IUPHAR/BPS Guide to Pharmacology CITE
type: channel
description: This journal is designed to house citation summaries for contributions to the IUPHAR/BPS Guide to Pharmacology (GtoPdb) database. The journal is not open to general submissions, only curators of the GtoPdb can submit to the journal. The citation summaries exist as an adjunct to the database to facilitate the recognition of citations to and from the database by citation analysers.
publisher: University of Edinburgh
language: en
publication name: IUPHAR/BPS Guide to Pharmacology CITE
issn: 2633-1020
items: Piezo channels in GtoPdb v.2025.4
items: 3.6.5.2 Small monomeric GTPases in GtoPdb v.2025.4
items: Orai channels in GtoPdb v.2025.4
items: 2A. Hepatocyte nuclear factor-4 receptors in GtoPdb v.2025.4
items: Voltage-gated sodium channels (NaV) in GtoPdb v.2025.4
items: Aquaporins in GtoPdb v.2025.4
items: Calcium activated chloride channel (CaCC) in GtoPdb v.2025.4
items: Epithelial sodium channel (ENaC) in GtoPdb v.2025.4
items: Voltage-gated potassium channels (Kv) in GtoPdb v.2025.4
items: Acid-sensing (proton-gated) ion channels (ASICs) in GtoPdb v.2025.4
items: Transient Receptor Potential channels (TRP) in GtoPdb v.2025.4
items: Ionotropic glutamate receptors in GtoPdb v.2025.4
items: Two-pore domain potassium channels (K2P) in GtoPdb v.2025.4
items: Inwardly rectifying potassium channels (KIR) in GtoPdb v.2025.4
items: Class A Orphans in GtoPdb v.2025.4
items: Cyclic nucleotide-regulated channels (CNG) in GtoPdb v.2025.4
items: Adenosine receptors in GtoPdb v.2025.4
items: S33: Prolyl aminopeptidase in GtoPdb v.2025.3
items: Receptor guanylyl cyclase (RGC) family in GtoPdb v.2025.3
items: Carnitine palmitoyltransferases in GtoPdb v.2025.3
items: Endocannabinoid turnover in GtoPdb v.2025.3
items: Coronavirus (CoV) proteins in GtoPdb v.2025.3
items: SLC54 Mitochondrial pyruvate carriers in GtoPdb v.2025.3
items: E3 ubiquitin ligase components in GtoPdb v.2025.3
items: Blood coagulation components in GtoPdb v.2025.3
items: Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2025.3
items: Peptidyl-prolyl cis/trans isomerases in GtoPdb v.2025.3
items: RAS subfamily in GtoPdb v.2025.3
items: Hydrolases & Lipases in GtoPdb v.2025.3
items: 3.6.5.2 Small monomeric GTPases in GtoPdb v.2025.3

Piezo channels in GtoPdb v.2025.4
type: item
description: PIEZO proteins are the pore-forming subunits of trimeric ion channels that open rapidly in response to mechanical stimuli such as membrane stretch, allowing positively charged ions such as the calcium ion to flow into the cell to change cellular structure and function. The proteins are eukaryotic, not prokaryotic, and lack sequence or structural homology to other proteins. There are two main types: In humans, there is PIEZO1 of 2521 amino acids and PIEZO2 of 2752 amino acids, which can form homomeric PIEZO1 and PIEZO2 channels. Membrane stretching causes complex changes in the channels that include a reduced inward curvature, an expansion of the N-terminal transmembrane helical units and an opening of the central ion pore region comprising the last two C-terminal helices. When there is sustained membrane stretching, the channels may adapt by inactivating at various rates depending on the cell type and context. There are many roles of the channels in diverse organ systems including cardiovascular, gastrointestinal, haematological, hepatobiliary, immune, integumental, musculoskeletal, neuronal, reproductive, respiratory and urinary systems as well as adipose tissue and cancers. The expression and functions of PIEZO1 are broad and diverse across many cell types and organs, whereas PIEZO2 is more restricted.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:39 2025; family F967, Piezo channels; version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F967 O2945 O2946 )
  topic: subjects
subject: GtoPdb_authors: 1148
  topic: subjects
subject: GtoPdb_references: 33356 34088 34404 34405 36290 36291 38177 42159 42743 48936 48937 49561 49562 49568 49583 49584 49585 49589 49590 49591 49592 49593
  topic: subjects
creator: David J. Beech
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F967/2025.4

3.6.5.2 Small monomeric GTPases in GtoPdb v.2025.4
type: item
description: Small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The best-known members are the Ras GTPases and hence they are sometimes called Ras subfamily GTPases.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:39 2025; family F896, 3.6.5.2 Small monomeric GTPases; version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F896 ( F897 O2822 O2823 O2824 O3324 O3328 I897 ) ( F938 O2916 O3292 ) )
  topic: subjects
subject: GtoPdb_authors: 706
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 26443 26444 26445 26446 26447 26448 26449 26453 26454 26455 26456 26457 26458 26459 26460 26461 26462 26463 26468 26469 26470 31925 31931 31932 31933 37762 37763 37764 38815 38817 39420 40027 42159 43284 43298 43591 43900 43901 43903 43919 44397 44682 45709 46111 46256 47580 47725 47726 47727 47728 47729 48683 50005 50006 50312 50313 50314 50315 50316 50321 50492 50493 50494 50495 50496
creator: Elena Faccenda
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F896/2025.4

Orai channels in GtoPdb v.2025.4
type: item
description: Orai channels are pore forming proteins which underlie calcium release-activated calcium (CRAC) channels. In numerous cell types, calcium influx is predominantly governed by store-operated calcium channels (SOCs). The process of store-operated calcium entry (SOCE) is orchestrated through the concerted interaction of two essential molecular components: the pore-forming Orai proteins (Orai1-3) and the endoplasmic reticulum calcium-sensing stromal interaction molecules (STIM1 and STIM2) [25].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:40 2025; family F977, Orai channels; version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F977 O2964 O2965 O2966 )
  topic: subjects
subject: GtoPdb_authors: 1150
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 33338 35924 35928 35929 35930 35931 35932 35933 35934 35935 35936 35937 35938 35939 35940 35944 35945 35946 35947 35948 35949 35950 35951 35952 35953 35954 36136 36172 36260 36261 42159 45621 48102 50264 50265 50266
creator: Hussein N. Rubaiy
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F977/2025.4

2A. Hepatocyte nuclear factor-4 receptors in GtoPdb v.2025.4
type: item
description: The nomenclature of hepatocyte nuclear factor-4 receptors is agreed by the NC-IUPHAR Subcommittee on Nuclear Hormone Receptors [9, 3]. While linoleic acid has been identified as the endogenous ligand for HNF4α its function remains ambiguous [80]. HNF4γ has yet to be paired with an endogenous ligand.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:36 2025; family F91, 2A. Hepatocyte nuclear factor-4 receptors; version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F91 O608 O609 I91 )
  topic: subjects
subject: GtoPdb_authors: 878 1185
  topic: subjects
subject:
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  value: GtoPdb_references: 10716 10725 10726 10727 10728 10729 10731 10732 10733 10734 10735 10737 10738 10739 10740 10741 10742 10743 10744 10745 10746 10748 10749 10750 10751 10752 10753 10754 10755 10757 10759 10761 10762 10763 10764 10768 10769 10770 10771 10772 10773 10774 10775 10776 10777 10778 10779 10780 10781 10782 10783 10784 10785 10786 10787 10788 10789 10790 10794 10795 10796 10797 10798 11410 11436 15346 22803 28021 28022 28023 28024 28025 28029 28828 40458 42159 50322 50325 50328 50329 50330
creator: Sarah Radi
creator: Frances M. Sladek
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F91/2025.4

Voltage-gated sodium channels (NaV) in GtoPdb v.2025.4
type: item
description: Sodium channels are voltage-gated sodium-selective ion channels present in the membrane of most excitable cells. Sodium channels comprise one pore-forming α subunit, which may be associated with either one or two β subunits [191]. α-Subunits consist of four homologous domains (I-IV), each containing six transmembrane segments (S1-S6) and a pore-forming loop. The positively charged fourth transmembrane segment (S4) acts as a voltage sensor and is involved in channel gating. The crystal structure of the bacterial NavAb channel has revealed a number of novel structural features compared to earlier potassium channel structures including a short selectivity filter with ion selectivity determined by interactions with glutamate side chains [298]. Interestingly, the pore region is penetrated by fatty acyl chains that extend into the central cavity which may allow the entry of small, hydrophobic pore-blocking drugs [298]. Auxiliary β1, β2, β3 and β4 subunits consist of a large extracellular N-terminal domain, a single transmembrane segment and a shorter cytoplasmic domain. Pharmacological targeting of voltage-gated sodium channels has long been a cornerstone of clinical treatment for a range of conditions. Classical sodium channel blockers, many of which act by occluding the central pore, are widely used as local anesthetics, antiarrhythmic agents, and anticonvulsants [135]. More recently, suzetrigine, a highly selective Nav1.8 inhibitor, received FDA approval for the treatment of acute post-operative pain [202, 419]. The nomenclature for sodium channels was proposed by Goldin et al., (2000) [155] and approved by the NC-IUPHAR Subcommittee on sodium channels (Catterall et al., 2005, [54]).
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:36 2025; family F82, Voltage-gated sodium channels (NaV); version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F82 O578 O579 O580 O581 O582 O583 O584 O585 O586 I82 )
  topic: subjects
subject: GtoPdb_authors: 418 430 431 1158
  topic: subjects
subject:
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  value: GtoPdb_references: 7693 7698 7699 7710 7711 7712 7713 7715 7716 7717 7718 7719 7720 9637 9807 9808 9809 9810 9811 9812 9813 9814 9815 9816 9817 9818 9819 9820 9821 9822 9823 9824 9825 9826 9827 9828 9829 9830 9831 9832 9833 9834 9835 9836 9837 9838 9839 9840 9841 9842 9843 9844 9845 9846 9847 9848 9849 9850 9851 9852 9853 9854 9855 9856 9857 9858 9859 9860 9861 9862 9863 9864 9865 9866 9867 9868 9869 9870 9871 9872 9873 9874 9875 9876 9877 9878 9879 9880 9881 9882 9883 9884 9885 9886 9887 9888 9889 9890 9891 9892 9893 9894 9895 9896 9897 9898 9899 9900 9901 9902 9903 9904 9905 9906 9907 9908 9909 9910 9911 9912 9913 9914 9915 9916 9917 9918 9919 9920 9921 9922 9923 9924 9925 9926 9927 9928 9929 9930 9931 9932 9933 9934 9935 9936 9937 9938 9939 9940 9941 9942 9943 9944 9945 9946 9947 9948 9949 9950 9951 9952 9953 9954 9955 9956 9957 9958 9959 9960 9961 9962 9963 9964 9965 9966 9967 9968 9969 9970 9971 9972 9973 9974 9975 9976 9977 9978 9979 9980 9981 9982 9983 9984 9985 9986 9987 9988 9989 9990 9991 9992 9993 9994 9995 9996 9997 9998 9999 10000 10001 10002 10003 10004 10005 10006 10007 10008 10009 10010 10011 10012 10013 10014 10015 10016 10017 10018 10019 10020 10021 10022 10023 10024 10025 10026 10027 10028 10029 10030 10031 10032 10033 10034 10035 10036 15450 15661 16038 16039 16049 16296 18708 18709 18710 18711 18713 18714 18715 18716 18717 18718 18719 18720 18721 18722 18723 18724 18725 18726 18727 18728 18729 18730 18731 18732 18733 18734 18735 18736 18737 18738 18739 18740 18741 18742 18743 18744 18745 18746 18747 18748 18749 18750 18751 18752 18753 18754 18755 18756 18757 18758 18759 18760 18761 18762 18763 18764 18765 18766 18767 18768 18769 18770 18771 18773 23555 24070 24073 24537 24767 24768 24769 24770 24771 24772 24773 24774 24775 24776 24777 24778 24779 24780 24781 24782 24783 24784 24785 24786 24787 24788 24789 24790 24791 24792 24793 24794 24795 24796 24797 24798 24799 24800 24801 24802 24803 24804 24805 24806 25575 25673 26556 27772 27893 28081 2808…
creator: William A. Catterall
creator: Mohammad-Reza Ghovanloo
creator: Alan L. Goldin
creator: Stephen G. Waxman
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F82/2025.4

Aquaporins in GtoPdb v.2025.4
type: item
description: Aquaporins and aquaglyceroporins are membrane channels that allow the permeation of water and certain other small solutes across the cell membrane, or in the case of AQP6, AQP11 and AQP12A, intracellular membranes, such as vesicles and the endoplasmic reticulum membrane [16]. Since the isolation and cloning of the first aquaporin (AQP1) [20], 12 additional mammalian members of the family have been identified, although little is known about the functional properties of one of these (AQP12A; Q8IXF9) and it is thus not tabulated. The other 12 aquaporins can be broadly divided into three families: orthodox aquaporins (AQP0,-1,-2,-4,-5, -6 and -8) permeable mainly to water, but for some additional solutes [4]; aquaglyceroporins (AQP3,-7 -9 and -10), additionally permeable to glycerol and for some isoforms urea [14], and superaquaporins (AQP11 and 12) located within cells [12]. Some aquaporins also conduct ammonia and/or H2O2 giving rise to the terms 'ammoniaporins' ('aquaammoniaporins') and 'peroxiporins', respectively. Aquaporins are impermeable to protons and other inorganic and organic cations, with the possible exception of AQP1, although this is controversial [14]. One or more members of this family of proteins have been found to be expressed in almost all tissues of the body [reviewed in Yang (2017) [27]]. AQPs are involved in numerous processes that include systemic water homeostasis, adipocyte metabolism, brain oedema, cell migration and fluid secretion by epithelia. Loss of function mutations of some human AQPs, or their disruption by autoantibodies further underscore their importance [reviewed by Verkman et al. (2014) [24], Kitchen et al. (2105) [14]]. Functional AQPs exist as homotetramers that are the water conducting units wherein individual AQP subunits (each a protomer) have six TM helices and two half helices that constitute a seventh 'pseudotransmembrane domain' that surrounds a narrow water conducting channel [16]. In addition to the four pores contribu…
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:37 2025; family F119, Aquaporins; version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F119 O687 O688 O689 O690 O691 O692 O693 O694 O695 O696 O697 O3062 )
  topic: subjects
subject: GtoPdb_authors: 1021 1081 1082 1083
  topic: subjects
subject: GtoPdb_references: 15642 35642 36681 36682 36683 36684 36685 36686 36687 36688 36689 36692 36694 36695 36696 36697 36699 36700 36701 36702 36703 36704 36705 36706 39507 41771 42159 46408
  topic: subjects
creator: Roslyn M. Bill
creator: Alex C. Conner
creator: Philip Kitchen
creator: Mootaz Salman
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F119/2025.4

Calcium activated chloride channel (CaCC) in GtoPdb v.2025.4
type: item
description: Chloride channels activated by intracellular Ca2+ (CaCC) are widely expressed in excitable and non-excitable cells where they perform diverse functions [29]. CaCCs are activated by a rise in intracellular free Ca2+ concentration ([Ca2+]i), typically following activation of Gq protein coupled receptors (GqPCR). This section centres on CaCC channels encoded by the TMEM16A gene (HUGO gene nomenclature: Anoctamin 1). The TMEM16 family consists of 10 paralogs (TMEM16A-K; Anoctamin 1-10). The TMEM16A and TMEM16B genes (ANO1 and ANO2) encode for CaCCs, while the other members function as lipid scramblases or have combined scramblase and non-selective ion channel function [31, 58, 22, 1, 52]. TMEM16A has a broad tissue distribution and a variety of established cellular roles, while the main physiological role for TMEM16B identified thus far is in olfaction [37, 18]. Alternative splicing regulates the voltage- and Ca2+-dependence of TMEM16A and such post-transcriptional process may be tissue-specific and contribute to functional diversity [23]. TMEM16A is a potential drug target for a variety of conditions spanning from respiratory to vascular (see "Comments" section for further detail).
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:38 2025; family F130, Calcium activated chloride channel (CaCC); version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F130 O708 I130 )
  topic: subjects
subject: GtoPdb_authors: 1161 1162 1163
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 15696 15697 15705 15706 15708 15709 15731 15732 15735 15836 15837 15838 15839 15840 15841 15842 15843 15844 15845 15846 24511 35644 40637 40638 40639 42159 44274 44354 48146 48148 48149 48443 48849 49970 49971 49972 49973 49974 49975 49976 49977 50277 50278 50279 50280 50281 50282 50283 50284 50285 50286 50287 50288 50289 50290 50291 50292 50293 50294 50295 50296 50297 50298 50299 50300 50301 50302 50303
creator: Henry Danahay
creator: Martin Gosling
creator: Paolo Tammaro
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F130/2025.4

Epithelial sodium channel (ENaC) in GtoPdb v.2025.4
type: item
description: Overview Epithelial sodium channels (ENaC) are located on the apical membrane of epithelial cells in the kidney tubules, lungs, respiratory tract, male and female reproductive tracts, sweat and salivary glands, placenta, colon, and several other organs [10, 17, 26, 25, 57]. In these epithelia, Na+ ions enter epithelial cells from the extracellular fluid via ENaC and are subsequently pumped out into the interstitial fluid by the Na+/K+-ATPase on the basolateral membrane [49]. Because sodium is a major electrolyte in the extracellular fluid (ECF), the osmotic changes caused by sodium flux are accompanied by parallel water movement [7]. Thus, ENaC plays a central role in regulating ECF volume and blood pressure, primarily through its function in the kidney [51]. The expression of ENaC subunits- and therefore its activity- is controlled by the renin-angiotensin-aldosterone system and other factors involved in electrolyte homeostasis [51, 36]. Genetic studies of systemic pseudohypoaldosteronism type I revealed that ENaC activity depends on three essential subunits encoded by three separate genes encoding homologous proteins [12, 26]. Within the wider protein superfamily that includes ENaC, the first crystal structure determined was that of ASIC, which revealed a trimeric structure with a large extracellular domain anchored in the membrane by a bundle of six transmembrane helices (two per subunit) [3, 30]. The first 3D structure of human ENaC was determined using single-particle cryo-electron microscopy at 3.7Å resolution [45], later improved to 3.0Å [46]. These structures confirmed that ENaC has a quaternary structure similar to ASIC. ENaC assembles as a heterotrimer, with α-, γ-, and β-subunits arranged in clockwise order when viewed from above [13]. In contrast to ASIC1, which can form a functional homotrimer, ENaC is only fully functional as a heterotrimer composed of either αβγ or δβγ [33]. Recently, Houser and Baconguis co-expressed human δ, β, and γ and determined …
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:38 2025; family F122, Epithelial sodium channel (ENaC); version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F122 O742 O738 O739 O741 O740 I122 )
  topic: subjects
subject: GtoPdb_authors: 889
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 15581 15785 15804 16163 16183 28143 30710 30712 32798 33131 33132 33134 33135 33137 33139 33140 33142 33143 33144 33146 33147 33148 33150 33151 33152 33155 33156 33157 33158 33159 37367 37369 37537 41132 41757 41758 41759 41760 41761 41762 41763 41764 41765 41766 41767 41768 41769 42159 42937 42938 45238 45239 45240 45241 45242 45243 45244 49696 49697 49804 50597 50598 50599 50600
creator: Israel Hanukoglu
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F122/2025.4

Voltage-gated potassium channels (Kv) in GtoPdb v.2025.4
type: item
description: The 6TM family of K channels comprises the voltage-gated KV subfamilies, the EAG subfamily (which includes hERG channels), the Ca2+-activated Slo subfamily (actually with 7TM, termed BK) and the Ca2+-activated SK subfamily. These channels possess a pore-forming α subunit that comprises tetramers of identical subunits (homomeric) or of different subunits (heteromeric). Heteromeric channels can only be formed within subfamilies (e.g. Kv1.1 with Kv1.2; Kv7.2 with Kv7.3). The pharmacology largely reflects the subunit composition of the functional channel.<heading>Kv7 channels</heading>Kv7.1-Kv7.5 (KCNQ1-5) K+ channels are voltage-gated K+ channels with major roles in neurons, muscle cells and epithelia where they underlie physiologically important K+ currents, such as the neuronal M-current and the cardiac IKs. Genetic deficiencies in all five KCNQ genes result in human excitability disorders, including epilepsy, autism spectrum disorders, cardiac arrhythmias and deafness. Thanks to the recent knowledge of the structure and function of human KCNQ-encoded proteins, these channels are increasingly used as drug targets for treating diseases [333, 2, 777, 294].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:35 2025; family F81, Voltage-gated potassium channels (Kv); version 2025.4.
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_hierarchy: ( F81 O538 O539 O540 O541 O542 O543 O544 O545 O546 O547 O548 O549 O550 O551 O552 O553 O554 O555 O556 O557 O558 O559 O560 O561 O562 O563 O564 O565 O566 O567 O568 O569 O570 O571 O572 O573 O574 O575 O576 O577 I81 )
subject: GtoPdb_authors: 386 387 395 397 419 423 424 425 426 427 428 429 761 762 812 969
  topic: subjects
subject:
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  value: GtoPdb_references: 3049 6595 7707 7806 7829 7862 7915 7935 7939 9183 9184 9186 9187 9188 9190 9191 9192 9194 9195 9196 9197 9198 9199 9200 9201 9203 9204 9205 9206 9207 9208 9209 9210 9211 9212 9213 9215 9216 9217 9218 9221 9223 9225 9226 9229 9232 9234 9235 9238 9240 9241 9242 9243 9244 9245 9246 9247 9248 9249 9250 9251 9252 9253 9254 9255 9256 9257 9258 9259 9260 9261 9262 9263 9264 9265 9266 9267 9268 9269 9270 9271 9272 9273 9274 9275 9276 9277 9278 9279 9280 9281 9282 9283 9284 9285 9286 9287 9288 9289 9290 9291 9292 9293 9294 9295 9296 9297 9299 9300 9301 9302 9303 9304 9305 9306 9308 9309 9310 9311 9313 9314 9315 9316 9317 9318 9319 9320 9321 9322 9323 9324 9325 9326 9327 9328 9329 9330 9331 9332 9333 9335 9336 9337 9338 9339 9340 9341 9342 9343 9344 9345 9346 9347 9348 9349 9350 9351 9353 9354 9355 9356 9357 9358 9359 9360 9361 9362 9363 9364 9365 9366 9367 9368 9369 9370 9371 9372 9373 9374 9375 9377 9378 9379 9380 9382 9383 9384 9385 9386 9387 9388 9389 9390 9391 9392 9393 9394 9395 9397 9398 9399 9401 9402 9403 9404 9405 9406 9407 9408 9409 9410 9411 9412 9413 9415 9416 9417 9418 9419 9420 9421 9422 9423 9424 9425 9426 9427 9428 9429 9430 9431 9432 9436 9439 9440 9441 9442 9443 9444 9445 9446 9447 9448 9449 9450 9451 9452 9453 9454 9455 9456 9457 9458 9459 9460 9461 9462 9463 9464 9465 9466 9467 9468 9469 9470 9471 9472 9473 9474 9475 9476 9477 9478 9479 9480 9481 9482 9483 9484 9485 9486 9487 9488 9489 9490 9491 9492 9493 9494 9495 9496 9497 9498 9499 9500 9501 9502 9503 9504 9505 9506 9507 9508 9509 9510 9511 9512 9513 9514 9515 9516 9517 9518 9519 9520 9521 9522 9524 9527 9528 9529 9530 9532 9533 9536 9537 9538 9539 9540 9541 9542 9544 9546 9547 9548 9549 9550 9551 9552 9553 9554 9555 9557 9558 9559 9560 9561 9562 9563 9565 9566 9567 9568 9569 9570 9571 9572 9573 9574 9575 9576 9577 9578 9579 9580 9581 9582 9583 9584 9585 9586 9587 9588 9589 9590 9592 9596 9597 9598 9599 9600 9601 9603 9604 9605 9606 9607 9608 9609 9610 9611 9612 9613 9614 9615 9616 9…
creator: Bernard Attali
creator: James S. Trimmer
creator: Walter Stühmer
creator: Michael C. Sanguinetti
creator: Bernardo Rudy
creator: Gail A. Robertson
creator: Luis A. Pardo
creator: Jeanne Nerbonne
creator: David Mckinnon
creator: Michel Lazdunski
creator: Lily Y. Jan
creator: George A. Gutman
creator: Stephan Grissmer
creator: M. Hunter Giese
creator: K. George Chandy
creator: Xiaoliang Wang
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F81/2025.4

Acid-sensing (proton-gated) ion channels (ASICs) in GtoPdb v.2025.4
type: item
description: Acid-sensing ion channels (ASICs, nomenclature as agreed by NC-IUPHAR [52, 2, 3]) are members of a Na+ channel superfamily that includes the epithelial Na+ channel (ENaC), the FMRF-amide activated channel (FaNaC) of invertebrates, the degenerins (DEG) of Caenorhabditis elegans, channels in Drosophila melanogaster and the mammalian bile acid-activated ion channel BASIC [94], previously known as BLINaC [75] and INaC [77]. ASIC subunits contain 2 TM domains and a large extracellular part whose shape resembles that of a hand, as shown by high-resolution structures of chicken and human ASIC1a [49, 43, 7, 101, 100, 81]. They assemble as homo- or heterotrimers to form proton-gated, voltage-insensitive, Na+ permeable, channels that are activated by levels of acidosis occurring in both physiological and pathophysiological conditions with ASIC3 also playing a role in mechanosensation (reviewed in [48, 93, 52, 74, 23]). Splice variants of ASIC1 [termed ASIC1a (ASIC, ASICα, BNaC2α) [88], ASIC1b (ASICβ, BNaC2β) [19] and ASIC1b2 (ASICβ2) [83]; note that ASIC1a is also permeable to Ca2+], ASIC2 [termed ASIC2a (MDEG1, BNaC1α, BNC1α) [70, 89, 42] and ASIC2b (MDEG2, BNaC1β) [60]] differ in the first third of the protein. Unlike ASIC2a (listed in table), heterologous expression of ASIC2b alone does not support H+-gated currents. A third member, ASIC3 (DRASIC, TNaC1) [87] is one of the most pH-sensitive isoforms (along with ASIC1a) and has the fastest activation and desensitisation kinetics, however can also carry small sustained currents. ASIC4 (SPASIC) evolved as a proton-sensitive channel but seems to have lost this function in mammals [62]. Mammalian ASIC4 does not support a proton-gated channel in heterologous expression systems but is reported to downregulate the expression of ASIC1a and ASIC3 [1, 47, 35, 58, 24]. ASICs channels are primarily expressed in central (ASIC1a, -2a, 2b and -4) and peripheral neurons including nociceptors (ASIC1-3) where they participate in neuronal sen…
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:37 2025; family F118, Acid-sensing (proton-gated) ion channels (ASICs); version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F118 O684 O685 O686 )
  topic: subjects
subject: GtoPdb_authors: 903 1056
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 15562 15573 15579 15580 15581 15582 15583 15584 15585 15586 15588 15593 15595 15596 15597 15598 15599 15600 15601 15602 15603 15604 15605 15609 15610 15611 15612 15614 15615 15616 15617 15618 15619 15620 15621 15622 15623 23171 28143 32798 32799 32800 32801 32802 32803 32804 32805 32809 32810 32817 32818 32819 32820 32821 32822 32823 34466 37351 37354 37355 37356 37357 37358 37359 37361 40456 40457 40862 40863 40864 40865 40866 40867 40868 40869 40870 40871 40872 40873 40874 40875 40876 40877 40878 40879 41773 41774 41775 41776 41777 41778 42159 45233 45234 45236 45237 49931 49932 49933 49934 49935 49937 49938 49969
creator: Stephan Kellenberger
creator: Lachlan D. Rash
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F118/2025.4

Transient Receptor Potential channels (TRP) in GtoPdb v.2025.4
type: item
description: The TRP superfamily of channels (nomenclature as agreed by NC-IUPHAR [177, 1080]), whose founder member is the Drosophila Trp channel, exists in mammals as six families; TRPC, TRPM, TRPV, TRPA, TRPP and TRPML based on amino acid homologies. TRP subunits contain six putative TM domains and assemble as homo- or hetero-tetramers to form cation selective channels with diverse modes of activation and varied permeation properties (reviewed by [734]). Established, or potential, physiological functions of the individual members of the TRP families are discussed in detail in the recommended reviews and in a number of books [404, 690, 1163, 258]. The established, or potential, involvement of TRP channels in disease [1134] is reviewed in [452, 689], [692] and [468], together with a special edition of Biochemica et Biophysica Acta on the subject [689]. Additional disease related reviews, for pain [637], stroke [1143], sensation and inflammation [994], itch [130], and airway disease [313, 1058], are available. The pharmacology of most TRP channels has been advanced in recent years. Broad spectrum agents are listed in the tables along with more selective, or recently recognised, ligands that are flagged by the inclusion of a primary reference. See Rubaiy (2019) for a review of pharmacological tools for TRPC1/C4/C5 channels [810]. Most TRP channels are regulated by phosphoinositides such as PtIns(4,5)P2 although the effects reported are often complex, occasionally contradictory, and likely to be dependent upon experimental conditions, such as intracellular ATP levels (reviewed by [1015, 693, 806]). Such regulation is generally not included in the tables.When thermosensitivity is mentioned, it refers specifically to a high Q10 of gating, often in the range of 10-30, but does not necessarily imply that the channel's function is to act as a 'hot' or 'cold' sensor. In general, the search for TRP activators has led to many claims for temperature sensing, mechanosensation, and lipid sen…
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:34 2025; family F78, Transient Receptor Potential channels (TRP); version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F78 O485 O486 O487 O488 O489 O490 O491 O492 O493 O494 O495 O496 O497 O498 O499 O500 O501 O502 O503 O504 O505 O506 O507 O508 O509 O510 O511 O512 I78 )
  topic: subjects
subject: GtoPdb_authors: 388 408 409 441 673 674 675 681 682 683 684 685 686 688 689 690 691 692 693 695 1059 1060 1061 1062 1063 1064 1109 1128 1129 1130 1131 1132 1141 1142
  topic: subjects
subject:
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  value: GtoPdb_references: 2031 4511 7672 7684 7948 8431 8432 8433 8434 8435 8436 8437 8438 8439 8440 8441 8442 8443 8444 8445 8446 8447 8448 8449 8450 8451 8452 8453 8454 8455 8456 8457 8458 8459 8460 8461 8462 8463 8464 8465 8466 8467 8468 8469 8470 8471 8472 8473 8474 8475 8476 8477 8478 8479 8480 8481 8482 8483 8484 8485 8486 8487 8488 8489 8490 8491 8492 8493 8494 8495 8496 8497 8498 8499 8500 8501 8502 8503 8504 8505 8506 8507 8508 8509 8510 8511 8512 8513 8514 8515 8516 8517 8518 8519 8520 8521 8522 8523 8524 8525 8526 8527 8528 8529 8530 8531 8532 8533 8534 8535 8536 8537 8538 8539 8540 8541 8542 8543 8544 8545 8546 8547 8548 8549 8550 8551 8552 8553 8554 8555 8556 8557 8558 8559 8561 8562 8563 8564 8565 8566 8567 8568 8569 8570 8571 8572 8573 8574 8575 8576 8577 8578 8579 8580 8581 8582 8583 8584 8585 8586 8587 8588 8589 8590 8591 8592 8593 8594 8595 8596 8597 8598 8599 8600 8601 8602 8603 8604 8605 8606 8607 8608 8609 8610 8611 8612 8613 8614 8615 8616 8617 8618 8619 8620 8621 8622 8623 8624 8625 8626 8627 8628 8629 8630 8631 8632 8633 8634 8635 8636 8637 8638 8639 8640 8641 8642 8643 8644 8645 8646 8647 8648 8649 8650 8651 8652 8653 8654 8655 8656 8657 8658 8659 8660 8661 8662 8663 8664 8665 8666 8667 8668 8669 8670 8671 8672 8673 8674 8675 8676 8677 8678 8679 8680 8681 8682 8683 8684 8685 8686 8687 8688 8689 8690 8691 8692 8693 8694 8695 8696 8697 8698 8699 8700 8701 8702 8703 8704 8705 8706 8707 8708 8709 8710 8711 8712 8713 8714 8715 8716 8717 8718 8719 8720 8721 8722 8723 8724 8725 8726 8727 8728 8729 8730 8731 8732 8733 8734 8735 8736 8737 8738 8739 8740 8741 8742 8743 8744 8745 8746 8747 8748 8749 8750 8751 8752 8753 8754 8755 8756 8757 8758 8759 8760 8761 8762 8763 8764 8765 8766 8767 8768 8769 8770 8771 8772 8773 8774 8775 8776 8777 8778 8779 8780 8781 8782 8783 8784 8785 8786 8787 8788 15667 16050 16051 16052 16053 16054 16055 16056 16057 16058 16059 16060 16061 16063 16064 16065 16067 16068 16069 16070 16072 16073 16074 16075 16077 16078 16079 16080 160…
creator: Nathaniel T. Blair
creator: David McKemy
creator: Bernd Nilius
creator: Elena Oancea
creator: Grzegorz Owsianik
creator: Antonio Riccio
creator: Rajan Sah
creator: Stephanie C. Stotz
creator: Jinbin Tian
creator: Dan Tong
creator: Joris Vriens
creator: Long-Jun Wu
creator: Haoxing Xu
creator: Fan Yang
creator: Wei Yang
creator: Lixia Yue
creator: Qiang Liu
creator: Boyi Liu
creator: Ana I. Caceres
creator: Ingrid Carvacho
creator: Dipayan Chaudhuri
creator: David E. Clapham
creator: Katrien De Clercq
creator: Markus Delling
creator: Julia F. Doerner
creator: Lu Fan
creator: Christian M. Grimm
creator: Kotdaji Ha
creator: Meiqin Hu
creator: Sairam V. Jabba
creator: Sven E. Jordt
creator: David Julius
creator: Kristopher T Kahle
creator: Michael X. Zhu
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F78/2025.4

Ionotropic glutamate receptors in GtoPdb v.2025.4
type: item
description: The ionotropic glutamate receptors comprise members of the NMDA (N-methyl-D-aspartate), AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid) and kainate receptor classes, named originally according to their preferred, synthetic, agonist [60, 99, 163]. Receptor heterogeneity within each class arises from the homo-oligomeric, or hetero-oligomeric, assembly of distinct subunits into cation-selective tetramers. Each subunit of the tetrameric complex comprises an extracellular amino terminal domain (ATD), an extracellular ligand binding domain (LBD), 3 TM domains (M1, M3 and M4), a channel lining re-entrant 'p-loop' (M2) located between M1 and M3 and an intracellular carboxy- terminal domain (CTD) [106, 74, 115, 163, 88]. The X-ray structure of a homomeric ionotropic glutamate receptor (GluA2- see below) has recently been solved at 3.6Å resolution [151] and although providing the most complete structural information current available may not be representative of the subunit arrangement of, for example, the heteromeric NMDA receptors [77]. It is beyond the scope of this supplement to discuss the pharmacology of individual ionotropic glutamate receptor isoforms in detail; such information can be gleaned from [60, 72, 34, 83, 44, 122, 27, 71, 163, 120, 121, 171]. Agents that discriminate between subunit isoforms are, where appropriate, noted in the tables and additional compounds that distinguish between receptor isoforms are indicated in the text below. The classification of glutamate receptor subunits has been re-addressed by NC-IUPHAR [31]. The scheme developed recommends a nomenclature for ionotropic glutamate receptor subunits that is adopted here. NMDA receptors NMDA receptors assemble as obligate heteromers that may be drawn from GluN1, GluN2A, GluN2B, GluN2C, GluN2D, GluN3A and GluN3B subunits. Alternative splicing can generate eight isoforms of GluN1 with differing pharmacological properties. Various splice variants of GluN2B, 2C, 2D and GluN3A have also be…
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:34 2025; family F75, Ionotropic glutamate receptors; version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F75 O444 O445 O446 O447 O448 O449 O450 O451 O452 O453 O454 O455 O456 O457 O458 O459 O460 O461 )
  topic: subjects
subject: GtoPdb_authors: 151 223 378 455 456 460 513 514 515 516 517 518 519 520 521 522 524
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 10499 11193 11417 11454 11455 11456 11457 11458 11459 11460 11461 11462 11463 11464 11465 11466 11467 11468 11469 11470 11471 11472 11473 11474 11475 11476 11477 11478 11479 11480 11482 11483 11484 11485 11486 11487 11488 11489 11490 11491 11492 11494 11495 11496 11497 11498 11499 11500 11501 11502 11503 11504 11505 11506 11507 11508 11509 11510 11511 11512 11513 11514 11515 11516 11517 11518 11519 11520 11521 11522 11523 13285 13286 13287 13288 13289 13290 13291 13293 14414 15455 15456 15458 15459 15460 15461 15462 15463 15464 15465 15466 15467 15468 15469 15470 15471 15472 15473 15474 15475 15476 15477 15478 15479 15480 15481 15482 15483 15484 15485 15486 15487 15488 15489 15490 15491 15492 15493 15494 15495 15496 15497 15498 15499 15500 16157 16179 16180 16181 16182 17436 22919 22920 22921 22922 22923 22924 22925 22926 24711 25101 25159 26072 26074 27346 30042 30043 30044 30045 30046 30047 30048 30049 30050 30051 38008 38009 38010 38011 38012 38013 38014 40775 40776 40896 42159 42993 43845 43847 44056 47296 47654 47655 47656 49014 50469
creator: Bernhard Bettler
creator: Michael Spedding
creator: Peter Seeburg
creator: John A. Peters
creator: Stephane Peineau
creator: Richard Olsen
creator: Shigetada Nakanishi
creator: Christophe Mulle
creator: Masayoshi Mishina
creator: Mark Mayer
creator: David Lodge
creator: Juan Lerma
creator: Michael Hollmann
creator: Stephen F. Heinemann
creator: Ray Dingledine
creator: Graham L. Collingridge
creator: Jeffrey C. Watkins
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F75/2025.4

Two-pore domain potassium channels (K2P) in GtoPdb v.2025.4
type: item
description: The 4TM family of K channels mediate many of the background potassium currents observed in native cells. They are open across the physiological voltage-range and are regulated by a wide array of neurotransmitters and biochemical mediators. The pore-forming α-subunit contains two pore loop (P) domains and two subunits assemble to form one ion conduction pathway lined by four P domains. It is important to note that single channels do not have two pores but that each subunit has two P domains in its primary sequence; hence the name two-pore domain, or K2P channels (and not two-pore channels). Some of the K2P subunits can form heterodimers across subfamilies (e.g. K2P3.1 with K2P9.1). The nomenclature of 4TM K channels in the literature is still a mixture of IUPHAR and common names. The suggested division into subfamilies, described in the more detailed introduction, is based on similarities in both structural and functional properties within subfamilies and this explains the "common abbreviation" nomenclature in the tables below.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:35 2025; family F79, Two-pore domain potassium channels (K2P); version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F79 O513 O514 O515 O516 O517 O518 O519 O520 O521 O522 O523 O524 O525 O526 O527 I79 )
  topic: subjects
subject: GtoPdb_authors: 410 412 413 414 772 773 774 957 1098
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 7686 7687 7688 7690 7691 7692 8789 8790 8791 8792 8793 8794 8795 8796 8797 8798 8799 8800 8801 8802 8803 8804 8805 8806 8807 8808 8809 8810 8811 8812 8813 8814 8815 8816 8817 8818 8819 8820 8821 8822 8823 8824 8825 8826 8827 8828 8829 8830 8831 8832 8833 8834 8835 8836 8837 8838 8839 8840 8841 8842 8843 8844 8845 8846 8847 8848 8849 8850 8851 13298 15974 15975 15977 25100 25619 25775 25776 25777 25778 25779 25780 25781 25782 25783 25784 25785 25786 25787 25788 25789 27359 27360 27361 27362 27363 27364 27365 27366 27367 27368 27369 27370 27371 27372 27373 27374 27376 27412 29654 30516 32395 32396 32399 32400 32403 32404 32436 32437 32438 32439 35800 35805 35809 37428 37429 37431 40293 42159 42793 42794 42795 42796 42797 42798 42799 42800 42801 42802 42803 42804 42805 42806 42807 42808 42809 42810 42811 42812 42813 42814 42815 42816 42817 42818 42819 42820 42821 42822 42823 42824 42825 42826 42827 42828 42829 42830 42831 42832 42833 42834 42835 42836 42837 42838 42839 42840 42841 42842 42843 42844 42845 42846 42847 42848 42849 42850 42851 42852 42853 42854 42855 42856 42857 42858 42859 42860 42861 42862 42863 42864 42865 42866 42867 42868 42869 42870 42871 47589 49899 49900 49901 49902 49903 49904 49905 49906 49907 49908
creator: Austin M. Baggetta
creator: Douglas A. Bayliss
creator: Gábor Czirják
creator: Péter Enyedi
creator: Steve A.N. Goldstein
creator: Florian Lesage
creator: Daniel L. Minor, Jr.
creator: Leigh D. Plant
creator: Francisco Sepúlveda
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F79/2025.4

Inwardly rectifying potassium channels (KIR) in GtoPdb v.2025.4
type: item
description: The 2TM domain family of K channels are also known as the inward-rectifier K channel family. This family includes the strong inward-rectifier K channels (Kir2.x) that are constitutively active, the G protein-activated inward-rectifier K channels (Kir3.x) and the ATP-sensitive K channels (Kir6.x, which combine with sulphonylurea receptors (SUR1-3)). The pore-forming α subunits form tetramers, and heteromeric channels may be formed within subfamilies (e.g. Kir3.2 with Kir3.3).
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:33 2025; family F74, Inwardly rectifying potassium channels (KIR); version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F74 O429 O430 O431 O432 O433 O434 O435 O436 O437 O438 O439 O440 O441 O442 O443 I74 )
  topic: subjects
subject: GtoPdb_authors: 388 393 395 396 397 398 399 400 401 402 403 404 405 406 765 766 767 768
  topic: subjects
subject:
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  value: GtoPdb_references: 6595 7657 7658 7659 7660 7661 7662 7663 7664 7665 7667 8165 8166 8167 8168 8169 8170 8171 8172 8173 8174 8175 8176 8177 8178 8179 8180 8181 8182 8183 8184 8185 8186 8187 8188 8189 8190 8191 8192 8193 8194 8195 8196 8197 8198 8199 8200 8201 8202 8203 8204 8205 8206 8207 8208 8209 8210 8211 8212 8213 8214 8215 8216 8217 8218 8219 8220 8221 8222 8223 8224 8225 8226 8227 8228 8229 8230 8231 8232 8233 8234 8235 8236 8237 8238 8239 8240 8241 8242 8243 8244 8245 8246 8247 8248 8249 8250 8251 8252 8253 8254 8255 8256 8257 8258 8259 8260 8261 8262 8263 8264 8265 8266 8267 8268 8269 8270 8271 8272 8273 8274 8275 8276 8277 8278 8279 8280 8281 8282 8283 8284 8285 8286 8287 8288 8289 8290 8291 8292 8293 8294 8295 8296 8297 8298 8299 8300 8301 8302 8303 8304 8305 8306 8307 8308 8309 8310 8311 8312 8313 8314 8315 8316 8317 8318 8319 8320 8321 8322 8323 8324 8325 8326 8327 8328 8329 8330 8331 8332 8333 8334 8335 8336 8337 8338 8339 8340 8341 8342 8343 8344 8345 8346 8347 8348 8349 8350 8351 8352 8353 8354 8355 8356 8357 8358 8359 8360 8361 8362 8363 8364 8365 8366 8367 8368 8369 8370 8371 8372 8373 8374 15979 15982 20587 23447 24056 25006 25313 25314 25315 25316 25317 25318 25319 25320 25321 25322 25323 25324 25325 25326 25327 25328 25341 25342 25343 25344 25345 25347 25348 25349 25350 25351 25352 25353 25354 25355 25356 25357 25360 25361 25363 25364 25401 25668 25669 25670 25671 25672 25728 25729 25730 25731 25734 25735 25736 25737 25738 25739 25740 25747 25748 25749 25750 25751 25752 25753 25754 25755 25756 25757 25758 25759 25760 25761 25762 25763 25764 25765 25766 25767 25768 25769 25770 25771 25772 25773 25774 25872 25873 25874 25875 25879 25880 25904 28697 30517 31969 37755 37756 37757 37758 37759 40471 42159 42781 42782 42783 42784 42785 42786 42787 42788 42789 42790 42791 42792 43236 45754
creator: John P. Adelman
creator: Stephen Tucker
creator: Paul A. Slesinger
creator: Susumu Seino
creator: Henry Sackin
creator: Wade L. Pearson
creator: Lawrence G. Palmer
creator: Colin G. Nichols
creator: Takashi Miki
creator: Michel Lazdunski
creator: Yoshihisa Kurachi
creator: Yoshihiro Kubo
creator: Andreas Karschin
creator: Lily Y. Jan
creator: Atsushi Inanobe
creator: Hiroshi Hibino
creator: David E. Clapham
creator: Carol A. Vandenberg
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F74/2025.4

Class A Orphans in GtoPdb v.2025.4
type: item
description: The class A orphan GPCRs have been organised into the subfamilies listed below, to better segregate them based on evidence (or lack of evidence) for endogenous ligand or surrogate ligand interactions, and potential for deorphanization.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:32 2025; family F16, Class A Orphans; version 2025.4.
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_hierarchy: ( F16 ( F1111 O91 O93 O96 O100 O106 O107 O111 O116 O117 O118 O129 O131 O134 O135 O136 O138 O139 O141 O637 O154 O155 O158 ) ( F1112 O92 O97 O108 O121 O123 ) ( F1113 O83 O84 O85 O86 O87 O90 O95 O98 O99 O101 O102 O103 O104 O105 O110 O112 O113 O114 O115 O119 O122 O125 O128 O130 O132 O133 O137 O140 O142 O143 O144 O145 O81 O151 O152 O153 O156 O157 O159 O164 O165 ) ( F1115 O228 O120 ) ( F1116 O147 O148 O149 ) ( F1114 O150 O40 O88 ) I16 )
subject: GtoPdb_authors: 71 74 75 76 77 146 158 344 369 457 459 521 532 554 560 562 584 585 586 598 662 708 714 715 716 836 958
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 1302 1323 1330 1337 1346 1348 1377 1378 1379 1380 1381 1382 1383 1384 1385 1386 1387 1388 1389 1390 1454 1455 2156 2399 2437 2565 2566 2567 2568 2569 2570 2571 2573 2574 2575 2576 2577 2578 2583 2584 2585 2586 2588 2590 2591 2592 2593 2650 2653 3190 3191 3194 3201 3202 3258 3276 3299 3869 4175 4394 4755 5219 5228 5922 6103 10912 11524 11525 11526 11527 11528 11529 11530 11531 11532 11629 11653 11678 11679 11680 11681 11682 11683 11684 11685 11688 11690 11691 11692 11694 11695 11696 11697 11698 11699 11741 11744 11745 11746 11747 11749 11750 11756 11759 11760 11766 11768 11769 11772 11774 11775 11778 11779 11780 11782 11784 11785 11790 11791 11795 11796 11797 11798 11799 11800 11802 11804 11805 11806 11807 11809 11810 11824 11825 11826 11828 11829 11832 11833 11834 11835 11837 11840 11841 11845 11857 11858 11859 11860 11861 11862 11864 11910 11914 11922 11923 11926 11935 11940 11943 11944 11945 11946 11950 11951 11952 11955 11956 11957 11970 11971 11972 11973 11974 11975 11980 11981 11982 11984 11986 11987 11988 11991 11993 11995 12000 12001 12002 12004 12005 12006 12007 12008 12009 12011 12014 12015 12017 12038 12040 12046 12088 12101 12103 12104 12107 12108 12109 12110 12111 12112 12113 12116 12118 12119 12121 12122 12123 12124 12125 12189 12215 12216 12217 12221 12222 12224 12225 12226 12241 12242 12245 12249 12251 12252 12254 12284 12287 12288 12291 12292 12293 12294 12296 12303 12435 12452 12453 12457 12475 12482 12487 12488 12490 12491 12496 12497 12498 12500 12501 12502 12505 12511 12512 12516 12519 12520 12526 12527 12529 12590 12591 12592 12596 12597 12598 12599 12600 12603 12604 12605 12606 12607 12753 12782 12783 12785 12786 12787 12828 12829 12831 12836 12837 12838 12839 12861 12866 12882 12884 12885 12886 12887 12888 12889 12890 12891 12892 12893 12894 12895 12908 12909 12910 12911 12912 12913 12918 12919 12921 12953 13017 13046 13053 13072 13076 13123 13197 13202 13215 13217 13235 13236 13717 14081 14164 14347 14394 14893 14923 15035 …
creator: Stephen P.H. Alexander
creator: Chido Mpamhanga
creator: Richard Neubig
creator: Adam J Pawson
creator: Jean-Philippe Pin
creator: Joanna L. Sharman
creator: Michael Spedding
creator: Eliot Spindel
creator: Leigh Stoddart
creator: Laura Storjohann
creator: Walter G. Thomas
creator: Kalyan Tirupula
creator: Amy E. Monaghan
creator: Wen Chiy Liew
creator: Evi Kostenis
creator: Jim Battey
creator: Helen E. Benson
creator: Richard V. Benya
creator: Tom I. Bonner
creator: Anthony P. Davenport
creator: Khuraijam Dhanachandra Singh
creator: Satoru Eguchi
creator: Anthony Harmar
creator: Nick Holliday
creator: Robert T. Jensen
creator: Sadashiva Karnik
creator: Patrick Vanderheyden
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F16/2025.4

Cyclic nucleotide-regulated channels (CNG) in GtoPdb v.2025.4
type: item
description: Cyclic nucleotide-gated (CNG) channels are responsible for signalling in the primary sensory cells of the vertebrate visual and olfactory systems. CNG channels are voltage-independent cation channels formed as tetramers. Each subunit has 6TM, with the pore-forming domain between TM5 and TM6. CNG channels were first found in rod photoreceptors [83, 120], where light signals through rhodopsin and transducin to stimulate phosphodiesterase and reduce intracellular cyclic GMP level. This results in a closure of CNG channels and a reduced ‘dark current’. Similar channels were found in the cilia of olfactory neurons [181] and the pineal gland [71]. The cyclic nucleotides bind to a domain in the C terminus of the subunit protein: other channels directly binding cyclic nucleotides include hyperpolarisation-activated, cyclic nucleotide-gated channels (HCN), ether-a-go-go and certain plant potassium channels. The HCN channels are cation channels that are activated by hyperpolarisation at voltages negative to ~-50 mV. The cyclic nucleotides cyclic AMP and cyclic GMP directly bind to the cyclic nucleotide-binding domain of HCN channels and shift their activation curves to more positive voltages, thereby enhancing channel activity. HCN channels underlie pacemaker currents found in many excitable cells including cardiac cells and neurons [65, 192]. In native cells, these currents have a variety of names, such as Ih, Iq and If. The four known HCN channels have six transmembrane domains and form tetramers. It is believed that the channels can form heteromers with each other, as has been shown for HCN1 and HCN4 [2]. High resolution structural studies of CNG and HCN channels has provided insight into the gating processes of these channels [139, 146, 140]. A standardised nomenclature for CNG and HCN channels has been proposed by the NC-IUPHAR Subcommittee on voltage-gated ion channels [108].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:33 2025; family F71, Cyclic nucleotide-regulated channels (CNG); version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F71 O394 O395 O396 O397 O398 O399 O400 O401 O402 O403 I71 )
  topic: subjects
subject: GtoPdb_authors: 389 390 391 687 704 1100
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 7600 7601 7602 7603 7604 7605 7606 7607 7608 7609 7610 7611 7612 7613 7614 7615 7616 7617 7618 7619 7621 7622 7624 7625 7626 7627 7628 7629 7630 7631 7632 7633 7634 7635 7636 7637 7638 7639 7640 7641 7974 7975 7976 7977 7978 7979 7980 7981 7982 7983 7984 7985 7986 7987 7988 7989 7990 7991 7992 7993 7994 7995 7996 7997 7998 7999 8000 8001 8002 8003 8004 8005 8006 8007 8008 8009 8010 8011 8012 8013 8014 8015 8016 8017 8018 8020 8021 8022 8023 8025 8026 8027 8028 8029 8030 8031 8032 8033 8034 8035 8036 8037 8038 8039 8040 8041 8042 8043 8044 8045 8046 8047 8048 8049 8050 8051 8052 8053 8054 8055 8056 8057 8058 8059 8060 8061 8062 8063 8064 8065 8066 8067 8068 8069 8070 8071 8072 8073 8074 8075 8076 15780 15781 15782 15783 15818 15824 15829 21147 21148 21149 21150 21151 21152 21153 21154 21155 21156 21157 21158 21159 21160 21161 21162 21167 21168 21169 21170 21171 21172 21173 21174 21175 21176 21177 21178 21179 21180 21181 21182 21183 21184 21185 21187 21189 21191 21192 21193 21194 21195 21196 21197 21198 21200 21201 21202 21203 21204 21206 21207 21208 21209 21210 21211 21212 21213 21214 21215 21216 21218 21220 21221 21222 21223 21224 21225 21226 21227 21228 21229 21232 21233 21234 21235 21236 21237 21238 21239 21240 21241 21242 21249 21254 21255 21256 21257 21258 21259 21260 21261 21262 21263 21264 21265 21266 21267 21268 21276 21282 21283 21284 21290 21291 21292 21295 21296 21297 21298 28663 28664 31970 37213 37217 41706 42159 42759 42760 42761 42762 42763 42764 42765 42766 42767 42768 42769 42770 42771 42772 42773 42774 42775 42776 45134 45135
creator: Elvir Becirovic
creator: Martin Biel
creator: Stefanie Fenske
creator: Verena Hammelmann
creator: Franz Hofmann
creator: U. Benjamin Kaupp
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F71/2025.4

Adenosine receptors in GtoPdb v.2025.4
type: item
description: Adenosine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Adenosine Receptors [114]) are activated by the endogenous ligand adenosine (potentially inosine also at A3 receptors). Crystal and cryo-EM structures for all four adenosine receptors have been solved, occupied by either agonists (sometimes in the presence of an allosteric modulator) or antagonists. Many of these structures were incorporated in a recent review [155]. More recently, structures for the A2B receptor [58, 48] and the A3 receptor [279, 47] were elucidated. The A2A receptor is used as a workhorse in GPCR structure elucidation: almost 100 structures are available in the Protein Data Bank (www.rcsb.org). istradefylline, a selective A2A receptor antagonist, is on the market for the treatment of Parkinson's disease, while caffeine's mechanism of action is largely due to its antagonism of at least three of the four adenosine receptor subtypes. Allosteric modulators, particular PAMs of A1 and A3 receptors, have been explored chemically and structurally [88, 293].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Thu Dec 11 12:34:31 2025; family F3, Adenosine receptors; version 2025.4.
  topic: subjects
subject: GtoPdb_hierarchy: ( F3 O18 O19 O20 O21 I3 )
  topic: subjects
subject: GtoPdb_authors: 43 44 47 48 49 50 253 305 597 763 1184
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 639 640 641 642 643 644 646 647 648 649 650 651 652 653 654 655 656 657 658 659 660 661 662 663 664 665 666 667 668 669 670 671 672 673 674 675 676 677 678 679 680 681 682 683 684 685 686 687 688 689 690 691 692 693 694 695 696 697 698 699 700 701 702 703 704 705 706 707 708 709 710 711 712 713 714 715 716 717 718 719 720 721 722 723 724 725 726 727 728 729 730 734 735 736 737 738 739 740 741 742 743 744 745 746 747 748 749 750 751 752 753 754 755 756 757 758 759 760 761 762 763 764 765 766 767 768 769 770 771 772 773 774 775 776 777 778 779 780 781 782 783 784 785 786 787 788 789 790 791 792 793 794 795 796 797 798 799 800 801 802 803 804 805 806 807 808 809 810 811 812 813 814 815 816 817 818 819 820 821 822 823 824 825 826 827 828 829 830 831 832 833 834 836 837 838 839 840 841 844 845 846 847 848 849 850 851 852 853 854 855 4080 5391 5747 11418 13668 13669 13670 13671 13672 13673 13674 13676 13809 13836 13837 13840 14834 18500 18501 18502 18503 18504 18505 18506 18507 18508 18510 18511 18512 18513 18514 18515 18516 18517 18518 18519 18520 18521 18522 18523 18524 18525 18526 18527 18528 18529 18530 18531 18532 18533 18534 18535 18536 18537 18538 18539 18540 18542 18543 18544 18546 18548 18549 18550 18551 18552 18554 18555 18556 18557 18558 18559 18560 18561 18681 18682 18806 20549 20550 20551 20552 20553 22135 22136 22137 22141 23144 23145 23146 23147 23148 23149 23150 23151 23152 23153 23154 23155 23156 23157 23158 23159 23160 23161 23162 23163 23164 23165 23166 23167 24030 24104 25366 25367 25368 25369 25370 25371 25372 25373 25374 25375 25376 25377 25378 25379 25380 25381 25382 25383 25384 25385 25386 25387 25388 27616 27934 27939 30082 30083 30412 30413 30414 30565 30900 31885 31904 32621 32736 32816 32824 33393 33528 33545 34292 34293 34297 35006 35316 36099 36710 36723 36724 36781 37000 37551 38121 38566 40026 40030 40332 40334 40336 40337 40338 40339 40340 42159 42904 43531 44041 44812 44813 50477 50478 50479 50480 50481 50482 50483 5048…
creator: Bertil B. Fredholm
creator: Ulrich Schwabe
creator: Lauren May
creator: Christa E. Müller
creator: Joel Linden
creator: Karl-Norbert Klotz
creator: Kenneth A. Jacobson
creator: Adriaan P. IJzerman
creator: Rebecca Hills
creator: Bruno G. Frenguelli
creator: Gary L. Stiles
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-12-10
publication date: 2025-12-10
doi: 10.2218/gtopdb/F3/2025.4

S33: Prolyl aminopeptidase in GtoPdb v.2025.3
type: item
description: Peptidase family S33 contains mainly exopeptidases that act at the N-terminus of peptides.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:40 2025; family F917, S33: Prolyl aminopeptidase; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F917 O2626 O2875 O1399 )
  topic: subjects
subject: GtoPdb_authors: 532 849 964
  topic: subjects
subject: GtoPdb_references: 17767 17864 22918 28714 30462 32363 35856 36033 38749 39791 42159 42987 43226 43227 43994 46269 47743 47833 48035
  topic: subjects
creator: Stephen P.H. Alexander
creator: Patrick Doherty
creator: Christopher J. Fowler
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F917/2025.3

Receptor guanylyl cyclase (RGC) family in GtoPdb v.2025.3
type: item
description: The mammalian genome encodes seven guanylyl cyclases, GC-A to GC-G, that are homodimeric transmembrane receptors activated by a diverse range of endogenous ligands. These enzymes convert guanosine-5'-triphosphate to the intracellular second messenger cyclic guanosine-3',5'-monophosphate (cyclic GMP). GC-A, GC-B and GC-C are expressed predominantly in the cardiovascular system, skeletal system and intestinal epithelium, respectively. GC-D and GC-G are found in the olfactory neuropepithelium and Grueneberg ganglion of rodents, respectively. GC-E and GC-F are expressed in retinal photoreceptors.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:42 2025; family F1022, Receptor guanylyl cyclase (RGC) family; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F1022 ( F662 O1747 O1748 O1750 O1749 O2898 O2031 O2899 O2900 ) ( F939 O1287 O2897 O1288 O1289 O1290 O1291 ) )
  topic: subjects
subject: GtoPdb_authors: 787 788 789 790 791 792 793 794 906 907 908 1067 1068
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 16489 16490 16491 16492 16493 17361 17362 17710 17712 17713 17714 17715 17718 17722 17728 17729 17730 17731 17814 17843 17847 17859 22113 24736 24737 29395 30713 30714 30716 30722 30946 30947 30948 30950 30951 30960 34835 35312 35313 36844 36845 36846 36847 36851 39927 40248 40249 40250 42159 44617 48802 49918 49919 49920 49921
creator: Annie Beuve
creator: Johannes-Peter Stasch
creator: Harald H.H.W. Schmidt
creator: Michael Russwurm
creator: Lincoln R. Potter
creator: Michaela Kuhn
creator: Doris Koesling
creator: Adrian J. Hobbs
creator: John Garthwaite
creator: Andreas Friebe
creator: John C. Burnett, Jr.
creator: Peter Brouckaert
creator: Scott A. Waldman
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F1022/2025.3

Carnitine palmitoyltransferases in GtoPdb v.2025.3
type: item
description: The CPT1 enzymes convert long chain (greater than ∼C12) acyl-CoA molecules to acylcarnitine derivatives to facilitate their transport from the cytosol into the mitochondrial matrix via the carnitine/acylcarnitine carrier (CACT; SLC25A20). The acylcarnitines are converted back to acyl-CoA by CPT2 to support the fatty acid oxidation (FAO) cycle in the mitochondria. CPT1s are allosterically inhibited by malonyl-CoA.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:43 2025; family F1089, Carnitine palmitoyltransferases; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F1089 O3249 O3250 O3251 O3252 )
  topic: subjects
subject: GtoPdb_authors: 1143 1144
  topic: subjects
subject: GtoPdb_references: 42159 46242 46243 46244 46245 46246 48729
  topic: subjects
creator: Núria Casals
creator: Rosalía Rodríguez
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F1089/2025.3

Endocannabinoid turnover in GtoPdb v.2025.3
type: item
description: The principle endocannabinoids are 2-acylglycerol esters, such as 2-arachidonoylglycerol (2-AG), and N-acylethanolamines, such as anandamide (N-arachidonoylethanolamine, AEA). The glycerol esters and ethanolamides are synthesised and hydrolysed by parallel, independent pathways. Mechanisms for release and re-uptake of endocannabinoids are unclear, although potent and selective inhibitors of facilitated diffusion of endocannabinoids across cell membranes have been developed [32]. FABP5 (Q01469) has been suggested to act as a canonical intracellular endocannabinoid transporter in vivo [19]. For the generation of 2-arachidonoylglycerol, the key enzyme involved is diacylglycerol lipase (DAGL), whilst several routes for anandamide synthesis have been described, the best characterized of which involves N-acylphosphatidylethanolamine-phospholipase D (NAPE-PLD, [79]). A transacylation enzyme which forms N-acylphosphatidylethanolamines has been identified as a cytosolic enzyme, PLA2G4E (Q3MJ16) [70]. In vitro experiments indicate that the endocannabinoids are also substrates for oxidative metabolism via cyclooxygenase, lipoxygenase and cytochrome P450 enzyme activities [6, 26, 81].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:41 2025; family F943, Endocannabinoid turnover; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F943 ( F273 O1398 O1400 O1401 O1402 ) ( F944 O1396 O1397 O1399 O3147 O2919 O3070 ) )
  topic: subjects
subject: GtoPdb_authors: 532 849 964 1035 1036
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 13691 16530 16531 16532 16533 16534 16536 16537 16547 16549 17766 17767 17854 17855 17861 17862 17864 17865 21959 22917 22918 24087 24954 25027 30430 30431 30460 30462 30474 30475 30476 30477 30478 30479 30505 30509 30673 30725 30727 30996 32361 32362 32363 32364 32365 32366 32367 32368 32391 32392 32616 32617 32618 33310 35856 36033 36314 36317 36318 36336 36337 37051 37052 37053 37054 37056 37057 37058 37069 37070 37078 37079 37080 37081 37082 37083 37084 37085 37086 37089 37543 38749 39002 39722 39724 39755 39791 40328 42159 42987 43226 43227 43230 43994 44524 46269 47833 48035 48698 49880
creator: Stephen P.H. Alexander
creator: Patrick Doherty
creator: Christopher J. Fowler
creator: Jürg Gertsch
creator: Mario van der Stelt
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F943/2025.3

Coronavirus (CoV) proteins in GtoPdb v.2025.3
type: item
description: Coronaviruses are large, often spherical, enveloped, single-stranded positive-sense RNA viruses, ranging in size from 80-220 nm. Their genomes and protein structures are highly conserved. Three coronaviruses have emerged over the last 20 years as serious human pathogens: SARS-CoV was identified as the causative agent in an outbreak in 2002-2003, Middle East respiratory syndrome (MERS) CoV emerged in 2012 and the novel coronavirus SARS-CoV-2 emerged in 2019-2020. SARS-CoV-2 is the virus responsible for the infectious disease termed COVID-19 (WHO Technical Guidance 2020).
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:43 2025; family F1034, Coronavirus (CoV) proteins; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F1034 O3116 O3111 O3117 O3118 O3123 O3120 O3275 O3261 O3198 O3206 O3276 O3121 O3277 O3132 O3115 O3119 O3122 O3124 O3125 O3139 O3114 I1034 )
  topic: subjects
subject: GtoPdb_authors: 532 1077 1078
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 38908 38932 38947 38951 38968 38972 38975 38977 39035 39036 39039 39040 39041 39042 39043 39044 39045 39046 39047 39048 39049 39050 39052 39053 39054 39055 39056 39057 39058 39059 39060 39061 39062 39063 39064 39065 39068 39069 39070 39071 39072 39073 39074 39075 39076 39077 39078 39079 39080 39081 39082 39083 39086 39099 39102 39110 39114 39403 39404 39408 39508 39756 39758 39759 39772 39773 39775 39776 39777 39778 39781 39934 39935 39974 39975 39976 39977 39978 39979 40004 40005 40142 40143 40144 40146 40218 40219 40220 40221 40222 40311 40418 40433 40461 40468 40476 40482 40614 40995 41121 41381 41394 41395 41396 41449 41450 41460 41534 41543 41756 41928 41929 41930 41957 41965 41968 41988 41990 41991 42109 42110 42152 42159 42448 42465 42474 42508 42553 42555 42556 42559 42561 42562 42563 42570 42571 42572 42591 42592 42593 42618 42620 42779 42780 42925 43070 43104 43105 43106 43107 43143 43276 43277 43278 43279 43285 43360 43361 43418 43486 43487 43491 43544 43575 43576 43577 43595 43596 43656 43740 43741 43742 43816 43817 44170 44171 44172 44173 44174 44175 44176 44177 44178 44179 44185 44189 44190 44191 44272 44273 44302 44313 44520 44726 45341 45343 45345 45346 45347 45348 45349 45350 45351 45415 45507 45655 45850 45851 45852 45853 45854 45855 45943 45980 45996 46003 46181 46296 46337 46350 46351 46352 46354 46355 46356 46357 46358 46359 46360 46361 46395 46396 46397 46398 46399 46448 46612 46891 46903 47118 47187 47292 47293 47337 47405 47406 47408 47410 47510 47573 47608 47622 47702 47825 47880 47881 47882 47883 47904 47905 47912 47914 48040 48150 48167 48183 48224 48308 48324 48325 48326 48327 48398 48403 48440 48609 48852 48929 49052 49162 49165 49214 49228 49230 49349 49438 49453 49928
creator: Stephen P.H. Alexander
creator: Jonathan K. Ball
creator: Theocharis Tsoleridis
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F1034/2025.3

SLC54 Mitochondrial pyruvate carriers in GtoPdb v.2025.3
type: item
description: The mitochondrial pyruvate carrier (MPC) is composed of SLC54 family members (MPC1 or MPC1L and MPC2) [1, 5, 10], which form functional hetero-dimers [9, 8]. The MPC is expressed in the inner mitochondrial membrane and is responsible for the import of pyruvate into mitochondria [1, 5]. Pyruvate is oxidized to acetyl-CoA by pyruvate dehydrogenase which is localized in the mitochondrial matrix. Ubiquitous disruption of either MPC1 or MPC2 expression results in embryonic lethality [11, 12]. Clinically relevant concentrations of the insulin sensitizers, thiazolidinediones, inhibit the MPC [3]. Other clinically relevant inhibitors of the MPC complex are lonidamine [7, 8], quinolone antibacterials [6], entacapone and nitrofurantoin [8].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:41 2025; family F1006, SLC54 Mitochondrial pyruvate carriers; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F1006 O3022 O3023 O3024 )
  topic: subjects
subject: GtoPdb_authors: 1084 1139
  topic: subjects
subject: GtoPdb_references: 36417 36418 36419 40853 40854 40855 40856 42159 45399 45400 45401 45402
  topic: subjects
creator: Sotiria Tavoulari
creator: Calum Wilson
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F1006/2025.3

E3 ubiquitin ligase components in GtoPdb v.2025.3
type: item
description: Ubiquitination (a.k.a. ubiquitylation) is a protein post-translational modification that typically requires the sequential action of three enzymes: E1 (ubiquitin-activating enzymes), E2 (ubiquitin-conjugating enzymes), and E3 (ubiquitin ligases) [50]. Ubiquitination of proteins can target them for proteasomal degradation, or modulate cellular processes including cell cycle progression, transcriptional regulation, DNA repair and signal transduction. E3 ubiquitin ligases, of which there are >600 in humans, are a family of highly heterogeneous proteins and protein complexes that recruit ubiquitin-loaded E2 enzymes to mediate transfer of the ubiquitin molecule from the E2 to protein substrates. Target substrate specificity is determined by a substrate recognition subunit within the E3 complex. E3 ligases are being exploited as pharmacological targets to facilitate targeted protein degradation (TPD), as an alternative to small molecule inhibitors [5], through the development of proteolysis targeting chimeras (PROTACs) and molecular glues.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:42 2025; family F1023, E3 ubiquitin ligase components; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F1023 O3234 O3086 O3244 O3233 O3262 O3136 O3235 O3202 O3204 O3254 )
  topic: subjects
subject: GtoPdb_authors: 706 1072
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 24033 24035 33255 33360 37799 37800 37801 37802 37803 37804 37805 37859 38419 38420 38421 38422 38423 38424 38425 38452 38465 39947 39948 39949 39951 42159 42491 42492 42493 42932 42963 43185 43702 43888 43889 43890 43891 43892 43893 44018 44034 44702 45323 45546 45554 45579 45583 45584 45585 45627 45670 45840 45841 45842 46137 46139 46286 46287 46288 46289 46336 46366 46367 46368 46369 46660 47167 47168
creator: Elena Faccenda
creator: Robert Layfield
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F1023/2025.3

Blood coagulation components in GtoPdb v.2025.3
type: item
description: Coagulation as a process is interpreted as a mechanism for reducing excessive blood loss through the generation of a gel-like clot local to the site of injury. The process involves the activation, adhesion (see Integrins), degranulation and aggregation of platelets, as well as proteins circulating in the plasma. The coagulation cascade involves multiple proteins being converted to more active forms from less active precursors (for example, prothrombin [Factor II] is converted to thrombin [Factor IIa]), typically through proteolysis (see Proteases). Listed here are the components of the coagulation cascade targeted by agents in current clinical usage or at an advanced level of development.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:39 2025; family F853, Blood coagulation components; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F853 O2362 O3192 O2606 O2607 O2359 O2360 O2632 )
  topic: subjects
subject: GtoPdb_authors: 1096
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 22292 22293 22308 22309 22318 22326 22341 22345 23362 23363 23364 23365 23366 23367 23368 23369 23873 23874 24811 25293 25431 25914 28691 28749 28751 29739 33261 33596 33597 33598 33974 34699 34700 34701 34702 36238 38989 41156 41157 41158 41159 41191 41192 41193 41195 41199 41200 42159 42913 42949 43063 43628 43674 44010 44740 44741 46494 49008 49851 49852 49853
creator: Szu S. Wong
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F853/2025.3

Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2025.3
type: item
description: Regulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [226, 530, 579, 584, 585, 744, 755, 445, 11].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:39 2025; family F891, Regulators of G protein Signaling (RGS) proteins; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F891 ( F892 O2801 O2802 O2803 ) ( F893 O2804 O2808 O2810 O2811 O2812 O2813 O2805 O2806 O2807 O2809 ) ( F894 O2815 O2816 O2817 O2814 ) ( F895 O2818 O2819 O2820 ) )
  topic: subjects
subject: GtoPdb_authors: 795 796 797 798 799 800 801 802 808 819 820 821 822 823 824 883 891 892 893 896 897 899 901 973 975 1085 1086 1087 1088 1104 1105 1106 1107
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 5594 6595 8242 8263 11956 19944 21640 21641 25576 25577 25881 26503 27712 27713 28362 28363 28364 28365 28366 28367 28368 28369 28370 28371 28372 28373 28374 28375 28376 28377 28378 28379 28380 28381 28382 28383 28384 28385 28386 28387 28388 28389 28391 28392 28393 28394 28395 28396 28397 28398 28399 28400 28401 28402 28403 28404 28405 28406 28407 28408 28409 28410 28411 28412 28413 28414 28415 28416 28417 28418 28419 28420 28422 28423 29416 29417 29418 29419 29420 29421 29422 29423 29424 29425 29426 29427 29428 29429 29430 29431 29432 29433 29434 29435 29436 29437 29438 29439 29440 29441 29442 29443 29444 29445 29446 29447 29448 29449 29450 29451 29452 29453 29454 29455 29456 29457 29458 29459 29460 29461 29462 29463 29464 29465 29466 29467 29468 29469 29470 29471 29472 29473 29474 29475 29476 29477 29478 29479 29480 29481 29482 29483 29484 29485 29486 29487 29488 29489 29490 29491 29492 29493 29494 29495 29496 29497 29498 29499 29501 29502 29503 29504 29505 29506 29507 29508 29509 29510 29511 29512 29513 29514 29515 29516 29517 29518 29519 29520 29521 29522 29523 29524 29525 29526 29527 29528 29529 29530 29531 29532 29533 29534 29535 29536 29537 29538 29539 29540 29541 29542 29543 29544 29545 29546 29547 29548 29549 29550 29551 29552 29553 29554 29555 29556 29557 29558 29559 29560 29561 29562 29563 29564 29565 29566 29567 29568 29569 29570 29571 29572 29573 29574 29575 29576 29577 29578 29579 29580 29581 29582 29583 29584 29585 29586 29587 29588 29589 29590 29591 29592 29593 29594 29595 29596 29597 29598 29599 29600 29601 29602 29603 29604 29605 29606 29607 29608 29609 29643 29644 29645 29646 29647 29648 29649 29650 29651 29758 29759 29760 29761 29762 29763 29764 29765 29766 29767 29768 29769 29770 29771 29772 29773 29774 29775 29776 29777 29778 29779 29780 29781 29782 29783 29784 29785 29786 29787 29788 29789 29790 29791 29792 29793 29794 29795 29796 29797 29798 29799 29800 30875 30876 30877 30878 30879 30880 31079 31080 31082 31083 31084 31085…
creator: Katelin E. Ahlers-Dannen
creator: Harrison J. McNabb
creator: Carolina Montañez-Miranda
creator: Osita W. Ogujiofor
creator: Hoa Phan Thi Nhu
creator: David L. Roman
creator: Vincent Shaw
creator: Benita Sjögren
creator: Mackenzie M. Spicer
creator: Katherine E. Squires
creator: Laurie Sutton
creator: Menbere Wendimu
creator: Thomas M. Wilkie
creator: Keqiang Xie
creator: Qian Zhang
creator: Luke D. Mascarenhas
creator: Kirill Martemyanov
creator: Zili Luo
creator: Mohammed Alqinyah
creator: Christopher Bodle
creator: Josephine Bou Dagher
creator: Bandana Chakravarti
creator: Shreoshi P. Choudhuri
creator: Kirk M. Druey
creator: Rory A. Fisher
creator: Kyle J. Gerber
creator: John R. Hepler
creator: Shelley B. Hooks
creator: Havish S. Kantheti
creator: Behirda Karaj
creator: Somayeh Layeghi-Ghalehsoukhteh
creator: Jae-Kyung Lee
creator: Yalda Zolghadri
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F891/2025.3

Peptidyl-prolyl cis/trans isomerases in GtoPdb v.2025.3
type: item
description: Peptidyl-prolyl cis/trans isomerases (PPIases) are an enzyme family which catalyse the cis/trans isomerisation of proline peptide bonds to promote the folding and re-folding of peptides and proteins. Three subfamilies have been identified: cyclophilins, FK506-binding proteins and parvulins. Individual PPIases are overexpressed in a number of cancers [65], and family members have been targetted for immunosuppressant effects.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:38 2025; family F845, Peptidyl-prolyl cis/trans isomerases; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F845 O2609 O3177 O3175 O3176 O3178 O3171 O2751 O3179 I845 )
  topic: subjects
subject: GtoPdb_authors: 1099 1101
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 23335 23377 23378 23379 23824 23825 23826 26345 41333 41364 41365 41366 41367 41368 41369 41370 41371 41372 41373 41374 41377 41402 41792 41793 41794 41795 41796 41797 41798 41799 41800 41801 41802 41803 41804 41805 41806 41807 41808 41809 41810 41811 41812 41813 41814 41815 41816 41817 41818 41820 41822 41824 41825 41827 41828 41829 41830 41831 41832 41833 41834 41835 41836 41837 41838 41839 41840 41915 41916 41917 42105 42159 42200 42201 42202 42203 42495 45327 45446 47417 47418 48502
creator: Stephanie Annett
creator: Tracy Robson
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F845/2025.3

RAS subfamily in GtoPdb v.2025.3
type: item
description: The RAS proteins (HRAS, NRAS and KRAS) are small membrane-localised G protein-like molecules of 21 kd. They act as an on/off switch linking receptor and non-receptor tyrosine kinase activation to downstream cytoplasmic or nuclear events. Binding of GTP activates the switch, and hydrolysis of the GTP to GDP inactivates the switch. The RAS proto-oncogenes are the most frequently mutated class of proteins in human cancers. Common mutations compromise the GTP-hydrolysing ability of the proteins causing constitutive activation [38], which leads to increased cell proliferation and decreased apoptosis [49]. Because of their importance in oncogenic transformation these proteins have become the targets of intense drug discovery effort [2].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:40 2025; family F897, RAS subfamily; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F897 O2822 O2823 O2824 O3324 I897 )
  topic: subjects
subject: GtoPdb_authors: 706
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 26443 26444 26445 26446 26447 26448 26449 26453 26454 26455 26456 26457 26458 26459 26460 26461 26462 26463 26468 26469 26470 37762 37763 37764 38815 38817 39420 40027 42159 43284 43298 43591 43900 43901 43903 43919 44397 44682 45709 46111 46256 47580 48683 50005 50006 50312 50313 50314 50315 50316 50321
creator: Elena Faccenda
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F897/2025.3

Hydrolases & Lipases in GtoPdb v.2025.3
type: item
description: Listed in this section are hydrolases not accumulated in other parts of the Concise Guide, such as monoacylglycerol lipase and acetylcholinesterase. Pancreatic lipase is the predominant mechanism of fat digestion in the alimentary system; its inhibition is associated with decreased fat absorption. CES1 is present at lower levels in the gut than CES2 (P23141), but predominates in the liver, where it is responsible for the hydrolysis of many aliphatic, aromatic and steroid esters. Hormone-sensitive lipase is also a relatively non-selective esterase associated with steroid ester hydrolysis and triglyceride metabolism, particularly in adipose tissue. Endothelial lipase is secreted from endothelial cells and regulates circulating cholesterol in high density lipoproteins.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:38 2025; family F799, Hydrolases & Lipases; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F799 O2465 O2471 O1396 O1397 O2592 O3298 O2888 O2889 O2970 O1400 O1395 O2593 O2591 O3290 O3291 O1399 O3085 O3214 O3258 O3101 O2590 O3253 O3307 O1432 O1417 O1434 O3063 )
  topic: subjects
subject: GtoPdb_authors: 532 707 748 749 750 751 849 964
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 16537 17767 17769 17806 17829 17849 17854 17861 17862 17864 17865 17866 22288 22424 22425 22906 22907 22908 22909 22910 22911 22913 22914 22915 22916 22917 22918 24087 24107 24108 24140 24950 24954 25027 29328 29837 29841 30431 30448 30449 30460 30462 30474 30478 30479 30505 30509 30575 30576 30577 30578 30597 30601 30602 30604 30605 30606 30607 30673 30724 30725 30727 30794 30796 30822 31786 32125 32363 32514 33310 33493 33510 33512 33727 33869 33870 33871 33872 33873 33877 33882 34193 34194 34201 34284 34755 35293 35856 36033 36090 36132 36336 36337 36743 36744 36745 36746 36747 36748 36749 36750 36751 36752 36753 36754 36755 36756 37051 37052 37053 37054 37069 37543 37765 37766 37767 37768 37769 38286 38287 38338 38341 38343 38502 38529 38749 38759 38760 38761 39791 40291 41463 42106 42159 42613 42940 42987 43226 43227 43230 43545 43604 43960 43994 44469 44524 44594 45679 46269 46272 46276 46277 46309 46633 46634 46635 46637 47721 47722 47833 48035 48162 48463 48592 48623 48696 48712 48714 48959 48965 48991 48992 48993 48994 49213 49880
creator: Stephen P.H. Alexander
creator: Patrick Doherty
creator: David Fairlie
creator: Christopher J. Fowler
creator: Christopher M. Overall
creator: Neil Rawlings
creator: Christopher Southan
creator: Anthony J. Turner
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F799/2025.3

3.6.5.2 Small monomeric GTPases in GtoPdb v.2025.3
type: item
description: Small G-proteins, are a family of hydrolase enzymes that can bind and hydrolyze guanosine triphosphate (GTP). They are a type of G-protein found in the cytosol that are homologous to the alpha subunit of heterotrimeric G-proteins, but unlike the alpha subunit of G proteins, a small GTPase can function independently as a hydrolase enzyme to bind to and hydrolyze a guanosine triphosphate (GTP) to form guanosine diphosphate (GDP). The best-known members are the Ras GTPases and hence they are sometimes called Ras subfamily GTPases.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:40 2025; family F896, 3.6.5.2 Small monomeric GTPases; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F896 ( F897 O2822 O2823 O2824 O3324 I897 ) ( F938 O2916 O3292 ) )
  topic: subjects
subject: GtoPdb_authors: 706
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 26443 26444 26445 26446 26447 26448 26449 26453 26454 26455 26456 26457 26458 26459 26460 26461 26462 26463 26468 26469 26470 31925 31931 31932 31933 37762 37763 37764 38815 38817 39420 40027 42159 43284 43298 43591 43900 43901 43903 43919 44397 44682 45709 46111 46256 47580 47725 47726 47727 47728 47729 48683 50005 50006 50312 50313 50314 50315 50316 50321
creator: Elena Faccenda
rights: Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
date: 2025-09-10
publication date: 2025-09-10
doi: 10.2218/gtopdb/F896/2025.3