Details for: PLA2G4B

Gene ID: 100137049

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PLA2G4B

Ensembl ID: ENSG00000243708

Description: phospholipase A2 group IVB

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • sst GABAergic cortical interneuron CL4023017
    CSI 4.41
    rCSI 5.69%
    PRS 99.91
  • VIP GABAergic cortical interneuron CL4023016
    CSI 3.09
    rCSI 3.69%
    PRS 99.84

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PLA2G4B](/details-gene/100137049), or Phospholipase A2 Group IVB, is a protein-coding gene located on chromosome 15q15.1. It encodes a cytosolic, calcium-dependent phospholipase A2 enzyme critical for lipid metabolism. The primary function of this enzyme is to catalyze the hydrolysis of glycerophospholipids, releasing fatty acids, most notably arachidonic acid. This process is a key step in the generation of eicosanoids and other lipid mediators involved in the [inflammatory response](/details-go/GO:0006954) and signal transduction. Expression data suggests a highly specialized role for [PLA2G4B](/details-gene/100137049), as it shows significant expression primarily within specific neuronal subtypes, including [sst GABAergic cortical interneurons](/details-cell/CL4023017) and [VIP GABAergic cortical interneurons](/details-cell/CL4023016), pointing towards a role in neuromodulation and cortical circuit function. ## Cellular Roles and Expression Landscape The expression profile of [PLA2G4B](/details-gene/100137049) indicates a highly specialized function within the central nervous system. **Overall**, the gene's significance is most pronounced in distinct populations of inhibitory neurons in the cerebral cortex. The top-ranked cell types are: * **[sst GABAergic cortical interneuron](/details-cell/CL4023017)** (CSI: 4.41) * **[VIP GABAergic cortical interneuron](/details-cell/CL4023016)** (CSI: 3.09) The high Cell Significance Index (CSI) in these specific interneuron subtypes suggests that [PLA2G4B](/details-gene/100137049) is not a general neuronal marker but rather a key functional component of circuits involving somatostatin (SST) and vasoactive intestinal peptide (VIP) expressing cells. These neurons are crucial for regulating cortical information processing, network oscillations, and synaptic plasticity. The prominent role of [PLA2G4B](/details-gene/100137049) in these cells may relate to the generation of lipid-based signaling molecules that modulate their excitability or synaptic transmission. Research has also identified isoforms of the protein localized to the [cytosol](/details-go/GO:0005829), [mitochondrial inner membrane](/details-go/GO:0005743), and [early endosome membrane](/details-go/GO:0031901) ([Link](https://doi.org/10.1074/jbc.m601770200)). ## Pathways and Molecular Function The functional annotations for [PLA2G4B](/details-gene/100137049) confirm its central role in phospholipid metabolism and calcium-dependent signaling. **Molecular Function:** The gene product exhibits [calcium-dependent phospholipase a2 activity](/details-go/GO:0047498) and [calcium ion binding](/details-go/GO:0005509) capabilities. This dual function allows it to sense intracellular calcium fluctuations and respond by remodeling cellular membranes. **Biological Processes:** Its activity is integral to the [arachidonate metabolic process](/details-go/GO:0019369), which is the starting point for producing powerful signaling molecules involved in the [inflammatory response](/details-go/GO:0006954). Furthermore, it participates in the acyl-chain remodeling of various phospholipids, including phosphatidylcholine ([GO:0036151](/details-go/GO:0036151)) and phosphatidylethanolamine ([GO:0036152](/details-go/GO:0036152)). **Reactome Pathways:** The gene is a key component of multiple lipid metabolism pathways, such as '[Acyl chain remodelling of pc](/details-pathway/R-HSA-1482788)', '[Phospholipid metabolism](/details-pathway/R-HSA-1483257)', and '[Glycerophospholipid biosynthesis](/details-pathway/R-HSA-1483206)'. Its involvement in '[Cellular responses to stimuli](/details-pathway/R-HSA-8953897)' and the '[Unfolded protein response (upr)](/details-pathway/R-HSA-381119)' highlights its role in cellular stress and signaling cascades, which is consistent with its enzymatic function that can be rapidly activated by cellular signals like increased calcium. ## Research Directions The specific expression of [PLA2G4B](/details-gene/100137049) in cortical interneurons, coupled with its role in producing potent lipid mediators, opens up several avenues for future investigation into its role in brain function and disease. **Proposed Testable Hypotheses:** 1. **Neuromodulation:** Given its function in producing arachidonic acid derivatives (e.g., prostaglandins, endocannabinoids), [PLA2G4B](/details-gene/100137049) may act as a key regulator of synaptic plasticity and excitability specifically within [sst GABAergic cortical interneurons](/details-cell/CL4023017) and [VIP GABAergic cortical interneurons](/details-cell/CL4023016), thereby fine-tuning cortical network activity. 2. **Neuroinflammation and Cellular Stress:** The involvement of [PLA2G4B](/details-gene/100137049) in the inflammatory response and unfolded protein response suggests it could be a critical link between cellular stress (e.g., excitotoxicity, metabolic dysfunction) and the initiation of localized neuroinflammatory processes within cortical microcircuits. Dysregulation of [PLA2G4B](/details-gene/100137049) in these interneurons could contribute to the pathology of neurological disorders characterized by interneuron dysfunction and inflammation. **Suggested Experimental Approach:** To test the first hypothesis regarding neuromodulation, a combination of genetic manipulation and electrophysiology could be employed. One could use a Cre-Lox system in mice to achieve cell-type-specific knockout of *Pla2g4b* in either SST-positive or VIP-positive cortical interneurons. Acute brain slices could then be prepared from these animals for whole-cell patch-clamp recordings. By stimulating presynaptic inputs and recording postsynaptic currents, one could determine if the loss of [PLA2G4B](/details-gene/100137049) alters short-term or long-term synaptic plasticity (e.g., LTP/LTD) at synapses onto or from these interneurons. Furthermore, lipidomics analysis on sorted neurons could directly quantify changes in arachidonic acid-derived lipid mediators. **Therapeutic Potential:** As an enzyme, [PLA2G4B](/details-gene/100137049) is a potentially druggable target. Its highly restricted expression pattern in specific interneuron populations is advantageous, as it could allow for targeted therapeutic intervention with a reduced risk of widespread side effects. In neurological or psychiatric conditions characterized by cortical hyperexcitability or neuroinflammation (e.g., certain forms of epilepsy, schizophrenia, or Alzheimer's disease), specific inhibitors of [PLA2G4B](/details-gene/100137049) could be developed to dampen the production of pro-inflammatory or excitatory lipid mediators. Inhibition, rather than activation, would likely be the most promising therapeutic strategy for pathologies linked to excessive neuronal activity or inflammation.

Genular Protein ID: 3666268887

Symbol: PA24B_HUMAN

Name: Phospholipase A2 group IVB

UniProtKB Accession Codes:

P0C869 B4DRT9 O95712 Q19KD5 Q19KD6 Q59GF9 Q8TB10 Q9UKV7

Database IDs:

AGR 2 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BindingDB 1 BioGRID 2 BioGRID-ORCS 2 BioMuta 1 CCDS 1 CDD 2 CTD 2 ChEBI 54 ChEMBL 1 DMDM 1 DNASU 1 DisGeNET 2 EC 2 EMBL 7 Ensembl 2 ExpressionAtlas 1 GO 18 Gene3D 2 GeneCards 1 GeneTree 1 GeneWiki 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 6 KEGG 2 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 2 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 2 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 3 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 5 RNAct 1 Reactome 7 RefSeq 3 Rhea 18 SMART 2 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 SwissLipids 2 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 2 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 10085124

Title: Molecular cloning of two new human paralogs of 85-kDa cytosolic phospholipase A2.

PubMed ID: 10085124

DOI: 10.1074/jbc.274.13.8823

PubMed ID: 10358058

Title: Molecular characterization of cytosolic phospholipase A2-beta.

PubMed ID: 10358058

DOI: 10.1074/jbc.274.24.17063

PubMed ID: 16617059

Title: Identification of the expressed form of human cytosolic phospholipase A2beta (cPLA2beta): cPLA2beta3 is a novel variant localized to mitochondria and early endosomes.

PubMed ID: 16617059

DOI: 10.1074/jbc.m601770200

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16572171

Title: Analysis of the DNA sequence and duplication history of human chromosome 15.

PubMed ID: 16572171

DOI: 10.1038/nature04601

Sequence Information:

  • Length: 781
  • Mass: 87978
  • Checksum: 4C5C6861E7BAB1B8
  • Sequence:
    • MAVAEVSRTC LLTVRVLQAH RLPSKDLVTP SDCYVTLWLP TACSHRLQTR TVKNSSSPVW 
NQSFHFRIHR QLKNVMELKV FDQDLVTGDD PVLSVLFDAG TLRAGEFRRE SFSLSPQGEG 
RLEVEFRLQS LADRGEWLVS NGVLVARELS CLHVQLEETG DQKSSEHRVQ LVVPGSCEGP 
QEASVGTGTF RFHCPACWEQ ELSIRLQDAP EEQLKAPLSA LPSGQVVRLV FPTSQEPLMR 
VELKKEAGLR ELAVRLGFGP CAEEQAFLSR RKQVVAAALR QALQLDGDLQ EDEIPVVAIM 
ATGGGIRAMT SLYGQLAGLK ELGLLDCVSY ITGASGSTWA LANLYEDPEW SQKDLAGPTE 
LLKTQVTKNK LGVLAPSQLQ RYRQELAERA RLGYPSCFTN LWALINEALL HDEPHDHKLS 
DQREALSHGQ NPLPIYCALN TKGQSLTTFE FGEWCEFSPY EVGFPKYGAF IPSELFGSEF 
FMGQLMKRLP ESRICFLEGI WSNLYAANLQ DSLYWASEPS QFWDRWVRNQ ANLDKEQVPL 
LKIEEPPSTA GRIAEFFTDL LTWRPLAQAT HNFLRGLHFH KDYFQHPHFS TWKATTLDGL 
PNQLTPSEPH LCLLDVGYLI NTSCLPLLQP TRDVDLILSL DYNLHGAFQQ LQLLGRFCQE 
QGIPFPPISP SPEEQLQPRE CHTFSDPTCP GAPAVLHFPL VSDSFREYSA PGVRRTPEEA 
AAGEVNLSSS DSPYHYTKVT YSQEDVDKLL HLTHYNVCNN QEQLLEALRQ AVQRRRQRRP 
H