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.
S33: Prolyl aminopeptidase in GtoPdb v.2025.3
Peptidase family S33 contains mainly exopeptidases that act at the N-terminus of peptides.
GtoPdb_general: generated Tue Oct 7 12:55:40 2025; family F917, S33: Prolyl aminopeptidase; version 2025.3.
GtoPdb_hierarchy: ( F917 O2626 O2875 O1399 )
Copyright (c) 2025 The authors http://creativecommons.org/licenses/by-sa/4.0
SLC54 Mitochondrial pyruvate carriers in GtoPdb v.2025.3
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].
GtoPdb_general: generated Tue Oct 7 12:55:41 2025; family F1006, SLC54 Mitochondrial pyruvate carriers; version 2025.3.
Coronavirus (CoV) proteins in GtoPdb v.2025.3
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).
GtoPdb_general: generated Tue Oct 7 12:55:43 2025; family F1034, Coronavirus (CoV) proteins; version 2025.3.
Endocannabinoid turnover in GtoPdb v.2025.3
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].
GtoPdb_general: generated Tue Oct 7 12:55:41 2025; family F943, Endocannabinoid turnover; version 2025.3.
Carnitine palmitoyltransferases in GtoPdb v.2025.3
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.
GtoPdb_general: generated Tue Oct 7 12:55:43 2025; family F1089, Carnitine palmitoyltransferases; version 2025.3.
Receptor guanylyl cyclase (RGC) family in GtoPdb v.2025.3
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.
GtoPdb_general: generated Tue Oct 7 12:55:42 2025; family F1022, Receptor guanylyl cyclase (RGC) family; version 2025.3.
E3 ubiquitin ligase components in GtoPdb v.2025.3
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.
GtoPdb_general: generated Tue Oct 7 12:55:42 2025; family F1023, E3 ubiquitin ligase components; version 2025.3.
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].
GtoPdb_general: generated Tue Oct 7 12:55:40 2025; family F897, RAS subfamily; version 2025.3.
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.
GtoPdb_general: generated Tue Oct 7 12:55:38 2025; family F799, Hydrolases & Lipases; version 2025.3.
Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2025.3
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].
GtoPdb_general: generated Tue Oct 7 12:55:39 2025; family F891, Regulators of G protein Signaling (RGS) proteins; version 2025.3.
3.6.5.2 Small monomeric GTPases in GtoPdb v.2025.3
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.
GtoPdb_general: generated Tue Oct 7 12:55:40 2025; family F896, 3.6.5.2 Small monomeric GTPases; version 2025.3.
Peptidyl-prolyl cis/trans isomerases in GtoPdb v.2025.3
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.
GtoPdb_general: generated Tue Oct 7 12:55:38 2025; family F845, Peptidyl-prolyl cis/trans isomerases; version 2025.3.
Blood coagulation components in GtoPdb v.2025.3
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.
GtoPdb_general: generated Tue Oct 7 12:55:39 2025; family F853, Blood coagulation components; version 2025.3.
Type VI RTKs: PTK7/CCK4 in GtoPdb v.2025.3
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.
GtoPdb_general: generated Tue Oct 7 12:55:36 2025; family F792, Type VI RTKs: PTK7/CCK4; version 2025.3.
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) chimeric monoclonal antibody, is no longer available for clinical use), (2) vedolizumab (α4β7) to reduce gastrointestinal inflammation, and (3) natalizumab (α4β1) in some cases of severe multiple sclerosis. Drugs targeting multiple integrins are under investigation for the treatment of dry eye disease, e.g., risuteganib, an anti-integrin peptide [44].
GtoPdb_general: generated Tue Oct 7 12:55:35 2025; family F760, Integrins; version 2025.3.
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].
GtoPdb_general: generated Tue Oct 7 12:55:37 2025; family F795, Type XV RTKs: RYK; version 2025.3.
Type III receptor serine/threonine kinases in GtoPdb v.2025.3
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].
GtoPdb_general: generated Tue Oct 7 12:55:37 2025; family F798, Type III receptor serine/threonine kinases; version 2025.3.
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.
GtoPdb_general: generated Tue Oct 7 12:55:35 2025; family F767, Ceramide turnover; version 2025.3.
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.
GtoPdb_general: generated Tue Oct 7 12:55:36 2025; family F793, Type IX RTKs: MuSK; version 2025.3.
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.
GtoPdb_general: generated Tue Oct 7 12:55:36 2025; family F794, Type XIV RTKs: RET; version 2025.3.
Ligand-gated ion channels in GtoPdb v.2025.3
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-gated ion channel (pLGIC) is gaining acceptance in the literature [573]. The ionotropic glutamate and P2X receptors are tetrameric and trimeric structures, respectively. Multiple genes encode the subunits of LGICs and the majority of these receptors are heteromultimers. Such combinational diversity results, within each class of LGIC, in a wide range of receptors with differing pharmacological and biophysical properties and varying patterns of expression within the nervous system and other tissues. The LGICs thus present attractive targets for new therapeutic agents with improved discrimination between receptor isoforms and a reduced propensity for off-target effects. The development of novel, faster screening techniques for compounds acting on LGICs [359] will greatly aid in the development of such agents.
GtoPdb_general: generated Tue Oct 7 12:55:34 2025; family F697, Ligand-gated ion channels; version 2025.3.
SLC51 family of steroid-derived molecule transporters in GtoPdb v.2025.3
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].
GtoPdb_general: generated Tue Oct 7 12:55:31 2025; family F337, SLC51 family of steroid-derived molecule transporters; version 2025.3.
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].
GtoPdb_general: generated Tue Oct 7 12:55:34 2025; family F668, Type XX RTKs: STYK1; version 2025.3.
PKCδ and PKCθ are PKC isoforms that are activated by diacylglycerol and may be inhibited by calphostin C, Gö 6983 and chelerythrine.
GtoPdb_general: generated Tue Oct 7 12:55:33 2025; family F533, Delta subfamily; version 2025.3.
GtoPdb_hierarchy: ( F533 O1482 O1485 O1488 )
Type XVIII RTKs: LMR family in GtoPdb v.2025.3
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].
GtoPdb_general: generated Tue Oct 7 12:55:33 2025; family F658, Type XVIII RTKs: LMR family; version 2025.3.
GtoPdb_hierarchy: ( F658 O1922 O2056 O2057 )
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].
GtoPdb_general: generated Tue Oct 7 12:55:32 2025; family F338, Chemerin receptors; version 2025.3.
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].
GtoPdb_general: generated Tue Oct 7 12:55:32 2025; family F446, Succinate receptor; version 2025.3.
Type VII RTKs: Neurotrophin receptor/Trk family in GtoPdb v.2025.3
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].
GtoPdb_general: generated Tue Oct 7 12:55:28 2025; family F326, Type VII RTKs: Neurotrophin receptor/Trk family; version 2025.3.
GtoPdb_hierarchy: ( F326 O1817 O1818 O1819 )
Type XI RTKs: TAM (TYRO3-, AXL- and MER-TK) receptor family in GtoPdb v.2025.3
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.
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.
Type XIII RTKs: Ephrin receptor family in GtoPdb v.2025.3
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].
GtoPdb_general: generated Tue Oct 7 12:55:28 2025; family F327, Type XIII RTKs: Ephrin receptor family; version 2025.3.