The IUPHAR database of
G protein-coupled receptors
and ion channels
http://www.iuphar-db.org
Joanna Sharman
Centre for Cardiovascular Science
QMRI, Little France
University of Edinburgh
Introduction to IUPHAR-DB
The International Union of Basic and
Clinical Pharmacology Committee on
Receptor Nomenclature and Drug
Classification (NC-IUPHAR)
• Founded 1987
• Classifying the major receptor and ion channel systems
• Working with HGNC to facilitate the classification of new
sequences discovered from the Human Genome Project
• Setting up a website with access to data on all known
receptor systems, freely available to all scientists,
anywhere in the world.
IUPHAR Database scope
• About 10% of the ~30,000 genes in the human genome are
estimated to express proteins able to bind drug-like
molecules - “the druggable genome”.
• G protein-coupled receptors (GPCRs) (~400)
• Voltage-gated ion channels (~150)
• Ligand-gated ion channels (~80)
• Nuclear hormone receptors (48)
• Transporters (~95)
• Receptor tyrosine kinases (~60)
• Peer-reviewed pharmacological, chemical, genomic,
functional and anatomical information
Quick tour of IUPHAR-DB
http://www.iuphar-db.org/GPCR/ReceptorFamiliesForward
A receptor family page
An individual receptor data page
Radioligand
Radioligand
Selectivity
Selectivity
Endogenous
Endogenous
PubChem
PubChem Link
Link
Tables of ligand affinity data
Other useful IUPHAR-DB.org features
•Receptor and ion channel lists and downloadable spreadsheets
•Reports of latest receptor-ligand pairings
•Hot topics page with recent publications of interest
•Receive news of updates via RSS feed or email subscription
Overview of biological data
complexities that need to be
represented
Increasing complexity in intercellular
signalling mechanisms
• Alternative splicing and RNA editing
• GPCR heterodimerisation
• GPCR accessory proteins (e.g. RAMPs)
GPCR subtypes can be generated in several ways
R1a
R1a
R1b
R1a
R1a
R1b
AP
R1a
Source: Debbie Hay, University of Auckland
Increasing complexity in intercellular
signalling mechanisms
• Alternative splicing and RNA editing
• GPCR heterodimerisation
• GPCR accessory proteins (e.g. RAMPs)
• Ion channels can exist as tissue-and cell-specific
heteromultimeric complexes with distinct pharmacological
and biophysical properties
Current and future work
Current work - Improvement of search facility
Current work - Ligand-centered pages
Current work – Depositing data in PubChem
Current work – Redesign database to merge GPCRs and
ion channels
Curation
process
• NC-IUPHAR
coordinates a
network of >60
expert
subcommittees
• How can we make
the process more
efficient?
• Future: enable
contributors to
submit data directly
e.g. using Wiki-style
pages?
NC-IUPHAR
IUPHAR Database Edinburgh Team
Tony Harmar (Chair)
Joanna Sharman (Database Developer)
Valerie Hale (Curator)
Alumni
Rebecca Hills (Elsevier)
Martin Jones (University of Edinburgh)
Stuart Greenhill (NeuroSolutions Ltd)
Ed Rosser (Lhasa Ltd)
Database group, School of Informatics
Peter Buneman
Heiko Mueller
Loreto Bravo
Bioinformatics Team, QMRI
Donald Dunbar
Ann Hedley
Jon Manning
Michael Spedding (Servier, France) (Chair)
Tony Harmar (Edinburgh, UK) (Vice-chair)
Eliot Ohlstein (Venuvics, USA) (Vice-chair)
Anthony Davenport (Cambridge, UK) (Vice-chair)
Tom Bonner (NIH, USA)
Vincent Laudet (Lyon, France)
William Catterall (Seattle, USA)
Graeme Milligan (Glasgow, UK)
Philippe Delagrange (Servier, France)
Rick Neubig (Ann Arbor, USA)
Sir Colin Dollery (GlaxoSmithKline, UK)
John Peters (Dundee, UK)
Steven Foord (GlaxoSmithKline, UK)
Jean-Philippe Pin (Montpellier, France)
Pierre Germain (Strasbourg, France)
David Searls (GlaxoSmithKline, USA)
Sue Duckles (Irvine, USA), IUPHAR president
Sam Enna, (Kansas, USA), IUPHAR Secretary General
Urs Ruegg (Geneva, Switzerland), IUPHAR treasurer
Matt Wright (London, UK), HUGO representative