PLCB1 (phospholipase C, beta 1 (phosphoinositide-specific))

2005-12-01   Matilde Y. Follo , Vincenza Rita Lo Vasco , Giovanni Martinelli , Giandomenico Palka , Lucio Cocco 

Cellular Signalling Laboratory, Department of Anatomical Sciences, University of Bologna, Via Irnerio, 48 I-40126 Bologna, Italy

Identity

HGNC
LOCATION
20p12.3
LOCUSID
ALIAS
DEE12,EIEE12,PI-PLC,PLC-154,PLC-I,PLC-beta-1,PLC154,PLCB1A,PLCB1B
FUSION GENES

DNA/RNA

Atlas Image
Panel A: structure of PLCB1a and PLCB1b human cDNAs. Upper, PLCB1a; middle, PLCB1b; lower, PLCB1b with different 3- UTR.
Panel B: structure of the splicing variant lacking exons 4 9.

Description

33 small exons and introns spanning about 250 kbp.

Transcription

By alternative splicing at the 3-prime end the gene produces 2 variants: PLCB1a (1.216 aminoacids, 6705 bp mRNA) and PLCB1b (1.173 aminoacids, 6823 bp mRNA). An additional exon at the 5-prime end was identified, which gives a smaller isoform, and another PLCB1b isoform, which is produced by using an alternative 3-UTR.

Pseudogene

No known pseudogenes.

Proteins

Atlas Image
PH = Pleckstrin Homology Domain;
EF = EF-Hand Domain;
X and Y = Catalytic Domain;
C2 = Calcium-binding Domain;
NLS = Nuclear Localisation Signal (common to both isoforms);
NES = Nuclear Export Signal

Description

PLC beta1 contains a PH-domain at the NH2-terminus, which is present in many signalling proteins, that binds to polyphosphoinositides and to inositol phosphates. Two additional modules are also present: an EF-hand domain, located between the PH and X domains, and a C2 domain, which is sometimes represented as part of an extended Y domain.

Expression

PLC beta1 is ubiquitous at different levels of expression: higher signal intensities were observed in some CNS areas, such as the amygdala, caudate nucleus, and hippocampus, and PLCB1a appeared to be expressed at slightly higher levels in most tissues. PCR analysis of embryonic and adult rat tissues indicated restricted expression of both isoforms to embryonic and adult brain, with lower levels of expression in lung and testis.

Localisation

By using confocal immunolocalization of endogenous or transfected epitope-tagged PLC beta1, for subcellular localisation it has been shown that PLCB1a is within the cytoplasm and at the plasma membrane but localises also in the nucleus. PLCB1b is almost completely nuclear.

Function

Phospholipase C-beta (PLC beta) catalyzes the generation of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) from phosphatidylinositol 4,5-bisphosphate (IP2), a key step in the intracellular transduction of many extracellular signals. PLCB1 is one of several mammalian PLCB isoforms which differ in their function and expression patterns in vivo. PLC beta1 protein is present in the nucleus and is involved in the control of the cell cycle.

Homology

96% with bovine PLC beta1; The amino acid sequences of PLC isozymes are relatively not conserved except for two regions, known as the X and Y domains that form the catalytic core which is 60% homologous among all mammalian isozymes.

Mutations

Note

Until now only deletions have been relevated by using FISH analysis.

Implicated in

Entity name
Myelodysplastic Syndrome
Note
Transition from Myelodysplastic Syndrome to Acute Myeloid Leukemia
Disease
In patients with normal GTG banding karyotype affected by Myelodysplastic Syndrome (MDS) (9 patients) and with Acute Myeloid Leukemia (AML) (6 patients), a monoallelic loss of the PLCB1 gene was detected. All the MDS patients, even though with normal karyotype, belonged to the high-risk group as scored by IPSS and FAB classifications. Out of 9 MDS patients with normal karyotype 4 had monoallelic deletion of the PLC beta1 gene, and all 4 died within 1 to 6 months after developing AML, compared to survival of over 30 months in the 5 MDS patients without the deletion. Two of 6 AML patients with normal karyotype had a monoallelic deletion of the PLCB1 gene; these 2 patients had a reduced survival (1 to 12 months) compared to the AML patients without the deletion (20 to 29 months). These evidences suggest a possible role for PLC beta1 in the progression of MDS to AML in high-risk patients.
Prognosis
Worse in patients having the deletion of the PLC beta1 gene.
Cytogenetics
FISH performed using a 115.000 bp probe (PAC clone 881E24) spanning from exon 19 to 32 of the gene.
FISH analysis, using KIAA 0581, i.e., part of human PLC beta1 cDNA, of human metaphases showing signals on both chromosomes 20 at band p12. (a) Q-Like banding; (b) fluorescence signals detected by FISH; (c) a partial karyotype along with a human chromosome 20 ideogram. (d) A schematic representation of the 1.9 cM interval, flanked by microsatellite markers D20S917 and D20S977, to which human PLC beta1 maps.
Oncogenesis
PLC beta1 is a key player in the control of cell cycle, namely the physiological progression through the G1 phase, in that the nuclear PLC beta1 evoked signalling targets the cyclin D3/cdk4 complex which phosphorylates retinoblastoma protein (pRb) that in turn activates the transcription factor E2F-1. Possibly alterations of this pathway could be involved in malignancies.

Bibliography

Pubmed IDLast YearTitleAuthors
111186172000Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC beta 1).Caricasole A et al
150851532004Inositide-specific phospholipase c beta1 gene deletion in the progression of myelodysplastic syndrome to acute myeloid leukemia.Lo Vasco VR et al
96285811998Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro.Nagase T et al
122134922002Molecular characterization of the human PLC beta1 gene.Peruzzi D et al
107604672000Identification and chromosomal localisation by fluorescence in situ hybridisation of human gene of phosphoinositide-specific phospholipase C beta(1).Peruzzi D et al

Other Information

Locus ID:

NCBI: 23236
MIM: 607120
HGNC: 15917
Ensembl: ENSG00000182621

Variants:

dbSNP: 23236
ClinVar: 23236
TCGA: ENSG00000182621
COSMIC: PLCB1

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000182621ENST00000338037Q9NQ66
ENSG00000182621ENST00000378637Q9NQ66
ENSG00000182621ENST00000378641Q9NQ66
ENSG00000182621ENST00000404098B1AK73
ENSG00000182621ENST00000437439Q8IV91
ENSG00000182621ENST00000439627Q8IV92
ENSG00000182621ENST00000475958A0A0D9SFA6
ENSG00000182621ENST00000487210H0YCJ2
ENSG00000182621ENST00000612075A0A087WW73
ENSG00000182621ENST00000617005A0A087WT80
ENSG00000182621ENST00000625874A0A0D9SF51
ENSG00000182621ENST00000626966A0A0D9SG17
ENSG00000182621ENST00000628239A0A0D9SGI7
ENSG00000182621ENST00000629992A0A0D9SFE7
ENSG00000182621ENST00000630495A0A0D9SFJ4
ENSG00000182621ENST00000635929A0A1B0GW62
ENSG00000182621ENST00000636319A0A1B0GVC1
ENSG00000182621ENST00000637204A0A1B0GW45
ENSG00000182621ENST00000637422A0A1B0GTC7
ENSG00000182621ENST00000637919A0A1B0GWB6
ENSG00000182621ENST00000637935A0A1B0GVT0

Expression (GTEx)

0
5
10
15
20

Pathways

PathwaySourceExternal ID
Inositol phosphate metabolismKEGGko00562
Calcium signaling pathwayKEGGko04020
Phosphatidylinositol signaling systemKEGGko04070
Wnt signaling pathwayKEGGko04310
Gap junctionKEGGko04540
Long-term potentiationKEGGko04720
Long-term depressionKEGGko04730
GnRH signaling pathwayKEGGko04912
MelanogenesisKEGGko04916
Alzheimer's diseaseKEGGko05010
Huntington's diseaseKEGGko05016
Inositol phosphate metabolismKEGGhsa00562
Calcium signaling pathwayKEGGhsa04020
Phosphatidylinositol signaling systemKEGGhsa04070
Wnt signaling pathwayKEGGhsa04310
Gap junctionKEGGhsa04540
Long-term potentiationKEGGhsa04720
Long-term depressionKEGGhsa04730
GnRH signaling pathwayKEGGhsa04912
MelanogenesisKEGGhsa04916
Alzheimer's diseaseKEGGhsa05010
Huntington's diseaseKEGGhsa05016
Pathways in cancerKEGGhsa05200
Vascular smooth muscle contractionKEGGhsa04270
Chemokine signaling pathwayKEGGko04062
Vascular smooth muscle contractionKEGGko04270
Chemokine signaling pathwayKEGGhsa04062
NOD-like receptor signaling pathwayKEGGko04621
NOD-like receptor signaling pathwayKEGGhsa04621
Metabolic pathwaysKEGGhsa01100
Chagas disease (American trypanosomiasis)KEGGko05142
Chagas disease (American trypanosomiasis)KEGGhsa05142
Salivary secretionKEGGko04970
Salivary secretionKEGGhsa04970
Gastric acid secretionKEGGko04971
Gastric acid secretionKEGGhsa04971
AmoebiasisKEGGko05146
AmoebiasisKEGGhsa05146
Pancreatic secretionKEGGko04972
Pancreatic secretionKEGGhsa04972
African trypanosomiasisKEGGko05143
African trypanosomiasisKEGGhsa05143
Endocrine and other factor-regulated calcium reabsorptionKEGGko04961
Endocrine and other factor-regulated calcium reabsorptionKEGGhsa04961
Glutamatergic synapseKEGGko04724
Glutamatergic synapseKEGGhsa04724
Cholinergic synapseKEGGhsa04725
Inositol phosphate metabolism, PI=> PIP2 => Ins(1,4,5)P3 => Ins(1,3,4,5)P4KEGGhsa_M00130
Inositol phosphate metabolism, PI=> PIP2 => Ins(1,4,5)P3 => Ins(1,3,4,5)P4KEGGM00130
Dopaminergic synapseKEGGko04728
Dopaminergic synapseKEGGhsa04728
Serotonergic synapseKEGGhsa04726
Retrograde endocannabinoid signalingKEGGhsa04723
Retrograde endocannabinoid signalingKEGGko04723
Circadian entrainmentKEGGhsa04713
Circadian entrainmentKEGGko04713
Insulin secretionKEGGhsa04911
Estrogen signaling pathwayKEGGhsa04915
Estrogen signaling pathwayKEGGko04915
Thyroid hormone synthesisKEGGhsa04918
Thyroid hormone synthesisKEGGko04918
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
Adrenergic signaling in cardiomyocytesKEGGhsa04261
Adrenergic signaling in cardiomyocytesKEGGko04261
Thyroid hormone signaling pathwayKEGGhsa04919
Inflammatory mediator regulation of TRP channelsKEGGhsa04750
Inflammatory mediator regulation of TRP channelsKEGGko04750
Platelet activationKEGGhsa04611
Oxytocin signaling pathwayKEGGhsa04921
Oxytocin signaling pathwayKEGGko04921
cGMP-PKG signaling pathwayKEGGhsa04022
cGMP-PKG signaling pathwayKEGGko04022
Sphingolipid signaling pathwayKEGGhsa04071
Glucagon signaling pathwayKEGGhsa04922
Sphingolipid signaling pathwayKEGGko04071
Glucagon signaling pathwayKEGGko04922
Renin secretionKEGGhsa04924
Renin secretionKEGGko04924
Neuronal SystemREACTOMER-HSA-112316
Transmission across Chemical SynapsesREACTOMER-HSA-112315
Neurotransmitter Receptor Binding And Downstream Transmission In The Postsynaptic CellREACTOMER-HSA-112314
Activation of Kainate Receptors upon glutamate bindingREACTOMER-HSA-451326
Presynaptic function of Kainate receptorsREACTOMER-HSA-500657
Signal TransductionREACTOMER-HSA-162582
Signaling by GPCRREACTOMER-HSA-372790
GPCR downstream signalingREACTOMER-HSA-388396
G alpha (q) signalling eventsREACTOMER-HSA-416476
G-protein beta:gamma signallingREACTOMER-HSA-397795
G beta:gamma signalling through PLC betaREACTOMER-HSA-418217
Opioid SignallingREACTOMER-HSA-111885
G-protein mediated eventsREACTOMER-HSA-112040
PLC beta mediated eventsREACTOMER-HSA-112043
Gastrin-CREB signalling pathway via PKC and MAPKREACTOMER-HSA-881907
Signaling by WntREACTOMER-HSA-195721
Beta-catenin independent WNT signalingREACTOMER-HSA-3858494
Ca2+ pathwayREACTOMER-HSA-4086398
MetabolismREACTOMER-HSA-1430728
Inositol phosphate metabolismREACTOMER-HSA-1483249
Synthesis of IP3 and IP4 in the cytosolREACTOMER-HSA-1855204
Integration of energy metabolismREACTOMER-HSA-163685
Regulation of insulin secretionREACTOMER-HSA-422356
Acetylcholine regulates insulin secretionREACTOMER-HSA-399997
Free fatty acids regulate insulin secretionREACTOMER-HSA-400451
Fatty Acids bound to GPR40 (FFAR1) regulate insulin secretionREACTOMER-HSA-434316
Aldosterone synthesis and secretionKEGGhsa04925
Aldosterone synthesis and secretionKEGGko04925
Phospholipase D signaling pathwayKEGGko04072
Phospholipase D signaling pathwayKEGGhsa04072
AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
Apelin signaling pathwayKEGGhsa04371

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA134864200GNB4GenePathwayassociated
PA164713257Selective serotonin reuptake inhibitorsChemicalClinicalAnnotationassociatedPD25649181
PA174GNAQGenePathwayassociated19741567, 20938371
PA176GNB3GenePathwayassociated20938371
PA179GP1BBGenePathwayassociated20938371
PA204ITGA2GenePathwayassociated20938371
PA205ITGB3GenePathwayassociated20938371
PA26097CASRGenePathwayassociated
PA26212CD36GenePathwayassociated20938371
PA270PLA2G2AGenePathwayassociated20938371
PA271PLA2G4AGenePathwayassociated20938371
PA28764GNA11GenePathwayassociated20938371
PA28765GNA12GenePathwayassociated20938371
PA28766GNA13GenePathwayassociated20938371
PA28768GNA15GenePathwayassociated20938371
PA28776GNB1GenePathwayassociated
PA28777GNB1LGenePathwayassociated
PA28778GNB2GenePathwayassociated
PA28784GNG2GenePathwayassociated
PA28785GNG3GenePathwayassociated
PA28786GNG4GenePathwayassociated
PA28787GNG5GenePathwayassociated
PA28789GNG7GenePathwayassociated
PA28823GP5GenePathwayassociated20938371
PA28824GP6GenePathwayassociated20938371
PA28825GP9GenePathwayassociated20938371
PA29938ITGA2BGenePathwayassociated20938371
PA33364PLA2G4BGenePathwayassociated20938371
PA33759PRKCAGenePathwayassociated
PA33761PRKCBGenePathwayassociated
PA33766PRKCGGenePathwayassociated
PA33767PRKCHGenePathwayassociated
PA33768PRKCIGenePathwayassociated
PA33771PRKD1GenePathwayassociated
PA33775PRKCZGenePathwayassociated
PA39ADRB2GenePathwayassociated
PA447278DepressionDiseaseClinicalAnnotationassociatedPD25649181

References

Pubmed IDYearTitleCitations
192400612009Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.75
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
168607582006Bacterial superantigens bypass Lck-dependent T cell receptor signaling by activating a Galpha11-dependent, PLC-beta-mediated pathway.39
182039562008Phosphatidylcholine-specific phospholipase C activation is required for CCR5-dependent, NF-kB-driven CCL2 secretion elicited in response to HIV-1 gp120 in human primary macrophages.28
266205502016PTPRN2 and PLCβ1 promote metastatic breast cancer cell migration through PI(4,5)P2-dependent actin remodeling.25
225077022012Deletion of PLCB1 gene in schizophrenia-affected patients.21
226907842012Homozygous PLCB1 deletion associated with malignant migrating partial seizures in infancy.20
210912632011Phospholipase C beta 1 expression in the dorsolateral prefrontal cortex from patients with schizophrenia at different stages of illness.16
228898342012Phospholipase Cβ1 is linked to RNA interference of specific genes through translin-associated factor X.15
230066642013PLCβ isoforms differ in their subcellular location and their CT-domain dependent interaction with Gαq.14

Citation

Matilde Y. Follo ; Vincenza Rita Lo Vasco ; Giovanni Martinelli ; Giandomenico Palka ; Lucio Cocco

PLCB1 (phospholipase C, beta 1 (phosphoinositide-specific))

Atlas Genet Cytogenet Oncol Haematol. 2005-12-01

Online version: http://atlasgeneticsoncology.org/gene/41742/plcb1