Ceramide synthase 4

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Structures	Swiss-model
Domains	InterPro

Ceramide synthase 4
Ceramide synthase 4
Identifiers
Symbol	CerS4
Alt. symbols	LASS4
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
Structures
Search for
Structures	Swiss-model
Domains	InterPro

CERS4
Identifiers
Aliases	CERS4, LASS4, Trh1, ceramide synthase 4, Ceramide synthase 4 (CerS4)
External IDs	OMIM: 615334; MGI: 1914510; GeneCards: CERS4
Enzyme activity
Gene location (Human)
Chr.	Chromosome 19 (human)
End	8,262,421 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	4,581,680 bp
RNA expression pattern
	Top expressed in
	body of pancreas; ; right lobe of thyroid gland; ; left lobe of thyroid gland; ; right lobe of liver; ; C1 segment; ; minor salivary glands; ; ectocervix; ; skin of abdomen; ; skin of leg; ; sural nerve;
	Top expressed in
	lip; ; skin of external ear; ; neural layer of retina; ; saccule; ; supraoptic nucleus; ; dorsomedial hypothalamic nucleus; ; median eminence; ; otic vesicle; ; interventricular septum; ; aortic valve;
	More reference expression data
	n/a
Gene ontology
Molecular function	DNA binding; sphingosine N-acyltransferase activity;
Cellular component	integral component of membrane; nuclear membrane; endoplasmic reticulum membrane; nucleus; membrane; endoplasmic reticulum;
Biological process	ceramide biosynthetic process; sphingolipid biosynthetic process; lipid metabolism;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	79603
	67260
	ENSG00000090661
	ENSMUSG00000008206
	Q9HA82
	Q9D6J1
	NM_024552
	NM_026058
	NP_078828
	NP_080334
	Wikidata
View/Edit Human	View/Edit Mouse

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.

Function and distribution

CerS4 synthesizes ceramides containing C18-22 fatty acids in a fumonisin B1-independent manner.^[5] It is expressed at highest levels in skin, leukocytes, heart and liver, although at much lower levels than other ceramide synthases.^[6]

Tissue and cellular distribution

CerS4 (TRH1) mRNA was found in all tissues and is strongly expressed in skin and muscle^[5]

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.^[7]^[8] Unlike CerS1 and CerS5, CerS4 does not sensitize cells to chemotherapeutic drugs.^[9]

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.^[10]

CerS4 expression was also found to be elevated in the brain of an Alzheimer's disease mouse model.^[11]

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000090661 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000008206 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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.
↑ 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.
↑ 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.
↑ 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. Bibcode:2010BBRC..391..219E. doi:10.1016/j.bbrc.2009.11.035. PMID 19912991.
↑ Levy M, Futerman AH (2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015.
↑ 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.
↑ 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.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000090661 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000008206 – 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.

[pmid12912983-5] 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.

[pmid18165233-6] 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.

[pmid19279183-7] 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.

[pmid19912991-8] 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. Bibcode:2010BBRC..391..219E. doi:10.1016/j.bbrc.2009.11.035. PMID 19912991.

[pmid20222015-9] Levy M, Futerman AH (2010). "Mammalian ceramide synthases". IUBMB Life. 62 (5): 347–56. doi:10.1002/iub.319. PMC 2858252. PMID 20222015.

[pmid18801905-10] 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.

[pmid18205190-11] 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.

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