Mouse anti-Human/Mouse/Rat sapiens (Human) CYP7B1 Monoclonal Antibody

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:10588945, PubMed:9802883). 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)

Subcellular Location

Endoplasmic reticulum membrane (Multi-pass membrane protein); Microsome membrane (Multi-pass membrane protein)

Disease Association

Spastic paraplegia 5A, autosomal recessive (SPG5A) : A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. [The disease is caused by variants affecting the gene represented in this entry] | Congenital bile acid synthesis defect 3 (CBAS3) : A disorder resulting in severe cholestasis, cirrhosis and liver synthetic failure. Hepatic microsomal oxysterol 7-alpha-hydroxylase activity is undetectable. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Widely expressed. Expressed in brain, testis, ovary, prostate, liver, colon, kidney, small intestine, thymus and spleen

Pathway

Steroid hormone biosynthesis

• Setchell K.D.R. et al. Identification of a new inborn error in bile acid synthesis: mutation of the oxysterol 7-alpha-hydroxylase gene causes severe neonatal liver disease. — J. Clin. Invest. (1998)
• Wu Z.L. et al. Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7B1. — J. Lipid Res. (1999)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Yantsevich A.V. et al. Human steroid and oxysterol 7alpha-hydroxylase CYP7B1: substrate specificity, azole binding and misfolding of clinically relevant mutants. — FEBS J. (2014)
• Bian Y. et al. An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. — J. Proteomics (2014)
• Tsaousidou M.K. et al. Sequence alterations within CYP7B1 implicate defective cholesterol homeostasis in motor-neuron degeneration. — Am. J. Hum. Genet. (2008)
• Goizet C. et al. CYP7B1 mutations in pure and complex forms of hereditary spastic paraplegia type 5. — Brain (2009)