Cholesterol 24-hydroxylase - Homo sapiens (Human)

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Q9Y6A2 (CP46A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 118. History...

Clusters with 100%, 90%, 50% identity |

Documents (4) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Cholesterol 24-hydroxylase
Short name=CH24H
EC=1.14.13.98

Alternative name(s):
Cytochrome P450 46A1

Gene names

Name:	CYP46A1
Synonyms:	CYP46

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	500 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Involved in the turnover of cholesterol. It converts cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol. Has also activity with xenobiotic compounds, such as clotrimazole.
Catalytic activity	Cholesterol + NADPH + O₂ = (24S)-24-hydroxycholesterol + NADP⁺ + H₂O.
Cofactor	Heme group.
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein. Microsome membrane; Single-pass membrane protein.
Tissue specificity	Expressed in brain. The mRNA was broadly distributed with higher levels in gray matter zones and lower levels in regions rich in white matter. Not detected in fetal sample but its expression increases linearly with age.
Sequence similarities	Belongs to the cytochrome P450 family.
Biophysicochemical properties	Kinetic parameters: K_M=2.2 µM for 24(S)-hydroxycholesterol Ref.3

Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism Sterol metabolism
Cellular component	Endoplasmic reticulum Membrane Microsome
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	bile acid biosynthetic process Traceable author statement. Source: Reactome cholesterol catabolic process Traceable author statement Ref.1. Source: ProtInc nervous system development Traceable author statement Ref.1. Source: ProtInc xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	cholesterol 24-hydroxylase activity Inferred from electronic annotation. Source: EC 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.1. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 500

500

Cholesterol 24-hydroxylase

PRO_0000051994

Regions

Transmembrane

3 – 23

Helical; Potential

Compositional bias

493 – 499

Poly-Pro

Sites

Metal binding

437

Iron (heme axial ligand)

Secondary structure

500

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q9Y6A2 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: AB9307749D9E5FDA
Show »

FASTA

500

56,821

        10         20         30         40         50         60 
MSPGLLLLGS AVLLAFGLCC TFVHRARSRY EHIPGPPRPS FLLGHLPCFW KKDEVGGRVL 

        70         80         90        100        110        120 
QDVFLDWAKK YGPVVRVNVF HKTSVIVTSP ESVKKFLMST KYNKDSKMYR ALQTVFGERL 

       130        140        150        160        170        180 
FGQGLVSECN YERWHKQRRV IDLAFSRSSL VSLMETFNEK AEQLVEILEA KADGQTPVSM 

       190        200        210        220        230        240 
QDMLTYTAMD ILAKAAFGME TSMLLGAQKP LSQAVKLMLE GITASRNTLA KFLPGKRKQL 

       250        260        270        280        290        300 
REVRESIRFL RQVGRDWVQR RREALKRGEE VPADILTQIL KAEEGAQDDE GLLDNFVTFF 

       310        320        330        340        350        360 
IAGHETSANH LAFTVMELSR QPEIVARLQA EVDEVIGSKR YLDFEDLGRL QYLSQVLKES 

       370        380        390        400        410        420 
LRLYPPAWGT FRLLEEETLI DGVRVPGNTP LLFSTYVMGR MDTYFEDPLT FNPDRFGPGA 

       430        440        450        460        470        480 
PKPRFTYFPF SLGHRSCIGQ QFAQMEVKVV MAKLLQRLEF RLVPGQRFGL QEQATLKPLD 

       490        500 
PVLCTLRPRG WQPAPPPPPC

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain." Lund E.G., Guileyardo J.M., Russell D.W. Proc. Natl. Acad. Sci. U.S.A. 96:7238-7243(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	"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.
[3]	"Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain." Mast N., Norcross R., Andersson U., Shou M., Nakayama K., Bjoerkhem I., Pikuleva I.A. Biochemistry 42:14284-14292(2003) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, BIOPHYSICOCHEMICAL PROPERTIES.
[4]	"Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain." Mast N., White M.A., Bjorkhem I., Johnson E.F., Stout C.D., Pikuleva I.A. Proc. Natl. Acad. Sci. U.S.A. 105:9546-9551(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 51-500 IN COMPLEX WITH HEME AND CHOLESTEROL 3-SULFATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR.
[5]	"Structural basis of drug binding to CYP46A1, an enzyme that controls cholesterol turnover in the brain." Mast N., Charvet C., Pikuleva I.A., Stout C.D. J. Biol. Chem. 285:31783-31795(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 51-500 IN COMPLEXES WITH HEME AND INHIBITORS, FUNCTION, COFACTOR.
[6]	"Binding of a cyano- and fluoro-containing drug bicalutamide to cytochrome P450 46A1: unusual features and spectral response." Mast N., Zheng W., Stout C.D., Pikuleva I.A. J. Biol. Chem. 288:4613-4624(2013) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 51-500 IN COMPLEXES WITH HEME AND THE INHIBITOR BICALUTAMIDE, COFACTOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF094480 mRNA. Translation: AAD41244.1.
BC022539 mRNA. Translation: AAH22539.1.

IPI

IPI00002133.

RefSeq

NP_006659.1. NM_006668.1.

UniGene

Hs.25121.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Q9F	X-ray	1.90	A	51-500	[»]
2Q9G	X-ray	2.40	A	51-500	[»]
3MDM	X-ray	1.60	A	51-500	[»]
3MDR	X-ray	2.00	A/B	51-500	[»]
3MDT	X-ray	2.30	A/B	51-500	[»]
3MDV	X-ray	2.40	A/B	51-500	[»]
4ENH	X-ray	2.50	A	51-500	[»]
4FIA	X-ray	2.10	A	51-500	[»]

ProteinModelPortal

Q9Y6A2.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000261835.

PTM databases

PhosphoSite

Q9Y6A2.

Polymorphism databases

DMDM

12585217.

Proteomic databases

PaxDb

Q9Y6A2.

PRIDE

Q9Y6A2.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000261835; ENSP00000261835; ENSG00000036530.

GeneID

10858.

KEGG

hsa:10858.

UCSC

uc001ygo.3. human.

Organism-specific databases

CTD

10858.

GeneCards

GC14P100150.

HGNC

HGNC:2641. CYP46A1.

HPA

HPA040702.

MIM

604087. gene.

neXtProt

NX_Q9Y6A2.

PharmGKB

PA27117.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOGENOM

HOG000290190.

HOVERGEN

HBG102502.

InParanoid

Q9Y6A2.

K07440.

OMA

TYFEDPL.

OrthoDB

EOG4JHCFW.

PhylomeDB

Q9Y6A2.

Enzyme and pathway databases

BRENDA

1.14.13.98. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

Q9Y6A2.

Bgee

Q9Y6A2.

CleanEx

HS_CYP46A1.

Genevestigator

Q9Y6A2.

GermOnline

ENSG00000036530. 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

ChiTaRS

CYP46A1. human.

EvolutionaryTrace

Q9Y6A2.

GenomeRNAi

10858.

NextBio

41219.

SOURCE

Search...

Entry information

Entry name

CP46A_HUMAN

Accession

Primary (citable) accession number: Q9Y6A2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 24, 2001
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 118 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.

Relevant documents

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents