O95992 (CH25H_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cholesterol 25-hydroxylase
EC=1.14.99.38

Alternative name(s):
Cholesterol 25-monooxygenase
Short name=h25OH

Gene names

Name:

CH25H

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	272 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the formation of 25-hydroxycholesterol from cholesterol, leading to repress cholesterol biosynthetic enzymes. May play an important role in regulating lipid metabolism by synthesizing a corepressor that blocks sterol regulatory element binding protein (SREBP) processing. In testis, production of 25-hydroxycholesterol by macrophages may play a role in Leydig cell differentiation. Ref.1
Catalytic activity	Cholesterol + AH2 + O2 = 25-hydroxycholesterol + A + H2O.
Cofactor	Iron.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein By similarity.
Post-translational modification	N-glycosylated. Ref.1
Sequence similarities	Belongs to the sterol desaturase family.

Ontologies

Keywords
Biological process	Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	bile acid biosynthetic process Traceable author statement. Source: Reactome fatty acid biosynthetic process Inferred from electronic annotation. Source: InterPro sterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Traceable author statement. Source: Reactome endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	cholesterol 25-hydroxylase activity Inferred from electronic annotation. Source: EC iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 272	272	Cholesterol 25-hydroxylase		PRO_0000226801
Regions
	Transmembrane	38 – 58	21	Helical; Potential
	Transmembrane	84 – 104	21	Helical; Potential
	Transmembrane	121 – 141	21	Helical; Potential
	Motif	142 – 146	5	Histidine box-1
	Motif	157 – 161	5	Histidine box-2
	Motif	238 – 244	7	Histidine box-3
Amino acid modifications
	Glycosylation	5	1	N-linked (GlcNAc...) Potential
	Glycosylation	163	1	N-linked (GlcNAc...) Potential
	Glycosylation	189	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	133	1	L → P. Corresponds to variant rs17117295 [ dbSNP | Ensembl ].		VAR_048899

Sequences

	Sequence		Length	Mass (Da)
	O95992 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: 0DF46BC21802008B	FASTA	272	31,745
	10 20 30 40 50 60 MSCHNCSDPQ VLCSSGQLFL QPLWDHLRSW EALLQSPFFP VIFSITTYVG FCLPFVVLDI 70 80 90 100 110 120 LCSWVPALRR YKIHPDFSPS AQQLLPCLGQ TLYQHVMFVF PVTLLHWARS PALLPHEAPE 130 140 150 160 170 180 LLLLLHHILF CLLLFDMEFF VWHLLHHKVP WLYRTFHKVH HQNSSSFALA TQYMSVWELF 190 200 210 220 230 240 SLGFFDMMNV TLLGCHPLTT LTFHVVNIWL SVEDHSGYNF PWSTHRLVPF GWYGGVVHHD 250 260 270 LHHSHFNCNF APYFTHWDKI LGTLRTASVP AR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic membrane proteins that synthesize a potent oxysterol regulator of lipid metabolism." Lund E.G., Kerr T.A., Sakai J., Li W.-P., Russell D.W. J. Biol. Chem. 273:34316-34327(1998) [PubMed: 9852097] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, GLYCOSYLATION. Tissue: Lung.
[2]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[3]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed: 15164054] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: Lung and Ovary.
[6]	"Association analysis of genes involved in cholesterol metabolism located within the linkage region on chromosome 10 and Alzheimer's disease." Riemenschneider M., Mahmoodzadeh S., Eisele T., Klopp N., Schwarz S., Wagenpfeil S., Diehl J., Mueller U., Foerstl H., Illig T., Kurz A. Neurobiol. Aging 25:1305-1308(2004) [PubMed: 15465627] [Abstract] Cited for: LACK OF INVOLVEMENT IN ALZHEIMER DISEASE.
[7]	"Association studies of cholesterol metabolism genes (CH25H, ABCA1 and CH24H) in Alzheimer's disease." Shibata N., Kawarai T., Lee J.H., Lee H.-S., Shibata E., Sato C., Liang Y., Duara R., Mayeux R.P., St George-Hyslop P.H., Rogaeva E. Neurosci. Lett. 391:142-146(2006) [PubMed: 16157450] [Abstract] Cited for: LACK OF INVOLVEMENT IN ALZHEIMER DISEASE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF059212 Genomic DNA. Translation: AAC97481.1. AF059214 mRNA. Translation: AAC97483.1. AK314865 mRNA. Translation: BAG37380.1. AL513533 Genomic DNA. Translation: CAI13519.1. CH471066 Genomic DNA. Translation: EAW50146.1. BC017843 mRNA. Translation: AAH17843.1. BC072430 mRNA. Translation: AAH72430.1.
IPI	IPI00022560.
RefSeq	NP_003947.1. NM_003956.3.
UniGene	Hs.47357.
3D structure databases
ProteinModelPortal	O95992.
ModBase	Search...
Protein-protein interaction databases
STRING	O95992.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371852; ENSP00000360918; ENSG00000138135.
GeneID	9023.
KEGG	hsa:9023.
UCSC	uc001kfz.1. human.
Organism-specific databases
CTD	9023.
GeneCards	GC10M090955.
H-InvDB	HIX0201504.
HGNC	HGNC:1907. CH25H.
MIM	604551. gene.
neXtProt	NX_O95992.
PharmGKB	PA26443.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG10264.
GeneTree	ENSGT00530000063017.
HOGENOM	HBG446427.
HOVERGEN	HBG080944.
InParanoid	O95992.
OMA	LVPFGWY.
OrthoDB	EOG4N04FP.
PhylomeDB	O95992.
Enzyme and pathway databases
BRENDA	1.14.99.38. 2681.
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	O95992.
Bgee	O95992.
CleanEx	HS_CH25H.
Genevestigator	O95992.
GermOnline	ENSG00000138135. Homo sapiens.
Family and domain databases
InterPro	IPR006694. Fatty_acid_hydroxylase. [Graphical view]
KO	K10223.
Pfam	PF04116. FA_hydroxylase. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	33805.
SOURCE	Search...

Entry information

Entry name

CH25H_HUMAN

Accession

Primary (citable) accession number: O95992
Secondary accession number(s): B2RBY3

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 7, 2006
Last sequence update:	May 1, 1999
Last modified:	January 25, 2012
This is version 87 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.