7-dehydrocholesterol reductase - Homo sapiens (Human)

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Q9UBM7 (DHCR7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified January 25, 2012. Version 113. History...

Clusters with 100%, 90%, 50% identity |

Documents (6) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
7-dehydrocholesterol reductase
Short name=7-DHC reductase
EC=1.3.1.21

Alternative name(s):
Putative sterol reductase SR-2
Sterol Delta(7)-reductase

Gene names

Name:	DHCR7
Synonyms:	D7SR

Organism

Homo sapiens (Human)

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.
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	Steroid biosynthesis; cholesterol biosynthesis.
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.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17
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 Transmembrane helix
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Inferred from mutant phenotype Ref.2. Source: UniProtKB
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nuclear outer membrane Inferred from direct assay Ref.3. Source: UniProtKB
Molecular function	7-dehydrocholesterol reductase activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

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

Helical; Potential

Transmembrane

154 – 174

Helical; Potential

Transmembrane

177 – 197

Helical; Potential

Transmembrane

266 – 286

Helical; Potential

Transmembrane

306 – 326

Helical; Potential

Transmembrane

331 – 351

Helical; Potential

Transmembrane

420 – 440

Helical; Potential

Amino acid modifications

Modified residue

Phosphoserine Ref.6 Ref.7 Ref.8 Ref.9

Natural variations

Natural variant

P → S in SLOS. Ref.11 Ref.12

VAR_012717

Natural variant

L → P in SLOS. Ref.17

VAR_023148

Natural variant

T → M in SLOS. Ref.11 Ref.12 Ref.14 Ref.15

VAR_012718

Natural variant

L → P in SLOS. Ref.11 Ref.12

VAR_012719

Natural variant

107

Q → H in SLOS. Ref.12

VAR_023149

Natural variant

109

L → P in SLOS. Ref.12 Ref.14

VAR_023150

Natural variant

113

S → C in SLOS. Ref.17

VAR_023151

Natural variant

119

H → L in SLOS. Ref.1 Ref.14
Corresponds to variant rs28938174 [ dbSNP | Ensembl ].

VAR_012720

Natural variant

138

G → V in SLOS. Ref.17

VAR_023152

Natural variant

145

I → L in SLOS. Ref.17

VAR_023153

Natural variant

147

G → D in SLOS. Ref.12

VAR_023154

Natural variant

154

T → M in SLOS. Ref.12 Ref.14

VAR_023155

Natural variant

157

L → P in SLOS. Ref.11 Ref.12

VAR_012721

Natural variant

169

S → L in SLOS. Ref.12

VAR_023156

Natural variant

182

W → C in SLOS. Ref.12

VAR_023157

Natural variant

182

W → L in SLOS. Ref.14

VAR_023158

Natural variant

183

C → Y in SLOS. Ref.14

VAR_023159

Natural variant

198

K → E in SLOS. Ref.14

VAR_023160

Natural variant

235

F → S in SLOS. Ref.17

VAR_023161

Natural variant

242

R → C in SLOS. Ref.12 Ref.17

VAR_023162

Natural variant

242

R → H in SLOS. Ref.14

VAR_023163

Natural variant

244

G → R in SLOS. Ref.1 Ref.14

VAR_012722

Natural variant

247

A → V in SLOS. Ref.11 Ref.12

VAR_012723

Natural variant

248

W → C in SLOS. Ref.1 Ref.14
Corresponds to variant rs28939698 [ dbSNP | Ensembl ].

VAR_012724

Natural variant

255

F → L in SLOS. Ref.14

VAR_023164

Natural variant

281

V → M in SLOS. Ref.12

VAR_023165

Natural variant

289

T → I in SLOS. Ref.12 Ref.13

VAR_012725

Natural variant

297

I → T in SLOS. Ref.17

VAR_023166

Natural variant

311

C → G in SLOS. Ref.12

VAR_023167

Natural variant

311

C → Y in SLOS. Ref.12

VAR_023168

Natural variant

324

Y → H in SLOS. Ref.12

VAR_023169

Natural variant

326

V → L in SLOS. Ref.11 Ref.12 Ref.15

VAR_012726

Natural variant

344

G → R in SLOS. Ref.17

VAR_023170

Natural variant

352

R → Q in SLOS. Ref.12

VAR_023171

Natural variant

352

R → W in SLOS. Ref.11 Ref.12 Ref.15

VAR_012727

Natural variant

353

V → A in SLOS. Ref.12

VAR_023172

Natural variant

362

R → C in SLOS. Ref.12

VAR_023173

Natural variant

380

C → R in SLOS. Ref.12

VAR_023174

Natural variant

380

C → S in SLOS. Ref.11 Ref.12

VAR_012728

Natural variant

380

C → Y in SLOS. Ref.12

VAR_023175

Natural variant

397

S → L in SLOS. Ref.12

VAR_023176

Natural variant

404

R → C in SLOS. Ref.11 Ref.12 Ref.15 Ref.17

VAR_012729

Natural variant

404

R → S in SLOS. Ref.12

VAR_023177

Natural variant

405

H → Y in SLOS. Ref.17

VAR_023178

Natural variant

408

Y → H in SLOS. Ref.12 Ref.17

VAR_023179

Natural variant

410

G → R in SLOS. Ref.12

VAR_023180

Natural variant

410

G → S in SLOS. Ref.11 Ref.12

VAR_012730

Natural variant

425

G → S.
Corresponds to variant rs760242 [ dbSNP | Ensembl ].

VAR_052154

Natural variant

426

H → P in SLOS. Ref.17

VAR_023181

Natural variant

443

R → C in SLOS. Ref.12

VAR_023182

Natural variant

446

R → Q in SLOS. Ref.12

VAR_023183

Natural variant

448

E → K in SLOS; mild. Ref.12 Ref.16

VAR_016975

Natural variant

448

E → Q in SLOS. Ref.12

VAR_023184

Natural variant

450

R → L in SLOS. Ref.12

VAR_023185

Experimental info

Sequence conflict

S → L in AAC05086. Ref.2

Sequence conflict

S → A in AAC18345. Ref.5

Sequences

Sequence

Length

Mass (Da)

Tools

Q9UBM7 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 7D726443834C4EEB
Show »

FASTA

475

54,489

        10         20         30         40         50         60 
MAAKSQPNIP KAKSLDGVTN DRTASQGQWG RAWEVDWFSL ASVIFLLLFA PFIVYYFIMA 

        70         80         90        100        110        120 
CDQYSCALTG PVVDIVTGHA RLSDIWAKTP PITRKAAQLY TLWVTFQVLL YTSLPDFCHK 

       130        140        150        160        170        180 
FLPGYVGGIQ EGAVTPAGVV NKYQINGLQA WLLTHLLWFA NAHLLSWFSP TIIFDNWIPL 

       190        200        210        220        230        240 
LWCANILGYA VSTFAMVKGY FFPTSARDCK FTGNFFYNYM MGIEFNPRIG KWFDFKLFFN 

       250        260        270        280        290        300 
GRPGIVAWTL INLSFAAKQR ELHSHVTNAM VLVNVLQAIY VIDFFWNETW YLKTIDICHD 

       310        320        330        340        350        360 
HFGWYLGWGD CVWLPYLYTL QGLYLVYHPV QLSTPHAVGV LLLGLVGYYI FRVANHQKDL 

       370        380        390        400        410        420 
FRRTDGRCLI WGRKPKVIEC SYTSADGQRH HSKLLVSGFW GVARHFNYVG DLMGSLAYCL 

       430        440        450        460        470 
ACGGGHLLPY FYIIYMAILL THRCLRDEHR CASKYGRDWE RYTAAVPYRL LPGIF

« Hide

References

	« Hide 'large scale' referencesShow '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]	"Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[7]	"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. Tissue: Cervix carcinoma.
[8]	"Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY.
[9]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	"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.
[16]	"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.
[17]	"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.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	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_001157289.1. NM_001163817.1. NP_001351.2. NM_001360.2.
UniGene	Hs.503134.
3D structure databases
ProteinModelPortal	Q9UBM7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UBM7. 1 interaction.
STRING	Q9UBM7.
PTM databases
PhosphoSite	Q9UBM7.
Polymorphism databases
DMDM	20138066.
Proteomic databases
PeptideAtlas	Q9UBM7.
PRIDE	Q9UBM7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000355527; ENSP00000347717; ENSG00000172893. ENST00000407721; ENSP00000384739; ENSG00000172893.
GeneID	1717.
KEGG	hsa:1717.
UCSC	uc001oqk.1. human.
Organism-specific databases
CTD	1717.
GeneCards	GC11M071145.
H-InvDB	HIX0009899.
HGNC	HGNC:2860. DHCR7.
HPA	HPA044280.
MIM	270400. phenotype. 602858. gene.
neXtProt	NX_Q9UBM7.
Orphanet	818. Smith-Lemli-Opitz syndrome.
PharmGKB	PA27321.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16272.
GeneTree	ENSGT00390000000417.
HOGENOM	HBG592488.
HOVERGEN	HBG007825.
InParanoid	Q9UBM7.
OMA	KDCKFTG.
OrthoDB	EOG4GQQ4Q.
PhylomeDB	Q9UBM7.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000172893-MONOMER.
BRENDA	1.3.1.21. 2681.
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q9UBM7.
Bgee	Q9UBM7.
CleanEx	HS_DHCR7.
Genevestigator	Q9UBM7.
GermOnline	ENSG00000172893. Homo sapiens.
Family and domain databases
InterPro	IPR001171. Ergosterol_biosynth_ERG4_ERG24. IPR018083. Sterol_reductase_CS. [Graphical view]
KO	K00213.
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
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

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	May 1, 2000
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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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

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Web resources

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents