SMPDL3A sphingomyelin phosphodiesterase acid like 3A [Homo sapiens (human)] - Gene

Summary

Official Symbol: SMPDL3Aprovided by HGNC
Official Full Name: sphingomyelin phosphodiesterase acid like 3Aprovided by HGNC
Primary source: HGNC:HGNC:17389
See related: Ensembl:ENSG00000172594 MIM:610728; AllianceGenome:HGNC:17389
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ASM3A; ASML3a; yR36GH4.1
Summary: Enables phosphoric diester hydrolase activity and zinc ion binding activity. Involved in negative regulation of cGAS/STING signaling pathway and nucleoside triphosphate catabolic process. Located in extracellular exosome. Is active in extracellular space. [provided by Alliance of Genome Resources, Dec 2024]
Expression: Ubiquitous expression in colon (RPKM 18.5), small intestine (RPKM 18.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 6q22.31

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (122789258..122809720)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	6	NC_060930.1 (123977551..123998013)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (123110403..123130865)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Activation of pregnane X receptor induces SMPDL3A expression in primary hepatocytes.
Title: Ligand-dependent and -independent regulation of human hepatic sphingomyelin phosphodiesterase acid-like 3A expression by pregnane X receptor and crosstalk with liver X receptor.
Site-specific N-glycosylation is essential for the intracellular stability, secretion and activity of human SMPDL3A.
Title: N-glycosylation of human sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is essential for stability, secretion and activity.
Solved the structure of SMPDL3a revealing a calcineurin-like fold. A dimetal site, glycosylation pattern and a disulfide bond network are likely to be conserved also in aSMase. We show that the binuclear site of SMPDL3a is occupied by two Zn(2+) ions.
Title: The structure and catalytic mechanism of human sphingomyelin phosphodiesterase like 3a--an acid sphingomyelinase homologue with a novel nucleotide hydrolase activity.
Data indicate that sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a nucleotide phosphodiesterase secreted from cholesterol-loaded macrophages.
Title: Sphingomyelin phosphodiesterase acid-like 3A (SMPDL3A) is a novel nucleotide phosphodiesterase regulated by cholesterol in human macrophages.
the induction of SMPDL3A is liver X receptor-dependent and is restricted to human blood cells with no induction observed in mouse cellular systems.
Title: Regulation of sphingomyelin phosphodiesterase acid-like 3A gene (SMPDL3A) by liver X receptors.
ASML3a is involved in the process of bladder tumorigenesis
Title: Increased expression of the acid sphingomyelinase-like protein ASML3a in bladder tumors.

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Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-148224 (e-PCR)
- UniSTS:172956

RH70964 (e-PCR)
- UniSTS:691

SMPDL3A (e-PCR)
- UniSTS:504530

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent H2AZ histone chaperone activity	IEA Inferred from Electronic Annotation more info
enables ATP-dependent H3-H4 histone complex chaperone activity	IEA Inferred from Electronic Annotation more info
enables DNA clamp loader activity	IEA Inferred from Electronic Annotation more info
enables chromatin extrusion motor activity	IEA Inferred from Electronic Annotation more info
enables cohesin loader activity	IEA Inferred from Electronic Annotation more info
enables phosphoric diester hydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphoric diester hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphoric diester hydrolase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
NOT enables sphingomyelin phosphodiesterase activity	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in chromatin looping	IEA Inferred from Electronic Annotation more info
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cGAS/STING signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleoside triphosphate catabolic process	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in sphingomyelin catabolic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in extracellular exosome	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
is_active_in extracellular space	IMP Inferred from Mutant Phenotype more info	PubMed
located_in extracellular space	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: cyclic GMP-AMP phosphodiesterase SMPDL3A

Names: 0610010C24Rik; 2',3'-cGAMP phosphodiesterase SMPDL3A; ASM-like phosphodiesterase 3a; acid sphingomyelinase-like phosphodiesterase 3a

NP_001273067.1

EC 3.6.1.15

NP_006705.1

EC 3.6.1.15

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001286138.2 → NP_001273067.1 cyclic GMP-AMP phosphodiesterase SMPDL3A isoform b

See identical proteins and their annotated locations for NP_001273067.1

Status: VALIDATED

Description

Transcript Variant: This variant (2) lacks an alternate exon in the 5' coding region and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a.

Source sequence(s)

AK301365, DA510600, Y08136

Consensus CDS

CCDS69190.1

UniProtKB/Swiss-Prot

Q92484

Related

ENSP00000442152.1, ENST00000539041.5

Conserved Domains (2) summary

COG1409
Location:13 → 206

CpdA; 3',5'-cyclic AMP phosphodiesterase CpdA [Signal transduction mechanisms]

cd00842
Location:1 → 205

MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain
NM_006714.5 → NP_006705.1 cyclic GMP-AMP phosphodiesterase SMPDL3A isoform a precursor

See identical proteins and their annotated locations for NP_006705.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (a).

Source sequence(s)

BC018999, DA510600, Y08136

Consensus CDS

CCDS5128.1

UniProtKB/Swiss-Prot

B7Z729, Q8WV13, Q92484

Related

ENSP00000357425.4, ENST00000368440.5

Conserved Domains (1) summary

cd00842
Location:40 → 336

MPP_ASMase; acid sphingomyelinase and related proteins, metallophosphatase domain