Protein:SMPD1 |
Protein Summary |
 Gene summary |
| Gene name: SMPD1 | ASpdb.0 ID: 6609 | Gene | Gene symbol | SMPD1 | Gene ID | 6609 |
| Gene name | sphingomyelin phosphodiesterase 1 |
| Synonyms | ASM|ASMASE|NPD |
| Cytomap | 11p15.4 |
| Type of gene | protein-coding |
| Description | sphingomyelin phosphodiesteraseNiemann-Pick type A/Bacid sphingomyelinasesphingomyelin phosphodiesterase 1, acid lysosomal |
| Modification date | 20240403 |
| UniProtAcc | P17405 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | SMPD1 | GO:0001778 | plasma membrane repair | 20530211 |
| Gene | SMPD1 | GO:0004767 | sphingomyelin phosphodiesterase activity | 9660788|21098024|22573858|33163980 |
| Gene | SMPD1 | GO:0005615 | extracellular space | 33163980 |
| Gene | SMPD1 | GO:0005615 | extracellular space | 8702487|9660788|16787399|17303575|20530211|20807762|21098024|22573858|27659707 |
| Gene | SMPD1 | GO:0005764 | lysosome | 33163980 |
| Gene | SMPD1 | GO:0005764 | lysosome | 9660788|16787399|18815062|20530211|20807762|20956541|21098024|27659707 |
| Gene | SMPD1 | GO:0005768 | endosome | 20956541 |
| Gene | SMPD1 | GO:0005886 | plasma membrane | 20956541 |
| Gene | SMPD1 | GO:0006685 | sphingomyelin catabolic process | 18815062|20807762|22573858 |
| Gene | SMPD1 | GO:0008270 | zinc ion binding | 8702487|9660788 |
| Gene | SMPD1 | GO:0009615 | response to virus | 22573858 |
| Gene | SMPD1 | GO:0034340 | response to type I interferon | 20807762 |
| Gene | SMPD1 | GO:0034612 | response to tumor necrosis factor | 20807762 |
| Gene | SMPD1 | GO:0034644 | cellular response to UV | 17303575 |
| Gene | SMPD1 | GO:0036019 | endolysosome | 17303575 |
| Gene | SMPD1 | GO:0042060 | wound healing | 20530211 |
| Gene | SMPD1 | GO:0045807 | positive regulation of endocytosis | 20530211 |
| Gene | SMPD1 | GO:0046513 | ceramide biosynthetic process | 17303575|18815062|20807762|33163980 |
| Gene | SMPD1 | GO:0046598 | positive regulation of viral entry into host cell | 33163980 |
| Gene | SMPD1 | GO:0046718 | symbiont entry into host cell | 33163980 |
| Gene | SMPD1 | GO:0046718 | symbiont entry into host cell | 33163980 |
| Gene | SMPD1 | GO:0046718 | symbiont entry into host cell | 22573858 |
| Gene | SMPD1 | GO:0061750 | acid sphingomyelin phosphodiesterase activity | 8702487|17303575|18815062|20807762 |
| Gene | SMPD1 | GO:0070555 | response to interleukin-1 | 20807762 |
| Gene | SMPD1 | GO:0071277 | cellular response to calcium ion | 20530211 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P17405-1 | P17405-1_5jg8_B.pdb | 5JG8 | X-ray | 2.8 | B | 84 | 613 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P17405 | SMPD1 | P17405-1 | P17405-2 | 631 | 587 | 365 | 376 | Substitution | IGGFYALSPYPG | YLSSVETQEGKR | 365 | 376 |
| P17405 | SMPD1 | P17405-1 | P17405-2 | 631 | 587 | 377 | 420 | Deletion | none | none | 376 | 376 |
| P17405 | SMPD1 | P17405-1 | P17405-3 | 631 | 575 | 365 | 420 | Deletion | none | none | 364 | 364 |
| P17405 | SMPD1 | P17405-1 | P17405-4 | 631 | 630 | 106 | 106 | Deletion | none | none | 105 | 105 |
| Multiple sequence alignment of our canonical and alternatively spliced SMPD1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of SMPD1 |
| UniProt-id | ENSG | ENST | ENSP |
| P17405-1 | ENSG00000166311.10 | ENST00000342245.9 | ENSP00000340409.4 |
| P17405-4 | ENSG00000166311.10 | ENST00000527275.5 | ENSP00000435350.1 |
| UniProt-id | NM ID | NP ID |
| P17405-1 | NM_000543.4 | NP_000534.3 |
| P17405-4 | NM_001007593.2 | NP_001007594.2 |
| Amino acid sequences of our canonical and alternatively spliced SMPD1 |
| accession_id | Protein sequence |
| P17405-1 | MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAEAHPLSPQGHPARLHRIVPRLRDVFGWGNLT CPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISL PTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPGAGYWGEYSKCDLPLRTLESLLSGLGPAG PFDMVYWTGDIPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEAL RTLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYYRIVARYEN TLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYR ARETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSARADSPALCRHLMPDGSLPEAQSLWPRPLF |
| P17405-2 | MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAEAHPLSPQGHPARLHRIVPRLRDVFGWGNLT CPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISL PTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPGAGYWGEYSKCDLPLRTLESLLSGLGPAG PFDMVYWTGDIPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEAL RTLRYLSSVETQEGKRKVHIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLN PGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYRARETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSE |
| P17405-3 | MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAEAHPLSPQGHPARLHRIVPRLRDVFGWGNLT CPICKGLFTAINLGLKKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISL PTVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPGAGYWGEYSKCDLPLRTLESLLSGLGPAG PFDMVYWTGDIPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEAL RTLRKVHIIGHIPPGHCLKSWSWNYYRIVARYENTLAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYRVYQIDGNY SGSSHVVLDHETYILNLTQANIPGAIPHWQLLYRARETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLC |
| P17405-4 | MPRYGASLRQSCPRSGREQGQDGTAGAPGLLWMGLVLALALALALALALSDSRVLWAPAEAHPLSPQGHPARLHRIVPRLRDVFGWGNLT CPICKGLFTAINLGLKEPNVARVGSVAIKLCNLLKIAPPAVCQSIVHLFEDDMVEVWRRSVLSPSEACGLLLGSTCGHWDIFSSWNISLP TVPKPPPKPPSPPAPGAPVSRILFLTDLHWDHDYLEGTDPDCADPLCCRRGSGLPPASRPGAGYWGEYSKCDLPLRTLESLLSGLGPAGP FDMVYWTGDIPAHDVWHQTRQDQLRALTTVTALVRKFLGPVPVYPAVGNHESTPVNSFPPPFIEGNHSSRWLYEAMAKAWEPWLPAEALR TLRIGGFYALSPYPGLRLISLNMNFCSRENFWLLINSTDPAGQLQWLVGELQAAEDRGDKVHIIGHIPPGHCLKSWSWNYYRIVARYENT LAAQFFGHTHVDEFEVFYDEETLSRPLAVAFLAPSATTYIGLNPGYRVYQIDGNYSGSSHVVLDHETYILNLTQANIPGAIPHWQLLYRA RETYGLPNTLPTAWHNLVYRMRGDMQLFQTFWFLYHKGHPPSEPCGTPCRLATLCAQLSARADSPALCRHLMPDGSLPEAQSLWPRPLFC |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| SMPD1 (go to UniProt):P17405 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P17405 | Domain | 87 | 171 | Note=Saposin B-type;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00415 | Type=Deletion;Start=106;End=106 |
Gene Isoform Structures and Expression Levels for SMPD1 |
| Gene structures of our canonical and alternative spliced genes of SMPD1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P17405-1 |
| 3D view using mol* of P17405-2 |
| 3D view using mol* of P17405-3 |
| 3D view using mol* of P17405-4 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P17405-1 |
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| pLDDT distribution across the protein length of P17405-2 |
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| pLDDT distribution across the protein length of P17405-3 |
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| pLDDT distribution across the protein length of P17405-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P17405-1 |
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| Ramachandran plot of P17405-2 |
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| Ramachandran plot of P17405-3 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P17405-1 | 1.059 | 337 | 1.086 | 888.37 | 0.534 | 0.759 | 1.002 | 0.876 | 0.948 | 0.924 | 0.981 | 26,27,28,30,31,32,33,34,35,37,38,140,144,148,152,1 73,320,326,327,385,388,389,390,391,392,395,428,431 ,432,459,460,462,464,491,492,493,570,573,576,577,5 80,581,582,583,584,585,586,587,590,593,594,596,597 ,600,602,603,604,605,606,608,624,625,626,627,628,6 29,630,631 |
| P17405-2 | 1.14 | 167 | 1.116 | 323.449 | 0.41 | 0.908 | 1.222 | 1.235 | 1.129 | 1.094 | 0.784 | 14,15,16,17,18,31,387,388,416,420,422,532,553,556, 558,559,560,561,562,564,581,582,583,584,585,586 |
| P17405-3 | 1.078 | 534 | 1.145 | 1792.175 | 0.614 | 0.712 | 0.854 | 1.229 | 0.68 | 1.807 | 1.146 | 29,30,32,33,34,35,36,37,39,40,42,43,44,47,101,105, 114,115,117,118,121,122,125,127,128,132,133,136,13 7,140,141,144,145,147,148,152,153,161,170,171,172, 173,174,175,176,177,210,226,280,284,286,318,320,32 1,326,327,329,368,370,371,372,374,375,376,377,378, 379,380,381,383,385,386,387,401,403,404,405,406,40 8,410,415,434,435,436,437,517,520,521,524,525,526, 527,534,537,538,541,544,546,547,548,549,568,569,57 0,571,572,573,574,575 |
| P17405-4 | 1.138 | 261 | 1.223 | 884.597 | 0.562 | 0.755 | 0.948 | 2.391 | 0.523 | 4.576 | 1.166 | 27,29,30,32,33,34,35,36,37,39,40,42,43,105,113,114 ,116,117,120,121,124,126,127,131,132,135,136,139,1 40,143,144,147,151,152,169,171,172,173,174,175,176 ,388,389,391,394,397,398,433,434,435,436,438,439,4 42,470,601 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P17405-1_P17405-1_5jg8_B.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P17405-1_5jg8_B_P17405-2.pdb |
| 3D view using mol* of P17405-1_5jg8_B_P17405-3.pdb |
| 3D view using mol* of P17405-1_5jg8_B_P17405-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P17405-1_P17405-2.pdb |
| 3D view using mol* of P17405-1_P17405-3.pdb |
| 3D view using mol* of P17405-1_P17405-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P17405-1_vs_P17405-2.png |
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| ./stats/secondary_structure/figure/P17405-1_vs_P17405-3.png |
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| ./stats/secondary_structure/figure/P17405-1_vs_P17405-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P17405-1_vs_P17405-2.png |
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| ./stats/relative_asa/P17405-1_vs_P17405-3.png |
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| ./stats/relative_asa/P17405-1_vs_P17405-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to SMPD1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P17405 | SMPD1 | DB14009 | Medical Cannabis | experimental, investigational | inducer |
| P17405 | SMPD1 | DB00381 | Amlodipine | approved | inhibitor |
| P17405 | SMPD1 | DB00477 | Chlorpromazine | approved, investigational, vet_approved | inhibitor |
| P17405 | SMPD1 | DB01151 | Desipramine | approved, investigational | inhibitor |
Related Diseases to SMPD1 |
| Previous studies relating to the alternative splicing of SMPD1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| SMPD1 | 8702487 | Zn2+-stimulated sphingomyelinase is secreted by many cell types and is a product of the acid sphingomyelinase gene. | Mammalian sphingomyelinases have been implicated in many important physiological and pathophysiological processes. Although several mammalian sphingomyelinases have been identified and studied, one of these, an acidic Zn2+-stimulated sphingomyelinase (Zn-SMase) originally found in fetal bovine serum, has received little attention since its first and only report 7 years ago. We now show that Zn-SMase activity is secreted by human and murine macrophages, human skin fibroblasts, microglial cells, and several other cells in culture and is markedly up-regulated during differentiation of human monocytes to macrophages. Remarkably, peritoneal macrophages from mice in which the acid SMase gene had been disrupted by homologous recombination secreted no Zn-SMase activity, indicating that this enzyme and the intracellular lysosomal SMase, which is Zn-independent, arise from the same gene. Furthermore, skin fibroblasts from patients with types A and B Niemann-Pick disease, which are known to lack lysosomal SMase activity, also lack Zn-SMase activity in their conditioned media. Chinese hamster ovary cells stably transfected with a cDNA encoding lysosomal SMase massively overexpress both cellular lysosomal SMase and secreted Zn-SMase activities. Thus, Zn-SMase arises independently of alternative splicing, suggesting a post-translational process. In summary, a wide variety of cell types secrete Zn-SMase activity, which arises from the same gene as lysosomal SMase. This secreted enzyme may play roles in physiological and pathophysiological processes involving extracellular sphingomyelin hydrolysis. | D009542 | Niemann-Pick Diseases |
| SMPD1 | 25898364 | Alternative splicing of SMPD1 in human sepsis. | Acid sphingomyelinase (ASM or sphingomyelin phosphodiesterase, SMPD) activity engages a critical role for regulation of immune response and development of organ failure in critically ill patients. Beside genetic variation in the human gene encoding ASM (SMPD1), alternative splicing of the mRNA is involved in regulation of enzymatic activity. Here we show that the patterns of alternatively spliced SMPD1 transcripts are significantly different in patients with systemic inflammatory response syndrome and severe sepsis/septic shock compared to control subjects allowing discrimination of respective disease entity. The different splicing patterns might contribute to the better understanding of the pathophysiology of human sepsis. | D018805 | Sepsis |
Clinically important variants in SMPD1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
| P17405 | P17405-1 | SMPD1 | Microsatellite | p.Ala44_Leu49del | Benign |
| P17405 | P17405-1 | SMPD1 | Microsatellite | p.Ala44_Leu49del | Benign |
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