. Ref.1
	Sequence conflict	198	1	K → R in BAF83684. Ref.3
	Sequence conflict	262	1	S → T in AAA36488. Ref.1
	Sequence conflict	281	1	K → R in BAH11883. Ref.3
	Sequence conflict	366	1	F → L in BAF83684. Ref.3
	Sequence conflict	500	1	R → G in BAF83684. Ref.3
	Sequence conflict	522	1	D → G in BAF83684. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: 21C316A4A2B418BD	FASTA	409	46,622
	10 20 30 40 50 60 MDSVMPSQEP PVDDKNEDAD LPSEETDGIA YISSSRKHDS IKDDSEDLKP VIDGMDGIKI 70 80 90 100 110 120 SQGLGLQDFD LIRVIGRGSY AKVLLVRLKK NDQIYAMKVV KKELVHDDED IDWVQTEKHV 130 140 150 160 170 180 FEQASSNPFL VGLHSCFQTT SRLFLVIEYV NGGDLMFHMQ RQRKLPEEHA RFYAAEICIA 190 200 210 220 230 240 LNFLHERGII YRDLKLDNVL LDADGHIKLT DYGMCKEGLG PGDTTSTFCG TPNYIAPEIL 250 260 270 280 290 300 RGEEYGFSVD WWALGVLMFE MMAGRSPFDI ITDNPDMNTE DYLFQVILEK PIRIPRFLSV 310 320 330 340 350 360 KASHVLKGFL NKDPKERLGC RPQTGFSDIK SHAFFRSIDW DLLEKKQALP PFQPQITDDY 370 380 390 400 GLDNFDTQFT SEPVQLTPDD EDAIKRIDQS EFEGFEYINP LLLSTEESV
	Isoform 3 [UniParc]. Checksum: 219A7C60FCEF0905	FASTA	488	56,136
	10 20 30 40 50 60 MLTPRTDESI YRRGARRWRK LYRANGHLFQ AKRFNRRAYC GQCSERIWGL ARQGYRCINC 70 80 90 100 110 120 KLLVHKRCHG LVPLTCRKHM DSVMPSQEPP VDDKNEDADL PSEETDGIAY ISSSRKHDSI 130 140 150 160 170 180 KDDSEDLKPV IDGMDGIKIS QGLGLQDFDL IRVIGRGSYA KVLLVRLKKN DQIYAMKVVK 190 200 210 220 230 240 KELVHDDEDI DWVQTEKHVF EQASSNPFLV GLHSCFQTTS RLFLVIEYVN GGDLMFHMQR 250 260 270 280 290 300 QRKLPEEHAR FYAAEICIAL NFLHERGIIY RDLKLDNVLL DADGHIKLTD YGMCKEGLGP 310 320 330 340 350 360 GDTTSTFCGT PNYIAPEILR GEEYGFSVDW WALGVLMFEM MAGRSPFDII TDNPDMNTED 370 380 390 400 410 420 YLFQVILEKP IRIPRFLSVK ASHVLKGFLN KDPKERLGCR PQTGFSDIKS HAFFRSIDWD 430 440 450 460 470 480 LLEKKQALPP FQPQITDDYG LDNFDTQFTS EPVQLTPDDE DAIKRIDQSE FEGFEYINPL LLSTEESV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Frontal cortex.
[2]	"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] (ISOFORM 1).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). Tissue: Brain and Teratocarcinoma.
[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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon and Ovary.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 7-592. Tissue: Hippocampus.
[7]	"Activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase pathway by conventional, novel, and atypical protein kinase C isotypes." Schoenwasser D.C., Marais R.M., Marshall C.J., Parker P.J. Mol. Cell. Biol. 18:790-798(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF MAP2K1/MEK1 AND MAPK1/ERK2.
[8]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SQSTM1, SUBCELLULAR LOCATION.
[9]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-410 BY PDPK1.
[10]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND IKBKB.
[11]	"Protein kinase C zeta plays a central role in activation of the p42/44 mitogen-activated protein kinase by endotoxin in alveolar macrophages." Monick M.M., Carter A.B., Flaherty D.M., Peterson M.W., Hunninghake G.W. J. Immunol. 165:4632-4639(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF MAPK1/ERK2.
[12]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARD6A; PARD6B AND PARD6G. Tissue: Neuroblastoma.
[13]	"Regulation of both PDK1 and the phosphorylation of PKC-zeta and -delta by a C-terminal PRK2 fragment." Hodgkinson C.P., Sale G.J. Biochemistry 41:561-569(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PDPK1, PHOSPHORYLATION.
[14]	"Characterization of PDK2 activity against protein kinase B gamma." Hodgkinson C.P., Sale E.M., Sale G.J. Biochemistry 41:10351-10359(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN ACTIVATION OF AKT3.
[15]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND PAWR.
[16]	"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 294:99-107(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PARD3.
[17]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ADAP1.
[18]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SQSTM1 AND PARD6B, DOMAIN, MUTAGENESIS OF LYS-19; ASP-62 AND ASP-66.
[19]	"Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity." Hurov J.B., Watkins J.L., Piwnica-Worms H. Curr. Biol. 14:736-741(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MARK2 AND MARK3.
[20]	"aPKC acts upstream of PAR-1b in both the establishment and maintenance of mammalian epithelial polarity." Suzuki A., Hirata M., Kamimura K., Maniwa R., Yamanaka T., Mizuno K., Kishikawa M., Hirose H., Amano Y., Izumi N., Miwa Y., Ohno S. Curr. Biol. 14:1425-1435(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF MARK2.
[21]	"Role of atypical protein kinase C in estradiol-triggered G1/S progression of MCF-7 cells." Castoria G., Migliaccio A., Di Domenico M., Lombardi M., de Falco A., Varricchio L., Bilancio A., Barone M.V., Auricchio F. Mol. Cell. Biol. 24:7643-7653(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-410 BY PI3K.
[22]	"KIBRA interacts with discoidin domain receptor 1 to modulate collagen-induced signalling." Hilton H.N., Stanford P.M., Harris J., Oakes S.R., Kaplan W., Daly R.J., Ormandy C.J. Biochim. Biophys. Acta 1783:383-393(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH WWC1 AND DDR1.
[23]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[24]	"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] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-560, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[25]	"CCM1 regulates vascular-lumen organization by inducing endothelial polarity." Lampugnani M.G., Orsenigo F., Rudini N., Maddaluno L., Boulday G., Chapon F., Dejana E. J. Cell Sci. 123:1073-1080(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, SUBUNIT, PHOSPHORYLATION AT THR-410.
[26]	"Protein kinase Czeta (PKCzeta): activation mechanisms and cellular functions." Hirai T., Chida K. J. Biochem. 133:1-7(2003) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[27]	"Protein kinase Czeta and glucose uptake." Liu L.Z., He A.B., Liu X.J., Li Y., Chang Y.S., Fang F.D. Biokhimiia 71:701-706(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[28]	"PKCzeta at the crossroad of NF-kappaB and Jak1/Stat6 signaling pathways." Moscat J., Rennert P., Diaz-Meco M.T. Cell Death Differ. 13:702-711(2006) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[29]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[30]	"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] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PHE-514.
[31]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] HIS-84 AND CYS-519.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	L14283 mRNA. Translation: AAA36488.1. BT007082 mRNA. Translation: AAP35745.1. AK290995 mRNA. Translation: BAF83684.1. AK294649 mRNA. Translation: BAH11833.1. AK294782 mRNA. Translation: BAH11883.1. AL162271 Genomic DNA. No translation available. 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. Z15108 mRNA. Translation: CAA78813.1. Different initiation.
IPI	IPI00013749. IPI00965675.
PIR	JN0877.
RefSeq	NP_001028753.1. NM_001033581.1. NP_001028754.1. NM_001033582.1. NP_001229803.1. NM_001242874.1. NP_002735.3. NM_002744.4.
UniGene	Hs.496255.
3D structure databases
ProteinModelPortal	Q05513.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q05513. 11 interactions.
MINT	MINT-5004464.
STRING	9606.ENSP00000367830.
PTM databases
PhosphoSite	Q05513.
Polymorphism databases
DMDM	68067736.
Proteomic databases
PaxDb	Q05513.
PRIDE	Q05513.
Protocols and materials databases
DNASU	5590.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378567; ENSP00000367830; ENSG00000067606. ENST00000400920; ENSP00000383711; ENSG00000067606. ENST00000400921; ENSP00000383712; ENSG00000067606. ENST00000461106; ENSP00000426412; ENSG00000067606.
GeneID	5590.
KEGG	hsa:5590.
UCSC	uc001aiq.3. human.
Organism-specific databases
CTD	5590.
GeneCards	GC01P001982.
H-InvDB	HIX0000049. HIX0029201.
HGNC	HGNC:9412. PRKCZ.
HPA	CAB004533. HPA021851.
MIM	176982. gene.
neXtProt	NX_Q05513.
PharmGKB	PA33775.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0515.
HOGENOM	HOG000233033.
HOVERGEN	HBG108317.
InParanoid	Q05513.
KO	K06069.
OMA	RCHVLVP.
OrthoDB	EOG4T782V.
PhylomeDB	Q05513.
Enzyme and pathway databases
BRENDA	2.7.11.13. 2681.
Pathway_Interaction_DB	amb2_neutrophils_pathway. amb2 Integrin signaling. ceramidepathway. Ceramide signaling pathway. igf1_pathway. IGF1 pathway. il1pathway. IL1-mediated signaling events. il2_pi3kpathway. IL2 signaling events mediated by PI3K. insulin_pathway. Insulin Pathway. insulin_glucose_pathway. Insulin-mediated glucose transport. trkrpathway. Neurotrophic factor-mediated Trk receptor signaling. p75ntrpathway. p75(NTR)-mediated signaling. nfat_3pathway. Role of Calcineurin-dependent NFAT signaling in lymphocytes. txa2pathway. Thromboxane A2 receptor signaling. tnfpathway. TNF receptor signaling pathway.
Reactome	REACT_111102. Signal Transduction. REACT_604. Hemostasis.
Gene expression databases
ArrayExpress	Q05513.
Bgee	Q05513.
CleanEx	HS_PRKCZ.
Genevestigator	Q05513.
GermOnline	ENSG00000067606. Homo sapiens.
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...
Other
BindingDB	Q05513.
ChEMBL	CHEMBL3438.
ChiTaRS	PRKCZ. human.
GenomeRNAi	5590.
NextBio	21684.
PMAP-CutDB	Q05513.
SOURCE	Search...

Entry information

Entry name

KPCZ_HUMAN

Accession

Primary (citable) accession number: Q05513
Secondary accession number(s): A8K4N0 , A8MU64, B7Z2J7, E9PCW2, Q15207, Q5SYT5, Q969S4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1994
Last sequence update:	June 21, 2005
Last modified:	May 1, 2013
This is version 157 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.