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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 2013 Dec 17;170(8):1449–1458. doi: 10.1111/bph.12444

The Concise Guide to Pharmacology 2013/14: Overview

Stephen PH Alexander 1,*, Helen E Benson 2, Elena Faccenda 2, Adam J Pawson 2, Joanna L Sharman 2, John C McGrath 3, William A Catterall 6, Michael Spedding 4, John A Peters 5, Anthony J Harmar 2
PMCID: PMC3892286  PMID: 24528237

Abstract

The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties from the IUPHAR database. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full.

This compilation of the major pharmacological targets is divided into seven areas of focus: G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets.

It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors & Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.

Table of contents

  1. 1449 OVERVIEW

  2. 1454 Adiponectin receptors

  3. 1455 Fatty acid binding proteins

  4. 1457 Sigma receptors

  5. 1459 G PROTEIN-COUPLED RECEPTORS

  6. 1462 Orphan GPCRs

  7. 1471 5-Hydroxytryptamine receptors

  8. 1474 Acetylcholine receptors (muscarinic)

  9. 1476 Adenosine receptors

  10. 1478 Adhesion Class GPCRs

  11. 1480 Adrenoceptors

  12. 1484 Angiotensin receptors

  13. 1485 Apelin receptor

  14. 1486 Bile acid receptor

  15. 1487 Bombesin receptors

  16. 1488 Bradykinin receptors

  17. 1489 Calcitonin receptors

  18. 1491 Calcium-sensing receptors

  19. 1492 Cannabinoid receptors

  20. 1494 Chemerin receptor

  21. 1495 Chemokine receptors

  22. 1500 Cholecystokinin receptors

  23. 1501 Complement peptide receptors

  24. 1502 Corticotropin-releasing factor receptors

  25. 1503 Dopamine receptors

  26. 1505 Endothelin receptors

  27. 1506 Estrogen (G protein-coupled) receptor

  28. 1507 Formylpeptide receptors

  29. 1508 Free fatty acid receptors

  30. 1510 Frizzled Class GPCRs

  31. 1511 GABAB receptors

  32. 1513 Galanin receptors

  33. 1514 Ghrelin receptor

  34. 1515 Glucagon receptor family

  35. 1517 Glycoprotein hormone receptors

  36. 1518 Gonadotrophin-releasing hormone receptors

  37. 1519 GPR18, GPR55 and GPR119

  38. 1520 Histamine receptors

  39. 1521 Hydroxycarboxylic acid receptors

  40. 1522 Kisspeptin receptors

  41. 1523 Leukotriene, lipoxin and oxoeicosanoid receptors

  42. 1525 Lysophospholipid (LPA) receptors

  43. 1526 Lysophospholipid (S1P) receptors

  44. 1527 Melanin-concentrating hormone receptors

  45. 1528 Melanocortin receptors

  46. 1529 Melatonin receptors

  47. 1530 Metabotropic glutamate receptors

  48. 1532 Motilin receptor

  49. 1533 Neuromedin U receptors

  50. 1534 Neuropeptide FF/neuropeptide AF receptors

  51. 1535 Neuropeptide S receptor

  52. 1536 Neuropeptide W/neuropeptide B receptors

  53. 1537 Neuropeptide Y receptors

  54. 1538 Neurotensin receptors

  55. 1539 Opioid receptors

  56. 1541 Orexin receptors

  57. 1542 Oxoglutarate receptor

  58. 1543 P2Y receptors

  59. 1545 Parathyroid hormone receptors

  60. 1546 Peptide P518 receptor

  61. 1547 Platelet-activating factor receptor

  62. 1548 Prokineticin receptors

  63. 1549 Prolactin-releasing peptide receptor

  64. 1550 Prostanoid receptors

  65. 1552 Proteinase-activated receptors

  66. 1553 Relaxin family peptide receptors

  67. 1555 Somatostatin receptors

  68. 1556 Succinate receptor

  69. 1557 Tachykinin receptors

  70. 1558 Thyrotropin-releasing hormone receptors

  71. 1559 Trace amine receptor

  72. 1560 Urotensin receptor

  73. 1561 Vasopressin and oxytocin receptors

  74. 1562 VIP and PACAP receptors

  75. 1582 LIGAND-GATED ION CHANNELS

  76. 1584 5-HT3 receptors

  77. 1586 GABAA receptors

  78. 1590 Glycine receptors

  79. 1592 Ionotropic glutamate receptors

  80. 1597 Nicotinic acetylcholine receptors

  81. 1601 P2X receptors

  82. 1603 ZAC

  83. 1607 ION CHANNELS

  84. 1609 Acid-sensing (proton-gated) ion channels (ASICs)

  85. 1611 Aquaporins

  86. 1612 CatSper and Two-Pore channels

  87. 1613 Chloride channels

  88. 1620 Connexins and Pannexins

  89. 1621 Cyclic nucleotide-regulated channels

  90. 1623 Epithelial sodium channels (ENaC)

  91. 1625 IP3 receptor

  92. 1626 Potassium channels

  93. 1630 Ryanodine receptor

  94. 1632 Sodium leak channel, non-selective

  95. 1633 Transient receptor potential channels

  96. 1643 Voltage-gated calcium channels

  97. 1645 Voltage-gated proton channel

  98. 1646 Voltage-gated sodium channels

  99. 1652 NUCLEAR HORMONE RECEPTORS

  100. 1654 1A. Thyroid Hormone Receptors

  101. 1655 1B. Retinoic acid receptors

  102. 1656 1C. Peroxisome proliferator-activated receptors

  103. 1657 1D. Rev-Erb receptors

  104. 1658 1F. Retinoic acid-related orphans

  105. 1659 1H. Liver X receptor-like receptors

  106. 1660 1I. Vitamin D receptor-like receptors

  107. 1661 2A. Hepatocyte nuclear factor-4 receptors

  108. 1662 2B. Retinoid X receptors

  109. 1663 2C. Testicular receptors

  110. 1664 2E. Tailless-like receptors

  111. 1665 2F. COUP-TF-like receptors

  112. 1666 3B. Estrogen-related receptors

  113. 1667 4A. Nerve growth factor IB-like receptors

  114. 1668 5A. Fushi tarazu F1-like receptors

  115. 1669 6A. Germ cell nuclear factor receptors

  116. 1670 0B. DAX-like receptors

  117. 1671 Steroid hormone receptors

  118. 1676 CATALYTIC RECEPTORS

  119. 1678 Cytokine receptor family

  120. 1684 GDNF receptor family

  121. 1685 Integrins

  122. 1688 Natriuretic peptide receptor family

  123. 1689 Pattern Recognition receptors

  124. 1692 Receptor serine/threonine kinase (RSTK) family

  125. 1695 Receptor tyrosine kinases

  126. 1702 Receptor tyrosine phosphatases (RTP)

  127. 1703 Tumour necrosis factor (TNF) receptor family

  128. 1706 TRANSPORTERS

  129. 1708 ATP-binding cassette transporter family

  130. 1712 F-type and V-type ATPases

  131. 1714 P-type ATPases

  132. 1717 SLC1 family of amino acid transporters

  133. 1719 SLC2 family of hexose and sugar alcohol transporters

  134. 1721 SLC3 and SLC7 families of heteromeric amino acid transporters (HATs)

  135. 1723 SLC4 family of bicarbonate transporters

  136. 1724 SLC5 family of sodium-dependent glucose transporters

  137. 1728 SLC6 neurotransmitter transporter family

  138. 1732 SLC8 family of sodium/calcium exchangers

  139. 1733 SLC9 family of sodium/hydrogen exchangers

  140. 1734 SLC10 family of sodium-bile acid co-transporters

  141. 1736 SLC11 family of proton-coupled metal ion transporters

  142. 1737 SLC12 family of cation-coupled chloride transporters

  143. 1739 SLC13 family of sodium-dependent sulphate/carboxylate transporters

  144. 1740 SLC14 family of facilitative urea transporters

  145. 1741 SLC15 family of peptide transporters

  146. 1742 SLC16 family of monocarboxylate transporters

  147. 1744 SLC17 phosphate and organic anion transporter family

  148. 1746 SLC18 family of vesicular amine transporters

  149. 1748 SLC19 family of vitamin transporters

  150. 1749 SLC20 family of sodium-dependent phosphate transporters

  151. 1750 SLC22 family of organic cation and anion transporters

  152. 1753 SLC23 family of ascorbic acid transporters

  153. 1754 SLC24 family of sodium/potassium/calcium exchangers

  154. 1755 SLC25 family of mitochondrial transporters

  155. 1760 SLC26 family of anion exchangers

  156. 1762 SLC27 family of fatty acid transporters

  157. 1763 SLC28 and SLC29 families of nucleoside transporters

  158. 1765 SLC30 zinc transporter family

  159. 1766 SLC31 family of copper transporters

  160. 1767 SLC32 vesicular inhibitory amino acid transporter

  161. 1768 SLC33 acetylCoA transporter

  162. 1769 SLC34 family of sodium phosphate co-transporters

  163. 1770 SLC35 family of nucleotide sugar transporters

  164. 1772 SLC36 family of proton-coupled amino acid transporters

  165. 1773 SLC37 family of phosphosugar/phosphate exchangers

  166. 1774 SLC38 family of sodium-dependent neutral amino acid transporters

  167. 1776 SLC39 family of metal ion transporters

  168. 1777 SLC40 iron transporter

  169. 1778 SLC41 family of divalent cation transporters

  170. 1779 SLC42 family of Rhesus glycoprotein ammonium transporters

  171. 1780 SLC43 family of large neutral amino acid transporters

  172. 1781 SLC44 choline transporter-like family

  173. 1782 SLC45 family of putative sugar transporters

  174. 1783 SLC46 family of folate transporters

  175. 1784 SLC47 family of multidrug and toxin extrusion transporters

  176. 1785 SLC48 heme transporter

  177. 1786 SLC49 family of FLVCR-related heme transporters

  178. 1787 SLC50 sugar transporter

  179. 1788 SLC51 family of steroid-derived molecule transporters

  180. 1789 SLC52 family of riboflavin transporters

  181. 1790 SLCO family of organic anion transporting polypeptides

  182. 1797 ENZYMES

  183. 1799 Acetylcholine turnover

  184. 1800 Adenosine turnover

  185. 1801 Amino acid hydroxylases

  186. 1802 L-Arginine turnover

  187. 1805 Carboxylases and decarboxylases

  188. 1807 Catecholamine turnover

  189. 1810 Ceramide turnover

  190. 1815 Cyclic nucleotide turnover

  191. 1820 Cytochrome P450

  192. 1824 Eicosanoid turnover

  193. 1828 Endocannabinoid turnover

  194. 1830 GABA turnover

  195. 1832 Glycerophospholipid turnover

  196. 1838 Haem oxygenase

  197. 1839 Hydrogen sulfide synthesis

  198. 1840 Inositol phosphate turnover

  199. 1842 Lanosterol biosynthesis pathway

  200. 1845 Peptidases and proteinases

  201. 1853 Protein serine/threonine kinases

  202. 1860 Sphingosine 1-phosphate turnover

  203. 1862 Thyroid hormone turnover

An Introduction to the Concise Guide to PHARMACOLOGY 2013/14

The great proliferation of drug targets in recent years has driven the need to provide a logically-organised synopsis of the nomenclature and pharmacology of these targets. This is the underlying reason for this Guide to PHARMACOLOGY 2013/14, distributed with the British Journal of Pharmacology, and produced in association with NC-IUPHAR, the Nomenclature Committees of the International Union of Basic and Clinical Pharmacology. Our intent is to produce an authoritative but user-friendly publication, which allows a rapid overview of the key properties of a wide range of established or potential pharmacological targets. The aim is to provide information succinctly, so that a newcomer to a particular target group can identify the main elements ‘at a glance’. It is not our goal to produce all-inclusive reviews of the targets presented; references to these are included in the Further Reading sections of the entries or, for many targets, the website www.guidetopharmacology.org provides access to more extensive information. The Guide to PHARMACOLOGY 2013/14 presents each entry, typically a circumscribed target class family on, wherever possible, a single page, so as to allow easy access and rapid oversight.

The list of targets present is, in many cases, a comprehensive reflection of the known targets within the particular group. Our philosophy has been to present data on human proteins wherever possible, both in terms of structural information and pharmacology. To this end, the HGNC gene nomenclature and UniProt unique ID are indicated to allow rapid access through free online databases for further information. In a few cases, where structural or pharmacological information is not available for human targets, we have used data from other species, as indicated. A priority in constructing these tables was to present agents which represent the most selective and which are available by donation or from commercial sources, now or in the near future.

The Guide is divided into seven further sections, which comprise pharmacological targets of similar structure/function. These are G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. In this overview are listed protein targets of pharmacological interest, which are not G protein-coupled receptors, ligand-gated ion channels, ion channels, nuclear hormone receptors, catalytic receptors, transporters or enzymes. In comparison with the Fifth Edition of the Guide to Receptors & Channels 1, we have added a number of new records, expanding the total to include over 2000 protein targets, primarily from increasing the content on transporters and enzymes.

The Editors of the Guide have compiled the individual records, taking advice from many Collaborators (listed on page 1452). Where appropriate, an indication is given of the status of the nomenclature, as proposed by NC-IUPHAR, published in Pharmacological Reviews. Where this guidance is lacking, advice from several prominent, independent experts has generally been obtained to produce an authoritative consensus, which attempts to fit in within the general guidelines from NC-IUPHAR 2. Tabulated data provide ready comparison of selective agents and probes (radioligands and PET ligands, where available) within a family of targets and additional commentary highlights whether species differences or ligand metabolism are potential confounding factors. We recommend that any citations to information in the Concise Guide are presented in the following format:

Alexander SPH et al. (2013). The Concise Guide to PHARMACOLOGY 2013/14. Br J Pharmacol 170: 1449–1867.

Acknowledgments

We are extremely grateful for the financial contributions from the British Pharmacological Society, the International Union of Basic and Clinical Pharmacology, the Wellcome Trust (099156/Z/12/Z]), which support the website and the University of Edinburgh, who host the guidetopharmacology.org website.

Acknowledgement of Collaborators

We are extremely grateful to the long list of collaborators who assisted in the construction of the Concise Guide to PHARMACOLOGY 2013/14 and to the website www.guidetopharmacology.org, as well as to the Guides to Receptors and Channels.

  1. N ABUL-HASN, New York, USA

  2. CM ANDERSON, Berkeley, USA

  3. CMH ANDERSON, Newcastle, UK

  4. MS AIRAKSINEN, Helsinki, Finland

  5. M ARITA, Boston, USA

  6. E ARTHOFER, Stockholm, Sweden

  7. EL BARKER, West Lafayette, USA

  8. C BARRATT, Dundee, UK

  9. NM BARNES, Birmingham, UK

  10. R BATHGATE, Melbourne, Australia

  11. PM BEART, Melbourne, Australia

  12. D BELELLI, Dundee, UK

  13. AJ BENNETT, Nottingham, UK

  14. NJM BIRDSALL, London, UK

  15. D BOISON, Portland, USA

  16. TI BONNER, Bethesda, USA

  17. L BRAILSFORD, Nottingham, UK

  18. S BRÖER, Canberra, Australia

  19. P BROWN, Manchester, UK

  20. G CALO’, Ferrara, Italy

  21. WG CARTER, Nottingham, UK

  22. WA CATTERALL, Seattle, USA

  23. SLF CHAN, Nottingham, UK

  24. MV CHAO, New York, USA

  25. N CHIANG, Boston, USA

  26. A CHRISTOPOULOS, Parkville, Australia

  27. JJ CHUN, La Jolla, USA

  28. J CIDLOWSKI, Bethesda, USA

  29. DE CLAPHAM, Boston, USA

  30. S COCKCROFT, London, UK

  31. MA CONNOR, Sydney, Australia

  32. BA COX, Bethesda, USA

  33. HM COX, London, UK

  34. A CUTHBERT, Cambridge, UK

  35. FM DAUTZENBERG, Allschwil, Switzerland

  36. AP DAVENPORT, Cambridge, UK

  37. PA DAWSON, Winston-Salem, USA

  38. G DENT, Keele, UK

  39. JP DIJKSTERHUIS, Stockholm, Sweden

  40. CT DOLLERY, Stevenage, UK

  41. AC DOLPHIN, London, UK

  42. M DONOWITZ, Baltimore, USA

  43. ML DUBOCOVICH, Buffalo, USA

  44. L EIDEN, Bethesda, USA

  45. K EIDNE, Nedlands, Australia

  46. BA EVANS, Melbourne, Australia

  47. D FABBRO, Basel, Switzerland

  48. C FAHLKE, Hannover, Germany

  49. R FARNDALE, Cambridge, UK

  50. GA FITZGERALD, Philadelphia, USA

  51. TM FONG, Jersey City, USA

  52. CJ FOWLER, Umea, Sweden

  53. JR FRY, Nottingham, UK

  54. CD FUNK, Kingston, Canada

  55. AH FUTERMAN, Tel Aviv, Israel

  56. V GANAPATHY, Augusta, USA

  57. B GASNIER, Paris, France

  58. MA GERSHENGORN, Bethesda, USA

  59. A GOLDIN, Irvine, USA

  60. ID GOLDMAN, New York, USA

  61. AL GUNDLACH, Melbourne, Australia

  62. B HAGENBUCH, Kansas, USA

  63. TG HALES, Dundee, UK

  64. JR HAMMOND, London, Canada

  65. M HAMON, Paris, France

  66. JC HANCOX, Bristol, UK

  67. RL HAUGER, San Diego, USA

  68. DL HAY, Auckland, New Zealand

  69. AJ HOBBS, London, UK

  70. MD HOLLENBERG, Calgary, Canada

  71. ND HOLLIDAY, Nottingham, UK

  72. D HOYER, Basel, Switzerland

  73. NA HYNES, Basel, Switzerland

  74. K-I INUI, Kyoto, Japan

  75. S ISHII, Tokyo, Japan

  76. KA JACOBSON, Bethesda, USA

  77. GE JARVIS, Cambridge, UK

  78. MF JARVIS, Chicago, USA

  79. R JENSEN, Washington DC, USA

  80. CE JONES, Horsham, UK

  81. RL JONES, Glasgow, UK

  82. K KAIBUCHI, Nagoya, Japan

  83. Y KANAI, Osaka, Japan

  84. C KENNEDY, Glasgow, UK

  85. ID KERR, Nottingham, UK

  86. AA KHAN, Chicago, USA

  87. MJ KLIENZ, Cambridge, UK

  88. JP KUKKONEN, Helsinki, Finland

  89. JY LAPOINT, Montreal, Canada

  90. R LEURS, Amsterdam, The Netherlands

  91. E LINGUEGLIA, Valbonne, France

  92. J LIPPIAT, Leeds, UK

  93. SJ LOLAIT, Bristol, UK

  94. SCR LUMMIS, Cambridge, UK

  95. JW LYNCH, Brisbane, Australia

  96. D MACEWAN, Norwich, UK

  97. JJ MAGUIRE, Cambridge, UK

  98. IL MARSHALL, Birmingham, UK

  99. JM MAY, Nashville, USA

  100. CA MCARDLE, Bristol, UK

  101. JC McGRATH, Glasgow, UK

  102. MC MICHEL, Amsterdam, The Netherlands

  103. NS MILLAR, London, UK

  104. LJ MILLER, Scotsdale, USA

  105. V MITOLO, Bari, Italy

  106. PN MONK, Sheffield, UK

  107. PK MOORE, Singapore

  108. AJ MOORHOUSE, Sydney, Australia

  109. B MOUILLAC, Montpellier, France

  110. PM MURPHY, Bethesda, USA

  111. RR NEUBIG, Ann Arbor, USA

  112. J NEUMAIER, Seattle, USA

  113. B NIESLER, Heidelberg, Germany

  114. A OBAIDAT, Kansas, USA

  115. S OFFERMANNS, Bad Nauheim, Germany

  116. E OHLSTEIN, Philadelphia, USA

  117. MA PANARO, Bari, Italy

  118. S PARSONS, Santa Barbara, USA

  119. RG PERTWEE, Aberdeen, UK

  120. J PETERSEN, Stockholm, Sweden

  121. J-P PIN, Montpellier, France

  122. DR POYNER, Birmingham, UK

  123. S PRIGENT, Leicester, UK

  124. ER PROSSNITZ, Albuquerque, USA

  125. NJ PYNE, Glasgow, UK

  126. S PYNE, Glasgow, UK

  127. JG QUIGLEY, Chicago, USA

  128. R RAMACHANDRAN, Calgary, Canada

  129. EL RICHELSON, Jacksonville, USA

  130. RE ROBERTS, Nottingham, UK

  131. R ROSKOSKI, New Orleans, USA

  132. RA ROSS, Toronto, Canada

  133. M ROTH, Kansas, USA

  134. G RUDNICK, New Haven, USA

  135. RM RYAN, Sydney, Australia

  136. SI SAID, Stony Brook, USA

  137. L SCHILD, Lausanne, Switzerland

  138. GJ SANGER, London, UK

  139. K SCHOLICH, Frankfurt, Germany

  140. A SCHOUSBOE, Copenhagen, Denmark

  141. G SCHULTE, Stockholm, Sweden

  142. S SCHULZ, Philadelphia, USA

  143. CN SERHAN, Boston, USA

  144. PM SEXTON, Melbourne, Australia

  145. DR SIBLEY, Bethesda, USA

  146. JM SIEGEL, Los Angeles, USA

  147. G SINGH, Cambridge, UK

  148. R SITSAPESAN, Bristol, UK

  149. TG SMART, London, UK

  150. DM SMITH, London, Australia

  151. T SOGA, Ibaraki, Japan

  152. A STAHL, Berkeley, USA

  153. G STEWART, Dublin, Ireland

  154. LA STODDART, Nottingham, UK

  155. RJ SUMMERS, Parkville, Australia

  156. B THORENS, Lausanne, Switzerland

  157. DT THWAITES, Newcastle, UK

  158. L TOLL, Port St Lucie, USA

  159. JR TRAYNOR, Ann Arbor, USA

  160. TB USDIN, Bethesda, USA

  161. RJ VANDENBERG, Sydney, Australia

  162. C VILLALON, Mexico, Mexico

  163. M VORE, Lexington, USA

  164. SA WALDMAN, Philadelphia, USA

  165. DT WARD, Manchester, UK

  166. GB WILLARS, Leicester, UK

  167. SJ WONNACOTT, Bath, UK

  168. E WRIGHT, Los Angeles, USA

  169. RD YE, Shanghai, China

  170. A YONEZAWA, Kyoto, Japan

  171. M ZIMMERMANN, Frankfurt, Germany

Conflict of interest

The authors state that there are no conflicts of interest to disclose.

List of records presented

  1. 1454 Adiponectin receptors

  2. 1455 Fatty acid binding proteins

  3. 1457 Sigma receptors

Adiponectin receptors

Overview

Adiponectin receptors (provisional nomenclature, ENSFM00500000270960<) respond to the 30 kDa complement-related protein hormone adiponectin (also known as ADIPOQ: adipocyte, C1q and collagen domain-containing protein; ACRP30, adipose most abundant gene transcript 1; apM-1; gelatin-binding protein: Q15848) originally cloned from adipocytes 4. Although sequence data suggest 7TM domains, immunological evidence indicates that, contrary to typical 7TM topology, the carboxyl terminus is extracellular, while the amino terminus is intracellular 6. Signalling through these receptors appears to avoid G proteins. Adiponectin receptors appear rather to stimulate protein phosphorylation via AMP-activated protein kinase and MAP kinase pathways 6, possibly through the protein partner APPL1 (adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 1, Q9UKG1 5). The adiponectin receptors are a class of proteins (along with membrane progestin receptors), which contain seven sequences of aliphatic amino acids reminiscent of GPCRs, but which are structurally and functionally distinct from that class of receptor.

Nomenclature Adipo1 receptor Adipo2 receptor
HGNC, UniProt ADIPOR1, Q96A54 ADIPOR2, Q86V24
Rank order of potency globular adiponectin > adiponectin globular adiponectin adiponectin

Comments

T-Cadherin (CDH13, P55290) has also been suggested to be a receptor for (hexameric) adiponectin 3.

Fatty acid binding proteins

Overview

Fatty acid-binding proteins are low molecular weight (100–130 aa) chaperones for long chain fatty acids, fatty acyl CoA esters, eicosanoids, retinols, retinoic acids and related metabolites and are usually regarded as being responsible for allowing the otherwise hydrophobic ligands to be mobile in aqueous media. These binding proteins may perform functions extracellularly (e.g. in plasma) or transport these agents; to the nucleus to interact with nuclear receptors (principally PPARs and retinoic acid receptors 16) or for interaction with metabolic enzymes. Although sequence homology is limited, crystallographic studies suggest conserved 3D structures across the group of binding proteins.

Preferred abbreviation FABP1 FABP2 FABP3 FABP4 FABP5
Nomenclature fatty acid binding protein 1, liver fatty acid binding protein 2, intestinal fatty acid binding protein 3, muscle and heart (mammary-derived growth inhibitor) fatty acid binding protein 4, adipocyte fatty acid binding protein 5 (psoriasis-associated)
HGNC, UniProt FABP1, P07148 FABP2, P12104 FABP3, P05413 FABP4, P15090 FABP5, Q01469
Rank order of potency stearic acid, oleic acid > palmitic acid, linoleic acid > arachidonic acid, α-linolenic acid 13 stearic acid > palmitic acid, oleic acid > linoleic acid > arachidonic acid, α-linolenic acid 13 stearic acid, oleic acid, palmitic acid > linoleic acid, α-linolenic acid, arachidonic acid 13 oleic acid, palmitic acid, stearic acid, linoleic acid > α-linolenic acid, arachidonic acid 13
Comment A broader substrate specificity than other FABPs, binding two fatty acids per protein 18 Crystal structure of the rat FABP2 15 Crystal structure of the human FABP3 19 Crystal structure of the human FABP5 11
Preferred abbreviation FABP6 FABP7 FABP8 FABP9 FABP12
Nomenclature fatty acid binding protein 6, ileal fatty acid binding protein 7, brain peripheral myelin protein 2 fatty acid binding protein 9, testis fatty acid binding protein 12
HGNC, UniProt FABP6, P51161 FABP7, O15540 PMP2, P02689 FABP9, Q0Z7S8 FABP12, A6NFH5
Comment Able to transport bile acids 20 Crystal structure of the human FABP7 7 In silico modelling suggests that FABP8 can bind both fatty acids and cholesterol 12
Preferred abbreviation RBP1 RBP2 RBP3 RBP4 RBP5
Nomenclature retinol binding protein 1, cellular retinol binding protein 2, cellular retinol binding protein 3, interstitial retinol binding protein 4, plasma retinol binding protein 5, cellular
HGNC, UniProt RBP1, P09455 RBP2, P50120 RBP3, P10745 RBP4, P02753 RBP5, P82980
Rank order of potency stearic acid > palmitic acid, oleic acid, linoleic acid, α-linolenic acid, arachidonic acid 14
Preferred abbreviation RBP7 RLBP1 CRABP1 CRABP2
Nomenclature retinol binding protein 7, cellular retinaldehyde binding protein 1 cellular retinoic acid binding protein 1 cellular retinoic acid binding protein 2
HGNC, UniProt RBP7, Q96R05 RLBP1, P12271 CRABP1, P29762 CRABP2, P29373
Rank order of potency 11-cis-retinal, 11-cis-retinol > 9-cis-retinal, 13-cis-retinal, 13-cis-retinol, all-trans-retinal, retinol 8 all-trans-retinoic acid > 9-cis-retinoic acid stearic acid > palmitic acid, oleic acid, linoleic acid, α-linolenic acid, arachidonic acid 14

Comments

Although not tested at all FABPs, BMS309403 exhibits high affinity for FABP4 (pIC50 ∼8.8) compared to FABP3 or FABP5 (pIC50 <6.6, 9,17). HTS01037 is reported to interfere with FABP4 action 10. Multiple pseudogenes for the FABPs have been identified in the human genome.

Sigma receptors

Overview

Although termed ‘receptors’, the evidence for coupling through conventional signalling pathways is lacking. Initially described as a subtype of opioid receptors, there is only a modest pharmacological overlap and no structural convergence with the G protein-coupled receptors. A wide range of compounds, ranging from psychoactive agents to antihistamines, have been observed to bind to these sites, which appear to be intracellular.

Nomenclature σ1 (sigma non-opioid intracellular receptor 1) σ2
HGNC, UniProt SIGMAR1, Q99720
Selective agonists (+)-SK&F10047, (RS)-PPCC (pKi 8.8) 25, PRE-084 (pIC50 7.4) 26 PB-28 (pKi 8.3) 21
Selective antagonists NE-100 (pIC50 8.4) 24, BD-1047 (pIC50 7.4) 23 (RS)-SM21 (pIC50 7.2) 22
Radioligands (Kd) [3H]-pentazocine (Agonist) [3H]-di-o-tolylguanidine (Agonist)

Comments

(-)-pentazocine also shows activity at opioid receptors. There is no molecular correlate of the sigma2 receptor.

Further reading

  1. Buechler C. Wanninger J. Neumeier M. Adiponectin receptor binding proteins–recent advances in elucidating adiponectin signalling pathways. FEBS Lett. 2010;584:4280–4286. doi: 10.1016/j.febslet.2010.09.035. [PMID:20875820] [DOI] [PubMed] [Google Scholar]
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Further reading

  1. Chmurzyńska A. The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism. J Appl Genet. 2006;47:39–48. doi: 10.1007/BF03194597. [PMID:16424607] [DOI] [PubMed] [Google Scholar]
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  1. Medina P. Paillasse MR. Ségala G. Khallouki F. Brillouet S. Dalenc F. Courbon F. Record M. Poirot M. Silvente-Poirot S. Importance of cholesterol and oxysterols metabolism in the pharmacology of tamoxifen and other AEBS ligands. Chem Phys Lipids. 2011;164:432–437. doi: 10.1016/j.chemphyslip.2011.05.005. [PMID:21641337] [DOI] [PubMed] [Google Scholar]
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