Membrane-associated guanylate kinase

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

Last updated September 10, 2024

The membrane-associated guanylate kinases (MAGUK) are a family 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 SRC Homology 3 Domain is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of phospholipase and several cytoplasmic tyrosine kinases such as Abl and Src. It has also been identified in several other protein families such as: PI3 Kinase, Ras GTPase-activating protein, CDC24 and cdc25. SH3 domains are found in proteins of signaling pathways regulating the cytoskeleton, the Ras protein, and the Src kinase and many others. The SH3 proteins interact with adaptor proteins and tyrosine kinases. Interacting with tyrosine kinases, SH3 proteins usually bind far away from the active site. Approximately 300 SH3 domains are found in proteins encoded in the human genome. In addition to that, the SH3 domain was responsible for controlling protein-protein interactions in the signal transduction pathways and regulating the interactions of proteins involved in the cytoplasmic signaling.

Voltage-gated calcium channels (VGCCs), also known as voltage-dependent calcium channels (VDCCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (e.g., muscle, glial cells, neurons, etc.) with a permeability to the calcium ion Ca²⁺. These channels are slightly permeable to sodium ions, so they are also called Ca²⁺–Na⁺ channels, but their permeability to calcium is about 1000-fold greater than to sodium under normal physiological conditions.

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.

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.

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

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.

Disks large-associated protein 1 (DAP-1), also known as guanylate 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.

A non-receptor tyrosine kinase (nRTK) is a cytosolic enzyme that is 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.

Src kinase family is a family of non-receptor tyrosine kinases that includes nine members: Src, Yes, Fyn, and Fgr, forming the SrcA subfamily, Lck, Hck, Blk, and Lyn in the SrcB subfamily, and Frk in its own subfamily. Frk has homologs in invertebrates such as flies and worms, and Src homologs exist in organisms as diverse as unicellular choanoflagellates, but the SrcA and SrcB subfamilies are specific to vertebrates. Src family kinases contain six conserved domains: a N-terminal myristoylated segment, a SH2 domain, a SH3 domain, a linker region, a tyrosine kinase domain, and C-terminal tail.

Caspase recruitment domain-containing protein 14, also known as D-containing MAGUK protein 2, is a protein in the CARD-CC protein family that in humans is encoded by the CARD14 gene.

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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