ACER2 alkaline ceramidase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACER2provided by HGNC
Official Full Name: alkaline ceramidase 2provided by HGNC
Primary source: HGNC:HGNC:23675
See related: Ensembl:ENSG00000177076 MIM:613492; AllianceGenome:HGNC:23675
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: ASAH3L; ALKCDase2
Summary: The sphingolipid metabolite sphingosine-1-phosphate promotes cell proliferation and survival, whereas its precursor, sphingosine, has the opposite effect. The ceramidase ACER2 hydrolyzes very long chain ceramides to generate sphingosine (Xu et al., 2006 [PubMed 16940153]).[supplied by OMIM, Jul 2010]
Expression: Biased expression in stomach (RPKM 29.1), urinary bladder (RPKM 17.8) and 8 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p22.1

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (19409009..19452505)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (19421828..19465242)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (19409007..19452503)

Chromosome 9 - NC_000009.12 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?

Targeting YTHDF2 inhibits tumorigenesis of diffuse large B-cell lymphoma through ACER2-mediated ceramide catabolism.
Title: Targeting YTHDF2 inhibits tumorigenesis of diffuse large B-cell lymphoma through ACER2-mediated ceramide catabolism.
miR-196a-5p Correlates with Chronic Atrophic Gastritis Progression to Gastric Cancer and Induces Malignant Biological Behaviors of Gastric Cancer Cells by Targeting ACER2.
Title: miR-196a-5p Correlates with Chronic Atrophic Gastritis Progression to Gastric Cancer and Induces Malignant Biological Behaviors of Gastric Cancer Cells by Targeting ACER2.
TIMELESS regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer.
Title: TIMELESS regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer.
These results suggest that p53 mediates DDR and exerts its tumor suppressive role in part by regulating the expression of ACER2, which in turn regulates the bioactive sphingolipid lipids.
Title: Tumor suppressor p53 links ceramide metabolism to DNA damage response through alkaline ceramidase 2.
Consistently, forced expression of p53 significantly stimulated ACER2 transcription. Notably, p53-mediated autophagy and apoptosis were markedly enhanced by ACER2. Depletion of the essential autophagy gene ATG5 revealed that ACER2-induced autophagy facilitates its effect on apoptosis.
Title: Alkaline ceramidase 2 is a novel direct target of p53 and induces autophagy and apoptosis through ROS generation.
Results suggest that the ACER2/sphingosine pathway mediates programmed cell death in response to DNA damage through ROS production.
Title: Alkaline ceramidase 2 and its bioactive product sphingosine are novel regulators of the DNA damage response.
c-Src-mediated signal positively regulates ACER activity in a Ca2+-independent manner.
Title: Regulation of alkaline ceramidase activity by the c-Src-mediated pathway.
Results suggest that up-regulation of the ACER2/DHS pathway mediates the cytotoxicity of 4-HPR in tumor cells and that up-regulating or activating ACER2 may improve the anti-cancer activity of 4-HRR and other DHC-inducing agents.
Title: Alkaline ceramidase 2 (ACER2) and its product dihydrosphingosine mediate the cytotoxicity of N-(4-hydroxyphenyl)retinamide in tumor cells.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
ACER2 has broad substrate specificity and requires Ca(2+) for its activity; ACER2 has the cytosolic C terminus and luminal N terminus, which are essential for its activity, correct cellular localization, and regulation for protein glycosylation
Title: Substrate specificity, membrane topology, and activity regulation of human alkaline ceramidase 2 (ACER2).

Submit: New GeneRIF Correction See all GeneRIFs (11)

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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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables N-acylsphingosine amidohydrolase activity	IBA Inferred from Biological aspect of Ancestor more info
enables N-acylsphingosine amidohydrolase activity	IDA Inferred from Direct Assay more info	PubMed
enables N-acylsphingosine amidohydrolase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables N-acylsphingosine amidohydrolase activity	TAS Traceable Author Statement more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA damage response, signal transduction by p53 class mediator	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to xenobiotic stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in ceramide catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in ceramide catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cell adhesion mediated by integrin	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell-matrix adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell population proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of autophagy	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein glycosylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to retinoic acid	IDA Inferred from Direct Assay more info	PubMed
involved_in sphingolipid catabolic process	TAS Traceable Author Statement more info
involved_in sphingosine biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in sphingosine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in sphingosine biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
is_active_in Golgi membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in Golgi membrane	IDA Inferred from Direct Assay more info	PubMed
located_in Golgi membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: alkaline ceramidase 2

Names: alkCDase 2; alkaline CDase 2; ceramide hydrolase; haCER2

NP_001010887.2

EC 3.5.1.23

XP_011516160.1

EC 3.5.1.23

XP_011516161.1

EC 3.5.1.23

XP_016870183.1

EC 3.5.1.23

XP_047279291.1

EC 3.5.1.23

XP_047279292.1

EC 3.5.1.23

XP_054218878.1

EC 3.5.1.23

XP_054218879.1

EC 3.5.1.23

XP_054218880.1

EC 3.5.1.23

XP_054218881.1

EC 3.5.1.23

XP_054218882.1

EC 3.5.1.23

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_001010887.3 → NP_001010887.2 alkaline ceramidase 2

See identical proteins and their annotated locations for NP_001010887.2

Status: VALIDATED

Source sequence(s)

AK123581, AL158206, AY312516, BC092487

Consensus CDS

CCDS34992.1

UniProtKB/Swiss-Prot

A2A3R8, Q569G5, Q5QJU3, Q5VZR7, Q71RD2

UniProtKB/TrEMBL

B3KVV5

Related

ENSP00000342609.2, ENST00000340967.3

Conserved Domains (1) summary

pfam05875
Location:13 → 261

Ceramidase

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

19409009..19452505

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047423336.1 → XP_047279292.1 alkaline ceramidase 2 isoform X2
XM_011517858.2 → XP_011516160.1 alkaline ceramidase 2 isoform X3

Conserved Domains (1) summary

pfam05875
Location:13 → 178

Ceramidase; Ceramidase
XM_047423335.1 → XP_047279291.1 alkaline ceramidase 2 isoform X1
XM_017014694.2 → XP_016870183.1 alkaline ceramidase 2 isoform X1

UniProtKB/TrEMBL

B3KVV5

Conserved Domains (1) summary

pfam05875
Location:1 → 212

Ceramidase
XM_011517859.3 → XP_011516161.1 alkaline ceramidase 2 isoform X4

Conserved Domains (1) summary

pfam05875
Location:1 → 171

Ceramidase; Ceramidase