DHC24_RAT
ID DHC24_RAT Reviewed; 516 AA.
AC Q5BQE6;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 2.
DT 03-AUG-2022, entry version 109.
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;
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 [MRNA].
RC STRAIN=IGS BR;
RA Samara A., Maggi R.;
RL Submitted (FEB-2005) 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}.
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DR EMBL; AY921220; AAX29968.2; -; mRNA.
DR AlphaFoldDB; Q5BQE6; -.
DR SMR; Q5BQE6; -.
DR STRING; 10116.ENSRNOP00000009402; -.
DR jPOST; Q5BQE6; -.
DR PaxDb; Q5BQE6; -.
DR PRIDE; Q5BQE6; -.
DR Ensembl; ENSRNOT00000009402; ENSRNOP00000009402; ENSRNOG00000006787.
DR UCSC; RGD:1306529; rat.
DR RGD; 1306529; Dhcr24.
DR eggNOG; KOG1262; Eukaryota.
DR GeneTree; ENSGT00390000008338; -.
DR HOGENOM; CLU_025883_4_0_1; -.
DR InParanoid; Q5BQE6; -.
DR OMA; YIPSRHY; -.
DR PhylomeDB; Q5BQE6; -.
DR TreeFam; TF313170; -.
DR BRENDA; 1.3.1.72; 5301.
DR Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR Reactome; R-RNO-6807047; Cholesterol biosynthesis via desmosterol.
DR Reactome; R-RNO-6807062; Cholesterol biosynthesis via lathosterol.
DR UniPathway; UPA00063; -.
DR PRO; PR:Q5BQE6; -.
DR Proteomes; UP000002494; Chromosome 5.
DR Bgee; ENSRNOG00000006787; Expressed in liver and 19 other tissues.
DR Genevisible; Q5BQE6; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005856; C:cytoskeleton; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
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:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0000246; F:delta24(24-1) sterol reductase activity; ISO:RGD.
DR GO; GO:0050614; F:delta24-sterol reductase activity; ISO:RGD.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; NAS:RGD.
DR GO; GO:0016628; F:oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor; ISO:RGD.
DR GO; GO:0042605; F:peptide antigen binding; ISS:UniProtKB.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:RGD.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISS:UniProtKB.
DR GO; GO:0033489; P:cholesterol biosynthetic process via desmosterol; ISO:RGD.
DR GO; GO:0008203; P:cholesterol metabolic process; ISO:RGD.
DR GO; GO:0030539; P:male genitalia development; ISO:RGD.
DR GO; GO:0061024; P:membrane organization; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:UniProtKB.
DR GO; GO:0031639; P:plasminogen activation; ISO:RGD.
DR GO; GO:0008104; P:protein localization; ISO:RGD.
DR GO; GO:0007265; P:Ras protein signal transduction; IMP:RGD.
DR GO; GO:0009725; P:response to hormone; IEP:RGD.
DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; ISS:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; IMP:RGD.
DR GO; GO:0016125; P:sterol metabolic process; ISO:RGD.
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_0000320301"
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; 60047 MW; 48CC4401E730569E CRC64;
MEPAVSLAVC ALLFLLWVRV KGLEFVLIHQ RWVFVCLFLL PLSLIFDIYY YVRAWVVFKL
SSAPRLHEQR VQDIQKQVRE WKEQGSKTFM CTGRPGWLTV SLRVGKYKKT HKNIMINLMD
ILEVDTKKQI VRVEPLVSMG QVTALLNSIG WTLPVLPELD DLTVGGLIMG TGIESSSHKY
GLFQHICTAY ELILADGSFV RCTPSENSDL FYAVPWSCGT LGFLVAAEIR IIPAKKYVKL
RFEPVRGLEA ICEKFTHESQ RLENHFVEGL LYSLDEAVIM TGVMTDDVEP SKLNSIGSYY
KPWFFKHVEN YLKTNREGLE YIPLRHYYHR HTRSIFWELQ DIIPFGNNPI FRYLFGWMVP
PKISLLKLTQ GETLRKLYEQ HHVVQDMLVP MKCLSQALHT FQNDIHVYPI WLCPFILPSQ
PGLVHPKGDE AELYVDIGAY GEPRVKHFEA RSCMRQLEKF VRSVHGFQML YADCYMNREE
FWEMFDGSLY HKLRKQLGCQ DAFPEVYDKI CKAARH