dbPTM

KPCZ_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	KPCZ_HUMAN
UniProt AC	Q05513
Protein Name	Protein kinase C zeta type
Gene Name	PRKCZ
Organism	Homo sapiens (Human).
Sequence Length	592
Subcellular Localization	Cytoplasm . Endosome . Cell junction . In the retina, localizes in the terminals of the rod bipolar cells. Associates with endosomes. Presence of KRIT1, CDH5 and RAP1B is required for its localization to the cell junction. Colocalizes with VAMP2 and
Protein Description	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 the inflammatory response, is required for the T-helper 2 (Th2) differentiation process, including interleukin 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 the NF-kappa-B-mediated inflammatory response, can relieve SETD6-dependent repression of NF-kappa-B target genes by phosphorylating the RELA subunit at 'Ser-311'. Necessary and sufficient for LTP maintenance in hippocampal CA1 pyramidal cells. In vein endothelial cells treated with the oxidant peroxynitrite, phosphorylates STK11 leading to nuclear export of STK11, subsequent inhibition of PI3K/Akt signaling, and increased apoptosis. Phosphorylates VAMP2 in vitro. [PubMed: 17313651]
Protein Sequence	MPSRTGPKMEGSGGRVRLKAHYGGDIFITSVDAATTFEELCEEVRDMCRLHQQHPLTLKWVDSEGDPCTVSSQMELEEAFRLARQCRDEGLIIHVFPSTPEQPGLPCPGEDKSIYRRGARRWRKLYRANGHLFQAKRFNRRAYCGQCSERIWGLARQGYRCINCKLLVHKRCHGLVPLTCRKHMDSVMPSQEPPVDDKNEDADLPSEETDGIAYISSSRKHDSIKDDSEDLKPVIDGMDGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRFLSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQALPPFQPQITDDYGLDNFDTQFTSEPVQLTPDDEDAIKRIDQSEFEGFEYINPLLLSTEESV

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
36	Ubiquitination	TSVDAATTFEELCEE EECCHHHCHHHHHHH	25.07	22505724
44	Ubiquitination	FEELCEEVRDMCRLH HHHHHHHHHHHHHHH	2.69	22505724
44	Phosphorylation	FEELCEEVRDMCRLH HHHHHHHHHHHHHHH	2.69	33259812
47	Ubiquitination	LCEEVRDMCRLHQQH HHHHHHHHHHHHHHC	0.72	22505724
86	Ubiquitination	AFRLARQCRDEGLII HHHHHHHHCCCCCEE	5.02	22505724
90	Ubiquitination	ARQCRDEGLIIHVFP HHHHCCCCCEEEEEC	26.85	22505724
94	Ubiquitination	RDEGLIIHVFPSTPE CCCCCEEEEECCCCC	14.26	22505724
97	Ubiquitination	GLIIHVFPSTPEQPG CCEEEEECCCCCCCC	35.88	22505724
98	Ubiquitination	LIIHVFPSTPEQPGL CEEEEECCCCCCCCC	45.16	22505724
101	Ubiquitination	HVFPSTPEQPGLPCP EEECCCCCCCCCCCC	70.29	22505724
143	Phosphorylation	KRFNRRAYCGQCSER CCCCCCCCCCHHHHH	8.70	28152594
148	Phosphorylation	RAYCGQCSERIWGLA CCCCCHHHHHHHHHH	23.25	33259812
169	Ubiquitination	INCKLLVHKRCHGLV ECEEEEEECCCCCCC	16.29	22505724
177	Ubiquitination	KRCHGLVPLTCRKHM CCCCCCCEEECHHHH	27.31	22505724
180	Ubiquitination	HGLVPLTCRKHMDSV CCCCEEECHHHHHHC	7.80	22505724
190	Phosphorylation	HMDSVMPSQEPPVDD HHHHCCCCCCCCCCC	29.13	-
191	Ubiquitination	MDSVMPSQEPPVDDK HHHCCCCCCCCCCCC	62.44	22505724
199	Ubiquitination	EPPVDDKNEDADLPS CCCCCCCCCCCCCCC	60.41	22505724
202	Ubiquitination	VDDKNEDADLPSEET CCCCCCCCCCCCCCC	17.67	22505724
206	Phosphorylation	NEDADLPSEETDGIA CCCCCCCCCCCCCEE	56.19	25849741
214	Phosphorylation	EETDGIAYISSSRKH CCCCCEEEEECCCCC	10.22	27642862
216	Phosphorylation	TDGIAYISSSRKHDS CCCEEEEECCCCCCC	15.02	24905233
217	Phosphorylation	DGIAYISSSRKHDSI CCEEEEECCCCCCCC	25.30	24905233
218	Phosphorylation	GIAYISSSRKHDSIK CEEEEECCCCCCCCC	38.26	24905233
223	Phosphorylation	SSSRKHDSIKDDSED ECCCCCCCCCCCCCC	31.12	25159151
228	Phosphorylation	HDSIKDDSEDLKPVI CCCCCCCCCCCHHHH	43.05	30624053
231	Phosphorylation	IKDDSEDLKPVIDGM CCCCCCCCHHHHCCC	6.24	32142685
262	Phosphorylation	IRVIGRGSYAKVLLV EEEECCCCCEEEEEE	22.13	28102081
263	Phosphorylation	RVIGRGSYAKVLLVR EEECCCCCEEEEEEE	17.17	11713277
273	Ubiquitination	VLLVRLKKNDQIYAM EEEEEECCCCEEEEE	71.05	22505724
281	Ubiquitination	NDQIYAMKVVKKELV CCEEEEEEEEEHHHC	35.39	22505724
284	Ubiquitination	IYAMKVVKKELVHDD EEEEEEEEHHHCCCC	43.44	22505724
310	Phosphorylation	VFEQASSNPFLVGLH HHHHHCCCCCEEEHH	28.93	32142685
395	Phosphorylation	GHIKLTDYGMCKEGL CCEEECCCCCCCCCC	11.09	-
407	Phosphorylation	EGLGPGDTTSTFCGT CCCCCCCCCCCCCCC	28.67	27050516
408	Phosphorylation	GLGPGDTTSTFCGTP CCCCCCCCCCCCCCC	30.43	30242111
409	Phosphorylation	LGPGDTTSTFCGTPN CCCCCCCCCCCCCCC	22.91	26657352
410	Phosphorylation	GPGDTTSTFCGTPNY CCCCCCCCCCCCCCE	22.35	22322096
414	Phosphorylation	TTSTFCGTPNYIAPE CCCCCCCCCCEECHH	15.00	30242111
417	Phosphorylation	TFCGTPNYIAPEILR CCCCCCCEECHHHHC	10.32	20407013
428	Phosphorylation	EILRGEEYGFSVDWW HHHCCCCCCCCHHHH	21.11	22817900
520	Phosphorylation	KSHAFFRSIDWDLLE HHHHHHHHCCHHHHH	21.53	28348404
560	Phosphorylation	TSEPVQLTPDDEDAI CCCCCCCCCCCHHHH	13.95	16051884
580	Phosphorylation	SEFEGFEYINPLLLS HHCCCCCEECCCCCC	12.07	27642862
587	Phosphorylation	YINPLLLSTEESV-- EECCCCCCCCCCC--	33.47	28348404
588	Phosphorylation	INPLLLSTEESV--- ECCCCCCCCCCC---	43.68	29523821
591	Phosphorylation	LLLSTEESV------ CCCCCCCCC------	27.22	29523821

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
410	T	Phosphorylation	Kinase	PDK1	Q15118	GPS
410	T	Phosphorylation	Kinase	PDK1	O15530	PSP
410	T	Phosphorylation	Kinase	PDPK1	Q9Z2A0	GPS
410	T	Phosphorylation	Kinase	PI3K	-	Uniprot
560	T	Phosphorylation	Kinase	PRKCZ	Q05513	GPS
-	K	Ubiquitination	E3 ubiquitin ligase	STUB1	Q9UNE7	PMID:21911421

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
410	T	Phosphorylation	9768361
CDH5 is required for its phosphorylation at Thr-410.
410	T	Phosphorylation	9768361
Phosphorylation at Thr-410 by PI3K activates the kinase.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of KPCZ_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PAR6A_HUMAN	PARD6A	physical	16189514
KIBRA_HUMAN	WWC1	physical	15081397
FEZ2_HUMAN	FEZ2	physical	14697253
ADAP1_HUMAN	ADAP1	physical	12893243
NFAC2_HUMAN	NFATC2	physical	12021260
PDPK1_HUMAN	PDPK1	physical	11781095
CSK2B_HUMAN	CSNK2B	physical	10764587
KS6B1_HUMAN	RPS6KB1	physical	16931574
NUCL_HUMAN	NCL	physical	9388266
AKT1_HUMAN	AKT1	physical	10085094
TF65_HUMAN	RELA	physical	11684013
1433G_HUMAN	YWHAG	physical	10620507
1433T_HUMAN	YWHAQ	physical	10620507
1433F_HUMAN	YWHAH	physical	10620507
RAF1_HUMAN	RAF1	physical	10620507
1433B_HUMAN	YWHAB	physical	10620507
1433Z_HUMAN	YWHAZ	physical	10620507
TIAM1_HUMAN	TIAM1	physical	10212259
PDPK1_HUMAN	PDPK1	physical	9748166
PDPK1_HUMAN	PDPK1	physical	10764742
AKT3_HUMAN	AKT3	physical	12162751
FEZ1_HUMAN	FEZ1	physical	9971736
SRC_HUMAN	SRC	physical	10527887
PAWR_HUMAN	PAWR	physical	8797824
MP2K5_HUMAN	MAP2K5	physical	11158308
PAR6B_HUMAN	PARD6B	physical	11260256
HS90A_HUMAN	HSP90AA1	physical	20936779
MSH6_HUMAN	MSH6	physical	15808853
MSH2_HUMAN	MSH2	physical	15808853
SP1_HUMAN	SP1	physical	16943418
SP1_HUMAN	SP1	physical	18258854
KPCZ_HUMAN	PRKCZ	physical	19920073
ZNF71_HUMAN	ZNF71	physical	21900206
UT14A_HUMAN	UTP14A	physical	21900206
NMT2_HUMAN	NMT2	physical	21900206
1433B_HUMAN	YWHAB	physical	21900206
DEN5A_HUMAN	DENND5A	physical	21900206
CC115_HUMAN	CCDC115	physical	21900206
PIAS4_HUMAN	PIAS4	physical	21624955
KPCZ_HUMAN	PRKCZ	physical	21624955
MBP_HUMAN	MBP	physical	21315177
TF65_HUMAN	RELA	physical	21131967
NCOA3_HUMAN	NCOA3	physical	18313384
TFF1_HUMAN	TFF1	genetic	18313384
SQSTM_HUMAN	SQSTM1	physical	15143057
VHL_HUMAN	VHL	physical	10491320
PAR6B_HUMAN	PARD6B	physical	12887891
PAR6A_HUMAN	PARD6A	physical	12813044
NCF1_HUMAN	NCF1	physical	12056906
H11_HUMAN	HIST1H1A	physical	12056906
PP14A_HUMAN	PPP1R14A	physical	15003508
KPCZ_HUMAN	PRKCZ	physical	7588787
MARCS_HUMAN	MARCKS	physical	7588787
NCF1_HUMAN	NCF1	physical	11145703
HS90A_HUMAN	HSP90AA1	physical	22939624
SQSTM_HUMAN	SQSTM1	physical	23023376
H15_HUMAN	HIST1H1B	physical	8663071
C1QBP_HUMAN	C1QBP	physical	23402259
NPM_HUMAN	NPM1	physical	23402259
COF1_HUMAN	CFL1	physical	23402259
NUMB_HUMAN	NUMB	physical	17203073
NUMB_DROME	numb	physical	17203073
AKT1_HUMAN	AKT1	physical	18353613
AKT2_HUMAN	AKT2	physical	18353613
AKT1_HUMAN	AKT1	physical	18650932
MK07_HUMAN	MAPK7	physical	20538799
C1QBP_HUMAN	C1QBP	physical	25852190
CKAP4_HUMAN	CKAP4	physical	25852190
DYL1_HUMAN	DYNLL1	physical	25852190
L2GL1_HUMAN	LLGL1	physical	25852190
L2GL2_HUMAN	LLGL2	physical	25852190
PAR6A_HUMAN	PARD6A	physical	25852190
PAR6B_HUMAN	PARD6B	physical	25852190
PAR6G_HUMAN	PARD6G	physical	25852190
KPCI_HUMAN	PRKCI	physical	25852190
SQSTM_HUMAN	SQSTM1	physical	25852190
KPCZ_HUMAN	PRKCZ	physical	8375396
GRM5_HUMAN	GRM5	physical	25241761
AKT3_HUMAN	AKT3	physical	25241761
JAM1_HUMAN	F11R	physical	25241761
GSK3B_HUMAN	GSK3B	physical	25241761
PIAS4_HUMAN	PIAS4	physical	27162139
L2GL2_HUMAN	LLGL2	physical	28514442
KPCI_HUMAN	PRKCI	physical	28514442
PAR6G_HUMAN	PARD6G	physical	28514442
L2GL1_HUMAN	LLGL1	physical	28514442
TRI41_HUMAN	TRIM41	physical	28514442
KIBRA_HUMAN	WWC1	physical	28514442
NIPS2_HUMAN	GBAS	physical	28514442
MRCKB_HUMAN	CDC42BPB	physical	28514442
SQSTM_HUMAN	SQSTM1	physical	28514442
PAR6A_HUMAN	PARD6A	physical	28514442
SQSTM_HUMAN	SQSTM1	physical	27143478
PAR6A_HUMAN	PARD6A	physical	27143478

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
DB00675	Tamoxifen

Regulatory Network of KPCZ_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-223, AND MASSSPECTROMETRY.	17081983 [Abstract]
"CCM1 regulates vascular-lumen organization by inducing endothelialpolarity."; Lampugnani M.G., Orsenigo F., Rudini N., Maddaluno L., Boulday G.,Chapon F., Dejana E.; J. Cell Sci. 123:1073-1080(2010). Cited for: SUBCELLULAR LOCATION, SUBUNIT, AND PHOSPHORYLATION AT THR-410.	20332120 [Abstract]
"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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-560, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Kinase-selective enrichment enables quantitative phosphoproteomics ofthe 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-410, AND MASSSPECTROMETRY.	18691976 [Abstract]
"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). Cited for: PHOSPHORYLATION AT THR-410 BY PDPK1.	9768361 [Abstract]

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