Human Gene PLCE1 (uc001kjk.3) Description and Page Index
  Description: Homo sapiens phospholipase C, epsilon 1 (PLCE1), transcript variant 1, mRNA.
RefSeq Summary (NM_016341): This gene encodes a phospholipase enzyme that catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate to generate two second messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG). These second messengers subsequently regulate various processes affecting cell growth, differentiation, and gene expression. This enzyme is regulated by small monomeric GTPases of the Ras and Rho families and by heterotrimeric G proteins. In addition to its phospholipase C catalytic activity, this enzyme has an N-terminal domain with guanine nucleotide exchange (GEF) activity. Mutations in this gene cause early-onset nephrotic syndrome; characterized by proteinuria, edema, and diffuse mesangial sclerosis or focal and segmental glomerulosclerosis. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Sep 2009].
Transcript (Including UTRs)
   Position: hg19 chr10:95,753,746-96,088,148 Size: 334,403 Total Exon Count: 33 Strand: +
Coding Region
   Position: hg19 chr10:95,790,804-96,084,837 Size: 294,034 Coding Exon Count: 31 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr10:95,753,746-96,088,148)mRNA (may differ from genome)Protein (2302 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
H-INVHGNCHPRDLynxMGIneXtProt
OMIMPubMedReactomeStanford SOURCETreefamUniProtKB
Wikipedia

-  Comments and Description Text from UniProtKB
  ID: PLCE1_HUMAN
DESCRIPTION: RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1; EC=3.1.4.11; AltName: Full=Pancreas-enriched phospholipase C; AltName: Full=Phosphoinositide phospholipase C-epsilon-1; AltName: Full=Phospholipase C-epsilon-1; Short=PLC-epsilon-1;
FUNCTION: The production of the second messenger molecules diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) is mediated by activated phosphatidylinositol-specific phospholipase C enzymes. PLCE1 is a bifunctional enzyme which also regulates small GTPases of the Ras superfamily through its Ras guanine- exchange factor (RasGEF) activity. As an effector of heterotrimeric and small G-protein, it may play a role in cell survival, cell growth, actin organization and T-cell activation.
CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.
COFACTOR: Calcium.
ENZYME REGULATION: Activated by the heterotrimeric G-protein subunits GNA12, GNA13 and GNB1-GNG2. Activated by HRAS, RAP1A, RHOA, RHOB, RHOC, RRAS and RRAS2. Activated by the G(s)-coupled GPCRs ADRB2, PTGER1 and CHRM3 through cyclic-AMP formation and RAP2B activation. Inhibited by G(i)-coupled GPCRs.
SUBUNIT: Interacts with RHOA (By similarity). Interacts with IQGAP1, HRAS, RAP1A, RAP2A, RAP2B and RRAS.
SUBCELLULAR LOCATION: Cytoplasm, cytosol. Cell membrane. Golgi apparatus membrane. Note=Recruited to plasma membrane by activated HRAS and RAP2. Recruited to perinuclear membrane by activated RAP1A. Isoform 1 and isoform 2 associates with Golgi membranes.
TISSUE SPECIFICITY: Widely expressed. Isoform 1 is broadly expressed and only absent in peripheral blood leukocytes. Isoform 2 is specifically expressed in placenta, lung and spleen.
INDUCTION: Overexpressed during heart failure.
DOMAIN: The Ras-associating domain 1 is degenerated and may not bind HRAS. The Ras-associating domain 2 mediates interaction with GTP-bound HRAS, RAP1A, RAP2A and RAP2B and recruitment of HRAS to the cell membrane.
DOMAIN: The Ras-GEF domain has a GEF activity towards HRAS and RAP1A. Mediates activation of the mitogen-activated protein kinase pathway.
DISEASE: Defects in PLCE1 are the cause of nephrotic syndrome type 3 (NPHS3) [MIM:610725]; also known as early-onset nephrotic syndrome type 3. Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, hypoalbuminemia, edema. End-stage kidney disease is observed in steroid-resistant nephrotic syndrome.
SIMILARITY: Contains 1 C2 domain.
SIMILARITY: Contains 1 PI-PLC X-box domain.
SIMILARITY: Contains 1 PI-PLC Y-box domain.
SIMILARITY: Contains 2 Ras-associating domains.
SIMILARITY: Contains 1 Ras-GEF domain.
SEQUENCE CAUTION: Sequence=AAF22005.1; Type=Frameshift; Positions=1131; Sequence=AAG17145.2; Type=Frameshift; Positions=2296; Sequence=BAA96040.2; Type=Erroneous initiation; Sequence=BAB14090.1; Type=Erroneous initiation; Sequence=CAH70739.1; Type=Erroneous gene model prediction; Sequence=CAH73288.1; Type=Erroneous gene model prediction; Sequence=CAH73757.1; Type=Erroneous gene model prediction; Sequence=CAI16674.1; Type=Erroneous gene model prediction;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PLCE1
CDC HuGE Published Literature: PLCE1
Positive Disease Associations: Blood Pressure , Death, Sudden, Cardiac , Dengue Hemorrhagic Fever , Esophageal Neoplasms , Hypertension , Pulmonary Disease, Chronic Obstructive , Religion and Psychology , Stomach Neoplasms , Stroke
Related Studies:
  1. Blood Pressure
    Louise V Wain et al. Nature genetics 2011, Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure., Nature genetics. [PubMed 21909110]
  2. Blood Pressure
    Georg B Ehret et al. Nature 2011, Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk., Nature. [PubMed 21909115]
  3. Death, Sudden, Cardiac
    Bradley E Aouizerat et al. BMC cardiovascular disorders 2012, GWAS for discovery and replication of genetic loci associated with sudden cardiac arrest in patients with coronary artery disease., BMC cardiovascular disorders. [PubMed 21658281]
    We demonstrate 11 gene associations for sudden cardiac arrest due to ventricular tachycardia/ventricular fibrillation in patients with coronary artery disease. Validation studies in independent cohorts and functional studies are required to confirm these associations.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PLCE1
Diseases sorted by gene-association score: nephrotic syndrome, type 3* (1318), sporadic idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis* (247), familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis* (202), glomerulosclerosis, focal segmental, 1* (143), diffuse mesangial sclerosis (28), nephrotic syndrome (28), familial nephrotic syndrome (23), gastric cardia adenocarcinoma (17), dengue shock syndrome (17), gastric cardia carcinoma (7), focal segmental glomerulosclerosis (7), frasier syndrome (5), esophageal cancer (4), stomach cancer (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 7.64 RPKM in Artery - Tibial
Total median expression: 122.66 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -226.34634-0.357 Picture PostScript Text
3' UTR -113.90448-0.254 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000008 - C2_Ca-dep
IPR008973 - C2_Ca/lipid-bd_dom_CaLB
IPR018029 - C2_membr_targeting
IPR011992 - EF-hand-like_dom
IPR001192 - Pinositol_PLipase_C
IPR017946 - PLC-like_Pdiesterase_TIM-brl
IPR015359 - PLipase_C_EF-hand-like
IPR000909 - PLipase_C_PInositol-sp_X_dom
IPR001711 - PLipase_C_Pinositol-sp_Y
IPR000159 - Ras-assoc
IPR023578 - Ras_GEF_dom
IPR001895 - RasGRF_CDC25

Pfam Domains:
PF00168 - C2 domain
PF00387 - Phosphatidylinositol-specific phospholipase C, Y domain
PF00388 - Phosphatidylinositol-specific phospholipase C, X domain
PF00617 - RasGEF domain
PF00788 - Ras association (RalGDS/AF-6) domain
PF09279 - Phosphoinositide-specific phospholipase C, efhand-like

SCOP Domains:
48366 - Ras GEF
47473 - EF-hand
49562 - C2 domain (Calcium/lipid-binding domain, CaLB)
51695 - PLC-like phosphodiesterases

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2BYE
- NMR MuPIT

2BYF
- NMR MuPIT

2C5L
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q9P212
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
      
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004435 phosphatidylinositol phospholipase C activity
GO:0004629 phospholipase C activity
GO:0004871 signal transducer activity
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005515 protein binding
GO:0008081 phosphoric diester hydrolase activity
GO:0016787 hydrolase activity
GO:0017016 Ras GTPase binding
GO:0019899 enzyme binding
GO:0046872 metal ion binding

Biological Process:
GO:0000187 activation of MAPK activity
GO:0001558 regulation of cell growth
GO:0006629 lipid metabolic process
GO:0006651 diacylglycerol biosynthetic process
GO:0006940 regulation of smooth muscle contraction
GO:0007010 cytoskeleton organization
GO:0007165 signal transduction
GO:0007173 epidermal growth factor receptor signaling pathway
GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway
GO:0007204 positive regulation of cytosolic calcium ion concentration
GO:0007264 small GTPase mediated signal transduction
GO:0007265 Ras protein signal transduction
GO:0007507 heart development
GO:0008277 regulation of G-protein coupled receptor protein signaling pathway
GO:0008283 cell proliferation
GO:0016042 lipid catabolic process
GO:0019722 calcium-mediated signaling
GO:0032835 glomerulus development
GO:0035556 intracellular signal transduction
GO:0043647 inositol phosphate metabolic process
GO:0045859 regulation of protein kinase activity
GO:0046578 regulation of Ras protein signal transduction
GO:0048016 inositol phosphate-mediated signaling

Cellular Component:
GO:0000139 Golgi membrane
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane


-  Descriptions from all associated GenBank mRNAs
  AB040949 - Homo sapiens KIAA1516 mRNA for KIAA1516 protein.
BC151854 - Homo sapiens phospholipase C, epsilon 1, mRNA (cDNA clone MGC:167842 IMAGE:8860521), complete cds.
AF190642 - Homo sapiens phosphoinositide-specific phospholipase C PLC-epsilon mRNA, complete cds.
LF214062 - JP 2014500723-A/21565: Polycomb-Associated Non-Coding RNAs.
BC140705 - Homo sapiens phospholipase C, epsilon 1, mRNA (cDNA clone MGC:176382 IMAGE:9021573), complete cds.
BC144286 - Homo sapiens phospholipase C, epsilon 1, mRNA (cDNA clone MGC:177823 IMAGE:9052806), complete cds.
AB384613 - Synthetic construct DNA, clone: pF1KA1516, Homo sapiens PLCE1 gene for phospholipase C, epsilon 1, complete cds, without stop codon, in Flexi system.
AK297779 - Homo sapiens cDNA FLJ53141 partial cds, highly similar to Homo sapiens phospholipase C, epsilon 1 (PLCE1), mRNA.
AK289852 - Homo sapiens cDNA FLJ75518 partial cds, highly similar to Homo sapiens phospholipase C epsilon mRNA.
AF170071 - Homo sapiens phospholipase C epsilon mRNA, partial cds.
AF117948 - Homo sapiens pancreas-enriched phospholipase C mRNA, complete cds.
AK022543 - Homo sapiens cDNA FLJ12481 fis, clone NT2RM1001072, weakly similar to 1-PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE PHOSPHODIESTERASE GAMMA 1 (EC 3.1.4.11).
AK074239 - Homo sapiens cDNA FLJ23659 fis, clone COLF6818, highly similar to Homo sapiens phospholipase C epsilon mRNA.
AY995135 - Homo sapiens phospholipase C epsilon 1 mRNA, partial cds.
BX641131 - Homo sapiens mRNA; cDNA DKFZp686H2494 (from clone DKFZp686H2494).
MA449639 - JP 2018138019-A/21565: Polycomb-Associated Non-Coding RNAs.
JD503807 - Sequence 484831 from Patent EP1572962.
JD313715 - Sequence 294739 from Patent EP1572962.
JD168461 - Sequence 149485 from Patent EP1572962.
AK025366 - Homo sapiens cDNA: FLJ21713 fis, clone COL10239.
JD183328 - Sequence 164352 from Patent EP1572962.
AL050031 - Homo sapiens mRNA; cDNA DKFZp566E0224 (from clone DKFZp566E0224).
JD309403 - Sequence 290427 from Patent EP1572962.
JD076839 - Sequence 57863 from Patent EP1572962.
JD087729 - Sequence 68753 from Patent EP1572962.
JD365335 - Sequence 346359 from Patent EP1572962.
JD270230 - Sequence 251254 from Patent EP1572962.
JD302179 - Sequence 283203 from Patent EP1572962.
JD187072 - Sequence 168096 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00562 - Inositol phosphate metabolism
hsa01100 - Metabolic pathways
hsa04020 - Calcium signaling pathway
hsa04070 - Phosphatidylinositol signaling system

BioCyc Knowledge Library
LIPASYN-PWY - phospholipases
PWY-6351 - D-myo-inositol (1,4,5)-trisphosphate biosynthesis
PWY-6367 - D-myo-inositol-5-phosphate metabolism
PWY3DJ-219 - PIP metabolism

BioCarta from NCI Cancer Genome Anatomy Project
h_plcePathway - Phospholipase C-epsilon pathway

Reactome (by CSHL, EBI, and GO)

Protein Q9P212 (Reactome details) participates in the following event(s):

R-HSA-1855221 PI(4,5)P2 is hydrolysed to I(1,4,5)P3 and DAG by tethered PLC[1] at the plasma membrane
R-HSA-1855204 Synthesis of IP3 and IP4 in the cytosol
R-HSA-1483249 Inositol phosphate metabolism
R-HSA-1430728 Metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: A6NGW0, A6NLA1, A7MBN7, A8K1D7, B9EIJ6, KIAA1516, NM_016341, NP_057425, PLCE, PLCE1_HUMAN, PPLC, Q1X6H8, Q5VWL4, Q5VWL5, Q9H9X8, Q9HBX6, Q9HC53, Q9P212, Q9UHV3
UCSC ID: uc001kjk.3
RefSeq Accession: NM_016341
Protein: Q9P212 (aka PLCE1_HUMAN)
CCDS: CCDS41552.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_016341.3
exon count: 33CDS single in 3' UTR: no RNA size: 7992
ORF size: 6909CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 13151.50frame shift in genome: no % Coverage: 99.99
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.