FA2H

Fatty acid 2-hydroxylase is a protein that in humans is encoded by the FA2H gene.[5]

FA2H
Identifiers
Aliases	FA2H, FAAH, FAH1, FAXDC1, SCS7, SPG35, fatty acid 2-hydroxylase
External IDs	OMIM: 611026 MGI: 2443327 HomoloGene: 56284 GeneCards: FA2H
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16q23.1 Start 74,712,955 bp[1] End 74,774,831 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8|8 E1 Start 111,345,135 bp[2] End 111,393,824 bp[2]
Gene ontology Molecular function • iron ion binding • metal ion binding • heme binding • oxidoreductase activity • fatty acid alpha-hydroxylase activity Cellular component • integral component of membrane • organelle membrane • endoplasmic reticulum membrane • membrane • intracellular membrane-bounded organelle • endoplasmic reticulum Biological process • central nervous system myelin maintenance • lipid modification • peripheral nervous system myelin maintenance • lipid metabolism • sphingolipid biosynthetic process • fatty acid metabolic process • fatty acid biosynthetic process • regulation of cell proliferation • regulation of hair cycle • sebaceous gland cell differentiation • oxidation-reduction process • lipid biosynthetic process • glucosylceramide biosynthetic process • galactosylceramide biosynthetic process • plasma membrane raft organization • ceramide biosynthetic process • establishment of skin barrier Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79152	338521
Ensembl	ENSG00000103089	ENSMUSG00000033579
UniProt	Q7L5A8	Q5MPP0
RefSeq (mRNA)	NM_024306	NM_178086
RefSeq (protein)	NP_077282	NP_835187
Location (UCSC)	Chr 16: 74.71 – 74.77 Mb	Chr 8: 111.35 – 111.39 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a protein that catalyzes the synthesis of 2-hydroxysphingolipids, a subset of sphingolipids that contain 2-hydroxy fatty acids. Sphingolipids play roles in many cellular processes and their structural diversity arises from modification of the hydrophobic ceramide moiety, such as by 2-hydroxylation of the N-acyl chain, and the existence of many different head groups.[5]

Mechanism of 2-hydroxylated sphingolipid generation. Essentially they are generated like their non-hydroxylated counterparts. The only difference is that fatty acids are hydroxylated by fatty acid 2-hydroxylase (FA2H) before being incorporated into dihydroceramide by ceramide synthases (CerS).

Clinical significance

Mutations in this gene have been associated with leukodystrophy dysmyelinating with spastic paraparesis with or without dystonia[5] as well as fatty acid hydroxylase-associated neurodegeneration.[6]

FA2H has been shown to modulate cell differentiation in vitro. FA2H is may be a Δ⁹-THC-regulated gene, as Δ⁹-THC induces differentiation signal(s) in poorly differentiated MDA-MB-231 cells.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000103089 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000033579 - 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. "Entrez Gene: Fatty acid 2-hydroxylase". Retrieved 2011-12-30.
6. Pierson TM, Simeonov DR, Sincan M, Adams DA, Markello T, Golas G, Fuentes-Fajardo K, Hansen NF, Cherukuri PF, Cruz P, Mullikin JC, Blackstone C, Tifft C, Boerkoel CF, Gahl WA (April 2012). "Exome sequencing and SNP analysis detect novel compound heterozygosity in fatty acid hydroxylase-associated neurodegeneration". European Journal of Human Genetics. 20 (4): 476–9. doi:10.1038/ejhg.2011.222. PMC 3306865. PMID 22146942.
7. Takeda S, Harada M, Su S, Okajima S, Miyoshi H, Yoshida K, Nishimura H, Okamoto Y, Amamoto T, Watanabe K, Omiecinski CJ, Aramaki H (2013). "Induction of the fatty acid 2-hydroxylase (FA2H) gene by Δ(9)-tetrahydrocannabinol in human breast cancer cells". The Journal of Toxicological Sciences. 38 (2): 305–8. PMC 4018719. PMID 23535410.

Further reading

• Alderson NL, Rembiesa BM, Walla MD, Bielawska A, Bielawski J, Hama H (November 2004). "The human FA2H gene encodes a fatty acid 2-hydroxylase". The Journal of Biological Chemistry. 279 (47): 48562–8. doi:10.1074/jbc.M406649200. PMID 15337768.
• Uchida Y, Hama H, Alderson NL, Douangpanya S, Wang Y, Crumrine DA, Elias PM, Holleran WM (May 2007). "Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation". The Journal of Biological Chemistry. 282 (18): 13211–9. doi:10.1074/jbc.M611562200. PMID 17355976.
• Dick KJ, Al-Mjeni R, Baskir W, Koul R, Simpson MA, Patton MA, Raeburn S, Crosby AH (July 2008). "A novel locus for an autosomal recessive hereditary spastic paraplegia (SPG35) maps to 16q21-q23". Neurology. 71 (4): 248–52. doi:10.1212/01.wnl.0000319610.29522.8a. PMID 18463364.
• Edvardson S, Hama H, Shaag A, Gomori JM, Berger I, Soffer D, Korman SH, Taustein I, Saada A, Elpeleg O (November 2008). "Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia". American Journal of Human Genetics. 83 (5): 643–8. doi:10.1016/j.ajhg.2008.10.010. PMC 2668027. PMID 19068277.
• Wheeler HE, Metter EJ, Tanaka T, Absher D, Higgins J, Zahn JM, Wilhelmy J, Davis RW, Singleton A, Myers RM, Ferrucci L, Kim SK (October 2009). Gibson G (ed.). "Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging". PLoS Genetics. 5 (10): e1000685. doi:10.1371/journal.pgen.1000685. PMC 2752811. PMID 19834535.
• Dastani Z, Pajukanta P, Marcil M, Rudzicz N, Ruel I, Bailey SD, Lee JC, Lemire M, Faith J, Platko J, Rioux J, Hudson TJ, Gaudet D, Engert JC, Genest J (March 2010). "Fine mapping and association studies of a high-density lipoprotein cholesterol linkage region on chromosome 16 in French-Canadian subjects". European Journal of Human Genetics. 18 (3): 342–7. doi:10.1038/ejhg.2009.157. PMC 2824775. PMID 19844255.
• Dick KJ, Eckhardt M, Paisán-Ruiz C, Alshehhi AA, Proukakis C, Sibtain NA, Maier H, Sharifi R, Patton MA, Bashir W, Koul R, Raeburn S, Gieselmann V, Houlden H, Crosby AH (April 2010). "Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35)". Human Mutation. 31 (4): E1251-60. doi:10.1002/humu.21205. PMID 20104589.
• Dan P, Edvardson S, Bielawski J, Hama H, Saada A (May 2011). "2-Hydroxylated sphingomyelin profiles in cells from patients with mutated fatty acid 2-hydroxylase". Lipids in Health and Disease. 10: 84. doi:10.1186/1476-511X-10-84. PMC 3107802. PMID 21599921.