CH25H_RAT
ID CH25H_RAT Reviewed; 298 AA.
AC Q4QQV7;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Cholesterol 25-hydroxylase {ECO:0000305};
DE EC=1.14.99.38 {ECO:0000250|UniProtKB:Q9Z0F5};
DE AltName: Full=Cholesterol 25-monooxygenase;
GN Name=Ch25h {ECO:0000312|RGD:1310575};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Thymus;
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 [2]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=11207193; DOI=10.1095/biolreprod64.3.790;
RA Lukyanenko Y.O., Chen J.-J., Hutson J.C.;
RT "Production of 25-hydroxycholesterol by testicular macrophages and its
RT effects on Leydig cells.";
RL Biol. Reprod. 64:790-796(2001).
RN [3]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=11967195; DOI=10.1095/biolreprod66.5.1336;
RA Chen J.-J., Lukyanenko Y., Hutson J.C.;
RT "25-hydroxycholesterol is produced by testicular macrophages during the
RT early postnatal period and influences differentiation of Leydig cells in
RT vitro.";
RL Biol. Reprod. 66:1336-1341(2002).
RN [4]
RP INDUCTION.
RX PubMed=12390873; DOI=10.1095/biolreprod.102.007575;
RA Lukyanenko Y., Chen J.-J., Hutson J.C.;
RT "Testosterone regulates 25-hydroxycholesterol production in testicular
RT macrophages.";
RL Biol. Reprod. 67:1435-1438(2002).
CC -!- FUNCTION: Catalyzes the formation of 25-hydroxycholesterol from
CC cholesterol, leading to repress cholesterol biosynthetic enzymes
CC (PubMed:11967195, PubMed:11207193). Plays a key role in cell
CC positioning and movement in lymphoid tissues: 25-hydroxycholesterol is
CC an intermediate in biosynthesis of 7-alpha,25-dihydroxycholesterol (7-
CC alpha,25-OHC), an oxysterol that acts as a ligand for the G protein-
CC coupled receptor GPR183/EBI2, a chemotactic receptor for a number of
CC lymphoid cells. May play an important role in regulating lipid
CC metabolism by synthesizing a corepressor that blocks sterol regulatory
CC element binding protein (SREBP) processing. In testis, production of
CC 25-hydroxycholesterol by macrophages plays a role in Leydig cell
CC differentiation (PubMed:11967195, PubMed:11207193). Interferon-
CC stimulated gene which has broad antiviral activities against a wide
CC range of enveloped viruses (By similarity).
CC {ECO:0000250|UniProtKB:O95992, ECO:0000250|UniProtKB:Q9Z0F5,
CC ECO:0000269|PubMed:11207193, ECO:0000269|PubMed:11967195}.
CC -!- FUNCTION: Catalyzes the formation of 25-hydroxycholesterol from
CC cholesterol, leading to repress cholesterol biosynthetic enzymes (By
CC similarity). 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 (By
CC similarity). May play an important role in regulating lipid metabolism
CC by synthesizing a corepressor that blocks sterol regulatory element
CC binding protein (SREBP) processing. As an interferon-stimulated gene,
CC has broad antiviral activities against a wide range of enveloped
CC viruses. Its product, 25-hydroxycholesterol, activates the ER-localized
CC enzyme ACAT to induce internalization of accessible cholesterol on the
CC plasma membrane and restricts virus-host membranes fusion which
CC inhibits virus replication (By similarity). In testis, production of
CC 25-hydroxycholesterol by macrophages plays a role in Leydig cell
CC differentiation (PubMed:11967195, PubMed:11207193).
CC {ECO:0000250|UniProtKB:O95992, ECO:0000250|UniProtKB:Q9Z0F5,
CC ECO:0000269|PubMed:11207193, ECO:0000269|PubMed:11967195}.
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:0000250|UniProtKB:Q9Z0F5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21105;
CC Evidence={ECO:0000250|UniProtKB:Q9Z0F5};
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:0000250|UniProtKB:Q9Z0F5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46133;
CC Evidence={ECO:0000250|UniProtKB:Q9Z0F5};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000250|UniProtKB:Q9Z0F5};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9Z0F5}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9Z0F5}.
CC -!- TISSUE SPECIFICITY: Expressed in testicular macrophages at all stages,
CC with the highest level in 10 day old animals.
CC {ECO:0000269|PubMed:11207193, ECO:0000269|PubMed:11967195}.
CC -!- INDUCTION: Down-regulated by testosterone.
CC {ECO:0000269|PubMed:12390873}.
CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9Z0F5}.
CC -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}.
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DR EMBL; BC097964; AAH97964.1; -; mRNA.
DR RefSeq; NP_001020586.1; NM_001025415.1.
DR RefSeq; XP_006231353.1; XM_006231291.3.
DR AlphaFoldDB; Q4QQV7; -.
DR STRING; 10116.ENSRNOP00000025856; -.
DR GlyGen; Q4QQV7; 2 sites.
DR PaxDb; Q4QQV7; -.
DR Ensembl; ENSRNOT00000025856; ENSRNOP00000025856; ENSRNOG00000019141.
DR GeneID; 309527; -.
DR KEGG; rno:309527; -.
DR UCSC; RGD:1310575; rat.
DR CTD; 9023; -.
DR RGD; 1310575; Ch25h.
DR eggNOG; KOG0873; Eukaryota.
DR GeneTree; ENSGT00940000162142; -.
DR HOGENOM; CLU_047036_5_1_1; -.
DR InParanoid; Q4QQV7; -.
DR OMA; YGGVAHH; -.
DR OrthoDB; 1493916at2759; -.
DR PhylomeDB; Q4QQV7; -.
DR TreeFam; TF353265; -.
DR BRENDA; 1.14.99.38; 5301.
DR Reactome; R-RNO-192105; Synthesis of bile acids and bile salts.
DR PRO; PR:Q4QQV7; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000019141; Expressed in lung and 18 other tissues.
DR Genevisible; Q4QQV7; RN.
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; ISS: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; ISO:RGD.
DR GO; GO:0035754; P:B cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0008203; P:cholesterol metabolic process; ISS:UniProtKB.
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 2: Evidence at transcript 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_0000226804"
FT TRANSMEM 38..58
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 84..104
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 124..144
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 167..187
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 190..210
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"
SQ SEQUENCE 298 AA; 34414 MW; 25BC9E1DDAC4AF3F CRC64;
MACHNVSELQ DLGCSNQLLL QPLWDSIRTG EASARSPFFP VIFSIFTYLG FCLPFVVLDV
LCPWVPILRR YKIHPDFSPS VRQLLPCLGL TLYQHLVFVF PVTLMHWARS PALLPREAPE
LSQLLSHVLI CLLLFDTEIF AWHLLHHKVP WLYRTFHKVH HQNSSSFALA TQYMSVWELL
SLTFFDVLNV AMLQCHPLTI LVFHVVNIWL SVEDHSGYDF PWSTHRLVPF GWYGGVAHHD
LHHSQFNCNF APYFTHWDKM LGTLRCAPHS KRLCAGSESC LDSGEQCTVH LNQKKKQT
