InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SMPD1

Summary

InnateDB Protein

IDBP-28683.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SMPD1

Protein Name

sphingomyelin phosphodiesterase 1, acid lysosomal

Synonyms

ASM; ASMASE; NPD;

Species

Homo sapiens

Ensembl Protein

ENSP00000340409

InnateDB Gene

IDBG-28681 (SMPD1)

Protein Structure

UniProt Annotation

Function

Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol. Isoform 2 and isoform 3 have lost catalytic activity.

Subcellular Localization

Lysosome.

Disease Associations

Niemann-Pick disease A (NPDA) [MIM:257200]: An early- onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Niemann-Pick disease type A is a primarily neurodegenerative disorder characterized by onset within the first year of life, mental retardation, digestive disorders, failure to thrive, major hepatosplenomegaly, and severe neurologic symptoms. The severe neurological disorders and pulmonary infections lead to an early death, often around the age of four. Clinical features are variable. A phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. {ECO:0000269PubMed:12556236, ECO:0000269PubMed:1391960, ECO:0000269PubMed:15221801, ECO:0000269PubMed:15877209, ECO:0000269PubMed:1618760, ECO:0000269PubMed:1718266, ECO:0000269PubMed:19405096, ECO:0000269PubMed:2023926, ECO:0000269PubMed:20386867, ECO:0000269PubMed:8680412, ECO:0000269PubMed:8693491, ECO:0000269PubMed:9266408}. Note=The disease is caused by mutations affecting the gene represented in this entry.Niemann-Pick disease B (NPDB) [MIM:607616]: A late-onset lysosomal storage disorder caused by failure to hydrolyze sphingomyelin to ceramide. It results in the accumulation of sphingomyelin and other metabolically related lipids in reticuloendothelial and other cell types throughout the body, leading to cell death. Clinical signs involve only visceral organs. The most constant sign is hepatosplenomegaly which can be associated with pulmonary symptoms. Patients remain free of neurologic manifestations. However, a phenotypic continuum exists between type A (basic neurovisceral) and type B (purely visceral) forms of Niemann-Pick disease, and the intermediate types encompass a cluster of variants combining clinical features of both types A and B. In Niemann-Pick disease type B, onset of the first symptoms occurs in early childhood and patients can survive into adulthood. {ECO:0000269PubMed:12369017, ECO:0000269PubMed:12556236, ECO:0000269PubMed:1301192, ECO:0000269PubMed:15241805, ECO:0000269PubMed:16010684, ECO:0000269PubMed:1618760, ECO:0000269PubMed:16472269, ECO:0000269PubMed:1885770, ECO:0000269PubMed:19050888, ECO:0000269PubMed:19405096, ECO:0000269PubMed:20386867, ECO:0000269PubMed:22613662, ECO:0000269PubMed:8051942, ECO:0000269PubMed:8664904}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 16 experimentally validated interaction(s) in this database.

Experimentally validated
Total	16 [view]
Protein-Protein	13 [view]
Protein-DNA	2 [view]
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004767	sphingomyelin phosphodiesterase activity
GO:0005515	protein binding
GO:0016787	hydrolase activity
GO:0016798	hydrolase activity, acting on glycosyl bonds

Biological Process

GO:0006665	sphingolipid metabolic process
GO:0006684	sphingomyelin metabolic process
GO:0006685	sphingomyelin catabolic process
GO:0006687	glycosphingolipid metabolic process
GO:0007165	signal transduction
GO:0007399	nervous system development
GO:0008219	cell death
GO:0023021	termination of signal transduction
GO:0035307	positive regulation of protein dephosphorylation
GO:0042220	response to cocaine
GO:0042493	response to drug
GO:0043065	positive regulation of apoptotic process
GO:0043407	negative regulation of MAP kinase activity
GO:0044281	small molecule metabolic process
GO:0046513	ceramide biosynthetic process

Cellular Component

GO:0005615	extracellular space
GO:0042599	lamellar body
GO:0043202	lysosomal lumen
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR004843 Calcineurin-like phosphoesterase domain, apaH type
IPR008139 Saposin B
IPR011001 Saposin-like
IPR011160 Sphingomyelin phosphodiesterase
IPR029052 Metallo-dependent phosphatase-like

PFAM

PF00149

PRINTS

PIRSF

PIRSF000948

SMART

SM00741

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt