Phospholipase D
| phospholipase D | |||||||
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| Identifiers | |||||||
| EC number | 3.1.4.4 | ||||||
| CAS number | 9001-87-0 | ||||||
| Databases | |||||||
| IntEnz | IntEnz view | ||||||
| BRENDA | BRENDA entry | ||||||
| ExPASy | NiceZyme view | ||||||
| KEGG | KEGG entry | ||||||
| MetaCyc | metabolic pathway | ||||||
| PRIAM | profile | ||||||
| PDB structures | RCSB PDB PDBe PDBsum | ||||||
| Gene Ontology | AmiGO / EGO | ||||||
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Phospholipase D is an enzyme which is located in the plasma membrane and catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid (PA), releasing the soluble choline headgroup into the cytosol. There are two mammalian isoforms of phospholipase D: PLD1 and PLD2.
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[edit] Function
Mammalian PLD directly interacts with kinases like PKC, ERK, TYK and controls the signalling indicating that PLD is activated by these kinases.[1] As choline is very abundant in the cell, PLD activity does not significantly affect choline levels, and choline is unlikely to play any role in signalling.
Phosphatidic acid is a signal molecule and acts to recruit SK1 to membranes. PA is extremely short lived and is rapidly hydrolysed by the enzyme PA phosphohydrolase to form diacylglycerol (DAG). DAG may also be converted to PA by DAG kinase. Although PA and DAG are interconvertible, they do not act in the same pathways. Stimuli that activate PLD do not activate enzymes downstream of DAG and vice versa.
It is possible that, though PA and DAG are interconvertible, separate pools of signalling and non-signalling lipids may be maintained. Studies have suggested that DAG signalling is mediated by polyunsaturated DAG while PLD derived PA is monounsaturated or saturated. Thus functional saturated/monounsaturated PA can be degraded by hydrolysing it to form non-functional saturated/monounsaturated DAG while functional polyunsaturated DAG can be degraded by converting it into non-functional polyunsaturated PA.[2][3][4]
Finally, a lysophospholipase D called autotaxin was recently identified as having an important role in cell-proliferation through its product, lysophosphatidic acid (LPA).
[edit] Isoforms
Human proteins possessing phospholipase D activity include:
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[edit] Active site motif
| Identifiers | |||||||||
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| Symbol | PLDc | ||||||||
| Pfam | PF00614 | ||||||||
| InterPro | IPR001736 | ||||||||
| SMART | SM00155 | ||||||||
| PROSITE | PDOC50035 | ||||||||
| SCOP | 1byr | ||||||||
| SUPERFAMILY | 1byr | ||||||||
| CDD | cd00138 | ||||||||
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Phosphatidylcholine-hydrolyzing phospholipase D (PLD) isoforms are activated by ADP-ribosylation factors (ARFs). PLD produces phosphatidic acid from phosphatidylcholine, which may be essential for the formation of certain types of transport vesicles or may be constitutive vesicular transport to signal transduction pathways. PC-hydrolyzing PLD is a homologue of cardiolipin synthase[5],[6], phosphatidylserine synthase, bacterial PLDs, and viral proteins. Each of these appears to possess a domain duplication which is apparent by the presence of two motifs containing well-conserved histidine, lysine, and/or asparagine residues which may contribute to the active site aspartic acid. An Escherichia coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs.[7][8][9][10]
Human proteins containing this motif include:
[edit] Gallery
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Phospholipase Cleavage Sites.
[edit] References
- ^ Paruch S, El-Benna J, Djerdjouri B, Marullo S, Périanin A (January 2006). "A role of p44/42 mitogen-activated protein kinases in formyl-peptide receptor-mediated phospholipase D activity and oxidant production". FASEB J. 20 (1): 142–4. doi:10.1096/fj.05-3881fje. PMID 16253958.
- ^ Bocckino S, Blackmore P, Wilson P, Exton J (1987). "Phosphatidate accumulation in hormone-treated hepatocytes via a phospholipase D mechanism". J Biol Chem 262 (31): 15309–15. PMID 3117799.
- ^ Bocckino S, Wilson P, Exton J (1987). "Ca2+-mobilizing hormones elicit phosphatidylethanol accumulation via phospholipase D activation". FEBS Lett 225 (1-2): 201–4. doi:10.1016/0014-5793(87)81157-2. PMID 3319693.
- ^ Hodgkin M, Pettitt T, Martin A, Michell R, Pemberton A, Wakelam M (1998). "Diacylglycerols and phosphatidates: which molecular species are intracellular messengers?". Trends Biochem Sci 23 (6): 200–4. doi:10.1016/S0968-0004(98)01200-6. PMID 9644971.
- ^ M. Nowicki and M. Frentzen (2005). "Cardiolipin synthase of Arabidopsis thaliana". FEBS Letters 579 (10): 2161–2165. doi:10.1016/j.febslet.2005.03.007. PMID 15811335.
- ^ M. Nowicki (2006). "Characterization of the Cardiolipin Synthase from Arabidopsis thaliana". Ph.D. thesis, RWTH-Aachen University. http://darwin.bth.rwth-aachen.de/opus/volltexte/2006/1629/.
- ^ Ponting CP, Kerr ID (1996). "A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues". Protein Sci. 5 (5): 914–922. doi:10.1002/pro.5560050513. PMC 2143407. PMID 8732763. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2143407.
- ^ Koonin EV (1996). "A duplicated catalytic motif in a new superfamily of phosphohydrolases and phospholipid synthases that includes poxvirus envelope proteins". Trends Biochem. Sci. 21 (7): 242–243. PMID 8755242.
- ^ Wang X, Xu L, Zheng L (1994). "Cloning and expression of phosphatidylcholine-hydrolyzing phospholipase D from Ricinus communis L". J. Biol. Chem. 269 (32): 20312–20317. PMID 8051126.
- ^ Singer WD, Brown HA, Sternweis PC (1997). "Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D". Annu. Rev. Biochem. 66: 475–509. doi:10.1146/annurev.biochem.66.1.475. PMID 9242915.
[edit] External links
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This article incorporates text from the public domain Pfam and InterPro IPR001734
