CYP4F22

CYP4F22
Identifiers
AliasesCYP4F22, ARCI5, INLNE, LI3, cytochrome P450 family 4 subfamily F member 22
External IDsOMIM: 611495; MGI: 2445210; HomoloGene: 69814; GeneCards: CYP4F22; OMA:CYP4F22 - orthologs
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: 32.67 – 32.71 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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]

Function

CYP4F22 is a Cytochrome P450 omega hydroxylase, an enzyme that catalyzes the omega oxidation of fatty acids by introducing a hydroxyl group at the terminal (omega) position.[7] In general, omega hydroxylation may: (a) generate biologically active signaling molecules (e.g. conversion of arachidonic acid to 20-Hydroxyeicosatetraenoic acid), (b) inactivate bioactive lipids (e.g. metabolism of 5-oxo-eicosatetraenoic acid to its ~100-fold less potent 5-oxo-20-hydroxy-eicosatetraenoic acid), or (c) initiate further metabolism of xenobiotics and endogenous compounds. CYP4F22 primarily fulfills the latter role.[8]

CYP4F22 is a type I integral membrane protein localized to the endoplasmic reticulum of keratinocytes in the stratum granulosum of mammalian skin. Its specific substrates are exceptionally long fatty acids (≥C28), known as very long chain fatty acids (VLCFA).[9][10] These VLCFA can exist as free fatty acids or be amide-linked to sphingosine to form acylceramide precursors.

The enzyme hydroxylates VLCFA within esterified omega-oxyacyl-sphingosine complexes, producing omega-hydroxyacyl-sphingosine derivatives. This modification is essential for trafficking these highly hydrophobic, wax-like VLCFA into the stratum corneum, where they are incorporated into the extracellular lipid matrix. These specialized lipids provide the physical basis of the skin’s water-impermeability barrier.[11][12][10]

Although CYP4F22, like other CYP4F isoforms, may have additional metabolic roles, its critical and well-defined function is in omega-hydroxylation of VLCFA for skin barrier formation, as confirmed by genetic and biochemical studies.[13]

Clinical significance

A small number of newborns with Congenital ichthyosiform erythroderma have been found to have autosomal recessive lose of function mutations in CYP4F22.[14][15] Of the varies subtypes of congenital ichthyosiform erythroderma, these mutations have been associated almost exclusively with the Lamellar ichthyosis subtype.[15]

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000171954 – Ensembl, May 2017
  2. ^ a b c 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, et al. (March 2006). "Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3". Human Molecular Genetics. 15 (5): 767–776. doi:10.1093/hmg/ddi491. PMID 16436457.
  6. ^ Public Domain This article incorporates public domain material from "Entrez Gene: CYP4F22". Reference Sequence collection. National Center for Biotechnology Information.
  7. ^ Johnson AL, Edson KZ, Totah RA, Rettie AE (2015). "Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer". Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer. Advances in Pharmacology. Vol. 74. pp. 223–262. doi:10.1016/bs.apha.2015.05.002. ISBN 978-0-12-803119-3. PMC 4667791. PMID 26233909.
  8. ^ Johnson AL, Edson KZ, Totah RA, Rettie AE (2015). "Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer". Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer. Advances in Pharmacology. Vol. 74. pp. 223–262. doi:10.1016/bs.apha.2015.05.002. ISBN 978-0-12-803119-3. PMC 4667791. PMID 26233909.
  9. ^ Ohno Y, Nakamichi S, Ohkuni A, Kamiyama N, Naoe A, Tsujimura H, et al. (Jun 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 of the United States of America. 112 (25): 7707–7712. Bibcode:2015PNAS..112.7707O. doi:10.1073/pnas.1503491112. PMC 4485105. PMID 26056268.
  10. ^ a b Krieg P, Fürstenberger G (Mar 2014). "The role of lipoxygenases in epidermis". Biochimica et Biophysica Acta. 1841 (3): 390–400. doi:10.1016/j.bbalip.2013.08.005. PMID 23954555.
  11. ^ Zheng Y, Yin H, Boeglin WE, Elias PM, Crumrine D, Beier DR, et al. (Jul 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". The Journal of Biological Chemistry. 286 (27): 24046–24056. doi:10.1074/jbc.M111.251496. PMC 3129186. PMID 21558561.
  12. ^ Muñoz-Garcia A, Thomas CP, Keeney DS, Zheng Y, Brash AR (Mar 2014). "The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal barrier". Biochimica et Biophysica Acta. 1841 (3): 401–408. doi:10.1016/j.bbalip.2013.08.020. PMC 4116325. PMID 24021977.
  13. ^ Ohno Y, Nakamichi S, Ohkuni A, Kamiyama N, Naoe A, Tsujimura H, et al. (Jun 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 of the United States of America. 112 (25): 7707–7712. Bibcode:2015PNAS..112.7707O. doi:10.1073/pnas.1503491112. PMC 4485105. PMID 26056268.
  14. ^ Sugiura K, Takeichi T, Tanahashi K, Ito Y, Kosho T, Saida K, et al. (Nov 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): 193–195. doi:10.1016/j.jdermsci.2013.06.008. PMID 23871423.
  15. ^ a b Sugiura K, Akiyama M (Jul 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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