FA2H

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

FA2H
Identifiers
AliasesFA2H, FAAH, FAH1, FAXDC1, SCS7, SPG35, fatty acid 2-hydroxylase
External IDsOMIM: 611026 MGI: 2443327 HomoloGene: 56284 GeneCards: FA2H
Orthologs
SpeciesHumanMouse
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 MbChr 8: 112.07 – 112.12 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/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 hereditary spastic paraplegia type 35 (SPG35) with or without dystonia[5] as well as fatty acid hydroxylase-associated neurodegeneration.[6] The largest cohort with a detailed phenotypical description and a highly sensitive imaging phenotype ('WHAT'- acronym for: white matter changes, hypointensity of the globus pallidus, ponto-cerebellar atrophy, and thin corpus callosum) was recently published.[7]

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.[8]

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, et al. (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. Rattay TW, Lindig T, Baets J, Smets K, Deconinck T, Söhn AS, et al. (June 2019). "FAHN/SPG35: a narrow phenotypic spectrum across disease classifications". Brain. 142 (6): 1561–1572. doi:10.1093/brain/awz102. PMC 6536916. PMID 31135052.
  8. 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. doi:10.2131/jts.38.305. PMC 4018719. PMID 23535410.

Further reading

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