View source for CYP4F22

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''CYP4F22''' ('''cy'''tochrome '''P'''450, family '''4''', subfamily '''F''', polypeptide '''22''') is a [[protein]] that in humans is encoded by the ''CYP4F22'' [[gene]].<ref name="pmid16436457">{{cite journal |vauthors=Lefèvre C, Bouadjar B, Ferrand V, Tadini G, Mégarbané A, Lathrop M, Prud'homme JF, Fischer J | title = Mutations in a new cytochrome P450 gene in lamellar ichthyosis type 3 | journal = Hum. Mol. Genet. | volume = 15 | issue = 5 | pages = 767–76 |date=March 2006 | pmid = 16436457 | doi = 10.1093/hmg/ddi491 | doi-access = free }}</ref>
This gene encodes a member of the [[cytochrome P450]] superfamily of [[enzyme]]s. The cytochrome P450 proteins are [[monooxygenase]]s 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 lamellaris|ichthyosis lamellar]] type 3.<ref name="entrez_2532">{{NCBI RefSeq| title = Entrez Gene: CYP4F22 | url =https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=126410 }}</ref>
==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<ref>{{cite book | pmid = 26233909 | pmc = 4667791 | year = 2015 | last1 = Johnson | first1 = A. L. | title = Cytochrome P450 Function and Pharmacological Roles in Inflammation and Cancer | volume = 74 | pages = 223–62 | last2 = Edson | first2 = K. Z. | last3 = Totah | first3 = R. A. | last4 = Rettie | first4 = A. E. | chapter = Cytochrome P450 ω-Hydroxylases in Inflammation and Cancer | doi = 10.1016/bs.apha.2015.05.002| series = Advances in Pharmacology | isbn = 9780128031193 }}</ref> 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).<ref>{{cite journal | pmid = 26056268 | pmc = 4485105 | year = 2015 | last1 = Ohno | first1 = Y | title = Essential role of the cytochrome P450 CYP4F22 in the production of acylceramide, the key lipid for skin permeability barrier formation | journal = Proceedings of the National Academy of Sciences | volume = 112 | issue = 25 | pages = 7707–12 | last2 = Nakamichi | first2 = S | last3 = Ohkuni | first3 = A | last4 = Kamiyama | first4 = N | last5 = Naoe | first5 = A | last6 = Tsujimura | first6 = H | last7 = Yokose | first7 = U | last8 = Sugiura | first8 = K | last9 = Ishikawa | first9 = J | last10 = Akiyama | first10 = M | last11 = Kihara | first11 = A | doi = 10.1073/pnas.1503491112 | bibcode = 2015PNAS..112.7707O | url = http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/60363/3/manuscript.pdf | doi-access = free }}</ref><ref name="auto">{{cite journal | pmid = 23954555 | year = 2014 | last1 = Krieg | first1 = P | title = The role of lipoxygenases in epidermis | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1841 | issue = 3 | pages = 390–400 | last2 = Fürstenberger | first2 = G | doi = 10.1016/j.bbalip.2013.08.005 }}</ref>  These VLCFA targets need not be free fatty acids but also can be acylated in an [[amide bond]] to [[sphingosine]] to form an acyl[[ceramide]].
==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.<ref>{{cite journal | pmid = 21558561 | pmc = 3129186 | year = 2011 | last1 = Zheng | first1 = Y | title = 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 = Journal of Biological Chemistry | volume = 286 | issue = 27 | pages = 24046–56 | last2 = Yin | first2 = H | last3 = Boeglin | first3 = W. E. | last4 = Elias | first4 = P. M. | last5 = Crumrine | first5 = D | last6 = Beier | first6 = D. R. | last7 = Brash | first7 = A. R. | doi = 10.1074/jbc.M111.251496 | doi-access = free }}</ref><ref>{{cite journal | pmid = 24021977 | pmc = 4116325 | year = 2014 | last1 = Muñoz-Garcia | first1 = A | title = The importance of the lipoxygenase-hepoxilin pathway in the mammalian epidermal barrier | journal = Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids | volume = 1841 | issue = 3 | pages = 401–8 | last2 = Thomas | first2 = C. P. | last3 = Keeney | first3 = D. S. | last4 = Zheng | first4 = Y | last5 = Brash | first5 = A. R. | doi = 10.1016/j.bbalip.2013.08.020 }}</ref><ref name="auto"/>
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.<ref>{{cite journal | pmid = 23871423 | year = 2013 | last1 = Sugiura | first1 = K | title = Lamellar ichthyosis in a collodion baby caused by CYP4F22 mutations in a non-consanguineous family outside the Mediterranean | journal = Journal of Dermatological Science | volume = 72 | issue = 2 | pages = 193–5 | last2 = Takeichi | first2 = T | last3 = Tanahashi | first3 = K | last4 = Ito | first4 = Y | last5 = Kosho | first5 = T | last6 = Saida | first6 = K | last7 = Uhara | first7 = H | last8 = Okuyama | first8 = R | last9 = Akiyama | first9 = M | doi = 10.1016/j.jdermsci.2013.06.008 }}</ref><ref name="pmid25982146">{{cite journal | pmid = 25982146 | year = 2015 | last1 = Sugiura | first1 = K | title = Update on autosomal recessive congenital ichthyosis: MRNA analysis using hair samples is a powerful tool for genetic diagnosis | journal = Journal of Dermatological Science | volume = 79 | issue = 1 | pages = 4–9 | last2 = Akiyama | first2 = M | doi = 10.1016/j.jdermsci.2015.04.009 }}</ref> Of the varies subtypes of congenital ichthyosiform erythroderma, these mutations have been associated almost exclusively with the [[Lamellar ichthyosis]] subtype.<ref name="pmid25982146"/>
==References==
{{Reflist|30em}}
==Further reading==
* {{cite journal  |last1=Strausberg |first1=RL |last2=Feingold |first2=EA |last3=Grouse |first3=LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2002 |pmid= 12477932 |doi= 10.1073/pnas.242603899  |pmc=139241 |bibcode=2002PNAS...9916899M |display-authors=etal|doi-access=free }}
* {{cite journal  |last1=Kimura |first1=K |last2=Wakamatsu |first2=A |last3=Suzuki |first3=Y |title=Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes |journal=Genome Res. |volume=16 |issue= 1 |pages= 55–65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406  |pmc=1356129 |display-authors=etal}}
* {{cite journal  |last1=Fischer |first1=J |last2=Faure |first2=A |last3=Bouadjar |first3=B |title=Two New Loci for Autosomal Recessive Ichthyosis on Chromosomes 3p21 and 19p12-q12 and Evidence for Further Genetic Heterogeneity |journal=Am. J. Hum. Genet. |volume=66 |issue= 3 |pages= 904–13 |year= 2000 |pmid= 10712205 |doi= 10.1086/302814  |pmc=1288171 |display-authors=etal}}
* {{cite journal  |last1=Elias |first1=PM |last2=Williams |first2=ML |last3=Holleran |first3=WM |title=Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism |journal=J. Lipid Res. |volume=49 |issue= 4 |pages= 697–714 |year= 2008 |pmid= 18245815 |doi= 10.1194/jlr.R800002-JLR200   |doi-access=free |pmc=2844331 |display-authors=etal}}
* {{cite journal  |last1=Nelson |first1=DR |last2=Zeldin |first2=DC |last3=Hoffman |first3=SM |title=Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants |journal=Pharmacogenetics |volume=14 |issue= 1 |pages= 1–18 |year= 2004 |pmid= 15128046 |doi=10.1097/00008571-200401000-00001  |display-authors=etal}}
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{{Cytochrome P450}}
{{gene-19-stub}}
[[Category:Cytochrome P450]]