PLCB3 phospholipase C beta 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PLCB3provided by HGNC
Official Full Name: phospholipase C beta 3provided by HGNC
Primary source: HGNC:HGNC:9056
See related: Ensembl:ENSG00000149782 MIM:600230; AllianceGenome:HGNC:9056
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: SMDCD
Summary: This gene encodes a member of the phosphoinositide phospholipase C beta enzyme family that catalyze the production of the secondary messengers diacylglycerol and inositol 1,4,5-triphosphate from phosphatidylinositol in G-protein-linked receptor-mediated signal transduction. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]
Expression: Broad expression in duodenum (RPKM 38.8), small intestine (RPKM 36.6) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.1

Exon count:: 33

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (64251530..64269452)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (64241551..64259480)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (64019002..64036924)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phospholipase C controls chloride-dependent short-circuit current in human bronchial epithelial cells.
Title: Phospholipase C controls chloride-dependent short-circuit current in human bronchial epithelial cells.
Intramolecular electrostatic interactions contribute to phospholipase Cbeta3 autoinhibition.
Title: Intramolecular electrostatic interactions contribute to phospholipase Cβ3 autoinhibition.
A homozygous loss of function variant in PLCB3 is associated with corneal dystrophy, developmental delay and spondylometaphyseal dysplasia.
Title: Defect in phosphoinositide signalling through a homozygous variant in PLCB3 causes a new form of spondylometaphyseal dysplasia with corneal dystrophy.
These results, besides identifying S845L as a loss-of-function variant, strengthen the importance of targeting PLCB3 to mitigate the cystic fibrosis inflammatory response in bronchial epithelial cells without blunting the immune response.
Title: PLCB3 Loss of Function Reduces Pseudomonas aeruginosa-Dependent IL-8 Release in Cystic Fibrosis.
This study reveals detailed mechanistic insight into the role of ORP4L in PLCbeta3 redistribution from storage within the nucleus to the plasma membrane via RAN activation and interaction with VAPA in Jurkat T-cells.
Title: OSBP-related protein 4L promotes phospholipase Cβ3 translocation from the nucleus to the plasma membrane in Jurkat T-cells.
Data suggest that 300-residue C-terminal domain of PLCB3 promotes adsorption to phospholipid monolayer/membrane bilayer and is required for spatial organization/adsorption of PLCB3 on membrane surface; defects in phosphatidylinositol 4,5-bisphosphate (PIP2) hydrolysis alter monolayer adsorption, thus, suggesting role of active site in this process; PLCB3 is preferentially adsorbed to region of bilayer enriched with PIP2.
Title: Phospholipase Cβ3 Membrane Adsorption and Activation Are Regulated by Its C-Terminal Domains and Phosphatidylinositol 4,5-Bisphosphate.
These results indicate that the mechanism by which Galphaq and PLC-beta3 mutually regulate each other is far more complex than a simple, two-state allosteric model and instead is probably kinetically determined.
Title: The binding of activated Gα(q) to phospholipase C-β exhibits anomalous affinity.
We propose that unliganded PLC-beta exists in equilibrium between a closed conformation observed in crystal structures and an open conformation where the PH domain moves away from the EF hands. Therefore, intrinsic movement of the PH domain in PLC-beta modulates Gbetagamma access to its binding site.
Title: Intrinsic Pleckstrin Homology (PH) Domain Motion in Phospholipase C-β Exposes a Gβγ Protein Binding Site.
the MCP1-induced cortactin phosphorylation is dependent on PLCb3-mediated PKC activation, and siRNA-mediated down-regulation of either of these molecules prevents cortactin interaction with WAVE2
Title: PLCβ3 mediates cortactin interaction with WAVE2 in MCP1-induced actin polymerization and cell migration.
Gnb isoforms control a signaling pathway comprising Rac1, Plcbeta2, and Plcbeta3 leading to LFA-1 activation and neutrophil arrest in vivo
Title: Gnb isoforms control a signaling pathway comprising Rac1, Plcβ2, and Plcβ3 leading to LFA-1 activation and neutrophil arrest in vivo.

Submit: New GeneRIF Correction See all GeneRIFs (32)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Spondylometaphyseal dysplasia with corneal dystrophy MedGen: C5394555 OMIM: 618961 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 envelope glycoproteins gp120 and gp160 directly and specifically impair the CD3/TcR-mediated activation of phospholipase C (PLC) via the CD4 molecule in uninfected T cells	PubMed
Tat	tat	Phospholipase C/protein kinase C pathway-dependent phosphorylation of p44/42 and JNK MAP kinases is partially involved in IL-1beta induction by HIV-1 Tat	PubMed
	tat	HIV-1 Tat induces release of calcium and TNF-alpha production, an effect mediated at least in part by activation of phospholipase C	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-82715 (e-PCR)
- UniSTS:102424

G33075 (e-PCR)
- UniSTS:73763

FKBP2 (e-PCR)
- UniSTS:3365

WI-14122 (e-PCR)
- UniSTS:30760

SHGC-83713 (e-PCR)
- UniSTS:104269

RH27714 (e-PCR)
- UniSTS:88669

SHGC-12383 (e-PCR)
- UniSTS:14686

RH27387 (e-PCR)
- UniSTS:84649

PLCB3sts2 (e-PCR)
- UniSTS:259010

fkbp2sts3 (e-PCR)
- UniSTS:259011

VEGFB_2536 (e-PCR)
- UniSTS:281074

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cadherin binding	HDA more info	PubMed
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables calmodulin binding	IBA Inferred from Biological aspect of Ancestor more info
enables calmodulin binding	IDA Inferred from Direct Assay more info	PubMed
enables molecular adaptor activity	EXP Inferred from Experiment more info	PubMed
enables molecular adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables molecular function activator activity	EXP Inferred from Experiment more info	PubMed
enables phosphatidylinositol phospholipase C activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphatidylinositol phospholipase C activity	IDA Inferred from Direct Assay more info	PubMed
enables phospholipase C activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in G protein-coupled receptor signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
involved_in lipid catabolic process	IEA Inferred from Electronic Annotation more info
involved_in phosphatidylinositol metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in phosphatidylinositol metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in phosphatidylinositol-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of systemic arterial blood pressure	IDA Inferred from Direct Assay more info	PubMed
involved_in release of sequestered calcium ion into cytosol	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in postsynaptic cytosol	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3

Names: PLC beta 3; phosphoinositide phospholipase C-beta-3; phospholipase C, beta 3 (phosphatidylinositol-specific)

NP_000923.1

EC 3.1.4.11

NP_001171812.1

EC 3.1.4.11

NP_001303243.1

EC 3.1.4.11

XP_016873414.1

EC 3.1.4.11

XP_054225108.1

EC 3.1.4.11

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_000932.5 → NP_000923.1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform 1

See identical proteins and their annotated locations for NP_000923.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1). Variants 1 and 3 both encode the same isoform (1).

Source sequence(s)

AP001453, BC142681

Consensus CDS

CCDS8064.1

UniProtKB/Swiss-Prot

A5PKZ6, G5E960, Q01970, Q8N1A4

Related

ENSP00000279230.6, ENST00000279230.12

Conserved Domains (7) summary

cd00275
Location:728 → 843

C2_PLC_like; C2 domain present in Phosphoinositide-specific phospholipases C (PLC)

cd08625
Location:316 → 693

PI-PLCc_beta3; Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3

cd13361
Location:22 → 149

PH_PLC_beta; Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain

pfam06631
Location:951 → 988

DUF1154; Protein of unknown function (DUF1154)

pfam08703
Location:1029 → 1202

PLC-beta_C; PLC-beta C terminal

pfam09279
Location:225 → 315

EF-hand_like; Phosphoinositide-specific phospholipase C, efhand-like

cl12013
Location:1023 → 1146

BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature
NM_001184883.2 → NP_001171812.1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform 2

See identical proteins and their annotated locations for NP_001171812.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame portion of the 5' coding region, compared to variant 1. This results in a shorter protein (isoform 2), compared to isoform 1.

Source sequence(s)

AP001453, BC032659

Consensus CDS

CCDS53654.1

UniProtKB/Swiss-Prot

Q01970

Related

ENSP00000324660.5, ENST00000325234.5

Conserved Domains (7) summary

cd00275
Location:661 → 776

C2_PLC_like; C2 domain present in Phosphoinositide-specific phospholipases C (PLC)

cd08625
Location:249 → 626

PI-PLCc_beta3; Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3

pfam06631
Location:884 → 921

DUF1154; Protein of unknown function (DUF1154)

pfam08703
Location:962 → 1135

PLC-beta_C; PLC-beta C terminal

pfam09279
Location:158 → 248

EF-hand_like; Phosphoinositide-specific phospholipase C, efhand-like

cl12013
Location:956 → 1079

BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature

cl17171
Location:33 → 82

PH-like; Pleckstrin homology-like domain
NM_001316314.3 → NP_001303243.1 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 3' UTR compared to variant 1. Variants 1 and 3 both encode the same isoform (1).

Source sequence(s)

AP001453, BC146645, CN278806, Z26649

Consensus CDS

CCDS8064.1

UniProtKB/Swiss-Prot

A5PKZ6, G5E960, Q01970, Q8N1A4

Related

ENSP00000443631.1, ENST00000540288.5

Conserved Domains (7) summary

cd00275
Location:728 → 843

C2_PLC_like; C2 domain present in Phosphoinositide-specific phospholipases C (PLC)

cd08625
Location:316 → 693

PI-PLCc_beta3; Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3

cd13361
Location:22 → 149

PH_PLC_beta; Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain

pfam06631
Location:951 → 988

DUF1154; Protein of unknown function (DUF1154)

pfam08703
Location:1029 → 1202

PLC-beta_C; PLC-beta C terminal

pfam09279
Location:225 → 315

EF-hand_like; Phosphoinositide-specific phospholipase C, efhand-like

cl12013
Location:1023 → 1146

BAR; The Bin/Amphiphysin/Rvs (BAR) domain, a dimerization module that binds membranes and detects membrane curvature