CYP17A1

CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1) is a Protein Coding gene. Diseases associated with CYP17A1 include Adrenal Hyperplasia, Congenital, Due To 17-Alpha-Hydroxylase Deficiency and Pseudohermaphroditism. Among its related pathways are superpathway of steroid hormone biosynthesis and Aldosterone synthesis and secretion. Gene Ontology (GO) annotations related to this gene include iron ion binding and oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen. An important paralog of this gene is CYP21A2.

Full Name

Cytochrome P450 Family 17 Subfamily A Member 1

Function

A cytochrome P450 monooxygenase involved in corticoid and androgen biosynthesis (PubMed:9452426, PubMed:27339894, PubMed:22266943, PubMed:25301938).

Catalyzes 17-alpha hydroxylation of C21 steroids, which is common for both pathways. A second oxidative step, required only for androgen synthesis, involves an acyl-carbon cleavage. The 17-alpha hydroxy intermediates, as part of adrenal glucocorticoids biosynthesis pathway, are precursors of cortisol (PubMed:9452426, PubMed:25301938) (Probable).

Hydroxylates steroid hormones, pregnenolone and progesterone to form 17-alpha hydroxy metabolites, followed by the cleavage of the C17-C20 bond to form C19 steroids, dehydroepiandrosterone (DHEA) and androstenedione (PubMed:9452426, PubMed:27339894, PubMed:22266943, PubMed:25301938).

Has 16-alpha hydroxylase activity. Catalyzes 16-alpha hydroxylation of 17-alpha hydroxy pregnenolone, followed by the cleavage of the C17-C20 bond to form 16-alpha-hydroxy DHEA. Also 16-alpha hydroxylates androgens, relevant for estriol synthesis (PubMed:27339894, PubMed:25301938).

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:9452426, PubMed:27339894, PubMed:22266943, PubMed:25301938).

Biological Process

Androgen biosynthetic process Source: Reactome
Glucocorticoid biosynthetic process Source: Reactome
Hormone biosynthetic process Source: UniProtKB
Progesterone metabolic process Source: UniProtKB
Sex differentiation Source: ProtInc
Steroid biosynthetic process Source: ProtInc
Steroid metabolic process Source: UniProtKB

Cellular Location

Endoplasmic reticulum membrane; Microsome membrane

Involvement in disease

Adrenal hyperplasia 5 (AH5):
A form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV, less severely affected patients), with normal aldosterone biosynthesis, 'non-classic form' or late-onset (NC or LOAH) and 'cryptic' (asymptomatic).

PTM

Phosphorylation is necessary for 17,20-lyase, but not for 17-alpha-hydroxylase activity.