Human Gene PLCG2 (ENST00000564138.6_6) from GENCODE V47lift37
  Description: phospholipase C gamma 2 (from RefSeq NM_002661.5)
Gencode Transcript: ENST00000564138.6_6
Gencode Gene: ENSG00000197943.13_14
Transcript (Including UTRs)
   Position: hg19 chr16:81,812,896-81,996,290 Size: 183,395 Total Exon Count: 33 Strand: +
Coding Region
   Position: hg19 chr16:81,819,595-81,991,603 Size: 172,009 Coding Exon Count: 32 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:81,812,896-81,996,290)mRNA (may differ from genome)Protein (1265 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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HGNCMalacardsMGIOMIMPubMedReactome
UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: PLCG2_HUMAN
DESCRIPTION: RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2; EC=3.1.4.11; AltName: Full=Phosphoinositide phospholipase C-gamma-2; AltName: Full=Phospholipase C-IV; Short=PLC-IV; AltName: Full=Phospholipase C-gamma-2; Short=PLC-gamma-2;
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. It is a crucial enzyme in transmembrane signaling.
CATALYTIC ACTIVITY: 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate + H(2)O = 1D-myo-inositol 1,4,5-trisphosphate + diacylglycerol.
COFACTOR: Calcium.
SUBUNIT: Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (By similarity).
INTERACTION: P19235:EPOR; NbExp=3; IntAct=EBI-617403, EBI-617321;
PTM: Phosphorylated on tyrosine residues by CSF1R (By similarity). Phosphorylated on tyrosine residues by BTK and SYK; upon ligand- induced activation of a variety of growth factor receptors and immune system receptors. Phosphorylation leads to increased phospholipase activity.
DISEASE: Defects in PLCG2 are the cause of familial cold autoinflammatory syndrome type 3 (FCAS3) [MIM:614468]. An autosomal dominant immune disorder characterized by the development of cutaneous urticaria, erythema, and pruritis in response to cold exposure. Affected individuals have variable additional immunologic defects, including antibody deficiency, decreased numbers of B cells, defective B cells, increased susceptibility to infection, and increased risk of autoimmune disorders.
SIMILARITY: Contains 1 C2 domain.
SIMILARITY: Contains 1 PH domain.
SIMILARITY: Contains 1 PI-PLC X-box domain.
SIMILARITY: Contains 1 PI-PLC Y-box domain.
SIMILARITY: Contains 2 SH2 domains.
SIMILARITY: Contains 1 SH3 domain.
SEQUENCE CAUTION: Sequence=AAA60112.1; Type=Frameshift; Positions=1242; Sequence=AAQ76815.1; Type=Frameshift; Positions=1242; Sequence=BAD92151.1; Type=Erroneous initiation; Sequence=CAA32194.1; Type=Frameshift; Positions=1242;

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
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To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: PLCG2
Diseases sorted by gene-association score: autoinflammation, antibody deficiency, and immune dysregulation syndrome* (1570), familial cold autoinflammatory syndrome 3* (1380), familial cold autoinflammatory syndrome (20), urticaria (16), agammaglobulinemia, x-linked 1 (13), cold urticaria (8), gray platelet syndrome (5)
* = 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
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+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -87.20181-0.482 Picture PostScript Text
3' UTR -1351.004687-0.288 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
IPR011993 - PH_like_dom
IPR001192 - Pinositol_PLipase_C
IPR016279 - PLC-gamma
IPR017946 - PLC-like_Pdiesterase_TIM-brl
IPR001849 - Pleckstrin_homology
IPR015359 - PLipase_C_EF-hand-like
IPR000909 - PLipase_C_PInositol-sp_X_dom
IPR001711 - PLipase_C_Pinositol-sp_Y
IPR000980 - SH2
IPR001452 - SH3_domain

Pfam Domains:
PF00017 - SH2 domain
PF00018 - SH3 domain
PF00168 - C2 domain
PF00387 - Phosphatidylinositol-specific phospholipase C, Y domain
PF00388 - Phosphatidylinositol-specific phospholipase C, X domain
PF07653 - Variant SH3 domain
PF14604 - Variant SH3 domain

SCOP Domains:
47473 - EF-hand
50044 - SH3-domain
50729 - PH domain-like
49562 - C2 domain (Calcium/lipid-binding domain, CaLB)
51695 - PLC-like phosphodiesterases
55550 - SH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2K2J - NMR MuPIT 2W2W - X-ray MuPIT 2W2X - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P16885
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-  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 DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0001784 phosphotyrosine binding
GO:0004435 phosphatidylinositol phospholipase C activity
GO:0004629 phospholipase C activity
GO:0004871 signal transducer activity
GO:0005515 protein binding
GO:0008081 phosphoric diester hydrolase activity
GO:0016787 hydrolase activity

Biological Process:
GO:0002092 positive regulation of receptor internalization
GO:0002223 stimulatory C-type lectin receptor signaling pathway
GO:0002316 follicular B cell differentiation
GO:0006629 lipid metabolic process
GO:0006661 phosphatidylinositol biosynthetic process
GO:0007165 signal transduction
GO:0009395 phospholipid catabolic process
GO:0010468 regulation of gene expression
GO:0016042 lipid catabolic process
GO:0016055 Wnt signaling pathway
GO:0019722 calcium-mediated signaling
GO:0030168 platelet activation
GO:0030183 B cell differentiation
GO:0032237 activation of store-operated calcium channel activity
GO:0032481 positive regulation of type I interferon production
GO:0032496 response to lipopolysaccharide
GO:0032959 inositol trisphosphate biosynthetic process
GO:0035556 intracellular signal transduction
GO:0038095 Fc-epsilon receptor signaling pathway
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0043069 negative regulation of programmed cell death
GO:0043647 inositol phosphate metabolic process
GO:0050852 T cell receptor signaling pathway
GO:0050853 B cell receptor signaling pathway
GO:0051209 release of sequestered calcium ion into cytosol

Cellular Component:
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  LF384470 - JP 2014500723-A/191973: Polycomb-Associated Non-Coding RNAs.
AB208914 - Homo sapiens mRNA for 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma 2 variant protein.
M37238 - Human phospholipase C mRNA, complete cds.
X14034 - Human mRNA for phospholipase C.
BC007565 - Homo sapiens phospholipase C, gamma 2 (phosphatidylinositol-specific), mRNA (cDNA clone MGC:15492 IMAGE:2989125), complete cds.
BC011772 - Homo sapiens phospholipase C, gamma 2 (phosphatidylinositol-specific), mRNA (cDNA clone MGC:19776 IMAGE:3678272), complete cds.
BC014561 - Homo sapiens phospholipase C, gamma 2 (phosphatidylinositol-specific), mRNA (cDNA clone MGC:1679 IMAGE:2989281), complete cds.
BC018646 - Homo sapiens phospholipase C, gamma 2 (phosphatidylinositol-specific), mRNA (cDNA clone MGC:1680 IMAGE:2989389), complete cds.
AK310042 - Homo sapiens cDNA, FLJ17084.
AB384772 - Synthetic construct DNA, clone: pF1KB3272, Homo sapiens PLCG2 gene for phospholipase C, gamma 2, complete cds, without stop codon, in Flexi system.
DQ896514 - Synthetic construct Homo sapiens clone IMAGE:100010974; FLH195047.01L; RZPDo839H1170D phospholipase C, gamma 2 (phosphatidylinositol-specific) (PLCG2) gene, encodes complete protein.
DQ893524 - Synthetic construct clone IMAGE:100006154; FLH195051.01X; RZPDo839H1180D phospholipase C, gamma 2 (phosphatidylinositol-specific) (PLCG2) gene, encodes complete protein.
AY364256 - Homo sapiens clone peg2500 phospholipase C gamma 2 (PLCG2) mRNA, complete cds.
KJ897342 - Synthetic construct Homo sapiens clone ccsbBroadEn_06736 PLCG2 gene, encodes complete protein.
AK304722 - Homo sapiens cDNA FLJ57018 complete cds, highly similar to 1-phosphatidylinositol-4,5-bisphosphatephosphodiesterase gamma 2 (EC 3.1.4.11).
MA620047 - JP 2018138019-A/191973: Polycomb-Associated Non-Coding RNAs.
LF212242 - JP 2014500723-A/19745: Polycomb-Associated Non-Coding RNAs.
LF374842 - JP 2014500723-A/182345: Polycomb-Associated Non-Coding RNAs.
LF374843 - JP 2014500723-A/182346: Polycomb-Associated Non-Coding RNAs.
LF374849 - JP 2014500723-A/182352: Polycomb-Associated Non-Coding RNAs.
MA447819 - JP 2018138019-A/19745: Polycomb-Associated Non-Coding RNAs.
MA610419 - JP 2018138019-A/182345: Polycomb-Associated Non-Coding RNAs.
MA610420 - JP 2018138019-A/182346: Polycomb-Associated Non-Coding RNAs.
MA610426 - JP 2018138019-A/182352: Polycomb-Associated Non-Coding RNAs.
LF374858 - JP 2014500723-A/182361: Polycomb-Associated Non-Coding RNAs.
LF374859 - JP 2014500723-A/182362: Polycomb-Associated Non-Coding RNAs.
LF374860 - JP 2014500723-A/182363: Polycomb-Associated Non-Coding RNAs.
LF374867 - JP 2014500723-A/182370: Polycomb-Associated Non-Coding RNAs.
JD282252 - Sequence 263276 from Patent EP1572962.
JD461211 - Sequence 442235 from Patent EP1572962.
LF374871 - JP 2014500723-A/182374: Polycomb-Associated Non-Coding RNAs.
JD438593 - Sequence 419617 from Patent EP1572962.
JD286949 - Sequence 267973 from Patent EP1572962.
LF374872 - JP 2014500723-A/182375: Polycomb-Associated Non-Coding RNAs.
BC018983 - Homo sapiens cDNA clone IMAGE:4309350, partial cds.
AK127374 - Homo sapiens cDNA FLJ45450 fis, clone BRSTN2002691.
MA610435 - JP 2018138019-A/182361: Polycomb-Associated Non-Coding RNAs.
MA610436 - JP 2018138019-A/182362: Polycomb-Associated Non-Coding RNAs.
MA610437 - JP 2018138019-A/182363: Polycomb-Associated Non-Coding RNAs.
MA610444 - JP 2018138019-A/182370: Polycomb-Associated Non-Coding RNAs.
MA610448 - JP 2018138019-A/182374: Polycomb-Associated Non-Coding RNAs.
MA610449 - JP 2018138019-A/182375: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCyc Knowledge Library
LIPASYN-PWY - phospholipases
PWY-6351 - D-myo-inositol (1,4,5)-trisphosphate biosynthesis
PWY-6367 - D-myo-inositol-5-phosphate metabolism
PWY-6371 - superpathway of inositol phosphate compounds

Reactome (by CSHL, EBI, and GO)

Protein P16885 (Reactome details) participates in the following event(s):

R-HSA-5607745 1,3-beta-D-glucan:p-Y15-CLEC7A:SYK phosphorylates PLCG
R-HSA-5621356 PLCG1 binds p-6Y-SYK:p-Y65,Y76-FCER1G
R-HSA-5607755 p-Y753,Y759-PLCG2 translocates from cytosol to plasma membrane
R-HSA-5621347 PLCG2 translocates from cytosol to plasma membrane
R-HSA-114689 PLC gamma 2-mediated PIP2 hydrolysis
R-HSA-5621363 SYK phosphorylates PLCG2 in p-6Y-SYK:p-Y65,Y76-FCER1G:PLCG2
R-HSA-2029270 Recruitment of PLCgamma to membrane
R-HSA-2396606 Recruitment of PLC-gamma to SLP-76 and p-5Y-LAT
R-HSA-2029272 Release of PLCG from FCGR
R-HSA-2424485 Release of p-PLCG1
R-HSA-5607735 p-Y753,Y759-PLCG2 hydrolyses PIP2
R-HSA-2029268 Phosphorylation and activation of PLCG
R-HSA-2396594 Phosphorylation of SLP-76 by p-SYK
R-HSA-2730851 Phosphorylation of SLP-76 by p-SYK
R-HSA-2424481 Recruitment of VAV and BTK to p-SLP-76
R-HSA-2730892 Recruitment of VAV to p-SLP-76
R-HSA-2424487 Phosphorylation of PLC-gamma by p-BTK/p-SYK
R-HSA-2424484 Phosphorylation of BTK by p-SYK
R-HSA-2424486 Phosphorylation and activation of VAV2/VAV3 by SYK
R-HSA-2730888 Phosphorylation of PLC-gamma
R-HSA-2730858 Autophosphorylation of BTK/ITK
R-HSA-2730840 Activation of RAC1 by VAV
R-HSA-2730841 Phosphorylation and activation of VAV
R-HSA-2730885 Recruitment of TEC kinases to p-SLP-76
R-HSA-2730833 Phosphorylation of TEC kinases by p-SYK
R-HSA-2730889 Recruitment of PAK to the membrane by binding active RAC1
R-HSA-2730856 Autophosphorylation of PAK
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-2424476 Activation of RAC1 by VAV2/3
R-HSA-1112666 BLNK (SLP-65) Signalosome hydrolyzes phosphatidyinositol bisphosphate forming diacylglycerol and inositol-1,4,5-trisphosphate
R-HSA-2730847 Hydrolysis of PIP2 by PLCG
R-HSA-114604 GPVI-mediated activation cascade
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5621480 Dectin-2 family
R-HSA-76002 Platelet activation, signaling and aggregation
R-HSA-983695 Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-2029485 Role of phospholipids in phagocytosis
R-HSA-2424491 DAP12 signaling
R-HSA-2871796 FCERI mediated MAPK activation
R-HSA-5621481 C-type lectin receptors (CLRs)
R-HSA-109582 Hemostasis
R-HSA-983705 Signaling by the B Cell Receptor (BCR)
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-2172127 DAP12 interactions
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-168249 Innate Immune System
R-HSA-2871809 FCERI mediated Ca+2 mobilization
R-HSA-1280218 Adaptive Immune System
R-HSA-168256 Immune System
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: D3DUL3, ENST00000564138.1, ENST00000564138.2, ENST00000564138.3, ENST00000564138.4, ENST00000564138.5, NM_002661, P16885, PLCG2 , PLCG2_HUMAN, Q3ZTS2, Q59H45, Q969T5, uc325svc.1, uc325svc.2
UCSC ID: ENST00000564138.6_6
RefSeq Accession: NM_002661.5
Protein: P16885 (aka PLCG2_HUMAN or PIG2_HUMAN)

-  Gene Model Information
  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.