Q07973 · CP24A_HUMAN
- Protein1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
- GeneCYP24A1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids514 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A cytochrome P450 monooxygenase with a key role in vitamin D catabolism and calcium homeostasis. Via C24- and C23-oxidation pathways, catalyzes the inactivation of both the vitamin D precursor calcidiol (25-hydroxyvitamin D3) and the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D3) (PubMed:11012668, PubMed:15574355, PubMed:16617161, PubMed:24893882, PubMed:29461981, PubMed:8679605).
With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid (PubMed:15574355, PubMed:24893882).
With initial hydroxylation at C-23 (via C23-oxidation pathway), catalyzes sequential oxidation of calcidiol leading to the formation of 25(OH)D3-26,23-lactone as end product (PubMed:11012668, PubMed:8679605).
Preferentially hydroxylates at C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol (PubMed:25727742).
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 FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:8679605).
With initial hydroxylation at C-24 (via C24-oxidation pathway), performs a sequential 6-step oxidation of calcitriol leading to the formation of the biliary metabolite calcitroic acid (PubMed:15574355, PubMed:24893882).
With initial hydroxylation at C-23 (via C23-oxidation pathway), catalyzes sequential oxidation of calcidiol leading to the formation of 25(OH)D3-26,23-lactone as end product (PubMed:11012668, PubMed:8679605).
Preferentially hydroxylates at C-25 other vitamin D active metabolites, such as CYP11A1-derived secosteroids 20S-hydroxycholecalciferol and 20S,23-dihydroxycholecalciferol (PubMed:25727742).
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 FDXR/adrenodoxin reductase and FDX1/adrenodoxin (PubMed:8679605).
Catalytic activity
- calcitriol + 2 H+ + O2 + 2 reduced [adrenodoxin] = calcitetrol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- calcitriol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 1alpha,23S,25-trihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 2 H+ + O2 + 2 reduced [adrenodoxin] + secalciferol = 25-hydroxy-24-oxocalciol + 2 H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 25-hydroxy-24-oxocalciol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 23S,25-dihydroxy-24-oxocholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- calcidiol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (23S)-23,25-dihydroxycalciol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 20S-hydroxycholecalciferol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 20S,25-dihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 20S-hydroxycholecalciferol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 20S,24R-dihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
- 20S,23-dihydroxycholecalciferol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 20S,23,25-trihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]This reaction proceeds in the forward direction.
Cofactor
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.16 μM | calcidiol | |||||
0.072 μM | calcitriol | |||||
0.35 μM | calcitriol |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
0.088 mol/min/mol | toward calcidiol | ||||
0.066 mol/min/mol | toward calcitriol |
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | mitochondrial inner membrane | |
Molecular Function | 1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity | |
Molecular Function | 1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity | |
Molecular Function | 25-hydroxycholecalciferol-23-hydroxylase activity | |
Molecular Function | 25-hydroxycholecalciferol-24-hydroxylase activity | |
Molecular Function | heme binding | |
Molecular Function | iron ion binding | |
Molecular Function | vitamin D 25-hydroxylase activity | |
Biological Process | osteoblast differentiation | |
Biological Process | response to vitamin D | |
Biological Process | vitamin D catabolic process | |
Biological Process | vitamin D metabolic process | |
Biological Process | vitamin D receptor signaling pathway | |
Biological Process | vitamin metabolic process |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Chemistry
Names & Taxonomy
Protein names
- Recommended name1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
- EC number
- Short names24-OHase; Vitamin D(3) 24-hydroxylase
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ07973
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Hypercalcemia, infantile, 1 (HCINF1)
- Note
- DescriptionA disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis.
- See alsoMIM:143880
Natural variants in HCINF1
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_066408 | 143 | missing | in HCINF1; complete loss of function | |
VAR_066409 | 159 | R>Q | in HCINF1; complete loss of function; dbSNP:rs387907322 | |
VAR_066410 | 322 | E>K | in HCINF1; complete loss of function; dbSNP:rs387907324 | |
VAR_066411 | 396 | R>W | in HCINF1; complete loss of function; dbSNP:rs114368325 | |
VAR_048466 | 409 | L>S | in HCINF1; retains small but measurable levels of activity; dbSNP:rs6068812 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_066408 | 143 | in HCINF1; complete loss of function | |||
Sequence: Missing | ||||||
Natural variant | VAR_048464 | 157 | in dbSNP:rs35051736 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_066409 | 159 | in HCINF1; complete loss of function; dbSNP:rs387907322 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_066410 | 322 | in HCINF1; complete loss of function; dbSNP:rs387907324 | |||
Sequence: E → K | ||||||
Natural variant | VAR_048465 | 374 | in dbSNP:rs6022990 | |||
Sequence: M → T | ||||||
Natural variant | VAR_066411 | 396 | in HCINF1; complete loss of function; dbSNP:rs114368325 | |||
Sequence: R → W | ||||||
Natural variant | VAR_048466 | 409 | in HCINF1; retains small but measurable levels of activity; dbSNP:rs6068812 | |||
Sequence: L → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 817 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for transit peptide, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transit peptide | 1-35 | Mitochondrion | ||||
Sequence: MSSPISKSRSLAAFLQQLRSPRQPPRLVTSTAYTS | ||||||
Chain | PRO_0000003615 | 36-514 | 1,25-dihydroxyvitamin D3 24-hydroxylase, mitochondrial | |||
Sequence: PQPREVPVCPLTAGGETQNAAALPGPTSWPLLGSLLQILWKGGLKKQHDTLVEYHKKYGKIFRMKLGSFESVHLGSPCLLEALYRTESAYPQRLEIKPWKAYRDYRKEGYGLLILEGEDWQRVRSAFQKKLMKPGEVMKLDNKINEVLADFMGRIDELCDERGHVEDLYSELNKWSFESICLVLYEKRFGLLQKNAGDEAVNFIMAIKTMMSTFGRMMVTPVELHKSLNTKVWQDHTLAWDTIFKSVKACIDNRLEKYSQQPSADFLCDIYHQNRLSKKELYAAVTELQLAAVETTANSLMWILYNLSRNPQVQQKLLKEIQSVLPENQVPRAEDLRNMPYLKACLKESMRLTPSVPFTTRTLDKATVLGEYALPKGTVLMLNTQVLGSSEDNFEDSSQFRPERWLQEKEKINPFAHLPFGVGKRMCIGRRLAELQLHLALCWIVRKYDIQATDNEPVEMLHSGTLVPSRELPIAFCQR |
Proteomic databases
PTM databases
Structure
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
Q07973-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length514
- Mass (Da)58,875
- Last updated2001-10-18 v2
- Checksum8862F63771981195
Q07973-2
- Name2
- Differences from canonical
- 413-478: Missing
Q07973-3
- Name3
- SynonymsCYP24-SV
- NoteSpecifically expressed in macrophages. Lacks the transit peptide. May be a dominant negative-acting isoform possibly by sequestering vitamin D metabolites.
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_053367 | 1-8 | in isoform 3 | |||
Sequence: MSSPISKS → MYSCFSHR | ||||||
Alternative sequence | VSP_053368 | 9-150 | in isoform 3 | |||
Sequence: Missing | ||||||
Sequence conflict | 68 | in Ref. 1; AAA62379/AAB03776 | ||||
Sequence: G → A | ||||||
Sequence conflict | 124-125 | in Ref. 1; AAA62379 | ||||
Sequence: AY → V | ||||||
Sequence conflict | 270 | in Ref. 1; AAA62379 | ||||
Sequence: D → G | ||||||
Sequence conflict | 365 | in Ref. 1; AAA62379 | ||||
Sequence: V → R | ||||||
Sequence conflict | 368 | in Ref. 1; AAA62379 | ||||
Sequence: A → E | ||||||
Sequence conflict | 390 | in Ref. 1; AAA62379 | ||||
Sequence: S → G | ||||||
Alternative sequence | VSP_043101 | 413-478 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 511 | in Ref. 6; AAB29308 | ||||
Sequence: F → S |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
L13286 EMBL· GenBank· DDBJ | AAA62379.1 EMBL· GenBank· DDBJ | mRNA | ||
AY858838 EMBL· GenBank· DDBJ | AAW50795.1 EMBL· GenBank· DDBJ | mRNA | ||
AL138805 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC109083 EMBL· GenBank· DDBJ | AAI09084.1 EMBL· GenBank· DDBJ | mRNA | ||
BC109084 EMBL· GenBank· DDBJ | AAI09085.1 EMBL· GenBank· DDBJ | mRNA | ||
U60669 EMBL· GenBank· DDBJ | AAB03776.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
S67623 EMBL· GenBank· DDBJ | AAB29308.1 EMBL· GenBank· DDBJ | mRNA |