{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc}} {{Infobox_gene}}

'''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.

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.<ref name="pmid20919646">{{cite book |vauthors=Stiban J, Tidhar R, Futerman AH |title=Sphingolipids as Signaling and Regulatory Molecules |chapter=Ceramide Synthases: Roles in Cell Physiology and Signaling |series=Advances in Experimental Medicine and Biology |volume=688 |pages=60–71 |year=2010 |pmid=20919646 |doi= 10.1007/978-1-4419-6741-1_4|isbn=978-1-4419-6740-4 }}<!--|accessdate=2014-02-17--></ref>

CerS2 was first identified in 2001.<ref name="pmid11543633">{{cite journal |vauthors=Pan H, Qin WX, Huo KK |title=Cloning, mapping, and characterization of a human homologue of the yeast longevity assurance gene LAG1 |journal=Genomics |volume=77 |issue=1–2 |pages=58–64 |date=September 2001 |pmid=11543633 |doi=10.1006/geno.2001.6614 |display-authors=etal}}<!--|accessdate=2014-02-17--></ref> It contains the conserved TLC domain and Hox-like domain common to almost all CerS.<ref name="Levy_Futerman_2010">{{cite journal |vauthors=Levy M, Futerman AH | title = Mammalian ceramide synthases | journal = IUBMB Life | volume = 62 | issue = 5 | pages = 347–56 |date=May 2010 | pmid = 20222015 | pmc = 2858252 | doi = 10.1002/iub.319 }}</ref>

==Distribution== CerS2 mRNA (TRH3) has been found in most tissues and it is strongly expressed in liver, intestine and brain.<ref name="RiebelingFuterman2003 Fig5">{{cite journal |vauthors=Riebeling C, Allegood JC, Wang E, ((Merrill AH Jr)), Futerman AH | title = Two mammalian longevity assurance gene (LAG1) family members, trh1 and trh4, regulate dihydroceramide synthesis using different fatty acyl-CoA donors | journal = J Biol Chem | volume = 278| issue = 44 | pages = 43452–9 |date=Oct 2003 | pmid = 12912983 | doi = 10.1074/jbc.M307104200 | doi-access = free }}</ref> 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.<ref name="Levy_Futerman_2010" /><ref name="pmid17901973">{{cite journal |vauthors=Becker I, Wang-Eckhardt L, Yaghootfam A, Gieselmann V, Eckhardt M |title=Differential expression of (dihydro)ceramide synthases in mouse brain: oligodendrocyte-specific expression of CerS2/Lass2 |journal=Histochemistry and Cell Biology |volume=129 |issue=2 |pages=233–41 |date=February 2008 |pmid=17901973 |doi=10.1007/s00418-007-0344-0 |s2cid=2595275 }}<!--|accessdate=2014-02-17--></ref>

==Function== Expression of CerS2 is transiently increased during periods of active myelination, suggesting that it is important for the synthesis of myelin sphingolipids.<ref name="pmid17901973" /> The lack of CerS2, as shown in knockout mice, induces the autophagy and activation of the unfolded protein response (UPR).<ref name="Levy_Futerman_2010" /> 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.<ref name="pmid20110366">{{cite journal |vauthors=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 | title = A critical role for ceramide synthase 2 in liver homeostasis: II. insights into molecular changes leading to hepatopathy | journal = J. Biol. Chem. | volume = 285 | issue = 14 | pages = 10911–23 |date=April 2010 | pmid = 20110366 | pmc = 2856297 | doi = 10.1074/jbc.M109.077610 | doi-access = free }}</ref>

The ''CerS2'' gene is compact in size and is located in a chromosomal region that is replicated early in the cell cycle.<ref name="Levy_Futerman_2010" /> CerS2 activity is regulated by sphingosine-1-phosphate (S1P) via two sphingosine-1-phosphate receptor-like residues on CerS2 that operate independently.<ref name="Levy_Futerman_2010" />

==Pathological significance== CerS2 levels are significantly elevated in breast cancer tissue compared to normal tissue, along with increased levels of ceramide synthase 6 (CerS6).<ref name="Levy_Futerman_2010" />

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.<ref name="Levy_Futerman_2010" />

==References== {{reflist|2}}

==Further reading== {{refbegin | 2}} *{{cite journal |vauthors=Rual JF, Venkatesan K, Hao T |title=Towards a proteome-scale map of the human protein-protein interaction network |journal=Nature |volume=437 |issue= 7062 |pages= 1173–8 |year= 2005 |pmid= 16189514 |doi= 10.1038/nature04209 |bibcode=2005Natur.437.1173R |s2cid=4427026 |display-authors=etal}} *{{cite journal |vauthors=Lewandrowski U, Moebius J, Walter U, Sickmann A |title=Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach |journal=Mol. Cell. Proteomics |volume=5 |issue= 2 |pages= 226–33 |year= 2006 |pmid= 16263699 |doi= 10.1074/mcp.M500324-MCP200 |s2cid=7856143 |doi-access= free}} *{{cite journal |vauthors=Oh JH, Yang JO, Hahn Y |title=Transcriptome analysis of human gastric cancer |journal=Mamm. Genome |volume=16 |issue= 12 |pages= 942–54 |year= 2006 |pmid= 16341674 |doi= 10.1007/s00335-005-0075-2 |s2cid=69278 |display-authors=etal}} *{{cite journal |vauthors=Olsen JV, Blagoev B, Gnad F |title=Global, in vivo, and site-specific phosphorylation dynamics in signaling networks |journal=Cell |volume=127 |issue= 3 |pages= 635–48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 |s2cid=7827573 |display-authors=etal|doi-access=free }} *{{cite journal |vauthors=Ewing RM, Chu P, Elisma F |title=Large-scale mapping of human protein-protein interactions by mass spectrometry |journal=Mol. Syst. Biol. |volume=3 |issue= 1|pages= 89 |year= 2007 |pmid= 17353931 |doi= 10.1038/msb4100134 | pmc=1847948 |display-authors=etal}} {{refend}}

Category:Integral membrane proteins