General Information of the Ferroptosis Regulator (ID: REG10109)
Regulator Name Sphingomyelin phosphodiesterase (SMPD1)
Synonyms
Acid sphingomyelinase
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Gene Name SMPD1
Gene ID 6609
Regulator Type Protein coding
Uniprot ID P17405
Sequence
MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAE
AHPLSPQGHPARLHRIVPRLRDVFGWGNLTCPICKGLFTAINLGLKKEPNVARVGSVAIK
LCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISL
PTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASR
PGAGYWGEYSKCDLPLRTLESLLSGLGPAGPFDMVYWTGDIPAHDVWHQTRQDQLRALTT
VTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEAL
RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGD
KVHIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAV
AFLAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYR
ARETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLS
ARADSPALCRHLMPDGSLPEAQSLWPRPLFC

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Family Acid sphingomyelinase family
Function
Converts sphingomyelin to ceramide. Exists as two enzymatic forms that arise from alternative trafficking of a single protein precursor, one that is targeted to the endolysosomal compartment, whereas the other is released extracellularly. However, in response to various forms of stress, lysosomal exocytosis may represent a major source of the secretory form.

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HGNC ID
HGNC:11120
KEGG ID hsa:6609
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
SMPD1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
Browse Drug
Phospholipid hydroperoxide glutathione peroxidase (GPX4) [Suppressor]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Fibrosarcoma ICD-11: 2B53
Responsed Drug Erastin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM ( SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [1]
Target for Ferroptosis Marker/Suppressor
Responsed Disease Fibrosarcoma ICD-11: 2B53
Responsed Drug Erastin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM (SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation.
Unspecific Target [Unspecific Target]
In total 1 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Injury of intra-abdominal organs ICD-11: NB91
Responsed Drug VBIT-12 Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
mPHs (Mouse primary hepatocytes)
In Vivo Model
Male C57 BL /6J mice (6-8 weeks; 18-22 g each) were procured from the Experimental Animal Centre of Shanghai SLAC. All mice were fed in laboratory in vivo facilities with ad libitum food and water, within a temperature-/humidity-regulated environment (22 ± 1 ; Rh. = 65 ± 5%), adopting a 12-h circadian cycling process. Mice fasted overnight for 12 h and were randomly divided into different groups.

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Response regulation The relative amounts of CER and CL in the liver tissues of VBIT-12- or UAMC3203-treated APAP-injured mice markedly increased compared to those of APAP-injured mice. Smpd1 was the CER synthesis gene that was most significantly upregulated by UAMC3203 and VBIT-12. In summary, protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury.
Fibrosarcoma [ICD-11: 2B53]
In total 2 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Sphingomyelin phosphodiesterase (SMPD1) Protein coding
Responsed Drug Erastin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM ( SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation.
Experiment 2 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Sphingomyelin phosphodiesterase (SMPD1) Protein coding
Responsed Drug Erastin Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM (SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation.
Injury of intra-abdominal organs [ICD-11: NB91]
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Sphingomyelin phosphodiesterase (SMPD1) Protein coding
Responsed Drug VBIT-12 Investigative
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
mPHs (Mouse primary hepatocytes)
In Vivo Model
Male C57 BL /6J mice (6-8 weeks; 18-22 g each) were procured from the Experimental Animal Centre of Shanghai SLAC. All mice were fed in laboratory in vivo facilities with ad libitum food and water, within a temperature-/humidity-regulated environment (22 ± 1 ; Rh. = 65 ± 5%), adopting a 12-h circadian cycling process. Mice fasted overnight for 12 h and were randomly divided into different groups.

    Click to Show/Hide
Response regulation The relative amounts of CER and CL in the liver tissues of VBIT-12- or UAMC3203-treated APAP-injured mice markedly increased compared to those of APAP-injured mice. Smpd1 was the CER synthesis gene that was most significantly upregulated by UAMC3203 and VBIT-12. In summary, protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury.
Erastin [Investigative]
In total 2 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
Responsed Disease Fibrosarcoma ICD-11: 2B53
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM ( SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation.
Experiment 2 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Phospholipid hydroperoxide glutathione peroxidase (GPX4) Suppressor
Responsed Disease Fibrosarcoma ICD-11: 2B53
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Autophagy hsa04140
Cell Process Cell ferroptosis
Cell autophagy
In Vitro Model
HT-1080 cells Fibrosarcoma Homo sapiens CVCL_0317
Calu-1 cells Lung squamous cell carcinoma Homo sapiens CVCL_0608
HeLa cells Endocervical adenocarcinoma Homo sapiens CVCL_0030
Response regulation Erastin (Era) treatment results in the activation of ASM and generation of ceramide, which are required for the Era-induced reactive oxygen species (ROS) generation and LPO in fibrosarcoma. ASM (SMPD1)-mediated activation of autophagy plays a critical role in ferroptosis inducers (FINs)-induced glutat hione peroxidase 4 (GPX4) degradation and ferroptosis activation.
VBIT-12 [Investigative]
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [2]
Drug for Ferroptosis Suppressor
Response Target Unspecific Target
Responsed Disease Injury of intra-abdominal organs ICD-11: NB91
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
mPHs (Mouse primary hepatocytes)
In Vivo Model
Male C57 BL /6J mice (6-8 weeks; 18-22 g each) were procured from the Experimental Animal Centre of Shanghai SLAC. All mice were fed in laboratory in vivo facilities with ad libitum food and water, within a temperature-/humidity-regulated environment (22 ± 1 ; Rh. = 65 ± 5%), adopting a 12-h circadian cycling process. Mice fasted overnight for 12 h and were randomly divided into different groups.

    Click to Show/Hide
Response regulation The relative amounts of CER and CL in the liver tissues of VBIT-12- or UAMC3203-treated APAP-injured mice markedly increased compared to those of APAP-injured mice. Smpd1 was the CER synthesis gene that was most significantly upregulated by UAMC3203 and VBIT-12. In summary, protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury.
References
Ref 1 Acid sphingomyelinase-dependent autophagic degradation of GPX4 is critical for the execution of ferroptosis. Cell Death Dis. 2021 Jan 7;12(1):26. doi: 10.1038/s41419-020-03297-w.
Ref 2 Protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury. Cell Biol Toxicol. 2022 Jun;38(3):505-530. doi: 10.1007/s10565-021-09624-x. Epub 2021 Aug 17.