DHC24_MACFA
ID DHC24_MACFA Reviewed; 516 AA.
AC Q60HC5;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Delta(24)-sterol reductase;
DE EC=1.3.1.72 {ECO:0000250|UniProtKB:Q15392};
DE AltName: Full=24-dehydrocholesterol reductase;
DE AltName: Full=3-beta-hydroxysterol Delta-24-reductase;
DE Flags: Precursor;
GN Name=DHCR24; ORFNames=QmoA-12363;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Medulla oblongata;
RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the reduction of the delta-24 double bond of sterol
CC intermediates during cholesterol biosynthesis. In addition to its
CC cholesterol-synthesizing activity, can protect cells from oxidative
CC stress by reducing caspase 3 activity during apoptosis induced by
CC oxidative stress. Also protects against amyloid-beta peptide-induced
CC apoptosis. {ECO:0000250|UniProtKB:Q15392}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + NADP(+) = desmosterol + H(+) + NADPH;
CC Xref=Rhea:RHEA:36391, ChEBI:CHEBI:15378, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:17737, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.72;
CC Evidence={ECO:0000250|UniProtKB:Q15392};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:36393;
CC Evidence={ECO:0000250|UniProtKB:Q15392};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + lanosterol + NADPH = 24,25-dihydrolanosterol + NADP(+);
CC Xref=Rhea:RHEA:33919, ChEBI:CHEBI:15378, ChEBI:CHEBI:16521,
CC ChEBI:CHEBI:28113, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000250|UniProtKB:Q15392};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33920;
CC Evidence={ECO:0000250|UniProtKB:Q15392};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-cholest-8-en-3beta-ol + NADP(+) = H(+) + NADPH +
CC zymosterol; Xref=Rhea:RHEA:36399, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16608, ChEBI:CHEBI:18252, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.3.1.72;
CC Evidence={ECO:0000250|UniProtKB:Q8VCH6};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:36401;
CC Evidence={ECO:0000250|UniProtKB:Q8VCH6};
CC -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC {ECO:0000250|UniProtKB:Q15392}.
CC -!- SUBUNIT: Interacts with DHCR7; this interaction regulates DHCR7
CC activity. {ECO:0000250|UniProtKB:Q15392}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q15392}; Single-pass membrane protein
CC {ECO:0000255}. Golgi apparatus membrane {ECO:0000250|UniProtKB:Q15392};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD51990.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AB125202; BAD51990.1; ALT_INIT; mRNA.
DR RefSeq; NP_001274624.1; NM_001287695.1.
DR AlphaFoldDB; Q60HC5; -.
DR STRING; 9541.XP_005543320.1; -.
DR GeneID; 102144711; -.
DR CTD; 1718; -.
DR eggNOG; KOG1262; Eukaryota.
DR OrthoDB; 733611at2759; -.
DR UniPathway; UPA00063; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0050614; F:delta24-sterol reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0042605; F:peptide antigen binding; ISS:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; ISS:UniProtKB.
DR GO; GO:0009888; P:tissue development; ISS:UniProtKB.
DR Gene3D; 3.30.465.10; -; 1.
DR InterPro; IPR040165; Diminuto-like.
DR InterPro; IPR016166; FAD-bd_PCMH.
DR InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR InterPro; IPR006094; Oxid_FAD_bind_N.
DR PANTHER; PTHR10801; PTHR10801; 1.
DR Pfam; PF01565; FAD_binding_4; 1.
DR SUPFAM; SSF56176; SSF56176; 1.
DR PROSITE; PS51387; FAD_PCMH; 1.
PE 2: Evidence at transcript level;
KW Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW FAD; Flavoprotein; Golgi apparatus; Lipid biosynthesis; Lipid metabolism;
KW Membrane; NADP; Oxidoreductase; Reference proteome; Signal;
KW Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW Sterol metabolism; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..516
FT /note="Delta(24)-sterol reductase"
FT /id="PRO_0000007231"
FT TOPO_DOM 23..31
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q15392"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..516
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q15392"
FT DOMAIN 58..234
FT /note="FAD-binding PCMH-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT BINDING 163..175
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000255"
FT SITE 122..123
FT /note="Cleavage; by caspase"
FT /evidence="ECO:0000255"
FT SITE 383..384
FT /note="Cleavage; by caspase"
FT /evidence="ECO:0000255"
SQ SEQUENCE 516 AA; 60087 MW; 615B1858CF2B5DF5 CRC64;
MEPAVSLAVC ALLFLLWVRV KGLEFVLIHQ RWVFVCLFLL PLSLIFDIYY YVRAWVVFKL
SSAPRLHEQR VRDIQKQVRE WKEQGSKTFM CTGRPGWLTV SLRVGKYKKT HKNIMINLMD
ILEVDTKKQI VRVEPLVTMG QVTALLTSIG WTLPVLPELD DLTVGGLIMG TGIESSSHKY
GLFQHICTAY ELVLADGSFV RCTPSENSDL FYAVPWSCGT LGFLVAAEIR IIPAKKYVKL
RFEPVQGLEA ICAKFTHESQ RQENHFVEGL LYSLDEAVIM TGVMTDEVEP SKLNSIGNYY
KPWFFKHVEN YLKTNREGLE YIPLRHYYHR HTRSIFWELQ DIIPFGNNPI FRYLFGWMVP
PKISLLKLTQ GETLRKLYEQ HHVVQDMLVP MKCLQQALHT FQNDIHVYPI WLCPFILPSQ
PGLVHPKGNE AELYIDIGAY GEPRVKHFEA RSCMRQLEKF VRSVHGFQML YADCYMNREE
FWEMFDGSLY HKLREKLGCQ DAFPEVYDKI CKAARH
