Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q02318 (CP27A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Sterol 26-hydroxylase, mitochondrial

EC=1.14.13.15
Alternative name(s):
5-beta-cholestane-3-alpha,7-alpha,12-alpha-triol 27-hydroxylase
Cytochrome P-450C27/25
Cytochrome P450 27
Sterol 27-hydroxylase
Vitamin D(3) 25-hydroxylase
Gene names
Name:CYP27A1
Synonyms:CYP27
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length531 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

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 + 3 NADPH + 3 O2 = (25R)-3-alpha,7-alpha,12-alpha-trihydroxy-5-beta-cholestan-26-oate + 3 NADP+ + 4 H2O.

Cofactor

Heme group.

Pathway

Hormone biosynthesis; cholecalciferol biosynthesis.

Subcellular location

Mitochondrion membrane.

Involvement in disease

Cerebrotendinous xanthomatosis (CTX) [MIM:213700]: Rare sterol storage disorder characterized clinically by progressive neurologic dysfunction, premature atherosclerosis, and cataracts.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Sequence similarities

Belongs to the cytochrome P450 family.

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
Reference proteome
Gene Ontology (GO)
   Biological_processbile acid biosynthetic process

Traceable author statement. Source: Reactome

bile acid metabolic process

Traceable author statement. Source: Reactome

cholesterol metabolic process

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

sterol metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial inner membrane

Inferred from electronic annotation. Source: Ensembl

mitochondrial matrix

Traceable author statement. Source: Reactome

   Molecular_functioncholestanetriol 26-monooxygenase activity

Inferred from electronic annotation. Source: UniProtKB-EC

cholesterol 26-hydroxylase activity

Inferred from electronic annotation. Source: Ensembl

heme binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: InterPro

steroid hydroxylase activity

Traceable author statement Ref.11. Source: ProtInc

vitamin D3 25-hydroxylase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

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 residue2831N6-acetyllysine By similarity
Modified residue5091N6-acetyllysine By similarity
Modified residue5201N6-acetyllysine By similarity

Natural variations

Natural variant1451G → E in CTX. Ref.12
VAR_016966
Natural variant1691A → V.
Corresponds to variant rs59443548 [ dbSNP | Ensembl ].
VAR_061046
Natural variant1751T → M.
Corresponds to variant rs2229381 [ dbSNP | Ensembl ].
VAR_048467
Natural variant3951R → C in CTX. Ref.8
VAR_001303
Natural variant3951R → S in CTX. Ref.11
VAR_012285
Natural variant4051R → Q in CTX. Ref.10
VAR_012286
Natural variant4741R → Q in CTX. Ref.9
VAR_012287
Natural variant4741R → W in CTX. Ref.9
VAR_012288
Natural variant4791R → C in CTX. Ref.8
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

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Q02318 [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

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] [Europe PMC] [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] [Europe PMC] [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]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Umbilical cord blood.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain and Colon.
[7]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
[8]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CTX CYS-395 AND CYS-479.
[9]"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] [Europe PMC] [Abstract]
Cited for: VARIANTS CTX GLN-474 AND TRP-474.
[10]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CTX GLN-405.
[11]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CTX SER-395.
[12]"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] [Europe PMC] [Abstract]
Cited for: VARIANT CTX GLU-145.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M62401 mRNA. Translation: AAA52142.1.
X59812 mRNA. Translation: CAA42481.1.
AY178622 mRNA. Translation: AAO21126.1.
AK290418 mRNA. Translation: BAF83107.1.
CH471063 Genomic DNA. Translation: EAW70654.1.
BC040430 mRNA. Translation: AAH40430.1.
BC051851 mRNA. Translation: AAH51851.1.
S62709 Genomic DNA. Translation: AAB27199.1.
CCDSCCDS2423.1.
PIRA39740.
RefSeqNP_000775.1. NM_000784.3.
UniGeneHs.516700.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1MFXmodel-A34-531[»]
ProteinModelPortalQ02318.
SMRQ02318. Positions 61-529.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107965. 1 interaction.
IntActQ02318. 1 interaction.
STRING9606.ENSP00000258415.

Chemistry

BindingDBQ02318.
ChEMBLCHEMBL5992.
DrugBankDB00169. Cholecalciferol.

PTM databases

PhosphoSiteQ02318.

Polymorphism databases

DMDM399288.

Proteomic databases

MaxQBQ02318.
PaxDbQ02318.
PeptideAtlasQ02318.
PRIDEQ02318.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000258415; ENSP00000258415; ENSG00000135929.
GeneID1593.
KEGGhsa:1593.
UCSCuc002viz.4. human.

Organism-specific databases

CTD1593.
GeneCardsGC02P219610.
GeneReviewsCYP27A1.
HGNCHGNC:2605. CYP27A1.
HPAHPA059155.
MIM213700. phenotype.
606530. gene.
neXtProtNX_Q02318.
Orphanet909. Cerebrotendinous xanthomatosis.
PharmGKBPA135.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000253961.
HOVERGENHBG106909.
InParanoidQ02318.
KOK00488.
OMAQISGYLH.
OrthoDBEOG7ZGX4B.
PhylomeDBQ02318.
TreeFamTF105094.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
UniPathwayUPA00955.

Gene expression databases

ArrayExpressQ02318.
BgeeQ02318.
CleanExHS_CYP27A1.
GenevestigatorQ02318.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCYP27A1. human.
GeneWikiCYP27A1.
GenomeRNAi1593.
NextBio6548.
PROQ02318.
SOURCESearch...

Entry information

Entry nameCP27A_HUMAN
AccessionPrimary (citable) accession number: Q02318
Secondary accession number(s): A8K303, Q6LDB4, Q86YQ6
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: July 9, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

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