Q02318 (CP27A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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

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 component	Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Cataract Disease mutation
Domain	Transit peptide
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid biosynthetic process Traceable author statement. Source: Reactome cholesterol metabolic process Inferred from electronic annotation. Source: Compara xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	mitochondrial inner membrane Inferred from electronic annotation. Source: Compara mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	cholestanetriol 26-monooxygenase activity Inferred from electronic annotation. Source: EC cholesterol 26-hydroxylase activity Inferred from electronic annotation. Source: Compara electron carrier activity Inferred from electronic annotation. Source: InterPro 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: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 33

33

Mitochondrion

Chain

34 – 531

498

Sterol 26-hydroxylase, mitochondrial

PRO_0000003618

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. Ref.12

VAR_016966

Natural variant

169

1

A → V.
Corresponds to variant rs59443548 [ dbSNP | Ensembl ].

VAR_061046

Natural variant

175

1

T → M.
Corresponds to variant rs2229381 [ dbSNP | Ensembl ].

VAR_048467

Natural variant

395

1

R → C in CTX. Ref.8

VAR_001303

Natural variant

395

1

R → S in CTX. Ref.11

VAR_012285

Natural variant

405

1

R → Q in CTX. Ref.10

VAR_012286

Natural variant

474

1

R → Q in CTX. Ref.9

VAR_012287

Natural variant

474

1

R → W in CTX. Ref.9

VAR_012288

Natural variant

479

1

R → C in CTX. Ref.8

VAR_001304

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

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531

Helix Strand Turn

Details...

Helix

67 – 71

5

Helix

83 – 91

9

Turn

92 – 94

3

Helix

101 – 103

3

Helix

111 – 114

4

Turn

115 – 117

3

Turn

120 – 122

3

Helix

131 – 140

10

Beta strand

142 – 147

6

Helix

152 – 160

9

Turn

161 – 166

6

Helix

170 – 190

21

Helix

207 – 222

16

Turn

228 – 230

3

Helix

236 – 252

17

Turn

262 – 264

3

Helix

266 – 268

3

Helix

269 – 293

25

Helix

304 – 310

7

Turn

314 – 316

3

Helix

322 – 353

32

Helix

355 – 368

14

Beta strand

370 – 375

6

Helix

377 – 381

5

Helix

384 – 396

13

Beta strand

404 – 406

3

Turn

413 – 415

3

Helix

428 – 431

4

Helix

435 – 438

4

Beta strand

439 – 442

4

Helix

446 – 448

3

Turn

449 – 451

3

Beta strand

458 – 460

3

Helix

464 – 466

3

Beta strand

468 – 470

3

Beta strand

472 – 476

5

Helix

479 – 496

18

Beta strand

512 – 516

5

Sequences

	Sequence		Length	Mass (Da)
	Q02318 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: 62025EB670DBD8E9	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

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] [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. , 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. , 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.

Web resources

GeneReviews

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.

IPI

IPI00025307.

PIR

A39740.

RefSeq

NP_000775.1. NM_000784.3.

UniGene

Hs.516700.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MFX	model	-	A	34-531	[»]

ProteinModelPortal

Q02318.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q02318. 1 interaction.

STRING

9606.ENSP00000258415.

PTM databases

PhosphoSite

Q02318.

Polymorphism databases

DMDM

399288.

Proteomic databases

PaxDb

Q02318.

PeptideAtlas

Q02318.

PRIDE

Q02318.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000258415; ENSP00000258415; ENSG00000135929.

GeneID

1593.

KEGG

hsa:1593.

UCSC

uc002viz.4. human.

Organism-specific databases

CTD

1593.

GeneCards

GC02P219610.

HGNC

HGNC:2605. CYP27A1.

MIM

213700. phenotype.
606530. gene.

neXtProt

NX_Q02318.

Orphanet

909. Cerebrotendinous xanthomatosis.

PharmGKB

PA135.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOGENOM

HOG000253961.

HOVERGEN

HBG106909.

InParanoid

Q02318.

KO

K00488.

OMA

EVIDDFM.

OrthoDB

EOG4WSW9K.

PhylomeDB

Q02318.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00955.

Gene expression databases

ArrayExpress

Q02318.

Bgee

Q02318.

CleanEx

HS_CYP27A1.

Genevestigator

Q02318.

GermOnline

ENSG00000135929. Homo sapiens.

Family and domain databases

Gene3D

1.10.630.10. 1 hit.

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q02318.

ChEMBL

CHEMBL5992.

ChiTaRS

CYP27A1. human.

DrugBank

DB00169. Cholecalciferol.

GenomeRNAi

1593.

NextBio

6548.

SOURCE

Search...

Entry information

Entry name

CP27A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 138 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.