SMPD3 sphingomyelin phosphodiesterase 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SMPD3provided by HGNC
Official Full Name: sphingomyelin phosphodiesterase 3provided by HGNC
Primary source: HGNC:HGNC:14240
See related: Ensembl:ENSG00000103056 MIM:605777; AllianceGenome:HGNC:14240
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: NSMASE2
Summary: Enables sphingomyelin phosphodiesterase activity. Involved in sphingomyelin catabolic process. Predicted to be located in plasma membrane. Predicted to be active in cytoplasm. Biomarker of pulmonary emphysema. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in duodenum (RPKM 22.0), small intestine (RPKM 21.4) and 11 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 16q22.1

Exon count:: 13

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	16	NC_000016.10 (68358327..68448508, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	16	NC_060940.1 (74154167..74244330, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	16	NC_000016.9 (68392230..68482411, complement)

Chromosome 16 - NC_000016.10 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Role of Neutral Sphingomyelinase-2 (NSM2) in the Control of Neutral Lipid Storage in T Cells.
Title: The Role of Neutral Sphingomyelinase-2 (NSM2) in the Control of Neutral Lipid Storage in T Cells.
Regulated translocation of neutral sphingomyelinase-2 to the plasma membrane drives insulin resistance in steatotic hepatocytes.
Title: Regulated translocation of neutral sphingomyelinase-2 to the plasma membrane drives insulin resistance in steatotic hepatocytes.
Inhibition of Neutral Sphingomyelinase 2 by Novel Small Molecule Inhibitors Results in Decreased Release of Extracellular Vesicles by Vascular Smooth Muscle Cells and Attenuated Calcification.
Title: Inhibition of Neutral Sphingomyelinase 2 by Novel Small Molecule Inhibitors Results in Decreased Release of Extracellular Vesicles by Vascular Smooth Muscle Cells and Attenuated Calcification.
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.
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.
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.
demonstrate that PS binding at the N-terminal and juxtamembrane regions of nSMase2 rather acts as a conformational switch leading to interdomain interactions that are critical to enzyme activation
Title: The juxtamembrane linker in neutral sphingomyelinase-2 functions as an intramolecular allosteric switch that activates the enzyme.
Compounds against human nSMase2 we identified.
Title: DPTIP, a newly identified potent brain penetrant neutral sphingomyelinase 2 inhibitor, regulates astrocyte-peripheral immune communication following brain inflammation.
These findings identify neutral sphingomyelinase 2 as essential in TCR signaling when dynamic cytoskeletal reorganization promotes continued lateral and vertical supply of TCR signaling components
Title: The Neutral Sphingomyelinase 2 Is Required to Polarize and Sustain T Cell Receptor Signaling.

Submit: New GeneRIF Correction See all GeneRIFs (40)

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

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	A redox-regulated translocation of neutral sphingomyelinase-2 to the plasma membrane is required for HIV-1 gp120-induced enlargement and stabilization of the structure of lipid microdomains on dendrites	PubMed
	env	HIV-1 gp120 binding to CXCR4 induces NADPH oxidase-mediated production of superoxide radicals in neurons, which is involved in the activation of neutral sphingomyelinase	PubMed
	env	In human primary neurons, HIV-1 gp120 induces the activation of sphingomyelinases (primarily neutral sphingomyelinase); antisense knockdown of neutral sphingomyelinase markedly inhibits gp120-mediated apoptosis and cell death of primary neurons	PubMed
Nef	nef	HIV-1 Nef inhibits sphingomyelinase activity in human podocyte	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

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

SHGC-61160 (e-PCR)
- UniSTS:37150

RH123348 (e-PCR)
- UniSTS:135725

RH92696 (e-PCR)
- UniSTS:93045

RH48608 (e-PCR)
- UniSTS:62362

G59890 (e-PCR)
- UniSTS:137172

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables identical protein binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables neutral sphingomyelin phosphodiesterase activity	IEA Inferred from Electronic Annotation more info
enables phosphatidic acid binding	ISS Inferred from Sequence or Structural Similarity more info
enables phosphatidylserine binding	ISS Inferred from Sequence or Structural Similarity more info
enables phosphoric diester hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
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	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in BMP signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in DNA biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in G1 to G0 transition	IEA Inferred from Electronic Annotation more info
involved_in bone growth	IEA Inferred from Electronic Annotation more info
involved_in bone mineralization	IEA Inferred from Electronic Annotation more info
involved_in cellular response to hydrogen peroxide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to magnesium ion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to oxidised low-density lipoprotein particle stimulus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to peptide	IEA Inferred from Electronic Annotation more info
involved_in cellular response to redox state	IEA Inferred from Electronic Annotation more info
involved_in cellular response to tumor necrosis factor	IEA Inferred from Electronic Annotation more info
involved_in ceramide metabolic process	IEA Inferred from Electronic Annotation more info
involved_in chondrocyte development involved in endochondral bone morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in collagen metabolic process	IEA Inferred from Electronic Annotation more info
involved_in dentinogenesis	IEA Inferred from Electronic Annotation more info
involved_in endochondral ossification	IEA Inferred from Electronic Annotation more info
involved_in extracellular matrix assembly	IEA Inferred from Electronic Annotation more info
involved_in hematopoietic progenitor cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in lung alveolus development	IEA Inferred from Electronic Annotation more info
involved_in mitotic nuclear division	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of hyaluronan biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IEA Inferred from Electronic Annotation more info
involved_in peptide hormone secretion	IEA Inferred from Electronic Annotation more info
involved_in platelet-derived growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in polysaccharide transport	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of exosomal secretion	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of mitotic nuclear division	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in regulation of cartilage development	IEA Inferred from Electronic Annotation more info
involved_in regulation of leukocyte migration	IEA Inferred from Electronic Annotation more info
involved_in sphingolipid mediated signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in sphingomyelin catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in sphingomyelin metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in sphingomyelin metabolic process	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in Golgi cis cisterna	IEA Inferred from Electronic Annotation more info
located_in Golgi membrane	IEA Inferred from Electronic Annotation more info
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 plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: sphingomyelin phosphodiesterase 3

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

NP_061137.1

EC 3.1.4.12

XP_005256089.1

EC 3.1.4.12

XP_011521509.1

EC 3.1.4.12

XP_011521512.1

EC 3.1.4.12

XP_016878895.1

EC 3.1.4.12

XP_047290292.1

EC 3.1.4.12

XP_047290293.1

EC 3.1.4.12

XP_047290294.1

EC 3.1.4.12

XP_047290295.1

EC 3.1.4.12

XP_047290296.1

EC 3.1.4.12

XP_047290297.1

EC 3.1.4.12

XP_054169385.1

EC 3.1.4.12

XP_054169386.1

EC 3.1.4.12

XP_054169387.1

EC 3.1.4.12

XP_054169388.1

EC 3.1.4.12

XP_054169389.1

EC 3.1.4.12

XP_054169390.1

EC 3.1.4.12

XP_054169391.1

EC 3.1.4.12

XP_054169392.1

EC 3.1.4.12

XP_054169393.1

EC 3.1.4.12

XP_054169394.1

EC 3.1.4.12

XP_054169395.1

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_018667.4 → NP_061137.1 sphingomyelin phosphodiesterase 3

See identical proteins and their annotated locations for NP_061137.1

Status: VALIDATED

Source sequence(s)

AC099521, AK289651, BC112238

Consensus CDS

CCDS10867.1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6

Related

ENSP00000219334.5, ENST00000219334.10

Conserved Domains (2) summary

cd09078
Location:338 → 646

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

PHA03307
Location:171 → 321

PHA03307; transcriptional regulator ICP4; Provisional

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000016.10 Reference GRCh38.p14 Primary Assembly

Range

68358327..68448508 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011523207.2 → XP_011521509.1 sphingomyelin phosphodiesterase 3 isoform X1

See identical proteins and their annotated locations for XP_011521509.1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6

Conserved Domains (2) summary

cd09078
Location:338 → 646

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

PHA03307
Location:171 → 321

PHA03307; transcriptional regulator ICP4; Provisional
XM_047434339.1 → XP_047290295.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_017023406.2 → XP_016878895.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6

Conserved Domains (2) summary

cd09078
Location:338 → 646

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

PHA03307
Location:171 → 321

PHA03307; transcriptional regulator ICP4; Provisional
XM_047434340.1 → XP_047290296.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_047434338.1 → XP_047290294.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_047434336.1 → XP_047290292.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6

Related

ENSP00000455955.1, ENST00000563226.1
XM_047434337.1 → XP_047290293.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_005256032.4 → XP_005256089.1 sphingomyelin phosphodiesterase 3 isoform X1

See identical proteins and their annotated locations for XP_005256089.1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6

Conserved Domains (2) summary

cd09078
Location:338 → 646

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

PHA03307
Location:171 → 321

PHA03307; transcriptional regulator ICP4; Provisional
XM_047434341.1 → XP_047290297.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_011523210.3 → XP_011521512.1 sphingomyelin phosphodiesterase 3 isoform X2

Conserved Domains (1) summary

cl00490
Location:338 → 441

EEP; Exonuclease-Endonuclease-Phosphatase (EEP) domain superfamily

RNA

XR_933371.3 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060940.1 Alternate T2T-CHM13v2.0

Range

74154167..74244330 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054313412.1 → XP_054169387.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313415.1 → XP_054169390.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313410.1 → XP_054169385.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313416.1 → XP_054169391.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313414.1 → XP_054169389.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313418.1 → XP_054169393.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313413.1 → XP_054169388.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313411.1 → XP_054169386.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313417.1 → XP_054169392.1 sphingomyelin phosphodiesterase 3 isoform X1

UniProtKB/Swiss-Prot

B7ZL82, Q2M1S8, Q9NY59

UniProtKB/TrEMBL

A8K0T6
XM_054313420.1 → XP_054169395.1 sphingomyelin phosphodiesterase 3 isoform X2
XM_054313419.1 → XP_054169394.1 sphingomyelin phosphodiesterase 3 isoform X2