SMPD1 sphingomyelin phosphodiesterase 1, acid lysosomal [Homo sapiens] - Gene

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Summary

Official Symbol: SMPD1provided by HGNC
Official Full Name: sphingomyelin phosphodiesterase 1, acid lysosomalprovided by HGNC
Primary source: HGNC:11120
See related: Ensembl:ENSG00000166311; HPRD:06353; MIM:607608; Vega:OTTHUMG00000165453
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: ASM; NPD; ASMASE
Summary: The protein encoded by this gene is a lysosomal acid sphingomyelinase that converts sphingomyelin to ceramide. The encoded protein also has phospholipase C activity. Defects in this gene are a cause of Niemann-Pick disease type A (NPA) and Niemann-Pick disease type B (NPB). Multiple transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2010]

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Genomic context

Location :: 11p15.4-p15.1

Sequence :: Chromosome: 11; NC_000011.9 (6411644..6416228)

See SMPD1 in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Acid sphingomyelinase was upregulated in gastric cancer SGC-7901 cells treated with evodiamine, which might contribute to apoptosis.
Title: Acid sphingomyelinase contributes to evodiamine-induced apoptosis in human gastric cancer SGC-7901 cells.
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.
TNF-R1-associated caspase-8 mediates activation of acid sphingomyelinase in late endosomes
Title: Compartmentalization of TNF-receptor 1 signaling: TNF-R1-associated caspase-8 mediates activation of acid sphingomyelinase in late endosomes.
mature L-SMase arises from C-terminal proteolytic processing of pro-aSMase and impaired C-terminal proteolysis may lead to severe defects in L-SMase function.
Title: A novel mechanism of lysosomal acid sphingomyelinase maturation: requirement for carboxyl-terminal proteolytic processing.
Data support a crucial role for Ser(508) in the regulation of S-SMase secretion, and they suggest distinct metabolic roles for S-SMase and L-SMase.
Title: Regulated secretion of acid sphingomyelinase: implications for selectivity of ceramide formation.
Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function.
Title: Syntaxin 4 is required for acid sphingomyelinase activity and apoptotic function.
Report the identification, characterization and genotype/phenotype correlations of eight novel SMPD1 mutations in six unrelated Types A and B Niemann-Pick disease (NPD) patients.
Title: Identification and characterization of eight novel SMPD1 mutations causing types A and B Niemann-Pick disease.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Alcohol-induced activation of sphingomyelin phosphodiesterase occured in human subjects who were alcohol dependent and appears to be responsible for the deleterious effects of ethanol intoxication.
Title: Increased acid sphingomyelinase activity in peripheral blood cells of acutely intoxicated patients with alcohol dependence.
inhibition of both A- and N1-Smase might explain the upregulatory effect of agLDL on TF activation, and suggest that this effect is related, at least in part, to membrane SM enrichment.
Title: Aggregated low density lipoprotein induces tissue factor by inhibiting sphingomyelinase activity in human vascular smooth muscle cells.

Submit: New GeneRIF Correction See all (46)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	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 expression in human glial cells modulates the sphingomyelinase signaling pathway triggered by TNF-alpha	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
P17405	Q13510	ASAH1	HPRD	PubMed
P17405	Q00994	NGFRAP1	HPRD	PubMed
BioGRID:112493	BioGRID:106804	ANXA4	BioGRID	PubMed	Two-hybrid
BioGRID:112493	BioGRID:106807	ANXA7	BioGRID	PubMed	Two-hybrid
BioGRID:112493	BioGRID:120275	DUSP23	BioGRID	PubMed	Two-hybrid
BioGRID:112493	BioGRID:113222	NR1H2	BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
hydrolase activity, acting on glycosyl bonds	IEA Inferred from Electronic Annotation more info
sphingomyelin phosphodiesterase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell death	IEA Inferred from Electronic Annotation more info
ceramide biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
glycosphingolipid metabolic process	TAS Traceable Author Statement more info
negative regulation of MAP kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
nervous system development	TAS Traceable Author Statement more info	PubMed
positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of protein dephosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
response to cocaine	IEA Inferred from Electronic Annotation more info
response to drug	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed
small molecule metabolic process	TAS Traceable Author Statement more info
sphingolipid metabolic process	TAS Traceable Author Statement more info
sphingomyelin catabolic process	IEA Inferred from Electronic Annotation more info
sphingomyelin metabolic process	TAS Traceable Author Statement more info	PubMed
termination of signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
extracellular space	IEA Inferred from Electronic Annotation more info
lamellar body	IEA Inferred from Electronic Annotation more info
lysosomal lumen	TAS Traceable Author Statement more info

General protein information

Preferred Names: sphingomyelin phosphodiesterase

Names: sphingomyelin phosphodiesterase; acid sphingomyelinase

NP_000534.3

EC 3.1.4.12

NP_001007594.2

EC 3.1.4.12

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NCBI Reference Sequences (RefSeq)

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.

Genomic

NG_011780.1 RefSeqGene

Range

4990..9574

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000543.4 → NP_000534.3 sphingomyelin phosphodiesterase isoform 1 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AA746054, AB209775, BI599208, M59916

Consensus CDS

CCDS44531.1

UniProtKB/Swiss-Prot

P17405

UniProtKB/TrEMBL

Q59EN6

Related

ENSP00000340409, OTTHUMP00000229836, ENST00000342245, OTTHUMT00000384205

Conserved Domains (2) summary

cd00842
Location:203 – 498
Blast Score: 987

MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain

smart00741
Location:89 – 162
Blast Score: 121

SapB; Saposin (B) Domains
NM_001007593.2 → NP_001007594.2 sphingomyelin phosphodiesterase isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. The encoded protein (isoform 2) is one amino acid shorter than isoform 1.

Source sequence(s)

AA746054, AB209775, BI599208, M59916

Consensus CDS

CCDS31409.2

UniProtKB/TrEMBL

E9PKS3

UniProtKB/Swiss-Prot

P17405

UniProtKB/TrEMBL

Q59EN6

Related

ENSP00000435350, OTTHUMP00000232789, ENST00000527275, OTTHUMT00000389550

Conserved Domains (2) summary

cd00842
Location:202 – 497
Blast Score: 986

MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain

smart00741
Location:89 – 161
Blast Score: 113

SapB; Saposin (B) Domains

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p5 Primary Assembly

Range

6411644..6416228

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

6070739..6075337

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NR_027400.1: Suppressed sequence

Description

NR_027400.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC068733.12 (128825..133396)	None
genomic	CH471064.2	EAW68726.1
		EAW68727.1
		EAW68728.1
		EAW68729.1
genomic	M59917.1	AAA58378.1
genomic	M81780.1	AAA75008.1
		AAA75009.1
genomic	X63600.1	CAA45145.1
mRNA	AA746054.1	None
mRNA	AB209775.1	BAD93012.1
mRNA	AK292388.1	BAF85077.1
mRNA	AY649987.1	AAV68198.1
mRNA	BC041164.1	AAH41164.1
mRNA	BI599208.1	None
mRNA	BM686561.1	None
mRNA	BU845962.1	None
mRNA	HQ132745.1	ADW08999.1
mRNA	HQ132746.1	ADW09000.1
mRNA	HQ132747.1	ADW09001.1
mRNA	HQ132748.1	ADW09002.1
mRNA	M59916.1	AAA58377.1
mRNA	X52678.1	CAA36901.1
mRNA	X52679.1	CAA36902.1
mRNA	X59960.1	CAA42584.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P17405.4	GenPept	UniProtKB/Swiss-Prot:P17405
Q59EN6	GenPept	UniProtKB/TrEMBL:Q59EN6
Q8IUN0	GenPept	UniProtKB/TrEMBL:Q8IUN0