Cytochrome P450 27, mitochondrial precursor

Names and origin

Protein names

Recommended name:
    Cytochrome P450 27, mitochondrial
    EC=1.14.13.15
Alternative name(s):
    Cytochrome P-450C27/25
    Sterol 26-hydroxylase
    Sterol 27-hydroxylase
    Vitamin D(3) 25-hydroxylase
    5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 27-hydroxylase

Gene names

Name:	CYP27A1
Synonyms:	CYP27

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	531 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Catalyzes the first step in the oxidation of the side chain of sterol intermediates; the 27-hydroxylation of 5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol. Has also a vitamin D3-25-hydroxylase activity.
Catalytic activity	5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol + NADPH + O(2) = (25R)-5-beta-cholestane-3-alpha,7-alpha,12-alpha,26-tetraol + NADP(+) + H(2)O.
Cofactor	Heme group.
Pathway	Hormone biosynthesis; cholecalciferol biosynthesis.
Subcellular location	Mitochondrion membrane.
Involvement in disease	Defects in CYP27A1 are the cause of cerebrotendinous xanthomatosis (CTX) [MIM:213700]. CTX is a rare sterol storage disorder characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts.
Sequence similarities	Belongs to the cytochrome P450 family.

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Ontologies

Keywords
Cellular component	Membrane Mitochondrion
Disease	Cataract Disease mutation
Domain	Transit peptide
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
PTM	Acetylation
Technical term	3D-structure
Gene Ontology (GO)
Cellular component	mitochondrial matrix Ref.1 Inferred from Experiment. Source: Reactome
Molecular function	steroid hydroxylase activity Ref.1 Ref.9 Traceable author statement. Source: ProtInc
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Transit peptide

1 – 33

33

Mitochondrion

Chain

34 – 531

498

Cytochrome P450 27, mitochondrial

Regions

Region

384 – 398

15

Sterol-binding Potential

Sites

Metal binding

476

1

Iron (heme axial ligand)

Amino acid modifications

Modified residue

123

1

N6-acetyllysine By similarity

Modified residue

283

1

N6-acetyllysine By similarity

Modified residue

496

1

N6-acetyllysine By similarity

Natural variations

Natural variant

145

1

G → E in CTX.

Natural variant

395

1

R → C in CTX.

Natural variant

395

1

R → S in CTX.

Natural variant

405

1

R → Q in CTX.

Natural variant

474

1

R → Q in CTX.

Natural variant

474

1

R → W in CTX.

Natural variant

479

1

R → C in CTX.

Experimental info

Sequence conflict

20 – 25

6

LCPHGA → SAPTG in CAA42481. Ref.2

Sequence conflict

171

1

A → R in CAA42481. Ref.2

Sequence conflict

359

1

E → K in AAO21126. Ref.3

Secondary structure

1

.

531

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q02318-1 [UniParc].

Last modified July 1, 1993. Version 1.
Checksum: 62025EB670DBD8E9
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FASTA

531

60,235

        10         20         30         40         50         60 
MAALGCARLR WALRGAGRGL CPHGARAKAA IPAALPSDKA TGAPGAGPGV RRRQRSLEEI 

        70         80         90        100        110        120 
PRLGQLRFFF QLFVQGYALQ LHQLQVLYKA KYGPMWMSYL GPQMHVNLAS APLLEQVMRQ 

       130        140        150        160        170        180 
EGKYPVRNDM ELWKEHRDQH DLTYGPFTTE GHHWYQLRQA LNQRLLKPAE AALYTDAFNE 

       190        200        210        220        230        240 
VIDDFMTRLD QLRAESASGN QVSDMAQLFY YFALEAICYI LFEKRIGCLQ RSIPEDTVTF 

       250        260        270        280        290        300 
VRSIGLMFQN SLYATFLPKW TRPVLPFWKR YLDGWNAIFS FGKKLIDEKL EDMEAQLQAA 

       310        320        330        340        350        360 
GPDGIQVSGY LHFLLASGQL SPREAMGSLP ELLMAGVDTT SNTLTWALYH LSKDPEIQEA 

       370        380        390        400        410        420 
LHEEVVGVVP AGQVPQHKDF AHMPLLKAVL KETLRLYPVV PTNSRIIEKE IEVDGFLFPK 

       430        440        450        460        470        480 
NTQFVFCHYV VSRDPTAFSE PESFQPHRWL RNSQPATPRI QHPFGSVPFG YGVRACLGRR 

       490        500        510        520        530 
IAELEMQLLL ARLIQKYKVV LAPETGELKS VARIVLVPNK KVGLQFLQRQ C

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of human sterol 27-hydroxylase. A mitochondrial cytochrome P-450 that catalyzes multiple oxidation reaction in bile acid biosynthesis." Cali J.J., Russell D.W. J. Biol. Chem. 266:7774-7778(1991) [PubMed: 1708392] [Abstract] Cited for: NUCLEOTIDE SEQUENCE. Tissue: Liver.
[2]	"Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions." Guo Y.-D., Strugnell S., Back D.W., Jones G. Proc. Natl. Acad. Sci. U.S.A. 90:8668-8672(1993) [PubMed: 7690968] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	Zhang H.T., Gong Y. Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE. Tissue: Kidney.
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain and Colon.
[5]	"Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin." Leitersdorf E., Reshef A., Meiner V., Levitzki R., Schwartz S.P., Dann E.J., Berkman N., Cali J.J., Klapholz L., Berginer V.M. J. Clin. Invest. 91:2488-2496(1993) [PubMed: 8514861] [Abstract] Cited for: NUCLEOTIDE SEQUENCE OF 1-15.
[6]	"Mutations in the bile acid biosynthetic enzyme sterol 27-hydroxylase underlie cerebrotendinous xanthomatosis." Cali J.J., Hsieh C.-L., Francke U., Russell D.W. J. Biol. Chem. 266:7779-7783(1991) [PubMed: 2019602] [Abstract] Cited for: VARIANTS CTX CYS-395 AND CYS-479.
[7]	"Identification of new mutations in sterol 27-hydroxylase gene in Japanese patients with cerebrotendinous xanthomatosis (CTX)." Kim K.-K., Kubota S., Kuriyama M., Fujiyama J., Bjorkhem I., Eggertsen G., Seyama Y. J. Lipid Res. 35:1031-1039(1994) [PubMed: 7915755] [Abstract] Cited for: VARIANTS CTX GLN-474 AND TRP-474.
[8]	"Novel homozygous and compound heterozygous mutations of sterol 27-hydroxylase gene (CYP27) cause cerebrotendinous xanthomatosis in three Japanese patients from two unrelated families." Chen W., Kubota S., Kim K.-S., Cheng J., Kuriyama M., Eggertsen G., Bjorkhem I., Seyama Y. J. Lipid Res. 38:870-879(1997) [PubMed: 9186905] [Abstract] Cited for: VARIANT CTX GLN-405.
[9]	"A novel arg362ser mutation in the sterol 27-hydroxylase gene (CYP27): its effects on pre-mRNA splicing and enzyme activity." Chen W., Kubota S., Ujike H., Ishihara T., Seyama Y. Biochemistry 37:15050-15056(1998) [PubMed: 9790667] [Abstract] Cited for: VARIANT CTX SER-395.
[10]	"Two novel mutations in the sterol 27-hydroxylase gene causing cerebrotendinous xanthomatosis." Lamon-Fava S., Schaefer E.J., Garuti R., Salen G., Calandra S. Clin. Genet. 61:185-191(2002) [PubMed: 12000359] [Abstract] Cited for: VARIANT CTX GLU-145.
+	Additional computationally mapped references.