CH25H_MOUSE
ID CH25H_MOUSE Reviewed; 298 AA.
AC Q9Z0F5; Q3TUM6; Q8CHQ2;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Cholesterol 25-hydroxylase {ECO:0000305};
DE EC=1.14.99.38 {ECO:0000269|PubMed:9852097};
DE AltName: Full=Cholesterol 25-monooxygenase;
DE Short=m25OH;
GN Name=Ch25h {ECO:0000312|MGI:MGI:1333869};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP COFACTOR, SUBCELLULAR LOCATION, GLYCOSYLATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF 242-HIS-HIS-243.
RC STRAIN=129/SvEv, and C57BL/6J;
RX PubMed=9852097; DOI=10.1074/jbc.273.51.34316;
RA Lund E.G., Kerr T.A., Sakai J., Li W.-P., Russell D.W.;
RT "cDNA cloning of mouse and human cholesterol 25-hydroxylases, polytopic
RT membrane proteins that synthesize a potent oxysterol regulator of lipid
RT metabolism.";
RL J. Biol. Chem. 273:34316-34327(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Adipose tissue, and Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=12543708; DOI=10.1146/annurev.biochem.72.121801.161712;
RA Russell D.W.;
RT "The enzymes, regulation, and genetics of bile acid synthesis.";
RL Annu. Rev. Biochem. 72:137-174(2003).
RN [5]
RP FUNCTION.
RX PubMed=22999953; DOI=10.1016/j.immuni.2012.06.015;
RA Yi T., Wang X., Kelly L.M., An J., Xu Y., Sailer A.W., Gustafsson J.A.,
RA Russell D.W., Cyster J.G.;
RT "Oxysterol gradient generation by lymphoid stromal cells guides activated B
RT cell movement during humoral responses.";
RL Immunity 37:535-548(2012).
CC -!- FUNCTION: Catalyzes the formation of 25-hydroxycholesterol from
CC cholesterol, leading to repress cholesterol biosynthetic enzymes
CC (PubMed:9852097). Plays a key role in cell positioning and movement in
CC lymphoid tissues: 25-hydroxycholesterol is an intermediate in
CC biosynthesis of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC), an
CC oxysterol that acts as a ligand for the G protein-coupled receptor
CC GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells
CC (PubMed:22999953). May play an important role in regulating lipid
CC metabolism by synthesizing a corepressor that blocks sterol regulatory
CC element binding protein (SREBP) processing (PubMed:9852097). In testis,
CC production of 25-hydroxycholesterol by macrophages may play a role in
CC Leydig cell differentiation (PubMed:9852097). Interferon-stimulated
CC gene which has broad antiviral activities against a wide range of
CC enveloped viruses (By similarity). {ECO:0000250|UniProtKB:O95992,
CC ECO:0000269|PubMed:22999953, ECO:0000269|PubMed:9852097}.
CC -!- FUNCTION: Catalyzes the formation of 25-hydroxycholesterol from
CC cholesterol, leading to repress cholesterol biosynthetic enzymes
CC (PubMed:9852097). Plays a key role in cell positioning and movement in
CC lymphoid tissues: 25-hydroxycholesterol is an intermediate in
CC biosynthesis of 7-alpha,25-dihydroxycholesterol (7-alpha,25-OHC), an
CC oxysterol that acts as a ligand for the G protein-coupled receptor
CC GPR183/EBI2, a chemotactic receptor for a number of lymphoid cells
CC (PubMed:22999953). May play an important role in regulating lipid
CC metabolism by synthesizing a corepressor that blocks sterol regulatory
CC element binding protein (SREBP) processing (PubMed:9852097). As an
CC interferon-stimulated gene, has broad antiviral activities against a
CC wide range of enveloped viruses. Its product, 25-hydroxycholesterol,
CC activates the ER-localized enzyme ACAT to induce internalization of
CC accessible cholesterol on the plasma membrane and restricts virus-host
CC membranes fusion which inhibits virus replication (By similarity). In
CC testis, production of 25-hydroxycholesterol by macrophages plays a role
CC in Leydig cell differentiation (By similarity).
CC {ECO:0000250|UniProtKB:O95992, ECO:0000250|UniProtKB:Q4QQV7,
CC ECO:0000269|PubMed:22999953, ECO:0000269|PubMed:9852097}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + cholesterol + O2 = 25-hydroxycholesterol + A + H2O;
CC Xref=Rhea:RHEA:21104, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16113, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:42977; EC=1.14.99.38;
CC Evidence={ECO:0000269|PubMed:9852097};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21105;
CC Evidence={ECO:0000269|PubMed:9852097};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + H(+) + NADPH + O2 = 25-hydroxycholesterol + H2O
CC + NADP(+); Xref=Rhea:RHEA:46132, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:42977, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:9852097};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46133;
CC Evidence={ECO:0000269|PubMed:9852097};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000269|PubMed:9852097};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9852097}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:9852097}.
CC -!- TISSUE SPECIFICITY: Widely expressed at low level and at higher level
CC in the lung. Weakly expressed in the heart, lung and kidney.
CC {ECO:0000269|PubMed:9852097}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9852097}.
CC -!- DISRUPTION PHENOTYPE: Mice do not display any apparent alteration in
CC bile acid synthesis and cholesterol metabolism (PubMed:12543708).
CC {ECO:0000269|PubMed:12543708}.
CC -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}.
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DR EMBL; AF059211; AAC97480.1; -; Genomic_DNA.
DR EMBL; AF059213; AAC97482.1; -; mRNA.
DR EMBL; AK140360; BAE24352.1; -; mRNA.
DR EMBL; AK152770; BAE31482.1; -; mRNA.
DR EMBL; AK160657; BAE35945.1; -; mRNA.
DR EMBL; BC039919; AAH39919.1; -; mRNA.
DR CCDS; CCDS29759.1; -.
DR RefSeq; NP_034020.1; NM_009890.1.
DR AlphaFoldDB; Q9Z0F5; -.
DR STRING; 10090.ENSMUSP00000049683; -.
DR SwissLipids; SLP:000001484; -.
DR GlyGen; Q9Z0F5; 2 sites.
DR PaxDb; Q9Z0F5; -.
DR PRIDE; Q9Z0F5; -.
DR ProteomicsDB; 281121; -.
DR Antibodypedia; 30238; 115 antibodies from 16 providers.
DR DNASU; 12642; -.
DR Ensembl; ENSMUST00000050562; ENSMUSP00000049683; ENSMUSG00000050370.
DR GeneID; 12642; -.
DR KEGG; mmu:12642; -.
DR UCSC; uc008hgj.1; mouse.
DR CTD; 9023; -.
DR MGI; MGI:1333869; Ch25h.
DR VEuPathDB; HostDB:ENSMUSG00000050370; -.
DR eggNOG; KOG0873; Eukaryota.
DR GeneTree; ENSGT00940000162142; -.
DR HOGENOM; CLU_047036_5_1_1; -.
DR InParanoid; Q9Z0F5; -.
DR OMA; YGGVAHH; -.
DR OrthoDB; 1493916at2759; -.
DR PhylomeDB; Q9Z0F5; -.
DR TreeFam; TF353265; -.
DR BRENDA; 1.14.99.38; 3474.
DR Reactome; R-MMU-192105; Synthesis of bile acids and bile salts.
DR BioGRID-ORCS; 12642; 3 hits in 73 CRISPR screens.
DR PRO; PR:Q9Z0F5; -.
DR Proteomes; UP000000589; Chromosome 19.
DR RNAct; Q9Z0F5; protein.
DR Bgee; ENSMUSG00000050370; Expressed in ciliary body and 63 other tissues.
DR Genevisible; Q9Z0F5; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0000254; F:C-4 methylsterol oxidase activity; IBA:GO_Central.
DR GO; GO:0001567; F:cholesterol 25-hydroxylase activity; IMP:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008395; F:steroid hydroxylase activity; IDA:MGI.
DR GO; GO:0035754; P:B cell chemotaxis; IMP:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; IDA:MGI.
DR GO; GO:1903914; P:negative regulation of fusion of virus membrane with host plasma membrane; ISS:UniProtKB.
DR GO; GO:0034340; P:response to type I interferon; ISS:UniProtKB.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR006694; Fatty_acid_hydroxylase.
DR Pfam; PF04116; FA_hydroxylase; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Iron; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..298
FT /note="Cholesterol 25-hydroxylase"
FT /id="PRO_0000226802"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 128..263
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT MOTIF 142..146
FT /note="Histidine box-1"
FT MOTIF 157..161
FT /note="Histidine box-2"
FT MOTIF 238..244
FT /note="Histidine box-3"
FT CARBOHYD 5
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 163
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT MUTAGEN 242..243
FT /note="HH->EE: Loss of function."
FT /evidence="ECO:0000269|PubMed:9852097"
FT CONFLICT 122
FT /note="V -> A (in Ref. 3; AAH39919)"
FT /evidence="ECO:0000305"
FT CONFLICT 199
FT /note="T -> S (in Ref. 2; BAE35945)"
FT /evidence="ECO:0000305"
FT CONFLICT 282
FT /note="N -> D (in Ref. 3; AAH39919)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 298 AA; 34672 MW; BBCE4A97A20284C6 CRC64;
MGCYNGSELQ DLGCSSQLLL QPLWDTIRTR EAFTRSPIFP VTFSIITYVG FCLPFVVLDV
LYPWVPILRR YKIHPDFSPS VKQLLPCLGL TLYQHLVFVF PVTLLHWVRS PALLPQEAPE
LVQLLSHVLI CLLLFDTEIF AWHLLHHKVP WLYRTFHKVH HQNSSSFALA TQYMSFWELL
SLTFFDVLNV AVLRCHPLTI FTFHVINIWL SVEDHSGYDF PWSTHRLVPF GWYGGVAHHD
MHHSQFNCNF APYFTHWDKM LGTLRSAPLP ESLCACGERC VNSRERCAVH LIQKKKQT
