Membrane-associated guanylate kinase
Encyclopedia
The membrane-associated guanylate kinases (MAGUK) are a superfamily of protein
s. The MAGUKs are defined by their inclusion of PDZ
, SH3
and GUK
domains, although many of them also contain regions homologous of CaMKII
, WW
and L27
domains. The GUK domain that they have is structurally very similar to that of the guanylate kinase
s, however it is known to be catalytically inactive as the P-Loop which binds ATP
is absent. It is thought that the MAGUKs have subfunctionalized the GUK domain for their own purposes, primarily based on its ability to form protein-protein interactions with cytoskeleton
proteins, microtubule
/actin
based machinery and molecules involved in signal transduction
.
The PDZ domain
which are contained in the MAGUKs in varying numbers. PDZ domains are short peptide binding sequences commonly found at the C-terminus of interacting proteins. Copies within each of the family members often have different binding partners, due to amino acid differences between the copies. The SH3 domain is again a protein-protein interaction domain. Its family generally bind to PXXP sites, but in MAGUKs it is known to bind to other sites as well. One of the most well known features is that it can form a intramolecular bond with the GUK domain, creating what is known as a GUK-SH3 'closed' state.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s. The MAGUKs are defined by their inclusion of PDZ
PDZ domain
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals...
, SH3
SH3 domain
The SRC Homology 3 Domain is a small protein domain of about 60 amino acids residues first identified as a conserved sequence in the viral adaptor protein v-Crk and the non-catalytic parts of enzymes such as phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src...
and GUK
Guanylate kinase
In enzymology, a guanylate kinase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are ATP and GMP, whereas its two products are ADP and GDP....
domains, although many of them also contain regions homologous of CaMKII
Ca2+/calmodulin-dependent protein kinase
/calmodulin-dependent protein kinases II or CaM kinases II are serine/threonine-specific protein kinases that are regulated by the /calmodulin complex...
, WW
WW domain
The WW domain is a protein domain with two highly conserved tryptophans that binds proline-rich peptide motifs...
and L27
L27 domain
The L27 domain is a protein domain that is found in receptor targeting proteins Lin-2 and Lin-7 , as well as some protein kinases and human MPP2 protein.- References :...
domains. The GUK domain that they have is structurally very similar to that of the guanylate kinase
Guanylate kinase
In enzymology, a guanylate kinase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are ATP and GMP, whereas its two products are ADP and GDP....
s, however it is known to be catalytically inactive as the P-Loop which binds ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
is absent. It is thought that the MAGUKs have subfunctionalized the GUK domain for their own purposes, primarily based on its ability to form protein-protein interactions with cytoskeleton
Cytoskeleton
The cytoskeleton is a cellular "scaffolding" or "skeleton" contained within a cell's cytoplasm and is made out of protein. The cytoskeleton is present in all cells; it was once thought to be unique to eukaryotes, but recent research has identified the prokaryotic cytoskeleton...
proteins, microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...
/actin
Actin
Actin is a globular, roughly 42-kDa moonlighting protein found in all eukaryotic cells where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans...
based machinery and molecules involved in signal transduction
Signal transduction
Signal transduction occurs when an extracellular signaling molecule activates a cell surface receptor. In turn, this receptor alters intracellular molecules creating a response...
.
The PDZ domain
PDZ domain
The PDZ domain is a common structural domain of 80-90 amino-acids found in the signaling proteins of bacteria, yeast, plants, viruses and animals...
which are contained in the MAGUKs in varying numbers. PDZ domains are short peptide binding sequences commonly found at the C-terminus of interacting proteins. Copies within each of the family members often have different binding partners, due to amino acid differences between the copies. The SH3 domain is again a protein-protein interaction domain. Its family generally bind to PXXP sites, but in MAGUKs it is known to bind to other sites as well. One of the most well known features is that it can form a intramolecular bond with the GUK domain, creating what is known as a GUK-SH3 'closed' state.
Examples
Humans genes encoding members of the MAGUK protein superfamily include:- DLG1DLG1Disks large homolog 1 , also known as synapse-associated protein 97 or SAP97, is a protein that in humans is encoded by the SAP97 gene....
, DLG2DLG2Disks large homolog 2 also known as channel-associated protein of synapse-110 or postsynaptic density protein 93 is a protein that in humans is encoded by the DLG2 gene.- Function :...
, DLG3DLG3Disks large homolog 3 also known as neuroendocrine-DLG or synapse-associated protein 102 is a protein that in humans is encoded by the DLG3 gene...
, DLG4DLG4PSD-95 also known as SAP-90 is a protein that in humans is encoded by the DLG4 gene....
, DLG5DLG5Disks large homolog 5 is a protein that in humans is encoded by the DLG5 gene.-Further reading:...