KPCD1_HUMAN - dbPTM
KPCD1_HUMAN - PTM Information in dbPTM
Basic Information of Protein
UniProt ID KPCD1_HUMAN
UniProt AC Q15139
Protein Name Serine/threonine-protein kinase D1
Gene Name PRKD1
Organism Homo sapiens (Human).
Sequence Length 912
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-463 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. [PubMed: 24623306 Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity]
Protein Sequence MSAPPVLRPPSPLLPVAAAAAAAAAALVPGSGPGPAPFLAPVAAPVGGISFHLQIGLSREPVLLLQDSSGDYSLAHVREMACSIVDQKFPECGFYGMYDKILLFRHDPTSENILQLVKAASDIQEGDLIEVVLSASATFEDFQIRPHALFVHSYRAPAFCDHCGEMLWGLVRQGLKCEGCGLNYHKRCAFKIPNNCSGVRRRRLSNVSLTGVSTIRTSSAELSTSAPDEPLLQKSPSESFIGREKRSNSQSYIGRPIHLDKILMSKVKVPHTFVIHSYTRPTVCQYCKKLLKGLFRQGLQCKDCRFNCHKRCAPKVPNNCLGEVTINGDLLSPGAESDVVMEEGSDDNDSERNSGLMDDMEEAMVQDAEMAMAECQNDSGEMQDPDPDHEDANRTISPSTSNNIPLMRVVQSVKHTKRKSSTVMKEGWMVHYTSKDTLRKRHYWRLDSKCITLFQNDTGSRYYKEIPLSEILSLEPVKTSALIPNGANPHCFEITTANVVYYVGENVVNPSSPSPNNSVLTSGVGADVARMWEIAIQHALMPVIPKGSSVGTGTNLHRDISVSISVSNCQIQENVDISTVYQIFPDEVLGSGQFGIVYGGKHRKTGRDVAIKIIDKLRFPTKQESQLRNEVAILQNLHHPGVVNLECMFETPERVFVVMEKLHGDMLEMILSSEKGRLPEHITKFLITQILVALRHLHFKNIVHCDLKPENVLLASADPFPQVKLCDFGFARIIGEKSFRRSVVGTPAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDEDIHDQIQNAAFMYPPNPWKEISHEAIDLINNLLQVKMRKRYSVDKTLSHPWLQDYQTWLDLRELECKIGERYITHESDDLRWEKYAGEQGLQYPTHLINPSASHSDTPETEETEMKALGERVSIL
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 Orthologous
Protein Cluster
95PhosphorylationKFPECGFYGMYDKIL
CCCCCCEEEEECEEE		6.0519060867
153PhosphorylationPHALFVHSYRAPAFC
CCEEEEEECCCCHHH		15.8323312004
154PhosphorylationHALFVHSYRAPAFCD
CEEEEEECCCCHHHH		8.9123312004
205PhosphorylationGVRRRRLSNVSLTGV
CCCCHHCCCCEEEEE		33.1219664994
208PhosphorylationRRRLSNVSLTGVSTI
CHHCCCCEEEEEEEE		25.1930266825
210PhosphorylationRLSNVSLTGVSTIRT
HCCCCEEEEEEEEEC		28.2030266825
213PhosphorylationNVSLTGVSTIRTSSA
CCEEEEEEEEECCCC		21.3323663014
214PhosphorylationVSLTGVSTIRTSSAE
CEEEEEEEEECCCCC		16.4523663014
217PhosphorylationTGVSTIRTSSAELST
EEEEEEECCCCCCCC		24.1530266825
218PhosphorylationGVSTIRTSSAELSTS
EEEEEECCCCCCCCC		20.0830266825
219PhosphorylationVSTIRTSSAELSTSA
EEEEECCCCCCCCCC		25.7530266825
223PhosphorylationRTSSAELSTSAPDEP
ECCCCCCCCCCCCCC		16.3030266825
224PhosphorylationTSSAELSTSAPDEPL
CCCCCCCCCCCCCCH		41.3430266825
225PhosphorylationSSAELSTSAPDEPLL
CCCCCCCCCCCCCHH		34.1330266825
235PhosphorylationDEPLLQKSPSESFIG
CCCHHCCCCCCCCCC		22.2430266825
237PhosphorylationPLLQKSPSESFIGRE
CHHCCCCCCCCCCCC		53.6230266825
239PhosphorylationLQKSPSESFIGREKR
HCCCCCCCCCCCCCC		26.8830266825
247PhosphorylationFIGREKRSNSQSYIG
CCCCCCCCCCCCCCC		52.4823927012
249PhosphorylationGREKRSNSQSYIGRP
CCCCCCCCCCCCCCC		23.0425159151
251PhosphorylationEKRSNSQSYIGRPIH
CCCCCCCCCCCCCEE		20.6625219547
252PhosphorylationKRSNSQSYIGRPIHL
CCCCCCCCCCCCEEH		10.3525219547
292UbiquitinationQYCKKLLKGLFRQGL
HHHHHHHHHHHHCCC		65.09-
345PhosphorylationDVVMEEGSDDNDSER
CEEEECCCCCCHHHC		45.1019369195
379PhosphorylationMAECQNDSGEMQDPD
HHHHHCCCCCCCCCC		44.1719369195
395PhosphorylationDHEDANRTISPSTSN
CCHHHCCCCCCCCCC		26.1330266825
397PhosphorylationEDANRTISPSTSNNI
HHHCCCCCCCCCCCC		16.5229255136
399PhosphorylationANRTISPSTSNNIPL
HCCCCCCCCCCCCCH		37.3630266825
400PhosphorylationNRTISPSTSNNIPLM
CCCCCCCCCCCCCHH		38.5730266825
401PhosphorylationRTISPSTSNNIPLMR
CCCCCCCCCCCCHHH		32.0123927012
412PhosphorylationPLMRVVQSVKHTKRK
CHHHHHHHHHCCCCC		22.8626699800
420PhosphorylationVKHTKRKSSTVMKEG
HHCCCCCCCCCCCCC		34.9628857561
421PhosphorylationKHTKRKSSTVMKEGW
HCCCCCCCCCCCCCE		28.2326657352
422PhosphorylationHTKRKSSTVMKEGWM
CCCCCCCCCCCCCEE		31.5428857561
432PhosphorylationKEGWMVHYTSKDTLR
CCCEEEEECCHHHHH		10.9912637538
434PhosphorylationGWMVHYTSKDTLRKR
CEEEEECCHHHHHHH		22.7430387612
443PhosphorylationDTLRKRHYWRLDSKC
HHHHHHEEEEECCCE		9.03-
448PhosphorylationRHYWRLDSKCITLFQ
HEEEEECCCEEEEEE		33.7428857561
458PhosphorylationITLFQNDTGSRYYKE
EEEEECCCCCCEEEC		44.6023898821
460PhosphorylationLFQNDTGSRYYKEIP
EEECCCCCCEEECCC		21.1423898821
463PhosphorylationNDTGSRYYKEIPLSE
CCCCCCEEECCCHHH		10.8816891660
473PhosphorylationIPLSEILSLEPVKTS
CCHHHCCCCCCCCCC		36.0322199227
502PhosphorylationTTANVVYYVGENVVN
ECCEEEEEECCCCCC		7.1412637538
548PhosphorylationMPVIPKGSSVGTGTN
CCEECCCCCCCCCCC		28.1625159151
549PhosphorylationPVIPKGSSVGTGTNL
CEECCCCCCCCCCCC		32.9825159151
552PhosphorylationPKGSSVGTGTNLHRD
CCCCCCCCCCCCCCC		38.3820873877
554PhosphorylationGSSVGTGTNLHRDIS
CCCCCCCCCCCCCEE		34.1521406692
612AcetylationTGRDVAIKIIDKLRF
CCCCHHHHHHHHHCC		24.7069167
622UbiquitinationDKLRFPTKQESQLRN
HHHCCCCCCHHHHHH		52.91-
675UbiquitinationEMILSSEKGRLPEHI
HHHHHCCCCCCCHHH		51.80-
708UbiquitinationNIVHCDLKPENVLLA
CCCCCCCCHHHEEEE		36.71-
716PhosphorylationPENVLLASADPFPQV
HHHEEEEECCCCCCC		32.9220068231
724UbiquitinationADPFPQVKLCDFGFA
CCCCCCCEECHHCCC		37.84-
737UbiquitinationFARIIGEKSFRRSVV
CCEECCCCCHHCCCC		50.08-
738PhosphorylationARIIGEKSFRRSVVG
CEECCCCCHHCCCCC		21.4923401153
742PhosphorylationGEKSFRRSVVGTPAY
CCCCHHCCCCCCHHH		19.5229255136
746PhosphorylationFRRSVVGTPAYLAPE
HHCCCCCCHHHHCHH		7.9821945579
749PhosphorylationSVVGTPAYLAPEVLR
CCCCCHHHHCHHHHH		12.4721945579
829PhosphorylationVKMRKRYSVDKTLSH
HHHHHCCCCCCCCCC		28.0719369195
888PhosphorylationPTHLINPSASHSDTP
CCCCCCCCCCCCCCC		37.6029116813
890PhosphorylationHLINPSASHSDTPET
CCCCCCCCCCCCCCC		28.0629116813
892PhosphorylationINPSASHSDTPETEE
CCCCCCCCCCCCCHH		40.4622496350
894PhosphorylationPSASHSDTPETEETE
CCCCCCCCCCCHHHH		26.4922496350
910PhosphorylationKALGERVSIL-----
HHHHHHCCCC-----		25.1330266825
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
95YPhosphorylationKinaseSRC64-PhosphoELM
95YPhosphorylationKinaseSRCP12931
PSP
205SPhosphorylationKinasePKD1P98161
PhosphoELM
205SPhosphorylationKinasePRKD1Q15139
GPS
249SPhosphorylationKinasePKC_GROUP-PhosphoELM
249SPhosphorylationKinasePKC-FAMILY-GPS
397SPhosphorylationKinaseMAPK13O15264
Uniprot
401SPhosphorylationKinaseMAPK13O15264
Uniprot
412SPhosphorylationKinasePRKCDQ05655
GPS
412SPhosphorylationKinasePKCAP17252
PSP
421SPhosphorylationKinasePKACAP17612
PSP
432YPhosphorylationKinaseABL-FAMILY-GPS
432YPhosphorylationKinaseSRCP12931
PSP
432YPhosphorylationKinaseABL1P00519
PhosphoELM
463YPhosphorylationKinaseABL-FAMILY-GPS
463YPhosphorylationKinaseSRCP12931
PSP
463YPhosphorylationKinaseABL1P00519
PhosphoELM
502YPhosphorylationKinaseABL1P00519
PhosphoELM
502YPhosphorylationKinaseABL-FAMILY-GPS
502YPhosphorylationKinaseSRCP12931
PSP
738SPhosphorylationKinasePRKCHP24723
GPS
738SPhosphorylationKinasePRKCAP17252
GPS
738SPhosphorylationKinaseKPCDQ05655
PhosphoELM
738SPhosphorylationKinasePRKD1Q15139
PSP
738SPhosphorylationKinasePRKD3O94806
PSP
738SPhosphorylationKinasePRKCEQ02156
GPS
742SPhosphorylationKinasePRKD1Q15139
PSP
742SPhosphorylationKinasePRKD3O94806
PSP
742SPhosphorylationKinaseKPCDQ05655
PhosphoELM
742SPhosphorylationKinasePRKCAP17252
GPS
742SPhosphorylationKinasePRKCHP24723
GPS
742SPhosphorylationKinasePRKCEQ02156
GPS
910SPhosphorylationKinasePKD1P98161
PhosphoELM
910SPhosphorylationKinasePRKD1Q15139
PSP
Functions of PTM Sites
Modified Location Modified Residue Modification Function Reference
397SPhosphorylation

19135240
401SPhosphorylation

19135240
738SOxidation

15024053
738SPhosphorylation

15024053
742SOxidation

15024053
742SPhosphorylation

15024053
910SPhosphorylation

17703233
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 KPCD1_HUMAN !!
Protein-Protein Interaction
Interacting Protein Gene Name Interaction Type PPI Reference Domain-Domain Interactions
ADAP1_HUMANADAP1physical
12893243
BTK_HUMANBTKphysical
10561498
JUN_HUMANJUNphysical
11948398
C1QBP_HUMANC1QBPphysical
10831594
HSPB1_HUMANHSPB1physical
15728188
CSN2_HUMANCOPS2physical
12628923
CSN5_HUMANCOPS5physical
12628923
CSN7A_HUMANCOPS7Aphysical
12628923
JUN_HUMANJUNphysical
12628923
P53_HUMANTP53physical
12628923
KPCD1_HUMANPRKD1physical
12628923
IBTK_HUMANIBTKphysical
21482705
AKP13_HUMANAKAP13physical
15383279
PP14A_HUMANPPP1R14Aphysical
15003508
BAD_HUMANBADphysical
20179209
AP2A_HUMANTFAP2Aphysical
18845787
NOS1_HUMANNOS1physical
24740233
UBP28_HUMANUSP28physical
24623306
NHRF2_HUMANSLC9A3R2physical
27173435
YAP1_HUMANYAP1physical
27173435
SPY2_HUMANSPRY2physical
19458088
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
There are no disease associations of PTM sites.
Regulatory Network of KPCD1_HUMAN

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Related Literatures of Post-Translational Modification
Phosphorylation
ReferencePubMed
"Large-scale proteomics analysis of the human kinome.";
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,Mann M., Daub H.;
Mol. Cell. Proteomics 8:1751-1764(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205; SER-208; THR-217;SER-235; SER-247; SER-249; SER-345; SER-379; THR-395; SER-397;SER-399; THR-400; SER-401; SER-420; SER-448; SER-460; SER-473;SER-548; SER-549; SER-742; SER-888; SER-890 AND SER-910, AND MASSSPECTROMETRY.
"Regulation of PKD by the MAPK p38delta in insulin secretion andglucose homeostasis.";
Sumara G., Formentini I., Collins S., Sumara I., Windak R.,Bodenmiller B., Ramracheya R., Caille D., Jiang H., Platt K.A.,Meda P., Aebersold R., Rorsman P., Ricci R.;
Cell 136:235-248(2009).
Cited for: PHOSPHORYLATION AT SER-397 AND SER-401, INTERACTION WITH MAPK13, ANDFUNCTION.
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach.";
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.;
Anal. Chem. 81:4493-4501(2009).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-217; SER-237; SER-397;SER-401 AND SER-910, AND MASS SPECTROMETRY.
"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 SER-742, AND MASSSPECTROMETRY.
"Toward a global characterization of the phosphoproteome in prostatecancer cells: identification of phosphoproteins in the LNCaP cellline.";
Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
Electrophoresis 28:2027-2034(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-205 AND THR-210, ANDMASS SPECTROMETRY.
"DAP kinase regulates JNK signaling by binding and activating proteinkinase D under oxidative stress.";
Eisenberg-Lerner A., Kimchi A.;
Cell Death Differ. 14:1908-1915(2007).
Cited for: PHOSPHORYLATION BY DAPK1, INTERACTION WITH DAPK1, AUTOPHOSPHORYLATIONAT SER-910, AND ENZYME REGULATION.
"A novel tyrosine phosphorylation site in protein kinase D contributesto oxidative stress-mediated activation.";
Doppler H., Storz P.;
J. Biol. Chem. 282:31873-31881(2007).
Cited for: PHOSPHORYLATION AT TYR-95.
"Tyrosine phosphorylation of protein kinase D in the pleckstrinhomology domain leads to activation.";
Storz P., Doppler H., Johannes F.J., Toker A.;
J. Biol. Chem. 278:17969-17976(2003).
Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT TYR-432; TYR-463 ANDTYR-502, AND MUTAGENESIS OF TYR-432; TYR-463; TYR-502 AND LYS-612.

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