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PLCG1 (Phospholipase C, Gamma 1)

Written2014-02Rebeca Manso
Pathology Department, Fundacion Conchita Rabago, IIS Fundacion Jimenez Diaz, E-28040 Madrid, Spain

(Note : for Links provided by Atlas : click)

Identity

Alias_namesPLC1
phospholipase C, gamma 1 (formerly subtype 148)
phospholipase C, gamma 1
Alias_symbol (synonym)PLC148
PLC-II
PLCgamma1
NCKAP3
Other alias
HGNC (Hugo) PLCG1
LocusID (NCBI) 5335
Atlas_Id 44163
Location 20q12  [Link to chromosome band 20q12]
Location_base_pair Starts at 41137521 and ends at 41175717 bp from pter ( according to hg19-Feb_2009)  [Mapping PLCG1.png]
Local_order From the cytosol.
 
  Figure 1. Schematic diagram of PLCG1 location on chromosome 20. PLCG1 localizes to chromosome 20q12, which is represented graphically. PLCG1 gene spans 38.762 kb on the genomic DNA.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
ARID1B (6q25.3) / PLCG1 (20q12)MYH14 (19q13.33) / PLCG1 (20q12)PLCG1 (20q12) / BPIFB1 (20q11.21)
PLCG1 (20q12) / FRMD8 (11q13.1)PLCG1 (20q12) / TAF4 (20q13.33)PLCG1 (20q12) / TAT (16q22.2)
ZBTB22 (6p21.32) / PLCG1 (20q12)ZEB2 (2q22.3) / PLCG1 (20q12)

DNA/RNA

Description The PLCG1 gene spans 38.762 kb on the genomic DNA. The gene includes 32 exons.
Transcription There are two transcript variants: 5205 bp (isoform a) and 5202 bp (isoform b).

Protein

 
  Figure 2. Schematic representation of the domains of PLCG1. The protein contains eight domains, four of which are unique to PLCG family. The PLCG 'specific array' of domains, comprising a "split" PH domain flanking two tandem SH2 domains and one SH3 domain, is inserted between the two halves (X and Y) of the TIM-barrel catalytic domain. Several other domains including two PH domains, one C2 domain and one EF hand motifs. The numering of the amino acid residues is for human PLCG1 (Suh et al., 2008; Bunney and Katan, 2011).
Description The PLCG1 protein encodes two alternative isoforms: variant a (P19174-1)-1290 amino acids, 148.53 Da; variant b (P19174-2)-1291 amino acids, 148.66 Da.
Expression PLCG1 is expressed ubiquitously, especially in the brain, thymus, intestine and lungs. Additionally, PLCG1 is overexpressed in numerous cancer types such as human colorectal cancer (Noh et al., 1994), breast carcinoma (Arteaga et al., 1991), prostate carcinoma (Peak et al., 2008), familial adenomatous polyposis (Park et al., 1994) and human skins under hypeproliferative conditions (Nanney et al., 1992).
Localisation PLCG1 localizes predominantly in the plasmatic membrane, cytoplasm and nucleus.
Function PLCG1 is a protein involved in multiple cellular processes. A potent inhibitor of PLCG1 (U-73122) has been reported to inhibit PLCG1-dependent processes in cells (Smith et al., 1990; Thompson et al., 1991; Thomas et al., 2003; Li et al., 2005). The inhibition of PLCG1 may be an important mechanism for an antiproliferative effect on the human cancer cells.
Role in the production of the second messenger molecules: PLCG1 mediates the production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) from the hydrolysis of phosphatidynositol-4,5-bisphosphate (PIP2) (Williams et al., 1996). These second messengers are essential for T cell activation (Lin et al., 2001).
Role in cellular proliferation: PLCG1 is associated with tumor development, and it is overexpressed in some tumors (Shin et al., 2007). This overexpression stimulates MMP-3 expression. PLCG1 is required for metastasis development (Sala et al., 2008).
Role in angiogenesis: PLCG1 plays an important role in angiogenesis (Husain et al., 2010). PLCG1 is activated by vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells (Singh et al., 2007) and in neoplastic Barrett's cells (Zhang et al., 2013).
Role in the regulation of intracellular signaling: PLCG1 plays a role in mediating T-cell activities downstream of TCR activity. PLCG1 can be activated by receptor tyrosine kinases: EGFR (Nishibe et al., 1990; Wu et al., 2009), PDGFR (Larose et al., 1993), FGFR (Peters et al., 1992), NGFR (Middlemas et al., 1994) and HGFR (Davies et al., 2008). PLCG1 is a molecule associate with lipid rafts, it translocates from the cytosol to lipid rafts during TCR signaling (Verí et al., 2001).
Role in the mobilization of Ca2+: this process is to activate phosphatase calcineurin, which in turn dephosphorylates and activates NFAT (Rao et al., 1997). Truncation of the N terminus of Vav1 is accompanied by a decrease in PLCG1 phosphorylation and this inhibits calcium mobilization (Knyazhitsky et al., 2012).
Role in cytoskeleton: PLCG1 plays a role in actin reorganization (Pei et al., 1996; Wells, 2000; Wang et al., 2007; Li et al., 2009).
Role in adhesion and migration: PLCG1 mediates cell adhesion and migration through an undefined mechanism (Wang et al., 2007; Crooke et al., 2009). PLCG1 plays a role in integrin-mediated cell motility processes (Jones et al., 2005).
Role in apoptosis: PLCG1 is proteolytically cleaved by group II caspases especially by caspase-3 and caspase-7 during apoptosis. This results in the loss of receptor-mediated tyrosine phosphorylation (Bae et al., 2000). PLCG1 plays a protective role in H2O2-induced PC12 cells death (Yuan et al., 2009). The Fas-mediated apoptosis requires endoplasmic reticulum-mediated calcium release in a mechanism dependent on PLCG1 activation (Wozniak et al., 2006).
Role in transformation: PLCG1 interacts with Middle tumor antigen (MT). The tyrosine phosphorylation level of PLCG1 is elevated in cells expressing wild type MT but not in cells expressing Tyr322→Phe MT (Su et al., 1995).
Role in autoimmune symptoms: PLCG1 deficiency impairs the development and function regulatory cells (FoxP3+), causing inflammatory/autoimmune symptoms (Fu et al., 2010).
Homology The protein contains eight domains, four of which are unique to PLCG family (Suh et al., 2008). The PLCG 'specific array' of domains, comprising a "split" PH domain flanking two tandem SH2 domains and one SH3 domain, is inserted between the two halves (X and Y) of the TIM-barrel catalytic domain (Bunney and Katan, 2011). Several other domains including two PH domains, one C2 domain and one EF hand motifs (Suh et al., 2008).

Mutations

Somatic 99 mutations have been described in the PLCG1 gene, according to the Catalogue of Somatic Mutations in Cancer (COSMIC) database. De novo mutation has been described in patients with Cutaneous T-cell lymphoma (CTCL): S345F (10/53 analyzed CTCL samples, 19%) (Vaqué et al., 2014).

Implicated in

Note
  
Entity Breast cancer
Oncogenesis Overexpression of PLCG1 is a marker of development of metastases in breast cancer (Lattanzio et al., 2013). Loss of PLCG1 in part mimicked the effect of miR-200b/miR-c/miR-429 overexpression in viability, apoptosis and EGF-driven cell invasion of breast cancer cells (Uhlmann et al., 2010).
  
  
Entity Colorectal cancer
Oncogenesis PLCG1 has a potencial role in colon cancer (Nomoto et al., 1995; Li et al., 2005; Reid et al., 2009). The activity of PLCG1 is reduced in STAT3 Y705F mutant colorectal cancer cells (Zhang et al., 2011), it shows that there is crosstalk between STAT3 and PLCG1 signaling pathways.
  
  
Entity Prostate carcinoma
Oncogenesis PLCG1 has a role in the regulation of PC3LN3 (human prostate carcinoma cells) cell adhesion that appears to be independent of its effects on tumour cell chemotactic migration and spreading in response to extracellular matrix (Peak et al., 2008).
  
  
Entity Gastric cancer
Oncogenesis PLCG1 plays a role in RhoGDI2-mediated cisplatin resistance and cell invasion in gastric cancer (Cho et al., 2011).
  
  
Entity Squamous cell carcinoma (SCC)
Oncogenesis PLCG1 is a downstream target of EGFR signaling. PLCG1 is required for EGFR-induced SCC cell mitogenesis (Xie et al., 2010).
  
  
Entity Oral potentially malignant lesions (OPLs)
Oncogenesis PLCG1 is highly expressed in oral cancer lesions compared with normal oral mucosa (Ma et al., 2013).
  
  
Entity Esophageal adenocarcinoma
Oncogenesis PLCG1-PKC-ERK pathway promotes proliferation and it is activated by VEGFR-2 in neoplastic Barrett's cells (Zhang et al., 2013).
  
  
Entity Pheochromocytoma (PC)
Oncogenesis PLCG1 plays a role in apoptosis of PC12 cells induced by H2O2 (Yuan et al., 2009).
  
  
Entity Glioblastoma
Oncogenesis PLCG1 is associated with lifetime and overall survival in glioblastoma and it can be a novel biomarker of this desease (Serão et al., 2011).
  
  
Entity Cutaneous T-cell lymphoma (CTCL)
Oncogenesis The mutation in the catalytic domain of PLCG1 (S345F) is detection in patients with CTCL. PLCG1 mutants induced enhanced PLCG1 downstream signaling towards NFAT activation (Vaqué et al., 2014).
  
  
Entity Brain disorders
Note Jang et al., 2013.
Oncogenesis PLCG1 is highly expressed in brain. Abnormal expression and activation of PLCG1 appears in epilepsy (He et al., 2010), bipolar disorder (Løvlie et al., 2001), depression (Dwivedi et al., 2005), Huntington's disease (Giralt et al., 2009) and Alzheimer's disease (Shimohama et al., 1995).
  
  
Entity Myocardial dysfunction in sepsis
Oncogenesis PLCG1 signaling induces cardiac TNF-alpha expression and myocardial dysfunction during Lipopolysaccharide (LPS) stimulation. Inhibition of PLCG1 decreased cardiac TNF-alpha expression and LPS-induced myocardial dysfunction was also attenuated (Peng et al., 2008).
  

To be noted

miR that target PLCG1: PLCG1 is target of different microRNAs, according to the bioinformatic algorithms microRNA (microRNA.org).

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Citation

This paper should be referenced as such :
R Manso
PLCG1 (Phospholipase C, Gamma 1)
Atlas Genet Cytogenet Oncol Haematol. 2014;18(9):668-672.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/PLCG1ID44163ch20q12.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  dic(17;20)(p11.2;q11.2)


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Bone: Angiosarcoma
Bone: Vascular Tumors


External links

Nomenclature
HGNC (Hugo)PLCG1   9065
Cards
AtlasPLCG1ID44163ch20q12
Entrez_Gene (NCBI)PLCG1  5335  phospholipase C gamma 1
AliasesNCKAP3; PLC-II; PLC1; PLC148; 
PLCgamma1
GeneCards (Weizmann)PLCG1
Ensembl hg19 (Hinxton)ENSG00000124181 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000124181 [Gene_View]  chr20:41137521-41175717 [Contig_View]  PLCG1 [Vega]
ICGC DataPortalENSG00000124181
TCGA cBioPortalPLCG1
AceView (NCBI)PLCG1
Genatlas (Paris)PLCG1
WikiGenes5335
SOURCE (Princeton)PLCG1
Genetics Home Reference (NIH)PLCG1
Genomic and cartography
GoldenPath hg38 (UCSC)PLCG1  -     chr20:41137521-41175717 +  20q12   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PLCG1  -     20q12   [Description]    (hg19-Feb_2009)
EnsemblPLCG1 - 20q12 [CytoView hg19]  PLCG1 - 20q12 [CytoView hg38]
Mapping of homologs : NCBIPLCG1 [Mapview hg19]  PLCG1 [Mapview hg38]
OMIM172420   
Gene and transcription
Genbank (Entrez)AB210028 AF147391 AK297370 AK309606 AL110247
RefSeq transcript (Entrez)NM_002660 NM_182811
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)PLCG1
Cluster EST : UnigeneHs.268177 [ NCBI ]
CGAP (NCI)Hs.268177
Alternative Splicing GalleryENSG00000124181
Gene ExpressionPLCG1 [ NCBI-GEO ]   PLCG1 [ EBI - ARRAY_EXPRESS ]   PLCG1 [ SEEK ]   PLCG1 [ MEM ]
Gene Expression Viewer (FireBrowse)PLCG1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5335
GTEX Portal (Tissue expression)PLCG1
Human Protein AtlasENSG00000124181-PLCG1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP19174   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP19174  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP19174
Splice isoforms : SwissVarP19174
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 ]   
PhosPhoSitePlusP19174
Domaine pattern : Prosite (Expaxy)C2 (PS50004)    EF_HAND_1 (PS00018)    EF_HAND_2 (PS50222)    PH_DOMAIN (PS50003)    PIPLC_X_DOMAIN (PS50007)    PIPLC_Y_DOMAIN (PS50008)    SH2 (PS50001)    SH3 (PS50002)   
Domains : Interpro (EBI)C2_dom    EF-hand-dom_pair    EF_Hand_1_Ca_BS    EF_hand_dom    PH_dom-like    PH_domain    PI-PLC_fam    PLC-gamma    PLC-gamma1    PLC-like_Pdiesterase_TIM-brl    PLipase_C_PInositol-sp_X_dom    PLipase_C_Pinositol-sp_Y    SH2    SH3_domain   
Domain families : Pfam (Sanger)C2 (PF00168)    PI-PLC-X (PF00388)    PI-PLC-Y (PF00387)    SH2 (PF00017)    SH3_1 (PF00018)   
Domain families : Pfam (NCBI)pfam00168    pfam00388    pfam00387    pfam00017    pfam00018   
Domain families : Smart (EMBL)C2 (SM00239)  PH (SM00233)  PLCXc (SM00148)  PLCYc (SM00149)  SH2 (SM00252)  SH3 (SM00326)  
Conserved Domain (NCBI)PLCG1
DMDM Disease mutations5335
Blocks (Seattle)PLCG1
PDB (SRS)1HSQ    2HSP    4EY0    4FBN   
PDB (PDBSum)1HSQ    2HSP    4EY0    4FBN   
PDB (IMB)1HSQ    2HSP    4EY0    4FBN   
PDB (RSDB)1HSQ    2HSP    4EY0    4FBN   
Structural Biology KnowledgeBase1HSQ    2HSP    4EY0    4FBN   
SCOP (Structural Classification of Proteins)1HSQ    2HSP    4EY0    4FBN   
CATH (Classification of proteins structures)1HSQ    2HSP    4EY0    4FBN   
SuperfamilyP19174
Human Protein Atlas [tissue]ENSG00000124181-PLCG1 [tissue]
Peptide AtlasP19174
HPRD01398
IPIIPI00016736   IPI00383849   IPI00745182   
Protein Interaction databases
DIP (DOE-UCLA)P19174
IntAct (EBI)P19174
FunCoupENSG00000124181
BioGRIDPLCG1
STRING (EMBL)PLCG1
ZODIACPLCG1
Ontologies - Pathways
QuickGOP19174
Ontology : AmiGOactivation of MAPKK activity  in utero embryonic development  ruffle  phosphatidylinositol phospholipase C activity  phosphatidylinositol phospholipase C activity  phospholipase C activity  signal transducer activity, downstream of receptor  neurotrophin TRKA receptor binding  calcium ion binding  protein binding  cytoplasm  cytosol  cytosol  plasma membrane  plasma membrane  cell-cell junction  signal transduction  signal transduction  epidermal growth factor receptor signaling pathway  axon guidance  COP9 signalosome  phospholipid catabolic process  positive regulation of epithelial cell migration  viral process  cell migration  calcium-mediated signaling  protein kinase binding  lamellipodium  receptor tyrosine kinase binding  glutamate receptor binding  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  cell projection  positive regulation of blood vessel endothelial cell migration  inositol phosphate metabolic process  positive regulation of angiogenesis  T cell receptor signaling pathway  leukocyte migration  positive regulation of release of sequestered calcium ion into cytosol  cellular response to epidermal growth factor stimulus  cellular response to epidermal growth factor stimulus  
Ontology : EGO-EBIactivation of MAPKK activity  in utero embryonic development  ruffle  phosphatidylinositol phospholipase C activity  phosphatidylinositol phospholipase C activity  phospholipase C activity  signal transducer activity, downstream of receptor  neurotrophin TRKA receptor binding  calcium ion binding  protein binding  cytoplasm  cytosol  cytosol  plasma membrane  plasma membrane  cell-cell junction  signal transduction  signal transduction  epidermal growth factor receptor signaling pathway  axon guidance  COP9 signalosome  phospholipid catabolic process  positive regulation of epithelial cell migration  viral process  cell migration  calcium-mediated signaling  protein kinase binding  lamellipodium  receptor tyrosine kinase binding  glutamate receptor binding  Fc-epsilon receptor signaling pathway  Fc-gamma receptor signaling pathway involved in phagocytosis  cell projection  positive regulation of blood vessel endothelial cell migration  inositol phosphate metabolic process  positive regulation of angiogenesis  T cell receptor signaling pathway  leukocyte migration  positive regulation of release of sequestered calcium ion into cytosol  cellular response to epidermal growth factor stimulus  cellular response to epidermal growth factor stimulus  
Pathways : BIOCARTA [Genes]   
Pathways : KEGG   
REACTOMEP19174 [protein]
REACTOME PathwaysR-HSA-983695 [pathway]   
NDEx NetworkPLCG1
Atlas of Cancer Signalling NetworkPLCG1
Wikipedia pathwaysPLCG1
Orthology - Evolution
OrthoDB5335
GeneTree (enSembl)ENSG00000124181
Phylogenetic Trees/Animal Genes : TreeFamPLCG1
HOVERGENP19174
HOGENOMP19174
Homologs : HomoloGenePLCG1
Homology/Alignments : Family Browser (UCSC)PLCG1
Gene fusions - Rearrangements
Fusion : MitelmanPLCG1/BPIFB1 [20q12/20q11.21]  
Fusion : MitelmanPLCG1/TAF4 [20q12/20q13.33]  [t(20;20)(q12;q13)]  
Fusion: TCGAPLCG1 20q12 BPIFB1 20q11.21 BRCA
Fusion: TCGAPLCG1 20q12 TAF4 20q13.33 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPLCG1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PLCG1
dbVarPLCG1
ClinVarPLCG1
1000_GenomesPLCG1 
Exome Variant ServerPLCG1
ExAC (Exome Aggregation Consortium)ENSG00000124181
GNOMAD BrowserENSG00000124181
Genetic variants : HAPMAP5335
Genomic Variants (DGV)PLCG1 [DGVbeta]
DECIPHERPLCG1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPLCG1 
Mutations
ICGC Data PortalPLCG1 
TCGA Data PortalPLCG1 
Broad Tumor PortalPLCG1
OASIS PortalPLCG1 [ Somatic mutations - Copy number]
Cancer Gene: CensusPLCG1 
Somatic Mutations in Cancer : COSMICPLCG1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDPLCG1
intOGen PortalPLCG1
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 PLCG1
DgiDB (Drug Gene Interaction Database)PLCG1
DoCM (Curated mutations)PLCG1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)PLCG1 (select a term)
intoGenPLCG1
NCG5 (London)PLCG1
Cancer3DPLCG1(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM172420   
Orphanet
MedgenPLCG1
Genetic Testing Registry PLCG1
NextProtP19174 [Medical]
TSGene5335
GENETestsPLCG1
Target ValidationPLCG1
Huge Navigator PLCG1 [HugePedia]
snp3D : Map Gene to Disease5335
BioCentury BCIQPLCG1
ClinGenPLCG1
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5335
Chemical/Pharm GKB GenePA33392
Clinical trialPLCG1
Miscellaneous
canSAR (ICR)PLCG1 (select the gene name)
Probes
Litterature
PubMed351 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMinePLCG1
EVEXPLCG1
GoPubMedPLCG1
iHOPPLCG1
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Thu Oct 12 16:30:41 CEST 2017

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