Ceramide synthase 4

Last updated
Ceramide synthase 4
Identifiers
SymbolCerS4
Alt. symbolsLASS4
NCBI gene 79603
HGNC 23747
OMIM 615334
RefSeq NM_024552.2
UniProt Q9HA82
Other data
EC number 2.3.1.24
Locus Chr. 19 p13.3
Search for
Structures Swiss-model
Domains InterPro

Ceramide synthase 4 (CerS4) is an enzyme that in humans is encoded by the CERS4 gene and is one of the least studied of the ceramide synthases.

Contents

Function and distribution

CerS4 synthesizes ceramides containing C18-22 fatty acids in a fumonisin B1-independent manner. [1] It is expressed at highest levels in skin, leukocytes, heart and liver, although at much lower levels than other ceramide synthases. [2]

Tissue and cellular distribution

CerS4 (TRH1) mRNA was found in all tissues and is strongly expressed in skin and muscle [1]

Clinical significance

In a 2009 study of breast cancer, total ceramide synthase levels were increased in malignant tissue, and CerS4 was one of three ceramide synthases to show an increase in mRNA levels. A significant correlation was found between CerS4 and CerS2/CerS6 expression. [3] [4] Unlike CerS1 and CerS5, CerS4 does not sensitize cells to chemotherapeutic drugs. [5]

CerS4 may also be involved in the control of body weight and food intake. Upon administration of leptin, a decrease in ceramide levels was observed in rat white adipose tissue, as were expression levels of a number of genes in the sphingolipid metabolic pathway, including CerS2 and CerS4. [6]

CerS4 expression was also found to be elevated in the brain of an Alzheimer's disease mouse model. [7]

Related Research Articles

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<span class="mw-page-title-main">Sphingolipid</span> Family of chemical compounds

Sphingolipids are a class of lipids containing a backbone of sphingoid bases, which are a set of aliphatic amino alcohols that includes sphingosine. They were discovered in brain extracts in the 1870s and were named after the mythological sphinx because of their enigmatic nature. These compounds play important roles in signal transduction and cell recognition. Sphingolipidoses, or disorders of sphingolipid metabolism, have particular impact on neural tissue. A sphingolipid with a terminal hydroxyl group is a ceramide. Other common groups bonded to the terminal oxygen atom include phosphocholine, yielding a sphingomyelin, and various sugar monomers or dimers, yielding cerebrosides and globosides, respectively. Cerebrosides and globosides are collectively known as glycosphingolipids.

<span class="mw-page-title-main">Fumonisin B1</span> Chemical compound

Fumonisin B1 is the most prevalent member of a family of toxins, known as fumonisins, produced by multiple species of Fusarium molds, such as Fusarium verticillioides, which occur mainly in maize (corn), wheat and other cereals. Fumonisin B1 contamination of maize has been reported worldwide at mg/kg levels. Human exposure occurs at levels of micrograms to milligrams per day and is greatest in regions where maize products are the dietary staple.

<span class="mw-page-title-main">Ceramide</span> Family of waxy lipid molecules

Ceramides are a family of waxy lipid molecules. A ceramide is composed of sphingosine and a fatty acid joined by an amide bond. Ceramides are found in high concentrations within the cell membrane of eukaryotic cells, since they are component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. Contrary to previous assumptions that ceramides and other sphingolipids found in cell membrane were purely supporting structural elements, ceramide can participate in a variety of cellular signaling: examples include regulating differentiation, proliferation, and programmed cell death (PCD) of cells.

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<span class="mw-page-title-main">Stearoyl-CoA 9-desaturase</span> Class of enzymes

Stearoyl-CoA desaturase (Δ-9-desaturase) is an endoplasmic reticulum enzyme that catalyzes the rate-limiting step in the formation of monounsaturated fatty acids (MUFAs), specifically oleate and palmitoleate from stearoyl-CoA and palmitoyl-CoA. Oleate and palmitoleate are major components of membrane phospholipids, cholesterol esters and alkyl-diacylglycerol. In humans, the enzyme is encoded by the SCD gene.

<span class="mw-page-title-main">GPR3</span> Protein

G-protein coupled receptor 3 is a protein that in humans is encoded by the GPR3 gene. The protein encoded by this gene is a member of the G protein-coupled receptor family of transmembrane receptors and is involved in signal transduction.

In enzymology, sphingosine N-acyltransferases (ceramide synthases (CerS), EC 2.3.1.24) are enzymes that catalyze the chemical reaction of synthesis of ceramide:

<span class="mw-page-title-main">USF1</span> Protein-coding gene in the species Homo sapiens

Upstream stimulatory factor 1 is a protein that in humans is encoded by the USF1 gene.

<span class="mw-page-title-main">Perilipin-2</span> Protein-coding gene in the species Homo sapiens

Adipose differentiation-related protein, also known as perilipin 2, ADRP or adipophilin, is a protein which belongs to the perilipin (PAT) family of cytoplasmic lipid droplet (CLD)–binding proteins. In humans it is encoded by the ADFP gene. This protein surrounds the lipid droplet along with phospholipids and is involved in assisting the storage of neutral lipids within the lipid droplets.

<span class="mw-page-title-main">Brain mitochondrial carrier protein 1</span> Protein-coding gene in the species Homo sapiens

Brain mitochondrial carrier protein 1 is a protein that in humans is encoded by the SLC25A14 gene.

<span class="mw-page-title-main">BCL2L13</span> Protein-coding gene in the species Homo sapiens

BCL2-like 13 , also known as BCL2L13 or Bcl-rambo, is a protein which in humans is encoded by the BCL2L13 gene on chromosome 22. This gene encodes a mitochondrially-localized protein which is classified under the Bcl-2 protein family. Overexpression of the encoded protein results in apoptosis. As a result, it has been implicated in cancers such as childhood acute lymphoblastic leukemia (ALL) and glioblastoma multiforme (GBM). Alternatively spliced transcript variants have been observed for this gene, such as Bcl-rambo beta.

<span class="mw-page-title-main">AGK (gene)</span> Protein-coding gene in the species Homo sapiens

The human gene AGK encodes the enzyme mitochondrial acylglycerol kinase.

<span class="mw-page-title-main">ALOXE3</span> Protein-coding gene in the species Homo sapiens

Epidermis-type lipoxygenase 3 is a member of the lipoxygenase family of enzymes; in humans, it is encoded by the ALOXE3 gene. This gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOX12B and ALOX15B. Among the human lipoxygenases, ALOXE3 is most closely related in amino acid sequence to ALOX12B. ALOXE3, ALOX12B, and ALOX15B are often classified as epidermal lipoxygenases, in distinction to the other three human lipoxygenases, because they were initially defined as being highly or even exclusively expressed and functioning in skin. The epidermis-type lipoxygenases are now regarded as a distinct subclass within the multigene family of mammalian lipoxygenases with mouse Aloxe3 being the ortholog to human ALOXE3, mouse Alox12b being the ortholog to human ALOX12B, and mouse Alox8 being the ortholog to human ALOX15B [supplied by OMIM]. ALOX12B and ALOXE3 in humans, Alox12b and Aloxe3 in mice, and comparable orthologs in other in other species are proposed to act sequentially in a multistep metabolic pathway that forms products that are structurally critical for creating and maintaining the skin's water barrier function.

<span class="mw-page-title-main">Teleost leptins</span>

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<span class="mw-page-title-main">Ceramide synthase 1</span> Protein-coding gene in the species Homo sapiens

Ceramide synthase 1 also known as LAG1 longevity assurance homolog 1 is an enzyme that in humans is encoded by the CERS1 gene.

<span class="mw-page-title-main">Ceramide synthase 2</span> Protein-coding gene in the species Homo sapiens

Ceramide synthase 2, also known as LAG1 longevity assurance homolog 2 or Tumor metastasis-suppressor gene 1 protein is an enzyme that in humans is encoded by the CERS2 gene.

<span class="mw-page-title-main">Ceramide synthase 3</span> Protein-coding gene in the species Homo sapiens

Ceramide synthase 3 (CersS3), also known as longevity assurance homologue 3, is an enzyme that is encoded in humans by the CERS3 gene.

Ceramide synthase 5 (CerS5) is the enzyme encoded in humans by the CERS5 gene.

References

  1. 1 2 Riebeling C, Allegood JC, Wang E, Merrill AH, Futerman AH (October 2003). "Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors". Journal of Biological Chemistry. 278 (44): 43452–43459. doi: 10.1074/jbc.M307104200 . PMID   12912983.
  2. Laviad EL, Albee L, Pankova-Kholmyansky I, Epstein S, Park H, Merrill AH, et al. (2008). "Characterization of ceramide synthase 2: tissue distribution, substrate specificity, and inhibition by sphingosine 1-phosphate". Journal of Biological Chemistry. 283 (9): 5677–5684. doi: 10.1074/jbc.M707386200 . PMID   18165233.
  3. Schiffmann S, Sandner J, Birod K, Wobst I, Angioni C, Ruckhäberle E, et al. (2009). "Ceramide synthases and ceramide levels are increased in breast cancer tissue". Carcinogenesis. 30 (5): 745–752. doi: 10.1093/carcin/bgp061 . PMID   19279183.
  4. Erez-Roman R, Pienik R, Futerman AH (2010). "Increased ceramide synthase 2 and 6 mRNA levels in breast cancer tissues and correlation with sphingosine kinase expression". Biochemical and Biophysical Research Communications. 391 (1): 219–223. doi:10.1016/j.bbrc.2009.11.035. PMID   19912991.
  5. Levy M, Futerman AH (2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC   2858252 . PMID   20222015.
  6. Bonzón-Kulichenko E, Schwudke D, Gallardo N, Moltó E, Fernández-Agulló T, Shevchenko A, et al. (2009). "Central leptin regulates total ceramide content and sterol regulatory element binding protein-1C proteolytic maturation in rat white adipose tissue". Endocrinology. 150 (1): 169–78. doi: 10.1210/en.2008-0505 . hdl: 10115/3350 . PMID   18801905.
  7. Wang G, Silva J, Dasgupta S, Bieberich E (2008). "Long-chain ceramide is elevated in presenilin 1 (PS1M146V) mouse brain and induces apoptosis in PS1 astrocytes". Glia. 56 (4): 449–56. doi:10.1002/glia.20626. PMID   18205190. S2CID   5324040.