DHC24_HUMAN
ID DHC24_HUMAN Reviewed; 516 AA.
AC Q15392; B7Z817; D3DQ51; Q9HBA8;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Delta(24)-sterol reductase;
DE EC=1.3.1.72 {ECO:0000269|PubMed:11519011, ECO:0000269|PubMed:21671375};
DE AltName: Full=24-dehydrocholesterol reductase;
DE AltName: Full=3-beta-hydroxysterol Delta-24-reductase;
DE AltName: Full=Diminuto/dwarf1 homolog;
DE AltName: Full=Seladin-1 {ECO:0000303|PubMed:11007892};
DE Flags: Precursor;
GN Name=DHCR24; Synonyms=KIAA0018;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=11007892; DOI=10.1523/jneurosci.20-19-07345.2000;
RA Greeve I., Hermans-Borgmeyer I., Brellinger C., Kasper D., Gomez-Isla T.,
RA Behl C., Levkau B., Nitsch R.M.;
RT "The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to
RT Alzheimer's disease-associated neurodegeneration and oxidative stress.";
RL J. Neurosci. 20:7345-7352(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, VARIANTS
RP DESMOS LYS-191; THR-294; ASN-306 AND SER-471, CATALYTIC ACTIVITY, AND
RP CHARACTERIZATION OF VARIANTS DESMOS LYS-191; THR-294; ASN-306 AND SER-471.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Bone marrow;
RX PubMed=7584026; DOI=10.1093/dnares/1.1.27;
RA Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S.,
RA Nagase T., Seki N., Ishikawa K., Tabata S.;
RT "Prediction of the coding sequences of unidentified human genes. I. The
RT coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of
RT randomly sampled cDNA clones from human immature myeloid cell line KG-1.";
RL DNA Res. 1:27-35(1994).
RN [4]
RP SEQUENCE REVISION TO C-TERMINUS.
RA Ohara O., Nagase T., Kikuno R., Nomura N.;
RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Placenta;
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 [9]
RP VARIANTS DESMOS HIS-94 AND LYS-480, CHARACTERIZATION OF VARIANTS DESMOS
RP HIS-94 AND LYS-480, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=21671375; DOI=10.1002/ajmg.a.34040;
RA Schaaf C.P., Koster J., Katsonis P., Kratz L., Shchelochkov O.A.,
RA Scaglia F., Kelley R.I., Lichtarge O., Waterham H.R., Shinawi M.;
RT "Desmosterolosis-phenotypic and molecular characterization of a third case
RT and review of the literature.";
RL Am. J. Med. Genet. A 155A:1597-1604(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [11]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=22178193; DOI=10.1016/j.bbalip.2011.11.009;
RA Zerenturk E.J., Kristiana I., Gill S., Brown A.J.;
RT "The endogenous regulator 24(S),25-epoxycholesterol inhibits cholesterol
RT synthesis at DHCR24 (Seladin-1).";
RL Biochim. Biophys. Acta 1821:1269-1277(2012).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=22010141; DOI=10.1530/jme-11-0132;
RA Lu X., Li Y., Liu J., Cao X., Wang X., Wang D., Seo H., Gao B.;
RT "The membrane topological analysis of 3 {beta}-hydroxysteroid-delta24
RT reductase (DHCR24) on endoplasmic reticulum.";
RL J. Mol. Endocrinol. 48:1-9(2012).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [14]
RP CATALYTIC ACTIVITY, AND INTERACTION WITH DHCR7.
RX PubMed=25637936; DOI=10.1194/jlr.m056986;
RA Luu W., Hart-Smith G., Sharpe L.J., Brown A.J.;
RT "The terminal enzymes of cholesterol synthesis, DHCR24 and DHCR7, interact
RT physically and functionally.";
RL J. Lipid Res. 56:888-897(2015).
RN [15]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
CC -!- FUNCTION: Catalyzes the reduction of the delta-24 double bond of sterol
CC intermediates during cholesterol biosynthesis (PubMed:11519011,
CC PubMed:21671375, PubMed:25637936, PubMed:22178193). 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 (PubMed:11007892, PubMed:22010141). Also protects
CC against amyloid-beta peptide-induced apoptosis (PubMed:11007892).
CC {ECO:0000269|PubMed:11007892, ECO:0000269|PubMed:11519011,
CC ECO:0000269|PubMed:21671375, ECO:0000269|PubMed:22010141,
CC ECO:0000269|PubMed:22178193, ECO:0000269|PubMed:25637936}.
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:0000269|PubMed:11519011, ECO:0000269|PubMed:21671375,
CC ECO:0000269|PubMed:25637936};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:36393;
CC Evidence={ECO:0000305|PubMed:11519011, ECO:0000305|PubMed:21671375};
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:0000269|PubMed:22178193};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:33920;
CC Evidence={ECO:0000269|PubMed:22178193};
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;
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC {ECO:0000269|PubMed:11519011, ECO:0000269|PubMed:21671375}.
CC -!- SUBUNIT: Interacts with DHCR7; this interaction regulates DHCR7
CC activity. {ECO:0000269|PubMed:25637936}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:11007892, ECO:0000269|PubMed:22010141}; Single-pass
CC membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000269|PubMed:11007892}; Single-pass membrane protein
CC {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15392-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15392-2; Sequence=VSP_056479;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and adrenal gland with
CC moderate expression in liver, lung, spleen, prostate and spinal cord.
CC Low expression in heart, uterus and prostate. Undetectable in blood
CC cells. In the brain, strongly expressed in cortical regions, substantia
CC nigra, caudate nucleus, hippocampus, medulla oblongata and pons. In
CC brains affected by Alzheimer disease, expression in the inferior
CC temporal lobe is substantially lower than in the frontal cortex.
CC {ECO:0000269|PubMed:11007892, ECO:0000269|PubMed:11519011}.
CC -!- DISEASE: Desmosterolosis (DESMOS) [MIM:602398]: Rare autosomal
CC recessive disorder characterized by multiple congenital anomalies and
CC elevated levels of the cholesterol precursor desmosterol in plasma,
CC tissue, and cultured cells. {ECO:0000269|PubMed:11519011,
CC ECO:0000269|PubMed:21671375}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the FAD-binding oxidoreductase/transferase type
CC 4 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA02806.3; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF261758; AAG17288.1; -; mRNA.
DR EMBL; AF398342; AAL15644.1; -; Genomic_DNA.
DR EMBL; AF398336; AAL15644.1; JOINED; Genomic_DNA.
DR EMBL; AF398337; AAL15644.1; JOINED; Genomic_DNA.
DR EMBL; AF398338; AAL15644.1; JOINED; Genomic_DNA.
DR EMBL; AF398339; AAL15644.1; JOINED; Genomic_DNA.
DR EMBL; AF398340; AAL15644.1; JOINED; Genomic_DNA.
DR EMBL; AF398341; AAL15644.1; JOINED; Genomic_DNA.
DR EMBL; D13643; BAA02806.3; ALT_INIT; mRNA.
DR EMBL; AK302774; BAH13803.1; -; mRNA.
DR EMBL; AC096536; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471059; EAX06663.1; -; Genomic_DNA.
DR EMBL; CH471059; EAX06664.1; -; Genomic_DNA.
DR EMBL; BC004375; AAH04375.1; -; mRNA.
DR EMBL; BC011669; AAH11669.1; -; mRNA.
DR CCDS; CCDS600.1; -. [Q15392-1]
DR RefSeq; NP_055577.1; NM_014762.3. [Q15392-1]
DR AlphaFoldDB; Q15392; -.
DR BioGRID; 108064; 153.
DR IntAct; Q15392; 57.
DR MINT; Q15392; -.
DR STRING; 9606.ENSP00000360316; -.
DR BindingDB; Q15392; -.
DR ChEMBL; CHEMBL2331059; -.
DR SwissLipids; SLP:000001223; -.
DR GlyGen; Q15392; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q15392; -.
DR MetOSite; Q15392; -.
DR PhosphoSitePlus; Q15392; -.
DR SwissPalm; Q15392; -.
DR BioMuta; DHCR24; -.
DR DMDM; 20141421; -.
DR EPD; Q15392; -.
DR jPOST; Q15392; -.
DR MassIVE; Q15392; -.
DR MaxQB; Q15392; -.
DR PaxDb; Q15392; -.
DR PeptideAtlas; Q15392; -.
DR PRIDE; Q15392; -.
DR ProteomicsDB; 60562; -. [Q15392-1]
DR ProteomicsDB; 6916; -.
DR Antibodypedia; 33226; 255 antibodies from 30 providers.
DR DNASU; 1718; -.
DR Ensembl; ENST00000371269.9; ENSP00000360316.3; ENSG00000116133.13. [Q15392-1]
DR Ensembl; ENST00000436604.2; ENSP00000416585.2; ENSG00000116133.13. [Q15392-1]
DR GeneID; 1718; -.
DR KEGG; hsa:1718; -.
DR MANE-Select; ENST00000371269.9; ENSP00000360316.3; NM_014762.4; NP_055577.1.
DR UCSC; uc001cyc.2; human. [Q15392-1]
DR CTD; 1718; -.
DR DisGeNET; 1718; -.
DR GeneCards; DHCR24; -.
DR HGNC; HGNC:2859; DHCR24.
DR HPA; ENSG00000116133; Tissue enhanced (adrenal gland, liver).
DR MalaCards; DHCR24; -.
DR MIM; 602398; phenotype.
DR MIM; 606418; gene.
DR neXtProt; NX_Q15392; -.
DR OpenTargets; ENSG00000116133; -.
DR Orphanet; 35107; Desmosterolosis.
DR PharmGKB; PA27320; -.
DR VEuPathDB; HostDB:ENSG00000116133; -.
DR eggNOG; KOG1262; Eukaryota.
DR GeneTree; ENSGT00390000008338; -.
DR InParanoid; Q15392; -.
DR OrthoDB; 733611at2759; -.
DR PhylomeDB; Q15392; -.
DR TreeFam; TF313170; -.
DR BRENDA; 1.3.1.72; 2681.
DR PathwayCommons; Q15392; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR Reactome; R-HSA-6807047; Cholesterol biosynthesis via desmosterol.
DR Reactome; R-HSA-6807062; Cholesterol biosynthesis via lathosterol.
DR SignaLink; Q15392; -.
DR SIGNOR; Q15392; -.
DR UniPathway; UPA00063; -.
DR BioGRID-ORCS; 1718; 21 hits in 1085 CRISPR screens.
DR ChiTaRS; DHCR24; human.
DR GeneWiki; 24-dehydrocholesterol_reductase; -.
DR GenomeRNAi; 1718; -.
DR Pharos; Q15392; Tchem.
DR PRO; PR:Q15392; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q15392; protein.
DR Bgee; ENSG00000116133; Expressed in adrenal tissue and 195 other tissues.
DR ExpressionAtlas; Q15392; baseline and differential.
DR Genevisible; Q15392; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
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; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0000246; F:delta24(24-1) sterol reductase activity; IMP:UniProtKB.
DR GO; GO:0050614; F:delta24-sterol reductase activity; EXP:Reactome.
DR GO; GO:0019899; F:enzyme binding; IPI: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; IDA:MGI.
DR GO; GO:0042605; F:peptide antigen binding; IPI:UniProtKB.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; NAS:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; IMP:MGI.
DR GO; GO:0033489; P:cholesterol biosynthetic process via desmosterol; IMP:UniProtKB.
DR GO; GO:0033490; P:cholesterol biosynthetic process via lathosterol; TAS:Reactome.
DR GO; GO:0030539; P:male genitalia development; IEA:Ensembl.
DR GO; GO:0061024; P:membrane organization; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0031639; P:plasminogen activation; IEA:Ensembl.
DR GO; GO:0008104; P:protein localization; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0051726; P:regulation of cell cycle; NAS:UniProtKB.
DR GO; GO:1901214; P:regulation of neuron death; NAS:UniProtKB.
DR GO; GO:0009725; P:response to hormone; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IEP:UniProtKB.
DR GO; GO:0043588; P:skin development; ISS:UniProtKB.
DR GO; GO:0008202; P:steroid metabolic process; IBA:GO_Central.
DR GO; GO:0009888; P:tissue development; IMP: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 1: Evidence at protein level;
KW Alternative splicing; Cholesterol biosynthesis; Cholesterol metabolism;
KW Disease variant; Endoplasmic reticulum; FAD; Flavoprotein; Golgi apparatus;
KW Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW Reference proteome; Signal; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; 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_0000007230"
FT TOPO_DOM 23..31
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:22010141"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 53..516
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:22010141"
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 VAR_SEQ 1..76
FT /note="MEPAVSLAVCALLFLLWVRLKGLEFVLIHQRWVFVCLFLLPLSLIFDIYYYV
FT RAWVVFKLSSAPRLHEQRVRDIQK -> MGAGEQNRQSAHCVQGICGYLEGDEEGEEGE
FT VRST (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056479"
FT VARIANT 94
FT /note="R -> H (in DESMOS; decreases production of
FT cholesterol from desmosterol; dbSNP:rs387906939)"
FT /evidence="ECO:0000269|PubMed:21671375"
FT /id="VAR_081889"
FT VARIANT 191
FT /note="E -> K (in DESMOS; decreases production of
FT cholesterol from desmosterol; dbSNP:rs119475041)"
FT /evidence="ECO:0000269|PubMed:11519011"
FT /id="VAR_012732"
FT VARIANT 294
FT /note="N -> T (in DESMOS; decreases production of
FT cholesterol from desmosterol; dbSNP:rs281797257)"
FT /evidence="ECO:0000269|PubMed:11519011"
FT /id="VAR_012733"
FT VARIANT 306
FT /note="K -> N (in DESMOS; decreases production of
FT cholesterol from desmosterol; dbSNP:rs281797256)"
FT /evidence="ECO:0000269|PubMed:11519011"
FT /id="VAR_012734"
FT VARIANT 471
FT /note="Y -> S (in DESMOS; complete loss of ability to
FT convert desmosterol to cholesterol; dbSNP:rs28939092)"
FT /evidence="ECO:0000269|PubMed:11519011,
FT ECO:0000269|PubMed:21671375"
FT /id="VAR_012735"
FT VARIANT 480
FT /note="E -> K (in DESMOS; decreases production of
FT cholesterol from desmosterol; dbSNP:rs387906940)"
FT /evidence="ECO:0000269|PubMed:21671375"
FT /id="VAR_081890"
SQ SEQUENCE 516 AA; 60101 MW; F9A769446FE19E59 CRC64;
MEPAVSLAVC ALLFLLWVRL KGLEFVLIHQ RWVFVCLFLL PLSLIFDIYY YVRAWVVFKL
SSAPRLHEQR VRDIQKQVRE WKEQGSKTFM CTGRPGWLTV SLRVGKYKKT HKNIMINLMD
ILEVDTKKQI VRVEPLVTMG QVTALLTSIG WTLPVLPELD DLTVGGLIMG TGIESSSHKY
GLFQHICTAY ELVLADGSFV RCTPSENSDL FYAVPWSCGT LGFLVAAEIR IIPAKKYVKL
RFEPVRGLEA ICAKFTHESQ RQENHFVEGL LYSLDEAVIM TGVMTDEAEP SKLNSIGNYY
KPWFFKHVEN YLKTNREGLE YIPLRHYYHR HTRSIFWELQ DIIPFGNNPI FRYLFGWMVP
PKISLLKLTQ GETLRKLYEQ HHVVQDMLVP MKCLQQALHT FQNDIHVYPI WLCPFILPSQ
PGLVHPKGNE AELYIDIGAY GEPRVKHFEA RSCMRQLEKF VRSVHGFQML YADCYMNREE
FWEMFDGSLY HKLREKLGCQ DAFPEVYDKI CKAARH
