Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002777
UniProt IDP17405
Primary gene name(s)SMPD1
Synonym gene name(s)ASM
Protein nameSphingomyelin phosphodiesterase
Protein functionConverts sphingomyelin to ceramide, PubMed:1840600, PubMed:18815062, PubMed:27659707, PubMed:25920558. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol. {ECO:0000269|PubMed:1840600, ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:25920558, ECO:0000269|PubMed:27659707, ECO:0000305}.; FUNCTION: Isoform 2 lacks residues that bind the cofactor Zn(2+ and has no enzyme activity. {ECO:0000269|PubMed:1840600, ECO:0000305}.; FUNCTION: Isoform 3 lacks residues that bind the cofactor Zn(2+ and has no enzyme activity. {ECO:0000269|PubMed:1840600, ECO:0000305}.
Subcellular locationLysosome {ECO:0000269|PubMed:18815062, ECO:0000269|PubMed:27659707}. Secreted {ECO:0000269|PubMed:25920558, ECO:0000269|PubMed:27659707, ECO:0000269|PubMed:8702487}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P17405
Gene Ontology
(Biological Process)
Complete annatation
ceramide biosynthetic process [GO:0046513];
glycosphingolipid metabolic process [GO:0006687];
negative regulation of MAP kinase activity [GO:0043407];
nervous system development [GO:0007399];
positive regulation of apoptotic process [GO:0043065];
positive regulation of protein dephosphorylation [GO:0035307];
response to cocaine [GO:0042220];
response to drug [GO:0042493];
signal transduction [GO:0007165];
sphingomyelin catabolic process [GO:0006685];
sphingomyelin metabolic process [GO:0006684];
termination of signal transduction [GO:0023021]
Gene Ontology
(Molecular Function)
Complete annatation
acid sphingomyelin phosphodiesterase activity [GO:0061750];
hydrolase activity, acting on glycosyl bonds [GO:0016798];
sphingomyelin phosphodiesterase activity [GO:0004767];
zinc ion binding [GO:0008270]
Gene Ontology
(Cellular Component)
Complete annatation
endosome [GO:0005768];
extracellular exosome [GO:0070062];
extracellular space [GO:0005615];
lamellar body [GO:0042599];
lysosomal lumen [GO:0043202];
lysosome [GO:0005764];
plasma membrane [GO:0005886]
Protein-protein interaction112493
Phylogenetic treeP17405
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD3-2.194028039309272.43012943101917e-103.93837750369042e-09
AZA vs. DISU-0.325911754566580.199128925150250.78864353066485
AZA vs. IL7-0.3566066858242370.06557618356699750.732712983621462
AZA vs. SAHA-0.1959375877675510.4235194626622420.77637509183639
DISU vs. CD31.856858325181739.39063827254394e-079.06819226907927e-06
DISU vs. IL7-0.04086604844178020.8715097315633390.97551616551746
DISU vs. SAHA0.1325609196755750.6499494213075470.891868135165805
DMSO vs. AZA-0.0303122850749290.857375385478171
DMSO vs. CD32.152771639532531.75513492628454e-102.64411076644766e-09
DMSO vs. DISU0.2938915378132870.2298581857623180.743536640190041
DMSO vs. IL7-0.3189378721294310.07821188278284320.527480723100474
DMSO vs. SAHA-0.1704760796419820.4713104927218780.796492535973473
HIV vs. Mock in Activation0.2372233128994010.7301729349428580.999983755607037
HIV vs. Mock in Latency0.006003317732761160.9711135129201980.999834320637052
IL7 vs. CD31.842258223060813.80793565568638e-085.1148010773314e-07
SAHA vs. CD31.974907315120561.16118787918396e-071.20103646803721e-06
SAHA vs. IL70.1586982573019050.5168969152159240.740223568353251
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change 1.906490976
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) TRUE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK -0.366938 0.00457947
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
unknown unknown unknown unknown unknown
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

Drugbank ID Drug Name Drug Status Pharmacological Action Drug Action
DB01151 Desipramine approved unknown inhibitor
DB00477 Chlorpromazine approved, vet_approved unknown unknown
DB00381 Amlodipine approved unknown unknown

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
5I81 X-ray 2.2Å A=47-629.
5I85 X-ray 2.5Å A=47-629.
5I8R X-ray 3.6Å A/B/C=47-629.
5JG8 X-ray 2.8Å A/B=47-629.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Nef modulates 9110068
Nef inhibits 22721673
Envelope surface glycoprotein gp120 inhibited by 17344303
Tat upregulates 23025307
Envelope surface glycoprotein gp120 activates 15509740

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00600 Sphingolipid metabolism - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)
hsa04071 Sphingolipid signaling pathway - Homo sapiens (human)
hsa04142 Lysosome - Homo sapiens (human)