Reviewed,
UniProtKB/Swiss-Prot Q9UBM7 (DHCR7_HUMAN)
Last modified
July 7, 2009.
Version 86.
History...
Clusters with 100%,
90%,
50% identity |
Documents (6) |
Third-party data |
Customize display | text xml rdf/xml gff fasta |
Names and origin
| Protein names | Recommended name: 7-dehydrocholesterol reductase Short name=7-DHC reductase EC=1.3.1.21 Alternative name(s): Sterol Delta(7)-reductase Putative sterol reductase SR-2 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 475 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Production of cholesterol by reduction of C7-C8 double bond of 7-dehydrocholesterol (7-DHC). |
| Catalytic activity | Cholesterol + NADP+ = cholesta-5,7-dien-3-beta-ol + NADPH. |
| Pathway | |
| Subcellular location | Endoplasmic reticulum membrane; Multi-pass membrane protein. Ref.3 |
| Tissue specificity | Most abundant in adrenal gland, liver, testis, and brain. Ref.3 |
| Involvement in disease | Defects in DHCR7 are the cause of Smith-Lemli-Opitz syndrome (SLOS) [MIM:270400]; also known as SLO syndrome or RSH syndrome. SLOS is an autosomal recessive frequent inborn disorder of sterol metabolism with characteristic congenital malformations and dysmorphias. All patients suffer from mental retardation. Children with SLOS have elevated serum 7-dehydrocholesterol (7-DHC) levels and low serum cholesterol levels. SLOS occurs in relatively high frequency: approximately 1 in 20,000 to 30,000 births in populations of northern and central European background. Historically, a clinical distinction often was made between classic ("type I") SLOS and the more severely affected ("type II") patients. There is, in reality, a clinical and biochemical continuum from mild to severe SLOS. Ref.1 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 |
| Sequence similarities | Belongs to the ERG4/ERG24 family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis |
| Cellular component | Endoplasmic reticulum Membrane |
| Coding sequence diversity | Polymorphism |
| Disease | Disease mutation |
| Domain | Transmembrane |
| Ligand | NADP |
| Molecular function | Oxidoreductase |
| PTM | Phosphoprotein |
| Technical term | Complete proteome |
| Gene Ontology (GO) | |
| Biological process | cholesterol biosynthetic process Ref.2 Inferred from mutant phenotype. Source: UniProtKB oxidation reductionInferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | endoplasmic reticulum membrane Ref.2 Inferred from Experiment. Source: Reactome integral to membraneInferred from electronic annotation. Source: UniProtKB-KW nuclear outer membrane Ref.3Inferred from direct assay. Source: UniProtKB |
| Molecular function | 7-dehydrocholesterol reductase activity Ref.2 Inferred from direct assay. Source: UniProtKB protein bindingInferred from physical interaction. Source: IntAct |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| FADS1 | O60427 | 1 | EBI-1054468,EBI-1055473 | |
| NDN | Q99608 | 1 | EBI-1054468,EBI-718177 | |
| TOR1A | O14656 | 1 | EBI-1054468,EBI-524257 |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 475 | 475 | 7-dehydrocholesterol reductase | PRO_0000207502 | |||||
Regions | |||||||||
| Transmembrane | 40 – 60 | 21 | Potential | ||||||
| Transmembrane | 154 – 174 | 21 | Potential | ||||||
| Transmembrane | 177 – 197 | 21 | Potential | ||||||
| Transmembrane | 266 – 286 | 21 | Potential | ||||||
| Transmembrane | 306 – 326 | 21 | Potential | ||||||
| Transmembrane | 331 – 351 | 21 | Potential | ||||||
| Transmembrane | 420 – 440 | 21 | Potential | ||||||
Amino acid modifications | |||||||||
| Modified residue | 14 | 1 | Phosphoserine Ref.6 | ||||||
Natural variations | |||||||||
| Natural variant | 51 | 1 | P → S in SLOS. Ref.8 Ref.9 | VAR_012717 | |||||
| Natural variant | 68 | 1 | L → P in SLOS. Ref.14 | VAR_023148 | |||||
| Natural variant | 93 | 1 | T → M in SLOS. Ref.8 Ref.9 Ref.11 Ref.12 | VAR_012718 | |||||
| Natural variant | 99 | 1 | L → P in SLOS. Ref.8 Ref.9 | VAR_012719 | |||||
| Natural variant | 107 | 1 | Q → H in SLOS. Ref.9 | VAR_023149 | |||||
| Natural variant | 109 | 1 | L → P in SLOS. Ref.9 Ref.11 | VAR_023150 | |||||
| Natural variant | 113 | 1 | S → C in SLOS. Ref.14 | VAR_023151 | |||||
| Natural variant | 119 | 1 | H → L in SLOS. Ref.1 Ref.11 | VAR_012720 | |||||
| Natural variant | 138 | 1 | G → V in SLOS. Ref.14 | VAR_023152 | |||||
| Natural variant | 145 | 1 | I → L in SLOS. Ref.14 | VAR_023153 | |||||
| Natural variant | 147 | 1 | G → D in SLOS. Ref.9 | VAR_023154 | |||||
| Natural variant | 154 | 1 | T → M in SLOS. Ref.9 Ref.11 | VAR_023155 | |||||
| Natural variant | 157 | 1 | L → P in SLOS. Ref.8 Ref.9 | VAR_012721 | |||||
| Natural variant | 169 | 1 | S → L in SLOS. Ref.9 | VAR_023156 | |||||
| Natural variant | 182 | 1 | W → C in SLOS. Ref.9 Ref.11 | VAR_023157 | |||||
| Natural variant | 182 | 1 | W → L in SLOS. Ref.9 Ref.11 | VAR_023158 | |||||
| Natural variant | 183 | 1 | C → Y in SLOS. Ref.11 | VAR_023159 | |||||
| Natural variant | 198 | 1 | K → E in SLOS. Ref.11 | VAR_023160 | |||||
| Natural variant | 235 | 1 | F → S in SLOS. Ref.14 | VAR_023161 | |||||
| Natural variant | 242 | 1 | R → C in SLOS. Ref.9 Ref.11 Ref.14 | VAR_023162 | |||||
| Natural variant | 242 | 1 | R → H in SLOS. Ref.9 Ref.11 Ref.14 | VAR_023163 | |||||
| Natural variant | 244 | 1 | G → R in SLOS. Ref.1 Ref.11 | VAR_012722 | |||||
| Natural variant | 247 | 1 | A → V in SLOS. Ref.8 Ref.9 | VAR_012723 | |||||
| Natural variant | 248 | 1 | W → C in SLOS. Ref.1 Ref.11 | VAR_012724 | |||||
| Natural variant | 255 | 1 | F → L in SLOS. Ref.11 | VAR_023164 | |||||
| Natural variant | 281 | 1 | V → M in SLOS. Ref.9 | VAR_023165 | |||||
| Natural variant | 289 | 1 | T → I in SLOS. Ref.9 Ref.10 | VAR_012725 | |||||
| Natural variant | 297 | 1 | I → T in SLOS. Ref.14 | VAR_023166 | |||||
| Natural variant | 311 | 1 | C → G in SLOS. Ref.9 | VAR_023167 | |||||
| Natural variant | 311 | 1 | C → Y in SLOS. Ref.9 | VAR_023168 | |||||
| Natural variant | 324 | 1 | Y → H in SLOS. Ref.9 | VAR_023169 | |||||
| Natural variant | 326 | 1 | V → L in SLOS. Ref.8 Ref.9 Ref.12 | VAR_012726 | |||||
| Natural variant | 344 | 1 | G → R in SLOS. Ref.14 | VAR_023170 | |||||
| Natural variant | 352 | 1 | R → Q in SLOS. Ref.8 Ref.9 Ref.12 | VAR_023171 | |||||
| Natural variant | 352 | 1 | R → W in SLOS. Ref.8 Ref.9 Ref.12 | VAR_012727 | |||||
| Natural variant | 353 | 1 | V → A in SLOS. Ref.9 | VAR_023172 | |||||
| Natural variant | 362 | 1 | R → C in SLOS. Ref.9 | VAR_023173 | |||||
| Natural variant | 380 | 1 | C → R in SLOS. Ref.8 Ref.9 | VAR_023174 | |||||
| Natural variant | 380 | 1 | C → S in SLOS. Ref.8 Ref.9 | VAR_012728 | |||||
| Natural variant | 380 | 1 | C → Y in SLOS. Ref.8 Ref.9 | VAR_023175 | |||||
| Natural variant | 397 | 1 | S → L in SLOS. Ref.9 | VAR_023176 | |||||
| Natural variant | 404 | 1 | R → C in SLOS. Ref.8 Ref.9 Ref.12 Ref.14 | VAR_012729 | |||||
| Natural variant | 404 | 1 | R → S in SLOS. Ref.8 Ref.9 Ref.12 Ref.14 | VAR_023177 | |||||
| Natural variant | 405 | 1 | H → Y in SLOS. Ref.14 | VAR_023178 | |||||
| Natural variant | 408 | 1 | Y → H in SLOS. Ref.9 Ref.14 | VAR_023179 | |||||
| Natural variant | 410 | 1 | G → R in SLOS. Ref.8 Ref.9 | VAR_023180 | |||||
| Natural variant | 410 | 1 | G → S in SLOS. Ref.8 Ref.9 | VAR_012730 | |||||
| Natural variant | 425 | 1 | G → S: dbSNP rs760242. | VAR_052154 | |||||
| Natural variant | 426 | 1 | H → P in SLOS. Ref.14 | VAR_023181 | |||||
| Natural variant | 443 | 1 | R → C in SLOS. Ref.9 | VAR_023182 | |||||
| Natural variant | 446 | 1 | R → Q in SLOS. Ref.9 | VAR_023183 | |||||
| Natural variant | 448 | 1 | E → K in SLOS; mild. Ref.9 Ref.13 | VAR_016975 | |||||
| Natural variant | 448 | 1 | E → Q in SLOS. Ref.9 Ref.13 | VAR_023184 | |||||
| Natural variant | 450 | 1 | R → L in SLOS. Ref.9 | VAR_023185 | |||||
Experimental info | |||||||||
| Sequence conflict | 5 | 1 | S → L in AAC05086. Ref.2 | ||||||
| Sequence conflict | 14 | 1 | S → A in AAC18345. Ref.5 | ||||||
Sequences
| ||||||||||||||||||
References
| « Hide 'large scale' references | |
| [1] | "Smith-Lemli-Opitz syndrome is caused by mutations in the 7-dehydrocholesterol reductase gene." Waterham H.R., Wijburg F.A., Hennekam R.C.M., Vreken P., Poll-The B.T., Dorland L., Duran M., Jira P.E., Smeitink J.A.M., Wevers R.A., Wanders R.J.A. Am. J. Hum. Genet. 63:329-338(1998) [PubMed: 9683613] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS SLOS LEU-119; ARG-244 AND CYS-248. |
| [2] | "Molecular cloning and expression of the human delta7-sterol reductase." Moebius F.F., Fitzky B.U., Lee J.N., Paik Y.K., Glossmann H. Proc. Natl. Acad. Sci. U.S.A. 95:1899-1902(1998) [PubMed: 9465114] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Liver. |
| [3] | "The human lamin B receptor/sterol reductase multigene family." Holmer L., Pezhman A., Worman H.J. Genomics 54:469-476(1998) [PubMed: 9878250] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. |
| [4] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain. |
| [5] | "Mutations in the human sterol delta 7-reductase gene at 11q12-13 cause Smith-Lemli-Opitz syndrome." Wassif C.A., Maslen C., Kachilele-Linjewile S., Lin D., Linck L.M., Conner W.E., Steiner R.D., Porter F.D. Am. J. Hum. Genet. 63:55-62(1998) [PubMed: 9634533] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 14-475. Tissue: Liver. |
| [6] | "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY. |
| [7] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [8] | "Mutations in the delta7-sterol reductase gene in patients with the Smith-Lemli-Opitz syndrome." Fitzky B.U., Witsch-Baumgartner M., Erdel M., Lee J.N., Paik Y.-K., Glossmann H., Utermann G., Moebius F.F. Proc. Natl. Acad. Sci. U.S.A. 95:8181-8186(1998) [PubMed: 9653161] [Abstract] Cited for: VARIANTS SLOS SER-51; MET-93; PRO-99; PRO-157; VAL-247; LEU-326; TRP-352; SER-380; CYS-404 AND SER-410. |
| [9] | "Mutational spectrum in the Delta7-sterol reductase gene and genotype-phenotype correlation in 84 patients with Smith-Lemli-Opitz syndrome." Witsch-Baumgartner M., Fitzky B.U., Ogorelkova M., Kraft H.G., Moebius F.F., Glossmann H., Seedorf U., Gillessen-Kaesbach G., Hoffmann G.F., Clayton P., Kelley R.I., Utermann G. Am. J. Hum. Genet. 66:402-412(2000) [PubMed: 10677299] [Abstract] Cited for: VARIANTS SLOS SER-51; MET-93; PRO-99; HIS-107; PRO-109; ASP-147; MET-154; PRO-157; LEU-169; CYS-182; CYS-242; VAL-247; MET-281; ILE-289; GLY-311; TYR-311; HIS-324; LEU-326; GLN-352; TRP-352; ALA-353; CYS-362; TYR-380; ARG-380; SER-380; LEU-397; CYS-404; SER-404; HIS-408; SER-410; ARG-410; CYS-443; GLN-446; GLN-448; LYS-448 AND LEU-450. |
| [10] | "Mutation analysis and description of sixteen RSH/Smith-Lemli-Opitz syndrome patients: polymerase chain reaction-based assays to simplify genotyping." Krakowiak P.A., Nwokoro N.A., Wassif C.A., Battaile K.P., Nowaczyk M.J.M., Connor W.E., Maslen C., Steiner R.D., Porter F.D. Am. J. Med. Genet. 94:214-227(2000) [PubMed: 10995508] [Abstract] Cited for: VARIANT SLOS ILE-289. |
| [11] | "Novel mutations in the 7-dehydrocholesterol reductase gene of 13 patients with Smith-Lemli-Opitz syndrome." Jira P.E., Wanders R.J.A., Smeitink J.A.M., De Jong J., Wevers R.A., Oostheim W., Tuerlings J.H.A.M., Hennekam R.C.M., Sengers R.C.A., Waterham H.R. Ann. Hum. Genet. 65:229-236(2001) [PubMed: 11427181] [Abstract] Cited for: VARIANTS SLOS MET-93; PRO-109; LEU-119; MET-154; LEU-182; TYR-183; GLU-198; HIS-242; ARG-244; CYS-248 AND LEU-255. |
| [12] | "Frequency gradients of DHCR7 mutations in patients with Smith-Lemli-Opitz syndrome in Europe: evidence for different origins of common mutations." Witsch-Baumgartner M., Ciara E., Loffler J., Menzel H.J., Seedorf U., Burn J., Gillessen-Kaesbach G., Hoffmann G.F., Fitzky B.U., Mundy H., Clayton P., Kelley R.I., Krajewska-Walasek M., Utermann G. Eur. J. Hum. Genet. 9:45-50(2001) [PubMed: 11175299] [Abstract] Cited for: VARIANTS SLOS MET-93; LEU-326; TRP-352 AND CYS-404. |
| [13] | "Identification of three patients with a very mild form of Smith-Lemli-Opitz syndrome." Langius F.A., Waterham H.R., Romeijn G.J., Oostheim W., de Barse M.M., Dorland L., Duran M., Beemer F.A., Wanders R.J., Poll-The B.T. Am. J. Med. Genet. A 122:24-29(2003) [PubMed: 12949967] [Abstract] Cited for: VARIANT SLOS LYS-448. |
| [14] | "Identification of nine novel DHCR7 missense mutations in patients with Smith-Lemli-Opitz syndrome (SLOS)." Waye J.S., Krakowiak P.A., Wassif C.A., Sterner A.L., Eng B., Nakamura L.M., Nowaczyk M.J.M., Porter F.D. Hum. Mutat. 26:59-59(2005) [PubMed: 15954111] [Abstract] Cited for: VARIANTS SLOS PRO-68; CYS-113; VAL-138; LEU-145; SER-235; CYS-242; THR-297; ARG-344; CYS-404; TYR-405; HIS-408 AND PRO-426. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| AF096305 mRNA. Translation: AAD09766.1. AF034544 mRNA. Translation: AAC05086.1. AF110060 Genomic DNA. Translation: AAD24762.1. AF067127 mRNA. Translation: AAD02816.1. BC000054 mRNA. Translation: AAH00054.1. AF062481 mRNA. Translation: AAC18345.1. | |
| IPI | IPI00294501. |
| RefSeq | NP_001351.2. |
| UniGene | Hs.503134 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | Q9UBM7. 7 interactions. |
PTM databases | |
| PhosphoSite | Q9UBM7. |
Proteomic databases | |
| PeptideAtlas | Q9UBM7. |
| PRIDE | Q9UBM7. |
Genome annotation databases | |
| Ensembl | ENSG00000172893. Homo sapiens. [Contig view] |
| GeneID | 1717. |
| KEGG | hsa:1717. |
| UCSC | uc001oqk.1. human. |
Organism-specific databases | |
| GeneCards | GC11M070823. |
| HGNC | HGNC:2860. DHCR7. |
| MIM | 270400. phenotype. 602858. gene. |
| Orphanet | 818. Smith-Lemli-Opitz syndrome. |
| PharmGKB | PA27321. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | Q9UBM7. |
| HOVERGEN | Q9UBM7. |
| OMA | Q9UBM7. WAKTPPV. |
Enzyme and pathway databases | |
| BRENDA | 1.3.1.21. 247. |
| Reactome | REACT_602. Metabolism of lipids and lipoproteins. |
Gene expression databases | |
| ArrayExpress | Q9UBM7. |
| Bgee | Q9UBM7. |
| CleanEx | HS_DHCR7. |
| GermOnline | ENSG00000172893. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR001171. Ergosterol_biosynth_ERG4_ERG24. IPR018083. Sterol_reductase_CS. [Graphical view] |
| Pfam | PF01222. ERG4_ERG24. 1 hit. [Graphical view] |
| PROSITE | PS01017. STEROL_REDUCT_1. 1 hit. PS01018. STEROL_REDUCT_2. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| DrugBank | DB00157. NADH. |
| NextBio | 6956. |
| SOURCE | Search... |
Entry information
| Entry name | DHCR7_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9UBM7 Secondary accession number(s): O60492, O60717 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 11 Human chromosome 11: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PATHWAY comments Index of metabolic and biosynthesis pathways |
| SIMILARITY comments Index of protein domains and families |

Clusters with


