Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

PLD1 (phospholipase D1, phosphatidylcholine-specific)

Written2010-10Chang Sup Lee, Sung Ho Ryu
Department of Life Science, Division of Molecular, Life Sciences, Division of Integrative Biosciences, Biotechnology, WCU program, Pohang University of Science, Technology, Pohang, 790-784, South Korea

(Note : for Links provided by Atlas : click)

Identity

Alias_namesphospholipase D1
Other alias
HGNC (Hugo) PLD1
LocusID (NCBI) 5337
Atlas_Id 43716
Location 3q26.31  [Link to chromosome band 3q26]
Location_base_pair Starts at 171600405 and ends at 171810494 bp from pter ( according to hg19-Feb_2009)  [Mapping PLD1.png]
Fusion genes
(updated 2016)
MGAT4C (12q21.31) / PLD1 (3q26.31)OSBPL2 (20q13.33) / PLD1 (3q26.31)PLD1 (3q26.31) / AGBL1 (15q25.3)
PLD1 (3q26.31) / RPS19 (19q13.2)TFDP2 (3q23) / PLD1 (3q26.31)

DNA/RNA

 
  Exons are represented by red rectangles and introns by lines. The picture is not represented by exact scale.
Description The PLD1 gene is composed of 27 exons (PLD1a) or 26 exons (PLD1b) and introns spanning 209658 bp. It starts at 171318616 and ends at 171528273 (NCBI database: entrez gene: PLD1 phospholipase D1, phosphatidylcholine-specific (Homo sapiens)).
Transcription PLD1 DNA has two transcripts by alternative splicing. (PLD1a: 27 exons, 5607 bp mRNA, 1074 amino acids, PLD1b: 26 exons, 5493 bp mRNA, 1036 amino acids) (NCBI database: NCBI Reference Sequence: NM_002662.3 (PLD1a), NM_001130081.1 (PLD1b)).

Protein

 
  PX: Phox homology (PX) domain; PH: Pleckstrin homology (PH) domain; Loop: Loop region; I, II, III, IV: conserved regions I, II, III, and IV; The red arrow indicates the difference between PLD1a and PLD1b.
Description PLD1 (MW: about 120 kDa) contains the several conserved domains/regions (Hammond et al., 1995). PLD superfamily has a well-conserved HKD motif (HXK[X]4D[X]6GSXN), which is in conserved regions II and IV that mediate PLD enzymatic activity. In addition, the PX and PH domains are known to be implicated in interactions with other proteins and phosphoinositide 4,5-bisphosphate (PtdIns (4,5)P2), respectively (Sung et al., 1999). Recently, the PX and PH domains of PLD have been reported to be the core binding regions of PLD and to mediate its functions.
For example, dynamin and μ2 showed the effects on EGFR-mediated endocytosis via R128/R197 of the PLD1-PX domain and R304 of the PLD1-PH domain, respectively (Lee et al., 2006; Lee et al., 2009b). Also, PLCgamma and munc18 can interact with the P161/P164 of the PLD1-PX domain and the C-terminal region (184~212 residues) of the PLD1-PX domain, respectively (Jang et al., 2003; Lee et al., 2004). These interactions occur in an EGF-dependent manner and contribute to the regulation of PLD activity. Furthermore, PKCalpha can phosphorylate the T147 of the PLD1-PX domain to increase PLD activity (Kim et al., 1999). In addition, to protein interactions, these domains can interact with phospholipids. Recently, it has been reported that phosphoinositide 3,4,5-bisphosphate (PtdIns (3,4,5)P3 interacts with the R179 of the PLD1-PX domain and can stimulate PLD activity (Lee et al., 2005).
Phosphatidic acid-(PA) can also bind to PLD via a secondary lipid-binding pocket residue (R158) in the PLD1-PX domain (Stahelin et al., 2004). In addition, PLD1-PH domain also interacts with phosphoinositide 4,5-bisphosphate (PtdIns (4,5)P2 (Hodgkin et al., 2000). It has been reported that this interaction can regulate PLD activity and localization.
Expression PLD1 is ubiquitously expressed in a variety of tissues including brain, lung, heart, liver, adipose tissue, and spleen (Meier et al., 1999). The expression level of PLD1 is elevated in several cancer cells (Noh et al., 2000; Buchanan et al., 2005).
Localisation It is believed that PLD1 is primarily localized in perinuclear regions, such as, endoplasmic reticulum (ER), Golgi apparatus, and secretory vesicles (Jenkins et al., 2005). Several reports have suggested that PLD1 is also localized in endosomes (early, late, and recycling) and lysomes (Toda et al., 1999; Hughes et al., 2001; Du et al., 2003). Furthermore, PLD1 can translocate to the plasma membrane in a signal-dependent manner (Brown et al., 1998), and can be localized in specialized region (caveolae) of the plasma membrane. The C240/C241 residues of PLD1 are palmitoylated to localize at caveolae, and this localization is important for mediating EGF signaling (Han et al., 2002). Recently, it was reported that PLD1 also has nuclear roles (Gayral et al., 2006).
Function PLD1 is a phospholipid-hydrolyzing enzyme that can catalyze phosphatidylcholine (PC) to generate phosphatidic acid (PA) and choline. PA can function as a second messenger and can be converted to other biomolecules, such as, LPA and DAG (Jenkins et al., 2005). PA can interact with a variety of molecules to recruit it to the membrane. For example, PA binds to mTOR-FRB domain and regulates its cell growth signaling activity (Fang et al., 2001), and can interact with PtdIns(4)P 5-Kinase (Honda et al., 1999); this latter interaction can modulate the generation of PtdIns(4,5)P2. Recently, it was been reported that PA can translocate SOS to the plasma membrane to mediate EGF signaling (Zhao et al., 2007). PLD can mediate many cellular phenomena, such as, proliferation, vesicle trafficking, cytoskeleton reorganization, and differentiation, and recently, Elvers et al. after a study on PLD1 knockout mice, reported that PLD1 can modulate thrombus formation via platelet aggregation (Elvers et al., 2010).

Proliferation
PLD can be activated by a variety of mitogenic signals - epidermal growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), insulin, growth hormones, lysophosphatidic acid (LPA), and spingosine 1-phosphate - all of which can directly bind with G-protein coupled receptors (GPCR) and receptor-tyrosine kinases (RTK). PLD activation via mitogenic signals can induce cell proliferation, cell survival, the suppression of cell cycle arrest, and the prevention of apoptosis (Foster et al., 2003; Lee et al., 2009a; Su et al., 2009). Furthermore, elevated PLD activity has been shown to transform cells (Buchanan et al., 2005).

Vesicle trafficking
It has been reported that PLD is critically involved in vesicle formation and trafficking, such as, in endocytosis, exocytosis, and vesicle formation from the trans-Golgi network (Cazzolli et al., 2006). PLD-derived PA generation can recruit downstream molecules (PtdIns(4)P 5-Kinase) that are involved in vesicle fusion and mediate the inner membrane curvature (Jenkins et al., 2005). Many reports have suggested that PA generation by PLD can contribute to exocytosis (immune cell degranulation, neurotransmitter secretion, and EGF secretion) in various cell lines, such as, mast cells, adipocytes, and neuroendocrine cells. Furthermore, endocytosis (receptor mediated endocytosis and phagocytosis) also depends on PA generation by PLD (Humeau et al., 2001; Hughes et al., 2004; Huang et al., 2005; Peng et al., 2005). Recently, we have been suggested that PLD protein can increase the GTPase activity of dynamin, which is important for endocytosis, and that PLD itself, and not PA, can increase EGFR endocytosis (Lee et al., 2006).

Cytoskeletal reorganization
PA generation by PLD activation has been shown to be a key regulator of cytoskeletal dynamics to induce cell adhesion, spreading, and migration. PLD can be activated by kinases (PKC and PtdIns(4)P 5-Kinase) and small G proteins (Rho, Rac, cdc42, Arf, and Ral) that mediate signaling essentially required for cytoskeletal reorganization (Rudge et al., 2009). Moreover, PLD-derived PA can translocate GTP-Rac to the plasma membrane and induce integrin-mediated cell spreading (Chae et al., 2008).

Differentiation
PLD appears to be involved in the differentiation of various cells. Prolonged PA generation by PLD activation is correlated with the differentiation of keratinocytes (Jung et al., 1999), and the PLD isozyme expression levels are increased during granulocytic differentiation (Di Fulvio et al., 2005). PLD is well known to have an essential role during neuronal cell differentiation (Kanaho et al., 2009). Recently, Yoon et al reported that PLD can induce myoblast differentiation via the secretion of IGF2 in an autocrine manner (Yoon et al., 2008).

Homology A blast search produced the following results:
85% sequence identity in Mus musculus.
87% sequence identity in Rattus norvegicus.
47% sequence identity in C. elegans.
56% sequence identity with PLD2 of Homo sapiens.

Implicated in

Note
  
Entity Various cancers
Note Several tumor cells (breast cancer, colon cancer) show elevated PLD1 expression and activity. For example, the expression and activity of PLD1 are upregulated in breast cancer tissue. Also, the expression of PLD1/PLD2 is upregulated in colon cancer (Noh et al., 2000; Buchanan et al., 2005; Saito et al., 2007). Furthermore, a polymorphism of PLD2 was shown to be associated with the prevalence of colorectal cancer (Yamada et al., 2003). Increased PLD1 activity/expression can transform rat fibroblasts. It has been shown that the mTor pathway can contribute to the growth and survival of cancer cells. Moreover, elevated PLD1 levels can increase the phosphorylation of S-6 kinase, which is a downstream molecule in mTor signaling (Hui et al., 2004).
Recently, PLD1 was shown to activate Rheb, which is upstream of the GTPase of mTor (Sun et al., 2008). Furthermore, PLD has also been implicated in the invasion of tumor cells and in the secretion of matrix metalloproteinases (MMP) (Pai et al., 1994; Wakelam et al., 1997; Knoepp et al., 2008; Park et al., 2009). In particular, the upregulation of PLD1 by PMA was shown to increase the secretion of MMP9 in colon cancer cells (Kang et al., 2008).
  
  
Entity Alzheimer's disease
Note The expression and activity of PLD1 is increased in the AD (Alzheimer Disease) brain.
Beta-Amyloid precursor protein (beta-APP), which is involved in the pathogenesis of AD, has been shown to interact with PLD1-PH domain and elevated APP levels increased PLD activity in astroglioma cells (Jin et al., 2006; Jin et al., 2007). Also, the presenilins (PS1/PS2), which can mediate the proteolysis of beta-amyloid precursor protein, have been shown to interact with PLD1. Furthermore, the generation of beta-amyloid from beta-APP containing vesicles was found to be decreased by the overexpression of PLD1, which also promoted the budding out of beta-APP containing vesicles (Cai et al., 2006a; Cai et al., 2006b). Although evidence exists that PLD1 is associated with AD, the pathophysiological relationship between PLD1 and AD needs further study.
  

To be noted

Acknowledgements: This work was supported in part by the FPR08B1-300 of the 21C Frontier functional proteomics project and by the World class university program through the National research foundation of Korea funded by the Ministry of education, science and technology (R31-2008-000-10105-0).

Bibliography

Phospholipase D1 localises to secretory granules and lysosomes and is plasma-membrane translocated on cellular stimulation.
Brown FD, Thompson N, Saqib KM, Clark JM, Powner D, Thompson NT, Solari R, Wakelam MJ.
Curr Biol. 1998 Jul 2;8(14):835-8.
PMID 9663393
 
Requirement of phospholipase D1 activity in H-RasV12-induced transformation.
Buchanan FG, McReynolds M, Couvillon A, Kam Y, Holla VR, Dubois RN, Exton JH.
Proc Natl Acad Sci U S A. 2005 Feb 1;102(5):1638-42. Epub 2005 Jan 24.
PMID 15668389
 
Presenilin-1 uses phospholipase D1 as a negative regulator of beta-amyloid formation.
Cai D, Netzer WJ, Zhong M, Lin Y, Du G, Frohman M, Foster DA, Sisodia SS, Xu H, Gorelick FS, Greengard P.
Proc Natl Acad Sci U S A. 2006a Feb 7;103(6):1941-6. Epub 2006 Jan 31.
PMID 16449386
 
Phospholipase D1 corrects impaired betaAPP trafficking and neurite outgrowth in familial Alzheimer's disease-linked presenilin-1 mutant neurons.
Cai D, Zhong M, Wang R, Netzer WJ, Shields D, Zheng H, Sisodia SS, Foster DA, Gorelick FS, Xu H, Greengard P.
Proc Natl Acad Sci U S A. 2006b Feb 7;103(6):1936-40. Epub 2006 Jan 31.
PMID 16449385
 
Phospholipid signalling through phospholipase D and phosphatidic acid.
Cazzolli R, Shemon AN, Fang MQ, Hughes WE.
IUBMB Life. 2006 Aug;58(8):457-61. (REVIEW)
PMID 16916782
 
Phospholipase D activity regulates integrin-mediated cell spreading and migration by inducing GTP-Rac translocation to the plasma membrane.
Chae YC, Kim JH, Kim KL, Kim HW, Lee HY, Heo WD, Meyer T, Suh PG, Ryu SH.
Mol Biol Cell. 2008 Jul;19(7):3111-23. Epub 2008 May 14.
PMID 18480413
 
Phospholipase D (PLD) gene expression in human neutrophils and HL-60 differentiation.
Di Fulvio M, Gomez-Cambronero J.
J Leukoc Biol. 2005 Jun;77(6):999-1007. Epub 2005 Mar 17.
PMID 15774548
 
Regulation of phospholipase D1 subcellular cycling through coordination of multiple membrane association motifs.
Du G, Altshuller YM, Vitale N, Huang P, Chasserot-Golaz S, Morris AJ, Bader MF, Frohman MA.
J Cell Biol. 2003 Jul 21;162(2):305-15.
PMID 12876278
 
Impaired alpha(IIb)beta(3) integrin activation and shear-dependent thrombus formation in mice lacking phospholipase D1.
Elvers M, Stegner D, Hagedorn I, Kleinschnitz C, Braun A, Kuijpers ME, Boesl M, Chen Q, Heemskerk JW, Stoll G, Frohman MA, Nieswandt B.
Sci Signal. 2010 Jan 5;3(103):ra1.
PMID 20051593
 
Phosphatidic acid-mediated mitogenic activation of mTOR signaling.
Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J.
Science. 2001 Nov 30;294(5548):1942-5.
PMID 11729323
 
Phospholipase D in cell proliferation and cancer.
Foster DA, Xu L.
Mol Cancer Res. 2003 Sep;1(11):789-800. (REVIEW)
PMID 14517341
 
Selective activation of nuclear phospholipase D-1 by g protein-coupled receptor agonists in vascular smooth muscle cells.
Gayral S, Deleris P, Laulagnier K, Laffargue M, Salles JP, Perret B, Record M, Breton-Douillon M.
Circ Res. 2006 Jul 21;99(2):132-9. Epub 2006 Jun 15.
PMID 16778131
 
Human ADP-ribosylation factor-activated phosphatidylcholine-specific phospholipase D defines a new and highly conserved gene family.
Hammond SM, Altshuller YM, Sung TC, Rudge SA, Rose K, Engebrecht J, Morris AJ, Frohman MA.
J Biol Chem. 1995 Dec 15;270(50):29640-3.
PMID 8530346
 
Localization of phospholipase D1 to caveolin-enriched membrane via palmitoylation: implications for epidermal growth factor signaling.
Han JM, Kim Y, Lee JS, Lee CS, Lee BD, Ohba M, Kuroki T, Suh PG, Ryu SH.
Mol Biol Cell. 2002 Nov;13(11):3976-88.
PMID 12429840
 
Phospholipase D regulation and localisation is dependent upon a phosphatidylinositol 4,5-biphosphate-specific PH domain.
Hodgkin MN, Masson MR, Powner D, Saqib KM, Ponting CP, Wakelam MJ.
Curr Biol. 2000 Jan 13;10(1):43-6.
PMID 10660303
 
Phosphatidylinositol 4-phosphate 5-kinase alpha is a downstream effector of the small G protein ARF6 in membrane ruffle formation.
Honda A, Nogami M, Yokozeki T, Yamazaki M, Nakamura H, Watanabe H, Kawamoto K, Nakayama K, Morris AJ, Frohman MA, Kanaho Y.
Cell. 1999 Nov 24;99(5):521-32.
PMID 10589680
 
Insulin-stimulated plasma membrane fusion of Glut4 glucose transporter-containing vesicles is regulated by phospholipase D1.
Huang P, Altshuller YM, Hou JC, Pessin JE, Frohman MA.
Mol Biol Cell. 2005 Jun;16(6):2614-23. Epub 2005 Mar 16.
PMID 15772157
 
Phospholipase D1 regulates secretagogue-stimulated insulin release in pancreatic beta-cells.
Hughes WE, Elgundi Z, Huang P, Frohman MA, Biden TJ.
J Biol Chem. 2004 Jun 25;279(26):27534-41. Epub 2004 Apr 14.
PMID 15087463
 
Endosomal localization of phospholipase D 1a and 1b is defined by the C-termini of the proteins, and is independent of activity.
Hughes WE, Parker PJ.
Biochem J. 2001 Jun 15;356(Pt 3):727-36.
PMID 11389680
 
Phospholipase D elevates the level of MDM2 and suppresses DNA damage-induced increases in p53.
Hui L, Abbas T, Pielak RM, Joseph T, Bargonetti J, Foster DA.
Mol Cell Biol. 2004 Jul;24(13):5677-86.
PMID 15199126
 
A role for phospholipase D1 in neurotransmitter release.
Humeau Y, Vitale N, Chasserot-Golaz S, Dupont JL, Du G, Frohman MA, Bader MF, Poulain B.
Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15300-5.
PMID 11752468
 
The direct interaction of phospholipase C-gamma 1 with phospholipase D2 is important for epidermal growth factor signaling.
Jang IH, Lee S, Park JB, Kim JH, Lee CS, Hur EM, Kim IS, Kim KT, Yagisawa H, Suh PG, Ryu SH.
J Biol Chem. 2003 May 16;278(20):18184-90. Epub 2003 Mar 19.
PMID 12646582
 
Phospholipase D: a lipid centric review.
Jenkins GM, Frohman MA.
Cell Mol Life Sci. 2005 Oct;62(19-20):2305-16. (REVIEW)
PMID 16143829
 
Phospholipase D1 is associated with amyloid precursor protein in Alzheimer's disease.
Jin JK, Ahn BH, Na YJ, Kim JI, Kim YS, Choi EK, Ko YG, Chung KC, Kozlowski PB, Min do S.
Neurobiol Aging. 2007 Jul;28(7):1015-27. Epub 2006 Jun 23.
PMID 16797788
 
Phospholipase D1 is up-regulated in the mitochondrial fraction from the brains of Alzheimer's disease patients.
Jin JK, Kim NH, Lee YJ, Kim YS, Choi EK, Kozlowski PB, Park MH, Kim HS, Min do S.
Neurosci Lett. 2006 Oct 30;407(3):263-7. Epub 2006 Sep 12.
PMID 16973278
 
Sustained phospholipase D activation is associated with keratinocyte differentiation.
Jung EM, Betancourt-Calle S, Mann-Blakeney R, Griner RD, Bollinger Bollag W.
Carcinogenesis. 1999 Apr;20(4):569-76.
PMID 10223183
 
Phospholipase D signalling and its involvement in neurite outgrowth.
Kanaho Y, Funakoshi Y, Hasegawa H.
Biochim Biophys Acta. 2009 Sep;1791(9):898-904. Epub 2009 Mar 31. (REVIEW)
PMID 19341813
 
Phorbol ester up-regulates phospholipase D1 but not phospholipase D2 expression through a PKC/Ras/ERK/NFkappaB-dependent pathway and enhances matrix metalloproteinase-9 secretion in colon cancer cells.
Kang DW, Park MH, Lee YJ, Kim HS, Kwon TK, Park WS, Min do S.
J Biol Chem. 2008 Feb 15;283(7):4094-104. Epub 2007 Dec 15.
PMID 18084005
 
Phosphorylation and activation of phospholipase D1 by protein kinase C in vivo: determination of multiple phosphorylation sites.
Kim Y, Han JM, Park JB, Lee SD, Oh YS, Chung C, Lee TG, Kim JH, Park SK, Yoo JS, Suh PG, Ryu SH.
Biochemistry. 1999 Aug 10;38(32):10344-51.
PMID 10441128
 
Effects of active and inactive phospholipase D2 on signal transduction, adhesion, migration, invasion, and metastasis in EL4 lymphoma cells.
Knoepp SM, Chahal MS, Xie Y, Zhang Z, Brauner DJ, Hallman MA, Robinson SA, Han S, Imai M, Tomlinson S, Meier KE.
Mol Pharmacol. 2008 Sep;74(3):574-84. Epub 2008 Jun 3.
PMID 18523140
 
The roles of phospholipase D in EGFR signaling.
Lee CS, Kim KL, Jang JH, Choi YS, Suh PG, Ryu SH.
Biochim Biophys Acta. 2009a Sep;1791(9):862-8. Epub 2009 May 4. (REVIEW)
PMID 19410013
 
Munc-18-1 inhibits phospholipase D activity by direct interaction in an epidermal growth factor-reversible manner.
Lee HY, Park JB, Jang IH, Chae YC, Kim JH, Kim IS, Suh PG, Ryu SH.
J Biol Chem. 2004 Apr 16;279(16):16339-48. Epub 2004 Jan 26.
PMID 14744865
 
Determination of EGFR endocytosis kinetic by auto-regulatory association of PLD1 with mu2.
Lee JS, Kim IS, Kim JH, Cho W, Suh PG, Ryu SH.
PLoS One. 2009b Sep 18;4(9):e7090.
PMID 19763255
 
Expression of phospholipase D isoforms in mammalian cells.
Meier KE, Gibbs TC, Knoepp SM, Ella KM.
Biochim Biophys Acta. 1999 Jul 30;1439(2):199-213. (REVIEW)
PMID 10425396
 
Overexpression of phospholipase D1 in human breast cancer tissues.
Noh DY, Ahn SJ, Lee RA, Park IA, Kim JH, Suh PG, Ryu SH, Lee KH, Han JS.
Cancer Lett. 2000 Dec 20;161(2):207-14.
PMID 11090971
 
Novel ketoepoxides block phospholipase D activation and tumor cell invasion.
Pai JK, Frank EA, Blood C, Chu M.
Anticancer Drug Des. 1994 Aug;9(4):363-72.
PMID 7916902
 
Overexpression of phospholipase D enhances matrix metalloproteinase-2 expression and glioma cell invasion via protein kinase C and protein kinase A/NF-kappaB/Sp1-mediated signaling pathways.
Park MH, Ahn BH, Hong YK, Min do S.
Carcinogenesis. 2009 Feb;30(2):356-65. Epub 2009 Jan 6.
PMID 19126647
 
An essential role for phospholipase D in the activation of protein kinase C and degranulation in mast cells.
Peng Z, Beaven MA.
J Immunol. 2005 May 1;174(9):5201-8.
PMID 15843515
 
Inter-regulatory dynamics of phospholipase D and the actin cytoskeleton.
Rudge SA, Wakelam MJ.
Biochim Biophys Acta. 2009 Sep;1791(9):856-61. Epub 2009 May 5. (REVIEW)
PMID 19422932
 
Expression of phospholipase D2 in human colorectal carcinoma.
Saito M, Iwadate M, Higashimoto M, Ono K, Takebayashi Y, Takenoshita S.
Oncol Rep. 2007 Nov;18(5):1329-34.
PMID 17914593
 
Mechanism of membrane binding of the phospholipase D1 PX domain.
Stahelin RV, Ananthanarayanan B, Blatner NR, Singh S, Bruzik KS, Murray D, Cho W.
J Biol Chem. 2004 Dec 24;279(52):54918-26. Epub 2004 Oct 8.
PMID 15475361
 
Targeting phospholipase D with small-molecule inhibitors as a potential therapeutic approach for cancer metastasis.
Su W, Chen Q, Frohman MA.
Future Oncol. 2009 Nov;5(9):1477-86. (REVIEW)
PMID 19903073
 
Phospholipase D1 is an effector of Rheb in the mTOR pathway.
Sun Y, Fang Y, Yoon MS, Zhang C, Roccio M, Zwartkruis FJ, Armstrong M, Brown HA, Chen J.
Proc Natl Acad Sci U S A. 2008 Jun 17;105(24):8286-91. Epub 2008 Jun 11.
PMID 18550814
 
Structural analysis of human phospholipase D1.
Sung TC, Zhang Y, Morris AJ, Frohman MA.
J Biol Chem. 1999 Feb 5;274(6):3659-66.
PMID 9920915
 
Colocalization of phospholipase D1 and GTP-binding-defective mutant of ADP-ribosylation factor 6 to endosomes and lysosomes.
Toda K, Nogami M, Murakami K, Kanaho Y, Nakayama K.
FEBS Lett. 1999 Jan 15;442(2-3):221-5.
PMID 9929005
 
Role and regulation of phospholipase D activity in normal and cancer cells.
Wakelam MJ, Martin A, Hodgkin MN, Brown F, Pettitt TR, Cross MJ, De Takats PG, Reynolds JL.
Adv Enzyme Regul. 1997;37:29-34.
PMID 9381975
 
Association of a polymorphism of the phospholipase D2 gene with the prevalence of colorectal cancer.
Yamada Y, Hamajima N, Kato T, Iwata H, Yamamura Y, Shinoda M, Suyama M, Mitsudomi T, Tajima K, Kusakabe S, Yoshida H, Banno Y, Akao Y, Tanaka M, Nozawa Y.
J Mol Med. 2003 Feb;81(2):126-31. Epub 2003 Feb 11.
PMID 12601529
 
PLD regulates myoblast differentiation through the mTOR-IGF2 pathway.
Yoon MS, Chen J.
J Cell Sci. 2008 Feb 1;121(Pt 3):282-9. Epub 2008 Jan 15.
PMID 18198186
 
Phospholipase D2-generated phosphatidic acid couples EGFR stimulation to Ras activation by Sos.
Zhao C, Du G, Skowronek K, Frohman MA, Bar-Sagi D.
Nat Cell Biol. 2007 Jun;9(6):706-12. Epub 2007 May 7.
PMID 17486115
 

Citation

This paper should be referenced as such :
Lee, CS ; Ryu, SH
PLD1 (phospholipase D1, phosphatidylcholine-specific)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(6):511-515.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PLD1ID43716ch3q26.html


External links

Nomenclature
HGNC (Hugo)PLD1   9067
Cards
AtlasPLD1ID43716ch3q26
Entrez_Gene (NCBI)PLD1  5337  phospholipase D1
Aliases
GeneCards (Weizmann)PLD1
Ensembl hg19 (Hinxton)ENSG00000075651 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000075651 [Gene_View]  chr3:171600405-171810494 [Contig_View]  PLD1 [Vega]
ICGC DataPortalENSG00000075651
TCGA cBioPortalPLD1
AceView (NCBI)PLD1
Genatlas (Paris)PLD1
WikiGenes5337
SOURCE (Princeton)PLD1
Genetics Home Reference (NIH)PLD1
Genomic and cartography
GoldenPath hg38 (UCSC)PLD1  -     chr3:171600405-171810494 -  3q26.31   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PLD1  -     3q26.31   [Description]    (hg19-Feb_2009)
EnsemblPLD1 - 3q26.31 [CytoView hg19]  PLD1 - 3q26.31 [CytoView hg38]
Mapping of homologs : NCBIPLD1 [Mapview hg19]  PLD1 [Mapview hg38]
OMIM602382   
Gene and transcription
Genbank (Entrez)AB209907 AJ276230 AK026225 AK091897 BC068976
RefSeq transcript (Entrez)NM_001130081 NM_002662
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PLD1
Cluster EST : UnigeneHs.732969 [ NCBI ]
CGAP (NCI)Hs.732969
Alternative Splicing GalleryENSG00000075651
Gene ExpressionPLD1 [ NCBI-GEO ]   PLD1 [ EBI - ARRAY_EXPRESS ]   PLD1 [ SEEK ]   PLD1 [ MEM ]
Gene Expression Viewer (FireBrowse)PLD1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5337
GTEX Portal (Tissue expression)PLD1
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13393   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ13393  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ13393
Splice isoforms : SwissVarQ13393
Catalytic activity : Enzyme3.1.4.4 [ Enzyme-Expasy ]   3.1.4.43.1.4.4 [ IntEnz-EBI ]   3.1.4.4 [ BRENDA ]   3.1.4.4 [ KEGG ]   
PhosPhoSitePlusQ13393
Domaine pattern : Prosite (Expaxy)PLD (PS50035)    PX (PS50195)   
Domains : Interpro (EBI)PH_dom-like    PH_domain    Phox    PLD-like_dom    PLipase_D/transphosphatidylase    PLipase_D1/D2    PLipase_D_fam   
Domain families : Pfam (Sanger)PH (PF00169)    PLDc (PF00614)    PLDc_2 (PF13091)    PX (PF00787)   
Domain families : Pfam (NCBI)pfam00169    pfam00614    pfam13091    pfam00787   
Domain families : Smart (EMBL)PH (SM00233)  PLDc (SM00155)  PX (SM00312)  
Conserved Domain (NCBI)PLD1
DMDM Disease mutations5337
Blocks (Seattle)PLD1
SuperfamilyQ13393
Human Protein AtlasENSG00000075651
Peptide AtlasQ13393
HPRD03855
IPIIPI00012865   IPI00218797   IPI00218798   IPI00218799   IPI00925723   
Protein Interaction databases
DIP (DOE-UCLA)Q13393
IntAct (EBI)Q13393
FunCoupENSG00000075651
BioGRIDPLD1
STRING (EMBL)PLD1
ZODIACPLD1
Ontologies - Pathways
QuickGOQ13393
Ontology : AmiGOGolgi membrane  phospholipase D activity  protein binding  lysosomal membrane  endosome  endoplasmic reticulum membrane  Golgi apparatus  plasma membrane  phosphatidic acid biosynthetic process  chemotaxis  small GTPase mediated signal transduction  Ras protein signal transduction  membrane  lipid catabolic process  apical plasma membrane  endocytic vesicle  late endosome membrane  regulation of microvillus assembly  phosphatidylinositol binding  specific granule membrane  neutrophil degranulation  inositol lipid-mediated signaling  perinuclear region of cytoplasm  cell motility  N-acylphosphatidylethanolamine-specific phospholipase D activity  tertiary granule membrane  
Ontology : EGO-EBIGolgi membrane  phospholipase D activity  protein binding  lysosomal membrane  endosome  endoplasmic reticulum membrane  Golgi apparatus  plasma membrane  phosphatidic acid biosynthetic process  chemotaxis  small GTPase mediated signal transduction  Ras protein signal transduction  membrane  lipid catabolic process  apical plasma membrane  endocytic vesicle  late endosome membrane  regulation of microvillus assembly  phosphatidylinositol binding  specific granule membrane  neutrophil degranulation  inositol lipid-mediated signaling  perinuclear region of cytoplasm  cell motility  N-acylphosphatidylethanolamine-specific phospholipase D activity  tertiary granule membrane  
Pathways : BIOCARTARas Signaling Pathway [Genes]    Rac 1 cell motility signaling pathway [Genes]    Metabolism of Anandamide, an Endogenous Cannabinoid [Genes]   
Pathways : KEGG   
REACTOMEQ13393 [protein]
REACTOME PathwaysR-HSA-6798695 [pathway]   
NDEx NetworkPLD1
Atlas of Cancer Signalling NetworkPLD1
Wikipedia pathwaysPLD1
Orthology - Evolution
OrthoDB5337
GeneTree (enSembl)ENSG00000075651
Phylogenetic Trees/Animal Genes : TreeFamPLD1
HOVERGENQ13393
HOGENOMQ13393
Homologs : HomoloGenePLD1
Homology/Alignments : Family Browser (UCSC)PLD1
Gene fusions - Rearrangements
Fusion : MitelmanMGAT4C/PLD1 [12q21.31/3q26.31]  [t(3;12)(q26;q21)]  
Fusion : MitelmanOSBPL2/PLD1 [20q13.33/3q26.31]  [t(3;20)(q26;q13)]  
Fusion : MitelmanPLD1/AGBL1 [3q26.31/15q25.3]  [t(3;15)(q26;q25)]  
Fusion : MitelmanTFDP2/PLD1 [3q23/3q26.31]  [t(3;3)(q23;q26)]  
Fusion: TCGAMGAT4C 12q21.31 PLD1 3q26.31 LUSC
Fusion: TCGAOSBPL2 20q13.33 PLD1 3q26.31 BRCA
Fusion: TCGATFDP2 3q23 PLD1 3q26.31 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPLD1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PLD1
dbVarPLD1
ClinVarPLD1
1000_GenomesPLD1 
Exome Variant ServerPLD1
ExAC (Exome Aggregation Consortium)PLD1 (select the gene name)
Genetic variants : HAPMAP5337
Genomic Variants (DGV)PLD1 [DGVbeta]
DECIPHERPLD1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPLD1 
Mutations
ICGC Data PortalPLD1 
TCGA Data PortalPLD1 
Broad Tumor PortalPLD1
OASIS PortalPLD1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPLD1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPLD1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PLD1
DgiDB (Drug Gene Interaction Database)PLD1
DoCM (Curated mutations)PLD1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PLD1 (select a term)
intoGenPLD1
NCG5 (London)PLD1
Cancer3DPLD1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM602382   
Orphanet
MedgenPLD1
Genetic Testing Registry PLD1
NextProtQ13393 [Medical]
TSGene5337
GENETestsPLD1
Target ValidationPLD1
Huge Navigator PLD1 [HugePedia]
snp3D : Map Gene to Disease5337
BioCentury BCIQPLD1
ClinGenPLD1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5337
Chemical/Pharm GKB GenePA164742228
Clinical trialPLD1
Miscellaneous
canSAR (ICR)PLD1 (select the gene name)
Probes
Litterature
PubMed141 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePLD1
EVEXPLD1
GoPubMedPLD1
iHOPPLD1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Wed Jun 7 12:11:34 CEST 2017

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.