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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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	Chondrodysplasia punctata 2, X-linked dominant (CDPX2) [MIM:302960]: 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-8(9)-en-3-beta-ol in the plasma and tissues. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.12 Ref.13
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 Cholesterol metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
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 hemopoiesis Inferred from electronic annotation. Source: Compara skeletal system development Traceable author statement Ref.11. Source: ProtInc
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	C-8 sterol isomerase activity Inferred from electronic annotation. Source: Compara cholestenol delta-isomerase activity Inferred from electronic annotation. Source: EC drug transmembrane transporter activity Traceable author statement Ref.1. Source: ProtInc steroid delta-isomerase activity Traceable author statement Ref.11. Source: ProtInc transmembrane signaling receptor activity Traceable author statement Ref.1. 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.11 Corresponds to variant rs28936073 [ dbSNP | Ensembl ].		VAR_012105
	Natural variant	110	1	R → Q in CDPX2. Ref.10		VAR_012106
	Natural variant	147	1	R → G in CDPX2. Ref.13		VAR_012107
	Natural variant	147	1	R → H in CDPX2. Ref.11 Ref.12 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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-111; MET-121 AND PHE-189.
[8]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]	"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] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CDPX2 GLN-110.
[11]	"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] [Europe PMC] [Abstract] Cited for: VARIANTS CDPX2 LYS-80 AND HIS-147.
[12]	"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] [Europe PMC] [Abstract] Cited for: VARIANT CDPX2 HIS-147.
[13]	"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] [Europe PMC] [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	9606.ENSP00000417052.
PTM databases
PhosphoSite	Q15125.
Polymorphism databases
DMDM	17374795.
Proteomic databases
PaxDb	Q15125.
PeptideAtlas	Q15125.
PRIDE	Q15125.
Protocols and materials databases
DNASU	10682.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000495186; ENSP00000417052; ENSG00000147155. ENST00000598515; ENSP00000471792; ENSG00000268394.
GeneID	10682.
KEGG	hsa:10682.
UCSC	uc004djx.4. human.
Organism-specific databases
CTD	10682.
GeneCards	GC0XP048380.
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	NOG331138.
HOGENOM	HOG000204543.
HOVERGEN	HBG018176.
InParanoid	Q15125.
KO	K01824.
OMA	VLVVTTW.
OrthoDB	EOG45490D.
PhylomeDB	Q15125.
Enzyme and pathway databases
BioCyc	MetaCyc:ENSG00000147155-MONOMER.
BRENDA	5.3.3.5. 2681.
Reactome	REACT_111217. Metabolism.
SABIO-RK	Q15125.
UniPathway	UPA00063.
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. PTHR14207. 1 hit.
Pfam	PF05241. EBP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q15125.
ChEMBL	CHEMBL4931.
GenomeRNAi	10682.
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:	May 1, 2013
This is version 117 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.