KPCZ_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KPCZ_RAT
• UniProt AC: P09217
• Protein Name: Protein kinase C zeta type
• Gene Name: Prkcz
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 592
• Subcellular Localization: Cytoplasm . Endosome . Cell junction . 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. 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 (By similarity)..
• Protein Sequence: MPSRTDPKMDRSGGRVRLKAHYGGDILITSVDPTTTFQDLCEEVRDMCGLHQQHPLTLKWVDSEGDPCTVSSQMELEEAFRLACQGRDEVLIIHVFPSIPEQPGMPCPGEDKSIYRRGARRWRKLYRANGHLFQAKRFNRRAYCGQCSERIWGLARQGYRCINCKLLVHKRCHVLVPLTCRRHMDSVMPSQEPPVDDKNDGVDLPSEETDGIAYISSSRKHDNIKDDSEDLKPVIDGVDGIKISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQASSNPFLVGLHSCFQTTSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGMCKEGLGPGDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFDIITDNPDMNTEDYLFQVILEKPIRIPRFLSVKASHVLKGFLNKDPKERLGCRPQTGFSDIKSHAFFRSIDWDLLEKKQTLPPFQPQITDDYGLDNFDTQFTSEPVQLTPDDEDVIKRIDQSEFEGFEYINPLLLSAEESV

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
57	O-linked_Glycosylation	LHQQHPLTLKWVDSE CCCCCCEEEEEECCC	30.64	12639255
148	O-linked_Glycosylation	RAYCGQCSERIWGLA CCCCCHHHHHHHHHH	23.25	12639247
179	O-linked_Glycosylation	CHVLVPLTCRRHMDS CCEEEEECHHHHHHH	9.63	18295358
179	Phosphorylation	CHVLVPLTCRRHMDS CCEEEEECHHHHHHH	9.63	-
186	Phosphorylation	TCRRHMDSVMPSQEP CHHHHHHHCCCCCCC	16.85	10620507
262	Phosphorylation	IRVIGRGSYAKVLLV EEEECCCCCEEEEEE	22.13	18295358
263	Phosphorylation	RVIGRGSYAKVLLVR EEECCCCCEEEEEEE	17.17	18295358
410	Phosphorylation	GPGDTTSTFCGTPNY CCCCCCCCCCCCCCE	22.35	16829026
490	Acetylation	VKASHVLKGFLNKDP ECHHHHHHHHCCCCH	46.67	22902405
560	Phosphorylation	TSEPVQLTPDDEDVI CCCCCCCCCCCHHHH	13.95	17724026
591	Phosphorylation	LLLSAEESV------ HHHHHHHCC------	25.32	12813044

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	O15530	PSP
410	T	Phosphorylation	Kinase	PDK1	O55173	PSP
410	T	Phosphorylation	Kinase	PI3K	-	Uniprot
560	T	Phosphorylation	Kinase	PRKCZ	P09217	GPS
560	T	Phosphorylation	Kinase	PDPK1	O55173	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
410	T	Phosphorylation	CDH5 is required for its phosphorylation at Thr-410.	14580237
410	T	Phosphorylation	Phosphorylation at Thr-410 by PI3K activates the kinase (By similarity).	14580237

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of KPCZ_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
S40A1_RAT	Slc40a1	physical	10477520
KCAB2_RAT	Kcnab2	physical	10477520
FEZ1_RAT	Fez1	physical	9971736
PEBP1_RAT	Pebp1	physical	12551925
MK01_XENLA	mapk1-a	physical	8026469
MP2K1_XENLA	map2k1	physical	8026469
MP2K1_RAT	Map2k1	physical	8026469
MP2K2_RAT	Map2k2	physical	8026469
KPCZ_RAT	Prkcz	physical	11463795
SQSTM_RAT	Sqstm1	physical	9177193
KCNA5_RAT	Kcna5	physical	17699685

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Molecular mechanisms regulating protein kinase Czeta turnover andcellular transformation.";
Le Good J.A., Brindley D.N.;
Biochem. J. 378:83-92(2004).
Cited for: PHOSPHORYLATION AT THR-410 AND THR-560.
PubMed: 14580237