Cytochrome P450 7B1

Details

Name
Cytochrome P450 7B1
Synonyms
  • 24-hydroxycholesterol 7-alpha-hydroxylase
  • 25/26-hydroxycholesterol 7-alpha-hydroxylase
  • 3-hydroxysteroid 7-alpha hydroxylase
  • Oxysterol 7-alpha-hydroxylase
Gene Name
CYP7B1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052703|Cytochrome P450 7B1
MAGEVSAATGRFSLERLGLPGLALAAALLLLALCLLVRRTRRPGEPPLIKGWLPYLGVVL
NLRKDPLRFMKTLQKQHGDTFTVLLGGKYITFILDPFQYQLVIKNHKQLSFRVFSNKLLE
KAFSISQLQKNHDMNDELHLCYQFLQGKSLDILLESMMQNLKQVFEPQLLKTTSWDTAEL
YPFCSSIIFEITFTTIYGKVIVCDNNKFISELRDDFLKFDDKFAYLVSNIPIELLGNVKS
IREKIIKCFSSEKLAKMQGWSEVFQSRQDVLEKYYVHEDLEIGAHHLGFLWASVANTIPT
MFWAMYYLLRHPEAMAAVRDEIDRLLQSTGQKKGSGFPIHLTREQLDSLICLESSIFEAL
RLSSYSTTIRFVEEDLTLSSETGDYCVRKGDLVAIFPPVLHGDPEIFEAPEEFRYDRFIE
DGKKKTTFFKRGKKLKCYLMPFGTGTSKCPGRFFALMEIKQLLVILLTYFDLEIIDDKPI
GLNYSRLLFGIQYPDSDVLFRYKVKS
Number of residues
506
Molecular Weight
58255.325
Theoretical pI
Not Available
GO Classification
Functions
25-hydroxycholesterol 7alpha-hydroxylase activity / 27-hydroxycholesterol 7-alpha-monooxygenase activity / heme binding / iron ion binding / oxysterol 7-alpha-hydroxylase activity / steroid hydroxylase activity
Processes
B cell chemotaxis / bile acid biosynthetic process / cholesterol homeostasis / cholesterol metabolic process / negative regulation of intracellular estrogen receptor signaling pathway / positive regulation of epithelial cell proliferation / prostate gland epithelium morphogenesis / sterol metabolic process
Components
endoplasmic reticulum membrane / integral component of membrane
General Function
A cytochrome P450 monooxygenase involved in the metabolism of endogenous oxysterols and steroid hormones, including neurosteroids (PubMed:10588945, PubMed:24491228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:10588945, PubMed:24491228). Catalyzes the hydroxylation of carbon hydrogen bonds of steroids with a preference for 7-alpha position (PubMed:10588945, PubMed:24491228). Usually metabolizes steroids carrying a hydroxy group at position 3, functioning as a 3-hydroxy steroid 7-alpha hydroxylase (PubMed:24491228). Hydroxylates oxysterols, including 25-hydroxycholesterol and (25R)-cholest-5-ene-3beta,26-diol toward 7-alpha hydroxy derivatives, which may be transported to the liver and converted to bile acids (PubMed:9802883, PubMed:10588945). Via its product 7-alpha,25-dihydroxycholesterol, a ligand for the chemotactic G protein-coupled receptor GPR183/EBI2, regulates B cell migration in germinal centers of lymphoid organs, thus guiding efficient maturation of plasma B cells and overall antigen-specific humoral immune response (By similarity). 7-alpha hydroxylates neurosteroids, including 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone) and pregnenolone, both involved in hippocampus-associated memory and learning (PubMed:24491228). Metabolizes androstanoids toward 6- or 7-alpha hydroxy derivatives (PubMed:24491228).
Specific Function
25-hydroxycholesterol 7alpha-hydroxylase activity
Pfam Domain Function
Transmembrane Regions
17-37 289-309
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0052704|Cytochrome P450 7B1 (CYP7B1)
ATGGCAGGAGAAGTGTCCGCGGCCACGGGCCGCTTTTCGCTGGAGCGGTTGGGCCTCCCG
GGCCTGGCCCTCGCCGCGGCCCTGCTGCTCCTGGCCCTCTGCTTGCTTGTCCGGCGCACC
AGGAGACCCGGTGAGCCTCCATTGATAAAAGGTTGGCTTCCTTATCTTGGAGTGGTCCTG
AACTTACGAAAAGACCCCTTAAGGTTCATGAAAACACTTCAAAAGCAACATGGTGACACT
TTCACAGTTCTTCTTGGTGGAAAGTACATAACATTTATCCTGGACCCCTTCCAGTACCAG
CTAGTGATAAAAAATCATAAACAATTAAGCTTTCGAGTATTTTCTAATAAATTATTAGAG
AAAGCATTTAGCATCAGTCAGTTGCAAAAAAATCATGACATGAATGATGAGCTTCACCTC
TGCTATCAATTTTTGCAAGGCAAATCTTTGGACATACTCTTGGAAAGCATGATGCAGAAT
CTAAAACAAGTTTTTGAACCCCAGCTGTTAAAAACCACAAGTTGGGACACGGCAGAACTG
TATCCATTCTGCAGCTCAATAATATTTGAGATCACATTTACAACTATATATGGAAAAGTT
ATTGTTTGTGACAACAACAAATTTATTAGTGAGCTAAGAGATGATTTTTTAAAATTTGAT
GACAAGTTTGCATATTTAGTATCCAACATACCCATTGAGCTTCTAGGAAATGTCAAGTCT
ATTAGAGAGAAAATTATAAAATGCTTCTCATCAGAAAAGTTAGCCAAGATGCAAGGATGG
TCAGAAGTTTTTCAAAGCAGGCAAGATGTCCTGGAGAAATATTATGTGCACGAGGACCTT
GAAATAGGAGCACATCATTTAGGCTTTCTCTGGGCCTCTGTGGCAAACACTATTCCAACT
ATGTTCTGGGCAATGTATTATCTTCTGCGGCACCCAGAAGCTATGGCAGCAGTGCGTGAC
GAAATTGACCGTTTGCTGCAGTCAACAGGTCAAAAGAAAGGGTCTGGATTTCCCATCCAC
CTCACCAGAGAACAATTGGACAGCCTAATCTGCCTAGAAAGCAGCATTTTTGAAGCTTTA
CGACTGTCCTCATATTCAACCACCATTCGTTTTGTTGAGGAGGATTTGACTCTCAGTTCA
GAGACCGGGGACTACTGTGTGCGAAAGGGAGACTTGGTAGCCATCTTTCCTCCAGTCCTA
CATGGTGACCCTGAAATCTTTGAAGCTCCAGAGGAGTTTAGATATGATCGTTTTATAGAA
GATGGTAAGAAGAAAACCACCTTTTTCAAAAGAGGGAAAAAGCTGAAGTGTTACCTAATG
CCGTTTGGAACTGGAACCAGCAAATGTCCAGGCCGATTTTTTGCACTTATGGAAATAAAA
CAATTGTTGGTTATACTTTTAACTTATTTTGATTTAGAAATAATTGATGATAAGCCCATA
GGACTAAACTACAGCCGCTTGTTGTTTGGTATTCAGTATCCAGATTCTGATGTTTTATTT
AGATACAAAGTGAAATCTTAG
Chromosome Location
8
Locus
8q12.3
External Identifiers
ResourceLink
UniProtKB IDO75881
UniProtKB Entry NameCP7B1_HUMAN
HGNC IDHGNC:2652
General References
  1. Setchell KD, Schwarz M, O'Connell NC, Lund EG, Davis DL, Lathe R, Thompson HR, Weslie Tyson R, Sokol RJ, Russell DW: Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7alpha-hydroxylase gene causes severe neonatal liver disease. J Clin Invest. 1998 Nov 1;102(9):1690-703. doi: 10.1172/JCI2962. [Article]
  2. Wu Z, Martin KO, Javitt NB, Chiang JY: Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1. J Lipid Res. 1999 Dec;40(12):2195-203. [Article]
  3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  4. Yantsevich AV, Dichenko YV, Mackenzie F, Mukha DV, Baranovsky AV, Gilep AA, Usanov SA, Strushkevich NV: Human steroid and oxysterol 7alpha-hydroxylase CYP7B1: substrate specificity, azole binding and misfolding of clinically relevant mutants. FEBS J. 2014 Mar;281(6):1700-13. doi: 10.1111/febs.12733. Epub 2014 Feb 20. [Article]
  5. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [Article]
  6. Tsaousidou MK, Ouahchi K, Warner TT, Yang Y, Simpson MA, Laing NG, Wilkinson PA, Madrid RE, Patel H, Hentati F, Patton MA, Hentati A, Lamont PJ, Siddique T, Crosby AH: Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. Am J Hum Genet. 2008 Feb;82(2):510-5. doi: 10.1016/j.ajhg.2007.10.001. Epub 2008 Jan 18. [Article]
  7. Goizet C, Boukhris A, Durr A, Beetz C, Truchetto J, Tesson C, Tsaousidou M, Forlani S, Guyant-Marechal L, Fontaine B, Guimaraes J, Isidor B, Chazouilleres O, Wendum D, Grid D, Chevy F, Chinnery PF, Coutinho P, Azulay JP, Feki I, Mochel F, Wolf C, Mhiri C, Crosby A, Brice A, Stevanin G: CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. Brain. 2009 Jun;132(Pt 6):1589-600. doi: 10.1093/brain/awp073. Epub 2009 May 12. [Article]
  8. Arnoldi A, Crimella C, Tenderini E, Martinuzzi A, D'Angelo MG, Musumeci O, Toscano A, Scarlato M, Fantin M, Bresolin N, Bassi MT: Clinical phenotype variability in patients with hereditary spastic paraplegia type 5 associated with CYP7B1 mutations. Clin Genet. 2012 Feb;81(2):150-7. doi: 10.1111/j.1399-0004.2011.01624.x. Epub 2011 Jan 31. [Article]
  9. Roos P, Svenstrup K, Danielsen ER, Thomsen C, Nielsen JE: CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities in hereditary spastic paraplegia type 5A. Acta Neurol Scand. 2014 May;129(5):330-4. doi: 10.1111/ane.12188. Epub 2013 Oct 1. [Article]
  10. Kara E, Tucci A, Manzoni C, Lynch DS, Elpidorou M, Bettencourt C, Chelban V, Manole A, Hamed SA, Haridy NA, Federoff M, Preza E, Hughes D, Pittman A, Jaunmuktane Z, Brandner S, Xiromerisiou G, Wiethoff S, Schottlaender L, Proukakis C, Morris H, Warner T, Bhatia KP, Korlipara LV, Singleton AB, Hardy J, Wood NW, Lewis PA, Houlden H: Genetic and phenotypic characterization of complex hereditary spastic paraplegia. Brain. 2016 Jul;139(Pt 7):1904-18. doi: 10.1093/brain/aww111. Epub 2016 May 23. [Article]
  11. Schubert SF, Hoffjan S, Dekomien G: Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal recessive hereditary spastic paraplegia. Mol Cell Probes. 2016 Feb;30(1):53-5. doi: 10.1016/j.mcp.2015.12.001. Epub 2015 Dec 20. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB015305alpha-androstane-3alpha,17beta-diolexperimental, illicitunknownsubstrateDetails