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Reviewed, UniProtKB/Swiss-Prot Q02318 (CP27A_HUMAN)

Last modified July 7, 2009. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Sterol 26-hydroxylase, mitochondrial
    EC=1.14.13.15
Alternative name(s):
    Cytochrome P450 27
    Cytochrome P-450C27/25
    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
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length531 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 + O2 = (25R)-5-beta-cholestane-3-alpha,7-alpha,12-alpha,26-tetraol + NADP+ + H2O.

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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10

Sequence similarities

Belongs to the cytochrome P450 family.

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Ontologies

Keywords
   Cellular componentMembrane
Mitochondrion
   Coding sequence diversityPolymorphism
   DiseaseCataract
Disease mutation
   DomainTransit peptide
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   PTMAcetylation
   Technical term3D-structure
Complete proteome
Gene Ontology (GO)
   Biological processoxidation reduction

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular componentmitochondrial matrix Ref.1

Inferred from Experiment. Source: Reactome

   Molecular functioncholestanetriol 26-monooxygenase activity

Inferred from electronic annotation. Source: EC

electron carrier activity

Inferred from electronic annotation. Source: InterPro

heme binding

Inferred from electronic annotation. Source: InterPro

steroid hydroxylase activity Ref.1 Ref.9

Inferred from Experiment. Source: Reactome

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3333Mitochondrion
Chain34 – 531498Sterol 26-hydroxylase, mitochondrial
PRO_0000003618

Regions

Region384 – 39815Sterol-binding Potential

Sites

Metal binding4761Iron (heme axial ligand)

Amino acid modifications

Modified residue1231N6-acetyllysine By similarity
Modified residue2831N6-acetyllysine By similarity
Modified residue4961N6-acetyllysine By similarity

Natural variations

Natural variant1451G → E in CTX. Ref.10
VAR_016966
Natural variant1751T → M: dbSNP rs2229381.
VAR_048467
Natural variant3951R → C in CTX. Ref.6 Ref.9
VAR_001303
Natural variant3951R → S in CTX. Ref.6 Ref.9
VAR_012285
Natural variant4051R → Q in CTX. Ref.8
VAR_012286
Natural variant4741R → Q in CTX. Ref.7
VAR_012287
Natural variant4741R → W in CTX. Ref.7
VAR_012288
Natural variant4791R → C in CTX. Ref.6
VAR_001304

Experimental info

Sequence conflict20 – 256LCPHGA → SAPTG in CAA42481. Ref.2
Sequence conflict1711A → R in CAA42481. Ref.2
Sequence conflict3591E → K in AAO21126. Ref.3

Secondary structure

1 ....................................................................... 531
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Q02318-1 [UniParc].

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

FASTA53160,235
        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

« Hide

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References

« Hide '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 [MRNA].
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 [MRNA].
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 [GENOMIC DNA] 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.

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Web resources

GeneReviews

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Cross-references

Sequence databases

M62401 mRNA. Translation: AAA52142.1.
X59812 mRNA. Translation: CAA42481.1.
AY178622 mRNA. Translation: AAO21126.1.
BC040430 mRNA. Translation: AAH40430.1.
BC051851 mRNA. Translation: AAH51851.1.
S62709 Genomic DNA. Translation: AAB27199.1.
IPIIPI00025307.
PIRA39740.
RefSeqNP_000775.1.
UniGeneHs.516700

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1MFXmodel-A34-531[»]
ModBaseSearch...

PTM databases

PhosphoSiteQ02318.

Proteomic databases

PeptideAtlasQ02318.
PRIDEQ02318.

Genome annotation databases

EnsemblENSG00000135929. Homo sapiens. [Contig view]
GeneID1593.
KEGGhsa:1593.
UCSCuc002viz.2. human.

Organism-specific databases

GeneCardsGC02P219354.
H-InvDBHIX0023981.
HGNCHGNC:2605. CYP27A1.
MIM213700. phenotype.
606530. gene.
Orphanet909. Xanthomatosis cerebrotendinous.
PharmGKBPA135.
GenAtlasSearch...

Phylogenomic databases

HOGENOMQ02318.
HOVERGENQ02318.
OMAQ02318. FYYFALE.

Enzyme and pathway databases

BRENDA1.14.13.15. 247.
ReactomeREACT_13433. Biological oxidations.
REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpressQ02318.
BgeeQ02318.
CleanExHS_CYP27A1.
GermOnlineENSG00000135929. Homo sapiens.

Family and domain databases

InterProIPR001128. Cyt_P450.
IPR017973. Cyt_P450_C.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
Gene3DG3DSA:1.10.630.10. Cyt_P450. 1 hit.
PANTHERPTHR19383. Cyt_P450. 1 hit.
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00169. Cholecalciferol.
NextBio6548.
SOURCESearch...

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Entry information

Entry nameCP27A_HUMAN
AccessionPrimary (citable) accession number: Q02318
Secondary accession number(s): Q6LDB4, Q86YQ6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: July 7, 2009
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents