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CYP27C1

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CYP27C1
Identifiers
AliasesCYP27C1, cytochrome P450 family 27 subfamily C member 1
External IDsHomoloGene: 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 Mbn/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]

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

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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

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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

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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

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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

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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.

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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.

References

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  1. ^ a b c 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. ^ a b "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. ^ Public Domain This article incorporates public domain material from "Entrez Gene: CYP27C1". Reference Sequence collection. National Center for Biotechnology Information.
  10. ^ a b c 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. ^ a b c 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. ^ a b 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. ^ a b 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

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  • Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (January 2004). "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants". Pharmacogenetics. 14 (1): 1–18. doi:10.1097/00008571-200401000-00001. PMID 15128046.
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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