[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Fetal brain; DOI=10.1073/pnas.96.13.7238; PubMed=10377398 [NCBI, ExPASy, EBI, Israel, Japan] Lund E.G., Guileyardo J.M., Russell D.W.; "cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain."; Proc. Natl. Acad. Sci. U.S.A. 96:7238-7243(1999).
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. TISSUE=Brain; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[3]	CHARACTERIZATION, AND BIOPHYSICOCHEMICAL PROPERTIES. DOI=10.1021/bi035512f; PubMed=14640697 [NCBI, ExPASy, EBI, Israel, Japan] Mast N., Norcross R., Andersson U., Shou M., Nakayama K., Bjoerkhem I., Pikuleva I.A.; "Broad substrate specificity of human cytochrome P450 46A1 which initiates cholesterol degradation in the brain."; Biochemistry 42:14284-14292(2003).

Comments

FUNCTION: Involved in the turnover of cholesterol. It converts cholesterol into 24S-hydroxycholesterol and, to a lesser extent, 25-hydroxycholesterol.
CATALYTIC ACTIVITY: Cholesterol + NADPH + O₂ = (24S)-24-hydroxycholesterol + NADP⁺ + H₂O.
COFACTOR: Heme group (By similarity).
BIOPHYSICOCHEMICAL PROPERTIES:

Kinetic parameters: K_M=2.2 µM for 24(S)-hydroxycholesterol;
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.
SIMILARITY: Belongs to the cytochrome P450 family.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AF094480; AAD41244.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC022539; AAH22539.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

RefSeq

NP_006659.1; -.

UniGene

Hs.25121

3D structure databases

PDB

2Q9F; X-ray; 1.90 A; A=51-500.	[ExPASy / RCSB / EBI]
2Q9G; X-ray; 2.40 A; A=51-500.	[ExPASy / RCSB / EBI]

Detailed list of linked structures.

2Q9F; -.
2Q9G; -.

PTM databases

Q9Y6A2; -.

Enzyme and pathway databases

Reactome

REACT_602; Lipid and lipoprotein metabolism.

Organism-specific databases

H-InvDB

HIX0011962; -.
HIX0057012; -.

HGNC:2641; CYP46A1.

604087; gene. [NCBI / EBI]

PharmGKB

PA27117; -.

GeneCards

Q9Y6A2.

Gene expression databases

ArrayExpress

Q9Y6A2; -.

CleanEx

HS_CYP46A1; -.

GermOnline

ENSG00000036530; Homo sapiens.

Ontologies

GO:0005789;	Cellular component: endoplasmic reticulum membrane (inferred from electronic annotation from UniProtKB-SubCell).
GO:0016021;	Cellular component: integral to membrane (inferred from electronic annotation from UniProtKB-KW).
GO:0005792;	Cellular component: microsome (inferred from electronic annotation from UniProtKB-KW).
GO:0033781;	Molecular function: cholesterol 24-hydroxylase activity (inferred from electronic annotation from EC).
GO:0009055;	Molecular function: electron carrier activity (inferred from electronic annotation from InterPro).
GO:0020037;	Molecular function: heme binding (inferred from electronic annotation from InterPro).
GO:0005506;	Molecular function: iron ion binding (inferred from electronic annotation from InterPro).
GO:0008395;	Molecular function: steroid hydroxylase activity (traceable author statement from ProtInc).
GO:0006707;	Biological process: cholesterol catabolic process (traceable author statement from ProtInc).
GO:0007399;	Biological process: nervous system development (traceable author statement from ProtInc).
GO:0055114;	Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.

Family and domain databases

InterPro

IPR001128; Cyt_P450.
IPR002401; Cyt_P450_E_grp-I.
Graphical view of domain structure.

Gene3D

G3DSA:1.10.630.10; Cyt_P450; 1.

PANTHER

PTHR19383; Cyt_P450; 1.

Pfam

PF00067; p450; 1.
Pfam graphical view of domain structure.

PRINTS

PR00463; EP450I.
PR00385; P450.

PROSITE

PS00086; CYTOCHROME_P450; 1.

ProtoNet

Q9Y6A2.

Genome annotation databases

Ensembl

ENSG00000036530; Homo sapiens. [Contig view]

GeneID

10858; -.

KEGG

hsa:10858; -.

Phylogenomic databases

HOGENOM

Q9Y6A2; -.

HOVERGEN

Q9Y6A2; -.

Other

LinkHub

Q9Y6A2; -.

NextBio

41219; -.

SOURCE

CYP46A1; Homo sapiens.

UniRef

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

3D-structure; Cholesterol metabolism; Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane; Metal-binding; Microsome; Monooxygenase; NADP; Oxidoreductase; Steroid metabolism; Transmembrane.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`CHAIN`	`1 500`	`500`	`Cytochrome P450 46A1.`	`PRO_0000051994`
`TRANSMEM`	`3 23`	`21`	`Potential.`
`COMPBIAS`	`493 499`	`7`	`Poly-Pro.`
`METAL`	`437 437`		`Iron (heme axial ligand) (By similarity).`
`HELIX`	`60 71`	`12`
`STRAND`	`73 77`	`5`
`STRAND`	`79 82`	`4`
`STRAND`	`84 87`	`4`
`HELIX`	`90 97`	`8`
`HELIX`	`106 113`	`8`
`STRAND`	`118 121`	`4`
`TURN`	`125 127`	`3`
`HELIX`	`131 141`	`11`
`HELIX`	`142 145`	`4`
`HELIX`	`147 152`	`6`
`HELIX`	`154 169`	`16`
`TURN`	`170 175`	`6`
`HELIX`	`180 197`	`18`
`HELIX`	`203 205`	`3`
`HELIX`	`209 224`	`16`
`TURN`	`227 229`	`3`
`HELIX`	`236 266`	`31`
`HELIX`	`275 282`	`8`
`TURN`	`283 285`	`3`
`STRAND`	`287 289`	`3`
`HELIX`	`290 302`	`13`
`HELIX`	`305 318`	`14`
`HELIX`	`322 336`	`15`
`HELIX`	`344 349`	`6`
`HELIX`	`351 363`	`13`
`STRAND`	`370 374`	`5`
`STRAND`	`378 380`	`3`
`STRAND`	`383 385`	`3`
`STRAND`	`387 393`	`7`
`HELIX`	`395 399`	`5`
`TURN`	`402 404`	`3`
`STRAND`	`405 407`	`3`
`HELIX`	`413 416`	`4`
`HELIX`	`433 435`	`3`
`HELIX`	`440 457`	`18`
`STRAND`	`458 462`	`5`
`STRAND`	`470 480`	`11`
`STRAND`	`483 489`	`7`

Sequence information

Length: 500 AA [This is the length of the unprocessed precursor]

Molecular weight: 56821 Da [This is the MW of the unprocessed precursor]

CRC64: AB9307749D9E5FDA [This is a checksum on the sequence]

        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

Q9Y6A2 in FASTA format

View entry in original UniProtKB/Swiss-Prot format
View entry in raw text format (no links)
Report form for errors/updates in this UniProtKB/Swiss-Prot entry

	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools