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
Aliases	CYP4F22, ARCI5, INLNE, LI3, cytochrome P450 family 4 subfamily F member 22
External IDs	OMIM: 611495; MGI: 2445210; HomoloGene: 69814; GeneCards: CYP4F22; OMA:CYP4F22 - orthologs
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.12 Start 15,508,525 bp[1] End 15,552,317 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17|17 B1 Start 32,671,697 bp[2] End 32,712,294 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of arm skin of leg skin of abdomen vulva human penis gonad skin of thigh gums granulocyte gingival epithelium Top expressed in lip esophagus spermatid skin of external ear primary oocyte skin of abdomen seminiferous tubule zygote skin of back lumbar spinal ganglion More reference expression data BioGPS n/a
Gene ontology Molecular function iron ion binding oxidoreductase activity heme binding oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen metal ion binding monooxygenase activity Cellular component organelle membrane endoplasmic reticulum membrane endoplasmic reticulum membrane intracellular membrane-bounded organelle Biological process icosanoid metabolic process Sources:Amigo / QuickGO
Orthologs Species Human Mouse 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 Mb Chr 17: 32.67 – 32.71 Mb PubMed search [3] [4]
Wikidata
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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]