PLA2G6: 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
'''85 kDa calcium-independent [[phospholipase A2]]''' is an [[enzyme]] that in humans is encoded by the ''PLA2G6'' [[gene]].<ref name="pmid9417066">{{cite journal | vauthors = Larsson PK, Claesson HE, Kennedy BP | title = Multiple splice variants of the human calcium-independent phospholipase A2 and their effect on enzyme activity | journal = The Journal of Biological Chemistry | volume = 273 | issue = 1 | pages = 207–14 | date = Jan 1998 | pmid = 9417066 | pmc =  | doi = 10.1074/jbc.273.1.207 }}</ref><ref name="pmid16799181">{{cite journal | vauthors = Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ | title = Characterization of the human patatin-like phospholipase family | journal = Journal of Lipid Research | volume = 47 | issue = 9 | pages = 1940–9 | date = Sep 2006 | pmid = 16799181 | pmc =  | doi = 10.1194/jlr.M600185-JLR200 }}</ref><ref name="pmid19029121">{{cite journal | vauthors = Kienesberger PC, Oberer M, Lass A, Zechner R | title = Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions | journal = Journal of Lipid Research | volume = 50 Suppl | issue =  | pages = S63-8 | date = Apr 2009 | pmid = 19029121 | pmc = 2674697 | doi = 10.1194/jlr.R800082-JLR200 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PLA2G6 phospholipase A2, group VI (cytosolic, calcium-independent)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8398| 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 =
| image_source =
| PDB =
| Name = Phospholipase A2, group VI (cytosolic, calcium-independent)
| HGNCid = 9039
| Symbol = PLA2G6
| AltSymbols =; PLA2; CaI-PLA2; GVI; INAD1; PNPLA9; iPLA2
| OMIM = 603604
| ECnumber = 
| Homologene = 2635
| MGIid = 1859152
| GeneAtlas_image1 = PBB_GE_PLA2G6_215938_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_PLA2G6_204691_x_at_tn.png
| GeneAtlas_image3 = PBB_GE_PLA2G6_210647_x_at_tn.png
| Function = {{GNF_GO|id=GO:0004623 |text = phospholipase A2 activity}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}}
| Component = {{GNF_GO|id=GO:0005737 |text = cytoplasm}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0006644 |text = phospholipid metabolic process}} {{GNF_GO|id=GO:0008219 |text = cell death}} {{GNF_GO|id=GO:0016042 |text = lipid catabolic process}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 8398
    | Hs_Ensembl = ENSG00000184381
    | Hs_RefseqProtein = NP_001004426
    | Hs_RefseqmRNA = NM_001004426
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 22
    | Hs_GenLoc_start = 36837449
    | Hs_GenLoc_end = 36907763
    | Hs_Uniprot = O60733
    | Mm_EntrezGene = 53357
    | Mm_Ensembl = ENSMUSG00000042632
    | Mm_RefseqmRNA = XM_001001101
    | Mm_RefseqProtein = XP_001001101
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 15
    | Mm_GenLoc_start = 79113485
    | Mm_GenLoc_end = 79155439
    | Mm_Uniprot = Q3U613
  }}
}}
'''Phospholipase A2, group VI (cytosolic, calcium-independent)''', also known as '''PLA2G6''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: PLA2G6 phospholipase A2, group VI (cytosolic, calcium-independent)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8398| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
The protein encoded by this gene is a [[phospholipase A2]] enzyme, a subclass of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, [[arachidonic acid]] release, leukotriene and prostaglandin synthesis, [[Fas receptor]]-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only two of them have been determined to date.<ref name="entrez"/>
{{PBB_Summary
| section_title =
| summary_text = The protein encoded by this gene is an A2 phospholipase, a class of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, fas-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only two of them have been determined to date.<ref name="entrez">{{cite web | title = Entrez Gene: PLA2G6 phospholipase A2, group VI (cytosolic, calcium-independent)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8398| accessdate = }}</ref>
}}


==References==
==Model organisms==
{{reflist|2}}
[[Model organism]]s have been used in the study of PLA2G6 function. A conditional [[knockout mouse]] line called ''Pla2g6<sup>tm1a(EUCOMM)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Pla2g6#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | date = Jul 2013 | pmid = 23870131 | doi = 10.1016/j.cell.2013.06.022 | pmc=3717207}}</ref> Additional screens performed:  - In-depth immunological phenotyping.<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Pla2g6&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref>
==Further reading==
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
{{refbegin | 2}}
|+ ''Pla2g6'' knockout mouse phenotype
{{PBB_Further_reading
|-
| citations =  
! Characteristic!! Phenotype
*{{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 | author=Leslie CC |title=Regulation of arachidonic acid availability for eicosanoid production. |journal=Biochem. Cell Biol. |volume=82 |issue= 1 |pages= 1-17 |year= 2004 |pmid= 15052324 |doi= 10.1139/o03-080 }}
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" />
*{{cite journal | author=Turk J, Ramanadham S |title=The expression and function of a group VIA calcium-independent phospholipase A2 (iPLA2beta) in beta-cells. |journal=Can. J. Physiol. Pharmacol. |volume=82 |issue= 10 |pages= 824-32 |year= 2005 |pmid= 15573142 |doi= 10.1139/y04-064 }}
|-
*{{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 }}
| Homozygous viability at P14 || bgcolor="#488ED3"|Normal
*{{cite journal  | author=Tang J, Kriz RW, Wolfman N, ''et al.'' |title=A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs. |journal=J. Biol. Chem. |volume=272 |issue= 13 |pages= 8567-75 |year= 1997 |pmid= 9079687 |doi=  }}
 
*{{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=Larsson PK, Claesson HE, Kennedy BP |title=Multiple splice variants of the human calcium-independent phospholipase A2 and their effect on enzyme activity. |journal=J. Biol. Chem. |volume=273 |issue= 1 |pages= 207-14 |year= 1998 |pmid= 9417066 |doi=  }}
| Homozygous Fertility || bgcolor="#C40000"|Abnormal
*{{cite journal  | author=Ma Z, Wang X, Nowatzke W, ''et al.'' |title=Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1. |journal=J. Biol. Chem. |volume=274 |issue= 14 |pages= 9607-16 |year= 1999 |pmid= 10092647 |doi=  }}
 
*{{cite journal  | author=Larsson Forsell PK, Kennedy BP, Claesson HE |title=The human calcium-independent phospholipase A2 gene multiple enzymes with distinct properties from a single gene. |journal=Eur. J. Biochem. |volume=262 |issue= 2 |pages= 575-85 |year= 1999 |pmid= 10336645 |doi=  }}
|-
*{{cite journal  | author=Dunham I, Shimizu N, Roe BA, ''et al.'' |title=The DNA sequence of human chromosome 22. |journal=Nature |volume=402 |issue= 6761 |pages= 489-95 |year= 1999 |pmid= 10591208 |doi= 10.1038/990031 }}
| Body weight || bgcolor="#488ED3"|Normal
*{{cite journal  | author=Kim SJ, Gershov D, Ma X, ''et al.'' |title=I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation. |journal=J. Exp. Med. |volume=196 |issue= 5 |pages= 655-65 |year= 2002 |pmid= 12208880 |doi=  }}
 
*{{cite journal  | author=Hichami A, Joshi B, Simonin AM, Khan NA |title=Role of three isoforms of phospholipase A2 in capacitative calcium influx in human T-cells. |journal=Eur. J. Biochem. |volume=269 |issue= 22 |pages= 5557-63 |year= 2003 |pmid= 12423354 |doi=  }}
|-
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
| Neurological assessment || bgcolor="#488ED3"|Normal
*{{cite journal | author=Cummings BS, McHowat J, Schnellmann RG |title=Role of an endoplasmic reticulum Ca2+-independent phospholipase A2 in cisplatin-induced renal cell apoptosis. |journal=J. Pharmacol. Exp. Ther. |volume=308 |issue= 3 |pages= 921-8 |year= 2004 |pmid= 14634037 |doi= 10.1124/jpet.103.060541 }}
 
*{{cite journal | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
|-
*{{cite journal | author=Bao S, Jin C, Zhang S, ''et al.'' |title=Beta-cell calcium-independent group VIA phospholipase A(2) (iPLA(2)beta): tracking iPLA(2)beta movements in response to stimulation with insulin secretagogues in INS-1 cells. |journal=Diabetes |volume=53 Suppl 1 |issue= |pages= S186-9 |year= 2004 |pmid= 14749286 |doi= }}
| Grip strength || bgcolor="#488ED3"|Normal
*{{cite journal | author=Tay HK, Melendez AJ |title=Fcgamma RI-triggered generation of arachidonic acid and eicosanoids requires iPLA2 but not cPLA2 in human monocytic cells. |journal=J. Biol. Chem. |volume=279 |issue= 21 |pages= 22505-13 |year= 2004 |pmid= 15007079 |doi= 10.1074/jbc.M308788200 }}
 
*{{cite journal | author=Tanaka H, Minakami R, Kanaya H, Sumimoto H |title=Catalytic residues of group VIB calcium-independent phospholipase A2 (iPLA2gamma). |journal=Biochem. Biophys. Res. Commun. |volume=320 |issue= 4 |pages= 1284-90 |year= 2004 |pmid= 15249229 |doi= 10.1016/j.bbrc.2004.05.225 }}
|-
}}
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Cytotoxic T Cell Function || bgcolor="#488ED3"|Normal
 
|-
| Spleen Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Mesenteric Lymph Node Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Bone Marrow Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Epidermal Immune Composition || bgcolor="#488ED3"|Normal
 
|-
| Trichuris Challenge || bgcolor="#488ED3"|Normal
 
|-
|}
{{clear|left}}
 
==Clinical==
 
Mutations in this gene have been associated with [[hereditary spastic paraplegia]].<ref name=Ozes2017>Ozes B, Karagoz N, Schüle R, Rebelo A, Sobrido MJ, Harmuth F, Synofzik M, Pascual SIP, Colak M, Ciftci-Kavaklioglu B, Kara B, Ordóñez-Ugalde A, Quintáns B, Gonzalez MA, Soysal A, Zuchner S, Battaloglu E (2017) PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia. Clin Genet 92(5):534-539</ref>
 
== References ==
{{reflist}}
{{clear}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE | 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 = Leslie CC | title = Regulation of arachidonic acid availability for eicosanoid production | journal = Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire | volume = 82 | issue = 1 | pages = 1–17 | date = Feb 2004 | pmid = 15052324 | doi = 10.1139/o03-080 }}
* {{cite journal | vauthors = Turk J, Ramanadham S | title = The expression and function of a group VIA calcium-independent phospholipase A2 (iPLA2beta) in beta-cells | journal = Canadian Journal of Physiology and Pharmacology | volume = 82 | issue = 10 | pages = 824–32 | date = Oct 2004 | pmid = 15573142 | doi = 10.1139/y04-064 }}
* {{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 = 547–56 | date = Jun 2006 | pmid = 16585943 | doi = 10.1038/sj.mp.4001819 }}
* {{cite journal | vauthors = Tang J, Kriz RW, Wolfman N, Shaffer M, Seehra J, Jones SS | title = A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs | journal = The Journal of Biological Chemistry | volume = 272 | issue = 13 | pages = 8567–75 | date = Mar 1997 | pmid = 9079687 | doi = 10.1074/jbc.272.13.8567 }}
* {{cite journal | vauthors = Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, Nguyen HT, Yaba P, Delicat A, Georges AJ, Russo-Marie F | 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 | date = Sep 1997 | pmid = 9377118 | doi = 10.1097/00042560-199709010-00001 }}
* {{cite journal | vauthors = Ma Z, Wang X, Nowatzke W, Ramanadham S, Turk J | title = Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1 | journal = The Journal of Biological Chemistry | volume = 274 | issue = 14 | pages = 9607–16 | date = Apr 1999 | pmid = 10092647 | doi = 10.1074/jbc.274.14.9607 }}
* {{cite journal | vauthors = Larsson Forsell PK, Kennedy BP, Claesson HE | title = The human calcium-independent phospholipase A2 gene multiple enzymes with distinct properties from a single gene | journal = European Journal of Biochemistry / FEBS | volume = 262 | issue = 2 | pages = 575–85 | date = Jun 1999 | pmid = 10336645 | doi = 10.1046/j.1432-1327.1999.00418.x }}
* {{cite journal | vauthors = Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP | title = The DNA sequence of human chromosome 22 | journal = Nature | volume = 402 | issue = 6761 | pages = 489–95 | date = Dec 1999 | pmid = 10591208 | doi = 10.1038/990031 }}
* {{cite journal | vauthors = Kim SJ, Gershov D, Ma X, Brot N, Elkon KB | title = I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation | journal = The Journal of Experimental Medicine | volume = 196 | issue = 5 | pages = 655–65 | date = Sep 2002 | pmid = 12208880 | pmc = 2194002 | doi = 10.1084/jem.20020542 }}
* {{cite journal | vauthors = Hichami A, Joshi B, Simonin AM, Khan NA | title = Role of three isoforms of phospholipase A2 in capacitative calcium influx in human T-cells | journal = European Journal of Biochemistry / FEBS | volume = 269 | issue = 22 | pages = 5557–63 | date = Nov 2002 | pmid = 12423354 | doi = 10.1046/j.1432-1033.2002.03261.x }}
* {{cite journal | vauthors = Cummings BS, McHowat J, Schnellmann RG | title = Role of an endoplasmic reticulum Ca2+-independent phospholipase A2 in cisplatin-induced renal cell apoptosis | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 308 | issue = 3 | pages = 921–8 | date = Mar 2004 | pmid = 14634037 | doi = 10.1124/jpet.103.060541 }}
* {{cite journal | vauthors = Bao S, Jin C, Zhang S, Turk J, Ma Z, Ramanadham S | title = Beta-cell calcium-independent group VIA phospholipase A(2) (iPLA(2)beta): tracking iPLA(2)beta movements in response to stimulation with insulin secretagogues in INS-1 cells | journal = Diabetes | volume = 53 Suppl 1 | issue = 90001 | pages = S186-9 | date = Feb 2004 | pmid = 14749286 | doi = 10.2337/diabetes.53.2007.S186 }}
* {{cite journal | vauthors = Tay HK, Melendez AJ | title = Fcgamma RI-triggered generation of arachidonic acid and eicosanoids requires iPLA2 but not cPLA2 in human monocytic cells | journal = The Journal of Biological Chemistry | volume = 279 | issue = 21 | pages = 22505–13 | date = May 2004 | pmid = 15007079 | doi = 10.1074/jbc.M308788200 }}
* {{cite journal | vauthors = Tanaka H, Minakami R, Kanaya H, Sumimoto H | title = Catalytic residues of group VIB calcium-independent phospholipase A2 (iPLA2gamma) | journal = Biochemical and Biophysical Research Communications | volume = 320 | issue = 4 | pages = 1284–90 | date = Aug 2004 | pmid = 15249229 | doi = 10.1016/j.bbrc.2004.05.225 }}
{{refend}}
{{refend}}
{{gene-22-stub}}
{{WikiDoc Sources}}

Revision as of 10:25, 11 November 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

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

85 kDa calcium-independent phospholipase A2 is an enzyme that in humans is encoded by the PLA2G6 gene.[1][2][3][4]

Function

The protein encoded by this gene is a phospholipase A2 enzyme, a subclass of enzyme that catalyzes the release of fatty acids from phospholipids. The encoded protein may play a role in phospholipid remodelling, arachidonic acid release, leukotriene and prostaglandin synthesis, Fas receptor-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only two of them have been determined to date.[4]

Model organisms

Model organisms have been used in the study of PLA2G6 function. A conditional knockout mouse line called Pla2g6tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[5] Male and female animals underwent a standardized phenotypic screen[6] to determine the effects of deletion.[7][8][9][10] Additional screens performed: - In-depth immunological phenotyping.[11]

Clinical

Mutations in this gene have been associated with hereditary spastic paraplegia.[12]

References

  1. ↑ Larsson PK, Claesson HE, Kennedy BP (Jan 1998). "Multiple splice variants of the human calcium-independent phospholipase A2 and their effect on enzyme activity". The Journal of Biological Chemistry. 273 (1): 207–14. doi:10.1074/jbc.273.1.207. PMID 9417066.
  2. ↑ Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (Sep 2006). "Characterization of the human patatin-like phospholipase family". Journal of Lipid Research. 47 (9): 1940–9. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
  3. ↑ Kienesberger PC, Oberer M, Lass A, Zechner R (Apr 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". Journal of Lipid Research. 50 Suppl: S63–8. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.
  4. ↑ 4.0 4.1 "Entrez Gene: PLA2G6 phospholipase A2, group VI (cytosolic, calcium-independent)".
  5. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  6. ↑ 6.0 6.1 "International Mouse Phenotyping Consortium".
  7. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  8. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  9. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  10. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  11. ↑ 11.0 11.1 "Infection and Immunity Immunophenotyping (3i) Consortium".
  12. ↑ Ozes B, Karagoz N, Schüle R, Rebelo A, Sobrido MJ, Harmuth F, Synofzik M, Pascual SIP, Colak M, Ciftci-Kavaklioglu B, Kara B, Ordóñez-Ugalde A, Quintáns B, Gonzalez MA, Soysal A, Zuchner S, Battaloglu E (2017) PLA2G6 mutations associated with a continuous clinical spectrum from neuroaxonal dystrophy to hereditary spastic paraplegia. Clin Genet 92(5):534-539

Further reading

  • Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death". Neurotoxicology. 19 (4–5): 683–8. PMID 9745929.
  • Leslie CC (Feb 2004). "Regulation of arachidonic acid availability for eicosanoid production". Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire. 82 (1): 1–17. doi:10.1139/o03-080. PMID 15052324.
  • Turk J, Ramanadham S (Oct 2004). "The expression and function of a group VIA calcium-independent phospholipase A2 (iPLA2beta) in beta-cells". Canadian Journal of Physiology and Pharmacology. 82 (10): 824–32. doi:10.1139/y04-064. PMID 15573142.
  • Law MH, Cotton RG, Berger GE (Jun 2006). "The role of phospholipases A2 in schizophrenia". Molecular Psychiatry. 11 (6): 547–56. doi:10.1038/sj.mp.4001819. PMID 16585943.
  • Tang J, Kriz RW, Wolfman N, Shaffer M, Seehra J, Jones SS (Mar 1997). "A novel cytosolic calcium-independent phospholipase A2 contains eight ankyrin motifs". The Journal of Biological Chemistry. 272 (13): 8567–75. doi:10.1074/jbc.272.13.8567. PMID 9079687.
  • Mavoungou E, Georges-Courbot MC, Poaty-Mavoungou V, Nguyen HT, Yaba P, Delicat A, Georges AJ, Russo-Marie F (Sep 1997). "HIV and SIV envelope glycoproteins induce phospholipase A2 activation in human and macaque lymphocytes". Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology. 16 (1): 1–9. doi:10.1097/00042560-199709010-00001. PMID 9377118.
  • Ma Z, Wang X, Nowatzke W, Ramanadham S, Turk J (Apr 1999). "Human pancreatic islets express mRNA species encoding two distinct catalytically active isoforms of group VI phospholipase A2 (iPLA2) that arise from an exon-skipping mechanism of alternative splicing of the transcript from the iPLA2 gene on chromosome 22q13.1". The Journal of Biological Chemistry. 274 (14): 9607–16. doi:10.1074/jbc.274.14.9607. PMID 10092647.
  • Larsson Forsell PK, Kennedy BP, Claesson HE (Jun 1999). "The human calcium-independent phospholipase A2 gene multiple enzymes with distinct properties from a single gene". European Journal of Biochemistry / FEBS. 262 (2): 575–85. doi:10.1046/j.1432-1327.1999.00418.x. PMID 10336645.
  • Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. doi:10.1038/990031. PMID 10591208.
  • Kim SJ, Gershov D, Ma X, Brot N, Elkon KB (Sep 2002). "I-PLA(2) activation during apoptosis promotes the exposure of membrane lysophosphatidylcholine leading to binding by natural immunoglobulin M antibodies and complement activation". The Journal of Experimental Medicine. 196 (5): 655–65. doi:10.1084/jem.20020542. PMC 2194002. PMID 12208880.
  • Hichami A, Joshi B, Simonin AM, Khan NA (Nov 2002). "Role of three isoforms of phospholipase A2 in capacitative calcium influx in human T-cells". European Journal of Biochemistry / FEBS. 269 (22): 5557–63. doi:10.1046/j.1432-1033.2002.03261.x. PMID 12423354.
  • Cummings BS, McHowat J, Schnellmann RG (Mar 2004). "Role of an endoplasmic reticulum Ca2+-independent phospholipase A2 in cisplatin-induced renal cell apoptosis". The Journal of Pharmacology and Experimental Therapeutics. 308 (3): 921–8. doi:10.1124/jpet.103.060541. PMID 14634037.
  • Bao S, Jin C, Zhang S, Turk J, Ma Z, Ramanadham S (Feb 2004). "Beta-cell calcium-independent group VIA phospholipase A(2) (iPLA(2)beta): tracking iPLA(2)beta movements in response to stimulation with insulin secretagogues in INS-1 cells". Diabetes. 53 Suppl 1 (90001): S186–9. doi:10.2337/diabetes.53.2007.S186. PMID 14749286.
  • Tay HK, Melendez AJ (May 2004). "Fcgamma RI-triggered generation of arachidonic acid and eicosanoids requires iPLA2 but not cPLA2 in human monocytic cells". The Journal of Biological Chemistry. 279 (21): 22505–13. doi:10.1074/jbc.M308788200. PMID 15007079.
  • Tanaka H, Minakami R, Kanaya H, Sumimoto H (Aug 2004). "Catalytic residues of group VIB calcium-independent phospholipase A2 (iPLA2gamma)". Biochemical and Biophysical Research Communications. 320 (4): 1284–90. doi:10.1016/j.bbrc.2004.05.225. PMID 15249229.
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