Sphingomyelin phosphodiesterase | Enzymes | IUPHAR/BPS Guide to PHARMACOLOGY

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Ceramide turnover
Sphingomyelin phosphodiesterase

Sphingomyelin phosphodiesterase C

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

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Also known as sphingomyelinase.

Enzymes

2514

sphingomyelin phosphodiesterase 1 C Show summary »« Hide summary

Target Id

2514

Nomenclature

sphingomyelin phosphodiesterase 1

Previous and unofficial names

Acid sphingomyelinase | ASM | aSMase | Zn-SMase | sphingomyelin phosphodiesterase 1, acid lysosomal

Genes

SMPD1 (Hs), Smpd1 (Mm), Smpd1 (Rn)

Ensembl ID

ENSG00000166311 (Hs), ENSMUSG00000037049 (Mm), ENSRNOG00000017977 (Rn)

UniProtKB AC

P17405 (Hs), Q04519 (Mm), Q5XIA6 (Rn)

EC number

3.1.4.12

sphingomyelin -> ceramide + phosphocholine

Inhibitors

compound 21b [PMID: 31944697] pIC₅₀ 6.5 [2]

WJYK50 pIC₅₀ 6.3 [1], 6.1 [2]

sphingomyelin phosphodiesterase 2 C Show summary »« Hide summary

Target Id

2515

Nomenclature

sphingomyelin phosphodiesterase 2

Previous and unofficial names

Genes

SMPD2 (Hs), Smpd2 (Mm), Smpd2 (Rn)

Ensembl ID

ENSG00000135587 (Hs), ENSMUSG00000019822 (Mm), ENSRNOG00000000306 (Rn)

UniProtKB AC

O60906 (Hs), O70572 (Mm), Q9ET64 (Rn)

EC number

3.1.4.12

sphingomyelin -> ceramide + phosphocholine

Inhibitors

inhibitor A [PMID: 12482429] pK_i 5.8 [3] - Bovine

sphingomyelin phosphodiesterase 3 C Show summary »« Hide summary

Target Id

2516

Nomenclature

sphingomyelin phosphodiesterase 3

Previous and unofficial names

Genes

SMPD3 (Hs), Smpd3 (Mm), Smpd3 (Rn)

Ensembl ID

ENSG00000103056 (Hs), ENSMUSG00000031906 (Mm), ENSRNOG00000000257 (Rn)

UniProtKB AC

Q9NY59 (Hs), Q9JJY3 (Mm), O35049 (Rn)

EC number

3.1.4.12

sphingomyelin -> ceramide + phosphocholine

sphingomyelin phosphodiesterase 4 C Show summary »« Hide summary

Target Id

2517

Nomenclature

sphingomyelin phosphodiesterase 4

Previous and unofficial names

NET13 | Neutral sphingomyelinase III | NSMASE3 | sphingomyelin phosphodiesterase 4, neutral membrane (neutral sphingomyelinase-3) | sphingomyelin phosphodiesterase 4, neutral membrane

Genes

SMPD4 (Hs), Smpd4 (Mm), Smpd4 (Rn)

Ensembl ID

ENSG00000136699 (Hs), ENSMUSG00000005899 (Mm), ENSRNOG00000001875 (Rn)

UniProtKB AC

Q9NXE4 (Hs), Q6ZPR5 (Mm)

EC number

3.1.4.12

sphingomyelin -> ceramide + phosphocholine

sphingomyelin phosphodiesterase acid-like 3A C Show summary »« Hide summary

Target Id

2518

Nomenclature

sphingomyelin phosphodiesterase acid-like 3A

Previous and unofficial names

Acid sphingomyelinase-like phosphodiesterase 3a | ASM3A | ASM-like phosphodiesterase 3a | sphingomyelin phosphodiesterase, acid-like 3A | sphingomyelin phosphodiesterase

Genes

SMPDL3A (Hs), Smpdl3a (Mm), Smpdl3a (Rn)

Ensembl ID

ENSG00000172594 (Hs), ENSMUSG00000019872 (Mm), ENSRNOG00000066945 (Rn)

UniProtKB AC

Q92484 (Hs), P70158 (Mm), Q641Z7 (Rn)

EC number

3.1.4.-

sphingomyelin -> ceramide + phosphocholine

sphingomyelin phosphodiesterase acid-like 3B C Show summary »« Hide summary

Target Id

2519

Nomenclature

sphingomyelin phosphodiesterase acid-like 3B

Previous and unofficial names

ASML3B | ASM-like phosphodiesterase 3b | sphingomyelin phosphodiesterase, acid-like 3B | sphingomyelin phosphodiesterase

Genes

SMPDL3B (Hs), Smpdl3b (Mm), Smpdl3b (Rn)

Ensembl ID

ENSG00000130768 (Hs), ENSMUSG00000028885 (Mm), ENSRNOG00000042326 (Rn)

UniProtKB AC

Q92485 (Hs), P58242 (Mm), Q4V7D9 (Rn)

EC number

3.1.4.-

sphingomyelin -> ceramide + phosphocholine

References

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1. Yang K, Nong K, Gu Q, Dong J, Wang J. (2018) Discovery of N-hydroxy-3-alkoxybenzamides as direct acid sphingomyelinase inhibitors using a ligand-based pharmacophore model. Eur J Med Chem, 151: 389-400. [PMID:29649738]

2. Yang K, Yu J, Nong K, Wang Y, Niu A, Chen W, Dong J, Wang J. (2020) Discovery of Potent, Selective, and Direct Acid Sphingomyelinase Inhibitors with Antidepressant Activity. J Med Chem, 63 (3): 961-974. [PMID:31944697]

3. Yokomatsu T, Murano T, Akiyama T, Koizumi J, Shibuya S, Tsuji Y, Soeda S, Shimeno H. (2003) Synthesis of non-competitive inhibitors of sphingomyelinases with significant activity. Bioorg Med Chem Lett, 13 (2): 229-36. [PMID:12482429]

How to cite this family page

Database page citation (select format):

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Fabbro D, Gibb AJ, Kelly E, Mathie AA, Peach CJ, Veale EL, Armstrong JF, Faccenda E, Harding SD, Southan C, Davies JA et al. (2025) The Concise Guide to PHARMACOLOGY 2025/26: Enzymes. Br J Pharmacol. 182: S307-S403.