Q07973 · CP24A_HUMAN

  • Protein
    1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
  • Gene
    CYP24A1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

  • calcitriol + 2 H+ + O2 + 2 reduced [adrenodoxin] = calcitetrol + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
    EC:1.14.15.16 (UniProtKB | ENZYME | Rhea)
  • calcitetrol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (1S)-1,25-dihydroxy-24-oxocalciol + 2 H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
    EC:1.14.15.16 (UniProtKB | ENZYME | Rhea)
  • (1S)-1,25-dihydroxy-24-oxocalciol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (1S)-1,23,25-trihydroxy-24-oxocalciol + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
    EC:1.14.15.16 (UniProtKB | ENZYME | Rhea)
  • (1S)-1,23-dihydroxy-24,25,26,27-tetranorcalciol + 2 H+ + O2 + 2 reduced [adrenodoxin] = (1S)-1-hydroxy-23-oxo-24,25,26,27-tetranorcalciol + 2 H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
    EC:1.14.15.16 (UniProtKB | ENZYME | Rhea)
  • (1S)-1-hydroxy-23-oxo-24,25,26,27-tetranorcalciol + H+ + O2 + 2 reduced [adrenodoxin] = calcitroate + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
    EC:1.14.15.16 (UniProtKB | ENZYME | Rhea)
  • calcitriol + 2 H+ + O2 + 2 reduced [adrenodoxin] = 1alpha,23S,25-trihydroxycholecalciferol + H2O + 2 oxidized [adrenodoxin]
    This reaction proceeds in the forward direction.
  • calcidiol + 2 H+ + O2 + 2 reduced [adrenodoxin] = H2O + 2 oxidized [adrenodoxin] + secalciferol
    This reaction proceeds in the forward direction.
    EC:1.14.15.16 (UniProtKB | ENZYME | Rhea)
  • 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

heme (UniProtKB | Rhea| CHEBI:30413 )

Kinetics

KM SUBSTRATE pH TEMPERATURE[C] NOTES EVIDENCE
0.16 μMcalcidiol
0.072 μMcalcitriol
0.35 μMcalcitriol
Vmax pH TEMPERATURE[C] NOTES EVIDENCE
0.088 mol/min/moltoward calcidiol
0.066 mol/min/moltoward calcitriol

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site462Fe (UniProtKB | ChEBI) of heme (UniProtKB | ChEBI); axial binding residue

GO annotations

AspectTerm
Cellular Componentmitochondrial inner membrane
Molecular Function1-alpha,25-dihydroxyvitamin D3 23-hydroxylase activity
Molecular Function1-alpha,25-dihydroxyvitamin D3 24-hydroxylase activity
Molecular Function25-hydroxycholecalciferol-23-hydroxylase activity
Molecular Function25-hydroxycholecalciferol-24-hydroxylase activity
Molecular Functionheme binding
Molecular Functioniron ion binding
Molecular Functionvitamin D 25-hydroxylase activity
Biological Processosteoblast differentiation
Biological Processresponse to vitamin D
Biological Processvitamin D catabolic process
Biological Processvitamin D metabolic process
Biological Processvitamin D receptor signaling pathway
Biological Processvitamin metabolic process

Keywords

Enzyme and pathway databases

Chemistry

Names & Taxonomy

Protein names

  • Recommended name
    1,25-dihydroxyvitamin D(3) 24-hydroxylase, mitochondrial
  • EC number
  • Short names
    24-OHase; Vitamin D(3) 24-hydroxylase
  • Alternative names
    • Cytochrome P450 24A1
    • Cytochrome P450-CC24

Gene names

    • Name
      CYP24A1
    • Synonyms
      CYP24

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo

Accessions

  • Primary accession
    Q07973
  • Secondary accessions
    • Q15807
    • Q32ML3
    • Q5I2W7

Proteomes

Organism-specific databases

Subcellular Location

Keywords

Disease & Variants

Involvement in disease

Hypercalcemia, infantile, 1 (HCINF1)

  • Note
    • The disease is caused by variants affecting the gene represented in this entry
  • Description
    A disorder characterized by abnormally high level of calcium in the blood, failure to thrive, vomiting, dehydration, and nephrocalcinosis.
  • See also
    MIM:143880
Natural variants in HCINF1
Variant IDPosition(s)ChangeDescription
VAR_066408143missingin HCINF1; complete loss of function
VAR_066409159R>Qin HCINF1; complete loss of function; dbSNP:rs387907322
VAR_066410322E>Kin HCINF1; complete loss of function; dbSNP:rs387907324
VAR_066411396R>Win HCINF1; complete loss of function; dbSNP:rs114368325
VAR_048466409L>Sin HCINF1; retains small but measurable levels of activity; dbSNP:rs6068812

Features

Showing features for natural variant.

TypeIDPosition(s)Description
Natural variantVAR_066408143in HCINF1; complete loss of function
Natural variantVAR_048464157in dbSNP:rs35051736
Natural variantVAR_066409159in HCINF1; complete loss of function; dbSNP:rs387907322
Natural variantVAR_066410322in HCINF1; complete loss of function; dbSNP:rs387907324
Natural variantVAR_048465374in dbSNP:rs6022990
Natural variantVAR_066411396in HCINF1; complete loss of function; dbSNP:rs114368325
Natural variantVAR_048466409in HCINF1; retains small but measurable levels of activity; dbSNP:rs6068812

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.

Go to variant viewer

Keywords

Organism-specific databases

Miscellaneous

Chemistry

Genetic variation databases

PTM/Processing

Features

Showing features for transit peptide, chain.

TypeIDPosition(s)Description
Transit peptide1-35Mitochondrion
ChainPRO_000000361536-5141,25-dihydroxyvitamin D3 24-hydroxylase, mitochondrial

Proteomic databases

PTM databases

Expression

Gene expression databases

    • ENSG00000019186Expressed in olfactory segment of nasal mucosa and 112 other cell types or tissues

Organism-specific databases

    • ENSG00000019186Group enriched (endometrium, kidney, lymphoid tissue, placenta, urinary bladder)

Interaction

Protein-protein interaction databases

Chemistry

Miscellaneous

Structure

Family & Domains

Sequence similarities

Belongs to the cytochrome P450 family.

Keywords

Phylogenomic databases

Family and domain databases

Sequence & Isoforms

Align isoforms (3)
  • Sequence status
    Complete
  • Sequence processing
    The 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.

  • Length
    514
  • Mass (Da)
    58,875
  • Last updated
    2001-10-18 v2
  • Checksum
    8862F63771981195
MSSPISKSRSLAAFLQQLRSPRQPPRLVTSTAYTSPQPREVPVCPLTAGGETQNAAALPGPTSWPLLGSLLQILWKGGLKKQHDTLVEYHKKYGKIFRMKLGSFESVHLGSPCLLEALYRTESAYPQRLEIKPWKAYRDYRKEGYGLLILEGEDWQRVRSAFQKKLMKPGEVMKLDNKINEVLADFMGRIDELCDERGHVEDLYSELNKWSFESICLVLYEKRFGLLQKNAGDEAVNFIMAIKTMMSTFGRMMVTPVELHKSLNTKVWQDHTLAWDTIFKSVKACIDNRLEKYSQQPSADFLCDIYHQNRLSKKELYAAVTELQLAAVETTANSLMWILYNLSRNPQVQQKLLKEIQSVLPENQVPRAEDLRNMPYLKACLKESMRLTPSVPFTTRTLDKATVLGEYALPKGTVLMLNTQVLGSSEDNFEDSSQFRPERWLQEKEKINPFAHLPFGVGKRMCIGRRLAELQLHLALCWIVRKYDIQATDNEPVEMLHSGTLVPSRELPIAFCQR

Q07973-2

  • Name
    2
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical

Q07973-3

  • Name
    3
  • Synonyms
    CYP24-SV
  • Note
    Specifically expressed in macrophages. Lacks the transit peptide. May be a dominant negative-acting isoform possibly by sequestering vitamin D metabolites.
  • See also
    sequence in UniParc or sequence clusters in UniRef
  • Differences from canonical
    • 1-8: MSSPISKS → MYSCFSHR
    • 9-150: Missing

Features

Showing features for alternative sequence, sequence conflict.

TypeIDPosition(s)Description
Alternative sequenceVSP_0533671-8in isoform 3
Alternative sequenceVSP_0533689-150in isoform 3
Sequence conflict68in Ref. 1; AAA62379/AAB03776
Sequence conflict124-125in Ref. 1; AAA62379
Sequence conflict270in Ref. 1; AAA62379
Sequence conflict365in Ref. 1; AAA62379
Sequence conflict368in Ref. 1; AAA62379
Sequence conflict390in Ref. 1; AAA62379
Alternative sequenceVSP_043101413-478in isoform 2
Sequence conflict511in Ref. 6; AAB29308

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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