CYP27C1

Last updated
CYP27C1
Identifiers
Aliases CYP27C1 , cytochrome P450 family 27 subfamily C member 1
External IDs HomoloGene: 70240; GeneCards: CYP27C1; OMA:CYP27C1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

339761

n/a

Ensembl

ENSG00000186684

n/a

UniProt

Q4G0S4

n/a

RefSeq (mRNA)

NM_001001665
NM_001367501
NM_001367502

n/a

RefSeq (protein)

NP_001001665
NP_001354430
NP_001354431

n/a

Location (UCSC) Chr 2: 127.18 – 127.22 Mb n/a
PubMed search [2] n/a
Wikidata
View/Edit Human

CYP27C1 (cytochrome P450, family 27, subfamily C, polypeptide 1) is a protein that in humans is encoded by the CYP27C1 gene. [3] [4] The Enzyme Commission number (EC) for this protein is EC 1.14.19.53. [5] The full accepted name is all-trans-retinol 3,4-desaturase and the EC number 1 classifies CYP27C1 as a oxidoreductase that acts on paired donor by reducing oxygen. [6] It is also identifiable by the UniProt code Q4G0S4. [7] [8]

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. [9]

The main function of the CYP27C1 enzyme is conversion of vitamin A1 (all-trans retinol) to vitamin A2 (all-trans 3,4-dehydroretinal). [10]

Activity

The basic reaction for CYP27C1 is as follows:

all-trans-retinol + 2 reduced adrenodoxin + 2 H+ + O2 = all-trans-3,4-didehydroretinol + 2 oxidized adrenodoxin + 2 H2O. [5]

The initial substrate for this reaction is ordinary retinol, which can come from a number of vitamers all known as vitamin A.

The catalytic efficiency of CYP27C1 was assessed for all trans-retinol, retinal, and retinoic acid, and was highest for retinol, indicating that this enzyme is primed to convert vitamin A1 to A2. [11] It does also convert all trans retinal, retinoic acid, and 11-cis retinal. [10]

Regulation

Thyroid hormones (TH) may play a role in inducing this change, as TH receptors have been shown to regulate CYP27C1 within the retinal pigment epithelium. [12] TH nuclear receptors thraa-I-, thrab-I-, and thrb-I- were needed for the successful conversion of vitamin A, however, no one receptor was identified as being absolutely necessary.

Structure

CYP27C1 is predicted to have many alpha helices and to be globular in shape. [13] It is unclear where the active site lies in the protein, but there is a low confidence loop region that would be able to fit a molecule of retinol.

Function in humans

CYP27C1 catalyzes 3,4-desaturation of retinoids, particularly all-trans-retinol (vitamin A1) to all-trans 3,4-dehydroretinal (vitamin A2). The enzyme is unusual among mammalian P450s in that the predominant oxidation is a desaturation and in that hydroxylation represents only a minor pathway - the enzyme catalyzes 3- and 4-hydroxylation as minor events. The enzyme is located in human skin epidermis. [14]

The function of the enzyme was only discovered in 2016. Before that, it was considered an "orphan" enzyme. [10] An orphan enzyme is an enzyme activity that has been experimentally characterized but for which there is no known amino-acid or nucleotide sequence data.

One of the functions in humans also involves negatively regulating lung cancer cell proliferation by means of regulating the IGF-1R/Akt/p53 signaling pathways. [15] Researches found that CYP27C1 knock-downs in mice led to increased tumor cell proliferation, colony formation, and tumor burden. Vinorelbine, a chemotherapy drug used to treat lung cancer, could potentially be a novel substrate for CYP27C1. [15]

Function in fish

Despite being found in human skin, CYP27C1 is also found in other mammals, birds, fish and amphibians. CYP27C1 is responsible for shifting photosensitivity by converting vitamin A1 to vitamin A2 in the rhodopsin in fish eyes. In zebrafish and lamprey, CYP27C1 is expressed in the retinal pigment epithelium. [11] [16] The replacement of A1 by A2 broadens the range of the spectral absorption bandwidth and shifts the sensitivity towards red. [17] This conversion also decreases photosensitivity.

In Pacific salmonids in particular, Coho salmon parr shift vitamin A1/A2 ratio in their rod visual pigments in accordance with temperature and day length. [18] A2 increases during winter and decreases in summer. The increased density ofA2 in winter may reduce the parr's ability to see and respond to near-infrared light, as occurs in zebrafish, [11] when there is less light availability. The seasonal differences in retinal expression in rods are indicative of plasticity in spectral scope driven by environmental conditions.

Similar shifts in vitamin A1 to A2 along with increased CYP7C1 expression in juvenile lampreys indicate that red-shifted vision is an ancestrally evolved mechanism that helped fish adapt to different spectral climates during ontogeny. [16] Differences in expression of CYP27C1 in the same species of lamprey in different areas further support that CYP27C1 is used in sensory plasticity and offer insights into the evolutionary history of the function of CYP27C1.

Recently, the gene sequence for CYP27C1 has been isolated, as least in goldfish.This gene is 540 amino acids long in Carassius auratus and has a GenBank reference number of XP-026113677.1. [19] This length is similar to other CYP reductases and is an average length for a protein.

CYP27C1 is the topic of the comic Sherman's lagoon for May 26, 2016. [20] In response to Hawthorne's inquiry about the chemical, Ernest explains that it is an enzyme that enhances ability to see infrared light, allowing fish to see better in murky waters. Ernest can see however that Hawthorne is more interested in how to synthesize it commercially.

Related Research Articles

<span class="mw-page-title-main">Vitamin A</span> Essential nutrient

Vitamin A is a fat-soluble vitamin, hence an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinal, retinoic acid, and several provitamin (precursor) carotenoids, most notably beta-carotene. Vitamin A has multiple functions: essential in embryo development for growth, maintaining the immune system, and healthy vision, where it combines with the protein opsin to form rhodopsin – the light-absorbing molecule necessary for both low-light and color vision.

<span class="mw-page-title-main">Retinol</span> Chemical compound

Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family that is found in food and used as a dietary supplement. Retinol or other forms of vitamin A are needed for vision, cellular development, maintenance of skin and mucous membranes, immune function and reproductive development. Dietary sources include fish, dairy products, and meat. As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xerophthalmia. It is taken by mouth or by injection into a muscle. As an ingredient in skin-care products, it is used to reduce wrinkles and other effects of skin aging.

β-Carotene Red-orange pigment of the terpenoids class

β-Carotene (beta-carotene) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons.

<span class="mw-page-title-main">Cytochrome P450</span> Class of enzymes

Cytochromes P450 are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for example, they have not been found in Escherichia coli. In mammals, these enzymes oxidize steroids, fatty acids, xenobiotics, and participate in many biosyntheses. By hydroxylation, CYP450 enzymes convert xenobiotics into hydrophilic derivatives, which are more readily excreted.

<span class="mw-page-title-main">Retinal</span> Chemical compound

Retinal is a polyene chromophore. Retinal, bound to proteins called opsins, is the chemical basis of visual phototransduction, the light-detection stage of visual perception (vision).

<span class="mw-page-title-main">Retinoic acid</span> Metabolite of vitamin A

Retinoic acid (used simplified here for all-trans-retinoic acid) is a metabolite of vitamin A1 (all-trans-retinol) that mediates the functions of vitamin A1 required for growth and development. All-trans-retinoic acid is required in chordate animals, which includes all higher animals from fish to humans. During early embryonic development, all-trans-retinoic acid generated in a specific region of the embryo helps determine position along the embryonic anterior/posterior axis by serving as an intercellular signaling molecule that guides development of the posterior portion of the embryo. It acts through Hox genes, which ultimately control anterior/posterior patterning in early developmental stages.

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

Carotenoid oxygenases are a family of enzymes involved in the cleavage of carotenoids to produce, for example, retinol, commonly known as vitamin A. This family includes an enzyme known as RPE65 which is abundantly expressed in the retinal pigment epithelium where it catalyzed the formation of 11-cis-retinol from all-trans-retinyl esters.

<span class="mw-page-title-main">Cholesterol 7 alpha-hydroxylase</span> Protein-coding gene in the species Homo sapiens

Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.

<span class="mw-page-title-main">21-Hydroxylase</span> Human enzyme that hydroxylates steroids

Steroid 21-hydroxylase is a protein that in humans is encoded by the CYP21A2 gene. The protein is an enzyme that hydroxylates steroids at the C21 position on the molecule. Naming conventions for enzymes are based on the substrate acted upon and the chemical process performed. Biochemically, this enzyme is involved in the biosynthesis of the adrenal gland hormones aldosterone and cortisol, which are important in blood pressure regulation, sodium homeostasis and blood sugar control. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively, within metabolic pathways which in humans ultimately lead to aldosterone and cortisol creation—deficiency in the enzyme may cause congenital adrenal hyperplasia.

<span class="mw-page-title-main">Prostacyclin synthase</span> Enzyme found in humans

Prostaglandin-I synthase also known as prostaglandin I2 (prostacyclin) synthase (PTGIS) or CYP8A1 is an enzyme involved in prostanoid biosynthesis that in humans is encoded by the PTGIS gene. This enzyme belongs to the family of cytochrome P450 isomerases.

The visual cycle is a process in the retina that replenishes the molecule retinal for its use in vision. Retinal is the chromophore of most visual opsins, meaning it captures the photons to begin the phototransduction cascade. When the photon is absorbed, the 11-cis retinal photoisomerizes into all-trans retinal as it is ejected from the opsin protein. Each molecule of retinal must travel from the photoreceptor cell to the RPE and back in order to be refreshed and combined with another opsin. This closed enzymatic pathway of 11-cis retinal is sometimes called Wald's visual cycle after George Wald (1906–1997), who received the Nobel Prize in 1967 for his work towards its discovery.

In enzymology, a retinol dehydrogenase (RDH) (EC 1.1.1.105) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">RPE65</span> Protein-coding gene in humans

Retinal pigment epithelium-specific 65 kDa protein is a retinoid isomerohydrolase enzyme of the vertebrate visual cycle. RPE65 is expressed in the retinal pigment epithelium and is responsible for the conversion of all-trans-retinyl esters to 11-cis-retinol during phototransduction. 11-cis-retinol is then used in visual pigment regeneration in photoreceptor cells. RPE65 belongs to the carotenoid oxygenase family of enzymes.

<span class="mw-page-title-main">CYP26A1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 26A1 is a protein that in humans is encoded by the CYP26A1 gene.

<span class="mw-page-title-main">CYP4F2</span> Enzyme protein in the species Homo sapiens

Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.

<span class="mw-page-title-main">CYP2R1</span> Mammalian protein found in Homo sapiens

CYP2R1 is cytochrome P450 2R1, an enzyme which is the principal vitamin D 25-hydroxylase. In humans it is encoded by the CYP2R1 gene located on chromosome 11p15.2. It is expressed in the endoplasmic reticulum in liver, where it performs the first step in the activation of vitamin D by catalyzing the formation of 25-hydroxyvitamin D.

<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

<span class="mw-page-title-main">Lecithin retinol acyltransferase</span> Mammalian protein found in Homo sapiens

Lecithin retinol acyltransferase is an enzyme that in humans is encoded by the LRAT gene.

Vitamin A2 is a subcategory of vitamin A.

11-cis-retinol dehydrogenase (EC 1.1.1.315, RDH5 (gene)) is an enzyme with systematic name 11-cis-retinol:NAD+ oxidoreductase. This enzyme catalyses the following chemical reaction

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000186684 – Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, et al. (January 2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics. 36 (1): 40–45. doi: 10.1038/ng1285 . PMID   14702039.
  4. ↑ Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, et al. (October 2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Research. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
  5. 1 2 "EC 1.14.19.53". iubmb.qmul.ac.uk. Archived from the original on 2023-12-11. Retrieved 2023-10-16.
  6. ↑ "EC 1.14". iubmb.qmul.ac.uk. Archived from the original on 2023-06-01. Retrieved 2023-10-16.
  7. ↑ "UniProt". www.uniprot.org. Retrieved 2023-10-17.
  8. ↑ Wenzel U, Kemper C, Köhl J (November 2021). "Canonical and non-canonical functions of the complement system in health and disease". British Journal of Pharmacology. 178 (22): 2751–2753. doi:10.1111/bph.v178.22. ISSN   0007-1188. PMID   34159599.
  9. ↑ PD-icon.svg This article incorporates public domain material from "Entrez Gene: CYP27C1". Reference Sequence collection . National Center for Biotechnology Information.
  10. 1 2 3 Kramlinger VM, Nagy LD, Fujiwara R, Johnson KM, Phan TT, Xiao Y, et al. (May 2016). "Human cytochrome P450 27C1 catalyzes 3,4-desaturation of retinoids". FEBS Letters. 590 (9): 1304–1312. doi:10.1002/1873-3468.12167. PMC   4864060 . PMID   27059013.
  11. 1 2 3 Enright JM, Toomey MB, Sato SY, Temple SE, Allen JR, Fujiwara R, et al. (December 2015). "Cyp27c1 Red-Shifts the Spectral Sensitivity of Photoreceptors by Converting Vitamin A1 into A2". Current Biology. 25 (23): 3048–3057. doi:10.1016/j.cub.2015.10.018. PMC   4910640 . PMID   26549260.
  12. ↑ Volkov LI, Kim-Han JS, Saunders LM, Poria D, Hughes AE, Kefalov VJ, et al. (June 2020). "Thyroid hormone receptors mediate two distinct mechanisms of long-wavelength vision". Proceedings of the National Academy of Sciences of the United States of America. 117 (26): 15262–15269. Bibcode:2020PNAS..11715262V. doi: 10.1073/pnas.1920086117 . PMC   7334509 . PMID   32541022.
  13. ↑ "AlphaFold Protein Structure Database". alphafold.ebi.ac.uk. Retrieved 2023-10-16.
  14. ↑ Johnson KM, Phan TT, Albertolle ME, Guengerich FP (August 2017). "Human mitochondrial cytochrome P450 27C1 is localized in skin and preferentially desaturates trans-retinol to 3,4-dehydroretinol". The Journal of Biological Chemistry. 292 (33): 13672–13687. doi: 10.1074/jbc.M116.773937 . PMC   5566523 . PMID   28701464.
  15. 1 2 Mo HY, Wei QY, Zhong QH, Zhao XY, Guo D, Han J, Noracharttiyapot W, Visser L, van den Berg A, Xu YM, Lau AT (January 2022). "Cytochrome P450 27C1 Level Dictates Lung Cancer Tumorigenicity and Sensitivity towards Multiple Anticancer Agents and Its Potential Interplay with the IGF-1R/Akt/p53 Signaling Pathway". International Journal of Molecular Sciences. 23 (14): 7853. doi: 10.3390/ijms23147853 . ISSN   1422-0067. PMC   9324654 . PMID   35887201.
  16. 1 2 Morshedian A, Toomey MB, Pollock GE, Frederiksen R, Enright JM, McCormick SD, et al. (July 2017). "Cambrian origin of the CYP27C1-mediated vitamin A1-to-A2 switch, a key mechanism of vertebrate sensory plasticity". Royal Society Open Science. 4 (7): 170362. Bibcode:2017RSOS....470362M. doi:10.1098/rsos.170362. PMC   5541561 . PMID   28791166.
  17. ↑ Corbo JC (July 2021). "Vitamin A1/A2 chromophore exchange: Its role in spectral tuning and visual plasticity". Developmental Biology. 475: 145–155. doi:10.1016/j.ydbio.2021.03.002. PMC   8900494 . PMID   33684435.
  18. ↑ Temple SE, Plate EM, Ramsden S, Haimberger TJ, Roth WM, Hawryshyn CW (March 2006). "Seasonal cycle in vitamin A1/A2-based visual pigment composition during the life history of coho salmon (Oncorhynchus kisutch)". Journal of Comparative Physiology A. 192 (3): 301–313. doi:10.1007/s00359-005-0068-3. PMID   16292551. S2CID   23080916.
  19. ↑ Li Q, He B, Ge C, Yu D (September 2022). "Transcriptomics-based systematic identification and tissue-specific distribution of cytochrome P450 genes in Carassius auratus". Aquaculture Research. 53 (13): 4567–4576. doi:10.1111/are.15958. ISSN   1355-557X. S2CID   250228435.
  20. ↑ Jim Toomey (May 26, 2016). "Sherman's lagoon". Archived from the original on May 28, 2016. Retrieved May 26, 2016.

Further reading

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

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.