Ceramide synthase 2

Last updated
CERS2
Identifiers
Aliases CERS2 , L3, LASS2, SP260, TMSG1, ceramide synthase 2
External IDs OMIM: 606920 MGI: 1924143 HomoloGene: 39581 GeneCards: CERS2
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_013384
NM_022075
NM_181746

NM_029789
NM_001320492

RefSeq (protein)

NP_071358
NP_859530

NP_001307421
NP_084065

Location (UCSC) Chr 1: 150.96 – 150.98 Mb Chr 3: 95.22 – 95.23 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

Contents

Ceramide synthase 2 is a ceramide synthase that catalyses the synthesis of very long acyl chain ceramides, including C20 and C26 ceramides. It is the most ubiquitously expressed of all CerS and has the broadest distribution in the human body. [5]

CerS2 was first identified in 2001. [6] It contains the conserved TLC domain and Hox-like domain common to almost all CerS. [7]

Distribution

CerS2 mRNA (TRH3) has been found in most tissues and it is strongly expressed in liver, intestine and brain. [8] CerS2 is much more widely distributed than Ceramide synthase 1 (CerS1) and is found in at least 12 tissues in the human body, with high expression in the kidney and liver, and moderate expression in the brain and other organs. In the mouse brain, CerS2 is mainly expressed white matter tracts, specifically in oligodendrocytes and Schwann cells. [7] [9]

Function

Expression of CerS2 is transiently increased during periods of active myelination, suggesting that it is important for the synthesis of myelin sphingolipids. [9] The lack of CerS2, as shown in knockout mice, induces the autophagy and activation of the unfolded protein response (UPR). [7] These mice showed no decrease in overall ceramide level, but levels of sphinganine were elevated. They also developed severe liver disease, but there was no observable change in the kidneys. [10]

The CerS2 gene is compact in size and is located in a chromosomal region that is replicated early in the cell cycle. [7] CerS2 activity is regulated by sphingosine-1-phosphate (S1P) via two sphingosine-1-phosphate receptor-like residues on CerS2 that operate independently. [7]

Pathological significance

CerS2 levels are significantly elevated in breast cancer tissue compared to normal tissue, along with increased levels of ceramide synthase 6 (CerS6). [7]

CerS2 was also implicated in the control of body weight. The administration of leptin to rats induced a decrease in CerS2 was observed in white adipose tissue. [7]

Related Research Articles

<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">Sphingomyelin</span> Class of chemical compounds

Sphingomyelin is a type of sphingolipid found in animal cell membranes, especially in the membranous myelin sheath that surrounds some nerve cell axons. It usually consists of phosphocholine and ceramide, or a phosphoethanolamine head group; therefore, sphingomyelins can also be classified as sphingophospholipids. In humans, SPH represents ~85% of all sphingolipids, and typically make up 10–20 mol % of plasma membrane lipids.

<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.

<span class="mw-page-title-main">Lipid signaling</span> Biological signaling using lipid molecules

Lipid signaling, broadly defined, refers to any biological cell signaling event involving a lipid messenger that binds a protein target, such as a receptor, kinase or phosphatase, which in turn mediate the effects of these lipids on specific cellular responses. Lipid signaling is thought to be qualitatively different from other classical signaling paradigms because lipids can freely diffuse through membranes. One consequence of this is that lipid messengers cannot be stored in vesicles prior to release and so are often biosynthesized "on demand" at their intended site of action. As such, many lipid signaling molecules cannot circulate freely in solution but, rather, exist bound to special carrier proteins in serum.

<span class="mw-page-title-main">S1PR2</span> Protein and coding gene in humans

Sphingosine-1-phosphate receptor 2, also known as S1PR2 or S1P2, is a human gene which encodes a G protein-coupled receptor which binds the lipid signaling molecule sphingosine 1-phosphate (S1P).

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

In enzymology, a ceramide kinase, also abbreviated as CERK, is an enzyme that catalyzes the chemical reaction:

<span class="mw-page-title-main">ST8SIA1</span> Protein-coding gene in the species Homo sapiens

Alpha-N-acetylneuraminide alpha-2,8-sialyltransferase is an enzyme that in humans is encoded by the ST8SIA1 gene.

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

Ceramide glucosyltransferase is an enzyme that in humans is encoded by the UGCG gene.

<span class="mw-page-title-main">SPTLC2</span> Protein-coding gene in the species Homo sapiens

Serine palmitoyltransferase, long chain base subunit 2, also known as SPTLC2, is a protein which in humans is encoded by the SPTLC2 gene. SPTLC2 belongs to the class-II pyridoxal-phosphate-dependent aminotransferase family.

<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">UGT8</span> Protein-coding gene in the species Homo sapiens

2-hydroxyacylsphingosine 1-beta-galactosyltransferase is an enzyme that in humans is encoded by the UGT8 gene.

<span class="mw-page-title-main">SGMS1</span> Protein-coding gene in the species Homo sapiens

Phosphatidylcholine:ceramide cholinephosphotransferase 1 is an enzyme that in humans is encoded by the SGMS1 gene.

<span class="mw-page-title-main">SGPL1</span> Protein-coding gene in the species Homo sapiens

Sphingosine-1-phosphate lyase 1 is an enzyme that in humans is encoded by the SGPL1 gene.

<span class="mw-page-title-main">ALAS1</span> Protein-coding gene in the species Homo sapiens

Delta-aminolevulinate synthase 1 also known as ALAS1 is a protein that in humans is encoded by the ALAS1 gene. ALAS1 is an aminolevulinic acid synthase.

<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 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 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.

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000143418 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000015714 - 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. Stiban J, Tidhar R, Futerman AH (2010). "Ceramide Synthases: Roles in Cell Physiology and Signaling". Sphingolipids as Signaling and Regulatory Molecules. Advances in Experimental Medicine and Biology. Vol. 688. pp. 60–71. doi:10.1007/978-1-4419-6741-1_4. ISBN   978-1-4419-6740-4. PMID   20919646.
  6. Pan H, Qin WX, Huo KK, et al. (September 2001). "Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1". Genomics . 77 (1–2): 58–64. doi:10.1006/geno.2001.6614. PMID   11543633.
  7. 1 2 3 4 5 6 7 Levy M, Futerman AH (May 2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC   2858252 . PMID   20222015.
  8. Riebeling C, Allegood JC, Wang E, Merrill AH Jr, Futerman AH (Oct 2003). "Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors". J Biol Chem. 278 (44): 43452–9. doi: 10.1074/jbc.M307104200 . PMID   12912983.
  9. 1 2 Becker I, Wang-Eckhardt L, Yaghootfam A, Gieselmann V, Eckhardt M (February 2008). "Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2". Histochemistry and Cell Biology . 129 (2): 233–41. doi:10.1007/s00418-007-0344-0. PMID   17901973. S2CID   2595275.
  10. Pewzner-Jung Y, Brenner O, Braun S, Laviad EL, Ben-Dor S, Feldmesser E, Horn-Saban S, Amann-Zalcenstein D, Raanan C, Berkutzki T, Erez-Roman R, Ben-David O, Levy M, Holzman D, Park H, Nyska A, Merrill AH, Futerman AH (April 2010). "A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy". J. Biol. Chem. 285 (14): 10911–23. doi: 10.1074/jbc.M109.077610 . PMC   2856297 . PMID   20110366.

Further reading