CYP4F22

CYP4F22 (cytochrome P450, family 4, subfamily F, polypeptide 22) is a protein that in humans is encoded by the CYP4F22 gene.[5]

CYP4F22
Identifiers
AliasesCYP4F22, ARCI5, INLNE, LI3, cytochrome P450 family 4 subfamily F member 22
External IDsOMIM: 611495 MGI: 2445210 HomoloGene: 69814 GeneCards: CYP4F22
Gene location (Human)
Chr.Chromosome 19 (human)[1]
Band19p13.12Start15,508,525 bp[1]
End15,552,317 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

126410

320997

Ensembl

ENSG00000171954

ENSMUSG00000061126

UniProt

Q6NT55

Q8BGU0

RefSeq (mRNA)

NM_173483

NM_177307

RefSeq (protein)

NP_775754

NP_796281

Location (UCSC)Chr 19: 15.51 – 15.55 MbChr 17: 32.45 – 32.49 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This gene is part of a cluster of cytochrome P450 genes on chromosome 19 and encodes an enzyme thought to play a role in the 12(R)-lipoxygenase pathway. Mutations in this gene are the cause of ichthyosis lamellar type 3.[6]

Activity

CYP4F22, like other CYP4F proteins, is a Cytochrome P450 omega hydroxylase, i.e. an enzyme that metabolizes fatty acids to their omega hydroxyl derivatives (see Omega oxidation). This hydroxylation may: a) produce a biologically important signaling molecule such as occurs in the metabolism of 20-carbon straight chain polyunsaturated fatty acid, arachidonic acid, to 20-Hydroxyeicosatetraenoic acid, b) inactivate a biologically important product such as the metabolism of the arachidonic acid metabolite, 5-oxo-eicosatetraenoic acid, to its ~100-fold less potent product, 5-oxo-20-hydroxy-eicosatetraenoic acid, or c) be the first step in the further metabolism of xenobiotics or natural compounds[7] CYP4F22 serves the latter function. It is a type 1 Integral membrane protein located in the endoplasmic reticulum of cells in the stratum granulosum of mammalian, including human, skin where it functions to attach an omega hydroxyl residue to fatty acids that are exceptionally long, 28 or more carbons, i.e. the very long chain fatty acids (VLCFA).[8][9] These VLCFA targets need not be free fatty acids but also can be acylated in an amide bond to sphingosine to form an acylceramide.

Function

CYP4F22 omega hydroxylates the VLCFA in esterified omega-oxyacyl-sphingosine complex to form an esterified omega-hydroxyacyl-sphingosine complex. This step is critical for delivering the wax-like, extremely hydrophobic VLCFA to the stratum corneum near the skin surface. It is these skin surface VLCFA which create and maintain the skin's ability to function as a water barrier.[10][11][12]

CYP4F22, like many of the CYP4F series of CYPs, may prove to serve other functions but its role in hydroxylating VLCFA in the skin's water barrier function, as defined in genetic studies (see below), has dominated research on it.

Genetic studies

A small number of newborns with Congenital ichthyosiform erythroderma have been found to have autosomal recessive lose of function mutations in CYP4F22.[13][14] Of the varies subtypes of congenital ichthyosiform erythroderma, these mutations have been associated almost exclusively with the Lamellar ichthyosis subtype.[14]

References

  1. GRCh38: Ensembl release 89: ENSG00000171954 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000061126 - 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. Lefèvre C, Bouadjar B, Ferrand V, Tadini G, Mégarbané A, Lathrop M, Prud'homme JF, Fischer J (March 2006). "Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3". Hum. Mol. Genet. 15 (5): 767–76. doi:10.1093/hmg/ddi491. PMID 16436457.
  6. "Entrez Gene: CYP4F22".
  7. Johnson, A. L.; Edson, K. Z.; Totah, R. A.; Rettie, A. E. (2015). Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer. Advances in Pharmacology. 74. pp. 223–62. doi:10.1016/bs.apha.2015.05.002. ISBN 9780128031193. PMC 4667791. PMID 26233909.
  8. Ohno, Y; Nakamichi, S; Ohkuni, A; Kamiyama, N; Naoe, A; Tsujimura, H; Yokose, U; Sugiura, K; Ishikawa, J; Akiyama, M; Kihara, A (2015). "Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation" (PDF). Proceedings of the National Academy of Sciences. 112 (25): 7707–12. doi:10.1073/pnas.1503491112. PMC 4485105. PMID 26056268.
  9. Krieg, P; Fürstenberger, G (2014). "The role of lipoxygenases in epidermis". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1841 (3): 390–400. doi:10.1016/j.bbalip.2013.08.005. PMID 23954555.
  10. Zheng, Y; Yin, H; Boeglin, W. E.; Elias, P. M.; Crumrine, D; Beier, D. R.; Brash, A. R. (2011). "Lipoxygenases mediate the effect of essential fatty acid in skin barrier formation: A proposed role in releasing omega-hydroxyceramide for construction of the corneocyte lipid envelope". Journal of Biological Chemistry. 286 (27): 24046–56. doi:10.1074/jbc.M111.251496. PMC 3129186. PMID 21558561.
  11. Muñoz-Garcia, A; Thomas, C. P.; Keeney, D. S.; Zheng, Y; Brash, A. R. (2014). "The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal barrier". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1841 (3): 401–8. doi:10.1016/j.bbalip.2013.08.020. PMC 4116325. PMID 24021977.
  12. Krieg, P; Fürstenberger, G (2014). "The role of lipoxygenases in epidermis". Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids. 1841 (3): 390–400. doi:10.1016/j.bbalip.2013.08.005. PMID 23954555.
  13. Sugiura, K; Takeichi, T; Tanahashi, K; Ito, Y; Kosho, T; Saida, K; Uhara, H; Okuyama, R; Akiyama, M (2013). "Lamellar ichthyosis in a collodion baby caused by CYP4F22 mutations in a non-consanguineous family outside the Mediterranean". Journal of Dermatological Science. 72 (2): 193–5. doi:10.1016/j.jdermsci.2013.06.008. PMID 23871423.
  14. Sugiura, K; Akiyama, M (2015). "Update on autosomal recessive congenital ichthyosis: MRNA analysis using hair samples is a powerful tool for genetic diagnosis". Journal of Dermatological Science. 79 (1): 4–9. doi:10.1016/j.jdermsci.2015.04.009. PMID 25982146.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.


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