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GRAFS
The GPCR superfamily is the largest gene family in the human genome containing approximately 800 genes. As the vertebrate superfamily can be phylogenetically grouped into five main families the GRAFS classification system has been proposed. GRAFS stands for Glutamate, Rhodopsin, Adhesion, Frizzled/ Taste2, Secretin. They correspond to classical classes C ( class C, glutamate), A ( rhodopsin-like), B2 ( Secretin receptor family, long N-terminal), F (Frizzled/Smoothened Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled (Class F) G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecula ...), and B1+3 (other secretin). ''Taste2'' has more recently considered to be closer to ''Rhodopsin-like'' receptors. See also * G protein-coupled receptor#Classification References Human genetics {{genetics-stub ...
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GPCR
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. Text was copied from this source, which is available under Attribution 2.5 Generic (CC BY 2.5) license. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and an ...
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G Protein-coupled Receptor
G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily-related proteins that are cell surface receptors that detect molecules outside the cell and activate cellular responses. Coupling with G proteins, they are called seven-transmembrane receptors because they pass through the cell membrane seven times. Text was copied from this source, which is available under Attribution 2.5 Generic (CC BY 2.5) license. Ligands can bind either to extracellular N-terminus and loops (e.g. glutamate receptors) or to the binding site within transmembrane helices (Rhodopsin-like family). They are all activated by agonists although a spontaneous auto-activation of an empty receptor can also be observed. G protein-coupled receptors are found only in eukaryotes, including yeast, choanoflagellates, and ...
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Adhesion-GPCR
Adhesion G protein-coupled receptors (adhesion GPCRs) are a class of 33 human protein receptors with a broad distribution in embryonic and larval cells, cells of the reproductive tract, neurons, leukocytes, and a variety of tumours. Adhesion GPCRs are found throughout metazoans and are also found in single-celled colony forming choanoflagellates such as ''Monosiga brevicollis'' and unicellular organisms such as Filasterea. The defining feature of adhesion GPCRs that distinguishes them from other GPCRs is their hybrid molecular structure. The extracellular region of adhesion GPCRs can be exceptionally long and contain a variety of structural domains that are known for the ability to facilitate cell and matrix interactions. Their extracellular region contains the membrane proximal GAIN (GPCR-Autoproteolsis INducing) domain. Crystallographic and experimental data has shown this structurally conserved domain to mediate autocatalytic processing at a GPCR-proteolytic site (GPS) proxi ...
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Metabotropic Glutamate Receptor
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter. Function and structure The mGluRs perform a variety of functions in the central and peripheral nervous systems: For example, they are involved in learning, memory, anxiety, and the perception of pain. They are found in pre- and postsynaptic neurons in synapses of the hippocampus, cerebellum, and the cerebral cortex, as well as other parts of the brain and in peripheral tissues. Like other metabotropic receptors, mGluRs have seven transmembrane domains that span the cell membrane. Unlike ionotropic receptors, metabotropic glutamate receptors are not ion channels. Instead, they activate biochemical cascades, leading to the modification of o ...
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Rhodopsin
Rhodopsin, also known as visual purple, is a protein encoded by the RHO gene and a G-protein-coupled receptor (GPCR). It is the opsin of the rod cells in the retina and a light-sensitive receptor protein that triggers visual phototransduction in rods. Rhodopsin mediates dim light vision and thus is extremely sensitive to light. When rhodopsin is exposed to light, it immediately photobleaches. In humans, it is regenerated fully in about 30 minutes, after which the rods are more sensitive. Defects in the rhodopsin gene cause eye diseases such as retinitis pigmentosa and congenital stationary night blindness. Names Rhodopsin was discovered by Franz Christian Boll in 1876. The name rhodospsin derives from Ancient Greek () for "rose", due to its pinkish color, and () for "sight". It was coined in 1878 by the German physiologist Wilhelm Friedrich Kühne (1837-1900). When George Wald discovered that rhodopsin is a holoprotein, consisting of retinal and an apoprotein, he c ...
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Frizzled
Frizzled is a family of atypical G protein-coupled receptors that serve as receptors in the Wnt signaling pathway and other signaling pathways. When activated, Frizzled leads to activation of Dishevelled in the cytosol. Species distribution Frizzled proteins and the genes that encode them have been identified in an array of animals, from sponges to humans. Function Frizzled proteins also play key roles in governing cell polarity, embryonic development, formation of neural synapses, cell proliferation, and many other processes in developing and adult organisms. These processes occur as a result of one of three signaling pathways. These include the canonical Wnt/β-catenin pathway, Wnt/calcium pathway, and planar cell polarity (PCP) pathway. Mutations in the human frizzled-4 receptor have been linked to familial exudative vitreoretinopathy, a rare disease affecting the retina at the back of the eye, and the vitreous, the clear fluid inside the eye. The frizzled (fz) locu ...
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Taste Receptor
A taste receptor or tastant is a type of cellular receptor which facilitates the sensation of taste. When food or other substances enter the mouth, molecules interact with saliva and are bound to taste receptors in the oral cavity and other locations. Molecules which give a sensation of taste are considered "sapid". Vertebrate taste receptors are divided into two families: * Type 1, sweet, first characterized in 2001: – * Type 2, bitter, first characterized in 2000: In humans there are 25 known different bitter receptors, in cats there are 12, in chickens there are three, and in mice there are 35 known different bitter receptors. Visual, olfactive, "sapictive" (the perception of tastes), trigeminal (hot, cool), mechanical, all contribute to the perception of ''taste''. Of these, transient receptor potential cation channel subfamily V member 1 (TRPV1) vanilloid receptors are responsible for the perception of heat from some molecules such as capsaicin, and a CMR1 receptor is r ...
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Secretin Receptor
Human secretin receptor (gene name SCTR) is a G protein-coupled receptor which binds secretin and is the leading member (''i.e.'', first cloned) of the class B GPCR subfamily. Interactions Secretin receptor has been shown to interact with pituitary adenylate cyclase activating peptide Pituitary adenylate cyclase-activating polypeptide also known as PACAP is a protein that in humans is encoded by the ''ADCYAP1'' gene. pituitary adenylate cyclase-activating polypeptide is similar to vasoactive intestinal peptide. One of its effect .... References Further reading * * * * * * * * * * * * * * * * * External links IUPHAR GPCR Database - Secretin receptor* G protein-coupled receptors {{transmembranereceptor-stub ...
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Class C GPCR
The class C G-protein-coupled receptors () are a class of G-protein coupled receptors that include the metabotropic glutamate receptors () and several additional receptors. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length. This protein family includes metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors. Subfamilies Calcium-sensing receptor-related * extracellular calcium-sensing receptor-related ** Calcium-sensing receptor () ** GPRC6A () GABAB receptors * GABAB receptor (gamma-aminobutyric acid) ** GABAB receptor 1 () ** GABAB receptor 2 () Metabotropic glutamate re ...
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Rhodopsin-like Receptors
Rhodopsin-like receptors are a family of proteins that comprise the largest group of G protein-coupled receptors. Scope G-protein-coupled receptors, GPCRs, constitute a vast protein family that encompasses a wide range of functions (including various autocrine, paracrine, and endocrine processes). They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups. GPCRs are usually described as "superfamily" because they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence. The currently known superfamily members include the rhodopsin-like GPCRs (this family), the secretin-like GPCRs, the cAMP receptors, the fungal mating pheromone receptors, and the metabotropic glutamate receptor family. There is a specialised database for GPCRs. Function The rhodopsin-like GPCRs themselves represent a widespread protein ...
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Secretin Receptor Family
Secretin family receptor proteins, also known as Family B or family 2 of G-protein coupled receptors are regulated by peptide hormones from the glucagon hormone family. The family is different from adhesion G protein-coupled receptors. The secretin-receptor family of GPCRs include vasoactive intestinal peptide receptors and receptors for secretin receptor, secretin, calcitonin receptor, calcitonin and parathyroid hormone receptor, parathyroid hormone/parathyroid hormone-related peptides. These receptors activate adenylyl cyclase and the Phospholipase C#Effects, phosphatidyl-inositol-calcium pathway. The receptors in this family have 7 Transmembrane domain, transmembrane Alpha helix, helices,; ; like rhodopsin-like GPCRs. However, there is no significant sequence identity between these two GPCR families and the secretin-receptor family has its own characteristic Seven transmembrane protein, 7TM signature. The secretin-receptor family GPCRs exist in many animal species. Data minin ...
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Smoothened
Smoothened is a protein that in humans is encoded by the SMO gene. Smoothened is a Class Frizzled (Class F) G protein-coupled receptor that is a component of the hedgehog signaling pathway and is conserved from flies to humans. It is the molecular target of the natural teratogen cyclopamine. It also is the target of vismodegib, the first hedgehog pathway inhibitor to be approved by the U.S. Food and Drug Administration (FDA). Smoothened (Smo) is a key transmembrane protein that is a key component of the hedgehog signaling pathway, a cell-cell communication system critical for embryonic development and adult tissue homeostasis. Mutations in proteins that relay Hh signals between cells cause birth defects and cancer. The protein that carries the Hh signal across the membrane is the oncoprotein and G-protein coupled receptor (GPCR) Smoothened (Smo). Smo is regulated by a separate transmembrane receptor for Hh ligands called Patched (Ptc). Ptc itself is a tumor suppressor that keeps ...
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