SMPD2 sphingomyelin phosphodiesterase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SMPD2provided by HGNC
Official Full Name: sphingomyelin phosphodiesterase 2provided by HGNC
Primary source: HGNC:HGNC:11121
See related: Ensembl:ENSG00000135587 MIM:603498; AllianceGenome:HGNC:11121
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: ISC1; NSMASE; NSMASE1
Summary: This gene encodes a protein which was initially identified as a sphingomyelinase based on sequence similarity between bacterial sphingomyelinases and a yeast protein. Subsequent studies showed that its biological function is less likely to be as a sphingomyelinase and instead as a lysophospholipase. [provided by RefSeq, Oct 2009]
Expression: Broad expression in testis (RPKM 17.9), skin (RPKM 6.8) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q21

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (109440724..109443919)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (110618762..110621957)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (109761927..109765122)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Neutral sphingomyelinase inhibition promotes local and network degeneration in vitro and in vivo.
Title: Neutral sphingomyelinase inhibition promotes local and network degeneration in vitro and in vivo.
Genome-wide methylation association with current suicidal ideation in schizophrenia.
Title: Genome-wide methylation association with current suicidal ideation in schizophrenia.
Low NSMase1 expression is associated with hepatocellular carcinoma.
Title: Exosomal neutral sphingomyelinase 1 suppresses hepatocellular carcinoma via decreasing the ratio of sphingomyelin/ceramide.
Interestingly, neutral but not acid sphingomyelinase was mandatory for PorBIA -mediated Neisseria gonorrhoeae invasion into host cells.
Title: Neutral sphingomyelinase 2 is a key factor for PorB-dependent invasion of Neisseria gonorrhoeae.
nSMase1 (sphingomyelin phosphodiesterase 2, SMPD2)has a common central role in ceramide signaling during the stress and cytokine responses and apoptosis.
Title: Stress-induced ceramide generation and apoptosis via the phosphorylation and activation of nSMase1 by JNK signaling.
These data suggest that Ox-LDL activates N-SMase-ceramide signaling pathway, and stimulates phosphorylation of p38 MAPK, leading to apoptosis in vascular smooth muscle cells, which initiates VSMC calcification.
Title: Ceramide mediates Ox-LDL-induced human vascular smooth muscle cell calcification via p38 mitogen-activated protein kinase signaling.
NSM2 plays a key role in the cellular response to hyperosmolar stress, and its activity regulates both cytokine secretion and lipid droplet formation.
Title: Hyperosmolarity-induced lipid droplet formation depends on ceramide production by neutral sphingomyelinase 2.
cells deficient in acid ceramidase (aCDase) also exhibited defects in CCL5 induction, whereas cells deficient in sphingosine kinase-1 and -2 exhibited higher levels of CCL5.
Title: Regulation of CC ligand 5/RANTES by acid sphingomyelinase and acid ceramidase.
nSMase2 has a role in ceramide generation, aberrant apoptosis, and lung injury under cigarette smoke exposure
Title: Neutral sphingomyelinase 2: a novel target in cigarette smoke-induced apoptosis and lung injury.
N-SMase at the cytofacial plasma membrane is an essential element for the proper orientation of PMNs in FMLP gradients, at least in part by polarizing the distribution of Rac 1/2 and RhoA GTPases.
Title: An obligate role for membrane-associated neutral sphingomyelinase activity in orienting chemotactic migration of human neutrophils.

Submit: New GeneRIF Correction See all GeneRIFs (20)

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

EBI GWAS Catalog

Description
Many sequence variants affecting diversity of adult human height. EBI GWAS Catalog EBI GWAS CatalogPubMed

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	Treatment of cells with sphingomyelinase inhibits viral fusion after the engagement of HIV-1 gp120 with CD4 and sphingomyelinase restricts CD4 mobility. This inhibition is dependent on CD4 expression levels	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

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metal ion binding	IEA Inferred from Electronic Annotation 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

Process	Evidence Code	Pubs
involved_in ceramide biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in sphingolipid catabolic process	IBA Inferred from Biological aspect of Ancestor 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

Component	Evidence Code	Pubs
is_active_in caveola	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cell periphery	IBA Inferred from Biological aspect of Ancestor more info
is_active_in endoplasmic reticulum	IBA Inferred from Biological aspect of Ancestor 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 2

Names: N-SMase; lyso-PAF-PLC; lyso-platelet-activating factor-phospholipase C; neutral sphingomyelinase

NP_003071.2

EC 3.1.4.12

XP_011534381.1

EC 3.1.4.12

XP_054212238.1

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_003080.3 → NP_003071.2 sphingomyelin phosphodiesterase 2

See identical proteins and their annotated locations for NP_003071.2

Status: VALIDATED

Source sequence(s)

AJ222801, AL109947, CA314251, DA672570

Consensus CDS

CCDS5075.1

UniProtKB/Swiss-Prot

O60906, Q5TED1, Q9BWR3

UniProtKB/TrEMBL

B2R8U8

Related

ENSP00000258052.3, ENST00000258052.8

Conserved Domains (1) summary

cl00490
Location:14 → 279

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

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_000006.12 Reference GRCh38.p14 Primary Assembly

Range

109440724..109443919

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011536079.2 → XP_011534381.1 sphingomyelin phosphodiesterase 2 isoform X1

Conserved Domains (1) summary

cl00490
Location:6 → 174

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