GNA12
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GNA12
Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the ''GNA12'' gene. Interactions and functions The GNA12 gene encodes the G12 G protein alpha subunit. Together with GNA13, these two proteins comprise one of the four classes of heterotrimeric G protein alpha subunits. Heterotrimeric G proteins function in transducing hormone and neurotransmitter signals detected by cell surface G protein-coupled receptors to intracellular signaling pathways to modulate cell functions. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to GTP but inactive and associated with the G beta-gamma complex when bound to GDP. Active GTP-bound G12 alpha subunit interacts with and activates ARHGEF1, ARHGEF11, and ARHGEF12. These ARHGEF proteins function as guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton. GNA12 also interacts with PPP5C, HSP90, ...
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G12/G13 Alpha Subunits
G12/G13 alpha subunits are alpha subunits of heterotrimeric G proteins that link cell surface G protein-coupled receptors primarily to guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton. Together, these two proteins comprise one of the four classes of G protein alpha subunits. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to GTP but inactive and associated with the G beta-gamma complex when bound to GDP. G12/G13 are not targets of pertussis toxin or cholera toxin, as are other classes of G protein alpha subunits. G proteins G12 and G13 regulate actin cytoskeletal remodeling in cells during movement and migration, including cancer cell metastasis. G13 is also essential for receptor tyrosine kinase-induced migration of fibroblast and endothelial cells. Genes * GNA12 () * GNA13 See also * Second messenger system * G protein-coupled receptor * Heterotrimeric G prot ...
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Heterotrimeric G Protein
Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest non-structural difference between heterotrimeric and monomeric G protein is that heterotrimeric proteins bind to their cell-surface receptors, called G protein-coupled receptors, directly. These G proteins are made up of ''alpha'' (α), ''beta'' (β) and ''gamma'' (γ) Protein subunit, subunits. The alpha subunit is attached to either a GTP or GDP, which serves as an on-off switch for the activation of G-protein. When ligands bind a GPCR, the GPCR acquires GEF (guanine nucleotide exchange factor) ability, which activates the G-protein by exchanging the GDP on the ''alpha'' subunit to GTP. The binding of GTP to the ''alpha'' subunit results in a structural change and its dissociation from the rest of the G-protein. Generally, the ''alpha'' su ...
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ARHGEF11
Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ''ARHGEF11'' gene. This protein is also called RhoGEF11 or PDZ-RhoGEF. Function Rho guanine nucleotide exchange factor 11 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions. In particular, active Rho is a major regulator of the cell actin cytoskeleton. RhoGEF11 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins. The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (al ...
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TEC (gene)
Tyrosine-protein kinase Tec is a tyrosine kinase that in humans is encoded by the ''TEC'' gene. Tec kinase is expressed in hematopoietic, liver, and kidney cells and plays an important role in T-helper cell processes. Tec kinase is the name-giving member of the Tec kinase family, a family of non-receptor protein-tyrosine kinases. Structure Tec kinase contains five protein interaction domains. The characteristic feature of Tec family kinases is a pleckstrin homology (PH) domain on the N-terminus of the molecule followed by a Tec homology (TH) domain. The TH domain of Tec kinase contains a Btk homology (BH) motif and two proline-rich (PR) regions. The other protein interaction domains of Tec kinase include Src homology (SH) domains SH2 and SH3 and a kinase domain with enzymatic activity. ''TEC'' produces two protein isoforms that differ in the SH3 domain through alternative splicing. Type IV isoform has a full length SH3 domain and is predominately expressed in hematopoietic ...
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PPP5C
Serine/threonine-protein phosphatase 5 is an enzyme that in humans is encoded by the ''PPP5C'' gene. Model organisms Model organisms have been used in the study of PPP5C function. A conditional knockout mouse line, called ''Ppp5ctm1a(EUCOMM)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and five significant abnormalities were observed. Homozygous mutant males had decreased body weight, body length and respiratory quotient. Both sexes had increased T cell numbers and a range of skeletal abnormalities identified by radiography. Interactions PPP5C has been shown to interact with ASK1, CRY2 GNA12 Guanine nucleotide-binding protein subunit alpha-12 is a protein that in ...
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ARHGEF12
Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ''ARHGEF12'' gene. This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG). Function Rho guanine nucleotide exchange factor 12 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions. In particular, active Rho is a major regulator of the cell actin cytoskeleton. RhoGEF12 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins. The others are ARHGEF1 (also known as p11 ...
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ARHGEF1
Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ''ARHGEF1'' gene. This protein is also called RhoGEF1 or p115-RhoGEF. Function Rho guanine nucleotide exchange factor 1 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions. In particular, active Rho is a major regulator of the cell actin cytoskeleton. RhoGEF1 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins. The others are ARHGEF11 (also known as PDZ-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (also ...
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Heterotrimeric G Protein
Heterotrimeric G protein, also sometimes referred to as the ''"large" G proteins'' (as opposed to the subclass of smaller, monomeric small GTPases) are membrane-associated G proteins that form a Heteromer, heterotrimeric complex. The biggest non-structural difference between heterotrimeric and monomeric G protein is that heterotrimeric proteins bind to their cell-surface receptors, called G protein-coupled receptors, directly. These G proteins are made up of ''alpha'' (α), ''beta'' (β) and ''gamma'' (γ) Protein subunit, subunits. The alpha subunit is attached to either a GTP or GDP, which serves as an on-off switch for the activation of G-protein. When ligands bind a GPCR, the GPCR acquires GEF (guanine nucleotide exchange factor) ability, which activates the G-protein by exchanging the GDP on the ''alpha'' subunit to GTP. The binding of GTP to the ''alpha'' subunit results in a structural change and its dissociation from the rest of the G-protein. Generally, the ''alpha'' su ...
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GNA13
Guanine nucleotide-binding protein subunit alpha-13 is a protein that in humans is encoded by the ''GNA13'' gene. Interactions and functions The GNA13 gene encodes the G13 G protein alpha subunit. Together with GNA12, these two proteins comprise one of the four classes of heterotrimeric G protein alpha subunits. Heterotrimeric G proteins function in transducing hormone and neurotransmitter signals detected by cell surface G protein-coupled receptors to intracellular signaling pathways to modulate cell functions. G protein alpha subunits bind to guanine nucleotides and function in a regulatory cycle, and are active when bound to GTP but inactive and associated with the G beta-gamma complex when bound to GDP. Active GTP-bound G12 alpha subunit interacts with and activates ARHGEF1, ARHGEF11, and ARHGEF12. These ARHGEF proteins function as guanine nucleotide exchange factors for the Rho small GTPases to regulate the actin cytoskeleton. GNA13 has been shown to interact with AKA ...
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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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Small GTPases
Small GTPases (), also known as 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. A typical G-protein is active when bound to GTP and inactive when bound to GDP (i.e. when the GTP is hydrolyzed to GDP). The GDP can be then replaced by free GTP. Therefore, a G-protein can be switched on and off. GTP hydrolysis is accelerated by GTPase activating proteins (GAPs), while GTP exchange is catalyzed by guanine nucleotide exchange factors (GEFs). Activation of a GEF typically activates its cognate G-protein, w ...
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G Alpha Subunit
G alpha subunits are one of the three types of subunit of guanine nucleotide binding proteins, which are membrane-associated, heterotrimeric G proteins. Background G proteins and their receptors (GPCRs) form one of the most prevalent signalling systems in mammalian cells, regulating systems as diverse as sensory perception, cell growth and hormonal regulation. At the cell surface, the binding of ligands such as hormones and neurotransmitters to a GPCR activates the receptor by causing a conformational change, which in turn activates the bound G protein on the intracellular-side of the membrane. The activated receptor promotes the exchange of bound GDP for GTP on the G protein alpha subunit. GTP binding changes the conformation of switch regions within the alpha subunit, which allows the bound trimeric G protein (inactive) to be released from the receptor, and to dissociate into active alpha subunit (GTP-bound) and beta/gamma dimer. The alpha subunit and the beta/gamma dimer go ...
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