Please note: this site relies heavily on the use of javascript. Without a javascript-enabled browser, this site will not function correctly. Please enable javascript and reload the page, or switch to a different browser.
3  structures 652  species 1  interaction 1567  sequences 33  architectures

Family: PLDc (PF00614)

Summary: Phospholipase D Active site motif

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Phospholipase D". More...

Phospholipase D Edit Wikipedia article

phospholipase D
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

Phospholipase D (EC 3.1.4.4, lipophosphodiesterase II, lecithinase D, choline phosphatase) 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.

Function[edit]

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]

A lysophospholipase D called autotaxin was recently identified as having an important role in cell-proliferation through its product, lysophosphatidic acid (LPA).

Phospholipase D3 (PLD3), a non-classical and poorly characterized member of the PLD superfamily, has been associated with the risk of developing Alzheimer's disease.[5]

Isoforms[edit]

Human proteins possessing phospholipase D activity include:

phospholipase D1, phosphatidylcholine-specific
Identifiers
Symbol PLD1
Entrez 5337
HUGO 9067
OMIM 602382
RefSeq NM_002662
UniProt Q13393
Other data
Locus Chr. 3 q26
phospholipase D2
Identifiers
Symbol PLD2
Entrez 5338
HUGO 9068
OMIM 602384
RefSeq NM_002663
UniProt O14939
Other data
Locus Chr. 17 p13.3

Active site motif[edit]

Phospholipase D Active site motif
Identifiers
Symbol PLDc
Pfam PF00614
InterPro IPR001736
SMART SM00155
PROSITE PDOC50035
SCOP 1byr
SUPERFAMILY 1byr
CDD cd00138

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,[6][7] 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.[8][9][10][11]

Human proteins containing this motif include:

Gallery[edit]

References[edit]

  1. ^ 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. 
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 
  5. ^ Cruchaga et al. (2013). "Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease". Nature. 
  6. ^ 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. 
  7. ^ M. Nowicki (2006). "Characterization of the Cardiolipin Synthase from Arabidopsis thaliana". Ph.D. thesis, RWTH-Aachen University. 
  8. ^ 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. 
  9. ^ 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. 
  10. ^ 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. 
  11. ^ 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. 

External links[edit]

This article incorporates text from the public domain Pfam and InterPro IPR001734

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

Phospholipase D Active site motif Provide feedback

Phosphatidylcholine-hydrolysing 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-hydrolysing PLD is a homologue of cardiolipin synthase, 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 E. coli endonuclease (nuc) and similar proteins appear to be PLD homologues but possess only one of these motifs. The profile contained here represents only the putative active site regions, since an accurate multiple alignment of the repeat units has not been achieved.

Literature references

  1. Ponting CP, Kerr ID; , Protein Sci 1996;5:914-922.: A novel family of phospholipase D homologues that includes phospholipid synthases and putative endonucleases: identification of duplicated repeats and potential active site residues. PUBMED:8732763 EPMC:8732763

  2. Koonin EV; , Trends Biochem Sci 1996;21:242-243.: A duplicated catalytic motif in a new superfamily of phosphohydrolases and phospholipid synthases that includes poxvirus envelope proteins. PUBMED:8755242 EPMC:8755242

  3. Wang X, Xu L, Zheng L; , J Biol Chem 1994;269:20312-20317.: Cloning and expression of phosphatidylcholine-hydrolyzing phospholipase D from Ricinus communis L. PUBMED:8051126 EPMC:8051126

  4. Singer WD, Brown HA, Sternweis PC; , Annu Rev Biochem 1997;66:475-509.: Regulation of eukaryotic phosphatidylinositol-specific phospholipase C and phospholipase D. PUBMED:9242915 EPMC:9242915

  5. Stuckey JA, Dixon JE; , Nat Struct Biol 1999;6:278-284.: Crystal structure of a phospholipase D family member. PUBMED:10074947 EPMC:10074947


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001736

Phosphatidylcholine-hydrolysing 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-hydrolysing PLD is a homologue of cardiolipin synthase, 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 [PUBMED:8732763, PUBMED:8755242, PUBMED:8051126, PUBMED:9242915].

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

Loading domain graphics...

Pfam Clan

This family is a member of clan PLD (CL0479), which has the following description:

This superfamily includes proteins that are related to Phospholiase D.

The clan contains the following 8 members:

DUF1669 PLDc PLDc_2 PLDc_3 PP_kinase_C RE_NgoFVII Regulator_TrmB Tyr-DNA_phospho

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(48)
Full
(1567)
Representative proteomes NCBI
(6708)
Meta
(176)
RP15
(219)
RP35
(475)
RP55
(677)
RP75
(833)
Jalview View  View  View  View  View  View  View  View 
HTML View  View  View  View  View  View     
PP/heatmap 1 View  View  View  View  View     
Pfam viewer View  View             

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(48)
Full
(1567)
Representative proteomes NCBI
(6708)
Meta
(176)
RP15
(219)
RP35
(475)
RP55
(677)
RP75
(833)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(48)
Full
(1567)
Representative proteomes NCBI
(6708)
Meta
(176)
RP15
(219)
RP35
(475)
RP55
(677)
RP75
(833)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Alignment kindly provided by SMART
Previous IDs: none
Type: Family
Author: Ponting C, Schultz J, Bork P
Number in seed: 48
Number in full: 1567
Average length of the domain: 29.50 aa
Average identity of full alignment: 40 %
Average coverage of the sequence by the domain: 4.30 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.9 21.9
Trusted cut-off 21.9 21.9
Noise cut-off 21.8 21.8
Model length: 28
Family (HMM) version: 17
Download: download the raw HMM for this family

Species distribution

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

PLDc

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PLDc domain has been found. There are 3 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

Loading structure mapping...