Q15125 (EBP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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)

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.8 Ref.9 Ref.10 Ref.11
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 Transmembrane helix
Molecular function	Isomerase
PTM	Acetylation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Traceable author statement. Source: Reactome skeletal system development Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	cholestenol delta-isomerase activity Inferred from electronic annotation. Source: EC drug transmembrane transporter activity Traceable author statement. Source: ProtInc steroid delta-isomerase activity Traceable author statement. Source: ProtInc transmembrane signaling receptor activity 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	Helical; Potential
	Transmembrane	66 – 86	21	Helical; Potential
	Transmembrane	121 – 141	21	Helical; Potential
	Transmembrane	185 – 205	21	Helical; Potential
Amino acid modifications
	Modified residue	2	1	N-acetylthreonine By similarity
Natural variations
	Natural variant	80	1	E → K in CDPX2. Ref.9 Corresponds to variant rs28936073 [ dbSNP | Ensembl ].		VAR_012105
	Natural variant	110	1	R → Q in CDPX2. Ref.8		VAR_012106
	Natural variant	147	1	R → G in CDPX2. Ref.11		VAR_012107
	Natural variant	147	1	R → H in CDPX2. Ref.9 Ref.10 Corresponds to variant rs28935174 [ dbSNP | Ensembl ].		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.7
	Mutagenesis	121	1	M → A: Reduces catalytic activity to less than 35% of wild-type. Ref.7
	Mutagenesis	121	1	M → V: No effect on catalytic activity. Ref.7
	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.7
	Mutagenesis	189	1	F → L: No effect on catalytic activity. Ref.7
	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 [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]	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 (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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
EMBL GenBank DDBJ	Z37986 mRNA. Translation: CAA86068.1. CR456815 mRNA. Translation: CAG33096.1. CR542094 mRNA. Translation: CAG46891.1. AF196969 Genomic DNA. No translation available. AF196972 Genomic DNA. No translation available. CH471224 Genomic DNA. Translation: EAW50773.1. BC001549 mRNA. Translation: AAH01549.1. BC001572 mRNA. Translation: AAH01572.1. BC046501 mRNA. Translation: AAH46501.1.
IPI	IPI00008599.
PIR	B56122.
RefSeq	NP_006570.1. NM_006579.2.
UniGene	Hs.30619.
3D structure databases
ProteinModelPortal	Q15125.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q15125. 1 interaction.
STRING	Q15125.
Polymorphism databases
DMDM	17374795.
Proteomic databases
PeptideAtlas	Q15125.
PRIDE	Q15125.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000495186; ENSP00000417052; ENSG00000147155.
GeneID	10682.
KEGG	hsa:10682.
UCSC	uc004djx.2. human.
Organism-specific databases
CTD	10682.
GeneCards	GC0XP048380.
H-InvDB	HIX0203294.
HGNC	HGNC:3133. EBP.
HPA	HPA003130.
MIM	300205. gene. 302960. phenotype.
neXtProt	NX_Q15125.
Orphanet	35173. X-linked dominant chondrodysplasia punctata.
PharmGKB	PA27587.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG10454.
GeneTree	ENSGT00530000063715.
HOGENOM	HBG590959.
HOVERGEN	HBG018176.
InParanoid	Q15125.
OMA	PTWHILA.
OrthoDB	EOG45490D.
PhylomeDB	Q15125.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000147155-MONOMER.
BRENDA	5.3.3.5. 2681.
Reactome	REACT_22258. 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]
KO	K01824.
PANTHER	PTHR14207. EBP. 1 hit.
Pfam	PF05241. EBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	40611.
SOURCE	Search...

Entry information

Entry name

EBP_HUMAN

Accession

Primary (citable) accession number: Q15125
Secondary accession number(s): Q6FGL3, Q6IBI9

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 18, 2001
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 104 of the entry and version 3 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.