Reviewed, UniProtKB/Swiss-Prot Q15125 (EBP_HUMAN)

Names and origin

Protein names

Recommended name:
    3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase
    EC=5.3.3.5
Alternative name(s):
    Cholestenol Delta-isomerase
    Delta(8)-Delta(7) sterol isomerase
      Short name=D8-D7 sterol isomerase
    Emopamil-binding protein

Gene names

Name:

EBP

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	230 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 conversion of Delta(8)-sterols to their corresponding Delta(7)-isomers.
Catalytic activity	5-alpha-cholest-7-en-3-beta-ol = 5-alpha-cholest-8-en-3-beta-ol.
Pathway	Steroid biosynthesis; cholesterol biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein.
Involvement in disease	Defects in EBP are the cause of chondrodysplasia punctata X-linked dominant type 2 (CDPX2) [MIM:302960]; also known as Conradi-Hunermann-Happle syndrome. CDP is a clinically and genetically heterogeneous disorder characterized by punctiform calcification of the bones. The key clinical features of CDPX2 are chondrodysplasia punctata, linear ichthyosis, cataracts and short stature. CDPX2 is a rare disorder of defective cholesterol biosynthesis, biochemically characterized by an increased amount of 8-dehydrocholesterol and cholest-89-en-3-beta-ol in the plasma and tissues. Ref.7 Ref.8 Ref.9 Ref.10
Miscellaneous	Binds to the phenylalkylamine calcium-ion antagonist emopamil, an anti-ischemic drug.
Sequence similarities	Belongs to the EBP family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Endoplasmic reticulum Membrane
Disease	Cataract Disease mutation Dwarfism Ichthyosis
Domain	Transmembrane
Molecular function	Isomerase
PTM	Acetylation
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW skeletal system development Ref.8 Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum Ref.1 Inferred from direct assay. Source: HPA integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	cholestenol delta-isomerase activity Inferred from electronic annotation. Source: EC drug transporter activity Ref.1 Traceable author statement. Source: ProtInc steroid delta-isomerase activity Ref.8 Traceable author statement. Source: ProtInc transmembrane receptor activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed By similarity
	Chain	2 – 230	229	3-beta-hydroxysteroid-Delta(8),Delta(7)-isomerase		PRO_0000174342
Regions
	Transmembrane	29 – 49	21	Potential
	Transmembrane	66 – 86	21	Potential
	Transmembrane	121 – 141	21	Potential
	Transmembrane	185 – 205	21	Potential
Amino acid modifications
	Modified residue	2	1	N-acetylthreonine By similarity
Natural variations
	Natural variant	80	1	E → K in CDPX2. Ref.8		VAR_012105
	Natural variant	110	1	R → Q in CDPX2. Ref.7		VAR_012106
	Natural variant	147	1	R → G in CDPX2. Ref.10		VAR_012107
	Natural variant	147	1	R → H in CDPX2. Ref.8 Ref.9		VAR_012108
Experimental info
	Mutagenesis	68	1	W → A: Reduces catalytic activity to less than 35% of wild-type.
	Mutagenesis	75	1	I → A: Reduces catalytic activity to less than 35% of wild-type.
	Mutagenesis	76	1	H → A: Reduces catalytic activity to less than 10% of wild-type.
	Mutagenesis	80	1	E → A: Reduces catalytic activity to less than 10% of wild-type.
	Mutagenesis	111	1	Y → W: Reduces catalytic activity to less than 2% of wild-type. Ref.6
	Mutagenesis	121	1	M → A: Reduces catalytic activity to less than 35% of wild-type. Ref.6
	Mutagenesis	121	1	M → V: No effect on catalytic activity. Ref.6
	Mutagenesis	122	1	E → A: Reduces catalytic activity to less than 10% of wild-type.
	Mutagenesis	125	1	T → A: Reduces catalytic activity to less than 10% of wild-type.
	Mutagenesis	188	1	Y → A: Reduces catalytic activity to less than 35% of wild-type.
	Mutagenesis	189	1	F → A: Reduces catalytic activity to less than 35% of wild-type. Ref.6
	Mutagenesis	189	1	F → L: No effect on catalytic activity. Ref.6
	Mutagenesis	193	1	N → A: Reduces catalytic activity to less than 10% of wild-type.
	Mutagenesis	196	1	W → A: Reduces catalytic activity to less than 10% of wild-type.
	Sequence conflict	187 – 188	2	FY → IF in CAG33096. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q15125-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 3931A9DE3DBAFA04	FASTA	230	26,353
	10 20 30 40 50 60 MTTNAGPLHP YWPQHLRLDN FVPNDRPTWH ILAGLFSVTG VLVVTTWLLS GRAAVVPLGT 70 80 90 100 110 120 WRRLSLCWFA VCGFIHLVIE GWFVLYYEDL LGDQAFLSQL WKEYAKGDSR YILGDNFTVC 130 140 150 160 170 180 METITACLWG PLSLWVVIAF LRQHPLRFIL QLVVSVGQIY GDVLYFLTEH RDGFQHGELG 190 200 210 220 230 HPLYFWFYFV FMNALWLVLP GVLVLDAVKH LTHAQSTLDA KATKAKSKKN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Phenylalkylamine Ca2+ antagonist binding protein. Molecular cloning, tissue distribution, and heterologous expression." Hanner M., Moebius F.F., Weber F., Grabner M., Striessnig J., Glossmann H. J. Biol. Chem. 270:7551-7557(1995) [PubMed: 7706302] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The DNA sequence of the human X chromosome." Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R. Nature 434:325-337(2005) [PubMed: 15772651] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: Cervix and Placenta.
[5]	"Histidine77, glutamic acid81, glutamic acid123, threonine126, asparagine194, and tryptophan197 of the human emopamil binding protein are required for in vivo sterol delta 8-delta 7 isomerization." Moebius F.F., Soellner K.E.M., Fiechtner B., Huck C.W., Bonn G., Glossmann H. Biochemistry 38:1119-1127(1999) [PubMed: 9894009] [Abstract] Cited for: MUTAGENESIS.
[6]	"Cloning of an emopamil-binding protein (EBP)-like protein that lacks sterol delta8-delta7 isomerase activity." Moebius F.F., Fitzky B.U., Wietzorrek G., Haidekker A., Eder A., Glossmann H. Biochem. J. 374:229-237(2003) [PubMed: 12760743] [Abstract] Cited for: MUTAGENESIS OF TYR-111; MET-121 AND PHE-189.
[7]	"Mutations in a delta(8)-delta(7) sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata." Derry J.M.J., Gormally E., Means G.D., Zhao W., Meindl A., Kelley R.I., Boyd Y., Herman G.E. Nat. Genet. 22:286-290(1999) [PubMed: 10391218] [Abstract] Cited for: VARIANT CDPX2 GLN-110.
[8]	"Mutations in the gene encoding 3-beta-hydroxysteroid-delta(8),delta(7)-isomerase cause X-linked dominant Conradi-Hunermann syndrome." Braverman N., Lin P., Moebius F.F., Obie C., Moser A., Glossmann H., Wilcox W.R., Rimoin D.L., Smith M., Kratz L., Kelley R.I., Valle D. Nat. Genet. 22:291-294(1999) [PubMed: 10391219] [Abstract] Cited for: VARIANTS CDPX2 LYS-80 AND HIS-147.
[9]	"The Conradi-Hunermann-Happle syndrome (CDPX2) and emopamil binding protein: novel mutations, and somatic and gonadal mosaicism." Has C., Bruckner-Tuderman L., Muller D., Floeth M., Folkers E., Donnai D., Traupe H. Hum. Mol. Genet. 9:1951-1955(2000) [PubMed: 10942423] [Abstract] Cited for: VARIANT CDPX2 HIS-147.
[10]	"Identification of a novel mutation in 3beta-hydroxysteroid-Delta8-Delta7-isomerase in a case of Conradi-Hunermann-Happle syndrome." Becker K., Csikos M., Horvath A., Karpati S. Exp. Dermatol. 10:286-289(2001) [PubMed: 11493318] [Abstract] Cited for: VARIANT CDPX2 GLY-147.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBLGenBankDDBJ	Z37986 mRNA. Translation: CAA86068.1. CR456815 mRNA. Translation: CAG33096.1. AF196969 Genomic DNA. No translation available. AF196972 Genomic DNA. No translation available. BC001549 mRNA. Translation: AAH01549.1. BC001572 mRNA. Translation: AAH01572.1. BC046501 mRNA. Translation: AAH46501.1.
IPI	IPI00008599.
PIR	B56122.
RefSeq	NP_006570.1.
UniGene	Hs.30619
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q15125.
Proteomic databases
PeptideAtlas	Q15125.
PRIDE	Q15125.
Genome annotation databases
Ensembl	ENST00000276096; ENSP00000276096; ENSG00000147155; Homo sapiens. [Genome view] ENST00000414061; ENSP00000405832; ENSG00000147155; Homo sapiens. [Genome view] ENST00000446158; ENSP00000390031; ENSG00000147155; Homo sapiens. [Genome view]
GeneID	10682.
KEGG	hsa:10682.
UCSC	uc004djx.2. human.
Organism-specific databases
CTD	10682.
GeneCards	GC0XP048264.
H-InvDB	HIX0016776.
HGNC	HGNC:3133. EBP.
HPA	HPA003130.
MIM	300205. gene. 302960. phenotype.
Orphanet	176. Chondrodysplasia punctata, nonrhizomelic type. 35173. X-linked dominant chondrodysplasia punctata.
PharmGKB	PA27587.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q15125.
HOVERGEN	Q15125.
OMA	PTWHILA.
Enzyme and pathway databases
BRENDA	5.3.3.5. 247.
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q15125.
Bgee	Q15125.
CleanEx	HS_EBP.
Genevestigator	Q15125.
GermOnline	ENSG00000147155. Homo sapiens.
Family and domain databases
InterPro	IPR007905. EBP. [Graphical view]
PANTHER	PTHR14207. EBP. 1 hit.
Pfam	PF05241. EBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	40611.
SOURCE	Search...

Entry information

Entry name

EBP_HUMAN

Accession

Primary (citable) accession number: Q15125
Secondary accession number(s): Q6IBI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 84 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.