Center for Bioinformatics
Oxidoreductases | Transferases | Hydrolases | Lyases | Isomerases | Ligases

Basic Information

Enzyme Number

3.1.1.4

Official Name

phospholipase A2

Name from literature

phospholipase a2

Pathway from literature

eicosanoid synthesis/arachidonic acid release and subsequent eicosanoid formation/prostaglandin synthesis

Pathway from KEGG

Cellular Processes; Immune System; Fc epsilon RI signaling pathway; map04664

Lipid Metabolism; Ether lipid metabolism; map00565

Lipid Metabolism; Linoleic acid metabolism; map00591

Lipid Metabolism; Glycerophospholipid metabolism; map00564

Lipid Metabolism; Arachidonic acid metabolism; map00590

Lipid Metabolism; alpha-Linolenic acid metabolism; map00592

Environmental Information Processing; Signal Transduction; MAPK signaling pathway; map04010

Environmental Information Processing; Signal Transduction; VEGF signaling pathway; map04370

Cellular Processes; Nervous System; Long-term depression; map04730

Cellular Processes; Endocrine System; GnRH signaling pathway; map04912

Organisms

Human (9606)

Genome localization

15q11.2-q21.3[8681 ], 22q11.2-q13.2[50487 ], 12q23-q24.1[5319 ], 10q22.1[84647 ], 16p13.1-p12[8399 ], 1p35[64600 ], 4q25[81579 ], 15q11.2-q21.3[100137049 ], 1p36-p34[5322 ], 1p36.12[26279 ], 1p36.13[30814 ], 1p35[5320 ], 22q13.1[8398 ], 1q25[5321 ],

Comments

Also acts on phosphatidylethanolamine, choline plasmalogen and phosphatides, removing the fatty acid attached to the 2-position. Requires Ca2+.

Rate-limiting Description

"Differences in patients' responses to niacin, a compound causing vasodilation via stimulation of phospholipid dependent signaling cascades, defines more homogeneous patient subgroups in which the rate limiting enzyme of this signaling pathway, phospholipase A2 (PLA2), can be studied." (10435206)

Regulatory Information

Upstream transcription factor

1432;5578;5319;1051;1050

Regulatory type

Detail

others;Activatted protein C

"Activatted protein C(APC) effectively suppresses up-regulated sPLA(2)-IIA expressionwhich might contribute to the reported beneficial effects of APC in the treatment of severe inflammatory disorders." (17936881)

phosphorylation;

"group IVA cytosolic phospholipase A(2) is activated by phosphorylation" (12885780)

signal pathway;p38(1432)

"HCy led to the phosphorylation of cytosolic phospholipase A2; HCy promoted cPLA2 activation; cPLA2 phosphorylation and activation required p38 MAPK" (16409471)

phosphorylation;PKCalpha(5578)

"Our data suggest that PKCalpha, but not PKCbeta, is the predominant cPKC isoenzyme required for cPLA(2) protein phosphorylation and maximal induction of cPLA(2) enzymatic activity upon activation of human monocytes." (16963226)

phosphorylation;

O60733

phosphorylation;

P04054

phosphorylation;

P47712

phosphorylation;

Q9NZ20

phosphorylation;

Q9UP65

phosphorylation;

O60733:from_uniprot:587_Phosphothreonine

phosphorylation;

P47712:from_uniprot:434_Phosphoserine

phosphorylation;

P47712:from_uniprot:435_Phosphoserine

phosphorylation;

P47712:from_uniprot:437_Phosphoserine

phosphorylation;

P47712:from_uniprot:505_Phosphoserine; by MAPK

phosphorylation;

P47712:from_uniprot:535_Phosphotyrosine

phosphorylation;

P47712:from_uniprot:727_Phosphoserine

phosphorylation;

P47712:from_uniprot:729_Phosphoserine

phosphorylation;

Q3MJ16:from_uniprot:723_Phosphotyrosine

phosphorylation;

Q9UP65:from_uniprot:530_Phosphotyrosine

transcriptional factor;C/EBP beta(1051),C/EBP alpha(1050),C/EBP delta

"C/EBP factor suppression of inhibition of type II secreted phospholipase A2 promoter in HepG2 cells: possible role of single-strand binding proteins." (9234681#8003480#11080684)

transcriptional factor;PLA2G1B(5319)

"The human 180-kDa receptor for secretory phospholipases A2. Molecular cloning, identification of a secreted soluble form, expression, and chromosomal localization." (7721806)

Gene ontology

Gene ontology

GO:0007242 (P) intracellular signaling cascade [Q9UP65 ];
GO:0032869 (P) cellular response to insulin stimulus [P04054 ];
GO:0005615 (C) extracellular space [Q9NZ20, P04054 ];
GO:0016020 (C) membrane [O60733, Q9UP65, P14555 ];
GO:0043498 (F) cell surface binding [P04054 ];
GO:0019370 (P) leukotriene biosynthetic process [P04054 ];
GO:0016021 (C) integral to membrane [Q6P1J6, P47712 ];
GO:0006663 (P) platelet activating factor biosynthetic pro... [P47712 ];
GO:0047499 (F) calcium-independent phospholipase A2 activity [Q9UP65 ];
GO:0010552 (P) positive regulation of specific transcripti... [P04054 ];
GO:0048146 (P) positive regulation of fibroblast prolifera... [P04054 ];
GO:0044240 (P) multicellular organismal lipid catabolic pr... [P04054 ];
GO:0045740 (P) positive regulation of DNA replication [P04054 ];
GO:0010524 (P) positive regulation of calcium ion transpor... [P04054 ];
GO:0050482 (P) arachidonic acid secretion [P04054 ];
GO:0030659 (C) cytoplasmic vesicle membrane [Q86XP0 ];
GO:0005576 (C) extracellular region [Q9UNK4, Q9BZM2, O15496, P39877, Q9BZM1, P14555, Q9NZK7 ];
GO:0005634 (C) nucleus [O60733 ];
GO:0005543 (F) phospholipid binding [Q9UP65 ];
GO:0016042 (P) lipid catabolic process [Q9BZM2, O15496, P39877, O60733, Q6P1J6, P14555, Q9UNK4, Q9BZM1, Q9NZ20, Q9NZK7 ];
GO:0050714 (P) positive regulation of protein secretion [P04054 ];
GO:0032637 (P) interleukin-8 production [P04054 ];
GO:0015758 (P) glucose transport [P04054 ];
GO:0006954 (P) inflammatory response [Q9UNK4, Q9UP65, Q9NZK7 ];
GO:0046475 (P) glycerophospholipid catabolic process [Q9UP65 ];
GO:0005737 (C) cytoplasm [Q9BZM1 ];
GO:0005829 (C) cytosol [Q9UP65, P47712 ];
GO:0005813 (C) centrosome [O60733 ];
GO:0032431 (P) activation of phospholipase A2 [P04054 ];
GO:0050778 (P) positive regulation of immune response [P04054 ];
GO:0005509 (F) calcium ion binding [P0C869, Q3MJ16, Q9BZM2, O15496, P39877, P14555, P04054, Q9UNK4, Q68DD2, Q86XP0, Q9BZM1, Q9NZ20, Q9NZK7, P47712 ];
GO:0051092 (P) positive regulation of NF-kappaB transcript... [P04054 ];
GO:0030593 (P) neutrophil chemotaxis [P04054 ];
GO:0019369 (P) arachidonic acid metabolic process [Q9UP65 ];
GO:0002446 (P) neutrophil mediated immunity [P04054 ];
GO:0007015 (P) actin filament organization [P04054 ];
GO:0046470 (P) phosphatidylcholine metabolic process [P04054 ];
GO:0005783 (C) endoplasmic reticulum [P14555 ];
GO:0031966 (C) mitochondrial membrane [P0C869 ];
GO:0008219 (P) cell death [O60733 ];
GO:0032052 (F) bile acid binding [P04054 ];
GO:0006644 (P) phospholipid metabolic process [Q9UNK4, Q9BZM2, O15496, P39877, O60733, Q9BZM1, Q9NZ20, P14555, Q9NZK7 ];
GO:0005886 (C) plasma membrane [Q9NZ20 ];
GO:0016324 (C) apical plasma membrane [Q6P1J6 ];
GO:0004622 (F) lysophospholipase activity [Q6P1J6, P47712 ];
GO:0007567 (P) parturition [Q9UP65 ];
GO:0031901 (C) early endosome membrane [P0C869 ];
GO:0004623 (F) phospholipase A2 activity [P0C869, Q3MJ16, Q9BZM2, O15496, O60733, Q6P1J6, Q9UNK4, Q68DD2, Q86XP0, Q9NZK7, P47712 ];
GO:0031410 (C) cytoplasmic vesicle [P47712 ];
GO:0005102 (F) receptor binding [P04054 ];
GO:0005765 (C) lysosomal membrane [Q68DD2, Q3MJ16 ];
GO:0009395 (P) phospholipid catabolic process [Q68DD2, P0C869, Q86XP0, Q3MJ16, P47712 ];
GO:0006690 (P) icosanoid metabolic process [P47712 ];
GO:0000187 (P) activation of MAPK activity [P04054 ];
GO:0047498 (F) calcium-dependent phospholipase A2 activity [P39877, Q9BZM1, Q9NZ20, P14555, P04054 ];

Tissue expression

Tissue From HPRD

Colon [17858, 04674, 07306, 10155, 07499, 07546, 04675 ];
Gall bladder [01397 ];
Hippocampus [04673 ];
Lymph node [04675 ];
Corpus callosum [04673 ];
Choriodecidua [08986 ];
Cartilage [01397 ];
Fetus [04674 ];
Urinary bladder [10155 ];
Testis [17858, 07306, 10155, 07499, 04675 ];
Macrophage [03117 ];
Endocrine pancreas [10155 ];
Brain [17858, 04673, 07143, 07306, 07499, 01397, 04675 ];
Spleen [01396, 04674, 07306, 07499, 07546, 04675 ];
Small intestine [17858, 07306, 10155, 07499, 07546, 04675 ];
Chorioamnionic membrane [03117 ];
Thalamus [04673 ];
Heart [04673, 07144, 17858, 07143, 01396, 07306, 07499, 10155, 03117, 04675 ];
Urine [01396 ];
Amygdala [04673 ];
Nasal mucosa [01396 ];
Mast cell [03117 ];
Umbilical vein endothelial cell [03117 ];
Thyroid gland [10155, 04675 ];
Thymus [17858, 01396, 04674, 07306, 07499, 07546, 04675 ];
Uterus [10155 ];
Substantia nigra [04673 ];
Vulva [10155 ];
Spinal cord [01396, 04675 ];
Tear [01396 ];
Leukocyte [17858, 04674, 07306, 07499, 07144, 04675 ];
Intestine [01397 ];
Caudate nucleus [04673 ];
Bone marrow [04675 ];
Liver [17858, 04673, 07306, 10155, 07499, 07144, 04675 ];
Skeletal muscle [17858, 04673, 07306, 10155, 07499, 07144, 04675 ];
Joints [01397 ];
Prostate [17858, 07306, 10155, 07499, 07546, 04675 ];
Platelet [01397 ];
Kidney [17858, 04673, 07306, 10155, 07499, 07144, 04675 ];
Mammary gland [10155 ];
Adrenal gland [04675 ];
Rectum [10155 ];
Neutrophil [03117 ];
Lung [04673, 17858, 07143, 01396, 04674, 07306, 07499, 10155, 03117, 04675 ];
Ovary [17858, 07306, 10155, 07546, 04675 ];
Epidermis [01396 ];
Ileum [01396 ];
Pancreas [04673, 17858, 04674, 07306, 01397, 07499, 04675, 07546 ];
Skin [10155, 01397 ];
Cervix [10155 ];
Trachea [10155, 04675 ];
Placenta [04673, 08986, 07144, 17858, 07143, 01396, 07306, 07499, 03117, 04675, 07546 ];
Subthalamic nucleus [04673 ];
Semen [01396 ];
Amnion [08986 ];
Stomach [10155, 04675 ];

Tissue specificity

Expressed in the epidermis (at protein level) [Q6P1J6 ];

Widely expressed. Expressed at higher level in brain, heart, liver, cerebellum and pancreas. Isoform 3 is widely expressed [P0C869 ];

Restricted to the brain, heart, lung, and placenta [Q9NZK7 ];

Four different transcripts were found to be expressed in a distinct tissue distribution [O60733 ];

Expressed in kidney, heart, liver, and skeletal muscle. Also present in placenta and peripheral blood leukocytes. Not detected in brain, colon, thymus, spleen and small intestine. In lung, expressed in bronchial epithelial cells and alveolar macrophages, but scarcely detected in alveolar epithelium, arterial walls and interstitial fibroblasts (at protein level). In joints of osteoarthritis and rheumatoid arthritis, expressed in endothelial cells (at protein level). In normal heart, detected in some vessels. In myocardial tissues with acute infarction, expressed in vascular endothelial cells adjacent to cardiomyocytes and those in lesions with granulation. Expression in cardiomyocytes is scarce (at protein level). In uterus, breast and colon cancers, detected in tumor cells and neighboring microvascular endothelium, but not in normal glandular tissues (at protein level) [Q9NZ20 ];

Abundantly expressed in heart, skeletal muscle, kidney, liver and pancreas [Q9BZM1 ];

Heart, placenta and less abundantly, in lung [P39877 ];

Highly expressed in heart and skeletal muscle [Q9UP65 ];

Found in spleen, thymus, peripheral blood leukocytes, pancreas, lung, and colon [O15496 ];

Broadly expressed [Q9UNK4 ];

Expressed in various tissues such as macrophages, platelets, neutrophils, fibroblasts and lung endothelium [P47712 ];

Expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. Strongly expressed in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin [Q86XP0 ];

Expressed at high levels in placenta, testis, thymus and at lower levels in heart, kidney, liver and prostate [Q9BZM2 ];

Subcellular localization

Localization

endosome [P0C869 ];

mitochondrion [P0C869 ];

cell membrane [Q68DD2, Q86XP0, Q3MJ16, O60733, Q6P1J6, Q9NZ20, P14555 ];

extracellular [Q9UNK4, Q9BZM2, O15496, P39877, Q9BZM1, Q9NZ20, Q9NZK7, P04054 ];

nucleus [Q86XP0 ];

membrane [P0C869, Q9UP65 ];

lysosome [Q68DD2, Q3MJ16 ];

cytoplasm [Q68DD2, P0C869, Q86XP0, Q3MJ16, O60733, Q9BZM1, P47712 ];

Disease relevance

Disease

Defects in PLA2G6 are the cause of Karak syndrome [MIM:608395]. Karak syndrome is a neurologic disease characterized by early-onset progressive cerebellar ataxia, dystonia, spasticity, intellectual and features compatible with iron deposition in the putamen and substantia nigra [O60733 ];

Defects in PLA2G6 are a cause of neurodegeneration with brain iron accumulation (NBIA) [MIM:610217]. NBIA comprises a clinically and genetically heterogeneous group of disorders with high basal ganglia iron [O60733 ];

Defects in PLA2G6 are the cause of infantile neuroaxonal dystrophy 1 (INAD1) [MIM:256600];
also known as Seitelberger disease. Infantile neuroaxonal dystrophy (INAD) is a neurodegenerative disease characterized by pathologic axonal swelling and spheroid bodies in the central nervous system. Onset is within the first 2 years of life with death by age 10 years [O60733 ];

Links

SwissProt

O15496; O60733; P04054; P0C869; P14555; P39877; P47712; Q3MJ16; Q68DD2; Q6P1J6; Q86XP0; Q9BZM1; Q9BZM2; Q9NZ20; Q9NZK7; Q9UNK4; Q9UP65

Entrez Gene

100137049; 26279; 30814; 50487; 5319; 5320; 5321; 5322; 64600; 81579; 8398; 8399; 84647; 8681

HPRD

07143; 17326; 08986; 07499; 04674; 01396; 07144; 17858; 04675; 07306; 07546; 10155; 13510; 07145; 04673; 01397; 03117



  Copyright 2009, Center for Bioinformatics 
  Last Modified: 2009-03-24  
  Design by Zhao Min