Q15392 (DHC24_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Delta(24)-sterol reductase
EC=1.3.1.72

Alternative name(s):
24-dehydrocholesterol reductase
3-beta-hydroxysterol delta-24-reductase
Diminuto/dwarf1 homolog
Seladin-1

Gene names

Name:	DHCR24
Synonyms:	KIAA0018

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	516 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the reduction of the delta-24 double bond of sterol intermediates. Protects cells from oxidative stress by reducing caspase 3 activity during apoptosis induced by oxidative stress. Also protects against amyloid-beta peptide-induced apoptosis. Ref.1 Ref.2 Ref.9
Catalytic activity	5-alpha-cholest-7-en-3-beta-ol + NADP+ = 5-alpha-cholesta-7,24-dien-3-beta-ol + NADPH.
Cofactor	FAD.
Pathway	Steroid biosynthesis; cholesterol biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein. Golgi apparatus membrane; Single-pass membrane protein Ref.1 Ref.9.
Tissue specificity	Highly expressed in brain and adrenal gland with moderate expression in liver, lung, spleen, prostate and spinal cord. Low expression in heart, uterus and prostate. Undetectable in blood cells. In the brain, strongly expressed in cortical regions, substantia nigra, caudate nucleus, hippocampus, medulla oblongata and pons. In brains affected by Alzheimer disease, expression in the inferior temporal lobe is substantially lower than in the frontal cortex. Ref.1 Ref.2
Involvement in disease	Defects in DHCR24 are the cause of desmosterolosis (DESMOS) [MIM:602398]. It is a rare autosomal recessive disorder characterized by multiple congenital anomalies and elevated levels of the cholesterol precursor desmosterol in plasma, tissue, and cultured cells. Ref.2
Sequence similarities	Belongs to the FAD-binding oxidoreductase/transferase type 4 family. Contains 1 FAD-binding PCMH-type domain.
Sequence caution	The sequence BAA02806.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Disease	Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Ligand	FAD NADP
Molecular function	Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	anti-apoptosis Inferred from direct assay. Source: UniProtKB cell cycle arrest Non-traceable author statement. Source: UniProtKB cholesterol biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from direct assay Ref.1. Source: UniProtKB neuroprotection Non-traceable author statement. Source: UniProtKB response to oxidative stress Inferred from expression pattern Ref.1. Source: UniProtKB skin development Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum membrane Non-traceable author statement Ref.1. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	UDP-N-acetylmuramate dehydrogenase activity Inferred from electronic annotation. Source: InterPro delta24-sterol reductase activity Inferred from electronic annotation. Source: EC enzyme binding Inferred from physical interaction. Source: UniProtKB flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro peptide antigen binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 22	22	Potential
	Chain	23 – 516	494	Delta(24)-sterol reductase		PRO_0000007230
Regions
	Topological domain	23 – 31	9	Lumenal Potential
	Transmembrane	32 – 52	21	Helical; Potential
	Topological domain	53 – 516	464	Cytoplasmic Potential
	Domain	58 – 234	177	FAD-binding PCMH-type
	Nucleotide binding	163 – 175	13	FAD Potential
Sites
	Site	122 – 123	2	Cleavage; by caspase Potential
	Site	383 – 384	2	Cleavage; by caspase Potential
Amino acid modifications
	Modified residue	110	1	Phosphothreonine Ref.7
Natural variations
	Natural variant	191	1	E → K in DESMOS. Ref.2 Corresponds to variant rs28939093 [ dbSNP | Ensembl ].		VAR_012732
	Natural variant	294	1	N → T in DESMOS. Ref.2		VAR_012733
	Natural variant	306	1	K → N in DESMOS. Ref.2		VAR_012734
	Natural variant	471	1	Y → S in DESMOS. Ref.2 Corresponds to variant rs28939092 [ dbSNP | Ensembl ].		VAR_012735

Sequences

	Sequence		Length	Mass (Da)
	Q15392 [UniParc]. Last modified January 31, 2002. Version 2. Checksum: F9A769446FE19E59	FASTA	516	60,101
	10 20 30 40 50 60 MEPAVSLAVC ALLFLLWVRL KGLEFVLIHQ RWVFVCLFLL PLSLIFDIYY YVRAWVVFKL 70 80 90 100 110 120 SSAPRLHEQR VRDIQKQVRE WKEQGSKTFM CTGRPGWLTV SLRVGKYKKT HKNIMINLMD 130 140 150 160 170 180 ILEVDTKKQI VRVEPLVTMG QVTALLTSIG WTLPVLPELD DLTVGGLIMG TGIESSSHKY 190 200 210 220 230 240 GLFQHICTAY ELVLADGSFV RCTPSENSDL FYAVPWSCGT LGFLVAAEIR IIPAKKYVKL 250 260 270 280 290 300 RFEPVRGLEA ICAKFTHESQ RQENHFVEGL LYSLDEAVIM TGVMTDEAEP SKLNSIGNYY 310 320 330 340 350 360 KPWFFKHVEN YLKTNREGLE YIPLRHYYHR HTRSIFWELQ DIIPFGNNPI FRYLFGWMVP 370 380 390 400 410 420 PKISLLKLTQ GETLRKLYEQ HHVVQDMLVP MKCLQQALHT FQNDIHVYPI WLCPFILPSQ 430 440 450 460 470 480 PGLVHPKGNE AELYIDIGAY GEPRVKHFEA RSCMRQLEKF VRSVHGFQML YADCYMNREE 490 500 510 FWEMFDGSLY HKLREKLGCQ DAFPEVYDKI CKAARH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The human DIMINUTO/DWARF1 homolog seladin-1 confers resistance to Alzheimer's disease-associated neurodegeneration and oxidative stress." Greeve I., Hermans-Borgmeyer I., Brellinger C., Kasper D., Gomez-Isla T., Behl C., Levkau B., Nitsch R.M. J. Neurosci. 20:7345-7352(2000) [PubMed: 11007892] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Tissue: Brain.
[2]	"Mutations in the 3beta-hydroxysterol delta24-reductase gene cause desmosterolosis, an autosomal recessive disorder of cholesterol biosynthesis." Waterham H.R., Koster J., Romeijn G.J., Hennekam R.C.M., Vreken P., Andersson H.C., FitzPatrick D.R., Kelley R.I., Wanders R.J.A. Am. J. Hum. Genet. 69:685-694(2001) [PubMed: 11519011] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, TISSUE SPECIFICITY, VARIANTS DESMOS LYS-191; THR-294; ASN-306 AND SER-471.
[3]	"Prediction of the coding sequences of unidentified human genes. I. The coding sequences of 40 new genes (KIAA0001-KIAA0040) deduced by analysis of randomly sampled cDNA clones from human immature myeloid cell line KG-1." Nomura N., Miyajima N., Sazuka T., Tanaka A., Kawarabayasi Y., Sato S., Nagase T., Seki N., Ishikawa K., Tabata S. DNA Res. 1:27-35(1994) [PubMed: 7584026] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow.
[4]	Ohara O., Nagase T., Kikuno R., Nomura N. Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO C-TERMINUS.
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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 and Placenta.
[7]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-110, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[8]	"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].
[9]	"The membrane topological analysis of 3 {beta}-hydroxysteroid-delta24 reductase (DHCR24) on endoplasmic reticulum." Lu X., Li Y., Liu J., Cao X., Wang X., Wang D., Seo H., Gao B. J. Mol. Endocrinol. 0:0-0(2011) [PubMed: 22010141] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF261758 mRNA. Translation: AAG17288.1. AF398342 , AF398336, AF398337, AF398338, AF398339, AF398340, AF398341 Genomic DNA. Translation: AAL15644.1. D13643 mRNA. Translation: BAA02806.3. Different initiation. CH471059 Genomic DNA. Translation: EAX06663.1. CH471059 Genomic DNA. Translation: EAX06664.1. BC004375 mRNA. Translation: AAH04375.1. BC011669 mRNA. Translation: AAH11669.1.
IPI	IPI00016703.
RefSeq	NP_055577.1. NM_014762.3.
UniGene	Hs.498727.
3D structure databases
ProteinModelPortal	Q15392.
SMR	Q15392. Positions 122-243.
ModBase	Search...
Protein-protein interaction databases
STRING	Q15392.
PTM databases
PhosphoSite	Q15392.
Polymorphism databases
DMDM	20141421.
Proteomic databases
PeptideAtlas	Q15392.
PRIDE	Q15392.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000371269; ENSP00000360316; ENSG00000116133.
GeneID	1718.
KEGG	hsa:1718.
UCSC	uc001cyc.1. human.
Organism-specific databases
CTD	1718.
GeneCards	GC01M055315.
H-InvDB	HIX0000624.
HGNC	HGNC:2859. DHCR24.
HPA	HPA028826.
MIM	602398. phenotype. 606418. gene.
neXtProt	NX_Q15392.
Orphanet	35107. Desmosterolosis.
PharmGKB	PA27320.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG04986.
HOGENOM	HBG389990.
HOVERGEN	HBG051349.
InParanoid	Q15392.
OMA	IESSSHI.
OrthoDB	EOG4FXR76.
PhylomeDB	Q15392.
Enzyme and pathway databases
Reactome	REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q15392.
Bgee	Q15392.
CleanEx	HS_DHCR24.
Genevestigator	Q15392.
GermOnline	ENSG00000116133. Homo sapiens.
Family and domain databases
InterPro	IPR016166. FAD-bd_2. IPR016168. FAD-linked_Oxase_FAD-bd_sub2. IPR006094. Oxid_FAD_bind_N. [Graphical view]
Gene3D	G3DSA:3.30.465.20. FAD-linked_oxidase_FAD-bd_sub2. 1 hit.
KO	K09828.
Pfam	PF01565. FAD_binding_4. 1 hit. [Graphical view]
SUPFAM	SSF56176. FAD-binding_2. 1 hit.
PROSITE	PS51387. FAD_PCMH. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	6960.
SOURCE	Search...

Entry information

Entry name

DHC24_HUMAN

Accession

Primary (citable) accession number: Q15392
Secondary accession number(s): D3DQ51, Q9HBA8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	January 31, 2002
Last modified:	January 25, 2012
This is version 108 of the entry and version 2 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.