DHC24_MOUSE
ID DHC24_MOUSE Reviewed; 516 AA.
AC Q8VCH6; Q6ZQK9; Q91ZD0; Q9CU63;
DT 26-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Delta(24)-sterol reductase;
DE EC=1.3.1.72 {ECO:0000269|PubMed:26114596};
DE AltName: Full=24-dehydrocholesterol reductase;
DE AltName: Full=3-beta-hydroxysterol Delta-24-reductase {ECO:0000303|PubMed:11519011};
DE Flags: Precursor;
GN Name=Dhcr24; Synonyms=Kiaa0018;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=11519011; DOI=10.1086/323473;
RA Waterham H.R., Koster J., Romeijn G.J., Hennekam R.C.M., Vreken P.,
RA Andersson H.C., FitzPatrick D.R., Kelley R.I., Wanders R.J.A.;
RT "Mutations in the 3beta-hydroxysterol delta24-reductase gene cause
RT desmosterolosis, an autosomal recessive disorder of cholesterol
RT biosynthesis.";
RL Am. J. Hum. Genet. 69:685-694(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Fetal brain;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 38-516.
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP CATALYTIC ACTIVITY.
RX PubMed=26114596; DOI=10.7554/elife.07999;
RA Mitsche M.A., McDonald J.G., Hobbs H.H., Cohen J.C.;
RT "Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue
RT and cell-type specific pathways.";
RL Elife 4:E07999-E07999(2015).
CC -!- FUNCTION: Catalyzes the reduction of the delta-24 double bond of sterol
CC intermediates during cholesterol biosynthesis (PubMed:26114596). In
CC addition to its cholesterol-synthesizing activity, can protect cells
CC from oxidative stress by reducing caspase 3 activity during apoptosis
CC induced by oxidative stress. Also protects against amyloid-beta
CC peptide-induced apoptosis (By similarity).
CC {ECO:0000250|UniProtKB:Q15392, ECO:0000269|PubMed:26114596}.
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:0000269|PubMed:26114596};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:36401;
CC Evidence={ECO:0000305|PubMed:26114596};
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=left-to-right; Xref=Rhea:RHEA:36392;
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 -!- COFACTOR:
CC Name=FAD; Xref=ChEBI:CHEBI:57692; Evidence={ECO:0000250};
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC {ECO:0000269|PubMed:26114596}.
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=BAC97846.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AY039762; AAK72106.1; -; mRNA.
DR EMBL; AK129036; BAC97846.1; ALT_INIT; mRNA.
DR EMBL; AL929585; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX511043; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC019797; AAH19797.1; -; mRNA.
DR EMBL; AK017937; BAB31012.1; -; mRNA.
DR CCDS; CCDS18420.1; -.
DR RefSeq; NP_444502.2; NM_053272.2.
DR AlphaFoldDB; Q8VCH6; -.
DR SMR; Q8VCH6; -.
DR BioGRID; 216997; 2.
DR STRING; 10090.ENSMUSP00000038063; -.
DR ChEMBL; CHEMBL3774292; -.
DR SwissLipids; SLP:000001298; -.
DR iPTMnet; Q8VCH6; -.
DR PhosphoSitePlus; Q8VCH6; -.
DR SwissPalm; Q8VCH6; -.
DR EPD; Q8VCH6; -.
DR jPOST; Q8VCH6; -.
DR MaxQB; Q8VCH6; -.
DR PaxDb; Q8VCH6; -.
DR PeptideAtlas; Q8VCH6; -.
DR PRIDE; Q8VCH6; -.
DR ProteomicsDB; 277331; -.
DR Antibodypedia; 33226; 255 antibodies from 30 providers.
DR DNASU; 74754; -.
DR Ensembl; ENSMUST00000047973; ENSMUSP00000038063; ENSMUSG00000034926.
DR GeneID; 74754; -.
DR KEGG; mmu:74754; -.
DR UCSC; uc008tyl.1; mouse.
DR CTD; 1718; -.
DR MGI; MGI:1922004; Dhcr24.
DR VEuPathDB; HostDB:ENSMUSG00000034926; -.
DR eggNOG; KOG1262; Eukaryota.
DR GeneTree; ENSGT00390000008338; -.
DR HOGENOM; CLU_025883_4_0_1; -.
DR InParanoid; Q8VCH6; -.
DR OMA; YIPSRHY; -.
DR OrthoDB; 733611at2759; -.
DR PhylomeDB; Q8VCH6; -.
DR TreeFam; TF313170; -.
DR BRENDA; 1.3.1.72; 3474.
DR Reactome; R-MMU-191273; Cholesterol biosynthesis.
DR Reactome; R-MMU-6807047; Cholesterol biosynthesis via desmosterol.
DR Reactome; R-MMU-6807062; Cholesterol biosynthesis via lathosterol.
DR UniPathway; UPA00063; -.
DR BioGRID-ORCS; 74754; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Dhcr24; mouse.
DR PRO; PR:Q8VCH6; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8VCH6; protein.
DR Bgee; ENSMUSG00000034926; Expressed in lip and 263 other tissues.
DR Genevisible; Q8VCH6; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000246; F:delta24(24-1) sterol reductase activity; ISO:MGI.
DR GO; GO:0050614; F:delta24-sterol reductase activity; ISO:MGI.
DR GO; GO:0019899; F:enzyme binding; ISS:UniProtKB.
DR GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR GO; GO:0016628; F:oxidoreductase activity, acting on the CH-CH group of donors, NAD or NADP as acceptor; ISO:MGI.
DR GO; GO:0042605; F:peptide antigen binding; ISS:UniProtKB.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IMP:MGI.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IMP:UniProtKB.
DR GO; GO:0033489; P:cholesterol biosynthetic process via desmosterol; ISO:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI.
DR GO; GO:0030539; P:male genitalia development; IMP:MGI.
DR GO; GO:0061024; P:membrane organization; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
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; IMP:MGI.
DR GO; GO:0008104; P:protein localization; IMP:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; ISO:MGI.
DR GO; GO:0009725; P:response to hormone; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0043588; P:skin development; IMP:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; ISO:MGI.
DR GO; GO:0016125; P:sterol metabolic process; IMP:MGI.
DR GO; GO:0009888; P:tissue development; IMP:MGI.
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 1: Evidence at protein 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_0000320300"
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"
FT CONFLICT 61..62
FT /note="SS -> TN (in Ref. 5; BAB31012)"
FT /evidence="ECO:0000305"
FT CONFLICT 68..71
FT /note="EQRV -> NXPL (in Ref. 5; BAB31012)"
FT /evidence="ECO:0000305"
FT CONFLICT 94
FT /note="R -> P (in Ref. 5; BAB31012)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="V -> VAV (in Ref. 1; AAK72106)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="P -> S (in Ref. 1; AAK72106)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 516 AA; 60112 MW; 7F41D598539E86E4 CRC64;
MEPAVSLAVC ALLFLLWVRV KGLEFVLIHQ RWVFVCLFLL PLSLIFDIYY YVRAWVVFKL
SSAPRLHEQR VRDIQKQVRE WKEQGSKTFM CTGRPGWLTV SLRVGKYKKT HKNIMINLMD
ILEVDTKKQI VRVEPLVSMG QVTALLNSIG WTLPVLPELD DLTVGGLIMG TGIESSSHKY
GLFQHICTAY ELILADGSFV RCTPSENSDL FYAVPWSCGT LGFLVAAEIR IIPAKKYVKL
RFEPVRGLEA ICEKFTRESQ RLENHFVEGL LYSLDEAVIM TGVMTDDVEP SKLNSIGSYY
KPWFFKHVEN YLKTNREGLE YIPLRHYYHR HTRSIFWELQ DIIPFGNNPI FRYLFGWMVP
PKISLLKLTQ GETLRKLYEQ HHVVQDMLVP MKCMSQALHT FQNDIHVYPI WLCPFILPSQ
PGLVHPKGDE AELYVDIGAY GEPRVKHFEA RSCMRQLEKF VRSVHGFQML YADCYMNREE
FWEMFDGSLY HKLRKQLGCQ DAFPEVYDKI CKAARH
