KPCD1_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: KPCD1_RAT
• UniProt AC: Q9WTQ1
• Protein Name: Serine/threonine-protein kinase D1
• Gene Name: Prkd1
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 918
• Subcellular Localization: Cytoplasm . Cell membrane . Golgi apparatus, trans-Golgi network . Translocation to the cell membrane is required for kinase activation..
• Protein Description: Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-469 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor. Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (By similarity). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity)..
• Protein Sequence: MSAPPLLRPPSPLLPAAAAVAAAAAALVPGSGPAPFPAPGAAPAGGISFHLQIGLSREPVLLLQDSSGDYSLAHVREMACSIVDQKFPECGFYGLYDKILLFRHDPASENILQLVKIASDIQEGDLIEVVLSASATFEDFQIRPHALFVHSYRAPAFCDHCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNCSGVRRRRLSNVSLTGLGTVRTASAEFSTSAPDEPLLSPVSPGFEQKSPSESFIGREKRSNSQSYVGRPIQLDKLLMSKVKVPHTFVIHSYTRPTVCQFCKKLLKGLFRQGLQCKDCRFNCHKRCAPKVPNNCLGEVTINGELLSPGAESDVVMEEGSDDNDSERNSGLMDDMDEAMVQDTEMALAEGQSDGAEMQDPDADQEDSNRTISPSTSNNIPLMRVVQSVKHTKRRSSTVMKEGWMVHYTSKDTLRKRHYWRLDSKSITLFQNDTGSRYYKEIPLSEILCLEPAKPSALIPTGANPHCFEITTANVVYYVGENVVNPSSPPPNNSVPPSGIGTDVARMWEVAIQHALMPVIPKGSSVGSGTNSHKDISVSISVSNSQIQENVDISTVYQIFPDEVLGSGQFGIVYGGKHRKTGRDVAIKIIDKLRFPTKQESQLRNEVAILQNLHHPGVVNLECMFETPERVFVVMEKLHGDMLEMILSSEKGRLPEHITKFLITQILVALRHLHFKNIVHCDLKPENVLLASADPFPQVKLCDFGFARIIGEKSFRRSVVGTPAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDEDIHDQIQNAAFMYPPNPWKEISHEAIDLINNLLQVKMRKRYSVDKTLSHPWLQDYQTWLDLRELECRIGERYITHESDDSRWEQYAGEQGLQYPAHLINLSASHGDSPEAEEREMKALSERVSIL

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
93	Phosphorylation	KFPECGFYGLYDKIL CCCCCCEEEEECEEE	7.48	-
203	Phosphorylation	GVRRRRLSNVSLTGL CCCCHHCCCCEEECC	33.12	27097102
206	Phosphorylation	RRRLSNVSLTGLGTV CHHCCCCEEECCCCE	25.19	27097102
208	Phosphorylation	RLSNVSLTGLGTVRT HCCCCEEECCCCEEE	23.89	27097102
212	Phosphorylation	VSLTGLGTVRTASAE CEEECCCCEEECCEE	16.32	28551015
217	Phosphorylation	LGTVRTASAEFSTSA CCCEEECCEEECCCC	27.93	-
221	Phosphorylation	RTASAEFSTSAPDEP EECCEEECCCCCCCC	16.98	-
241	Phosphorylation	SPGFEQKSPSESFIG CCCCCCCCCCCCCCC	33.09	27097102
243	Phosphorylation	GFEQKSPSESFIGRE CCCCCCCCCCCCCCC	53.62	27097102
253	Phosphorylation	FIGREKRSNSQSYVG CCCCCCCCCCCCCCC	52.48	27097102
255	Phosphorylation	GREKRSNSQSYVGRP CCCCCCCCCCCCCCC	23.04	27097102
257	Phosphorylation	EKRSNSQSYVGRPIQ CCCCCCCCCCCCCEE	22.93	25575281
258	Phosphorylation	KRSNSQSYVGRPIQL CCCCCCCCCCCCEEH	10.17	25575281
351	Phosphorylation	DVVMEEGSDDNDSER CEEECCCCCCCCCCC	45.10	-
401	Phosphorylation	DQEDSNRTISPSTSN CHHHCCCCCCCCCCC	30.01	27097102
403	Phosphorylation	EDSNRTISPSTSNNI HHCCCCCCCCCCCCC	16.52	27097102
405	Phosphorylation	SNRTISPSTSNNIPL CCCCCCCCCCCCCCH	37.36	27097102
406	Phosphorylation	NRTISPSTSNNIPLM CCCCCCCCCCCCCHH	38.57	27097102
407	Phosphorylation	RTISPSTSNNIPLMR CCCCCCCCCCCCHHH	32.01	27097102
438	Phosphorylation	KEGWMVHYTSKDTLR CCCEEEEECCHHHCC	10.99	-
454	Phosphorylation	RHYWRLDSKSITLFQ CEEEEECCCEEEEEE	32.66	-
464	Phosphorylation	ITLFQNDTGSRYYKE EEEEECCCCCCEEEE	44.60	27097102
466	Phosphorylation	LFQNDTGSRYYKEIP EEECCCCCCEEEECC	21.14	27097102
469	Phosphorylation	NDTGSRYYKEIPLSE CCCCCCEEEECCHHH	10.88	-
508	Phosphorylation	TTANVVYYVGENVVN ECCEEEEEECCCCCC	7.14	-
554	Phosphorylation	MPVIPKGSSVGSGTN CCEECCCCCCCCCCC	28.16	-
744	Phosphorylation	ARIIGEKSFRRSVVG CEECCCCCHHCCCCC	21.49	25575281
748	Phosphorylation	GEKSFRRSVVGTPAY CCCCHHCCCCCCHHH	19.52	29779826
752	Phosphorylation	FRRSVVGTPAYLAPE HHCCCCCCHHHHCHH	7.98	23984901
755	Phosphorylation	SVVGTPAYLAPEVLR CCCCCHHHHCHHHHH	12.47	25575281
835	Phosphorylation	VKMRKRYSVDKTLSH HHHHHCCCCCCCCCC	28.07	22673903
912	Phosphorylation	EREMKALSERVSIL- HHHHHHHHHHHCCC-	28.37	23984901
916	Phosphorylation	KALSERVSIL----- HHHHHHHCCC-----	25.13	23984901

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
203	S	Phosphorylation	Kinase	PAK1	P35465	PSP
203	S	Phosphorylation	Kinase	PAK2	Q64303	PSP
403	S	Phosphorylation	Kinase	MAPK13	Q9WTY9	Uniprot
407	S	Phosphorylation	Kinase	MAPK13	Q9WTY9	Uniprot
469	Y	Phosphorylation	Kinase	ABL	-	Uniprot
744	S	Phosphorylation	Kinase	PKCD	P09215	PSP
744	S	Phosphorylation	Kinase	PRKD1	Q15139	PSP
744	S	Phosphorylation	Kinase	PRKCE	P16054	GPS
744	S	Phosphorylation	Kinase	PRKCH	P23298	GPS
748	S	Phosphorylation	Kinase	PKCD	P09215	PSP
748	S	Phosphorylation	Kinase	PRKD1	Q15139	PSP
748	S	Phosphorylation	Kinase	PRKCE	P16054	GPS
748	S	Phosphorylation	Kinase	PRKCH	P23298	GPS
916	S	Phosphorylation	Kinase	PRKD1	Q9WTQ1	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
403	S	Phosphorylation	Phosphorylated at Ser-403 and Ser-407 by MAPK13 during regulation of insulin secretion in pancreatic beta cells.	-
407	S	Phosphorylation	Phosphorylated at Ser-403 and Ser-407 by MAPK13 during regulation of insulin secretion in pancreatic beta cells.	-
744	S	Oxidation	Phosphorylated at Tyr-93 and by ABL at Tyr-469, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-744/Ser-748 by PKRD.	15145937
744	S	Phosphorylation	Phosphorylated at Tyr-93 and by ABL at Tyr-469, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-744/Ser-748 by PKRD.	15145937
748	S	Oxidation	Phosphorylated at Tyr-93 and by ABL at Tyr-469, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-744/Ser-748 by PKRD.	15145937
748	S	Phosphorylation	Phosphorylated at Tyr-93 and by ABL at Tyr-469, which primes the kinase in response to oxidative stress, and promotes a second step activating phosphorylation at Ser-744/Ser-748 by PKRD.	15145937
916	S	Phosphorylation	Phosphorylated on Ser-916 upon S.enterica infection in macrophages.	15145937

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of KPCD1_RAT !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
UNC18_CAEEL	unc-18	physical	22593072
EGFR_HUMAN	EGFR	physical	12359306

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Hepatocyte resistance to oxidative stress is dependent on proteinkinase C-mediated down-regulation of c-Jun/AP-1.";
Wang Y., Schattenberg J.M., Rigoli R.M., Storz P., Czaja M.J.;
J. Biol. Chem. 279:31089-31097(2004).
Cited for: PHOSPHORYLATION AT SER-744; SER-748 AND SER-916.
PubMed: 15145937