Cell surface receptor

Class of ligand activated receptors localized in surface of plama cell membrane

Main article: Receptor (biochemistry)

The seven-transmembrane α-helix structure of a G-protein-coupled receptor

Cell surface receptors (membrane receptors, transmembrane receptors) are receptors that are embedded in the plasma membrane of cells.[1] They act in cell signaling by receiving (binding to) extracellular molecules. They are specialized integral membrane proteins that allow communication between the cell and the extracellular space. The extracellular molecules may be hormones, neurotransmitters, cytokines, growth factors, cell adhesion molecules, or nutrients; they react with the receptor to induce changes in the metabolism and activity of a cell. In the process of signal transduction, ligand binding affects a cascading chemical change through the cell membrane.

## Structure and mechanism

[edit]

Many membrane receptors are transmembrane proteins. There are various kinds, including glycoproteins and lipoproteins.[2] Hundreds of different receptors are known and many more have yet to be studied.[3][4] Transmembrane receptors are typically classified based on their tertiary (three-dimensional) structure. If the three-dimensional structure is unknown, they can be classified based on membrane topology. In the simplest receptors, polypeptide chains cross the lipid bilayer once, while others, such as the G-protein coupled receptors, cross as many as seven times. Each cell membrane can have several kinds of membrane receptors, with varying surface distributions. A single receptor may also be differently distributed at different membrane positions, depending on the sort of membrane and cellular function. Receptors are often clustered on the membrane surface, rather than evenly distributed.[5][6]

### Mechanism

[edit]

Two models have been proposed to explain transmembrane receptors' mechanism of action.

* Dimerization: The dimerization model suggests that prior to ligand binding, receptors exist in a monomeric form. When agonist binding occurs, the monomers combine to form an active dimer.
* Rotation: Ligand binding to the extracellular part of the receptor induces a rotation (conformational change) of part of the receptor's transmembrane helices. The rotation alters which parts of the receptor are exposed on the intracellular side of the membrane, altering how the receptor can interact with other proteins within the cell.[7]

## Domains

[edit]

E = extracellular space
P = plasma membrane
I = intracellular space

Transmembrane receptors in plasma membrane can usually be divided into three parts.

### Extracellular domains

[edit]

The extracellular domain is just externally from the cell or organelle. If the polypeptide chain crosses the bilayer several times, the external domain comprises loops entwined through the membrane. By definition, a receptor's main function is to recognize and respond to a type of ligand. For example, a neurotransmitter, hormone, or atomic ions may each bind to the extracellular domain as a ligand coupled to receptor. Klotho is an enzyme which effects a receptor to recognize the ligand (FGF23).[citation needed]

### Transmembrane domains

[edit]

Two most abundant classes of transmembrane receptors are GPCR and single-pass transmembrane proteins.[8][9] In some receptors, such as the nicotinic acetylcholine receptor, the transmembrane domain forms a protein pore through the membrane, or around the ion channel. Upon activation of an extracellular domain by binding of the appropriate ligand, the pore becomes accessible to ions, which then diffuse. In other receptors, the transmembrane domains undergo a conformational change upon binding, which affects intracellular conditions. In some receptors, such as members of the 7TM superfamily, the transmembrane domain includes a ligand binding pocket.[citation needed]

### Intracellular domains

[edit]

The intracellular (or cytoplasmic) domain of the receptor interacts with the interior of the cell or organelle, relaying the signal. There are two fundamental paths for this interaction:[citation needed]

* The intracellular domain communicates via protein-protein interactions against effector proteins, which in turn pass a signal to the destination.
* With enzyme-linked receptors, the intracellular domain has enzymatic activity. Often, this is tyrosine kinase activity. The enzymatic activity can also be due to an enzyme associated with the intracellular domain.

## Signal transduction

[edit]

External reactions and internal reactions for signal transduction (click to enlarge)

Signal transduction processes through membrane receptors involve the external reactions, in which the ligand binds to a membrane receptor, and the internal reactions, in which intracellular response is triggered.[10][11]

Signal transduction through membrane receptors requires four parts:

* Extracellular signaling molecule: an extracellular signaling molecule is produced by one cell and is at least capable of traveling to neighboring cells.[citation needed]
* Receptor protein: cells must have cell surface receptor proteins which bind to the signaling molecule and communicate inward into the cell.[citation needed]
* Intracellular signaling proteins: these pass the signal to the organelles of the cell. Binding of the signal molecule to the receptor protein will activate intracellular signaling proteins that initiate a signaling cascade.[citation needed]
* Target proteins: the conformations or other properties of the target proteins are altered when a signaling pathway is active and changes the behavior of the cell.[11]

Three conformation states of acetylcholine receptor (click to enlarge)

Membrane receptors are mainly divided by structure and function into 3 classes: The ion channel linked receptor; The enzyme-linked receptor; and The G protein-coupled receptor.

* Ion channel linked receptors have ion channels for anions and cations, and constitute a large family of multipass transmembrane proteins. They participate in rapid signaling events usually found in electrically active cells such as neurons. They are also called ligand-gated ion channels. Opening and closing of ion channels is controlled by neurotransmitters.[citation needed]
* Enzyme-linked receptors are either enzymes themselves, or directly activate associated enzymes. These are typically single-pass transmembrane receptors, with the enzymatic component of the receptor kept intracellular. The majority of enzyme-linked receptors are, or associate with, protein kinases.[citation needed]
* G protein-coupled receptors are integral membrane proteins that possess seven transmembrane helices. These receptors activate a G protein upon agonist binding, and the G-protein mediates receptor effects on intracellular signaling pathways.[citation needed]

### Ion channel-linked receptor

[edit]

Main article: Ligand-gated ion channel

During the signal transduction event in a neuron, the neurotransmitter binds to the receptor and alters the conformation of the protein. This opens the ion channel, allowing extracellular ions into the cell. Ion permeability of the plasma membrane is altered, and this transforms the extracellular chemical signal into an intracellular electric signal which alters the cell excitability.[12]

The acetylcholine receptor is a receptor linked to a cation channel. The protein consists of four subunits: alpha (α), beta (β), gamma (γ), and delta (δ) subunits. There are two α subunits, with one acetylcholine binding site each. This receptor can exist in three conformations. The closed and unoccupied state is the native protein conformation. As two molecules of acetylcholine both bind to the binding sites on α subunits, the conformation of the receptor is altered and the gate is opened, allowing for the entry of many ions and small molecules. However, this open and occupied state only lasts for a minor duration and then the gate is closed, becoming the closed and occupied state. The two molecules of acetylcholine will soon dissociate from the receptor, returning it to the native closed and unoccupied state.[13][14]

### Enzyme-linked receptors

[edit]

Main article: Enzyme-linked receptor

Sketch of an enzyme-linked receptor structure (structure of IGF-1R) (click to enlarge)

As of 2009, there are 6 known types of enzyme-linked receptors: Receptor tyrosine kinases; Tyrosine kinase associated receptors; Receptor-like tyrosine phosphatases; Receptor serine/threonine kinases; Receptor guanylyl cyclases and histidine kinase associated receptors. Receptor tyrosine kinases have the largest population and widest application. The majority of these molecules are receptors for growth factors such as epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), hepatocyte growth factor (HGF), nerve growth factor (NGF) and hormones such as insulin. Most of these receptors will dimerize after binding with their ligands, in order to activate further signal transductions. For example, after the epidermal growth factor (EGF) receptor binds with its ligand EGF, the two receptors dimerize and then undergo phosphorylation of the tyrosine residues in the enzyme portion of each receptor molecule. This will activate the tyrosine kinase and catalyze further intracellular reactions.[citation needed]

### G protein-coupled receptors

[edit]

Main article: G protein-coupled receptor

G protein-coupled receptors comprise a large protein family of transmembrane receptors. They are found only in eukaryotes.[15] The ligands which bind and activate these receptors include: photosensitive compounds, odors, pheromones, hormones, and neurotransmitters. These vary in size from small molecules to peptides and large proteins. G protein-coupled receptors are involved in many diseases, and thus are the targets of many modern medicinal drugs.[16]

There are two principal signal transduction pathways involving the G-protein coupled receptors: the cAMP signaling pathway and the phosphatidylinositol signaling pathway.[17] Both are mediated via G protein activation. The G-protein is a trimeric protein, with three subunits designated as α, β, and γ. In response to receptor activation, the α subunit releases bound guanosine diphosphate (GDP), which is displaced by guanosine triphosphate (GTP), thus activating the α subunit, which then dissociates from the β and γ subunits. The activated α subunit can further affect intracellular signaling proteins or target functional proteins directly.[citation needed]

## Membrane receptor-related disease

[edit]

If the membrane receptors are denatured or deficient, the signal transduction can be hindered and cause diseases. Some diseases are caused by disorders of membrane receptor function. This is due to deficiency or degradation of the receptor via changes in the genes that encode and regulate the receptor protein. The membrane receptor TM4SF5 influences the migration of hepatic cells and hepatoma.[18] Also, the cortical NMDA receptor influences membrane fluidity, and is altered in Alzheimer's disease.[19] When the cell is infected by a non-enveloped virus, the virus first binds to specific membrane receptors and then passes itself or a subviral component to the cytoplasmic side of the cellular membrane. In the case of poliovirus, it is known in vitro that interactions with receptors cause conformational rearrangements which release a virion protein called VP4.The N terminus of VP4 is myristylated and thus hydrophobic【myristic acid=CH3(CH2)12COOH】. It is proposed that the conformational changes induced by receptor binding result in the attachment of myristic acid on VP4 and the formation of a channel for RNA.[citation needed]

## Structure-based drug design

[edit]

Flow charts of two strategies of structure-based drug design

Main article: Drug design

Through methods such as X-ray crystallography and NMR spectroscopy, the information about 3D structures of target molecules has increased dramatically, and so has structural information about the ligands. This drives rapid development of structure-based drug design. Some of these new drugs target membrane receptors. Current approaches to structure-based drug design can be divided into two categories. The first category is about determining ligands for a given receptor. This is usually accomplished through database queries, biophysical simulations, and the construction of chemical libraries. In each case, a large number of potential ligand molecules are screened to find those fitting the binding pocket of the receptor. This approach is usually referred to as ligand-based drug design. The key advantage of searching a database is that it saves time and power to obtain new effective compounds. Another approach of structure-based drug design is about combinatorially mapping ligands, which is referred to as receptor-based drug design. In this case, ligand molecules are engineered within the constraints of a binding pocket by assembling small pieces in a stepwise manner. These pieces can be either atoms or molecules. The key advantage of such a method is that novel structures can be discovered.[20][21][22]

### Other examples

[edit]

* Adrenergic receptor
* Olfactory receptors
* Receptor tyrosine kinases
* Epidermal growth factor receptor
* Insulin Receptor
* Fibroblast growth factor receptors,
* High affinity neurotrophin receptors
* Ephrin receptors
* Integrins
* Low Affinity Nerve Growth Factor Receptor
* NMDA receptor
* Several Immune receptors
* Toll-like receptor
* T cell receptor
* CD28
* SCIMP protein

## See also

[edit]

* Neuromodulators
* Second messenger
* Signalling lymphocyte activation molecule family

## References

[edit]

1. ^ "9.3: Signaling Molecules and Cellular Receptors - Types of Receptors". Biology LibreTexts. 12 July 2018. Retrieved 24 July 2023.
2. ^ Cuatrecasas P. (1974). "Membrane Receptors". Annual Review of Biochemistry. 43: 169–214\. doi:10.1146/annurev.bi.43.070174.001125. PMID 4368906. S2CID 44727052.
3. ^ Dautzenberg FM, Hauger RL (February 2002). "The CRF peptide family and their receptors: yet more partners discovered". Trends Pharmacol. Sci. 23 (2): 71–7\. doi:10.1016/S0165-6147(02)01946-6. PMID 11830263.
4. ^ Rivière S, Challet L, Fluegge D, Spehr M, Rodriguez I (May 2009). "Formyl peptide receptor-like proteins are a novel family of vomeronasal chemosensors". Nature. 459 (7246): 574–7\. Bibcode:2009Natur.459..574R. doi:10.1038/nature08029. PMID 19387439.
5. ^ Rothberg K.G.; Ying Y.S.; Kamen B.A.; Anderson R.G. (1990). "Cholesterol controls the clustering of the glycophospholipid-anchored membrane receptor for 5-methyltetrahydrofolate". The Journal of Cell Biology. 111 (6): 2931–2938\. doi:10.1083/jcb.111.6.2931. PMC 2116385. PMID 2148564.
6. ^ Jacobson C.; Côté P.D.; Rossi S.G.; Rotundo R.L.; Carbonetto S. (2001). "The Dystroglycan Complex Is Necessary for Stabilization of Acetylcholine Receptor Clusters at Neuromuscular Junctions and Formation of the Synaptic Basement Membrane". The Journal of Cell Biology. 152 (3): 435–450\. doi:10.1083/jcb.152.3.435. PMC 2195998. PMID 11157973.
7. ^ Maruyama, Ichiro N. (2015-09-01). "Activation of transmembrane cell-surface receptors via a common mechanism? The "rotation model"". BioEssays. 37 (9): 959–967\. doi:10.1002/bies.201500041. ISSN 1521-1878. PMC 5054922. PMID 26241732.
8. ^ Superfamilies of single-pass transmembrane receptors in Membranome database
9. ^ Superfamilies of single-pass transmembrane protein ligands and regulators of receptors in Membranome database
10. ^ Ullricha A., Schlessingerb J.; Schlessinger, J (1990). "Signal transduction by receptors with tyrosine kinase activity". Cell. 61 (2): 203–212\. doi:10.1016/0092-8674(90)90801-K. PMID 2158859.
11. ^ a b Kenneth B. Storey (1990). Functional Metabolism. Wiley-IEEE. pp. 87–94\. ISBN 978-0-471-41090-4.
12. ^ Hille B. (2001). Ion channels of excitable membranes. Sunderland, Mass. ISBN 978-0-87893-321-1.
13. ^ Miyazawa A.; Fujiyoshi Y.; Unwin N. (2003). "Structure and gating mechanism of the acetylcholine receptor pore". Nature. 423 (6943): 949–955\. Bibcode:2003Natur.423..949M. doi:10.1038/nature01748. PMID 12827192.
14. ^ Akabas M.H.; Stauffer D.A.; Xu M.; Karlin A. (1992). "Acetylcholine receptor channel structure probed in cysteine-substitution mutants". Science. 258 (5080): 307–310\. Bibcode:1992Sci...258..307A. doi:10.1126/science.1384130. PMID 1384130.
15. ^ King N, Hittinger CT, Carroll SB (2003). "Evolution of key cell signaling and adhesion protein families predates animal origins". Science. 301 (5631): 361–3\. Bibcode:2003Sci...301..361K. doi:10.1126/science.1083853. PMID 12869759.
16. ^ Filmore, David (2004). "It's a GPCR world". Modern Drug Discovery. 2004 (November): 24–28.
17. ^ Gilman A.G. (1987). "G Proteins: Transducers of Receptor-Generated Signals". Annual Review of Biochemistry. 56: 615–649\. doi:10.1146/annurev.bi.56.070187.003151. PMID 3113327. S2CID 33992382.
18. ^ Müller-Pillascha F.; Wallrappa C.; Lachera U.; Friessb H.; Büchlerb M.; Adlera G.; Gress T. M. (1998). "Identification of a new tumour-associated antigen TM4SF5 and its expression in human cancer". Gene. 208 (1): 25–30\. doi:10.1016/S0378-1119(97)00633-1. PMID 9479038.
19. ^ Scheuer K.; Marasb A.; Gattazb W.F.; Cairnsc N.; Förstlb H.; Müller W.E. (1996). "Cortical NMDA Receptor Properties and Membrane Fluidity Are Altered in Alzheimer's Disease". Dementia. 7 (4): 210–214\. doi:10.1159/000106881. PMID 8835885.
20. ^ Wang R.; Gao Y.; Lai L. (2000). "LigBuilder: A Multi-Purpose Program for Structure-Based Drug Design". Journal of Molecular Modeling. 6 (7–8): 498–516\. doi:10.1007/s0089400060498.7–8&rft.pages=498-516&rft.date=2000&rft_id=info:doi/10.1007/s0089400060498&rft.au=Wang+R.&rft.au=Gao+Y.&rft.au=Lai+L.&rfr_id=info:sid/en.wikipedia.org:Cell+surface+receptor" class="Z3988">
21. ^ Schneider G.; Fechner U. (2005). "Computer-based de novo design of drug-like molecules". Nature Reviews Drug Discovery. 4 (8): 649–663\. doi:10.1038/nrd1799. PMID 16056391.
22. ^ Jorgensen W.L. (2004). "The Many Roles of Computation in Drug Discovery". Science. 303 (5665): 1813–1818\. Bibcode:2004Sci...303.1813J. doi:10.1126/science.1096361. PMID 15031495. S2CID 1307935.

## External links

[edit]

* IUPHAR GPCR Database Archived 2019-03-23 at the Wayback Machine
* Cell+Surface+Receptors at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

* v
* t
* e

Cell signaling / Signal transduction

Signaling pathways|

* GPCR
*   * Wnt
* RTK
* TGF beta
* MAPK/ERK
* Notch
* JAK-STAT
* Akt/PKB
* Fas apoptosis
* Hippo
* PI3K/AKT/mTOR pathway
* Integrin receptors

Agents|

| Receptor ligands|

* Hormones
* Neurotransmitters/Neuropeptides/Neurohormones
* Cytokines
* Growth factors
* Signaling molecules

|

Receptors|

* Cell surface
* Intracellular
* Co-receptor

Second messenger|

* cAMP-dependent pathway
* Ca2+ signaling
* Lipid signaling

Assistants:|

* Signal transducing adaptor protein
* Scaffold protein

Transcription factors|

* General
* Transcription preinitiation complex
* TFIID
* TFIIH

By distance|

* Juxtacrine
* Autocrine / Paracrine
* Endocrine

Other concepts|

* Intracrine action
* Neurocrine signaling
* Synaptic transmission
* Chemical synapse
* Neuroendocrine signaling
* Exocrine signalling
* Pheromones
* Mechanotransduction
* Phototransduction
* Ion channel gating
* Gap junction

* v
* t
* e

Membrane proteins, receptors: cell surface receptors

G protein-coupled receptor|

| Class A|

* Eicosanoid receptor (Prostaglandin receptor)
* Protease-activated receptor
* Neurotransmitter receptor
* Purinergic receptor
* Biogenic amine receptor
* Olfactory receptor

|

Class B|

* Secretin receptor

Class C|

* Metabotropic glutamate receptor

Class D|

* Pheromone receptor

Class E|

* cAMP receptor

Class F|

* Frizzled/smoothened

Ligand-gated ion channel|

* Purinergic receptor

Enzyme-linked receptor|

* Serine/threonine-specific protein kinase
* Receptor tyrosine kinase
* Guanylate cyclase

Other/ungrouped|

* Asialoglycoprotein receptor
* Tumor necrosis factor receptor
* Immunoglobulin superfamily
* N-Acetylglucosamine receptor
* Neuropilins
* Transferrin receptor
* EDAR
* Lipoprotein receptor-related protein
* Progestin and adipoQ receptor

* v
* t
* e

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin-like

| Neurotransmitter|

| Adrenergic|

* α1 (A
* B
* D)
* α2 (A
* B
* C)
* β1
* β2
* β3

|

Purinergic|

* Adenosine (A1
* A2A
* A2B
* A3)
* P2Y (1
* 2
* 4
* 5
* 6
* 8
* 9
* 10
* 11
* 12
* 13
* 14)

Serotonin|

* (all but 5-HT3) 5-HT1 (A
* B
* D
* E
* F)
* 5-HT2 (A
* B
* C)
* 5-HT (4
* 5A
* 6
* 7)

Other|

* Acetylcholine (M1
* M2
* M3
* M4
* M5)
* Dopamine
* D1
* D2
* D3
* D4
* D5
* GHB receptor
* Histamine
* H1
* H2
* H3
* H4
* Melatonin (1A
* 1B
* 1C)
* TAAR (1
* 2
* 5
* 6
* 8
* 9)

Metabolites and
signaling molecules|

| Eicosanoid|

* CysLT (1
* 2)
* LTB4
* 1
* 2
* FPRL1
* OXE
* Prostaglandin
* DP (1
* 2), EP (1
* 2
* 3
* 4), FP
* Prostacyclin
* Thromboxane

|

Other|

* Bile acid
* Cannabinoid (CB1
* CB2, GPR (18
* 55
* 119))
* EBI2
* Estrogen
* Free fatty acid (1
* 2
* 3
* 4)
* Hydroxycarboxylic acids
* 1
* 2
* 3
* Lysophosphatidic acid (1
* 2
* 3
* 4
* 5
* 6)
* Lysophospholipid (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8)
* Oxoglutarate
* PAF
* Sphingosine-1-phosphate (1
* 2
* 3
* 4
* 5)
* Succinate

Peptide|

| Neuropeptide|

* B/W (1
* 2)
* FF (1
* 2)
* S
* Y (1
* 2
* 4
* 5)
* Neuromedin (B
* U (1
* 2))
* Neurotensin (1
* 2)

|

Other|

* Anaphylatoxin (C3a
* C5a (1
* 2))
* Angiotensin (1
* 2)
* Apelin
* Bombesin
* BRS3
* GRPR
* NMBR)
* Bradykinin (B1
* B2)
* Chemerin
* 1
* 2
* Chemokine
* Cholecystokinin (A
* B)
* Endothelin
* A
* B
* Formyl peptide (1
* 2
* 3)
* FSH
* Galanin (1
* 2
* 3)
* Gonadotropin-releasing hormone (1
* 2)
* Ghrelin
* Kisspeptin
* Luteinizing hormone/choriogonadotropin
* MAS (1
* 1L
* D
* E
* F
* G
* X1
* X2
* X3
* X4)
* Melanocortin (1
* 2
* 3
* 4
* 5)
* MCHR (1
* 2)
* Motilin
* Opioid (Delta
* Kappa
* Mu
* Nociceptin & Zeta, but not Sigma)
* Orexin (1
* 2)
* Oxytocin
* Prokineticin (1
* 2)
* Prolactin-releasing peptide
* Relaxin (1
* 2
* 3
* 4)
* Somatostatin (1
* 2
* 3
* 4
* 5)
* Tachykinin (1
* 2
* 3)
* Thyrotropin
* Thyrotropin-releasing hormone
* Urotensin-II
* Vasopressin (1A
* 1B
* 2)

Miscellaneous|

| Taste, bitter|

* TAS2R
* 1
* 3
* 4
* 5
* 7
* 8
* 9
* 10
* 13
* 14
* 16
* 19
* 20
* 30
* 31
* 38
* 39
* 40
* 41
* 42
* 43
* 45
* 46
* 50
* 60
* Vomeronasal receptor type 1

|

Orphan|

* GPR (3
* 4
* 6
* 12
* 15
* 17
* 18
* 19
* 20
* 21
* 22
* 25
* 26
* 27
* 31
* 32
* 33
* 34
* 35
* 37
* 39
* 42
* 44
* 45
* 50
* 52
* 55
* 61
* 62
* 63
* 65
* 68
* 75
* 78
* 81
* 82
* 83
* 84
* 85
* 87
* 88
* 92
* 101
* 103
* 109A
* 109B
* 119
* 120
* 132
* 135
* 137B
* 139
* 141
* 142
* 146
* 148
* 149
* 150
* 151
* 152
* 153
* 160
* 161
* 162
* 171
* 173
* 174
* 176
* 177
* 182
* 183)

Other|

* Adrenomedullin
* Olfactory
* Opsin (3
* 4
* 5
* 1LW
* 1MW
* 1SW
* RGR
* RRH)
* Protease-activated (1
* 2
* 3
* 4)
* SREB (1
* 2
* 3)

Class B: Secretin-like

| Adhesion|

* ADGRB
* Brain-specific angiogenesis inhibitor
* 1
* 2
* 3
* ADGRC
* Cadherin
* 1
* 2
* 3
* ADGRE
* EMR
* 1
* 2
* 3
* CD97
* ADGRG
* 1
* 2
* 3
* 4
* 5
* 6
* 7
* ADGRL
* Latrophilin
* 1
* 2
* 3
* ELTD1

|

Orphan|

* GPR (56
* 64
* 97
* 98
* 110
* 111
* 112
* 113
* 114
* 115
* 116
* 123
* 124
* 125
* 126
* 128
* 133
* 143
* 144
* 155
* 157)

Other|

* Calcitonin
* CALCRL
* Corticotropin-releasing hormone (1
* 2)
* Glucagon (GR
* GIPR
* GLP1R
* GLP2R)
* Growth-hormone-releasing hormone
* PACAPR1
* GPR
* Methuselah-like proteins
* Parathyroid hormone (1
* 2)
* Secretin
* Vasoactive intestinal peptide (1
* 2)

Class C: Metabotropic glutamate / pheromone

| Taste, sweet|

* TAS1R
* 1
* 2
* 3
* Vomeronasal receptor, type 2

|

Other|

* Calcium-sensing receptor
* GABAB (1
* 2)
* Glutamate receptor (Metabotropic glutamate (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8))
* GPRC6A
* GPR (156
* 158
* 179)
* RAIG (1
* 2
* 3
* 4)

Class F: Frizzled & Smoothened

| Frizzled|

* Frizzled (1
* 2
* 3
* 4
* 5
* 6
* 7
* 8
* 9
* 10)

|

Smoothened|

* Smoothened

* v
* t
* e

Ion channel, cell surface receptor: ligand-gated ion channels

Cys-loop receptors|

| 5-HT/serotonin|

* 5-HT3
* A
* B
* C
* D
* E

|

GABA|

* GABAA
* α1
* α2
* α3
* α4
* α5
* α6
* β1
* β2
* β3
* γ1
* γ2
* γ3
* δ
* ε
* π
* θ
* GABAA-ρ
* ρ1
* ρ2
* ρ3

Glycine|

* α1
* α2
* α3
* α4
* β

Nicotinic acetylcholine|

* monomers: α1
* α2
* α3
* α4
* α5
* α6
* α7
* α9
* α10
* β1
* β2
* β3
* β4
* δ
* ε

* pentamers: (α3)2(β4)3
* (α4)2(β2)3
* (α7)5
* (α1)2(β4)3 \- Ganglion type
* (α1)2β1δε - Muscle type

Zinc|

* Zinc-activated

Ionotropic glutamates|

| Ligand-gated only|

* AMPA (1
* 2
* 3
* 4)
* Kainate
* 1
* 2
* 3
* 4
* 5

|

Voltage- and ligand-gated|

* NMDA
* 1
* 2A
* 2B
* 2C
* 2D
* 3A
* 3B
* L1A
* L1B

‘Orphan’|

* GluD
* δ1
* δ2

ATP-gated channels|

| Purinergic receptors|

* P2X
* 1
* 2
* 3
* 4
* 5
* 6
* 7

|

* v
* t
* e

Cell surface receptors: enzyme-linked receptors

Receptor protein serine/threonine kinase|

* Bone morphogenetic protein receptors
* BMPR1
* BMPR1A
* BMPR1B
* BMPR2
* ACVR1
* ACVR1B
* ACVR1C
* ACVR2A
* ACVR2B
* ACVRL1
* Anti-Müllerian hormone receptor

Receptor tyrosine kinase|

| EGF receptor family|

* EGFR
* ERBB2
* ERBB3
* ERBB4

|

Insulin receptor family|

* IGF1R
* INSR
* INSRR

PDGF receptor family|

* CSF1R
* FLT3
* KIT
* PDGFR
* PDGFRA
* PDGFRB

FGF receptor family|

* FGFR1
* FGFR2
* FGFR3
* FGFR4

VEGF receptors family|

* VEGFR1
* VEGFR2
* VEGFR3
* VEGFR4

HGF receptor family|

* MET
* RON

Trk receptor family|

* NTRK1
* NTRK2
* NTRK3

EPH receptor family|

* EPHA1
* EPHA2
* EPHA3
* EPHA4
* EPHA5
* EPHA6
* EPHA7
* EPHA8
* EPHB1
* EPHB2
* EPHB3
* EPHB4
* EPHB5
* EPHB6
* EPHX

LTK receptor family|

* LTK
* ALK

TIE receptor family|

* TIE
* TEK

ROR receptor family|

* ROR1
* ROR2

DDR receptor family|

* DDR1
* DDR2

PTK7 receptor family|

* PTK7

RYK receptor family|

* RYK

MuSK receptor family|

* MUSK

ROS receptor family|

* ROS1

AATYK receptor family|

* AATYK
* AATYK2
* AATYK3

AXL receptor family|

* AXL
* MER
* TYRO3

RET receptor family|

* RET

uncategorised|

* STYK1

Guanylate cyclase-coupled receptor|

* ANP: NPR1
* NPR2

* GUCY2C
* GUCY2D

Receptor tyrosine phosphatase|

* PTPRA
* PTPRB
* PTPRC
* PTPRD
* PTPRE
* PTPRF
* PTPRG
* PTPRH
* PTPRJ
* PTPRK
* PTPRM
* PTPRN
* PTPRN2
* PTPRO
* PTPRQ
* PTPRR
* PTPRS
* PTPRT
* PTPRU
* PTPRZ

Authority control databases

National|

* United States
* Czech Republic
* Israel

Other|

* Yale LUX

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