* 611545

CYTOCHROME P450, FAMILY 4, SUBFAMILY F, POLYPEPTIDE 8; CYP4F8


Alternative titles; symbols

CYTOCHROME P450, SUBFAMILY IVF, POLYPEPTIDE 8


HGNC Approved Gene Symbol: CYP4F8

Cytogenetic location: 19p13.12     Genomic coordinates (GRCh38): 19:15,615,218-15,630,639 (from NCBI)


TEXT

Cloning and Expression

By RT-PCR of human seminal vesicles using degenerate CYP4 primers as probe, Bylund et al. (1999) cloned CYP4F8. The deduced 520-amino acid protein has a heme-binding region and conserved heme ligand cys468. CYP4F8 shares 81.2% and 76.7% amino acid identity with CYP4F2 (604426) and CYP4F3 (601270), respectively. Northern blot analysis of human seminal vesicles detected 2.1-kb and 2.3-kb transcripts.

By immunohistochemical and Western blot analysis of a wide range of tissues, Stark et al. (2003) localized CYP4F8 to human seminal vesicle epithelium, epidermis, corneal epithelium, and proximal renal tubules. Staining in healthy epidermis extended from the basal cell to granular cell layers. Northern blot analysis of human tissues detected 2.1-, 2.5-, and 5.8-kb transcripts in kidney and liver, and 2.1- and 2.5-kb transcripts in seminal vesicles. RT-PCR analysis confirmed CYP4F8 expression in scalp hair roots. RT-PCR and immunohistochemical studies showed increased CYP4F8 mRNA and protein expression in psoriatic lesions compared to unaffected epidermis in 4 patients with psoriasis (see 177900).

By RT-PCR, immunohistochemical analysis, and in situ hybridization, Stark et al. (2005) detected CYP4F8 expression in epithelial linings of seminal vesicles and the ampulla of the vas deferens and in transitional epithelium of the ureter and bladder. Immunofluorescence studies colocalized CYP4F8 protein with PTGS2 (600262) in distal vas deferens epithelium.


Gene Function

Using CYP4F8 expressed in yeast, Bylund et al. (2000) demonstrated that CYP4F8 catalyzed omega-2-hydroxylation of prostaglandin H1 (PGH1) and prostaglandin H2 (PGH2). CYP4F8 showed little activity against prostaglandins D2, E1, E2, F2-alpha, and leukotriene B4. Stark et al. (2005) showed that CYP4F8 metabolized prostaglandin I2 (PGI2) and a stable analog of PGI2 to 19-hydroxyl compounds.

Stark et al. (2005) characterized CYP4F8 enzyme activity against polyunsaturated long chain fatty acids. CYP4F8 catalyzed epioxidation of docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-3) and omega-3-hydroxylation of 22:5n-6, the latter forming 20-hydroxy-22:5n-6 as the main product. Single amino acid substitutions in substrate recognition site-1 (SRS1) and SRS4 of CYP4F8 affected oxygenation of arachidonic acid but did not affect oxygenation of PGH2 analogs.


Gene Structure

Bylund et al. (1999) determined that the CYP4F8 gene contains 13 exons.


Mapping

By genomic sequence analysis, Bylund et al. (1999) mapped the CYP4F8 gene to chromosome 19p13.1.


REFERENCES

  1. Bylund, J., Finnstrom, N., Oliw, E. H. Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles. Biochem. Biophys. Res. Commun. 261: 169-174, 1999. [PubMed: 10405341, related citations] [Full Text]

  2. Bylund, J., Hidestrand, M., Ingelman-Sundberg, M., Oliw, E. H. Identification of CYP4F8 in human seminal vesicles as a prominent 19-hydroxylase of prostaglandin endoperoxides. J. Biol. Chem. 275: 21844-21849, 2000. [PubMed: 10791960, related citations] [Full Text]

  3. Stark, K., Bylund, J., Torma, H., Sahlen, G., Oliw, E. H. On the mechanism of biosynthesis of 19-hydroxyprostaglandins of human seminal fluid and expression of cyclooxygenase-2, PGH 19-hydroxylase (CYP4F8) and microsomal PGE synthase-1 in seminal vesicles and vas deferens. Prostaglandins Other Lipid Mediat. 75: 47-64, 2005. [PubMed: 15789615, related citations] [Full Text]

  4. Stark, K., Torma, H., Cristea, M., Oliw, E. H. Expression of CYP4F8 (prostaglandin H 19-hydroxylase) in human epithelia and prominent induction in epidermis of psoriatic lesions. Arch. Biochem. Biophys. 409: 188-196, 2003. [PubMed: 12464258, related citations] [Full Text]

  5. Stark, K., Wongsud, B., Burman, R., Oliw, E. H. Oxygenation of polyunsaturated long chain fatty acids by recombinant CYP4F8 and CYP4F12 and catalytic importance of Tyr-125 and Gly-328 of CYP4F8. Arch. Biochem. Biophys. 441: 174-181, 2005. [PubMed: 16112640, related citations] [Full Text]


Creation Date:
Dorothy S. Reilly : 10/22/2007
Edit History:
wwang : 10/22/2007

* 611545

CYTOCHROME P450, FAMILY 4, SUBFAMILY F, POLYPEPTIDE 8; CYP4F8


Alternative titles; symbols

CYTOCHROME P450, SUBFAMILY IVF, POLYPEPTIDE 8


HGNC Approved Gene Symbol: CYP4F8

Cytogenetic location: 19p13.12     Genomic coordinates (GRCh38): 19:15,615,218-15,630,639 (from NCBI)


TEXT

Cloning and Expression

By RT-PCR of human seminal vesicles using degenerate CYP4 primers as probe, Bylund et al. (1999) cloned CYP4F8. The deduced 520-amino acid protein has a heme-binding region and conserved heme ligand cys468. CYP4F8 shares 81.2% and 76.7% amino acid identity with CYP4F2 (604426) and CYP4F3 (601270), respectively. Northern blot analysis of human seminal vesicles detected 2.1-kb and 2.3-kb transcripts.

By immunohistochemical and Western blot analysis of a wide range of tissues, Stark et al. (2003) localized CYP4F8 to human seminal vesicle epithelium, epidermis, corneal epithelium, and proximal renal tubules. Staining in healthy epidermis extended from the basal cell to granular cell layers. Northern blot analysis of human tissues detected 2.1-, 2.5-, and 5.8-kb transcripts in kidney and liver, and 2.1- and 2.5-kb transcripts in seminal vesicles. RT-PCR analysis confirmed CYP4F8 expression in scalp hair roots. RT-PCR and immunohistochemical studies showed increased CYP4F8 mRNA and protein expression in psoriatic lesions compared to unaffected epidermis in 4 patients with psoriasis (see 177900).

By RT-PCR, immunohistochemical analysis, and in situ hybridization, Stark et al. (2005) detected CYP4F8 expression in epithelial linings of seminal vesicles and the ampulla of the vas deferens and in transitional epithelium of the ureter and bladder. Immunofluorescence studies colocalized CYP4F8 protein with PTGS2 (600262) in distal vas deferens epithelium.


Gene Function

Using CYP4F8 expressed in yeast, Bylund et al. (2000) demonstrated that CYP4F8 catalyzed omega-2-hydroxylation of prostaglandin H1 (PGH1) and prostaglandin H2 (PGH2). CYP4F8 showed little activity against prostaglandins D2, E1, E2, F2-alpha, and leukotriene B4. Stark et al. (2005) showed that CYP4F8 metabolized prostaglandin I2 (PGI2) and a stable analog of PGI2 to 19-hydroxyl compounds.

Stark et al. (2005) characterized CYP4F8 enzyme activity against polyunsaturated long chain fatty acids. CYP4F8 catalyzed epioxidation of docosahexaenoic acid (22:6n-3) and docosapentaenoic acid (22:5n-3) and omega-3-hydroxylation of 22:5n-6, the latter forming 20-hydroxy-22:5n-6 as the main product. Single amino acid substitutions in substrate recognition site-1 (SRS1) and SRS4 of CYP4F8 affected oxygenation of arachidonic acid but did not affect oxygenation of PGH2 analogs.


Gene Structure

Bylund et al. (1999) determined that the CYP4F8 gene contains 13 exons.


Mapping

By genomic sequence analysis, Bylund et al. (1999) mapped the CYP4F8 gene to chromosome 19p13.1.


REFERENCES

  1. Bylund, J., Finnstrom, N., Oliw, E. H. Gene expression of a novel cytochrome P450 of the CYP4F subfamily in human seminal vesicles. Biochem. Biophys. Res. Commun. 261: 169-174, 1999. [PubMed: 10405341] [Full Text: https://doi.org/10.1006/bbrc.1999.1011]

  2. Bylund, J., Hidestrand, M., Ingelman-Sundberg, M., Oliw, E. H. Identification of CYP4F8 in human seminal vesicles as a prominent 19-hydroxylase of prostaglandin endoperoxides. J. Biol. Chem. 275: 21844-21849, 2000. [PubMed: 10791960] [Full Text: https://doi.org/10.1074/jbc.M001712200]

  3. Stark, K., Bylund, J., Torma, H., Sahlen, G., Oliw, E. H. On the mechanism of biosynthesis of 19-hydroxyprostaglandins of human seminal fluid and expression of cyclooxygenase-2, PGH 19-hydroxylase (CYP4F8) and microsomal PGE synthase-1 in seminal vesicles and vas deferens. Prostaglandins Other Lipid Mediat. 75: 47-64, 2005. [PubMed: 15789615] [Full Text: https://doi.org/10.1016/j.prostaglandins.2004.09.014]

  4. Stark, K., Torma, H., Cristea, M., Oliw, E. H. Expression of CYP4F8 (prostaglandin H 19-hydroxylase) in human epithelia and prominent induction in epidermis of psoriatic lesions. Arch. Biochem. Biophys. 409: 188-196, 2003. [PubMed: 12464258] [Full Text: https://doi.org/10.1016/s0003-9861(02)00511-8]

  5. Stark, K., Wongsud, B., Burman, R., Oliw, E. H. Oxygenation of polyunsaturated long chain fatty acids by recombinant CYP4F8 and CYP4F12 and catalytic importance of Tyr-125 and Gly-328 of CYP4F8. Arch. Biochem. Biophys. 441: 174-181, 2005. [PubMed: 16112640] [Full Text: https://doi.org/10.1016/j.abb.2005.07.003]


Creation Date:
Dorothy S. Reilly : 10/22/2007

Edit History:
wwang : 10/22/2007