DLG1
Encyclopedia
Disks large homolog 1 also known as synapse-associated protein 97 or SAP97, is a protein
that in humans is encoded by the SAP97 gene
.
SAP97 is a mammalian MAGUK
-family member protein that is similar to the Drosophila protein Dlg1
(the protein is alternatively referred to as hDlg1, and the human gene is DLG1). SAP97 is expressed throughout the body in epithelial cells. In the brain it is involved in the trafficking of ionotropic receptors from the endoplasmic Reticulum
to the plasma membrane, and may be involved in the trafficking AMPAR during synaptic plasticity.
SAP97's function has been investigated by reducing its expression by knockout
or increasing its expression heterologously. Mice in which the SAP97 gene has been knocked out die perinatally, have a cleft palate, and deficiencies in renal function. Overexpression of SAP97 in mammalian neurons leads to increased synaptic strength.
s, an SH3 domain
, hook domain, I3 domain, and finally an inactive guanylate kinase
(GK) domain. Each of these domains has specific interacting partners that help define SAP97's unique function.
The n-terminal of SAP97 can be alternatively spliced to contain a double-cysteine/palmitoylation site (α-isoform), or an L27 domain (β-isoform. The L27 domain is involved in SAP97 oligomerization with other SAP97 molecules, CASK, and other L27-domain-containing proteins. There is also a myosin
VI binding site near n-terminal which may be involved in the internalization of AMPAR.
Each of SAP97's PDZ domains have different binding partners, including the AMPAR subunit GluR1 for the first PDZ domain, and neuroligin
for the last. SAP97's I3 domain is unique to SAP97 among the MAGUK family, and is known to regulate the post-synaptic localization of SAP97 and to bind the protein 4.1N. The GK domain allows SAP97 to bind to GKAP/SAPAP-family proteins.
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...
that in humans is encoded by the SAP97 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
SAP97 is a mammalian MAGUK
Membrane-associated guanylate kinase
The membrane-associated guanylate kinases are a superfamily of proteins. 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...
-family member protein that is similar to the Drosophila protein Dlg1
DLG1
Disks large homolog 1 , also known as synapse-associated protein 97 or SAP97, is a protein that in humans is encoded by the SAP97 gene....
(the protein is alternatively referred to as hDlg1, and the human gene is DLG1). SAP97 is expressed throughout the body in epithelial cells. In the brain it is involved in the trafficking of ionotropic receptors from the endoplasmic Reticulum
Endoplasmic reticulum
The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...
to the plasma membrane, and may be involved in the trafficking AMPAR during synaptic plasticity.
Function
SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain. There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with HPV. In the brain, SAP97's function is involved in the trafficking of transmembrane receptors from the ER to the plasma membrane.SAP97's function has been investigated by reducing its expression by knockout
Knockout
A knockout is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, Karate and others sports involving striking...
or increasing its expression heterologously. Mice in which the SAP97 gene has been knocked out die perinatally, have a cleft palate, and deficiencies in renal function. Overexpression of SAP97 in mammalian neurons leads to increased synaptic strength.
Structure
SAP97's protein structure consists of an alternatively-spliced n-terminal domain, three PDZ domainPDZ 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...
s, an SH3 domain
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...
, hook domain, I3 domain, and finally an inactive 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....
(GK) domain. Each of these domains has specific interacting partners that help define SAP97's unique function.
The n-terminal of SAP97 can be alternatively spliced to contain a double-cysteine/palmitoylation site (α-isoform), or an L27 domain (β-isoform. The L27 domain is involved in SAP97 oligomerization with other SAP97 molecules, CASK, and other L27-domain-containing proteins. There is also a myosin
Myosin
Myosins comprise a family of ATP-dependent motor proteins and are best known for their role in muscle contraction and their involvement in a wide range of other eukaryotic motility processes. They are responsible for actin-based motility. The term was originally used to describe a group of similar...
VI binding site near n-terminal which may be involved in the internalization of AMPAR.
Each of SAP97's PDZ domains have different binding partners, including the AMPAR subunit GluR1 for the first PDZ domain, and neuroligin
Neuroligin
300px|thumb|right|alt = Colored dice with checkered background|Tertiary structure of Neuroligin 4.Neuroligin , a type I membrane protein, is a protein on the postsynaptic membrane that mediates synapse formation between neurons. Neuroligins mediate signaling across the synapse and affect the...
for the last. SAP97's I3 domain is unique to SAP97 among the MAGUK family, and is known to regulate the post-synaptic localization of SAP97 and to bind the protein 4.1N. The GK domain allows SAP97 to bind to GKAP/SAPAP-family proteins.