PDPK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: PDPK1_MOUSE
• UniProt AC: Q9Z2A0
• Protein Name: 3-phosphoinositide-dependent protein kinase 1
• Gene Name: Pdpk1
• Organism: Mus musculus (Mouse).
• Sequence Length: 559
• Subcellular Localization: Cytoplasm . Nucleus. Cell membrane ; Peripheral membrane protein . Cell junction, focal adhesion. Tyrosine phosphorylation seems to occur only at the cell membrane. Translocates to the cell membrane following insulin stimulation by a mechanism that i
• Protein Description: Serine/threonine kinase which acts as a master kinase, phosphorylating and activating a subgroup of the AGC family of protein kinases. Its targets include: protein kinase B (PKB/AKT1, PKB/AKT2, PKB/AKT3), p70 ribosomal protein S6 kinase (RPS6KB1), p90 ribosomal protein S6 kinase (RPS6KA1, RPS6KA2 and RPS6KA3), cyclic AMP-dependent protein kinase (PRKACA), protein kinase C (PRKCD and PRKCZ), serum and glucocorticoid-inducible kinase (SGK1, SGK2 and SGK3), p21-activated kinase-1 (PAK1), protein kinase PKN (PKN1 and PKN2). Plays a central role in the transduction of signals from insulin by providing the activating phosphorylation to PKB/AKT1, thus propagating the signal to downstream targets controlling cell proliferation and survival, as well as glucose and amino acid uptake and storage. Negatively regulates the TGF-beta-induced signaling by: modulating the association of SMAD3 and SMAD7 with TGF-beta receptor, phosphorylating SMAD2, SMAD3, SMAD4 and SMAD7, preventing the nuclear translocation of SMAD3 and SMAD4 and the translocation of SMAD7 from the nucleus to the cytoplasm in response to TGF-beta. Activates PPARG transcriptional activity and promotes adipocyte differentiation. Activates the NF-kappa-B pathway via phosphorylation of IKKB. The tyrosine phosphorylated form is crucial for the regulation of focal adhesions by angiotensin II. Controls proliferation, survival, and growth of developing pancreatic cells. Participates in the regulation of Ca(2+) entry and Ca(2+)-activated K(+) channels of mast cells. Essential for the motility of vascular endothelial cells (ECs) and is involved in the regulation of their chemotaxis. Plays a critical role in cardiac homeostasis by serving as a dual effector for cell survival and beta-adrenergic response. Plays an important role during thymocyte development by regulating the expression of key nutrient receptors on the surface of pre-T cells and mediating Notch-induced cell growth and proliferative responses. Provides negative feedback inhibition to toll-like receptor-mediated NF-kappa-B activation in macrophages..
• Protein Sequence: MARTTSQLYDAVPIQSSVVLCSCPSPSMVRSQTEPGSSPGIPSGVSRQGSTMDGTTAEARPSTNPLQQHPAQLPPQPRKKRPEDFKFGKILGEGSFSTVVLARELATSREYAIKILEKRHIIKENKVPYVTRERDVMSRLDHPFFVKLYFTFQDDEKLYFGLSYAKNGELLKYIRKIGSFDETCTRFYTAEIVSALEYLHGKGIIHRDLKPENILLNEDMHIQITDFGTAKVLSPESKQARANSFVGTAQYVSPELLTEKSACKSSDLWALGCIIYQLVAGLPPFRAGNEYLIFQKIIKLEYHFPEKFFPKARDLVEKLLVLDATKRLGCEEMEGYGPLKAHPFFETITWENLHQQTPPKLTAYLPAMSEDDEDCYGNYDNLLSQFGFMQVSSSSSSHSLSTVETSLPQRSGSNIEQYIHDLDTNSFELDLQFSEDEKRLLLEKQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTEGPHLYYVDPVNKVLKGEIPWSQELRPEAKNFKTFFVHTPNRTYYLMDPSGNAHKWCRKIQEVWRQQYQSNPDAAVQ

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
3	Methylation	-----MARTTSQLYD -----CCCCHHHHHH	36.92	16188535
9	Phosphorylation	ARTTSQLYDAVPIQS CCCHHHHHHCCCCCC	8.33	29514104
22	Phosphorylation	QSSVVLCSCPSPSMV CCEEEEEECCCHHHC	25.54	26643407
25	Phosphorylation	VVLCSCPSPSMVRSQ EEEEECCCHHHCCCC	33.65	25266776
27	Phosphorylation	LCSCPSPSMVRSQTE EEECCCHHHCCCCCC	33.96	26643407
33	Phosphorylation	PSMVRSQTEPGSSPG HHHCCCCCCCCCCCC	45.45	25619855
37	Phosphorylation	RSQTEPGSSPGIPSG CCCCCCCCCCCCCCC	44.04	25619855
38	Phosphorylation	SQTEPGSSPGIPSGV CCCCCCCCCCCCCCC	32.82	25619855
43	Phosphorylation	GSSPGIPSGVSRQGS CCCCCCCCCCCCCCC	50.32	25619855
46	Phosphorylation	PGIPSGVSRQGSTMD CCCCCCCCCCCCCCC	23.55	25619855
50	Phosphorylation	SGVSRQGSTMDGTTA CCCCCCCCCCCCCCC	16.54	22817900
51	Phosphorylation	GVSRQGSTMDGTTAE CCCCCCCCCCCCCCC	26.55	28464351
55	Phosphorylation	QGSTMDGTTAEARPS CCCCCCCCCCCCCCC	20.69	22817900
56	Phosphorylation	GSTMDGTTAEARPST CCCCCCCCCCCCCCC	28.20	22817900
63	Phosphorylation	TAEARPSTNPLQQHP CCCCCCCCCCCCCCC	43.46	22817900
98	Phosphorylation	LGEGSFSTVVLAREL CCCCCCHHHHHHHHH	16.78	18779572
126	Ubiquitination	RHIIKENKVPYVTRE HHCHHCCCCCEEECC	45.75	-
163	Phosphorylation	EKLYFGLSYAKNGEL CEEEEEEEECCCCHH	24.35	22817900
234	Phosphorylation	FGTAKVLSPESKQAR CCCEEECCHHHHHHH	29.61	25521595
244	Phosphorylation	SKQARANSFVGTAQY HHHHHHHCCCCCCCC	21.96	22322096
248	Phosphorylation	RANSFVGTAQYVSPE HHHCCCCCCCCCCHH	12.80	22322096
251	Phosphorylation	SFVGTAQYVSPELLT CCCCCCCCCCHHHHC	10.63	25619855
253	Phosphorylation	VGTAQYVSPELLTEK CCCCCCCCHHHHCCH	14.02	25619855
260	Ubiquitination	SPELLTEKSACKSSD CHHHHCCHHCCCCHH	37.81	-
299	Ubiquitination	LIFQKIIKLEYHFPE EEEEEEHHHHHCCCH	38.45	-
307	Acetylation	LEYHFPEKFFPKARD HHHCCCHHHCHHHHH	53.17	23806337
357	Phosphorylation	WENLHQQTPPKLTAY CHHHHCCCCCCEEEE	34.68	-
376	Phosphorylation	SEDDEDCYGNYDNLL CCCCCCCCCCHHHHH	22.26	-
379	Phosphorylation	DEDCYGNYDNLLSQF CCCCCCCHHHHHHHH	11.22	-
396	Phosphorylation	MQVSSSSSSHSLSTV EEECCCCCCCCCEEE	33.74	-
397	Phosphorylation	QVSSSSSSHSLSTVE EECCCCCCCCCEEEE	21.02	-
399	Phosphorylation	SSSSSSHSLSTVETS CCCCCCCCCEEEEEC	26.43	12923190
401	Phosphorylation	SSSSHSLSTVETSLP CCCCCCCEEEEECCC	33.16	-
413	Phosphorylation	SLPQRSGSNIEQYIH CCCCCCCCCHHHHEE	35.56	-
504	Phosphorylation	LKGEIPWSQELRPEA HCCCCCCCCCCCCCC	14.39	22817900
516	Phosphorylation	PEAKNFKTFFVHTPN CCCCCCCEEEEECCC	20.40	25521595
532	Phosphorylation	TYYLMDPSGNAHKWC EEEEECCCCCHHHHH	40.18	22817900

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
9	Y	Phosphorylation	Kinase	INSR	P15208	Uniprot
9	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
244	S	Phosphorylation	Kinase	PDPK1	Q9Z2A0	GPS
357	T	Phosphorylation	Kinase	MELK	Q61846	Uniprot
376	Y	Phosphorylation	Kinase	INSR	P15208	Uniprot
376	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
379	Y	Phosphorylation	Kinase	INSR	P15208	Uniprot
379	Y	Phosphorylation	Kinase	SRC	P05480	Uniprot
397	S	Phosphorylation	Kinase	MAP3K5	O35099	Uniprot
399	S	Phosphorylation	Kinase	PDPK1	Q9Z2A0	GPS
401	S	Phosphorylation	Kinase	MAP3K5	O35099	Uniprot
504	S	Phosphorylation	Kinase	PKCT	Q04759	PSP
504	S	Phosphorylation	Kinase	PKCT	Q02111	PSP
516	T	Phosphorylation	Kinase	PDPK1	Q9Z2A0	GPS
532	S	Phosphorylation	Kinase	PKCT	Q04759	PSP
532	S	Phosphorylation	Kinase	PKCT	Q02111	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
244	S	Phosphorylation	PDPK1 itself can autophosphorylate Ser-244, leading to its own activation.	15345747
244	S	Phosphorylation	Palmitate negatively regulates autophosphorylation at Ser-244 and palmitate-induced phosphorylation at Ser-532 and Ser-504 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1.	15345747
244	S	Phosphorylation	Phosphorylation on Ser-244 in the activation loop is required for full activity.	15345747
357	T	Phosphorylation	Phosphorylation at Thr-357 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-397 and Ser-401 by MAP3K5 (By similarity).	-
397	S	Phosphorylation	Phosphorylation at Thr-357 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-397 and Ser-401 by MAP3K5 (By similarity).	-
401	S	Phosphorylation	Phosphorylation at Thr-357 by MELK partially inhibits kinase activity, the inhibition is cooperatively enhanced by phosphorylation at Ser-397 and Ser-401 by MAP3K5 (By similarity).	-
504	S	Phosphorylation	Palmitate negatively regulates autophosphorylation at Ser-244 and palmitate-induced phosphorylation at Ser-532 and Ser-504 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1.	19047061
532	S	Phosphorylation	Palmitate negatively regulates autophosphorylation at Ser-244 and palmitate-induced phosphorylation at Ser-532 and Ser-504 by PKC/PRKCQ negatively regulates its ability to phosphorylate PKB/AKT1.	19047061

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of PDPK1_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of PDPK1_MOUSE !!

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Protein kinase C theta (PKCtheta)-dependent phosphorylation of PDK1at Ser504 and Ser532 contributes to palmitate-induced insulinresistance.";
Wang C., Liu M., Riojas R.A., Xin X., Gao Z., Zeng R., Wu J.,Dong L.Q., Liu F.;
J. Biol. Chem. 284:2038-2044(2009).
Cited for: PHOSPHORYLATION AT SER-504 AND SER-532 BY PKC/PRKCQ.
PubMed: 19047061