CYP4F22

Last updated
CYP4F22
Identifiers
Aliases CYP4F22 , ARCI5, INLNE, LI3, cytochrome P450 family 4 subfamily F member 22
External IDs OMIM: 611495 MGI: 2445210 HomoloGene: 69814 GeneCards: CYP4F22
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_173483

NM_177307

RefSeq (protein)

NP_775754

NP_796281

Location (UCSC) Chr 19: 15.51 – 15.55 Mb Chr 17: 32.67 – 32.71 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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

Contents

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] [9]

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. [12] [13] Of the varies subtypes of congenital ichthyosiform erythroderma, these mutations have been associated almost exclusively with the Lamellar ichthyosis subtype. [13]

Related Research Articles

<span class="mw-page-title-main">CYP2E1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.

<span class="mw-page-title-main">Lipoxygenase</span>

Lipoxygenases are a family of (non-heme) iron-containing enzymes most of which catalyze the dioxygenation of polyunsaturated fatty acids in lipids containing a cis,cis-1,4-pentadiene into cell signaling agents that serve diverse roles as autocrine signals that regulate the function of their parent cells, paracrine signals that regulate the function of nearby cells, and endocrine signals that regulate the function of distant cells.

<span class="mw-page-title-main">ABCA12</span> Protein-coding gene in the species Homo sapiens

ATP-binding cassette sub-family A member 12 also known as ATP-binding cassette transporter 12 is a protein that in humans is encoded by the ABCA12 gene.

<span class="mw-page-title-main">CYP1A2</span> Enzyme in the human body

Cytochrome P450 1A2, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.

<span class="mw-page-title-main">CYP2C9</span> Enzyme protein

Cytochrome P450 family 2 subfamily C member 9 is an enzyme protein. The enzyme is involved in metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme.

<span class="mw-page-title-main">CYP2C8</span> Gene-coded protein involved in metabolism of xenobiotics

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<span class="mw-page-title-main">CYP1A1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.

<span class="mw-page-title-main">CYP2J2</span> Gene of the species Homo sapiens

Cytochrome P450 2J2 (CYP2J2) is a protein that in humans is encoded by the CYP2J2 gene. CYP2J2 is a member of the cytochrome P450 superfamily of enzymes. The enzymes are oxygenases which catalyze many reactions involved in the metabolism of drugs and other xenobiotics) as well as in the synthesis of cholesterol, steroids and other lipids.

<span class="mw-page-title-main">CYP4A11</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4A11 is a protein that in humans is codified by the CYP4A11 gene.

<span class="mw-page-title-main">ALOX12B</span> Protein-coding gene in the species Homo sapiens

Arachidonate 12-lipoxygenase, 12R type, also known as ALOX12B, 12R-LOX, and arachidonate lipoxygenase 3, is a lipoxygenase-type enzyme composed of 701 amino acids and encoded by the ALOX12B gene. The gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOXE3 and ALOX15B. Among the human lipoxygenases, ALOX12B is most closely related in amino acid sequence to ALOXE3

<span class="mw-page-title-main">CYP4F8</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4F8 is a protein that in humans is encoded by the CYP4F8 gene.

<span class="mw-page-title-main">CYP4F12</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 4F12 is a protein that in humans is encoded by the CYP4F12 gene.

<span class="mw-page-title-main">CYP4F3</span> Protein-coding gene in the species Homo sapiens

Leukotriene-B(4) omega-hydroxylase 2 is an enzyme that in humans is encoded by the CYP4F3 gene. CYP4F3 encodes two distinct enzymes, CYP4F3A and CYP4F3B, which originate from the alternative splicing of a single pre-mRNA precursor molecule; selection of either isoform is tissue-specific with CYP3F3A being expressed mostly in leukocytes and CYP4F3B mostly in the liver.

<span class="mw-page-title-main">ALOXE3</span> Protein-coding gene in the species Homo sapiens

Epidermis-type lipoxygenase 3 is a member of the lipoxygenase family of enzymes; in humans, it is encoded by the ALOXE3 gene. This gene is located on chromosome 17 at position 13.1 where it forms a cluster with two other lipoxygenases, ALOX12B and ALOX15B. Among the human lipoxygenases, ALOXE3 is most closely related in amino acid sequence to ALOX12B. ALOXE3, ALOX12B, and ALOX15B are often classified as epidermal lipoxygenases, in distinction to the other three human lipoxygenases, because they were initially defined as being highly or even exclusively expressed and functioning in skin. The epidermis-type lipoxygenases are now regarded as a distinct subclass within the multigene family of mammalian lipoxygenases with mouse Aloxe3 being the ortholog to human ALOXE3, mouse Alox12b being the ortholog to human ALOX12B, and mouse Alox8 being the ortholog to human ALOX15B [supplied by OMIM]. ALOX12B and ALOXE3 in humans, Alox12b and Aloxe3 in mice, and comparable orthologs in other in other species are proposed to act sequentially in a multistep metabolic pathway that forms products that are structurally critical for creating and maintaining the skin's water barrier function.

Epoxygenases are a set of membrane-bound, heme-containing cytochrome P450 enzymes that metabolize polyunsaturated fatty acids to epoxide products that have a range of biological activities. The most thoroughly studied substrate of the CYP epoxylgenases is arachidonic acid. This polyunsaturated fatty acid is metabolized by cyclooxygenases to various prostaglandin, thromboxane, and prostacyclin metabolites in what has been termed the first pathway of eicosanoid production; it is also metabolized by various lipoxygenases to hydroxyeicosatetraenoic acids and leukotrienes in what has been termed the second pathway of eicosanoid production. The metabolism of arachidonic acid to epoxyeicosatrienoic acids by the CYP epoxygenases has been termed the third pathway of eicosanoid metabolism. Like the first two pathways of eicosanoid production, this third pathway acts as a signaling pathway wherein a set of enzymes metabolize arachidonic acid to a set of products that act as secondary signals to work in activating their parent or nearby cells and thereby orchestrate functional responses. However, none of these three pathways is limited to metabolizing arachidonic acid to eicosanoids. Rather, they also metabolize other polyunsaturated fatty acids to products that are structurally analogous to the eicosanoids but often have different bioactivity profiles. This is particularly true for the CYP epoxygenases which in general act on a broader range of polyunsaturated fatty acids to form a broader range of metabolites than the first and second pathways of eicosanoid production. Furthermore, the latter pathways form metabolites many of which act on cells by binding with and thereby activating specific and well-characterized receptor proteins; no such receptors have been fully characterized for the epoxide metabolites. Finally, there are relatively few metabolite-forming lipoxygenases and cyclooxygenases in the first and second pathways and these oxygenase enzymes share similarity between humans and other mammalian animal models. The third pathway consists of a large number of metabolite-forming CYP epoxygenases and the human epoxygenases have important differences from those of animal models. Partly because of these differences, it has been difficult to define clear roles for the epoxygenase-epoxide pathways in human physiology and pathology.

<span class="mw-page-title-main">CYP4F11</span> Protein-coding gene in the species Homo sapiens

CYP4F11 is a protein that in humans is encoded by the CYP4F11 gene. 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. Another member of this family, CYP4F2, is approximately 16 kb away. Alternatively spliced transcript variants encoding the same protein have been found for this gene.

<span class="mw-page-title-main">CYP4A22</span> Protein-coding gene in the species Homo sapiens

CYP4A22 also known as fatty acid omega-hydroxylase is a protein which in humans is encoded by the CYP4A22 gene.

<span class="mw-page-title-main">CYP2U1</span> Protein-coding gene in the species Homo sapiens

CYP2U1 is a protein that in humans is encoded by the CYP2U1 gene

Cytochrome P450 omega hydroxylases, also termed cytochrome P450 ω-hydroxylases, CYP450 omega hydroxylases, CYP450 ω-hydroxylases, CYP omega hydroxylase, CYP ω-hydroxylases, fatty acid omega hydroxylases, cytochrome P450 monooxygenases, and fatty acid monooxygenases, are a set of cytochrome P450-containing enzymes that catalyze the addition of a hydroxyl residue to a fatty acid substrate. The CYP omega hydroxylases are often referred to as monoxygenases; however, the monooxygenases are CYP450 enzymes that add a hydroxyl group to a wide range of xenobiotic and naturally occurring endobiotic substrates, most of which are not fatty acids. The CYP450 omega hydroxylases are accordingly better viewed as a subset of monooxygenases that have the ability to hydroxylate fatty acids. While once regarded as functioning mainly in the catabolism of dietary fatty acids, the omega oxygenases are now considered critical in the production or break-down of fatty acid-derived mediators which are made by cells and act within their cells of origin as autocrine signaling agents or on nearby cells as paracrine signaling agents to regulate various functions such as blood pressure control and inflammation.

<span class="mw-page-title-main">NIPAL4</span> Gene

Nipa‐Like Domain‐Containing 4, also known as NIPAL4 or Ichthyin, is a gene that is predicted to code for a transmembrane protein with nine transmembrane domains. NIPAL4 codes for the protein magnesium transporter NIPA4, which acts as a Mg2+
transporter.

References

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  2. 1 2 3 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. PD-icon.svg This article incorporates public domain material from "Entrez Gene: CYP4F22". Reference Sequence collection . National Center for Biotechnology Information.
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  12. 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.
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Further reading

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