Membrane-associated guanylate kinase

Membrane-associated guanylate kinase (MAGUK) scaffold protein
Identifiers
Symbol	MAGUK
InterPro	IPR016313

Last updated December 14, 2020

The membrane-associated guanylate kinases (MAGUK) are a superfamily of proteins.^[1] 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.^[2] The GUK domain that they have is structurally very similar to that of the guanylate kinases, 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.

MAGUKs also contain multiple PDZ domains, or short peptide binding sequences commonly bind to the C-terminus of interacting proteins. The number of PDZ domain copies varies between different members of the MAGUK family. The PDZ domains found within each family member often have different binding partners, due to variations in their amino acid compositions. 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 an 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:

DLG1, DLG2, DLG3, DLG4, DLG5

Related Research Articles

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. Proteins containing PDZ domains play a key role in anchoring receptor proteins in the membrane to cytoskeletal components. Proteins with these domains help hold together and organize signaling complexes at cellular membranes. These domains play a key role in the formation and function of signal transduction complexes. PDZ domains also play a highly significant role in the anchoring of cell surface receptors to the actin cytoskeleton via mediators like NHERF and ezrin.

Platelet-derived growth factor receptors (PDGF-R) are cell surface tyrosine kinase receptors for members of the platelet-derived growth factor (PDGF) family. PDGF subunits -A and -B are important factors regulating cell proliferation, cellular differentiation, cell growth, development and many diseases including cancer. There are two forms of the PDGF-R, alpha and beta each encoded by a different gene. Depending on which growth factor is bound, PDGF-R homo- or heterodimerizes.

PSD-95 also known as SAP-90 is a protein that in humans is encoded by the DLG4 gene.

Discs large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a scaffold protein that in humans is encoded by the SAP97 gene.

Peripheral plasma membrane protein CASK is a protein that in humans is encoded by the CASK gene. This gene is also known by several other names: CMG 2, calcium/calmodulin-dependent serine protein kinase 3 and membrane-associated guanylate kinase 2.

Protein Interacting with C Kinase - 1 is a protein that in humans is encoded by the PICK1 gene.

Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the DLG3 gene. DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfamily of proteins.

Disks large homolog 2 (DLG2) also known as channel-associated protein of synapse-110 (chapsyn-110) or postsynaptic density protein 93 (PSD-93) is a protein that in humans is encoded by the DLG2 gene.

Tyrosine-protein phosphatase non-receptor type 13 is an enzyme that in humans is encoded by the PTPN13 gene.

Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.

Potassium voltage-gated channel subfamily A member 4 also known as K_v1.4 is a protein that in humans is encoded by the KCNA4 gene. It contributes to the cardiac transient outward potassium current (I_to1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

Disks large homolog 5 is a protein that in humans is encoded by the DLG5 gene.

MAGUK p55 subfamily member 5 is a protein that in humans is encoded by the MPP5 gene. Members of the peripheral membrane-associated guanylate kinase (MAGUK) family function in tumor suppression and receptor clustering by forming multiprotein complexes containing distinct sets of transmembrane, cytoskeletal, and cytoplasmic signaling proteins. All MAGUKs contain a PDZ-SH3-GUK core and are divided into 4 subfamilies, DLG-like, ZO1-like, p55-like, and LIN2-like, based on their size and the presence of additional domains. MPP5 is a member of the p55-like MAGUK subfamily.[supplied by OMIM]

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 1 is an enzyme that in humans is encoded by the MAGI1 gene.

MAGUK p55 subfamily member 6 is a protein that in humans is encoded by the MPP6 gene.

kinase-associated protein (GKAP), is a protein that in humans is encoded by the DLGAP1 gene. DAP-1 is known to be highly enriched in synaptosomal preparations of the brain, and present in the post-synaptic density.

Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 also known as membrane-associated guanylate kinase inverted 2 (MAGI-2) and atrophin-1-interacting protein 1 (AIP-1) is an enzyme that in humans is encoded by the MAGI2 gene.

55 kDa erythrocyte membrane protein is a protein that in humans is encoded by the MPP1 gene.

Disks large-associated protein 2 is a protein that in humans is encoded by the DLGAP2 gene.

Non-receptor tyrosine kinases (nRTKs) are cytosolic enzymes that are responsible for catalysing the transfer of a phosphate group from a nucleoside triphosphate donor, such as ATP, to tyrosine residues in proteins. Non-receptor tyrosine kinases are a subgroup of protein family tyrosine kinases, enzymes that can transfer the phosphate group from ATP to a tyrosine residue of a protein (phosphorylation). These enzymes regulate many cellular functions by switching on or switching off other enzymes in a cell.

References

↑ Godreau D, Neyroud N, Vranckx R, Hatem S (January 2004). "[MAGUKs: beyond ionic channel anchoring]" (PDF). Med Sci (Paris) (in French). 20 (1): 84–8. doi:10.1051/medsci/200420184. PMID 14770369.
↑ Woods DF, Bryant PJ (December 1993). "ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate and synaptic cell junctions". Mech. Dev. 44 (2–3): 85–9. doi:10.1016/0925-4773(93)90059-7. PMID 8155583.

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[pmid14770369-1] Godreau D, Neyroud N, Vranckx R, Hatem S (January 2004). "[MAGUKs: beyond ionic channel anchoring]" (PDF). Med Sci (Paris) (in French). 20 (1): 84–8. doi:10.1051/medsci/200420184. PMID 14770369.

[pmid8155583-2] Woods DF, Bryant PJ (December 1993). "ZO-1, DlgA and PSD-95/SAP90: homologous proteins in tight, septate and synaptic cell junctions". Mech. Dev. 44 (2–3): 85–9. doi:10.1016/0925-4773(93)90059-7. PMID 8155583.

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