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ACER2 alkaline ceramidase 2 [ Homo sapiens (human) ]

Gene ID: 340485, updated on 11-Apr-2024

Summary

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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
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Genomic context

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See ACER2 in Genome Data Viewer
Location:
9p22.1
Exon count:
11
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (19409009..19452505)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (19421828..19465242)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (19409007..19452503)

Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr9:19379549-19380748 Neighboring gene H3K27ac-H3K4me1 hESC enhancers GRCh37_chr9:19407977-19408834 and GRCh37_chr9:19408835-19409690 Neighboring gene NADH:ubiquinone oxidoreductase subunit A5 pseudogene 3 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr9:19446057-19447256 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28222 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr9:19457239-19457834 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:19460877-19461378 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19795 Neighboring gene uncharacterized LOC105375988 Neighboring gene ribosomal protein S6 Neighboring gene microtubule associated protein 1 light chain 3 beta pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:19492981-19493504 Neighboring gene solute carrier family 24 member 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Alkaline ceramidase 2 and its bioactive product sphingosine are novel regulators of the DNA damage response. Xu R, et al. Oncotarget, 2016 Apr 5. PMID 26943039, Free PMC Article
  2. Regulation of alkaline ceramidase activity by the c-Src-mediated pathway. Sasaki H, et al. Arch Biochem Biophys, 2014 May 15. PMID 24708996
  3. Substrate specificity, membrane topology, and activity regulation of human alkaline ceramidase 2 (ACER2). Sun W, et al. J Biol Chem, 2010 Mar 19. PMID 20089856, Free PMC Article
  4. TIMELESS regulates sphingolipid metabolism and tumor cell growth through Sp1/ACER2/S1P axis in ER-positive breast cancer. Zhang S, et al. Cell Death Dis, 2020 Oct 22. PMID 33093451, Free PMC Article
  5. Tumor suppressor p53 links ceramide metabolism to DNA damage response through alkaline ceramidase 2. Xu R, et al. Cell Death Differ, 2018 May. PMID 29229990, Free PMC Article

See all (17) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. 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.
  2. 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.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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).
  10. ACER2/sphingosine pathway plays an important role in regulating beta1 maturation and cell adhesion mediated by beta1 integrins
    Title: Alkaline ceramidase 2 regulates beta1 integrin maturation and cell adhesion.
Submit: New GeneRIF Correction

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)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ41587

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables N-acylsphingosine amidohydrolase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables N-acylsphingosine amidohydrolase activity TAS
Traceable Author Statement
more info
  
enables ceramidase activity IEA
Inferred from Electronic Annotation
more info
  
enables dihydroceramidase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables dihydroceramidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables dihydroceramidase activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
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 activation of cysteine-type endopeptidase activity involved in apoptotic process 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
XP_011516160.1
XP_011516161.1
XP_016870183.1
XP_047279291.1
XP_047279292.1
XP_054218878.1
XP_054218879.1
XP_054218880.1
XP_054218881.1
XP_054218882.1

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)

  1. 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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000009.12 Reference GRCh38.p14 Primary Assembly

    Range
    19409009..19452505
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047423336.1 → XP_047279292.1  alkaline ceramidase 2 isoform X2

  2. XM_011517858.2 → XP_011516160.1  alkaline ceramidase 2 isoform X3

    Conserved Domains (1) summary
    pfam05875
    Location:13 → 178
    Ceramidase; Ceramidase

  3. XM_047423335.1 → XP_047279291.1  alkaline ceramidase 2 isoform X1

  4. XM_017014694.2 → XP_016870183.1  alkaline ceramidase 2 isoform X1

    UniProtKB/TrEMBL
    B3KVV5
    Conserved Domains (1) summary
    pfam05875
    Location:1 → 212
    Ceramidase

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

    Conserved Domains (1) summary
    pfam05875
    Location:1 → 171
    Ceramidase; Ceramidase

RNA

  1. XR_002956780.2 RNA Sequence

  2. XR_002956781.2 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060933.1 Alternate T2T-CHM13v2.0

    Range
    19421828..19465242
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054362905.1 → XP_054218880.1  alkaline ceramidase 2 isoform X2

  2. XM_054362906.1 → XP_054218881.1  alkaline ceramidase 2 isoform X3

  3. XM_054362903.1 → XP_054218878.1  alkaline ceramidase 2 isoform X1

  4. XM_054362904.1 → XP_054218879.1  alkaline ceramidase 2 isoform X1

  5. XM_054362907.1 → XP_054218882.1  alkaline ceramidase 2 isoform X4

RNA

  1. XR_008488012.1 RNA Sequence

  2. XR_008488013.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q5QJU3.2 GenPept UniProtKB/Swiss-Prot:Q5QJU3

Gene LinkOut

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