Smpd3 sphingomyelin phosphodiesterase 3, neutral [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Smpd3provided by MGI
Official Full Name: sphingomyelin phosphodiesterase 3, neutralprovided by MGI
Primary source: MGI:MGI:1927578
See related: Ensembl:ENSMUSG00000031906 AllianceGenome:MGI:1927578
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: fro; Nsm2; nSMase2; 4631433G07Rik
Summary: Enables identical protein binding activity; neutral sphingomyelin phosphodiesterase activity; and phospholipid binding activity. Involved in sphingomyelin metabolic process. Acts upstream of or within several processes, including animal organ development; enzyme linked receptor protein signaling pathway; and sphingolipid metabolic process. Located in Golgi cis cisterna and plasma membrane. Is expressed in several structures, including alimentary system; limb; nervous system; sensory organ; and skeleton. Used to study hypopituitarism; osteogenesis imperfecta; osteogenesis imperfecta type 2; and osteogenesis imperfecta type 3. Orthologous to human SMPD3 (sphingomyelin phosphodiesterase 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in colon adult (RPKM 31.2), large intestine adult (RPKM 26.1) and 17 other tissues See more
Orthologs: human all
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Genomic context

Location:: 8 D3; 8 53.12 cM

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	8	NC_000074.7 (106979180..107064597, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	8	NC_000074.6 (106252548..106337965, complement)

Chromosome 8 - NC_000074.7 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: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Activation of Sphingomyelin Phosphodiesterase 3 in Liver Regeneration Impedes the Progression of Colorectal Cancer Liver Metastasis Via Exosome-Bound Intercellular Transfer of Ceramides.
Title: Activation of Sphingomyelin Phosphodiesterase 3 in Liver Regeneration Impedes the Progression of Colorectal Cancer Liver Metastasis Via Exosome-Bound Intercellular Transfer of Ceramides.
Neuronal deletion of nSMase2 reduces the production of Abeta and directly protects neurons.
Title: Neuronal deletion of nSMase2 reduces the production of Aβ and directly protects neurons.
Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects.
Title: Neutral sphingomyelinase mediates the co-morbidity trias of alcohol abuse, major depression and bone defects.
Neonatal stroke enhances interaction of microglia-derived extracellular vesicles with microglial cells.
Title: Neonatal stroke enhances interaction of microglia-derived extracellular vesicles with microglial cells.
Pharmacological inhibition of nSMase2 reduces brain exosome release and alpha-synuclein pathology in a Parkinson's disease model.
Title: Pharmacological inhibition of nSMase2 reduces brain exosome release and α-synuclein pathology in a Parkinson's disease model.
Activation of neutral sphingomyelinase 2 through hyperglycemia contributes to endothelial apoptosis via vesicle-bound intercellular transfer of ceramides.
Title: Activation of neutral sphingomyelinase 2 through hyperglycemia contributes to endothelial apoptosis via vesicle-bound intercellular transfer of ceramides.
Neutral Sphingomyelinase 2 Heightens Anti-Melanoma Immune Responses and Anti-PD-1 Therapy Efficacy.
Title: Neutral Sphingomyelinase 2 Heightens Anti-Melanoma Immune Responses and Anti-PD-1 Therapy Efficacy.
Regulatory T cells reduce endothelial neutral sphingomyelinase 2 to prevent T-cell migration into tumors.
Title: Regulatory T cells reduce endothelial neutral sphingomyelinase 2 to prevent T-cell migration into tumors.
Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis.
Title: Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis.
Loss of HAMP expression is associated with Chondrodysplasia with Unimpaired Skeletal Mineralization.
Title: Neutral Sphingomyelinase 2 (SMPD3) Deficiency in Mice Causes Chondrodysplasia with Unimpaired Skeletal Mineralization.

Submit: New GeneRIF Correction See all GeneRIFs (43)

Phenotypes

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Associated conditions

Description	Tests
fragilitas ossium GeneReviews: Not available

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (other) (1) 1 citation
Targeted (4) 1 citation
Endonuclease-mediated (5)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Smpd3 (e-PCR), detects polymorphism
- UniSTS:498448

Smpd3 (e-PCR), detects polymorphism
- UniSTS:498449

AI427456 (e-PCR)
- UniSTS:159805

Smpd3 (e-PCR), detects polymorphism
- UniSTS:507236

Smpd3 (e-PCR), detects polymorphism
- UniSTS:502672

UniSTS:498356 (e-PCR)
- UniSTS:498356

Smpd3 (e-PCR), detects polymorphism
- UniSTS:498356

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables neutral sphingomyelin phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylserine binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphoric diester hydrolase activity	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables sphingomyelin phosphodiesterase activity	IBA Inferred from Biological aspect of Ancestor more info
enables sphingomyelin phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
enables sphingomyelin phosphodiesterase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables sphingomyelin phosphodiesterase activity	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within BMP signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within DNA biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within G1 to G0 transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in artery smooth muscle contraction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within bone development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within bone growth	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within bone mineralization	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within bone mineralization	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cartilage development	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cartilage development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cell cycle	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cellular response to hydrogen peroxide	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to magnesium ion	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cellular response to oxidised low-density lipoprotein particle stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to peptide	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to reactive oxygen species	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to redox state	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cellular response to tumor necrosis factor	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within ceramide metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chondrocyte development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within chondrocyte development involved in endochondral bone morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within collagen metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within dentinogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dopamine uptake	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within endochondral ossification	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within extracellular matrix assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hematopoietic progenitor cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lipid metabolic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within lung alveolus development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within lung development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within mitotic nuclear division	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within multicellular organism growth	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within multicellular organism growth	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cytosolic calcium ion concentration	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of hyaluronan biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within ossification	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within peptide hormone secretion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within platelet-derived growth factor receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within polysaccharide transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of ceramide biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of exosomal secretion	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of mitotic nuclear division	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of nitric oxide biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of cartilage development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of hyaluronan biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of leukocyte migration	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within respiratory system development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within signal transduction	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within skeletal system development	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within skeletal system development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within sphingolipid mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within sphingolipid metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within sphingomyelin catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sphingomyelin catabolic process	ISO Inferred from Sequence Orthology more info
involved_in sphingomyelin metabolic process	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within sphingomyelin metabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in sphingomyelin metabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi cis cisterna	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: sphingomyelin phosphodiesterase 3

Names: nSMase-2; neutral sphingomyelinase 2; neutral sphingomyelinase II

NP_067466.1

EC 3.1.4.12

XP_006531304.1

EC 3.1.4.12

XP_011246764.1

EC 3.1.4.12

XP_011246765.1

EC 3.1.4.12

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_021491.4 → NP_067466.1 sphingomyelin phosphodiesterase 3

See identical proteins and their annotated locations for NP_067466.1

Status: VALIDATED

Source sequence(s)

AC124544, AC134615

Consensus CDS

CCDS22634.1

UniProtKB/Swiss-Prot

Q3UTQ5, Q9JJY3

Related

ENSMUSP00000069255.8, ENSMUST00000067512.8

Conserved Domains (2) summary

cd09078
Location:336 → 646

nSMase; Neutral sphingomyelinases (nSMase) catalyze the hydrolysis of sphingomyelin in biological membranes to ceramide and phosphorylcholine

PRK12372
Location:181 → 305

PRK12372; ribonuclease III; Reviewed

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000074.7 Reference GRCm39 C57BL/6J

Range

106979180..107064597 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006531241.5 → XP_006531304.1 sphingomyelin phosphodiesterase 3 isoform X1

See identical proteins and their annotated locations for XP_006531304.1

UniProtKB/Swiss-Prot

Q3UTQ5, Q9JJY3

Conserved Domains (2) summary

cd09078
Location:336 → 646

nSMase; Neutral sphingomyelinases (nSMase) catalyze the hydrolysis of sphingomyelin in biological membranes to ceramide and phosphorylcholine

PRK12372
Location:181 → 305

PRK12372; ribonuclease III; Reviewed
XM_011248462.1 → XP_011246764.1 sphingomyelin phosphodiesterase 3 isoform X1

See identical proteins and their annotated locations for XP_011246764.1

UniProtKB/Swiss-Prot

Q3UTQ5, Q9JJY3

Related

ENSMUSP00000148282.2, ENSMUST00000212896.2

Conserved Domains (2) summary

cd09078
Location:336 → 646

nSMase; Neutral sphingomyelinases (nSMase) catalyze the hydrolysis of sphingomyelin in biological membranes to ceramide and phosphorylcholine

PRK12372
Location:181 → 305

PRK12372; ribonuclease III; Reviewed
XM_011248463.4 → XP_011246765.1 sphingomyelin phosphodiesterase 3 isoform X1

See identical proteins and their annotated locations for XP_011246765.1

UniProtKB/Swiss-Prot

Q3UTQ5, Q9JJY3

Conserved Domains (2) summary

cd09078
Location:336 → 646

nSMase; Neutral sphingomyelinases (nSMase) catalyze the hydrolysis of sphingomyelin in biological membranes to ceramide and phosphorylcholine

PRK12372
Location:181 → 305

PRK12372; ribonuclease III; Reviewed