Rho guanine nucleotide exchange factor 11 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...
that in humans is encoded by the ''ARHGEF11''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
This protein is also called RhoGEF11 or PDZ-RhoGEF.
Function
Rho guanine nucleotide exchange factor 11 is
guanine nucleotide exchange factor
Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structu ...
(GEF) for the
RhoA
Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the ''RHOA'' gene. While the effects of RhoA activity are not all well known, it is ...
small GTPase
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 heterotrim ...
protein.
Rho is a
small GTPase
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 heterotrim ...
protein that is inactive when bound to the
guanine
Guanine () (symbol G or Gua) is one of the four main nucleotide bases found in the nucleic acids DNA and RNA, the others being adenine, cytosine, and thymine ( uracil in RNA). In DNA, guanine is paired with cytosine. The guanine nucleoside ...
nucleotide
Nucleotides are Organic compound, organic molecules composed of a nitrogenous base, a pentose sugar and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both o ...
GDP
Gross domestic product (GDP) is a monetary measure of the total market value of all the final goods and services produced and rendered in a specific time period by a country or countries. GDP is often used to measure the economic performance o ...
. 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
Effector may refer to:
*Effector (biology), a molecule that binds to a protein and thereby alters the activity of that protein
* ''Effector'' (album), a music album by the Experimental Techno group Download
* ''EFFector'', a publication of the El ...
proteins and
enzymes
An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as pro ...
to regulate cellular functions.
[
] In particular, active Rho is a major regulator of the cell
actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of ...
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
.
RhoGEF11 is a member of a group of four
RhoGEF
RhoGEF domain describes two distinct structural domains with guanine nucleotide exchange factor (GEF) activity to regulate small GTPases in the Rho family. Rho small GTPases are inactive when bound to GDP but active when bound to GTP; RhoGEF ...
proteins known to be activated by
G protein coupled receptors
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 ...
coupled to the
G12 and G13 heterotrimeric G proteins.
The others are
ARHGEF1 (also known as p115-RhoGEF),
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 nucleoti ...
(also known as LARG) and
AKAP13 (also known as ARHGEF13 and Lbc).
GPCR-regulated RhoGEF11 (and these related GEF proteins) acts as an effector for G
12 and G
13 G proteins. In addition to being activated by G
12 or G
13 G proteins, three of these four RhoGEF proteins (ARHGEF1/11/12) also function as
RGS family GTPase-activating proteins (GAPs) to increase the rate of GTP hydrolysis of G
12/G
13 alpha proteins (which are themselves GTPase proteins). This action increases the rate of G protein deactivation, limiting the time during which these RhoGEFs activate Rho.
Two alternative transcripts encoding different isoforms have been described.
Interactions
ARHGEF11 has been shown to
interact with:
*
GNA12
*
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 com ...
*
PLXNB1
Plexin B1 is a protein of the plexin family that in humans is encoded by the ''PLXNB1'' gene.
Function
Within neural tissues, the plexin
A plexin is a protein which acts as a receptor for semaphorin family signaling proteins. It is classic ...
,
[
* ]RHOA
Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the ''RHOA'' gene. While the effects of RhoA activity are not all well known, it is ...
See also
* Second messenger system
Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form of cell signaling, encompassing both first me ...
* 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 ...
* 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 no ...
* Small GTPases
* Rho family of GTPases
The Rho family of GTPases is a family of small (~21 kDa) signaling G proteins, and is a subfamily of the Ras superfamily. The members of the Rho GTPase family have been shown to regulate many aspects of intracellular actin dynamics, and are found ...
References
Further reading
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External links
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{{PDB Gallery, geneid=9826