ACER1

Alkaline ceramidase 1 also known as ACER1 is a ceramidase enzyme which in humans is encoded by the ACER1 gene.[5]

ACER1
Identifiers
Aliases	ACER1, ALKCDase1, ASAH3, alkaline ceramidase 1
External IDs	OMIM: 613491 MGI: 2181962 HomoloGene: 15853 GeneCards: ACER1
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.3 Start 6,306,142 bp[1] End 6,333,612 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 D Start 56,953,490 bp[2] End 56,982,126 bp[2]
Gene ontology Molecular function • dihydroceramidase activity • hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides • hydrolase activity • acylsphingosine deacylase activity • ceramidase activity • metal ion binding Cellular component • membrane • integral component of membrane • endoplasmic reticulum membrane • endoplasmic reticulum Biological process • cellular response to calcium ion • regulation of lipid metabolic process • cell differentiation • sphingosine biosynthetic process • sphingolipid biosynthetic process • response to alkaline pH • keratinocyte differentiation • ceramide metabolic process • epidermis development • lipid metabolism • ceramide catabolic process • sphingolipid metabolic process • regulation of water loss via skin • sebaceous gland development Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	125981	171168
Ensembl	ENSG00000167769	ENSMUSG00000045019
UniProt	Q8TDN7	Q8R4X1
RefSeq (mRNA)	NM_133492	NM_175731
RefSeq (protein)	NP_597999	NP_783858
Location (UCSC)	Chr 19: 6.31 – 6.33 Mb	Chr 17: 56.95 – 56.98 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

ACER1 mediates cellular differentiation by controlling the generation of sphingosine (SPH) and sphingosine-1-phosphate (S1P).[5]

Model organisms

Acer1 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[6][7][8]
Peripheral blood leukocytes 6 Weeks	Normal
Haematology 6 Weeks	Normal
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
General Observations	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Abnormal
Indirect calorimetry	Abnormal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Anti-nuclear Antibody Assay	Normal
Influenza Challenge	Normal

Model organisms have been used in the study of ACER1 function. A conditional knockout mouse line called Acer1^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.[9] Male and female animals underwent a standardized phenotypic screen[6] to determine the effects of deletion.[10][11][12][13] Additional screens performed: - In-depth immunological phenotyping[7] - in-depth bone and cartilage phenotyping[8]

References

1. GRCh38: Ensembl release 89: ENSG00000167769 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000045019 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Mao C, Xu R, Szulc ZM, Bielawski J, Becker KP, Bielawska A, Galadari SH, Hu W, Obeid LM (Aug 2003). "Cloning and characterization of a mouse endoplasmic reticulum alkaline ceramidase: an enzyme that preferentially regulates metabolism of very long chain ceramides". The Journal of Biological Chemistry. 278 (33): 31184–91. doi:10.1074/jbc.M303875200. PMID 12783875.
6. "International Mouse Phenotyping Consortium".
7. "Infection and Immunity Immunophenotyping (3i) Consortium".
8. "OBCD Consortium".
9. Gerdin AK (Sep 2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (Supplement s246): 4142. doi:10.1111/j.1755-3768.2010.4142.x.
10. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
11. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
13. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.

External links

• Human ACER1 genome location and ACER1 gene details page in the UCSC Genome Browser.

Further reading

• Sun W, Xu R, Hu W, Jin J, Crellin HA, Bielawski J, Szulc ZM, Thiers BH, Obeid LM, Mao C (Feb 2008). "Upregulation of the human alkaline ceramidase 1 and acid ceramidase mediates calcium-induced differentiation of epidermal keratinocytes". The Journal of Investigative Dermatology. 128 (2): 389–97. doi:10.1038/sj.jid.5701025. PMID 17713573.
• Toulza E, Mattiuzzo NR, Galliano MF, Jonca N, Dossat C, Jacob D, de Daruvar A, Wincker P, Serre G, Guerrin M (2007). "Large-scale identification of human genes implicated in epidermal barrier function". Genome Biology. 8 (6): R107. doi:10.1186/gb-2007-8-6-r107. PMC 2394760. PMID 17562024.
• Ito M, Okino N, Tani M, Mitsutake S, Mori K (Mar 2002). "[Molecular evolution of neutral ceramidase: signalling molecule and virulence factor]". Tanpakushitsu Kakusan Koso. Protein, Nucleic Acid, Enzyme. 47 (4 Suppl): 455–62. PMID 11915342.
• Houben E, Holleran WM, Yaginuma T, Mao C, Obeid LM, Rogiers V, Takagi Y, Elias PM, Uchida Y (May 2006). "Differentiation-associated expression of ceramidase isoforms in cultured keratinocytes and epidermis". Journal of Lipid Research. 47 (5): 1063–70. doi:10.1194/jlr.M600001-JLR200. PMID 16477081.