ID CH25H_PIG Reviewed; 270 AA. AC Q4G1G8; DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 30-AUG-2005, sequence version 1. DT 24-JAN-2024, entry version 71. DE RecName: Full=Cholesterol 25-hydroxylase; DE EC=1.14.99.38 {ECO:0000250|UniProtKB:Q9Z0F5}; DE AltName: Full=Cholesterol 25-monooxygenase; GN Name=CH25H; OS Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus. OX NCBI_TaxID=9823; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Cheng H.C., Deng C.Y., Zhang F.W.; RT "Cloning and identification of a new single gene in pigs."; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. 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 (By similarity). Required to restrain inflammation in CC macrophages: production of 25-hydroxycholesterol protects macrophages CC from cholesterol overload, thereby preventing mitochondrial DNA release CC and subsequent activation of the AIM2 inflammasome (By similarity). CC {ECO:0000250|UniProtKB:O95992, ECO:0000250|UniProtKB:Q4QQV7, CC ECO:0000250|UniProtKB:Q9Z0F5}. 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 -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:Q9Z0F5}. CC -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AY974088; AAY40559.1; -; Genomic_DNA. DR AlphaFoldDB; Q4G1G8; -. DR STRING; 9823.ENSSSCP00000058740; -. DR GlyCosmos; Q4G1G8; 2 sites, No reported glycans. DR PaxDb; 9823-ENSSSCP00000011138; -. DR eggNOG; KOG0873; Eukaryota. DR InParanoid; Q4G1G8; -. DR Proteomes; UP000008227; Unplaced. DR Proteomes; UP000314985; Unplaced. DR Proteomes; UP000694570; Unplaced. DR Proteomes; UP000694571; Unplaced. DR Proteomes; UP000694720; Unplaced. DR Proteomes; UP000694722; Unplaced. DR Proteomes; UP000694723; Unplaced. DR Proteomes; UP000694724; Unplaced. DR Proteomes; UP000694725; Unplaced. DR Proteomes; UP000694726; Unplaced. DR Proteomes; UP000694727; Unplaced. DR Proteomes; UP000694728; Unplaced. DR GO; GO:0005789; C:endoplasmic reticulum 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:0008395; F:steroid hydroxylase activity; IBA:GO_Central. 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 PANTHER; PTHR11863:SF213; CHOLESTEROL 25-HYDROXYLASE; 1. DR PANTHER; PTHR11863; STEROL DESATURASE; 1. 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..270 FT /note="Cholesterol 25-hydroxylase" FT /id="PRO_0000226803" FT TRANSMEM 38..58 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 81..103 FT /note="Helical" FT /evidence="ECO:0000255" FT TRANSMEM 127..147 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 270 AA; 31482 MW; 6BAEA05DBEAE1AA4 CRC64; MSGHNNSELF VLCSSSQLFL QPLWDHLKTW ETLILSPFFP VFFSITTYLG FCLPFVVLDV LCPWVPALRR YKIHPDFSPS VWQLLPCLGL TLYQHVVFVF PMTLLHWAAS PVLLPPEAPE LLQLVRHIVL CLLLFDTEFF IWHVLHHKVP WLYRTFHKMH HQNSSSFALA TQYMSVGELL SLGVFDMVNI MLLRCHPLTV LIFHVINIWL SVEDHSGYDF PWSAHRLVPF GWYGGVTHHD LHHSQFNCNF APYFTHWDKI LGTLRSAHAK //