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   24-JAN-2024, entry version 165.
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,
RC   Spleen, 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. Interacts with TMEM147. {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; 93.
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; 10090-ENSMUSP00000073541; -.
DR   PeptideAtlas; O88455; -.
DR   ProteomicsDB; 277332; -.
DR   Pumba; O88455; -.
DR   TopDownProteomics; O88455; -.
DR   Antibodypedia; 30720; 193 antibodies from 26 providers.
DR   DNASU; 13360; -.
DR   Ensembl; ENSMUST00000073878.12; ENSMUSP00000073541.6; ENSMUSG00000058454.16.
DR   Ensembl; ENSMUST00000124340.8; ENSMUSP00000117659.2; ENSMUSG00000058454.16.
DR   Ensembl; ENSMUST00000141916.8; ENSMUSP00000121782.2; ENSMUSG00000058454.16.
DR   GeneID; 13360; -.
DR   KEGG; mmu:13360; -.
DR   UCSC; uc009kqc.1; mouse.
DR   AGR; MGI:1298378; -.
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   OrthoDB; 275939at2759; -.
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 81 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 252 other cell types or tissues.
DR   ExpressionAtlas; O88455; baseline and differential.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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: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   Gene3D; 1.20.120.1630; -; 1.
DR   InterPro; IPR001171; ERG24_DHCR-like.
DR   InterPro; IPR018083; Sterol_reductase_CS.
DR   PANTHER; PTHR21257:SF38; 7-DEHYDROCHOLESTEROL REDUCTASE; 1.
DR   PANTHER; PTHR21257; DELTA(14)-STEROL REDUCTASE; 1.
DR   Pfam; PF01222; ERG4_ERG24; 1.
DR   PROSITE; PS01017; STEROL_REDUCT_1; 1.
DR   PROSITE; PS01018; STEROL_REDUCT_2; 1.
DR   Genevisible; O88455; MM.
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
//