PLA2G4A: Difference between revisions

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<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''Cytosolic [[phospholipase A2]]''' is an [[enzyme]] that in humans is encoded by the ''PLA2G4A'' [[gene]].<ref name="pmid8175726">{{cite journal | author = Dennis EA | title = Diversity of group types, regulation, and function of phospholipase A2 | journal = Journal of Biological Chemistry | volume = 269 | issue = 18 | pages = 13057–13060 |date=Jun 1994 | pmid = 8175726 | pmc = | doi =  }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PLA2G4A phospholipase A2, group IVA (cytosolic, calcium-dependent)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5321| accessdate = }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image = PBB_Protein_PLA2G4A_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1bci.
| PDB = {{PDB2|1bci}}, {{PDB2|1cjy}}, {{PDB2|1rlw}}
| Name = Phospholipase A2, group IVA (cytosolic, calcium-dependent)
| HGNCid = 9035
| Symbol = PLA2G4A
| AltSymbols =; MGC126350; PLA2G4; cPLA2-alpha
| OMIM = 600522
| ECnumber = 
| Homologene = 32059
| MGIid = 1195256
| GeneAtlas_image1 = PBB_GE_PLA2G4A_210145_at_tn.png
| Function = {{GNF_GO|id=GO:0004622 |text = lysophospholipase activity}} {{GNF_GO|id=GO:0004623 |text = phospholipase A2 activity}} {{GNF_GO|id=GO:0005509 |text = calcium ion binding}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}}
| Component = {{GNF_GO|id=GO:0005829 |text = cytosol}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0006663 |text = platelet activating factor biosynthetic process}} {{GNF_GO|id=GO:0006690 |text = icosanoid metabolic process}} {{GNF_GO|id=GO:0009395 |text = phospholipid catabolic process}} {{GNF_GO|id=GO:0016042 |text = lipid catabolic process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5321
    | Hs_Ensembl = ENSG00000116711
    | Hs_RefseqProtein = NP_077734
    | Hs_RefseqmRNA = NM_024420
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 185064708
    | Hs_GenLoc_end = 185224736
    | Hs_Uniprot = P47712
    | Mm_EntrezGene = 18783
    | Mm_Ensembl = ENSMUSG00000056220
    | Mm_RefseqmRNA = NM_008869
    | Mm_RefseqProtein = NP_032895
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 1
    | Mm_GenLoc_start = 151591836
    | Mm_GenLoc_end = 151723502
    | Mm_Uniprot = Q3UMQ1
  }}
}}
'''Phospholipase A2, group IVA (cytosolic, calcium-dependent)''', also known as '''PLA2G4A''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PLA2G4A phospholipase A2, group IVA (cytosolic, calcium-dependent)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5321| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
This gene encodes a member of the [[cytosol]]ic [[phospholipase A2]] group IV family. The enzyme catalyzes the [[hydrolysis]] of membrane [[phospholipid]]s to release [[arachidonic acid]] which is subsequently metabolized into [[eicosanoid]]s. Eicosanoids, including [[prostaglandin]]s and [[leukotriene]]s, are lipid-based cellular hormones that regulate [[hemodynamic]]s, [[Inflammation|inflammatory responses]], and other intracellular pathways. The hydrolysis reaction also produces [[lysophospholipid]]s that are converted into [[platelet-activating factor]]. The enzyme is activated by increased intracellular [[calcium in biology|Ca<sup>2+</sup>]] levels and [[phosphorylation]], resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles.<ref name="entrez" />
{{PBB_Summary
 
| section_title =
== Interactions ==
| summary_text = This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca(2+) levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles.<ref name="entrez">{{cite web | title = Entrez Gene: PLA2G4A phospholipase A2, group IVA (cytosolic, calcium-dependent)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5321| accessdate = }}</ref>
 
}}
PLA2G4A has been shown to [[Protein-protein interaction|interact]] with [[HTATIP]].<ref name="pmid11416127">{{cite journal |vauthors=Sheridan AM, Force T, Yoon HJ, O'Leary E, Choukroun G, Taheri MR, Bonventre JV | title = PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production | journal = Molecular and Cellular Biology | volume = 21 | issue = 14 | pages = 4470–4481 |date=July 2001 | pmid = 11416127 | pmc = 87107 | doi = 10.1128/MCB.21.14.4470-4481.2001 }}</ref>
 
== Clinical significance ==
 
Mutations in this gene have been associated with [[multifocal stenosing ulceration of the small intestine]].<ref name="Brooke_2012">{{cite journal |vauthors=Brooke MA, Longhurst HJ, Plagnol V, Kirkby NS, Mitchell JA, Rüschendorf F, Warner TD, Kelsell DP, Macdonald TT | title = Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-α | journal = Gut | volume = 63| issue = | pages = 96–104|date=December 2012 | pmid = 23268370 | doi = 10.1136/gutjnl-2012-303581 | url = }}</ref>


==References==
==References==
{{reflist|2}}
{{reflist}}
 
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
*{{cite journal   |vauthors=Schröder HC, Perovic S, Kavsan V, etal |title=Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death |journal=Neurotoxicology |volume=19 |issue= 4–5 |pages= 683–688 |year= 1998 |pmid= 9745929 |doi=  }}
| citations =
*{{cite journal  |vauthors=Hirabayashi T, Murayama T, Shimizu T |title=Regulatory mechanism and physiological role of cytosolic phospholipase A2 |journal=Biological and Pharmaceutical Bulletin |volume=27 |issue= 8 |pages= 1168–1173 |year= 2005 |pmid= 15305015 |doi=10.1248/bpb.27.1168 }}
*{{cite journal  | author=Dennis EA |title=Diversity of group types, regulation, and function of phospholipase A2. |journal=J. Biol. Chem. |volume=269 |issue= 18 |pages= 13057-60 |year= 1994 |pmid= 8175726 |doi=  }}
*{{cite journal  |vauthors=Law MH, Cotton RG, Berger GE |title=The role of phospholipases A2 in schizophrenia |journal=Molecular Psychiatry |volume=11 |issue= 6 |pages= 547–556 |year= 2006 |pmid= 16585943 |doi= 10.1038/sj.mp.4001819 }}
*{{cite journal | author=Schröder HC, Perovic S, Kavsan V, ''et al.'' |title=Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death. |journal=Neurotoxicology |volume=19 |issue= 4-5 |pages= 683-8 |year= 1998 |pmid= 9745929 |doi=  }}
*{{cite journal  |vauthors=Shimizu T, Ohto T, Kita Y |title=Cytosolic phospholipase A2: biochemical properties and physiological roles |journal=IUBMB Life |volume=58 |issue= 5–6 |pages= 328–333 |year= 2006 |pmid= 16754327 |doi= 10.1080/15216540600702289 }}
*{{cite journal  | author=Hirabayashi T, Murayama T, Shimizu T |title=Regulatory mechanism and physiological role of cytosolic phospholipase A2. |journal=Biol. Pharm. Bull. |volume=27 |issue= 8 |pages= 1168-73 |year= 2005 |pmid= 15305015 |doi=  }}
*{{cite journal   |vauthors=Sharp JD, White DL, Chiou XG, etal |title=Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2 |journal=Journal of Biological Chemistry |volume=266 |issue= 23 |pages= 14850–14853 |year= 1991 |pmid= 1869522 |doi=  }}
*{{cite journal  | author=Law MH, Cotton RG, Berger GE |title=The role of phospholipases A2 in schizophrenia. |journal=Mol. Psychiatry |volume=11 |issue= 6 |pages= 547-56 |year= 2006 |pmid= 16585943 |doi= 10.1038/sj.mp.4001819 }}
*{{cite journal   |vauthors=Clark JD, Lin LL, Kriz RW, etal |title=A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP |journal=Cell |volume=65 |issue= 6 |pages= 1043–1051 |year= 1991 |pmid= 1904318 |doi=10.1016/0092-8674(91)90556-E }}
*{{cite journal  | author=Shimizu T, Ohto T, Kita Y |title=Cytosolic phospholipase A2: biochemical properties and physiological roles. |journal=IUBMB Life |volume=58 |issue= 5-6 |pages= 328-33 |year= 2006 |pmid= 16754327 |doi= 10.1080/15216540600702289 }}
*{{cite journal   |vauthors=Tay A, Simon JS, Squire J, etal |title=Cytosolic phospholipase A2 gene in human and rat: chromosomal localization and polymorphic markers |journal=Genomics |volume=26 |issue= 1 |pages= 138–141 |year= 1995 |pmid= 7782073 |doi=10.1016/0888-7543(95)80093-2 }}
*{{cite journal | author=Sharp JD, White DL, Chiou XG, ''et al.'' |title=Molecular cloning and expression of human Ca(2+)-sensitive cytosolic phospholipase A2. |journal=J. Biol. Chem. |volume=266 |issue= 23 |pages= 14850-3 |year= 1991 |pmid= 1869522 |doi=  }}
*{{cite journal  |vauthors=Wu T, Ikezono T, Angus CW, Shelhamer JH |title=Characterization of the promoter for the human 85 kDa cytosolic phospholipase A2 gene |journal=Nucleic Acids Research |volume=22 |issue= 23 |pages= 5093–5098 |year= 1995 |pmid= 7800505 |doi=10.1093/nar/22.23.5093  | pmc=523783 }}
*{{cite journal | author=Clark JD, Lin LL, Kriz RW, ''et al.'' |title=A novel arachidonic acid-selective cytosolic PLA2 contains a Ca(2+)-dependent translocation domain with homology to PKC and GAP. |journal=Cell |volume=65 |issue= 6 |pages= 1043-51 |year= 1991 |pmid= 1904318 |doi=  }}
*{{cite journal  |vauthors=Miyashita A, Crystal RG, Hay JG |title=Identification of a 27 bp 5'-flanking region element responsible for the low level constitutive expression of the human cytosolic phospholipase A2 gene |journal=Nucleic Acids Research |volume=23 |issue= 2 |pages= 293–301 |year= 1995 |pmid= 7862535 |doi=10.1093/nar/23.2.293 | pmc=306668 }}
*{{cite journal | author=Tay A, Simon JS, Squire J, ''et al.'' |title=Cytosolic phospholipase A2 gene in human and rat: chromosomal localization and polymorphic markers. |journal=Genomics |volume=26 |issue= 1 |pages= 138-41 |year= 1995 |pmid= 7782073 |doi=  }}
*{{cite journal  |vauthors=Morri H, Ozaki M, Watanabe Y |title=5'-flanking region surrounding a human cytosolic phospholipase A2 gene |journal=Biochemical and Biophysical Research Communications |volume=205 |issue= 1 |pages= 6–11 |year= 1995 |pmid= 7999086 |doi=10.1006/bbrc.1994.2621 }}
*{{cite journal  | author=Wu T, Ikezono T, Angus CW, Shelhamer JH |title=Characterization of the promoter for the human 85 kDa cytosolic phospholipase A2 gene. |journal=Nucleic Acids Res. |volume=22 |issue= 23 |pages= 5093-8 |year= 1995 |pmid= 7800505 |doi=  }}
*{{cite journal   |vauthors=Sharp JD, Pickard RT, Chiou XG, etal |title=Serine 228 is essential for catalytic activities of 85-kDa cytosolic phospholipase A2 |journal=Journal of Biological Chemistry |volume=269 |issue= 37 |pages= 23250–23254 |year= 1994 |pmid= 8083230 |doi=  }}
*{{cite journal  | author=Miyashita A, Crystal RG, Hay JG |title=Identification of a 27 bp 5'-flanking region element responsible for the low level constitutive expression of the human cytosolic phospholipase A2 gene. |journal=Nucleic Acids Res. |volume=23 |issue= 2 |pages= 293-301 |year= 1995 |pmid= 7862535 |doi=  }}
*{{cite journal   |vauthors=Lin LL, Wartmann M, Lin AY, etal |title=cPLA2 is phosphorylated and activated by MAP kinase |journal=Cell |volume=72 |issue= 2 |pages= 269–78 |year= 1993 |pmid= 8381049 |doi=10.1016/0092-8674(93)90666-E }}
*{{cite journal  | author=Morri H, Ozaki M, Watanabe Y |title=5'-flanking region surrounding a human cytosolic phospholipase A2 gene. |journal=Biochem. Biophys. Res. Commun. |volume=205 |issue= 1 |pages= 6-11 |year= 1995 |pmid= 7999086 |doi=  }}
*{{cite journal  |vauthors=Flati V, Haque SJ, Williams BR |title=Interferon-alpha-induced phosphorylation and activation of cytosolic phospholipase A2 is required for the formation of interferon-stimulated gene factor three |journal=EMBO Journal |volume=15 |issue= 7 |pages= 1566–1571 |year= 1996 |pmid= 8612580 |doi= | pmc=450066 }}
*{{cite journal | author=Sharp JD, Pickard RT, Chiou XG, ''et al.'' |title=Serine 228 is essential for catalytic activities of 85-kDa cytosolic phospholipase A2. |journal=J. Biol. Chem. |volume=269 |issue= 37 |pages= 23250-4 |year= 1994 |pmid= 8083230 |doi=  }}
*{{cite journal   |vauthors=de Carvalho MG, McCormack AL, Olson E, etal |title=Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A2 expressed in insect cells and present in human monocytes |journal=Journal of Biological Chemistry |volume=271 |issue= 12 |pages= 6987–6997 |year= 1996 |pmid= 8636128 |doi=10.1074/jbc.271.12.6987 }}
*{{cite journal | author=Lin LL, Wartmann M, Lin AY, ''et al.'' |title=cPLA2 is phosphorylated and activated by MAP kinase. |journal=Cell |volume=72 |issue= 2 |pages= 269-78 |year= 1993 |pmid= 8381049 |doi=  }}
*{{cite journal  |vauthors=Freed KA, Moses EK, Brennecke SP, Rice GE |title=Differential expression of type II, IV and cytosolic PLA2 messenger RNA in human intrauterine tissues at term |journal=Molecular Human Reproduction |volume=3 |issue= 6 |pages= 493–499 |year= 1997 |pmid= 9239738 |doi=10.1093/molehr/3.6.493 }}
*{{cite journal  | author=Flati V, Haque SJ, Williams BR |title=Interferon-alpha-induced phosphorylation and activation of cytosolic phospholipase A2 is required for the formation of interferon-stimulated gene factor three. |journal=EMBO J. |volume=15 |issue= 7 |pages= 1566-71 |year= 1996 |pmid= 8612580 |doi=  }}
*{{cite journal   |vauthors=Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, etal |title=HIV and SIV envelope glycoproteins induce phospholipase A2 activation in human and macaque lymphocytes |journal=Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology |volume=16 |issue= 1 |pages= 1–9 |year= 1997 |pmid= 9377118 |doi=10.1097/00042560-199709010-00001 }}
*{{cite journal | author=de Carvalho MG, McCormack AL, Olson E, ''et al.'' |title=Identification of phosphorylation sites of human 85-kDa cytosolic phospholipase A2 expressed in insect cells and present in human monocytes. |journal=J. Biol. Chem. |volume=271 |issue= 12 |pages= 6987-97 |year= 1996 |pmid= 8636128 |doi=  }}
*{{cite journal   |vauthors=Perisic O, Fong S, Lynch DE, etal |title=Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2 |journal=Journal of Biological Chemistry |volume=273 |issue= 3 |pages= 1596–1604 |year= 1998 |pmid= 9430701 |doi=10.1074/jbc.273.3.1596 }}
*{{cite journal  | author=Freed KA, Moses EK, Brennecke SP, Rice GE |title=Differential expression of type II, IV and cytosolic PLA2 messenger RNA in human intrauterine tissues at term. |journal=Mol. Hum. Reprod. |volume=3 |issue= 6 |pages= 493-9 |year= 1997 |pmid= 9239738 |doi=  }}
*{{cite journal   |vauthors=Börsch-Haubold AG, Bartoli F, Asselin J, etal |title=Identification of the phosphorylation sites of cytosolic phospholipase A2 in agonist-stimulated human platelets and HeLa cells |journal=Journal of Biological Chemistry |volume=273 |issue= 8 |pages= 4449–4458 |year= 1998 |pmid= 9468497 |doi=10.1074/jbc.273.8.4449 }}
*{{cite journal | author=Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, ''et al.'' |title=HIV and SIV envelope glycoproteins induce phospholipase A2 activation in human and macaque lymphocytes. |journal=J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. |volume=16 |issue= 1 |pages= 1-9 |year= 1997 |pmid= 9377118 |doi=  }}
*{{cite journal | author=Perisic O, Fong S, Lynch DE, ''et al.'' |title=Crystal structure of a calcium-phospholipid binding domain from cytosolic phospholipase A2. |journal=J. Biol. Chem. |volume=273 |issue= 3 |pages= 1596-604 |year= 1998 |pmid= 9430701 |doi=  }}
*{{cite journal | author=Börsch-Haubold AG, Bartoli F, Asselin J, ''et al.'' |title=Identification of the phosphorylation sites of cytosolic phospholipase A2 in agonist-stimulated human platelets and HeLa cells. |journal=J. Biol. Chem. |volume=273 |issue= 8 |pages= 4449-58 |year= 1998 |pmid= 9468497 |doi=  }}
}}
{{refend}}
{{refend}}


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Latest revision as of 22:03, 5 November 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Cytosolic phospholipase A2 is an enzyme that in humans is encoded by the PLA2G4A gene.[1][2]

Function

This gene encodes a member of the cytosolic phospholipase A2 group IV family. The enzyme catalyzes the hydrolysis of membrane phospholipids to release arachidonic acid which is subsequently metabolized into eicosanoids. Eicosanoids, including prostaglandins and leukotrienes, are lipid-based cellular hormones that regulate hemodynamics, inflammatory responses, and other intracellular pathways. The hydrolysis reaction also produces lysophospholipids that are converted into platelet-activating factor. The enzyme is activated by increased intracellular Ca2+ levels and phosphorylation, resulting in its translocation from the cytosol and nucleus to perinuclear membrane vesicles.[2]

Interactions

PLA2G4A has been shown to interact with HTATIP.[3]

Clinical significance

Mutations in this gene have been associated with multifocal stenosing ulceration of the small intestine.[4]

References

  1. ↑ Dennis EA (Jun 1994). "Diversity of group types, regulation, and function of phospholipase A2". Journal of Biological Chemistry. 269 (18): 13057–13060. PMID 8175726.
  2. ↑ 2.0 2.1 "Entrez Gene: PLA2G4A phospholipase A2, group IVA (cytosolic, calcium-dependent)".
  3. ↑ Sheridan AM, Force T, Yoon HJ, O'Leary E, Choukroun G, Taheri MR, Bonventre JV (July 2001). "PLIP, a novel splice variant of Tip60, interacts with group IV cytosolic phospholipase A(2), induces apoptosis, and potentiates prostaglandin production". Molecular and Cellular Biology. 21 (14): 4470–4481. doi:10.1128/MCB.21.14.4470-4481.2001. PMC 87107. PMID 11416127.
  4. ↑ Brooke MA, Longhurst HJ, Plagnol V, Kirkby NS, Mitchell JA, Rüschendorf F, Warner TD, Kelsell DP, Macdonald TT (December 2012). "Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-α". Gut. 63: 96–104. doi:10.1136/gutjnl-2012-303581. PMID 23268370.

Further reading


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