TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*9.A.14.1.1









Long wave-sensitive opsin (red cone photoreceptor pigment). Phosphorylated on Thr and Ser in the C-terminal region. Defects cause color blindness (protanopia). Catalyzes phospholipid flipping (Menon et al., 2011).

Eukaryota
Metazoa
Opsin of Homo sapiens (P04000)
*9.A.14.1.2









Rhodopsin. Photoreceptor required for image-forming vision at low light intensity. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change leading to G-protein activation and release of all-trans retinal. The tetraspanning peripherin-2 (TC# 8.A.40.1.2) links rhodopsin to a cyclic nucleotide-dependent channel (TC# 1.A.1.5.3) in the outer segments of rod photoreceptors.  The G266D retinitis pigmentosa mutation in TMS4 of rhodopsin abolishes binding of peripherin-2 and prevents association with the CNGA1/CNGB1a subunits present in the complex (Becirovic et al. 2014).  A channel through opsin, responsible for the passage of retinal from and to its central site where it forms a Schiff's base with a lysine in TMS7 has been proposed (Hildebrand et al. 2009). Blankenship et al. 2015 presented the 2.3-A resolution structure of native source rhodopsin stabilized in a conformation competent for G protein binding. An extensive water-mediated hydrogen bond network linking the chromophore binding site to the site of G protein binding was observed, providing connections to conserved motifs essential for GPCR activation.  Both Opsin and Rhodopsin serve as phospholipid flippases (scramblases) and thus have been implicated in photoreceptor disc membrane homeostasis (Menon et al. 2011; Goren et al. 2014; Ernst and Menon 2015Wang et al. 2018). One particular conformation of rhodopsin is an open channel connecting the ligand binding site with the membrane and the intradiscal lumen of rod outer segments. Sufficient in size, the passageway permits the exchange of hydrophobic ligands such as retinal (Mattle et al. 2018).

Eukaryota
Metazoa
Rhodopsin of Homo sapiens (P08100)
*9.A.14.1.3









Melatonin receptor type 1A, or MT1 of 350 aas and 7 TMSs.  Although the MT1 and 5-HT receptors have similar endogenous ligands, and agomelatine acts on both receptors, the receptors differ markedly in the structure and composition of their ligand pockets; in MT1, access to the ligand pocket is tightly sealed from solvent by extracellular loop 2, leaving only a narrow channel between transmembrane helices IV and V that connects it to the lipid bilayer (Stauch et al. 2019). The binding site is extremely compact, and ligands interact with MT1 mainly by strong aromatic stacking with Phe179 and auxiliary hydrogen bonds with Asn162 and Gln181.

Eukaryota
Metazoa
Melatonin receptor type 1A of Homo sapiens (P48039)
*9.A.14.1.4









Thyrotropin-releasing hormone receptor

Eukaryota
Metazoa
Thyrotropin-releasing hormone receptor of Homo sapiens (P34981)
*9.A.14.1.5









Follicle-stimulating hormone receptor

Eukaryota
Metazoa
Follicle-stimulating hormone receptor of Homo sapiens (P23945)
*9.A.14.1.6









The ghrelin receptor, a peptide-activated (Growth hormone secretagogue) class A GPCR, GHS-R or GH-releasing peptide receptor (Mary et al., 2012).

Eukaryota
Metazoa
Ghrelin receptor of Homo sapiens (Q92847)
*9.A.14.1.7









Photoreceptor melanopsin implicated in non-image formation in response to light.

Eukaryota
Metazoa
Melanopsin of Xenopus laevis
*9.A.14.1.8









Photoreceptor melanopsin that regulates circadian rhythms (Melyan et al. 2005).

Eukaryota
Metazoa
Melanopsin of Homo sapiens
*9.A.14.1.9









Rhadbomeric opsin of the clam worm.

Eukaryota
Metazoa
Rhabdomeric opsin of Platynereesis dumerilii
*9.A.14.1.10









Opsin of the green sea urchin

Eukaryota
Metazoa
Opsin of Strongylocentrotus droebachiensis
*9.A.14.1.11









G-protein coupled receptor 161, Gpr161 of 529 aas.  Key negative regulator of Shh signaling and the sonic hedgehog pathway via cAMP signaling.  Shh signalling promotes the processing of GLI3 into GLI3R during neural tube development (Mukhopadhyay et al. 2013).

Eukaryota
Metazoa
Gpr161 of Homo sapiens
*9.A.14.1.12









Rhodopsin of 359 aas and 7 TMSs, Rho or Zfo2.  Light activated retinal release has been studied (Morrow and Chang 2015).

Eukaryota
Metazoa
Zfo2 of Danio rerio (Zebrafish) (Brachydanio rerio)
*9.A.14.1.13









Neurotensin receptor (β group of peptide-activated G-protein receptors) of 426 aas and 7 TMSs. Receptor for the neuromedin-U and neuromedin-S neuropeptides (Raddatz et al. 2000;  Krumm and Grisshammer 2015).

Eukaryota
Metazoa
Nmur1 of Homo sapiens
*9.A.14.1.14









Neurotensin receptor type 1, Ntr1, of 418 aas and 7 TMSs.  G-protein coupled receptor for the tridecapeptide neurotensin (NTS). Signaling is effected via G proteins that activate a phosphatidylinositol-calcium second messenger system. Signaling leads to the activation of downstream MAP kinases and protects cells against apoptosis (Da Costa et al. 2013).

Eukaryota
Metazoa
Ntr1 of Homo sapiens
*9.A.14.1.15









Zinc receptor, GPR39 of 453 aas and 7 TMSs.  It  localizes mainly to the sperm tail. Zn2+ at micromolar concentrations stimulates sperm hyperactivated motility, which is mediated by a cascade involving GPR39-adenylyl cyclase (AC)-cyclic AMP (cAMP)-protein kinase A-tyrosine kinase Src (Src)-epidermal growth factor receptor and phospholipase (Allouche-Fitoussi et al. 2018).

Eukaryota
Metazoa
GPR39 of Homo sapiens
*9.A.14.1.16









G-protein coupled receptor, GRL101-like protein of 340 aas and 7 TM

Eukaryota
Metazoa
GPCR of Trichoplax sp. H2
*9.A.14.1.17









Bovine rhodopsin of 348 aas and 7 TMSs.  It is the photoreceptor required for image-forming vision at low light intensity. Also required for photoreceptor cell viability after birth. Light-induced isomerization of 11-cis to all-trans retinal triggers a conformational change that activates signaling via G-proteins (Singhal et al. 2016; Deupi et al. 2012). The x-ray structure has been determined at high resolution, and the folding and oligomerization (Okada and Palczewski 2001; Brown and Ernst 2017). This protein is 93% identical to the human ortholog (TC# 9.A.14.1.2).

Eukaryota
Metazoa
Rhodopsin of Bos tauris
*9.A.14.1.18









RH1 rhodopsin of 310 aas and 7 TMSs. This deep sea species dwells at depths of 1 - 2 km and has 38 rhodopsins, all similar in sequence, but different so that each one absorbs only an overlapping limited range of wavelengths (Musilova et al. 2019).  This way they can detect biologically produced light in an ecosystem where no light from the sun penetrates (Pennisi 2019).

Eukaryota
Metazoa
Rhodopsin of Diretmus argenteus (Silver spinyfin)
*9.A.14.2.1









Sphingosine 1-phosphate receptor, Edg-1 or S1PR1. The 3-d structure in known (Hanson et al., 2012). The activation mechanism has been proposed (Caliman et al. 2017).

Eukaryota
Metazoa
Edg-1 of Homo sapiens (P21453)
*9.A.14.2.2









Cannabinoid receptor 1. The endocannabinoid system is widely present in the retina where it can modulate neurotransmitter release and ion channel activity (Bouchard et al. 2016). Endogenous endocannabinoids such as anandamide and 2-arachidonoyl glycerol (2AG) bind to the receptor and influence many processes including feeding, learning, memory, pain, emotions, sleep and dreams (Murillo-Rodriguez et al. 2017).

Eukaryota
Metazoa
Cannabinoid receptor 1 of Homo sapiens (P21554)
*9.A.14.2.3









Melanocortin receptor 4. At least 4% of childhood obesity is due to mutations in the hypothalamic melanocortin-4 receptor (MC4R) which is important in the regulation of feeding behavior and body weight. MC4R activates the Galphaq/phospholipase C signaling pathway, resulting in alterations of cytoplasmic calcium in immortalized hypothalamic (GT1-1)neurons. Thus, upon agonist binding, MC4R mediates increases in intracellular calcium through the Galphaq-protein/phospholipase C dependent signaling pathway (Newman et al. 2006).

Eukaryota
Metazoa
MC4R of Homo sapiens (P32245)
*9.A.14.2.4









ACTH-specific receptor, MC2R, in the melanocortin receptor family that includes MC1R - MC5R which recognize different melanocortin peptides.  Domains responsible for specific membrane transport and lignad specificity in MC2R have been identified (Fridmanis et al. 2010). MC accessory protein (MRAP) facilitates MC2 receptor trafficking and allows properly localized receptor to bind ACTH and consequently signal (Sebag and Hinkle 2009).

Eukaryota
Metazoa
MC2R of Homo sapiens
*9.A.14.2.5









Lysophosphosphatidic acid (LPA) receptor, Edg4, of 351 aas and 7 TMSs.  Mediates fibroblast chemotaxis (Ren et al. 2014), and forms a coplex with CFTR (3.A.1.202.1) (Zhang et al. 2017).

Eukaryota
Metazoa
Edg4 of Homo sapiens
*9.A.14.2.6









Cannabinoid receptor 2, CNR2. The endocannabinoid system is widely present in the retina where it can modulate neurotransmitter release and ion channel activity (Bouchard et al. 2016). Endogenous endocannabinoids such as anandamide and 2-arachidonoyl glycerol (2AG) bind to the receptor and influence many processes including feeding, learning, memory, pain, emotions, sleep and dreams (Murillo-Rodriguez et al. 2017).  It plays a vital role in regulation of immune response, inflammation, pain, and other metabolic processes. Its 3-d structure has been studied by NMR (Yeliseev and Gawrisch 2017).

Eukaryota
Metazoa
CNR2 of Homo sapiens
*9.A.14.3.1









Tyramine/octopamine receptor.  Inhibited by amitraz metabolites (Casida and Durkin 2013).

Eukaryota
Metazoa
Tyramine/octopamine receptor of Schistosoma mansoni (G4VI72)
*9.A.14.3.2









The muscarinic acetylcholine G-protein-coupled receptor (Jo et al., 2010). Endothelial-dependent muscarinic receptor signaling acts largely through TRPV4 sparklet-mediated stimulation of IK (1.A.1.16.2) and SK (1.A.1.16.1) channels to promote vasodilation. There are five muscarinic receptor subtypes (M1R to M5R), which, despite sharing a high degree of sequence identity in the transmembrane region, couple to different heterotrimeric G proteins to transmit signals. M1R, M3R, and M5R couple to the Gq/ 11 family, whereas M2R and M4R couple to the Gi/ o family. Maeda et al. 2019 presented and compared the cryo-electron microscopy structures of M1R in complex with G11 and M2R in complex with GoA. The M1R-G11 complex exhibits distinct features, including an extended transmembrane helix 5 and carboxyl-terminal receptor tail that interacts with the G protein. Detailed analysis provides a framework for understanding the molecular determinants of G-protein coupling selectivity (Maeda et al. 2019).

Eukaryota
Metazoa
The muscarinic acetylcholine receptor (7TMSs; rhodopsin superfamily) of Mus musculus (P12657)
*9.A.14.3.3









Tryamine receptor isoform A

Eukaryota
Metazoa
Tyramine receptor of Drosophila melanogaster (E1JI27)
*9.A.14.3.4









Adenosine receptor A1

Eukaryota
Metazoa
Adenosine receptor A1 of Homo sapiens (P30542)
*9.A.14.3.5









β-2 adrenergic receptor, β2-AR. Activates adenylate cyclase through G proteins. Binds epinephrine with 30x greater affinity than norepenephrine.  Functions as an ATP-independent phospholipid flippase (scramblase) (Goren et al. 2014). A parameterized MARTINI program can be used to predict the hinging motions of the protein (Li et al. 2019Li et al. 2019).

Eukaryota
Metazoa
β-2-AR of Homo sapiens (P07550)
*9.A.14.3.6









The serotonin or 5-hydroxytrytamine (5-HT) G protein-coupled receptor, 5HT1B.  Wang et al (2013) reported the crystal structures of the human 5-HT1B  bound to the agonist antimigraine medications ergotamine and dihydroergotamine. The structures revealed similar binding modes for these ligands, which occupy the orthosteric pocket and an extended binding pocket close to the extracellular loops. The orthosteric pocket is formed by residues conserved in the 5-HT receptor family.

Eukaryota
Metazoa
5-HT1B of Homo sapiens
*9.A.14.3.7









The serotonic or 5-hydroxytrytamine (5-HT) G protein-coupled receptor, 5HT2B. The structure of this receptor bound to ergotamine, the precursor of the hallucinogen, lysergic acid diethylamide, has been determined (Wacker et al., 2013). It reveals differences from those observed for 5-HT1B (9.B.14.3.6).

 

Eukaryota
Metazoa
5-HT2B of Homo sapiens
*9.A.14.3.8









Adenosine A2a receptor of 412 aas and 7 TMSs. It is a lipid flippase and a water channel (see below). The activity of this receptor is mediated by G proteins which activate adenylyl cyclase.  The crystal structure has been solved revealing a continuous water channel (Yuan et al. 2015).  Tryptophan-246 in TMS6 forms the gate. Conformational changes in TMSs 6 and 7 produce local changes in the lipid bilayer (Yuan et al. 2015).  The protein can function as an ATP-independent phopholipid flippase (scramblase) (Goren et al. 2014). Yuan et al. 2015 found that the conserved W246(6.48) residue in transmembrane helix TM6 performs a key rotamer toggle switch. Agonist binding induces the sidechain of W246(6.48) to fluctuate between two distinct conformations, enabling the diffusion of water molecules from the bulk into the center of the receptor. After passing the W246(6.48) gate, the internal water molecules induce another conserved residue, Y288(7.53), to switch to a distinct rotamer conformation establishing a continuous transmembrane water pathway. Further, structural changes of TM6 and TM7 induce local structural changes of the adjacent lipid bilayer (Yuan et al. 2015).

Eukaryota
Metazoa
Adenosine receptor A2a of Homo sapiens
*9.A.14.3.9









The dopamine receptor D3, DRD3, of 400 aas.  Residues involved in receptor signaling have been identified (Kota et al. 2015), and several agonists are known (Xu et al. 2016). The atomic-level dopamine activation mechanism for transmitting extracellular ligand binding events through transmembrane helices to the cytoplasmic G protein has been elucidated (Weng et al. 2017). In agonist-bound systems, the D3R N-terminus forms a "lid-like" structure and lies flat on the binding site opening, whereas in antagonist-bound systems, the N-terminus exposes the binding cavity. A continuous water pathway is present only in the dopamine-Galphai-bound system. In the inactive D3Rs, water entry is hindered by the hydrophobic layers. It was proposed that upon agonist binding, the "lid-like" conformation of the N-terminus induces a series of molecular switches to increase the volume of the D3R cytoplasmic binding part for G protein association. Water enters the transmembrane region, inducing molecular switches to assist in opening the hydrophobic layers to form a continuous water channel, which is crucial for maintaining a fully active conformation for signal transduction (Weng et al. 2017).

Eukaryota
Metazoa
DRD3 of Homo sapiens
*9.A.14.3.10









Dopamine receptor D2, DRD2, of 443 aas.  Residues involved in signaling have been identified (Kota et al. 2015).

Eukaryota
Metazoa
DRD2 of Homo sapiens
*9.A.14.3.11









β1-adrenergic receptor of 477 aas and 7 TMSs.  It can serve as an ATP-independent phospholipid flippase (scramblase) (Goren et al. 2014; Chauhan et al. 2016). Active-state structures of the β1-adrenoceptor (β1AR) bound to conformation-specific nanobodies in the presence of agonists of varying efficacy have been solved (Warne et al. 2019). Comparison with inactive-state structures of β1AR bound to the identical ligands showed a 24 to 42% reduction in the volume of the orthosteric binding site. Potential hydrogen bonds were also shorter, and there was up to a 30% increase in the number of atomic contacts between the receptor and ligand. This explains the increase in agonist affinity of GPCRs in the active state for a wide range of structurally distinct agonists (Warne et al. 2019).

Eukaryota
Metazoa
β1-adrenergic receptor of Homo sapiens
*9.A.14.3.12









Serotonin receptor, Cg5-HTR-1, of 382 aas. It mediates immune responses in the oyster (Jia et al. 2018).

Eukaryota
Metazoa
Cg5-HTR-1 of Crassostrea gigas
*9.A.14.4.1









Calcitonin receptor 

Eukaryota
Metazoa
Calcitonin receptor of Homo sapiens (P30988)
*9.A.14.4.2









PDF receptor

Eukaryota
Metazoa
PDF receptor of Drosophila melanogaster (Q9W4Y2)
*9.A.14.4.3









Corticotropin-releasing factor receptor-1, CRHR1. The structure is known (Hollenstein et al. 2013). Structural changes in CRFR1 upon antagonist binding and the role of single nucleotide polymorphisms have been investigated (Latek 2017). This G-protein coupled receptor for CRH (corticotropin-releasing factor) and UCN (urocortin) has high affinity for CRH and UCN. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and down-stream effectors such as adenylate cyclase. CRHR1 promotes the activation of adenylate cyclase, leading to increased intracellular cAMP levels. It inhibits the activity of the calcium channel CACNA1H (TC# 1.A.1.11.5) (Tao et al. 2008). Required for normal embryonic development of the adrenal gland and for normal hormonal responses to stress. Plays a role in the response to anxiogenic stimuli.

Eukaryota
Metazoa
CRHR1 of Homo sapiens (P34998)
*9.A.14.4.4









Diuretic hormone receptor

Eukaryota
Metazoa
Diuretic hormone receptor of Acheta domesticus (Q16983)
*9.A.14.4.5









Gastric inhibitory polypeptide receptor 

Eukaryota
Metazoa
Gastric inhibitory polypeptide receptor of Homo Sapiens (P48546)
*9.A.14.4.6









Glucagon-like peptide 1 receptor

Eukaryota
Metazoa
Glucagon-like peptide 1 receptor of Homo sapiens (P43220)
*9.A.14.4.7









Growth hormone-releasing hormone receptor

Eukaryota
Metazoa
Growth hormone-releasing hormone receptor of Homo sapiens (Q02643)
*9.A.14.4.8









Pituitary adenylate cyclase-activating polypeptide type 1 receptor

Eukaryota
Metazoa
Pituitary adenylate cyclase-activating polypeptide type 1 receptor of Homo sapiens (P41586)
*9.A.14.4.9









Vasoactive intestinal polypeptide receptor 1

Eukaryota
Metazoa
Vasoactive intestinal polypeptide receptor 1 of Homo sapiens (P32241)
*9.A.14.4.10









Secretin receptor

Eukaryota
Metazoa
Secretin receptor of Homo sapiens (P47872)
*9.A.14.4.11









Parathyroid hormone/parathyroid hormone-related peptide-1 receptor, PTH1R, of 573 aas and 8 or 9 TMSs in a 1 + 7 or 8 TMS arrangement. PTH1R is a class B G protein-coupled receptor central to calcium homeostasis and a therapeutic target for osteoporosis and hypoparathyroidism. Zhao et al. 2019 reported the cryo-EM structure of human PTH1R bound to a long-acting PTH analog and the stimulatory G protein. The bound peptide adopted an extended helix with its amino terminus inserted deeply into the receptor TMS, which led to partial unwinding of the carboxyl terminus of TMS6 and induceed a sharp kink at the middle of this helix to allow the receptor to couple with the G protein, while the extracellular domain adopted multiple conformations (Zhao et al. 2019).

Eukaryota
Metazoa
Parathyroid hormone/parathyroid hormone-related peptide receptor of Homo sapiens (Q03431)
*9.A.14.4.12









Calcitonin gene-related peptide type 1 receptor (CGRP type 1 receptor) (Calcitonin receptor-like receptor)
Eukaryota
Metazoa
CALCRL of Homo sapiens
*9.A.14.5.1









Cyclic AMP receptor 1

Eukaryota
Dictyosteliida
Cyclic AMP receptor 1 of Dictyostelium discoideum (P13773)
*9.A.14.5.2









GCR1 of 326 aas and 7 TMSs. Together with GPA1, may regulate the cell cycle via a signaling cascade that uses phosphatidylinositol-specific phospholipase C (PI-PLC) as an effector and inositol 1,4,5-trisphosphate (IP3) as a second messenger. Mediates responses to blue light and abscisic acid (Warpeha et al. 2007).

Eukaryota
Viridiplantae
GCR1 of Arabidopsis thaliana (Mouse-ear cress)
*9.A.14.6.1









EGF-like module-containing mucin-like hormone receptor-like 1

Eukaryota
Metazoa
EGF-like module-containing mucin-like hormone receptor-like 1 of Homo sapiens (Q14246)
*9.A.14.6.2









CD97 antigen

Eukaryota
Metazoa
CD97 antigen of Homo sapiens (P48960)
*9.A.14.6.3









EGF, latrophilin and seven transmembrane domain-containing protein 1

Eukaryota
Metazoa
EGF, latrophilin and seven transmembrane domain-containing protein 1 of Homo sapiens (Q9HBW9)
*9.A.14.6.4









Cadherin EGF LAG seven-pass G-type receptor 1

Eukaryota
Metazoa
Cadherin EGF LAG seven-pass G-type receptor 1 of Homo sapiens (Q9NYQ6)
*9.A.14.6.5









Latrophilin receptor (Lat-2)

Eukaryota
Metazoa
Lat-2 of Caenorhabditis elegans (B2MZA8)
*9.A.14.6.6









Brain-specific angiogenesis inhibitor 2

Eukaryota
Metazoa
Brain-specific angiogenesis inhibitor 2 of Homo sapiens (O60241)
*9.A.14.6.7









Adhesin G-protein-coupled receptor, BAI3 (ARGRB3) of 1522 aas.  It plays a role in the regulation of synaptogenesis and dendritic spine formation, at least partly via interaction with ELMO1 and RAC1. It promotes myoblast fusion through ELMO/DOCK1 (Hamoud et al. 2014). Complement 1q-like protein inhibits insulin secretion froms pancreatic β-cells via BAI3 (Gupta et al. 2018).

Eukaryota
Metazoa
BAI3 of Homo sapiens (Human)
*9.A.14.6.8









Adhesion 6 protein-coupled receptor, ADGRL3, or latrophilin-3, LPHN3, of 1447 aas and 7 central TMSs.  It plays a role in cell-cell adhesion and neuron guidance via its interactions with FLRT2 and FLRT3 that are expressed at the surface of adjacent cells (Lu et al. 2015). It also plays a role in the development of glutamatergic synapses in the cortex and determines the connectivity rates between the principal neurons in the cortex.  Knockout of latrophilin-3 in rats causes hyperactivity, hyper-reactivity, under-response to amphetamine, and disrupted dopamine markers (Regan et al. 2019).

 

Eukaryota
Metazoa
ADGRL3 of Homo sapiens
*9.A.14.7.1









Metabotropic glutamate receptor 1, class C.  The parallel 7TM dimer is mediated by cholesterol, which suggests that signaling initiated by glutamate's interaction with the extracellular domain might be mediated via 7TM interactions within the full-length receptor dimer (Wu et al. 2014).

Eukaryota
Metazoa
Metabotropic glutamate receptor 1 of Homo sapiens (Q13255)
*9.A.14.7.2









Extracellular calcium-sensing receptor

Eukaryota
Metazoa
Extracellular calcium-sensing receptor of Homo sapiens (P41180)
*9.A.14.7.3









G-protein coupled receptor family C group 6 member A

Eukaryota
Metazoa
G-protein coupled receptor family C group 6 member A of Homo sapiens (Q5T6X5)
*9.A.14.7.4









Taste receptor type 1 member 2

Eukaryota
Metazoa
Taste receptor type 1 member 2 of Homo sapiens (Q8TE23)
*9.A.14.7.5









Taste receptor type 1 member 1, TAS1

Eukaryota
Metazoa
TAS1 of Homo spaiens
*9.A.14.8.1









Olfactory receptor 1E1

Eukaryota
Metazoa
Olfactory receptor 1E1 of Homo sapiens (P30953)
*9.A.14.8.2









Olfactory receptor, OR2AG1 of 316 aas and 7 TMSs (Song et al. 2009).

Eukaryota
Metazoa
Olfactory receptor, OR2AG1 of Homo sapiens
*9.A.14.9.1









Prostaglandin E2 receptor EP1 subtype

Eukaryota
Metazoa
Prostaglandin E2 receptor EP1 subtype of Homo sapiens (P34995)
*9.A.14.10.1









Gonadotropin-releasing hormone receptor

Eukaryota
Metazoa
Gonadotropin-releasing hormone receptor of Homo sapiens (P30968)
*9.A.14.10.2









Renal vasopressin receptor V1b (Hagiwara et al. 2013).

Eukaryota
Metazoa
Vasopressin receptor V1b of Homo sapiens
*9.A.14.10.3









Vasopressin receptor 2, AVPR2

Eukaryota
Metazoa
AVPR2 of Homo sapiens
*9.A.14.10.4









Dimeric oxytosin receptor. OxtR, of 389 aas and 7 TMSs. Superpotent behavior follows from the binding of oxytosin receptor-specific bivalent ligands to dimeric receptors based on a TMS1-TMS2 interface, and in this arrangement, only analogues with a well-defined spacer length (approximately 25 Å) precisely fit inside a channel-like passage between the two protomers of the dimer (Busnelli et al. 2016).

Eukaryota
Metazoa
OxtR of Homo sapiens
*9.A.14.11.1









G-protein-coupled receptor, GH10049p

Eukaryota
Metazoa
GH10049p of Drosophila melanogaster (Q8MSJ2)
*9.A.14.11.2









G-protein-coupled receptor, GPCR, family C, group 5 member C, isoform a

Eukaryota
Metazoa
GPCR of Homo sapiens (Q9NQ84)
*9.A.14.12.1









Vomeronasal type-1 receptor 1

Eukaryota
Metazoa
Vomeronasal type-1 receptor 1 of Homo sapiens (Q9GZP7)
*9.A.14.13.1









Type-1a angiotensin II receptor of 395 aas and 7 or 8 TMSs, AGTR1(A and B), AT2R1, AT2R1B.  A single mutation in the amphipahtic helix 8 enhances its transport and signalling (Zhu et al. 2015).

Eukaryota
Metazoa
Type-1 angiotensin II receptor of Homo sapiens (P30556)
*9.A.14.13.2









Cysteinyl leukotriene receptor 1

Eukaryota
Metazoa
Cysteinyl leukotriene receptor 1 of Homo sapiens (Q9Y271)
*9.A.14.13.3









Platelet-activating factor receptor

Eukaryota
Metazoa
Platelet-activating factor receptor of Homo sapiens (P25105)
*9.A.14.13.4









G-protein coupled receptor 81

Eukaryota
Metazoa
G-protein coupled receptor 81 of Homo sapiens (Q9BXC0)
*9.A.14.13.5









Leukotriene B4 receptor 1

Eukaryota
Metazoa
Leukotriene B4 receptor 1 of Homo sapiens (Q15722)
*9.A.14.13.6









Melanin-concentrating hormone receptor 1

Eukaryota
Metazoa
MCHR1 of Homo sapiens
*9.A.14.13.7









Mas-related G-protein coupled receptor member F (Mas-related gene F protein) (G-protein coupled receptor 140) (G-protein coupled receptor 168)
Eukaryota
Metazoa
MRGPRF of Homo sapiens
*9.A.14.13.8









G-protein-coupled receptor GPR35.  Agonists include the tryptophan metabolite kynurenic acid, the synthetic ligand zaprinast and two thiazolidinediones.  Agonist activation involves TMSIII and is transduced via Galpha(1)(3) and beta-arrestin-2 (Jenkins et al. 2011).

Eukaryota
Metazoa
GPR35 of Homo sapiens
*9.A.14.13.9









Lysophosphatidic acid receptor 4 (LPA-4; G-protein receptor 23; purinoreceptor 9 (purinurgic receptor 9), P2Y9.  The C-terminal tail directs the protein to the apical membrane of polarized epithelial cells (DuBose et al. 2013).

Eukaryota
Metazoa
LPA-4 of Homo sapiens
*9.A.14.13.10









The apelin hormone receptor (angiotensin receptor; GPCR APJ; GPCR HC11) of 380 aas.  The human apelin (77 aas) receptor is coupled to G proteins that inhibit adenylate cyclase activity.
It plays a role in various processes in adults such as regulation of blood pressure, heart contractility, and heart failure. During heart formation, it acts as a receptor for elabela hormone (ELA). It influences cell movement during embryonic development and serves as an alternative coreceptor with CD4 for HIV-1 infection (Pauli et al. 2014); it may be involved in the development of AIDS dementia.

Eukaryota
Metazoa
Apelin receptor of Homo sapiens
*9.A.14.13.11









Uncharacterized protein of 317 aas and 7 TMSs.  Shows sequence similarity to proteins in 9.B.190.

Eukaryota
Metazoa
UP of Danio rerio (Zebrafish) (Brachydanio rerio)
*9.A.14.13.12









Proteinase-activated receptor-2 of 397 aas and 7 TMSs (δ group), F2RL1, GPR11. PAR2.  Receptor for trypsin and trypsin-like enzymes coupled to G proteins. Its function is mediated through the activation of several signaling pathways including phospholipase C (PLC), intracellular calcium, mitogen-activated protein kinase (MAPK), I-kappaB kinase/NF-kappaB and Rho. Can also be transactivated by cleaved F2R/PAR1. Involved in modulation of inflammatory responses and regulation of innate and adaptive immunity, and acts as a sensor for proteolytic enzymes generated during infection (Krumm and Grisshammer 2015).

Eukaryota
Metazoa
PAR2 of Homo sapiens
*9.A.14.13.13









Neuropeptides B/W receptor type 2, Npbwr2 of 333 aas and 7 TMSs. Of the γ-group.  Interacts specifically with a number of opioid ligands. Receptor for neuropeptides B and W, which may be involved in neuroendocrine system regulation, food intake and the organization of other signals (Krumm and Grisshammer 2015).


Eukaryota
Metazoa
Npbwr2 of Homo sapiens
*9.A.14.13.14









The KiSS receptor (KiSSR) or G-protein receptor 54.  Receptor for metastin (kisspeptin-54 or kp-54), a C-terminally amidated peptide of KiSS1. KiSS1 is a metastasis suppressor protein that suppresses metastases in malignant melanomas and in some breast carcinomas without affecting tumorigenicity. Kisspeptin and GABA interact to modulate secretion and reproduction (Di Giorgio et al. 2019).

Eukaryota
Metazoa
KiSS receptor of Homo sapiens
*9.A.14.13.15









Chemokine-like receptor 1, Cmklr1, of 373 aas and 7 TMSs.  Receptor for the chemoattractant, adipokine chemerin/RARRES2, and for the omega-3 fatty acid-derived molecule, resolvin E1. Interaction with RARRES2 induces activation of intracellular signaling molecules leading to multifunctional effects, e.g., reduction of immune responses, enhancment of adipogenesis and angionesis. Resolvin E1 down-regulates cytokine production in macrophages. Positively regulates adipogenesis and adipocyte metabolism (Krumm and Grisshammer 2015).

Eukaryota
Metazoa
*9.A.14.13.16









The P2Y purinoreceptor 2, P2Y2 of 377 aas and 7 TMSs.  Receptor for ATP and UTP coupled to G-proteins that activate a phosphatidylinositol-calcium second messenger system. The affinity range is UTP = ATP > ATP-gamma-S >> 2-methylthio-ATP = ADP.  Plays a role in shedding (Pupovac and Sluyter 2016).  There are eight mammalian P2Y receptor subtypes (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, and P2Y14), and they play a variety of roles in cell physiology (von Kügelgen and Hoffmann 2016).  The 3-d x-ray structure of a P2Y2 receptor is known (Jacobson et al. 2015).  Antagonists stabilize an ionic lock within the P2T1 receptor, but binding of ADP breaks this ionic lock, forming a continuous water channel that leads to P2Y1 receptor activation (Yuan et al. 2016).

P2Y2 of Homo sapiens
*9.A.14.13.17









Chemokine receptor type 4, CXCR4 of 352 aas and 7 TMSs.  The majority of essential residues form a continuous intramolecular signaling chain through the transmembrane helices.  This chain connects chemokine binding residues on the extracellular side of CXCR4 to G protein-coupling residues on its intracellular side. Integrated into a cohesive model of signal transmission, these CXCR4 residues cluster into five functional groups that mediate (i) chemokine engagement, (ii) signal initiation, (iii) signal propagation, (iv) microswitch activation, and (v) G protein coupling. Propagation of the signal passes through a "hydrophobic bridge" on helix VI (Wescott et al. 2016).

Eukaryota
Metazoa
CXCR4 of Homo sapiens
*9.A.14.13.18









Mu-type opioid receptor of 400 aas and 7 TMSs, OprM1. Receptor for endogenous opioids such as beta-endorphin and endomorphin and for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity as well as both N-type and L-type calcium channels, and activation of inward rectifying potassium channels (Knapman and Connor 2015). Activation of the astrocytic μ-opioid receptor elicits fast glutamate release through TREK-1-containing K2P channel in hippocampal astrocytes (Woo et al. 2018).

Eukaryota
Metazoa
OprM1 of Homo sapiens
*9.A.14.13.19









The G-protein-coupled estrogen receptor, GPER of 375 aas and 7 TMSs.  GPER binds to 17-beta-estradiol (E2) with high affinity and aldosterone with lower affinity, leading to rapid and transient activation of numerous intracellular signaling pathways. It stimulates cAMP production, calcium mobilization and tyrosine kinase Src (Gros et al. 2013; Gaudet et al. 2015).

Eukaryota
Metazoa
GPER of Homo sapiens
*9.A.14.13.20









Prosaposin receptor, Gpr37 of 613 aas and 7 TMSs. Receptor for the neuroprotective and glioprotective factor, prosaposin. Ligand binding induces endocytosis, followed by an ERK phosphorylation cascade (Meyer et al. 2013).

Eukaryota
Metazoa
*9.A.14.13.21









Prorelaxin receptor RXFP3 (RLN3R1, SALPR) of 469 aas and 7 TMSs.  Relaxin is an ovarian hormone that acts with estrogen to produce dilatation of the birth canal in many mammals. Cholesterol modulates the binding properties of human RXFP3 with its ligands, enhancing that of some, and decreasing that of others (Wang et al. 2018).

Eukaryota
Metazoa
RXFP3 of Homo sapiens
*9.A.14.13.22









P2Y1 purinoceptor of 373 aas and 7 TMSs.  Receptor for extracellular adenine nucleotides such as ATP and ADP. In platelets binding to ADP leads to mobilization of intracellular calcium ions via activation of phospholipase C, a change in platelet shape, and probably to platelet aggregation (Jin et al. 1998).

Eukaryota
Metazoa
P2Y1 of Homo sapiens
*9.A.14.13.23









Receptor for somatostatin-14 and -28 of 418 aas and 7 TMSs, SSTR3. This receptor is coupled via pertussis toxin sensitive G proteins to inhibition of adenylyl cyclase (Yamada et al. 1992). Motility and signaling functions of the primary cilium require a unique protein and lipid composition that is determined by gating mechanisms localized at the base of the cilium, and SSTR3 plays a direct role (Takao et al. 2017). B9D1, AHI1, and the N termini of NPHP4 and NPHP5 interact with SSTR3 and thus spatially map to the outer region of the ciliary gating zone.

 

Eukaryota
Metazoa
SSTR3 of Homo sapiens
*9.A.14.13.24









Long neuropeptide F receptor (NPFR) isoform 1 of 390 aas and 7 TMSs. NPFR may play roles within the CNS in digestion and possibly egg production and/or egg development in R. prolixus (Sedra et al. 2018).

Eukaryota
Metazoa
NPFR of Rhodnius prolixus
*9.A.14.14.1









Probable G-protein coupled receptor Mth-like 10

Eukaryota
Metazoa
Probable G-protein coupled receptor Mth-like 10 of Drosophila melanogaster (Q9W0R5)
*9.A.14.14.2









Methuselah (Mth) G-protein receptor.  Involved in biological aging and stress responses. Essential for adult survival. Required in the presynaptic motor neuron to up-regulate neurotransmitter exocytosis at larval glutamatergic neuromuscular junctions. Regulates a step associated with docking and clustering of vesicles at release sites.

Eukaryota
Metazoa
Methusalah of Drosophila melanogaster
*9.A.14.15.1









Gamma-aminobutyric acid type B receptor subunit 2

Eukaryota
Metazoa
Gamma-aminobutyric acid type B receptor subunit 2 of Homo sapiens (O75899)
*9.A.14.15.2









Probable G-protein coupled receptor CG31760

Eukaryota
Metazoa
CG31760 of Drosophila melanogaster
*9.A.14.15.3









Metabolomic GABA-B receptor, GrlE or GluPR, of 816 aas and 7 TMSs. May be involved in the early development of cAMP sensing and subsequent chemotactic responses. It is the receptor for GABA and glutamate, leading respectively to the induction or inhibition of SDF-2 formation (Anjard and Loomis 2006; Prabhu et al. 2007).

 

Eukaryota
Dictyosteliales
GrlE of Dictyostelium discoideum (Slime mold)
*9.A.14.16.1









Frizzled-1, FZD1. Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members.

Eukaryota
Metazoa
FZD1 of Homo sapiens
*9.A.14.16.2









Frizzled-2, Fe2 of 694 aas and 7 TMSs.  Receptor for Wnt proteins. Most frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. Required to coordinate the cytoskeletons of epidermal cells to produce a parallel array of cuticular hairs and bristles (Hsieh et al. 1999).

Eukaryota
Metazoa
Fr2 of Drosophila melanogaster (Fruit fly)
*9.A.14.16.3









Frizzled 6, FZD6 of 712 aas and 7 TMSs. FZD6  functions in multiple signal transduction pathways, for example, as a receptor in Wnt/planar cell polarity (PCP) signaling pathway for polarized cell migration and organ morphogenesis. Mutations in FZD6 have been identified in a variety of tumors (Zou et al. 2017).  Sfz6 mRNA is ubiquitously expressed, being highest in kidney and heart, and moderate in jejunum, ileum, colon, liver, and spleen.In the jejunum, FZD6 protein is more prevalent in the villus than in the crypt cells (Zou et al. 2017). FZD6 forms dimers, whose association is regulated by WNT proteins, and dimer dissociation is crucial for FZD6 signaling (Petersen et al. 2017).

Eukaryota
Metazoa
FZD6 of Sus scrofa (Pig)
*9.A.14.16.4









G-protein homologue, Smoothed; Smo; Smoh, of 787 aas and 7 TMSs. It is regulated via the Hedgehog pathway by the RND-like protein, Patched1 ((PTCH1; TC# 2.A.6.6.13) (Myers et al. 2017). The cryoEM structure of SMO bound to Patched reveals that SMO also a channel open to the membrane as well as to the extracellular cysteine-rich domain (CRD). This domain, like that in Patched, is large enough to accomodate cholesterol, so SMO could be a transporter as well as a receptor (Sommer and Lemmon 2018; Qi et al. 2018).

 

Eukaryota
Metazoa
Smoothed of Homo sapiens
*9.A.14.16.5









Frizzled, Fz, of 468 aas and 7 TMSs, a receptor for Wnt proteins. Involved in transcriptional regulation of synapse development (Mathew et al. 2005). It is a target of insecticides (Audsley and Down 2015).

Eukaryota
Metazoa
Frizzled of Drosophila melanogaster (Fruit fly)
*9.A.14.17.1









Taste receptor type 2 member 1, TAS2.  Glutamate (bitter) taste receptor expressed in the tongue and palate epithelia.

Eukaryota
Metazoa
TAS2 of Homo sapiens
*9.A.14.17.2









Taste receptor type 2 member 4 of 299 aas and 7 TMSs, TAS2R4.

Eukaryota
Metazoa
TAS2R4 of Homo sapiens
*9.A.14.17.3









Taste receptor type 2 member 40 of 315 aas and 7 TMSs, TAS2R40.

Eukaryota
Metazoa
TAS2RX of Latimeria chalumnae (West Indian ocean coelacanth)
*9.A.14.17.4









Taste receptor type 2 of 316 aas and 7 TMSs, TR2

Eukaryota
Metazoa
TR2 of Pelodiscus sinensis (Chinese softshell turtle) (Trionyx sinensis)
*9.A.14.17.5









Taste receptor type 2 member 38 (T2R38; bitter taste receptor of 333 aas and 7 TMSs) (Gaida et al. 2016).  Activated by the bona fide ligand for T2R38, phenylthiourea (PTU), and by N-acetyl-dodecanoyl homoserine (AHL-12), a quorum sensing molecule of Pseudomonas aeruginosa. The latter is the only known natural ligand for T2R38. In response to PTU or AHL-12, key transcription factors are activated including phosphorylation of the MAP kinases p38 and ERK1/2, and upregulation of NFATc1. Increased expression of the multi-drug resistance protein 1 (ABCB1, TC# 3.A.1.201.1) is also observed, a transporter that shuttles a plethora of drugs, such as chemotherapeutics and antibiotics (Gaida et al. 2016).

Eukaryota
Metazoa
Bitter taste receptor of Homo sapiens
*9.A.14.18.1









Cytomegalovirus M78 receptor of 473 aas and 7 TMSs.  It's trafficing has been studied (Sharp et al. 2009).  This protein is a member of the β-herpesvirus 'UL78 family' of seven transmembrane receptors which are required for efficient cell-cell spread of the virus in tissue culture, and M78 knockout viruses are attenuated for replication in vivo. M78 forms dimers, a property common to several cellular 7TMR. It traffics to the cell surface but is rapidly and constitutively endocytosed.  In MCMV-infected cells, the subcellular localization of M78 is modified during the course of infection, which may be related to the incorporation of M78 into the virion envelope during the course of virion maturation (Sharp et al. 2009).  This protein is a member of the β-herpesvirus 'UL78 family' of seven transmembrane receptors which are required for efficient cell-cell spread of the virus in tissue culture, and M78 knockout viruses are attenuated for replication in vivo. M78 forms dimers, a property common to several cellular 7TMR. It traffics to the cell surface but is rapidly and constitutively endocytosed.  In MCMV-infected cells, the subcellular localization of M78 is modified during the course of infection, which may be related to the incorporation of M78 into the virion envelope during the course of virion maturation (Sharp et al. 2009).

Viruses
Herpesvirales
M78 of murine cytomegalovirus
*9.A.14.18.2









pR78 protein of 474 aas and 7 TMSs.

Viruses
Herpesvirales
pR78 of Rat cytomegalovirus
*9.A.14.18.3









Envelope protein UL78 of 431 aas and 7 TMSs.

Viruses
Herpesvirales
UL78 of Human cytomegalovirus (strain Toledo) (HHV-5) (Human herpesvirus 5)
*9.A.14.18.4









Envelope protein U78 of 333 aas and 7 TMSs

Viruses
Herpesvirales
UL78 of Saimiriine herpesvirus 4
*9.A.14.19.1









G-protein receptor, GPR160 of 338 aas and 8 putative TMSs. The expression level of endogenous GPR160 is associated with the pathogenesis of prostate cancer as well as apoptosis and cell cycle arrest (Zhou et al. 2016).

Eukaryota
Metazoa
GPR160 of Homo sapiens
*9.A.14.20.1









The Ocular albinism type 1 gene product, OA1, or G-protein coupled receptor 143 (GPR143) of 404 aas and 7 established TMSs (Sone and Orlow 2007).  OA1 (GPR143) is a pigment cell-specific intracellular glycoprotein that is mutated in patients with ocular albinism type 1, the most common form of ocular albinism. Its cellular localization appears to be endolysosomal and melanosomal.  It is a receptor for tyrosine, L-DOPA and dopamine. Binding of L-DOPA stimulates Ca2+ influx into the cytoplasm, increases secretion of the neurotrophic factor SERPINF1 and relocalizes beta arrestin at the plasma membrane; this ligand-dependent signaling occurs through a G(q)-mediated pathway in melanocytic cells. Its activity is mediated by G proteins which activate the phosphoinositide signaling pathway. It also plays a role as an intracellular G protein-coupled receptor involved in melanosome biogenesis, organization and transport (Palmisano et al. 2008; Giordano et al. 2009).

 

Eukaryota
Metazoa
OA1 of Homo sapiens
*9.A.14.21.1









The G-protein-coupled bile acid receptor of 330 aas and 7 TMSs, GPCR19. Bile acid-binding induces its internalization, activation of extracellular signal-regulated kinase and intracellular cAMP production. May be involved in the suppression of macrophage functions by bile acids (Maruyama et al. 2002; Kawamata et al. 2003; Häussinger and Kordes 2017).

Eukaryota
Metazoa
GPCR19 of Homo sapiens
*9.A.14.22.1









Putative G-protein receptor, GPCR, of 505 aas and 7 TMSs.

Eukaryota
Oomycetes
GPCR of Phytophthora sojae (Soybean stem and root rot agent) (Phytophthora megasperma f. sp. glycines)
*9.A.14.22.2









Putative G-protein receptor of 600 aas and 7 TMSs, GPR107.

Eukaryota
Metazoa
GPR107 of Homo sapiens
*9.A.14.22.3









Uncharacterized protein, putative G-protein receptor of 421 aas and 7 TMSs.

Eukaryota
Entamoebidae
UP of Entamoeba histolytica
*9.A.14.23.1









Serpentine receptor, class alpha-6 (α6) of 329 aas and 7 TMSs, Sra-6.  Chemoreception is mediated in Caenorhabditis elegans by members of the seven-transmembrane G-protein-coupled receptor class (7TM GPCRs) of proteins which are of the serpentine type. Sra is part of the Sra superfamily of chemoreceptors. Chemoperception is one of the central senses of soil nematodes like C. elegans which are otherwise 'blind' and 'deaf'.

Eukaryota
Metazoa
Sra of Caenorhabditis elegans
*9.A.14.23.2









Serpentine Receptor, class AB (class A-like) of 331 aas and 7 TMSs.

Eukaryota
Metazoa
SraR, class AB of Caenorhabditis elegans
*9.A.14.23.3









Serpentine Receptor, class B (beta) of 350 aas and 7 TMSs.

Eukaryota
Metazoa
Sra-B of Caenorhabditis elegans
*9.A.14.23.4









Uncharacterized serpentine receptor of 336 aas and 7 TMSs. 

Eukaryota
Metazoa
Receptor of Caenorhabditis elegans
*9.A.14.23.5









Serpentine receptor class alpha/beta-14 of 280 aas and 7 TMSs.

Eukaryota
Metazoa
SraA14 of Toxocara canis
*9.A.14.23.6









Uncharacterized protein of 334 aas and 7 TMSs.

Eukaryota
Metazoa
UP of Ancylostoma ceylanicum
*9.A.14.23.7









Uncharacterized protein of 575 aas and 7 TMSs.

Eukaryota
Metazoa
UP of Caenorhabditis elegans