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PLCB2 (phospholipase C, beta 2)

Written2007-05Valeria Bertagnolo, Federica Brugnoli, Mascia Benedusi, Silvano Capitani
Signal Transduction Unit, Laboratory of Cell Biology, Section of Human Anatomy, Department of Morphology, Embryology, University of Ferrara, Ferrara, Italy

(Note : for Links provided by Atlas : click)

Identity

Alias_namesphospholipase C
Alias_symbol (synonym)FLJ38135
Other alias
HGNC (Hugo) PLCB2
LocusID (NCBI) 5330
Atlas_Id 41743
Location 15q15.1  [Link to chromosome band 15q15]
Location_base_pair Starts at 40580098 and ends at 40600174 bp from pter ( according to hg19-Feb_2009)  [Mapping PLCB2.png]
Fusion genes
(updated 2016)
INS-IGF2 (11p15.5) / PLCB2 (15q15.1)LTBP2 (14q24.3) / PLCB2 (15q15.1)PLCB2 (15q15.1) / JUP (17q21.2)
PLCB2 (15q15.1) / PLCB2 (15q15.1)

DNA/RNA

Note 32 exons; DNA size 19,93 Kb.
Transcription mRNA size 4518 bp. Two alternatively spliced forms of PLC-b2 have been identified:
PLC-b2a and PLC-b2b.
The sequence of PLC-b2a consists of 1181 amino acids (molecular weight 133.7 kDa). PLC-b2b transcript lacks 45 nucleotides in the carboxyl-terminal region and the two splice variants differ by 15 amino acid residues, corresponding to aa 864-878.
Pseudogene No known pseudogenes.

Protein

 
  PH: pleckstrin homology domain
EF: EF-hand domain
X and Y: catalytic domains
C2: calcium-binding domain
Description The sequence of PLC-b2 contains a PH-domain in the amino-terminal region, that binds to polyhosphoinositides and to cytoskeleton proteins. The catalytic site corresponds to the X and Y domains, highly conserved among PLCs. A C2 domain, present in numerous signaling molecules, is involved in the calcium binding. The long carboxyl-terminal region, located downstream to the C2 domain, is involved in the Gaq mediated activation of the catalytic domains and contains a nuclear localization signal. Additional EF domains are located between the PH and X regions and seem to simply constitute a flexible linker to the X-Y domain.
Expression PLC-b2, first isolated from a HL-60 cDNA library, is expressed predominantly in cells of haematopoietic origin. The amount of PLC-b2 correlates with the functional maturation of differentiating cells. In platelets, leukocytes and erythroleukemia cells, both the two alternatively spliced forms are present.
PLC-b2 is weakly expressed in breast epithelial cells and shows high levels in tumoral mammary tissues. PLC-b2 was also identified in ATP-secreting taste bud cells.
Localisation PLC-b2 has both a cytoplasmic and a nuclear localization. In particular, PLC-b2 accumulates inside the nuclear compartment during agonist-induced granulocytic differentiation of tumoral myeloid precursors.
In platelets, expressing both splicing variants, PLC-b2a is most abundant in the nuclear compartment.
By means of immunocytochemical analysis, it has been demonstrated that in promyelocytes differentiating along the neutrophil lineage, PLC-b2 distribution evokes the spatial organization of the cytoskeleton.
Function PLC-b2 catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP2) generating the second messenger molecules inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG).
In hematopoietic cells, PLC-b2 plays a crucial role in platelet activation and in response of neutrophils to chemoattractants.
During maturation of tumoral myeloid precursors, it has been demonstrated that the phosphodiesterase activity of PLC-b2 on the actin-associated PIP2 may be responsible, by modifying the phosphoinositide pools, for the modifications of cytoskeleton architecture that take place during motility of differentiating promyelocytes.
In taste bud cells, PLC-b2 is a marker of early differentiation and functional taste signalling.
Homology PLC-b2 is related to PLC-b1 with an amino acid sequence identity of 48%.

Implicated in

Note
  
Entity Acute Promyelocytic Leukaemia (APL)
Note This hematopoietic disorder is a M3 subtype of acute myeloblastic leukemia and is characterized by a block of granulocytopoiesis at the promyelocytic stage. APL blasts present a balanced reciprocal t(15;17) chromosomal translocation encoding the PML/ RARA fusion protein that plays a key role in the pathogenesis of the disease.
Disease PLC-b2, highly present in neutrophils of peripheral blood, is weakly expressed in blasts purified from patients with APL and in APL-derived cell lines.
Prognosis PLC-b2 shows a large increase of expression during ATRA (all-trans-retinoic acid ) and/or As2O3-induced granulocytic differentiation of both APL-derived cell lines and blasts purified from patients with APL. PLC-b2 expression during differentiating treatments correlates with the granulocytic maturation levels reached by myeloid precursors. In addition, the level of PLC-b2 after ex-vivo ATRA treatment of APL blasts strikingly correlates with the responsiveness of APL patients to ATRA-based therapies.
This evidence demonstrates that PLC-b2 represents a specific marker for monitoring the agonist-induced overcoming of the maturation blockade of tumoral promyelocytes.
Oncogenesis It has been reported that co-repressors bound to PML-RARa are released from DNA upon both ATRA and As2O3-treatment of APL cells leading to the activation of genes repressed by the fusion protein. This suggests that the reduced expression of PLC-b2, whose gene is located on chromosome 15, which is involved in the (15;17) translocation, may be related to the presence of the fusion protein. The increased expression of PLC-b2, induced by both ATRA and As2O3, may be related indeed to the removal of the fusion protein, that seems to constitute a common step of the differentiation pathways activated by the two agonists.
  
  
Entity Breast cancer
Note Breast cancer is highly heterogeneous and, during its sequential in vivo progression from atypical hyperproliferation to metastatic disease, tumor cells undergo phenotype alterations, including the loss, to a variable extent, of epithelial-like features, and the gain of more aggressive and invasive mesenchymal-like traits. Like most human neoplasm, breast cancer has aberrations in signal transduction elements that can lead to increased proliferative potential, sustained angiogenesis, apoptosis inhibition and tissue invasion and metastasis. The portrait of breast tumors remains stable during progression and no major changes appear to explain why a tumor may evolve to the metastatic stage and, at present, no marker has been clearly associated with the progression from in situ to invasiveness.
Disease It has recently been demonstrated, by means of immunohistochemical analysis on tissue microarrays composed of breast cancer specimens and normal epithelia, that PLC-b2, poorly expressed in normal tissues, is up-regulated in almost all tumor cells. In particular, the amount of PLC-b2 correlates with morphological features of the different primary cancers, since weak expression is showed by tumors that retain a differentiated appearance, while a progressively higher amount of protein was revealed in poorly differentiated and undifferentiated tumors.
Prognosis By analyzing the relationship between PLC-b2 levels and biological and clinic-pathological factors, it has been found that the expression of PLC-b2 strikingly correlates with histological grade, mitotic index and size of primary tumors. No differences in PLC-b2 amount were found in breast tumors that express estrogens and/or progesterone receptors, while tumors negative for at least one of the two receptors showed elevated expression of this enzyme, as well as the majority of HER-2 positive tumours. These data suggest that high amounts of PLC-b2 might be associated to a worse response to therapy.
Survival analysis of cancer-related death indicates that patients whose primary tumors express low levels of PLC-b2 show an overall survival significantly higher in comparison to patients whose primary tumors express high levels of protein. In addition, elevated PLC-b2 expression of primary breast cancer is associated with a shorter relapse-free time interval.
  

Bibliography

Phospholipase C-beta 2 promotes mitosis and migration of human breast cancer-derived cells.
Bertagnolo V, Benedusi M, Brugnoli F, Lanuti P, Marchisio M, Querzoli P, Capitani S
Carcinogenesis. 2007 ; 28 (8) : 1638-1645.
PMID 17429106
 
PLC-beta2 activity on actin-associated polyphosphoinositides promotes migration of differentiating tumoral myeloid precursors.
Brugnoli F, Bavelloni A, Benedusi M, Capitani S, Bertagnolo V
Cellular signalling. 2007 ; 19 (8) : 1701-1712.
PMID 17478077
 
Taste bud contains both short-lived and long-lived cell populations.
Hamamichi R, Asano-Miyoshi M, Emori Y
Neuroscience. 2006 ; 141 (4) : 2129-2138.
PMID 16843606
 
Roles of PLC-beta2 and -beta3 and PI3Kgamma in chemoattractant-mediated signal transduction.
Li Z, Jiang H, Xie W, Zhang Z, Smrcka AV, Wu D
Science (New York, N.Y.). 2000 ; 287 (5455) : 1046-1049.
PMID 10669417
 
Cloning, sequencing, expression, and Gq-independent activation of phospholipase C-beta 2.
Park D, Jhon DY, Kriz R, Knopf J, Rhee SG
The Journal of biological chemistry. 1992 ; 267 (23) : 16048-16055.
PMID 1644792
 
Structure, function, and control of phosphoinositide-specific phospholipase C.
Rebecchi MJ, Pentyala SN
Physiological reviews. 2000 ; 80 (4) : 1291-1335.
PMID 11015615
 
Alternative splice variants of phospholipase C-beta2 are expressed in platelets: effect on Galphaq-dependent activation and localization.
Sun L, Mao G, Kunapuli SP, Dhanasekaran DN, Rao AK
Platelets. 2007 ; 18 (3) : 217-223.
PMID 17497434
 

Citation

This paper should be referenced as such :
Bertagnolo, Valeria ; Brugnoli, Federica ; Benedusi, Mascia ; Capitani, Silvano
PLCB2 (phospholipase C, beta 2)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(4):308-310.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PLCB2ID41743ch15q15.html


External links

Nomenclature
HGNC (Hugo)PLCB2   9055
Cards
AtlasPLCB2ID41743ch15q15
Entrez_Gene (NCBI)PLCB2  5330  phospholipase C beta 2
AliasesPLC-beta-2
GeneCards (Weizmann)PLCB2
Ensembl hg19 (Hinxton)ENSG00000137841 [Gene_View]  chr15:40580098-40600174 [Contig_View]  PLCB2 [Vega]
Ensembl hg38 (Hinxton)ENSG00000137841 [Gene_View]  chr15:40580098-40600174 [Contig_View]  PLCB2 [Vega]
ICGC DataPortalENSG00000137841
TCGA cBioPortalPLCB2
AceView (NCBI)PLCB2
Genatlas (Paris)PLCB2
WikiGenes5330
SOURCE (Princeton)PLCB2
Genetics Home Reference (NIH)PLCB2
Genomic and cartography
GoldenPath hg19 (UCSC)PLCB2  -     chr15:40580098-40600174 -  15q15.1   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)PLCB2  -     15q15.1   [Description]    (hg38-Dec_2013)
EnsemblPLCB2 - 15q15.1 [CytoView hg19]  PLCB2 - 15q15.1 [CytoView hg38]
Mapping of homologs : NCBIPLCB2 [Mapview hg19]  PLCB2 [Mapview hg38]
OMIM604114   
Gene and transcription
Genbank (Entrez)AB209583 AK130831 AK291657 BC000939 BC009009
RefSeq transcript (Entrez)NM_001284297 NM_001284298 NM_001284299 NM_004573
RefSeq genomic (Entrez)NC_000015 NC_018926 NT_010194 NW_004929398
Consensus coding sequences : CCDS (NCBI)PLCB2
Cluster EST : UnigeneHs.355888 [ NCBI ]
CGAP (NCI)Hs.355888
Alternative Splicing GalleryENSG00000137841
Gene ExpressionPLCB2 [ NCBI-GEO ]   PLCB2 [ EBI - ARRAY_EXPRESS ]   PLCB2 [ SEEK ]   PLCB2 [ MEM ]
Gene Expression Viewer (FireBrowse)PLCB2 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5330
GTEX Portal (Tissue expression)PLCB2
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ00722   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ00722  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ00722
Splice isoforms : SwissVarQ00722
Catalytic activity : Enzyme3.1.4.11 [ Enzyme-Expasy ]   3.1.4.113.1.4.11 [ IntEnz-EBI ]   3.1.4.11 [ BRENDA ]   3.1.4.11 [ KEGG ]   
PhosPhoSitePlusQ00722
Domaine pattern : Prosite (Expaxy)C2 (PS50004)    PIPLC_X_DOMAIN (PS50007)    PIPLC_Y_DOMAIN (PS50008)   
Domains : Interpro (EBI)C2_dom    EF-hand-dom_pair    PH_dom-like    PI-PLC_fam    PLC-beta    PLC-beta2    PLC-beta_C    PLC-like_Pdiesterase_TIM-brl    PLC_EF-hand-like    PLipase_C_PInositol-sp_X_dom    PLipase_C_Pinositol-sp_Y   
Domain families : Pfam (Sanger)C2 (PF00168)    EF-hand_like (PF09279)    PI-PLC-X (PF00388)    PI-PLC-Y (PF00387)    PLC-beta_C (PF08703)   
Domain families : Pfam (NCBI)pfam00168    pfam09279    pfam00388    pfam00387    pfam08703   
Domain families : Smart (EMBL)C2 (SM00239)  PLCXc (SM00148)  PLCYc (SM00149)  
Conserved Domain (NCBI)PLCB2
DMDM Disease mutations5330
Blocks (Seattle)PLCB2
PDB (SRS)2FJU    2ZKM   
PDB (PDBSum)2FJU    2ZKM   
PDB (IMB)2FJU    2ZKM   
PDB (RSDB)2FJU    2ZKM   
Structural Biology KnowledgeBase2FJU    2ZKM   
SCOP (Structural Classification of Proteins)2FJU    2ZKM   
CATH (Classification of proteins structures)2FJU    2ZKM   
SuperfamilyQ00722
Human Protein AtlasENSG00000137841
Peptide AtlasQ00722
HPRD04985
IPIIPI00784327   IPI00914935   IPI00744517   IPI01013842   
Protein Interaction databases
DIP (DOE-UCLA)Q00722
IntAct (EBI)Q00722
FunCoupENSG00000137841
BioGRIDPLCB2
STRING (EMBL)PLCB2
ZODIACPLCB2
Ontologies - Pathways
QuickGOQ00722
Ontology : AmiGOphosphatidylinositol phospholipase C activity  phosphatidylinositol phospholipase C activity  phospholipase C activity  signal transducer activity  calcium ion binding  cytosol  phospholipid metabolic process  activation of phospholipase C activity  Wnt signaling pathway, calcium modulating pathway  lipid catabolic process  intracellular signal transduction  inositol phosphate metabolic process  sensory perception of bitter taste  
Ontology : EGO-EBIphosphatidylinositol phospholipase C activity  phosphatidylinositol phospholipase C activity  phospholipase C activity  signal transducer activity  calcium ion binding  cytosol  phospholipid metabolic process  activation of phospholipase C activity  Wnt signaling pathway, calcium modulating pathway  lipid catabolic process  intracellular signal transduction  inositol phosphate metabolic process  sensory perception of bitter taste  
Pathways : KEGGInositol phosphate metabolism    Rap1 signaling pathway    Calcium signaling pathway    Chemokine signaling pathway    Phosphatidylinositol signaling system    Adrenergic signaling in cardiomyocytes    Vascular smooth muscle contraction    Wnt signaling pathway    Gap junction    Circadian entrainment    Long-term potentiation    Retrograde endocannabinoid signaling    Glutamatergic synapse    Cholinergic synapse    Serotonergic synapse    Dopaminergic synapse    Long-term depression    Taste transduction    Insulin secretion    GnRH signaling pathway    Estrogen signaling pathway    Melanogenesis    Thyroid hormone synthesis    Thyroid hormone signaling pathway    Endocrine and other factor-regulated calcium reabsorption    Salivary secretion    Gastric acid secretion    Pancreatic secretion    Carbohydrate digestion and absorption    Alzheimer's disease    Huntington's disease    Chagas disease (American trypanosomiasis)    African trypanosomiasis    Amoebiasis   
REACTOMEQ00722 [protein]
REACTOME Pathways112043 [pathway]   1855204 [pathway]   399997 [pathway]   4086398 [pathway]   416476 [pathway]   418217 [pathway]   434316 [pathway]   500657 [pathway]   
NDEx NetworkPLCB2
Atlas of Cancer Signalling NetworkPLCB2
Wikipedia pathwaysPLCB2
Orthology - Evolution
OrthoDB5330
GeneTree (enSembl)ENSG00000137841
Phylogenetic Trees/Animal Genes : TreeFamPLCB2
HOVERGENQ00722
HOGENOMQ00722
Homologs : HomoloGenePLCB2
Homology/Alignments : Family Browser (UCSC)PLCB2
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPLCB2 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PLCB2
dbVarPLCB2
ClinVarPLCB2
1000_GenomesPLCB2 
Exome Variant ServerPLCB2
ExAC (Exome Aggregation Consortium)PLCB2 (select the gene name)
Genetic variants : HAPMAP5330
Genomic Variants (DGV)PLCB2 [DGVbeta]
DECIPHER (Syndromes)15:40580098-40600174  ENSG00000137841
CONAN: Copy Number AnalysisPLCB2 
Mutations
ICGC Data PortalPLCB2 
TCGA Data PortalPLCB2 
Broad Tumor PortalPLCB2
OASIS PortalPLCB2 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPLCB2  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPLCB2
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch PLCB2
DgiDB (Drug Gene Interaction Database)PLCB2
DoCM (Curated mutations)PLCB2 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PLCB2 (select a term)
intoGenPLCB2
NCG5 (London)PLCB2
Cancer3DPLCB2(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM604114   
Orphanet
MedgenPLCB2
Genetic Testing Registry PLCB2
NextProtQ00722 [Medical]
TSGene5330
GENETestsPLCB2
Huge Navigator PLCB2 [HugePedia]
snp3D : Map Gene to Disease5330
BioCentury BCIQPLCB2
ClinGenPLCB2
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5330
Chemical/Pharm GKB GenePA33385
Clinical trialPLCB2
Miscellaneous
canSAR (ICR)PLCB2 (select the gene name)
Probes
Litterature
PubMed62 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePLCB2
EVEXPLCB2
GoPubMedPLCB2
iHOPPLCB2
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Mar 14 13:47:09 CET 2017

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