Information on EC 1.14.13.13 - calcidiol 1-monooxygenase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
1.14.13.13
-
RECOMMENDED NAME
GeneOntology No.
calcidiol 1-monooxygenase
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
ferredoxin, ferredoxin reductase and cytochrome P-450
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
reconstituted with cytochrome P-450, adrenal ferredoxin, i.e. adrenodoxin, and adrenodoxin reductase
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
ferredoxin, ferredoxin reductase and cytochrome P-450; kidney mitochondrial 25-hydroxyvitamin D3-1alpha-hydroxylation system consists of a renal ferredoxin reductase (flavoprotein), renal ferredoxin and cytochrome P-450; reconstituted with cytochrome P-450, adrenal ferredoxin, i.e. adrenodoxin, and adrenodoxin reductase
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
cytochrome P-450 type is specific for hydroxylation site of 25-hydroxyvitamin D3; ferredoxin, ferredoxin reductase and cytochrome P-450
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
enzyme can be reconstituted with the 3 components: cytochrome P-450D1alpha, NADPH-renodoxin reductase and renodoxin
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
25-hydroxyvitamin D3 1alpha-hydroxylase is a cytochrome P-450-dependent mixed-function oxidase
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
25-hydroxyvitamin D3 1alpha-hydroxylase is a cytochrome P-450-dependent mixed-function oxidase; ferredoxin, ferredoxin reductase and cytochrome P-450
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
amino acid composition and terminal sequence determination
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
25-hydroxyvitamin D3 1alpha-hydroxylase is a cytochrome P-450-dependent mixed-function oxidase
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
reconstituted with cytochrome P-450, adrenal ferredoxin, i.e. adrenodoxin, and adrenodoxin reductase
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
25-hydroxyvitamin D3 1alpha-hydroxylase is a cytochrome P-450-dependent mixed-function oxidase; amino acid sequence determination; reconstituted with cytochrome P-450, adrenal ferredoxin, i.e. adrenodoxin, and adrenodoxin reductase
O35084
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
reconstituted with cytochrome P-450, adrenal ferredoxin, i.e. adrenodoxin, and adrenodoxin reductase
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
cytochrome P-450 enzyme; reconstituted with cytochrome P-450, adrenal ferredoxin, i.e. adrenodoxin, and adrenodoxin reductase
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
cytochrome P-450 enzyme
Q9XS57, -
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
cytochrome P-450 enzyme; reconstituted with cytochrome P-450, adrenal ferredoxin, i.e. adrenodoxin, and adrenodoxin reductase; reconstitution of the enzyme system in E. coli cells, consisting of NADH-adrenodoxin reductase, adrenodoxin and CYP27B1
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
cytochrome P-450 enzyme
-
calcidiol + NADPH + H+ + O2 = calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
oxidation
-
-
-
-
redox reaction
-
-
-
-
reduction
-
-
-
-
PATHWAY
KEGG Link
MetaCyc Link
1,25-dihydroxyvitamin D3 biosynthesis
-
Metabolic pathways
-
Steroid biosynthesis
-
SYSTEMATIC NAME
IUBMB Comments
calcidiol,NADPH:oxygen oxidoreductase (1-hydroxylating)
-
SYNONYMS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1-hydroxylase-25-hydroxyvitamin D3
-
-
-
-
1-OHase
-
-
1?-hydroxylase
-
-
1alpha,25-dihydroxyvitamin D hydroxylase
-
-
1alpha-hydroxylase
-
-
1alpha-OHase
-
-
1alphaOHase
-
-
25 hydroxy-vitamin D3-1alpha hydroxylase
-
-
25(OH)VD3 1alpha-hydroxylase
-
-
25-hydroxy D3-1alpha-hydroxylase
-
-
-
-
25-hydroxycholecalciferol 1-hydroxylase
-
-
-
-
25-hydroxycholecalciferol 1-monooxygenase
-
-
-
-
25-hydroxycholecalciferol 1alpha-hydroxylase
-
-
-
-
25-hydroxycholecalciferol-1-hydroxylase
-
-
-
-
25-hydroxyvitamin D 1alpha-hydroxylase
-
-
25-hydroxyvitamin D-1 alpha-hydroxylase
-
-
25-hydroxyvitamin D-1-alpha-hydroxylase
-
-
25-hydroxyvitamin D-1alpha-hydroxylase
O15528
-
25-hydroxyvitamin D-1alpha-hydroxylase
-
-
25-hydroxyvitamin D-1alpha-hydroxylase
-
-
25-hydroxyvitamin D3 1?-hydroxylase
-
-
25-hydroxyvitamin D3 1alpha-hydroxylase
-
-
-
-
25-hydroxyvitamin D3 1alpha-hydroxylase
-
-
25-hydroxyvitamin D3 1alpha-hydroxylase
-
-
25-hydroxyvitamin D3 1alpha-hydroxylase
B0BCH8
-
25-hydroxyvitamin D3 1alpha-hydroxylase
-
-
25-hydroxyvitamin D3-1alpha-hydroxylase
-
-
25-hydroxyvitamin-D3-1alpha-hydroxylase
-
-
CYB27B1
-
-
CYB27B1
Q9XS57
-
CYP1alpha
-
-
CYP27B1
-
-
cytochrome P450 25-hydroxyvitamin D3-1alpha-hydroxylase
-
-
extra-renal 25-hydroxyvitamin D-1alpha-hydroxylase
-
-
extra-renal 25-hydroxyvitamin D3 1alpha-hydroxylase
-
-
oxygenase, 25-hydroxycholecalciferol 1-mono-
-
-
-
-
P450 cytochrome 25-hydroxyvitamin D3 1alpha-hydroxylase
-
-
VD3 25-hydroxylase
-
-
vitamin D 1alpha-hydroxylase
-
-
vitamin D hydroxylase
-
-
vitamin D3 25- and 1alpha-hydroxylase
-
i.e. CYP2D25, microsomal, higher 25-hydroxylating than 1alpha-hydroxylating activity
vitamin D3 25-hydroxylase
-
-
vitamin D3 hydroxylase
-
-
[25(OH)D3]-1alpha-hydroxylase
-
-
hydroxylase, 25-hydroxcholecalciferol 1-
-
-
-
-
additional information
-
cf. EC 1.14.13.15
CAS REGISTRY NUMBER
COMMENTARY
9081-36-1
-
ORGANISM
COMMENTARY
LITERATURE
SEQUENCE CODE
SEQUENCE DB
SOURCE
female patients with papillary thyroid carcinoma
-
-
Manually annotated by BRENDA team
several splicing variants
-
-
Manually annotated by BRENDA team
women with and without breast cancer
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
CYP27B1 knockout mice, normal development when fed a 1alpha,25-dihydroxyvitamin D replacement or a high-calcium diet
-
-
Manually annotated by BRENDA team
full-length and truncated enzyme forms
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
physiological function
-
mechanisms for involvement of 1alpha-hydroxylase in antimicrobial responses within different barrier tissues, overview
malfunction
-
Hypercalcaemia in subcutaneous fat necrosis appears to be due to abundant levels of 25-hydroxyvitamin D3-1alpha-hydroxylase in immune infiltrates associated with tissue lesions
additional information
-
25OHD action involves localized extrarenal conversion to 1,25-dihydroxyvitamin D via tissue-specific expression of the enzyme 25-hydroxyvitamin D-1alpha-hydroxylase. Expression of 1alpha-hydroxylase is intimately associated with toll-like receptor, TLR, recognition of pathogens in macrophages
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
(24R),25-dihydroxycholecalciferol + NADPH + O2
1alpha,24,25-trihydroxycholecalciferol + NADP+ + H2O
show the reaction diagram
-
-
-
?
(24R),25-dihydroxycholecalciferol + NADPH + O2
1alpha,24,25-trihydroxycholecalciferol + NADP+ + H2O
show the reaction diagram
-
recombinant enzyme, higher activity than with 25-hydroxycholecalciferol
-
-
?
(24R),25-dihydroxycholecalciferol + NADPH + O2
1alpha,24,25-trihydroxycholecalciferol + NADP+ + H2O
show the reaction diagram
-
higher activity than with 25-hydroxycholecalciferol
-
?
(24R),25-dihydroxycholecalciferol + NADPH + O2
1alpha,24,25-trihydroxycholecalciferol + NADP+ + H2O
show the reaction diagram
-
higher activity than with 25-hydroxycholecalciferol
-
-
?
(24R),25-dihydroxycholecalciferol + NADPH + O2
1alpha,24,25-trihydroxycholecalciferol + NADP+ + H2O
show the reaction diagram
-
higher activity than with 25-hydroxycholecalciferol
-
?
(24R),25-dihydroxycholecalciferol + NADPH + O2
1alpha,24,25-trihydroxycholecalciferol + NADP+ + H2O
show the reaction diagram
-
reconstituted system
-
-
?
(24R),25-dihydroxyvitamin D3 + NADPH + O2
1alpha,24,25-trihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
1alpha-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
20-hydroxyvitamin D3 + NADPH + O2
1alpha,20-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
23,25-dihydroxycholecalciferol + NADPH + O2
?
show the reaction diagram
-
low activity, recombinant enzyme
-
-
?
24-oxo-23,25-dihydroxycholecalciferol + NADPH + O2
?
show the reaction diagram
-
low activity, recombinant enzyme
-
-
?
24-oxo-25-hydroxycholecalciferol + NADPH + O2
?
show the reaction diagram
-
recombinant enzyme
-
-
?
24-oxo-25-hydroxycholecalciferol + NADPH + O2
?
show the reaction diagram
-
low activity, reconstituted system
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
-
-
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
-
-
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
-
-
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
recombinant in E. coli
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
recombinant in E. coli
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
enzyme activity is correlated with phosphate content in serum
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
central role in calcium regulation
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
central role in calcium regulation
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
central role in calcium regulation
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
central role in calcium regulation
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
energy-dependent transhydrogenation is of importance
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
O15528
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
1,25(OH)2D3 is an antiproliferative agent that may inhibit proliferation of breast cancer cells
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
1,25-dihydroxyvitamin D3 (1,25-D3) is a key determinant of calcium homeostasis, cell proliferation and differentiation, calcium and vitamin D might have a protective function against colorectal tumor pathogenesis, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
bioactivation
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
deficiency of the enzyme, due to mutation of residues Q65 and T409, in substrate binding causes vitamin D-dependent rickets type 1, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
extra-renal functions of 1alpha-hydroxylase in vitamin D physiology, regulation, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
regulation of enzyme expression in kidney proximal tubules, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
substrate activation by the rate-limiting enzyme 1alpha-hydroxylase in cells of the immune system under control of immune stimuli, such as interferon-gamma, in pathological situations, such as sarcoidosis, this can lead to systemic excess of 1,25(OH)2D3 and hypercalcemia
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
O15528
the enzyme hydroxylates the major circulating form of vitamin D to the active systemic hormone 1,25(OH)2D3, local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
the enzyme is involved in the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate, mechanism, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
the enzyme is responsible for final hydroxylation of vitamin D3, in response to IFNgamma and CD14/TLR4 activation
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
binding of 25-hydroxyvitamin D3 in a structural pocket involving residues Q65, S408, and T409, molecular modeling and substrate docking
-
-
?
25-hydroxyvitamin D2 + NADPH + O2
1,25-dihydroxyvitamin D2 + NADPH + O2
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
final step of the activation of vitamin D
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
final step of the activation of vitamin D
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
final step of the activation of vitamin D, involved in tumor suppressing activity due to the tumor growth inhibiting effect of 1alpha,25-dihydroxyvitamin D3
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1,25-dihydroxyvitamin D3 + NADPH + O2
show the reaction diagram
-
-
-
-
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
recombinant enzyme
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
enzyme shows vitamin D3 25- and 1alpha-hydroxylase activity
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
O35084
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
calcidiol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
Q9XS57, -
highly specific for calcidiol, calcidiol is identical with 25-hydroxycholecalciferol
calcitriol is identical with 1,25-dihydroxycholecalciferol
?
cholecalciferol + NADPH + O2
25-hydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
the 25-hydroxy group is essential for 1alpha-hydroxylating activity, the 24-hydroxy group enhances the activity, the 23-hydroxy group strongly reduces activity
-
-
-
additional information
?
-
-
the 25-hydroxy group is essential for 1alpha-hydroxylating activity, the 24-hydroxy group enhances the activity, the 23-hydroxy group strongly reduces activity
-
-
-
additional information
?
-
-
not: cholecalciferol, dihydrotachysterol
-
-
-
additional information
?
-
-
not active with (23S),25-dihydroxycholecalciferol and 24-oxo-23,25-dihydroxycholecalciferol
-
-
-
additional information
?
-
-
no activity with 24,25,26,27-tetranor-23-hydroxyvitamin D3 and vitamin D3
-
-
-
additional information
?
-
-
25(OH)D3 therapy is useful for colorectal cancer chemoprevention but provitamin D is less likely to be useful for colorectal cancer chemotherapy, overview
-
-
-
additional information
?
-
-
both butyrate and 1alpha-25(OH)2D3 stimulate differentiation of Caco-2 cells, while 25(OH)2D3 has no impact on cell differentiation
-
-
-
additional information
?
-
-
colonic and renal vitamin D hydroxylases are regulated independently
-
-
-
additional information
?
-
-
functional analysis of vitamin D metabolism in cancer, locally synthesized 1,25(OH)2D3 may be inefficient in preventing tumor progression, mechanism, overview
-
-
-
additional information
?
-
-
immune regulation of the enzyme in monocytes, cross-talk between the JAK-STAT, the NFkappaB, and the p38 MAPK pathways is necessary, and direct binding of C/EBPbeta to its recognition sites in the promoter of the 1alpha-hydroxylase gene is a prerequisite, overview
-
-
-
additional information
?
-
-
PTH and PTHrP are involved in enzyme regulation, PTH is the major protein hormone regulating calcium homeostasis, PTHrP is a PTH-like factor responsible for humoral hypercalcemia of malignancy, both peptides are required to achieve normal fetal skeletal morphogenesis, overview
-
-
-
additional information
?
-
-
the enzyme is involved in local production of 1alpha,25-dihydroxyvitamin D, i.e. 1alpha,25(OH)2D3, in tumorigenesis
-
-
-
additional information
?
-
-
a multifunctional enzyme catalyzing also the reaction of cholestanetriol 26-monooxygenase, EC 1.14.13.15, as well as oxidation of 5beta-cholestane-3alpha,7alpha,12alpha,27-tetraol into the corresponding C27-acid, and the 24- and 25-hydroxylation of cholesterol, the truncated enzyme form is less efficient than the full-length CYP27A in the 27-hydroxylation of C27-sterols, and much less efficient in the 25-hydroxylation of 1alpha-hydroxyvitamin D3
-
-
-
additional information
?
-
-
the 1alpha-OHase gene is a tumor suppressor gene responsible for the normal regulation of prostate cell growth
-
-
-
additional information
?
-
-
1alpha,25(OH)2-19-nor-D3 is not converted to 1alpha,25(OH)2-19-nor-D3 by CYP27B1
-
-
-
additional information
?
-
-
Vdh, a cytochrome P450 enzyme, is responsible for the biocatalytic conversion of vitamin D3, catalyzing the two-step hydroxylation of VD3, i.e. the conversion of VD3 to 25-hydroxyvitamin D3 (25(OH)VD3) and then of 25(OH)VD3 to 1alpha,25(OH)2VD3, a hormonal form of VD3. Anti-parallel substrate binding modes enable sequential hydroxylation, structure-function analysis, overview
-
-
-
additional information
?
-
-
25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in vesicles undergo 1alpha-hydroxylation with similar kinetics. CYP27B1 also catalyzes 1alpha-hydroxylation of vesicle-associated 24R,25-dihydroxyvitamin D3 and 20-hydroxyvitamin D3, and 25-hydroxylation of 1alpha-hydroxyvitamin D3 and 1alpha-hydroxyvitamin D2, but with much lower efficiency than for 25(OH)D3, reactions in reconstituted phospholipid vesicles with the substrates associating to the membrane, effect of vesicle phospholipid composition on metabolism of 25(OH)D3 by CYP27B1, overview
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
(24R),25-dihydroxycholecalciferol + NADPH + O2
1alpha,24,25-trihydroxycholecalciferol + NADP+ + H2O
show the reaction diagram
-
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
recombinant in E. coli
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
recombinant in E. coli
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
enzyme activity is correlated with phosphate content in serum
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
central role in calcium regulation
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
central role in calcium regulation
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
central role in calcium regulation
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
central role in calcium regulation
-
-
?
25-hydroxycholecalciferol + NADPH + O2
calcitriol + NADP+ + H2O
show the reaction diagram
-
energy-dependent transhydrogenation is of importance
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
1,25(OH)2D3 is an antiproliferative agent that may inhibit proliferation of breast cancer cells
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
1,25-dihydroxyvitamin D3 (1,25-D3) is a key determinant of calcium homeostasis, cell proliferation and differentiation, calcium and vitamin D might have a protective function against colorectal tumor pathogenesis, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
bioactivation
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
deficiency of the enzyme, due to mutation of residues Q65 and T409, in substrate binding causes vitamin D-dependent rickets type 1, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
extra-renal functions of 1alpha-hydroxylase in vitamin D physiology, regulation, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
regulation of enzyme expression in kidney proximal tubules, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
substrate activation by the rate-limiting enzyme 1alpha-hydroxylase in cells of the immune system under control of immune stimuli, such as interferon-gamma, in pathological situations, such as sarcoidosis, this can lead to systemic excess of 1,25(OH)2D3 and hypercalcemia
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
O15528
the enzyme hydroxylates the major circulating form of vitamin D to the active systemic hormone 1,25(OH)2D3, local production of 1,25(OH)2D3 appears to occur also at other sites where 1alpha-hydroxylase is expressed for autocrine/paracrine regulation, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
the enzyme is involved in the vitamin D signaling pathway in colonic epithelial cell differentiation by butyrate, mechanism, overview
-
-
?
25-hydroxyvitamin D + NADPH + O2
1alpha,25-dihydroxyvitamin D + NADP+ + H2O
show the reaction diagram
-
the enzyme is responsible for final hydroxylation of vitamin D3, in response to IFNgamma and CD14/TLR4 activation
-
-
?
25-hydroxyvitamin D2 + NADPH + O2
1,25-dihydroxyvitamin D2 + NADPH + O2
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
final step of the activation of vitamin D
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
final step of the activation of vitamin D
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1alpha,25-dihydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
final step of the activation of vitamin D, involved in tumor suppressing activity due to the tumor growth inhibiting effect of 1alpha,25-dihydroxyvitamin D3
-
-
?
25-hydroxyvitamin D3 + NADPH + O2
1,25-dihydroxyvitamin D3 + NADPH + O2
show the reaction diagram
-
-
-
-
?
cholecalciferol + NADPH + O2
25-hydroxyvitamin D3 + NADP+ + H2O
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
25(OH)D3 therapy is useful for colorectal cancer chemoprevention but provitamin D is less likely to be useful for colorectal cancer chemotherapy, overview
-
-
-
additional information
?
-
-
both butyrate and 1alpha-25(OH)2D3 stimulate differentiation of Caco-2 cells, while 25(OH)2D3 has no impact on cell differentiation
-
-
-
additional information
?
-
-
colonic and renal vitamin D hydroxylases are regulated independently
-
-
-
additional information
?
-
-
functional analysis of vitamin D metabolism in cancer, locally synthesized 1,25(OH)2D3 may be inefficient in preventing tumor progression, mechanism, overview
-
-
-
additional information
?
-
-
immune regulation of the enzyme in monocytes, cross-talk between the JAK-STAT, the NFkappaB, and the p38 MAPK pathways is necessary, and direct binding of C/EBPbeta to its recognition sites in the promoter of the 1alpha-hydroxylase gene is a prerequisite, overview
-
-
-
additional information
?
-
-
PTH and PTHrP are involved in enzyme regulation, PTH is the major protein hormone regulating calcium homeostasis, PTHrP is a PTH-like factor responsible for humoral hypercalcemia of malignancy, both peptides are required to achieve normal fetal skeletal morphogenesis, overview
-
-
-
additional information
?
-
-
the enzyme is involved in local production of 1alpha,25-dihydroxyvitamin D, i.e. 1alpha,25(OH)2D3, in tumorigenesis
-
-
-
additional information
?
-
-
the 1alpha-OHase gene is a tumor suppressor gene responsible for the normal regulation of prostate cell growth
-
-
-
additional information
?
-
-
Vdh, a cytochrome P450 enzyme, is responsible for the biocatalytic conversion of vitamin D3, catalyzing the two-step hydroxylation of VD3, i.e. the conversion of VD3 to 25-hydroxyvitamin D3 (25(OH)VD3) and then of 25(OH)VD3 to 1alpha,25(OH)2VD3, a hormonal form of VD3. Anti-parallel substrate binding modes enable sequential hydroxylation, structure-function analysis, overview
-
-
-
METALS and IONS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
Mg2+
-
required
Mg2+
-
10 mM used in standard incubation
additional information
-
highest conversion with a hypo-osmolar buffer
additional information
-
almost any other Krebs cycle substrate supports 1-alpha-hydroxylation
INHIBITORS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,25-Dihydroxycholecalciferol
-
calcitriol
1,25-Dihydroxycholecalciferol
-
calcitriol
1,25-Dihydroxycholecalciferol
-
calcitriol
1,25-Dihydroxycholecalciferol
O35084
calcitriol; in vivo only inhibitory in vitamin D receptor containing cells, therefore: negative feedback inhibition is mediated by the enzyme through liganded vitamin D receptor
1,25-Dihydroxycholecalciferol
-
calcitriol; decreases mRNA expression in less differentiated cells like Caco-2/AQ and COGA-1A and -1E
22-oxacalcitriol
-
vitamin D3 analogue, inhibits in vitro and in vivo
25-hydroxy-3-deoxy-2-oxavitamin D3
-
vitamin D3 analogue, competitive inhibition
25-hydroxydihydrotachysterol3
-
-
25-hydroxyvitamin D2
-
CYP27B1 shows inhibition when substrate concentrations in the membrane are greater than 4 times Km, more pronounced with 25-hydroxyvitamin D3 than with 25-hydroxyvitamin D2
-
25-hydroxyvitamin D3
-
CYP27B1 shows inhibition when substrate concentrations in the membrane are greater than 4 times Km, more pronounced with 25-hydroxyvitamin D3 than with 25-hydroxyvitamin D2
3-deoxy-2-oxa-9(11)-didehydro-25-hydroxyvitamin D3
-
vitamin D3 analogue, competitive inhibition
A-homo-3-deoxy-2-oxa-25-hydroxyvitamin D3
-
vitamin D3 analogue, competitive inhibition
-
Aminoglutethimide
-
enzyme of intact mitochondria
antimycin A
-
-
antimycin A
-
inhibition occurs with succinate reaction support, no inhibition together with malate
antimycin A
-
higher inhibition rate with succinate as electron donor than with malate
antimycin A
-
no inhibition of hydroxylation
antimycin A
-
-
clotrimazole
-
in vivo in MCF-7 cells
CO
-
50% O2/50% CO2 incubation atmosphere
CO
-
no inhibition
cyanide
-
-
Dinitrophenol
-
-
Dinitrophenol
-
-
Dinitrophenol
-
higher inhibition rate with malate as electron donor than with succinate
Dinitrophenol
-
-
diphenyl-p-phenylenediamine
-
-
diphenyl-p-phenylenediamine
-
no inhibition
diphenyl-p-phenylenediamine
-
-
Epidermal growth factor
-
decreases mRNA expression in less differentiated cells like Caco-2/AQ and COGA-1A and -1E; i.e. EGF
ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid
-
-
Glutethimide
-
-
Ketoconazole
-
-
metapyrone
-
-
Metyrapone
-
-
Metyrapone
-
enzyme of intact mitochondria
Metyrapone
-
-
Metyrapone
-
-
Natural inhibitors
-
from rat and pig tissues
-
Natural inhibitors
-
rat plasma 25-hydroxyvitamin D3 binding protein
-
Natural inhibitors
-
from rat serum
-
Natural inhibitors
-
vitamin D binding protein
-
oligomycin
-
-
p-chloromercuribenzoate
-
-
p-Trifluoromethoxyphenylhydrazone
-
-
phosphate
-
no inhibition
rotenone
-
no inhibition of hydroxylation
rotenone
-
-
Sucrose
-
hypertonic
Tris-chloride buffer
-
-
vitamin D3
-
-
additional information
-
inhibition by renal mitochondrial protein kinase-catalyzed phosphorylation
-
additional information
-
no inhibition with Ba2+, acetate, sulfate
-
additional information
-
overview, inhibitory potency of several vitamin D3 analogues
-
additional information
-
the enzyme is not affected by cardiolipin and dilauroylphosphatidylcholine
-
additional information
-
inhibitory effects of the MEK inhibitor PD98059, p38 MAPK inhibitor SB203580, and JNK inhibitor SP600125 on the IFNgamma/PMA-induced or IFNgamma/LPS-induced 1alpha-hydroxylase mRNA expression in THP1 cells, overview
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1,25-Dihydroxycholecalciferol
-
increases mRNA expression in highly differentiated cells like Caco-2/15
8-bromo-cAMP
Q9XS57, -
enhances mRNA expression level
adrenodoxin
-
mouse and bovine adrenodoxin display similar abilities to support CYP27B1 activity
-
CN-
-
activates with malate as electron donor
Epidermal growth factor
-
i.e. EGF; increases mRNA expression in highly differentiated cells like Caco-2/15
Epidermal growth factor
-
i.e. EGF; stimulates
forskolin
Q9XS57, -
enhances mRNA expression level
malate
-
supports 1alpha-hydroxylation as electron donor
malate
-
supports 1alpha-hydroxylation as electron donor
succinate
-
supports 1alpha-hydroxylation as electron donor
succinate
-
supports 1alpha-hydroxylation as electron donor
succinate
-
supports 1alpha-hydroxylation as electron donor
additional information
-
treatment of cells with parathyroid hormone, estradiol-17beta, raloxifene, genistein, biochainin A, or 6-carboxy biochainin A increases cellular mRNA-level
-
additional information
-
5-aza-2-deoxycytidine together with trichostatin A increases mRNA expression in DU-145 cells
-
additional information
-
the enzyme is not affected by cardiolipin and dilauroylphosphatidylcholine
-
additional information
-
EB1285, a non-1alpha-hydroxylated vitamin D analogue prodrug of EB1089, shows about 20% ketoconazole-sensitive transcription activation of the enzyme
-
additional information
-
enzyme expression in monocytes is synergistically induced by IFNgamma and CD14/TLR4 ligation and paralleled by 1,25(OH)2D3 production, the induction essentially requires the JAK-STAT, NF-kappaB, and p38 MAPK pathways, expression analysis, overview
-
additional information
-
phorbol myristate acetate, lipopolysaccharide, and IFNgamma induce enzyme expression in monocytes, regulation, the induction essentially requires the JAK-STAT, NF-kappaB, and p38 MAPK pathways, chromatin remodeling is required for immune-mediated up-regulation of 1alpha-hydroxylase, overview
-
additional information
-
dietary calcium and vitamin D depletion induces the enzyme expression
-
additional information
-
butyrate transiently upregulates enzyme expression 2.3fold
-
KM VALUE [mM]
KM VALUE [mM] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.0011
-
(24R),25-dihydroxycholecalciferol
-
reconstituted system
0.0011
-
(24R),25-dihydroxycholecalciferol
-
-
26
-
(24R),25-dihydroxyvitamin D3
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
-
0.00052
-
1alpha-hydroxyvitamin D
-
pH 7.4, 37C, recombinant wild-type enzyme
0.00066
-
1alpha-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408V
49
-
20-hydroxyvitamin D3
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
0.0013
-
24,25-dihydroxycholecalciferol
-
-
8.8e-05
-
25-hydroxycholecalciferol
-
-
0.00097
-
25-hydroxycholecalciferol
-
reconstituted system
0.001
-
25-hydroxycholecalciferol
-
-
0.0022
-
25-hydroxycholecalciferol
-
-
0.0027
-
25-hydroxycholecalciferol
-
reconstituted system
0.0027
-
25-hydroxycholecalciferol
-
-
0.0027
-
25-hydroxycholecalciferol
-
-
0.014
-
25-hydroxycholecalciferol
-
-
0.89
-
25-hydroxycholecalciferol
-
-
0.00013
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408T
0.00018
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408I
0.00024
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408A
0.00028
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant wild-type enzyme
0.00054
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408V
4.6
-
25-hydroxyvitamin D2
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
-
4.8
-
25-hydroxyvitamin D2
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
-
5.9
-
25-hydroxyvitamin D3
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
9.7
-
25-hydroxyvitamin D3
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
additional information
-
additional information
-
-
-
additional information
-
additional information
-
Michaelis-Menten kinetics, and by a kinetic model with substrate binding at two inhibitory sites, overview
-
TURNOVER NUMBER [1/s]
TURNOVER NUMBER MAXIMUM[1/s]
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.9
-
(24R),25-dihydroxyvitamin D3
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
-
0.0004
-
1alpha-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408V
0.01
-
1alpha-hydroxyvitamin D
-
pH 7.4, 37C, recombinant wild-type enzyme
0.14
-
20-hydroxyvitamin D3
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
0.0733
-
25-hydroxycholecalciferol
-
-
0.0008
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408I
0.006
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408A
0.013
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408V
0.098
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant mutant S408T
0.385
-
25-hydroxyvitamin D
-
pH 7.4, 37C, recombinant wild-type enzyme
0.8
-
25-hydroxyvitamin D2
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
-
0.82
-
25-hydroxyvitamin D2
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
-
0.68
-
25-hydroxyvitamin D3
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
0.92
-
25-hydroxyvitamin D3
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
kcat/KM VALUE [1/mMs-1]
kcat/KM VALUE [1/mMs-1] Maximum
SUBSTRATE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
0.035
-
(24R),25-dihydroxyvitamin D3
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
0
0.003
-
20-hydroxyvitamin D3
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
293052
0.17
-
25-hydroxyvitamin D2
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
0
0.171
-
25-hydroxyvitamin D2
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
0
0.094
-
25-hydroxyvitamin D3
-
pH 7.4, 37C, parameters using a kinetic model with substrate binding at two inhibitory sites
218613
0.115
-
25-hydroxyvitamin D3
-
pH 7.4, 37C, Michaelis-Menten kinetic parameters
218613
Ki VALUE [mM]
Ki VALUE [mM] Maximum
INHIBITOR
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
IMAGE
1.1
-
Aminoglutethimide
-
-
0.16
-
metapyrone
-
-
0.001
0.002
vitamin D3
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
SPECIFIC ACTIVITY MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
1e-07
-
-
female human kidney
2e-07
-
-
substrate 23,25-dihydroxycholecalciferol
2e-07
-
-
male human kidney
2e-07
-
-
-
2e-07
-
-
substrate 23,25-dihydroxycholecalciferol
4.2e-07
-
-
substrate 24-oxo-25-hydroxycholecalciferol, recombinant reconstituted system
5.8e-07
-
-
substrate 25-hydroxycholecalciferol, recombinant reconstituted system
1.1e-06
-
-
substrate 24-oxo-25-hydroxycholecalciferol
1.5e-06
-
-
-
1.5e-06
-
-
substrate 24,25-dihydroxycholecalciferol
1.5e-06
-
-
-
3.1e-06
-
-
-
4.3e-06
-
-
substrate 24,25-dihydroxycholecalciferol
4.8e-06
-
-
with malate as electron source
7.2e-06
-
-
purified cytochrome P-450 component of 1alpha-hydroxylase, reconstituted system
8.2e-06
-
-
purified cytochrome P-450 component of 1alpha-hydroxylase, reconstituted system
0.00125
-
-
-
0.0048
-
-
purified enzyme
0.602
-
-
reduction of cytochrome P-450 at non-saturating level of enzyme components
0.687
-
-
ferredoxin activity, reduction of cytochrome c
6.758
-
-
purified ferredoxin, reduction of cytochrome c
11.38
-
-
reconstituted system of cytochrome P-450, cytochrome b5, adrenocortical ferredoxin reductase, and renal ferredoxin
additional information
-
-
-
additional information
-
-
higher activity in male kidney compared to female kidney
additional information
-
-
-
additional information
-
-
1alpha-hydroxylation activity of the full-length enzyme form is 10fold higher than the activity of the truncated enzyme form
pH OPTIMUM
pH MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.4
8.4
-
-
7.4
-
-
-
7.4
-
-
assay at
7.4
-
-
assay at
7.4
-
-
assay at
pH RANGE
pH RANGE MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
7.1
7.7
-
about 50% of activity maximum at pH 7.1 and pH 7.7
TEMPERATURE OPTIMUM
TEMPERATURE OPTIMUM MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
25
-
-
assay at
37
-
-
assay at
37
-
-
assay at
SOURCE TISSUE
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
SOURCE
-
parathyroid hormone increases CYP1alpha mRNA and protein in a time-dependent manner. H2O2 inhibits parathyroid hormone-stimulated CYP1alpha protein levels and 1,25(OH)2D production in a dose dependent manner. The catalytic activity of the CYP1alpha protein may be reduced by free radical damage in CYP27B1 cells
Manually annotated by BRENDA team
-
distributed throughout all brain regions, neurons and glial cells
Manually annotated by BRENDA team
-
enzyme expression analysis in different samples of women with and without breast cancer, no correlation with breast cancer development
Manually annotated by BRENDA team
-
the enzyme expression is reduced in breast cancer cell specimen compared to healthy breast tissue
Manually annotated by BRENDA team
-
intestinal cell line, both butyrate and 1alpha-25(OH)2D3 stimulate differentiation of Caco-2 cells, while 25(OH)2D3 has no impact on cell differentiation
Manually annotated by BRENDA team
-
healthy and malignant, high expression level, 1alpha-hydroxylase is present at equal high levels in normal colonic epithelium as in ACFs, polyps, and colorectal cancer irrespective of tumor cell differentiation
Manually annotated by BRENDA team
-
tissue-specific enzyme regulation
Manually annotated by BRENDA team
-
monocyte-derived
Manually annotated by BRENDA team
-
renal distal tubular epithelial cell line. CYP27B1 gene expression is unchanged after treatement with parathyroid hormone or after high Ca2+ exposure
Manually annotated by BRENDA team
-
malignant prostate cell line
Manually annotated by BRENDA team
-
prostate cancer cell line, greatly decreased activity of 25-hydroxyvitamin D-1alpha-hydroxylase due to decreased RNA transcription
Manually annotated by BRENDA team
-
colonic, healthy and malignant, high expression level
Manually annotated by BRENDA team
-
high enzyme level
Manually annotated by BRENDA team
-
renal cortex; tumour tissue
Manually annotated by BRENDA team
-
proximal tubular cells
Manually annotated by BRENDA team
-
truncated enzyme form
Manually annotated by BRENDA team
-
proximal convoluted tubule
Manually annotated by BRENDA team
-
RT-PCR expression and immunohistochemic analysis, low CYP27B1 expression in the atrophic kidney, predominantly expressed in proximal tubules
Manually annotated by BRENDA team
-
truncated enzyme form
Manually annotated by BRENDA team
-
prostate cancer cell line, greatly decreased activity of 25-hydroxyvitamin D-1alpha-hydroxylase due to decreased RNA transcription
Manually annotated by BRENDA team
-
epidermal growth factor does not upregulate 1alpha-OHase promoter activity in the carcinogenic prostate cells. Dysregulation of 1alpha-OHase in cancer cells may lead to the aberrant growth of prostate cancer cells
Manually annotated by BRENDA team
-
monocyte-derived
Manually annotated by BRENDA team
-
expression of 1alpha-hydroxylase is intimately associated with toll-like receptor, TLR, recognition of pathogens in macrophages
Manually annotated by BRENDA team
-
expression of 1alpha-OHase is 1.25fold higher in MCF-7 compared to MCF-10A cells. In MCF-10A cells, at least 6 splice variants are detected. Alternative splicing of 1alpha-OHase can regulate the level of active enzyme
Manually annotated by BRENDA team
-
expression of 1alpha-OHase is 1.25fold higher in MCF-7 compared to MCF-10A cells. MCF-7 cells show no or marginal expression levels of splice variants
Manually annotated by BRENDA team
-
renal proximal tubular epithelial cell line. CYP27B1 gene expression is elevated in response to parathyroid hormone. High Ca2+ exposure represses CYP27B1 gene expression in both dose and time-dependent fashion
Manually annotated by BRENDA team
-
1-OHase mRNA expression is highest in pre-menopausal women and is increased by all hormones tested. In post-menopausal osteoblasts all hormones except biochainin A and genistein increase 1-OHase mRNA expressions to less extent. In male-derived osteoblasts only dihydrotestosterone and carboxybiochainin A increase 1-OHase mRNA expression
Manually annotated by BRENDA team
-
high enzyme and vitamin D receptor expression level, especially in regions of lymphocyte infiltration
Manually annotated by BRENDA team
-
enzyme expression in secondary hyperparathyroidism
Manually annotated by BRENDA team
-
prostate cancer cell line, greatly decreased activity of 25-hydroxyvitamin D-1alpha-hydroxylase due to decreased RNA transcription
Manually annotated by BRENDA team
-
syncytiotrophoblast cells from preeclamptic pregnancies
Manually annotated by BRENDA team
-
normal prostate cell line
Manually annotated by BRENDA team
-
tumor tissue
Manually annotated by BRENDA team
-
tissue obtained from normal prostate, benign prostatic hyperplastia or cancer, primary and cultured prostate cancer cells have greatly decreased activity of 25-hydroxyvitamin D-1alpha-hydroxylase and are therefore resistant to the tumor suppressing activity of circulating 25-hydroxyvitamin D3
Manually annotated by BRENDA team
-
the enzyme is up-regulated by suberoylanilide hydroxamic acid, a histone deacetylase inhibitor
Manually annotated by BRENDA team
-
epidermal growth factor upregulates 1alpha-OHase promoter activity in the noncarcinogenic prostate cells
Manually annotated by BRENDA team
-
RT-PCR and immunohistochemic expression analysis
Manually annotated by BRENDA team
-
highest activity in proximal tubule
Manually annotated by BRENDA team
-
truncated enzyme form
Manually annotated by BRENDA team
-
truncated enzyme form
Manually annotated by BRENDA team
-
high enzyme level in large dopaminergic neurons
Manually annotated by BRENDA team
-
monocytic cell line
Manually annotated by BRENDA team
additional information
-
no truncated enzyme form in lung, testis, heart, or brain mitochondria
Manually annotated by BRENDA team
additional information
-
both 1alpha-hydroxylase and vitaminD receptor levels are negligible in tumor cells metastasizing to regional lymph nodes
Manually annotated by BRENDA team
additional information
-
tissue-specific expression analysis, colonic and renal vitamin D hydroxylases are regulated independently, while low dietary calcium does not affect colonic expression of vitamin D receptor, VDR, or 25-hydroxyvitamin D3 1alpha-hydroxylase, it influences their renal expression by elevating CYP27B1 expression and reducing VDR and 25-hydroxyvitamin D3 24-hydroxylase expression, overview
Manually annotated by BRENDA team
additional information
-
altered expression of 1alpha-hydroxylase in different types of neoplasm including breast, prostate and colon cancers, autocrine/paracrine synthesis of 1,25(OH)2D3 is decreased in tumor cells and cell lines
Manually annotated by BRENDA team
additional information
-
25OHD action involves localized extrarenal conversion to 1,25-dihydroxyvitamin D via tissue-specific expression of the enzyme 25-hydroxyvitamin D-1alpha-hydroxylase
Manually annotated by BRENDA team
MOLECULAR WEIGHT
MOLECULAR WEIGHT MAXIMUM
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
11900
-
-
ferredoxin component, SDS-PAGE
12500
-
-
ferredoxin component, gel filtration
49000
-
-
cytochrome P-450D1alpha, SDS-PAGE
50000
-
-
recombinant enzyme
53000
-
-
MW of ferredoxin component, SDS-PAGE, gel filtration
55000
-
-
gel filtration
55000
-
O35084
SDS-PAGE after in vitro-translation
56000
-
-
SDS-PAGE
56370
-
-
predicted from DNA sequence analysis
additional information
-
-
ferredoxin, ferredoxin reductase and cytochrome P-450
additional information
-
-
kidney mitochondrial 25-hydroxyvitamin D3-1alpha-hydroxylation system consists of a renal ferredoxin reductase (flavoprotein), renal ferredoxin and cytochrome P-450
additional information
-
-
enzyme can be reconstituted with the 3 components: cytochrome P-450D1alpha, NADPH-renodoxin reductase and renodoxin
additional information
-
-
ferredoxin, ferredoxin reductase and cytochrome P-450
SUBUNITS
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
?
-
x * 52000, full-length enzyme form, SDS-PAGE, x * 51000, truncated enzyme form, SDS-PAGE
additional information
-
amino acid sequence comparison of full-length and truncated enzyme forms
additional information
-
three-dimensional structure analysis of wild-type and mutant enzymes, molecular modeling and substrate docking, overview
additional information
-
Vdh structure analysis, overview
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
proteolytic modification
-
the naturally occuring truncated enzyme form is formed by via proteolytic processing of CYP27A by endogenous protease
Crystallization/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purified recombinant wild-type Vdh and mutant Vdh-K1 in complex with substrates VD3 and 25(OH)VD3, 20 mg/ml wild-type protein in 20 mM Tris-HCl, pH 7.5, supplemented with 0-0.2% PMbetaCD for VD3 complex or 0-0.2% gammaCD for 25(OH)VD3 complex, 20 mg/ml mutant protein in 20 mM Tris-HCl, pH 7.5, supplemented with 20 mM NaCl, sitting-drop method, 20C. Vdh-WT crystals are grown using reservoir solution containing 0.1 M BisTris, pH 7.5, 50 mM CaCl2, 40-120 mM NaCl or KCl, and 32-40% PEG 400 or PEG 550 monomethyl ether or 20% PEG 1000, Vdh-K1 is crystallized using reservoir solution containing 0.1 M calcium acetate and 10-14% PEG 3350, X-ray diffraction structure determination and analysis at 1.75-3.05 A resolution
-
GENERAL STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
CYP27B1 is labile during purification despite the presence of 20% glycerol as a stabilizing agent
-
STORAGE STABILITY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
-80C, in the dark, stable for at least 3 months, cytochrome P-450D1alpha
-
4C, prolonged standing of the enzyme, including overnight dialysis, causes marked loss of the holo-enzyme
-
-30C, stable without significant loss of activity for at least 6 months
-
0-4C, rapid loss of activity
-
Purification/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
purification of cytochrome P-450D1alpha
-
partially
-
purification of ferredoxin component
-
recombinant His-tagged CYP27B1 from Escherichia coli strain JM109 by nickel affinity chromatoghraphy, followed by affinity chromatography on a bovine adrenodoxin-coupled resin with elution by 1.0% CHAPS
-
full-length and truncated enzyme forms from liver mitochondria
-
recombinant wild-type Vdh and mutant Vdh-K1 from Escherichia coli
-
purification of 1alpha-hydroxylating cytochrome P-450
-
vitamin D3 25- and 1alpha-hydroxylase
-
Cloned/COMMENTARY
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
cloning of several novel intron 2-containing, noncoding splice variant mRNAs for CYP27b1 in 1,25(OH)2D3-producing HKC-8 human proximal tubule and THP-1 monocytic cells. Noncoding splice variants of CYP27b1 are functionally active and may play a significant role in the regulation of 1,25(OH)2D3 synthesis during normal physiology
-
expression in Escherichia coli JM109, coexpression of adrenodoxin and NADPH-adrenodoxin reductase for reconstitution of the system
-
expression of vitamin D hydroxylases in the VDR-/- mouse model, overview
-
expressionin RAW264.7 cells
-
quantitative PCR analysis of gene expression in different tissues/cells, overview
-
expression in COS cells, reconstituted with recombinant cytochrome P-450, recombinant adrenodoxin, and recombinant adrenodoxin reductase
O35084
expression in Escherichia coli
-
expression of His-tagged CYP27B1 in Escherichia coli strain JM109
-
expression of wild-type and mutant enzymes in Escherichia coli strain DH5alpha
-
expression of wild-type Vdh and mutant Vdh-K1 in Escherichia coli
-
His-tag, expressed in Rhodococcus erythropolis and Escherichia coli
-
expression in COS cells, vitamin D3 25- and 1alpha-hydroxylase, DNA sequence analysis
-
expression in LLC-PK1-cells
Q9XS57, -
EXPRESSION
ORGANISM
UNIPROT ACCESSION NO.
LITERATURE
statistically significantly lower protein expression in malignant ovarian tissue
-
expression of 1alpha-hydroxylase is induced via toll-like receptor, TLR, recognition of pathogens in macrophages, but not in colonic cells, i.e. Caco-2 and BBe colonic cell lines. Colonic epithelial cells may require specific factors to initiate intracrine responses to vitamin D.
-
genes CYP2R1 encoding vitamin D 25-hydroxylase, CYP27B1 encoding 25-hydroxyvitamin D-1 alpha hydroxylase and CYP24A1 encoding 1,25-dihydroxyvitamin D(3) 24-hydroxylase are upregulated in clear cell renal cell carcinomas compared with normal tissue. CYP24A1 displays a significantly higher expression in tumors than CYP27B1 and CYP2R1, whereas no differences in the expression of these genes are found in healthy renal tissue
-
hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. 25-hydroxyvitamin D3 1alpha-hydroxylase is expressed at much higher levels in oxyphil cells than in chief cells in these patients. The calcimimetic cinacalcet increases the expression of the enzyme in human parathyroid cultures
-
in Klotho knockout mice
-
kidney: 25-hydroxycholecalciferol induces a significant downregulation 3 days after injection
B0BCH8
kidney: calcitriol and 25-hydroxycholecalciferol induce a significant upregulation 6 days after injection; kidney: parathyroid hormone-related protein induces significant upregulation 6 h after injection
B0BCH8
calcitonin induces 25-hydroxyvitamin D3 1alpha-hydroxylase protein levels in AOK-B50 cells transfected with a mouse 25-hydroxyvitamin D3 1alpha-hydroxylase promoter construct (transcription factor C/EBPbeta is involved)
-
ENGINEERING
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
P382S
-
native mutant, no enzyme activity but normal expression level
R107H
-
native mutant, no enzyme activity but normal expression level
Q65A
-
site-directed mutagenesis, three-dimensional structure analysis and comparison to the wild-type enzyme
Q65E
-
site-directed mutagenesis, three-dimensional structure analysis and comparison to the wild-type enzyme
Q65H
-
site-directed mutagenesis, three-dimensional structure analysis and comparison to the wild-type enzyme
Q65L
-
site-directed mutagenesis, three-dimensional structure analysis and comparison to the wild-type enzyme
Q65N
-
site-directed mutagenesis, three-dimensional structure analysis and comparison to the wild-type enzyme
S408A
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme, three-dimensional structure analysis and comparison to the wild-type enzyme
S408I
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme, three-dimensional structure analysis and comparison to the wild-type enzyme
S408T
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme, three-dimensional structure analysis and comparison to the wild-type enzyme
S408V
-
site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type enzyme, three-dimensional structure analysis and comparison to the wild-type enzyme
T70R/V156L/E216M/E384R
-
mutant Vdh-K1, 22fold more active in the hydroxylation of VD3 to 25(OH)VD3 than wild-type Vdh in in vivo bioconversion using Escherichia coli cells. backbone and side chain conformations at the active-site pocket are identical among the substrate-free, VD3-bound, and 25(OH)VD3-bound forms of Vdh-K1, and no induced-fit mechanisms are observed, although VD3 is asymmetric
G125E
-
native mutant, no enzyme activity but normal expression level
additional information
-
expression of vitamin D hydroxylases in the VDR-/- mouse model, overview
additional information
-
construction of a transgenic mouse line expressing 1501 bp of 58 flanking region together with 44 bp of 58 untranslated region of the human CYP27B1 gene fused to the firefly luciferase reporter gene, luciferase protein and mRNA for CYP27B1 are localized to proximal convoluted tubule cells of the kidney with highest levels in 2-week-old animals, overview
R335P
-
native mutant, no enzyme activity but normal expression level
additional information
O35084
construction and expression in COS cell line of a chimeric fusion protein: vitaminD receptor ligand-binding domain with the yeast GAL4 DNA-binding domain, also expression of lacZ containing reporter plasmid
additional information
-
construction of 25-hydroxyvitamin D-1alpha-hydroxylase and PTH double knockout mice, NH2-terminal fragments of PTH and PTH-related protein, PTHrP, on the skeleton of young mutant mice is an increase in both endochondral bone and appositional formation without increased bone resorption, phenotype, overview, PTH is the major protein hormone regulating calcium homeostasis, PTHrP is a PTH-like factor responsible for humoral hypercalcemia of malignancy, both peptides are required to achieve normal fetal skeletal morphogenesis
APPLICATION
ORGANISM
UNIPROT ACCESSION NO.
COMMENTARY
LITERATURE
medicine
-
the enzyme is a target in cancer therapy and prevention
medicine
-
genes CYP2R1 encoding vitamin D 25-hydroxylase, CYP27B1 encoding 25-hydroxyvitamin D-1 alpha hydroxylase and CYP24A1 encoding 1,25-dihydroxyvitamin D(3) 24-hydroxylase are upregulated in clear cell renal cell carcinomas compared with normal tissue. CYP24A1 displays a significantly higher expression in tumors than CYP27B1 and CYP2R1, whereas no differences in the expression of these genes are found in healthy renal tissue. Gene expression of CYP2R1, CYP27B1 and CYP24A does not differ between pathological classifications
medicine
-
hyperplastic parathyroid glands from patients with chronic kidney failure normally display a heterogeneous cellularity. 25-hydroxyvitamin D3 1alpha-hydroxylase is expressed at much higher levels in oxyphil cells than in chief cells in these patients. The calcimimetic cinacalcet increases the expression of the enzyme in human parathyroid cultures. The enzyme in human parathyroid cultures is functionally active