CH25H_PIG
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 25-MAY-2022, entry version 65.
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). {ECO:0000250|UniProtKB:O95992,
CC ECO:0000250|UniProtKB:Q4QQV7, 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}.
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DR EMBL; AY974088; AAY40559.1; -; Genomic_DNA.
DR AlphaFoldDB; Q4G1G8; -.
DR STRING; 9823.ENSSSCP00000011138; -.
DR PaxDb; Q4G1G8; -.
DR eggNOG; KOG0873; Eukaryota.
DR InParanoid; Q4G1G8; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
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; 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 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
