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| | 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 |
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| 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. |
| Note | |
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| Entity | 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. |
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| Cloning and characterization of the human phosphoinositide-specific phospholipase C-beta 1 (PLC beta 1). |
| Caricasole A, Sala C, Roncarati R, Formenti E, Terstappen GC |
| Biochimica et biophysica acta. 2000 ; 1517 (1) : 63-72. |
| PMID 11118617 |
| |
| Inositide-specific phospholipase c beta1 gene deletion in the progression of myelodysplastic syndrome to acute myeloid leukemia. |
| Lo Vasco VR, Calabrese G, Manzoli L, Palka G, Spadano A, Morizio E, Guanciali-Franchi P, Fantasia D, Cocco L |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 ; 18 (6) : 1122-1126. |
| PMID 15085153 |
| |
| Prediction 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, Ishikawa K, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O |
| DNA research : an international journal for rapid publication of reports on genes and genomes. 1998 ; 5 (1) : 31-39. |
| PMID 9628581 |
| |
| Molecular characterization of the human PLC beta1 gene. |
| Peruzzi D, Aluigi M, Manzoli L, Billi AM, Di Giorgio FP, Morleo M, Martelli AM, Cocco L |
| Biochimica et biophysica acta. 2002 ; 1584 (1) : 46-54. |
| PMID 12213492 |
| |
| Identification and chromosomal localisation by fluorescence in situ hybridisation of human gene of phosphoinositide-specific phospholipase C beta(1). |
| Peruzzi D, Calabrese G, Faenza I, Manzoli L, Matteucci A, Gianfrancesco F, Billi AM, Stuppia L, Palka G, Cocco L |
| Biochimica et biophysica acta. 2000 ; 1484 (2-3) : 175-182. |
| PMID 10760467 |
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| Nomenclature |
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| HGNC (Hugo) | PLCB1 15917 |
| Cards |
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| Atlas | PLCB1ID41742ch20p12 |
| Entrez_Gene (NCBI) | PLCB1 23236 phospholipase C beta 1 |
| Aliases | EIEE12; PI-PLC; PLC-154; PLC-I; |
| PLC-beta-1; PLC154; PLCB1A; PLCB1B |
| GeneCards (Weizmann) | PLCB1 |
| Ensembl hg19 (Hinxton) | ENSG00000182621 [Gene_View] |
| Ensembl hg38 (Hinxton) | ENSG00000182621 [Gene_View] ENSG00000182621 [Sequence] chr20:8132265-8884900 [Contig_View] PLCB1 [Vega] |
| ICGC DataPortal | ENSG00000182621 |
| TCGA cBioPortal | PLCB1 |
| AceView (NCBI) | PLCB1 |
| Genatlas (Paris) | PLCB1 |
| WikiGenes | 23236 |
| SOURCE (Princeton) | PLCB1 |
| Genetics Home Reference (NIH) | PLCB1 |
| Genomic and cartography |
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| GoldenPath hg38 (UCSC) | PLCB1 - chr20:8132265-8884900 + 20p12.3 [Description] (hg38-Dec_2013) |
| GoldenPath hg19 (UCSC) | PLCB1 - 20p12.3 [Description] (hg19-Feb_2009) |
| GoldenPath | PLCB1 - 20p12.3 [CytoView hg19] PLCB1 - 20p12.3 [CytoView hg38] |
| ImmunoBase | ENSG00000182621 |
| Mapping of homologs : NCBI | PLCB1 [Mapview hg19] PLCB1 [Mapview hg38] |
| OMIM | 607120 613722 |
| Gene and transcription |
|---|
| Genbank (Entrez) | AB011153 AJ278313 AJ278314 AK023689 AK127693 |
| RefSeq transcript (Entrez) | NM_015192 NM_182734 |
| RefSeq genomic (Entrez) | |
| Consensus coding sequences : CCDS (NCBI) | PLCB1 |
| Cluster EST : Unigene | Hs.431173 [ NCBI ] |
| CGAP (NCI) | Hs.431173 |
| Alternative Splicing Gallery | ENSG00000182621 |
| Gene Expression | PLCB1 [ NCBI-GEO ] PLCB1 [ EBI - ARRAY_EXPRESS ]
PLCB1 [ SEEK ] PLCB1 [ MEM ] |
| Gene Expression Viewer (FireBrowse) | PLCB1 [ Firebrowse - Broad ] |
| SOURCE (Princeton) | Expression in : [Datasets] [Normal Tissue Atlas] [carcinoma Classsification] [NCI60] |
| Genevestigator | Expression in : [tissues] [cell-lines] [cancer] [perturbations] |
| BioGPS (Tissue expression) | 23236 |
| GTEX Portal (Tissue expression) | PLCB1 |
| Human Protein Atlas | ENSG00000182621-PLCB1 [pathology] [cell] [tissue] |
| Protein : pattern, domain, 3D structure |
|---|
| UniProt/SwissProt | Q9NQ66 [function] [subcellular_location] [family_and_domains] [pathology_and_biotech] [ptm_processing] [expression] [interaction] |
| NextProt | Q9NQ66 [Sequence] [Exons] [Medical] [Publications] |
| With graphics : InterPro | Q9NQ66 |
| Splice isoforms : SwissVar | Q9NQ66 |
| Catalytic activity : Enzyme | 3.1.4.11 [ Enzyme-Expasy ] 3.1.4.113.1.4.11 [ IntEnz-EBI ] 3.1.4.11 [ BRENDA ] 3.1.4.11 [ KEGG ] |
| PhosPhoSitePlus | Q9NQ66 |
| Domaine pattern : Prosite (Expaxy) | C2 (PS50004) PIPLC_X_DOMAIN (PS50007) PIPLC_Y_DOMAIN (PS50008) |
| Domains : Interpro (EBI) | C2_dom C2_domain_sf EF-hand-dom_pair PI-PLC_fam PLC-beta PLC-beta1 PLC-beta_C PLC-beta_CS PLC-beta_PH PLC-like_Pdiesterase_TIM-brl PLC_EF-hand-like PLipase_C_PInositol-sp_X_dom PLipase_C_Pinositol-sp_Y |
| Domain families : Pfam (Sanger) | DUF1154 (PF06631) EF-hand_like (PF09279) PI-PLC-X (PF00388) PI-PLC-Y (PF00387) PLC-beta_C (PF08703) |
| Domain families : Pfam (NCBI) | pfam06631 pfam09279 pfam00388 pfam00387 pfam08703 |
| Domain families : Smart (EMBL) | C2 (SM00239) PLCXc (SM00148) PLCYc (SM00149) |
| Conserved Domain (NCBI) | PLCB1 |
| DMDM Disease mutations | 23236 |
| Blocks (Seattle) | PLCB1 |
| Superfamily | Q9NQ66 |
| Human Protein Atlas [tissue] | ENSG00000182621-PLCB1 [tissue] |
| Peptide Atlas | Q9NQ66 |
| HPRD | 06177 |
| IPI | IPI00219563 IPI00395561 IPI00976468 IPI00216924 IPI01013139 IPI00216920 IPI00641825 |
| Protein Interaction databases |
|---|
| DIP (DOE-UCLA) | Q9NQ66 |
| IntAct (EBI) | Q9NQ66 |
| FunCoup | ENSG00000182621 |
| BioGRID | PLCB1 |
| STRING (EMBL) | PLCB1 |
| ZODIAC | PLCB1 |
| Ontologies - Pathways |
|---|
| QuickGO | Q9NQ66 |
| Ontology : AmiGO | G2/M transition of mitotic cell cycle nuclear chromatin phosphatidylinositol phospholipase C activity phosphatidylinositol phospholipase C activity phosphatidylinositol phospholipase C activity phospholipase C activity GTPase activator activity calcium ion binding protein binding protein binding calmodulin binding calmodulin binding lamin binding phosphatidylinositol-4,5-bisphosphate binding nucleus nucleus cytoplasm cytoplasm cytosol signal transduction G protein-coupled receptor signaling pathway G protein-coupled acetylcholine receptor signaling pathway glutamate receptor signaling pathway Wnt signaling pathway, calcium modulating pathway memory memory regulation of G protein-coupled receptor signaling pathway lipid catabolic process nuclear speck nuclear speck enzyme binding cerebral cortex development nuclear membrane positive regulation of interleukin-12 production inositol trisphosphate biosynthetic process protein-containing complex interleukin-12-mediated signaling pathway interleukin-15-mediated signaling pathway positive regulation of embryonic development protein homodimerization activity positive regulation of GTPase activity inositol phosphate metabolic process fat cell differentiation positive regulation of myoblast differentiation negative regulation of transcription, DNA-templated positive regulation of transcription, DNA-templated positive regulation of JNK cascade phosphatidylinositol metabolic process insulin-like growth factor receptor signaling pathway phosphatidylinositol-mediated signaling positive regulation of developmental growth release of sequestered calcium ion into cytosol activation of meiosis involved in egg activation extracellular exosome interleukin-1-mediated signaling pathway regulation of fertilization postsynapse glutamatergic synapse GABA-ergic synapse postsynaptic modulation of chemical synaptic transmission regulation of retrograde trans-synaptic signaling by endocanabinoid positive regulation of G1/S transition of mitotic cell cycle positive regulation of acrosome reaction negative regulation of monocyte extravasation positive regulation of CD24 biosynthetic process |
| Ontology : EGO-EBI | G2/M transition of mitotic cell cycle nuclear chromatin phosphatidylinositol phospholipase C activity phosphatidylinositol phospholipase C activity phosphatidylinositol phospholipase C activity phospholipase C activity GTPase activator activity calcium ion binding protein binding protein binding calmodulin binding calmodulin binding lamin binding phosphatidylinositol-4,5-bisphosphate binding nucleus nucleus cytoplasm cytoplasm cytosol signal transduction G protein-coupled receptor signaling pathway G protein-coupled acetylcholine receptor signaling pathway glutamate receptor signaling pathway Wnt signaling pathway, calcium modulating pathway memory memory regulation of G protein-coupled receptor signaling pathway lipid catabolic process nuclear speck nuclear speck enzyme binding cerebral cortex development nuclear membrane positive regulation of interleukin-12 production inositol trisphosphate biosynthetic process protein-containing complex interleukin-12-mediated signaling pathway interleukin-15-mediated signaling pathway positive regulation of embryonic development protein homodimerization activity positive regulation of GTPase activity inositol phosphate metabolic process fat cell differentiation positive regulation of myoblast differentiation negative regulation of transcription, DNA-templated positive regulation of transcription, DNA-templated positive regulation of JNK cascade phosphatidylinositol metabolic process insulin-like growth factor receptor signaling pathway phosphatidylinositol-mediated signaling positive regulation of developmental growth release of sequestered calcium ion into cytosol activation of meiosis involved in egg activation extracellular exosome interleukin-1-mediated signaling pathway regulation of fertilization postsynapse glutamatergic synapse GABA-ergic synapse postsynaptic modulation of chemical synaptic transmission regulation of retrograde trans-synaptic signaling by endocanabinoid positive regulation of G1/S transition of mitotic cell cycle positive regulation of acrosome reaction negative regulation of monocyte extravasation positive regulation of CD24 biosynthetic process |
| Pathways : KEGG | Inositol 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 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 Alzheimer's disease Huntington's disease Chagas disease (American trypanosomiasis) African trypanosomiasis Amoebiasis |
| REACTOME | Q9NQ66 [protein] |
| REACTOME Pathways | R-HSA-500657 [pathway] |
| NDEx Network | PLCB1 |
| Atlas of Cancer Signalling Network | PLCB1 |
| Wikipedia pathways | PLCB1 |
| Orthology - Evolution |
|---|
| OrthoDB | 23236 |
| GeneTree (enSembl) | ENSG00000182621 |
| Phylogenetic Trees/Animal Genes : TreeFam | PLCB1 |
| HOGENOM | Q9NQ66 |
| Homologs : HomoloGene | PLCB1 |
| Homology/Alignments : Family Browser (UCSC) | PLCB1 |
| Gene fusions - Rearrangements |
|---|
| Fusion : Mitelman | PLCB1/GPCPD1 [20p12.3/20p12.3] |
| Fusion Portal | PLCB1 20p12.3 GPCPD1 20p12.3 BRCA |
| Fusion : FusionGDB | 18817 21566 27476 27477 27478 27479 27480 27481 27482 27483 27484 27485 27486 27487 27488 |
| 33781 43866 5324 |
| Fusion : Fusion_Hub | AC011997.1--PLCB1 C20ORF94--PLCB1 CALR3--PLCB1 KIF16B--PLCB1 PARD3B--PLCB1 PLCB1--ACTR2 PLCB1--CYYR1 PLCB1--DSTN PLCB1--FAM161B PLCB1--GMPR PLCB1--GPCPD1 PLCB1--GTF2A1 PLCB1--HADH PLCB1--KMT2C PLCB1--MACROD2 |
| PLCB1--MCM8 PLCB1--MOSPD2 PLCB1--NFIB PLCB1--NLGN2 PLCB1--PLCB1 PLCB1--PQLC1 PLCB1--RBL1 PLCB1--ROR1 PLCB1--SNX5 PLCB1--STATH PLCB1--USP25 PLCB1--WTIP PLCB4--PLCB1 RP4-594A5.1--PLCB1 RPS6KA2--PLCB1 |
| SHH--PLCB1 SPOCK1--PLCB1 TASP1--PLCB1 ZSWIM4--PLCB1 |
| Fusion : Quiver | PLCB1 |
| Polymorphisms : SNP and Copy number variants |
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| NCBI Variation Viewer | PLCB1 [hg38] |
| dbSNP Single Nucleotide Polymorphism (NCBI) | PLCB1 |
| dbVar | PLCB1 |
| ClinVar | PLCB1 |
| 1000_Genomes | PLCB1 |
| Exome Variant Server | PLCB1 |
| ExAC (Exome Aggregation Consortium) | ENSG00000182621 |
| GNOMAD Browser | ENSG00000182621 |
| Varsome Browser | PLCB1 |
| Genetic variants : HAPMAP | 23236 |
| Genomic Variants (DGV) | PLCB1 [DGVbeta] |
| DECIPHER | PLCB1 [patients] [syndromes] [variants] [genes] |
| CONAN: Copy Number Analysis | PLCB1 |
| Mutations |
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| ICGC Data Portal | PLCB1 |
| TCGA Data Portal | PLCB1 |
| Broad Tumor Portal | PLCB1 |
| OASIS Portal | PLCB1 [ Somatic mutations - Copy number] |
| Somatic Mutations in Cancer : COSMIC | PLCB1 [overview] [genome browser] [tissue] [distribution] |
| Somatic Mutations in Cancer : COSMIC3D | PLCB1 |
| Mutations and Diseases : HGMD | PLCB1 |
| intOGen Portal | PLCB1 |
| 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 |
| BioMuta | search PLCB1 |
| DgiDB (Drug Gene Interaction Database) | PLCB1 |
| DoCM (Curated mutations) | PLCB1 (select the gene name) |
| CIViC (Clinical Interpretations of Variants in Cancer) | PLCB1 (select a term) |
| intoGen | PLCB1 |
| NCG5 (London) | PLCB1 |
| Cancer3D | PLCB1(select the gene name) |
| Impact of mutations | [PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser] |
| Diseases |
|---|
| OMIM | 607120 613722 |
| Orphanet | 894 20841 |
| DisGeNET | PLCB1 |
| Medgen | PLCB1 |
| Genetic Testing Registry | PLCB1
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| NextProt | Q9NQ66 [Medical] |
| TSGene | 23236 |
| GENETests | PLCB1 |
| Target Validation | PLCB1 |
| Huge Navigator |
PLCB1 [HugePedia] |
| snp3D : Map Gene to Disease | 23236 |
| BioCentury BCIQ | PLCB1 |
| ClinGen | PLCB1 |
| Clinical trials, drugs, therapy |
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| Chemical/Protein Interactions : CTD | 23236 |
| Chemical/Pharm GKB Gene | PA33384 |
| Clinical trial | PLCB1 |
| Miscellaneous |
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| canSAR (ICR) | PLCB1 (select the gene name) |
| DataMed Index | PLCB1 |
| Probes |
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| Litterature |
|---|
| PubMed | 118 Pubmed reference(s) in Entrez |
| GeneRIFs | Gene References Into Functions (Entrez) |
| CoreMine | PLCB1 |
| EVEX | PLCB1 |
| GoPubMed | PLCB1 |
| iHOP | PLCB1 |
