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: S33: Prolyl aminopeptidase in GtoPdb v.2025.3
items: SLC54 Mitochondrial pyruvate carriers in GtoPdb v.2025.3
items: Coronavirus (CoV) proteins in GtoPdb v.2025.3
items: Endocannabinoid turnover in GtoPdb v.2025.3
items: Carnitine palmitoyltransferases in GtoPdb v.2025.3
items: Receptor guanylyl cyclase (RGC) family in GtoPdb v.2025.3
items: E3 ubiquitin ligase components in GtoPdb v.2025.3
items: RAS subfamily in GtoPdb v.2025.3
items: Hydrolases & Lipases in GtoPdb v.2025.3
items: Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2025.3
items: 3.6.5.2 Small monomeric GTPases in GtoPdb v.2025.3
items: Peptidyl-prolyl cis/trans isomerases in GtoPdb v.2025.3
items: Blood coagulation components in GtoPdb v.2025.3
items: Type VI RTKs: PTK7/CCK4 in GtoPdb v.2025.3
items: Integrins in GtoPdb v.2025.3
items: Type XV RTKs: RYK in GtoPdb v.2025.3
items: Type III receptor serine/threonine kinases in GtoPdb v.2025.3
items: Ceramide turnover in GtoPdb v.2025.3
items: Type IX RTKs: MuSK in GtoPdb v.2025.3
items: Type XIV RTKs: RET in GtoPdb v.2025.3
items: Ligand-gated ion channels in GtoPdb v.2025.3
items: SLC51 family of steroid-derived molecule transporters in GtoPdb v.2025.3
items: Type XX RTKs: STYK1 in GtoPdb v.2025.3
items: Delta subfamily in GtoPdb v.2025.3
items: Type XVIII RTKs: LMR family in GtoPdb v.2025.3
items: Chemerin receptors in GtoPdb v.2025.3
items: Succinate receptor in GtoPdb v.2025.3
items: Type VII RTKs: Neurotrophin receptor/Trk family in GtoPdb v.2025.3
items: Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family in GtoPdb v.2025.3
items: Type XIII RTKs: Ephrin receptor family in GtoPdb v.2025.3

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

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

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

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

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

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

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

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

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

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

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

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

Type VI RTKs: PTK7/CCK4 in GtoPdb v.2025.3
type: item
description: The PTK7 receptor is associated with polarization of epithelial cells and the development of neural structures. Sequence analysis suggests that the gene product is catalytically inactive as a protein kinase, hence acting as a pseudokinase. There is, however, evidence for a role in Wnt signalling [2], as well as an ability to form heteromers with other RTKs, such as VEGFR2 and ROR2.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:36 2025; family F792, Type VI RTKs: PTK7/CCK4; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F792 O1848 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject: GtoPdb_references: 17386 42159
  topic: subjects
creator: Chloe J. Peach
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/F792/2025.3

Integrins in GtoPdb v.2025.3
type: item
description: Integrins are unusual signalling proteins that function to signal both from the extracellular environment into the cell, but also from the cytoplasm to the external of the cell. The intracellular signalling cascades associated with integrin activation focus on protein kinase activities, such as focal adhesion kinase and Src. Based on this association between extracellular signals and intracellular protein kinase activity, we have chosen to include integrins in the 'Catalytic receptors' section of the database until more stringent criteria from NC-IUPHAR allows precise definition of their classification. Integrins are heterodimeric entities, composed of α and β subunits, each 1TM proteins, which bind components of the extracellular matrix or counter-receptors expressed on other cells. One class of integrin contains an inserted domain (I) in its α subunit, and if present (in α1, α2, α10, α11, αD, αE, αL, αM and αX), this I domain contains the ligand binding site. All β subunits possess a similar I-like domain, which has the capacity to bind ligand, often recognising the RGD motif. The presence of an α subunit I domain precludes ligand binding through the β subunit. Integrins provide a link between ligand and the actin cytoskeleton (through typically short intracellular domains). Integrins bind several divalent cations, including a Mg2+ ion in the I or I-like domain that is essential for ligand binding. Other cation binding sites may regulate integrin activity or stabilise the 3D structure. Integrins regulate the activity of particular protein kinases, including focal adhesion kinase and integrin-linked kinase. Cellular activation regulates integrin ligand affinity via inside-out signalling and ligand binding to integrins can regulate cellular activity via outside-in signalling. Several drugs that target integrins are in clinical use including: (1) tirofiban (αIIbβ3) for short term prevention of coronary thrombosis (abciximab, the first clinically approved (1994) chime…
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:35 2025; family F760, Integrins; version 2025.3.
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_hierarchy: ( F760 O2437 O2440 O2441 O2442 O2443 O2444 O2445 O2446 O2447 O2448 O2438 O2439 O2449 O2450 O2451 O2452 O2453 O2454 O2455 O2456 O2457 O2458 O2459 O2460 O2461 O2462 O2577 O2578 O2579 O2580 O2770 O2581 O2867 O2868 O2869 O2799 O2582 O2583 )
subject: GtoPdb_authors: 846 847
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 22405 22411 22414 22416 22418 22419 22420 23104 24489 24643 26490 26516 27105 27113 27878 29943 30052 30053 30054 30055 31394 31471 31763 32882 33248 33252 33701 33883 33884 37023 37027 37564 37565 37566 38142 38288 38289 38352 38517 41842 41844 41846 41849 41850 42056 42159 43823 43826 43968 45648 47848 50341 50363 50365
creator: Richard W. Farndale
creator: Gavin E. Jarvis
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/F760/2025.3

Type XV RTKs: RYK in GtoPdb v.2025.3
type: item
description: The 'related to tyrosine kinase receptor' (Ryk) is structurally atypical of the family of RTKs, particularly in the activation and ATP-binding domains, lacking kinase activity akin to ROR1/2. Similarly, however, there is evidence that RTK is involved in Wnt signalling [2].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:37 2025; family F795, Type XV RTKs: RYK; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F795 O1849 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject: GtoPdb_references: 17386 42159
  topic: subjects
creator: Chloe J. Peach
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/F795/2025.3

Type III receptor serine/threonine kinases in GtoPdb v.2025.3
type: item
description: Type III serine/threonine kinase is often referred to as an accessory protein. While it has no known enzymatic activity, it can regulate the signalling of RSTKs [3, 2].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:37 2025; family F798, Type III receptor serine/threonine kinases; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F798 O1796 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject: GtoPdb_references: 42159 50440 50441
  topic: subjects
creator: Chloe J. Peach
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/F798/2025.3

Ceramide turnover in GtoPdb v.2025.3
type: item
description: Ceramides are a family of sphingophospholipids synthesized in the endoplasmic reticulum, which mediate cell stress responses, including apoptosis, autophagy and senescence, Serine palmitoyltransferase generates 3-ketosphinganine, which is reduced to dihydrosphingosine. N-Acylation allows the formation of dihydroceramides, which are subsequently reduced to form ceramides. Once synthesized, ceramides are trafficked from the ER to the Golgi bound to the ceramide transfer protein, CERT (COL4A3BP, Q9Y5P4). Ceramide can be metabolized via multiple routes, ensuring tight regulation of its cellular levels. Addition of phosphocholine generates sphingomyelin while carbohydrate is added to form glucosyl- or galactosylceramides. Ceramidase re-forms sphingosine or sphinganine from ceramide or dihydroceramide. Phosphorylation of ceramide generates ceramide phosphate. The determination of accurate kinetic parameters for many of the enzymes in the sphingolipid metabolic pathway is complicated by the lipophilic nature of the substrates.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:35 2025; family F767, Ceramide turnover; version 2025.3.
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_hierarchy: ( F767 ( F788 O2509 O2510 O2511 O2512 O2513 ) ( F791 O2463 ) ( F789 O2474 O2475 O2476 O2477 O2478 O2479 ) ( F790 O2484 O2485 ) ( F774 O2520 O2521 O2525 I774 ) ( F773 O2514 O2515 O2516 O2517 O2518 O2519 ) ( F772 O2487 O2495 ) ( F775 O2528 ) ( F769 O2491 ) ( F770 O2492 O2493 ) ( F768 O2468 O2469 O2470 ) ( F771 O2473 ) )
subject: GtoPdb_authors: 1022
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 121 22572 22584 22585 22586 22654 22664 22665 22666 22669 22670 22671 22679 22683 22685 22687 22688 22689 22690 22692 23105 29912 29913 29914 29915 29916 29917 29918 29941 30019 32636 32637 32638 32640 32730 36009 36010 36876 38381 38658 38659 40041 42003 42146 42159 43156 43517 49172
creator: Anthony H. Futerman
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/F767/2025.3

Type IX RTKs: MuSK in GtoPdb v.2025.3
type: item
description: The muscle-specific kinase MuSK is associated with the formation and organisation of the neuromuscular junction from the skeletal muscle side. agrin forms a complex with low-density lipoprotein receptor-related protein 4 to activate MuSK [5]. MuSK-mediated phosphorylation of downstream targets is involved in stabilised neuromuscular function. It is the target of pathogenic autoantibodies in myasthenia gravis, an autoimmune neuromuscular disease.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:36 2025; family F793, Type IX RTKs: MuSK; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F793 O1847 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject: GtoPdb_references: 17384 19282 19283 19750 20479 20480 26906 26907 42159
  topic: subjects
creator: Chloe J. Peach
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/F793/2025.3

Type XIV RTKs: RET in GtoPdb v.2025.3
type: item
description: The RET (REarranged during Transfection) receptor is a transmembrane tyrosine kinase enzyme enzyme. RET forms a complex with members of the GPI-linked GDNF family receptors (GFR) to respond to GDNF family ligands, including glial cell-derived neurotrophic factors including glial cell-derived neurotrophic factor GDNF (211 aa); neurturin (197 aa); artemin (237 aa) and persephin (156 aa). RET also forms a complex with GFRAL, which is activated by growth differentiation factor 15 (GDF15) [25, 35]. RET is involved in neural crest development. Loss of function mutations lead to Hirschprung's disease, while gain of function mutations lead to multiple endocrine neoplasias type 2A and 2B. There are isoforms - RET51 and RET9 - with distinct signalling properties.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:36 2025; family F794, Type XIV RTKs: RET; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F794 O2185 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 19282 19283 19821 19822 20479 20480 22626 22942 22953 24397 25192 25193 26003 26751 26822 26823 26907 26965 27003 33704 33917 33919 34915 35886 36515 37384 37604 38912 41412 42159 42668 43291 44666 47097 47934 50434 50443
creator: Chloe J. Peach
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/F794/2025.3

Ligand-gated ion channels in GtoPdb v.2025.3
type: item
description: Ligand-gated ion channels (LGICs) are integral membrane proteins that contain a pore which allows the regulated flow of selected ions across the plasma membrane. Ion flux is passive and driven by the electrochemical gradient for the permeant ions. These channels are open, or gated, by the binding of a neurotransmitter to an orthosteric site(s) that triggers a conformational change that results in the conducting state. Modulation of gating can occur by the binding of endogenous, or exogenous, modulators to allosteric sites. LGICs mediate fast synaptic transmission, on a millisecond time scale, in the nervous system and at the somatic neuromuscular junction. Such transmission involves the release of a neurotransmitter from a pre-synaptic neurone and the subsequent activation of post-synaptically located receptors that mediate a rapid, phasic, electrical signal (the excitatory, or inhibitory, post-synaptic potential). However, in addition to their traditional role in phasic neurotransmission, it is now established that some LGICs mediate a tonic form of neuronal regulation that results from the activation of extra-synaptic receptors by ambient levels of neurotransmitter. The expression of some LGICs by non-excitable cells is suggestive of additional functions. By convention, the LGICs comprise the excitatory, cation-selective, nicotinic acetylcholine [959, 210], 5-HT3 [68, 1441], ionotropic glutamate [856, 1375] and P2X receptors [659, 1330] and the inhibitory, anion-selective, GABAA [1066, 83] and glycine receptors [878, 1539]. The nicotinic acetylcholine, 5-HT3, GABAA and glycine receptors (and an additional zinc-activated channel) are pentameric structures and are frequently referred to as the Cys-loop receptors due to the presence of a defining loop of residues formed by a disulphide bond in the extracellular domain of their constituent subunits [966, 1357]. However, the prokaryotic ancestors of these receptors contain no such loop and the term pentameric ligand-ga…
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:34 2025; family F697, Ligand-gated ion channels; version 2025.3.
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_hierarchy: ( F697 ( F68 O378 O379 O373 O374 O375 O376 O377 I68 ) ( F118 O684 O685 O686 ) ( F122 O742 O738 O739 O741 O740 I122 ) ( F72 O404 O405 O406 O407 O408 O409 O410 O411 O412 O413 O414 O415 O416 O417 O418 O419 O420 O421 O422 I72 ) ( F73 O423 O424 O425 O426 O427 O428 I73 ) ( F75 O444 O445 O446 O447 O448 O449 O450 O451 O452 O453 O454 O455 O456 O457 O458 O459 O460 O461 ) ( F123 O743 O744 O745 ) ( F76 O462 O463 O464 O465 O466 O467 O468 O752 O469 O470 O471 O472 O473 O474 O475 O476 O477 I76 ) ( F77 O478 O479 O480 O481 O482 O483 O484 I77 ) ( F83 O587 I83 ) )
subject:
  topic: subjects
  value: GtoPdb_authors: 151 223 297 298 377 378 380 381 392 433 455 456 458 460 462 464 465 466 467 468 469 470 476 513 514 515 516 517 518 519 520 521 522 524 531 889 902 903 905 978 1019 1020 1056 1079 1080 1115 1116
subject:
  topic: subjects
  value: GtoPdb_references: 174 403 612 5744 5775 7516 7517 7518 7519 7521 7522 7523 7524 7525 7526 7527 7528 7529 7530 7531 7532 7533 7534 7535 7536 7537 7538 7539 7540 7541 7542 7543 7544 7545 7546 7547 7548 7549 7550 7551 7552 7553 7554 7555 7556 7557 7558 7560 7561 7562 7563 7564 7565 7566 7567 7568 7569 7570 7642 7643 7644 7645 7646 7647 7652 7653 7654 7655 7656 7721 7722 7723 7724 7725 7726 7727 7728 7729 7730 7731 7732 7733 7734 7735 7736 7737 7738 7739 7740 7741 7742 7743 7744 7745 7746 7747 7748 7749 7750 7751 7752 7753 7754 7755 7756 7757 7758 7759 7760 7761 7762 7763 7764 7765 7766 7767 7768 7769 7770 7771 7772 7773 7774 7775 7776 7777 7778 7779 7780 7781 7782 7783 7784 7785 7786 7787 7788 7789 7790 7791 7792 7793 7794 7795 7796 7797 7798 7799 7800 7801 7802 7803 8077 8078 8079 8080 8081 8082 8083 8084 8085 8086 8087 8088 8089 8090 8091 8092 8093 8094 8095 8096 8097 8098 8099 8100 8101 8102 8103 8104 8105 8106 8107 8108 8109 8110 8111 8112 8113 8114 8115 8116 8117 8118 8119 8120 8121 8122 8123 8124 8125 8126 8127 8128 8129 8130 8131 8132 8133 8134 8135 8136 8137 8138 8139 8140 8141 8142 8143 8144 8145 8146 8147 8148 8149 8150 8151 8152 8153 8154 8155 8156 8157 8158 8159 8160 8161 8162 8163 8164 8375 8376 8377 8378 8379 8380 8381 8382 8383 8384 8385 8386 8387 8388 8389 8390 8391 8392 8393 8394 8395 8396 8397 8398 8399 8400 8401 8402 8403 8404 8405 8406 8407 8408 8409 8410 8411 8412 8413 8414 8415 8416 8417 8418 8419 8420 8421 8422 8423 8424 8425 8426 8427 8428 8429 8430 9432 9823 10412 10413 10414 10415 10416 10499 10606 10607 10609 10610 10611 10612 10613 10614 10615 10616 10617 10618 10619 10620 10621 10622 10623 10624 10625 10626 10627 10628 10629 10630 10631 10632 10633 10634 10635 10636 10637 10638 10639 10640 10641 10642 10643 10644 10645 10646 10647 10648 10649 10650 10651 10652 10653 10654 10655 10656 10657 10658 10659 10660 11126 11193 11417 11454 11455 11456 11457 11458 11459 11460 11461 11462 11463 11464 11465 11466 11467 11468 11469 11470 11471 11472 11…
creator: Susan Wonnacott
creator: Annette Nicke
creator: Shigetada Nakanishi
creator: Christophe Mulle
creator: Masayoshi Mishina
creator: Neil S. Millar
creator: Jessica Meades
creator: Mark Mayer
creator: Michael. J. Marks
creator: Joseph. W. Lynch
creator: Beate Niesler
creator: Richard Olsen
creator: Stephane Peineau
creator: Jeffrey C. Watkins
creator: Michael Spedding
creator: Trevor G. Smart
creator: Lucia G. Sivilotti
creator: Werner Sieghart
creator: Peter Seeburg
creator: Uwe Rudolph
creator: Lachlan D. Rash
creator: John A. Peters
creator: Bernhard Luscher
creator: Sarah C. R. Lummis
creator: David Lodge
creator: Samuel J. Fountain
creator: Anna Fortuny-Gomez
creator: Simonetta Falzoni
creator: Ray Dingledine
creator: Francesco Di Virgilio
creator: Paul Davies
creator: Graham L. Collingridge
creator: Bernhard Bettler
creator: Delia Belelli
creator: Cecilia Gotti
creator: Tim G. Hales
creator: Israel Hanukoglu
creator: Juan Lerma
creator: Jeremy J. Lambert
creator: Brian F. King
creator: Charles Kennedy
creator: Stephan Kellenberger
creator: Anders A. Jensen
creator: Michael F. Jarvis
creator: Michael Hollmann
creator: Stephen F. Heinemann
creator: Nicholas M. Barnes
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/F697/2025.3

SLC51 family of steroid-derived molecule transporters in GtoPdb v.2025.3
type: item
description: The SLC51 organic solute transporter family of transporters is a pair of heterodimeric proteins which regulate bile salt movements in the small intestine, bile duct, and liver, as part of the enterohepatic circulation [2, 5, 1]. OSTα/OSTβ is also expressed in steroidogenic cells of the brain and adrenal gland, where it may contribute to neurosteroid and steroid sulphate movement [6]. Bile acid and steroid sulphate transport is suggested to be bidirectional, facilitative and independent of sodium, potassium, chloride ions or protons [5, 2]. OSTα/OSTβ heterodimers have been shown to transport [3H]taurocholic acid, [3H]dehydroepiandrosterone sulphate, [3H]estrone-3-sulphate, [3H]pregnenolone sulphate and [3H]dehydroepiandrosterone sulphate[2, 5, 6]. OSTα/OSTβ-mediated transport is inhibited by clofazimine and fidaxomicin [9, 11]. OSTα is suggested to be a seven TM protein, while OSTβ is a single TM 'ancillary' protein, both of which are thought to have intracellular C-termini [8]. Both proteins function in solute transport [8, 4]. Inherited mutations in OSTα and OSTβ are associated with liver disease and congenital diarrhea in children [10, 7].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:31 2025; family F337, SLC51 family of steroid-derived molecule transporters; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F337 O1915 O1916 )
  topic: subjects
subject: GtoPdb_authors: 984
  topic: subjects
subject: GtoPdb_references: 18271 18272 18273 22045 22047 37155 37156 40235 40459 42159 45128
  topic: subjects
creator: Paul A. Dawson
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/F337/2025.3

Type XX RTKs: STYK1 in GtoPdb v.2025.3
type: item
description: Similar to the LMR RTK family, STYK1 has a truncated extracellular domain, but also displays a relatively short intracellular tail beyond the split kinase domain. Also known as NOK, STYK1 has been linked to EGFR signalling [2, 3].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:34 2025; family F668, Type XX RTKs: STYK1; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F668 O2229 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject: GtoPdb_references: 22630 42159 50428
  topic: subjects
creator: Chloe J. Peach
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/F668/2025.3

Delta subfamily in GtoPdb v.2025.3
type: item
description: PKCδ and PKCθ are PKC isoforms that are activated by diacylglycerol and may be inhibited by calphostin C, Gö 6983 and chelerythrine.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:33 2025; family F533, Delta subfamily; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F533 O1482 O1485 O1488 )
  topic: subjects
subject: GtoPdb_authors: 1074
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 17822 17863 19282 19283 19796 20479 20480 23973 23978 24402 24403 24497 25798 25799 25945 25946 26176 26286 26865 26930 31788 32148 32149 32152 32163 32164 32165 36062 38522 40205 42159 42628 42630 42631 43877 46576 47707 47712 48695 48704
creator: Mohib Uddin
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/F533/2025.3

Type XVIII RTKs: LMR family in GtoPdb v.2025.3
type: item
description: The lemur tail kinase (LMR) family are are unusual amongst the RTKs in possessing a short extracellular domain and extended intracellular domain (hence the 'Lemur' name reflecting the long tail). LMR1 was identified as a potential marker of apoptosis [2], giving rise to the name AATYK (Apoptosis-Associated Tyrosine Kinase); while over-expression induces differentiation in neuroblastoma cells [3]. The LMTK/LMR family have since been identified to have serine/threonine kinase activity, as opposed to tyrosine kinase [4].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:33 2025; family F658, Type XVIII RTKs: LMR family; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F658 O1922 O2056 O2057 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject: GtoPdb_references: 22628 22629 42159 50425
  topic: subjects
creator: Chloe J. Peach
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/F658/2025.3

Chemerin receptors in GtoPdb v.2025.3
type: item
description: Nomenclature for the chemerin receptors is presented as recommended by NC-IUPHAR [15, 44]). The chemoattractant protein and adipokine, chemerin, has been shown to be the endogenous ligand for both chemerin family receptors. Chemerin1 was the founding family member, and when GPR1 was de-orphanised it was re-named Chermerin2 [44]. Chemerin1 is also activated by the lipid-derived, anti-inflammatory ligand resolvin E1 (RvE1), which is formed via the sequential metabolism of EPA by aspirin-modified cyclooxygenase and lipoxygenase [2, 3]. In addition, two GPCRs for resolvin D1 (RvD1) have been identified: FPR2/ALX, the lipoxin A4 receptor, and GPR32, an orphan receptor [47].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:32 2025; family F338, Chemerin receptors; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F338 O79 O82 I338 )
  topic: subjects
subject: GtoPdb_authors: 71 585
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 2275 2564 11867 11870 11872 11873 11979 11980 12435 12452 12453 12457 12475 12482 12487 12488 12615 12622 12629 12674 12678 12681 12688 12695 12697 12974 12975 12979 12982 12983 12985 12987 12991 12998 12999 13000 13002 13005 13008 13015 13016 13017 13019 13021 13023 13024 13025 18389 18390 18391 18392 18393 18394 18395 18396 18397 18398 18399 18400 18401 18402 18403 18404 18405 18406 18407 18408 18410 18411 18412 18413 18414 18415 18416 18417 18418 18419 18420 18421 18422 18423 18424 18425 18426 20402 20426 20447 32012 33979 34154 34160 38463 42159 43518 46248
creator: Anthony P. Davenport
creator: Amy E. Monaghan
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/F338/2025.3

Succinate receptor in GtoPdb v.2025.3
type: item
description: Nomenclature as recommended by NC-IUPHAR [8]. The succinate receptor (GPR91, SUCNR1) is activated by the tricarboxylic acid (or Krebs) cycle intermediate succinate and other dicarboxylic acids with less clear physiological relevance such as maleate [17]. Since its pairing with its endogenous ligand in 2004, intense research has focused on the receptor-ligand pair role in various (patho)physiological processes such as regulation of renin production [17, 40], ischemia injury [17], fibrosis [26], retinal angiogenesis [35], inflammation [26, 24], immune response [33], obesity [45, 27, 21], diabetes [43, 22, 40], platelet aggregation [39, 37] or cancer [29, 47]. The succinate receptor is coupled to Gi/o [11, 17] and Gq/11 protein families [32, 17, 41], whilst coupling to these G proteins is dependent on the cellular, metabolic and spatial context [23, 41]. Although the receptor is, upon ligand addition, rapidly desensitized [19, 32], and in some cells internalized [17], it seems to recruit arrestins weakly [10]. The cellular activation of the succinate receptor triggers various signalling pathways such as decrease of cAMP levels, [Ca2+]i mobilization and activation of kinases (ERK, c-Jun, Akt, Src, p38, PI3Kβ, etc.) [12]. The receptor is broadly expressed but is notably abundant in immune cells (M2 macrophages [41, 21], monocytes [33], immature dendritic cells [33], adipocytes [45], platelets [39, 37], etc.) and in the kidney [17].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:32 2025; family F446, Succinate receptor; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F446 O166 I446 )
  topic: subjects
subject: GtoPdb_authors: 71 584 989 1172
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 2572 2593 6154 11862 12525 12529 12972 14360 15277 18159 18161 18162 18163 18164 18165 18166 18167 18168 18169 18170 18171 19086 20426 20447 24093 24317 28038 32044 33417 33418 33423 33689 33690 37302 37304 38400 42159 45416 45417 45418 45419 45420 45421 45422 45423 45424 45425 45426 45427 50131
creator: Anthony P. Davenport
creator: Julien Hanson
creator: Wen Chiy Liew
creator: Claudia Stäubert
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/F446/2025.3

Type VII RTKs: Neurotrophin receptor/Trk family in GtoPdb v.2025.3
type: item
description: The neurotrophin receptor family of RTKs include tropomyosin-related kinase (Trk) receptors TrkA, TrkB and TrkC. Their cognate ligands are NGF, BDNF and neurotrophin-3, respectively. They are associated primarily with proliferative and migration effects in neural systems. Various isoforms of neurotrophin receptors exist, including truncated forms of TrkB and TrkC, which lack catalytic domains. p75 (TNFRSF16, also known as nerve growth factor receptor) can interact with neurotrophins and their propeptides. While p75 can lead to apoptosis, it can also form a complex with Trk receptors to mediate survival signalling [10].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:28 2025; family F326, Type VII RTKs: Neurotrophin receptor/Trk family; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F326 O1817 O1818 O1819 )
  topic: subjects
subject: GtoPdb_authors: 1145 1178
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 17380 17381 17382 19282 19283 19810 19811 19812 19813 20479 20480 22621 22622 24001 24318 24932 25397 26256 26325 26773 26907 26922 27003 30140 30308 34914 36254 36515 36553 37180 37376 37380 37600 39029 39516 40274 42159 42482 43343 43938 44217 44246 44307 44661 44676 44689 45451 47858 49791 50407
creator: Francis S. Lee
creator: Chloe J. Peach
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/F326/2025.3

Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family in GtoPdb v.2025.3
type: item
description: The TAM receptor family, named from the first letter of each of its constituents, respond to growth arrest specific protein 6 and protein S. These ligands are secreted plasma proteins which undergo vitamin K-dependent post-translational modifications generating carboxyglutamate-rich domains which are able to bind to negatively-charged surfaces of apoptotic cells. Members of this RTK family represented a novel structural motif, when originally sequenced.
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:29 2025; family F328, Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F328 O1835 O1836 O1837 I328 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 17716 17719 19282 19283 19607 19612 19732 19829 20479 20480 22625 26303 26325 26848 26918 27185 32132 32133 32134 32135 32136 32137 32138 32139 32141 32142 32143 32144 32145 32146 32794 32796 32797 34467 34470 34914 36366 36515 36553 36665 37672 38235 38511 41160 42159 42535 43948 44336 44512 44658 45452 45944 47346 48180 49209 49795
creator: Chloe J. Peach
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/F328/2025.3

Type XIII RTKs: Ephrin receptor family in GtoPdb v.2025.3
type: item
description: Ephrin receptors are a family of 15 RTKs - the largest family of RTKs - with two identified subfamilies (EphA and EphB), which have a role in the regulation of neuronal development, cell migration, patterning and angiogenesis. Their ligands are membrane-associated proteins, thought to be glycosylphosphatidylinositol-linked for EphA (ephrin-A1 , ephrin-A2, ephrin-A3, ephrin-A4 and ephrin-A5) and transmembrane proteins for Ephrin B (ENSFM00250000002014: ephrin-B1, ephrin-B2 and ephrin-B3). Ephrin-A3 and ephrin-B3 have also been shown to interact with heparan sulphate proteoglycans [22].
subject: Articles
  topic: section
subject: GtoPdb_general: generated Tue Oct 7 12:55:28 2025; family F327, Type XIII RTKs: Ephrin receptor family; version 2025.3.
  topic: subjects
subject: GtoPdb_hierarchy: ( F327 O1821 O1822 O1823 O1824 O1825 O1826 O1827 O1828 O1829 O1830 O1831 O1832 O1833 O1834 I327 )
  topic: subjects
subject: GtoPdb_authors: 1178
  topic: subjects
subject:
  topic: subjects
  value: GtoPdb_references: 19282 19283 19610 19658 19659 19663 19664 19665 20479 20480 24931 26274 26395 26908 26925 26965 30257 34302 34303 34304 34305 34306 34307 34308 34310 34311 34312 34313 34314 34315 34316 34317 34318 34319 34320 34321 34322 34323 34914 36254 37791 42159 49247 50408
creator: Chloe J. Peach
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/F327/2025.3