DHCR7_MOUSE
ID DHCR7_MOUSE Reviewed; 471 AA.
AC O88455;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 157.
DE RecName: Full=7-dehydrocholesterol reductase;
DE Short=7-DHC reductase;
DE EC=1.3.1.21 {ECO:0000269|PubMed:11230174};
DE AltName: Full=Sterol Delta(7)-reductase;
GN Name=Dhcr7;
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].
RC STRAIN=C57BL/6J;
RX PubMed=9653161; DOI=10.1073/pnas.95.14.8181;
RA Fitzky B.U., Witsch-Baumgartner M., Erdel M., Lee J.N., Paik Y.-K.,
RA Glossmann H., Utermann G., Moebius F.F.;
RT "Mutations in the delta7-sterol reductase gene in patients with the Smith-
RT Lemli-Opitz syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8181-8186(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [3]
RP DISRUPTION PHENOTYPE, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=11230174; DOI=10.1093/hmg/10.6.555;
RA Wassif C.A., Zhu P., Kratz L., Krakowiak P.A., Battaile K.P., Weight F.F.,
RA Grinberg A., Steiner R.D., Nwokoro N.A., Kelley R.I., Stewart R.R.,
RA Porter F.D.;
RT "Biochemical, phenotypic and neurophysiological characterization of a
RT genetic mouse model of RSH/Smith--Lemli--Opitz syndrome.";
RL Hum. Mol. Genet. 10:555-564(2001).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC and Testis;
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).
CC -!- FUNCTION: 7-dehydrocholesterol reductase of the cholesterol
CC biosynthetic pathway reducing the C7-C8 double bond of cholesta-5,7-
CC dien-3beta-ol (7-dehydrocholesterol/7-DHC) and cholesta-5,7,24-trien-
CC 3beta-ol, two intermediates in that pathway.
CC {ECO:0000269|PubMed:11230174}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cholesterol + NADP(+) = 7-dehydrocholesterol + H(+) + NADPH;
CC Xref=Rhea:RHEA:23984, ChEBI:CHEBI:15378, ChEBI:CHEBI:16113,
CC ChEBI:CHEBI:17759, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.3.1.21;
CC Evidence={ECO:0000305|PubMed:11230174};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23986;
CC Evidence={ECO:0000305|PubMed:11230174};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7-dehydrodesmosterol + H(+) + NADPH = desmosterol + NADP(+);
CC Xref=Rhea:RHEA:46740, ChEBI:CHEBI:15378, ChEBI:CHEBI:17737,
CC ChEBI:CHEBI:27910, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349;
CC Evidence={ECO:0000269|PubMed:11230174};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46741;
CC Evidence={ECO:0000305|PubMed:11230174};
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC {ECO:0000269|PubMed:11230174}.
CC -!- SUBUNIT: Interacts with DHCR24; this interaction regulates DHCR7
CC activity. {ECO:0000250|UniProtKB:Q9UBM7}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9UBM7}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice die within one day of birth due to
CC respiratory and suckling problems. They exhibit abnormal cholesterol
CC homeostasis with reduced tissue cholesterol levels and total sterol
CC levels, enlarged bladders and sometimes cleft palate.
CC {ECO:0000269|PubMed:11230174}.
CC -!- SIMILARITY: Belongs to the ERG4/ERG24 family. {ECO:0000305}.
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DR EMBL; AF057368; AAC40164.1; -; mRNA.
DR EMBL; BC006854; AAH06854.1; -; mRNA.
DR CCDS; CCDS22048.1; -.
DR RefSeq; NP_031882.1; NM_007856.2.
DR RefSeq; XP_006508541.1; XM_006508478.1.
DR RefSeq; XP_006508542.1; XM_006508479.3.
DR RefSeq; XP_006508543.1; XM_006508480.2.
DR RefSeq; XP_006508544.1; XM_006508481.2.
DR AlphaFoldDB; O88455; -.
DR SMR; O88455; -.
DR BioGRID; 199217; 2.
DR STRING; 10090.ENSMUSP00000073541; -.
DR SwissLipids; SLP:000001320; -.
DR iPTMnet; O88455; -.
DR PhosphoSitePlus; O88455; -.
DR SwissPalm; O88455; -.
DR EPD; O88455; -.
DR jPOST; O88455; -.
DR MaxQB; O88455; -.
DR PaxDb; O88455; -.
DR PeptideAtlas; O88455; -.
DR PRIDE; O88455; -.
DR ProteomicsDB; 277332; -.
DR TopDownProteomics; O88455; -.
DR Antibodypedia; 30720; 176 antibodies from 25 providers.
DR DNASU; 13360; -.
DR Ensembl; ENSMUST00000073878; ENSMUSP00000073541; ENSMUSG00000058454.
DR Ensembl; ENSMUST00000124340; ENSMUSP00000117659; ENSMUSG00000058454.
DR Ensembl; ENSMUST00000141916; ENSMUSP00000121782; ENSMUSG00000058454.
DR GeneID; 13360; -.
DR KEGG; mmu:13360; -.
DR UCSC; uc009kqc.1; mouse.
DR CTD; 1717; -.
DR MGI; MGI:1298378; Dhcr7.
DR VEuPathDB; HostDB:ENSMUSG00000058454; -.
DR eggNOG; KOG1435; Eukaryota.
DR GeneTree; ENSGT00390000000417; -.
DR HOGENOM; CLU_015631_0_0_1; -.
DR InParanoid; O88455; -.
DR PhylomeDB; O88455; -.
DR TreeFam; TF101180; -.
DR BRENDA; 1.3.1.21; 3474.
DR Reactome; R-MMU-6807047; Cholesterol biosynthesis via desmosterol.
DR Reactome; R-MMU-6807062; Cholesterol biosynthesis via lathosterol.
DR UniPathway; UPA00063; -.
DR BioGRID-ORCS; 13360; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Dhcr7; mouse.
DR PRO; PR:O88455; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O88455; protein.
DR Bgee; ENSMUSG00000058454; Expressed in adrenal gland and 249 other tissues.
DR ExpressionAtlas; O88455; baseline and differential.
DR Genevisible; O88455; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005640; C:nuclear outer membrane; ISO:MGI.
DR GO; GO:0047598; F:7-dehydrocholesterol reductase activity; IDA:MGI.
DR GO; GO:0050661; F:NADP binding; ISS:UniProtKB.
DR GO; GO:0016627; F:oxidoreductase activity, acting on the CH-CH group of donors; IBA:GO_Central.
DR GO; GO:0009918; F:sterol delta7 reductase activity; IBA:GO_Central.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0016132; P:brassinosteroid biosynthetic process; IBA:GO_Central.
DR GO; GO:0006695; P:cholesterol biosynthetic process; ISO:MGI.
DR GO; GO:0030324; P:lung development; IMP:MGI.
DR GO; GO:0060487; P:lung epithelial cell differentiation; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0045540; P:regulation of cholesterol biosynthetic process; ISO:MGI.
DR GO; GO:0016126; P:sterol biosynthetic process; IMP:MGI.
DR InterPro; IPR001171; ERG24_DHCR-like.
DR InterPro; IPR018083; Sterol_reductase_CS.
DR Pfam; PF01222; ERG4_ERG24; 1.
DR PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR PROSITE; PS01018; STEROL_REDUCT_2; 1.
PE 1: Evidence at protein level;
KW Cholesterol biosynthesis; Cholesterol metabolism; Endoplasmic reticulum;
KW Lipid biosynthesis; Lipid metabolism; Membrane; NADP; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..471
FT /note="7-dehydrocholesterol reductase"
FT /id="PRO_0000207503"
FT TRANSMEM 36..56
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 144..164
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 173..193
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 327..347
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 416..436
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..23
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 354
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 358
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 391
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 396
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 403..404
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 443
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 447..451
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT BINDING 458
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:G4SW86"
FT MOD_RES 14
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBM7"
SQ SEQUENCE 471 AA; 53919 MW; 6B1BC356CC539290 CRC64;
MASKSQHNAP KVKSPNGKAG SQGQWGRAWE VDWFSLASII FLLLFAPFIV YYFIMACDQY
SCSLTAPALD IATGHASLAD IWAKTPPVTA KAAQLYALWV SFQVLLYSWL PDFCHRFLPG
YVGGVQEGAI TPAGVVNKYE VNGLQAWLIT HILWFVNAYL LSWFSPTIIF DNWIPLLWCA
NILGYAVSTF AMIKGYLFPT SAEDCKFTGN FFYNYMMGIE FNPRIGKWFD FKLFFNGRPG
IVAWTLINLS FAAKQQELYG HVTNSMILVN VLQAIYVLDF FWNETWYLKT IDICHDHFGW
YLGWGDCVWL PYLYTLQGLY LVYHPVQLST PNALGILLLG LVGYYIFRMT NHQKDLFRRT
DGRCLIWGKK PKAIECSYTS ADGLKHHSKL LVSGFWGVAR HFNYTGDLMG SLAYCLACGG
GHLLPYFYII YMTILLTHRC LRDEHRCANK YGRDWERYTA AVPYRLLPGI F
