DLG1

Last updated
DLG1
Protein DLG1 PDB 1iu0.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases DLG1 , DLGH1, SAP-97, SAP97, dJ1061C18.1.1, hdlg, B130052P05Rik, E-dlg/SAP97, mKIAA4187, discs large homolog 1, scribble cell polarity complex component, discs large MAGUK scaffold protein 1
External IDs OMIM: 601014 MGI: 107231 HomoloGene: 20869 GeneCards: DLG1
Orthologs
SpeciesHumanMouse
Entrez

1739

13383

Ensembl

ENSG00000075711

ENSMUSG00000022770

UniProt

Q12959

Q811D0

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC) Chr 3: 197.04 – 197.3 Mb Chr 16: 31.48 – 31.69 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.

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.

Function

SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain. [5] 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. [6]

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. [7] [8] Overexpression of SAP97 in mammalian neurons leads to increased synaptic strength. [9]

Clinical significance

Mutations in DLG1 are associated to Crohn's disease. [10]

Structure

SAP97's protein structure consists of an alternatively-spliced N-terminal domain, three PDZ domains, 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. [11] There is also a myosin VI binding site near N-terminal which may be involved in the internalization of AMPAR. [12] [13]

Each of SAP97's PDZ domains have different binding partners, including the AMPAR subunit GluR1 [14] [15] 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 [9] and to bind the protein 4.1N. The GK domain allows SAP97 to bind to GKAP/SAPAP-family proteins.

Related Research Articles

<span class="mw-page-title-main">AMPA receptor</span> Transmembrane protein family

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor is an ionotropic transmembrane receptor for glutamate (iGluR) that mediates fast synaptic transmission in the central nervous system (CNS). It has been traditionally classified as a non-NMDA-type receptor, along with the kainate receptor. Its name is derived from its ability to be activated by the artificial glutamate analog AMPA. The receptor was first named the "quisqualate receptor" by Watkins and colleagues after a naturally occurring agonist quisqualate and was only later given the label "AMPA receptor" after the selective agonist developed by Tage Honore and colleagues at the Royal Danish School of Pharmacy in Copenhagen. The GRIA2-encoded AMPA receptor ligand binding core was the first glutamate receptor ion channel domain to be crystallized.

<span class="mw-page-title-main">PDZ domain</span>

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.

K<sub>ir</sub>2.1 Protein-coding gene in the species Homo sapiens

The Kir2.1 inward-rectifier potassium channel is a lipid-gated ion channel encoded by the KCNJ2 gene.

<span class="mw-page-title-main">DLG4</span> Mammalian protein found in Homo sapiens

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

<span class="mw-page-title-main">CASK</span> Protein-coding gene in humans

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. CASK gene mutations are the cause of XL-ID with or without nystagmus and MICPCH, an X-linked neurological disorder.

<span class="mw-page-title-main">PICK1</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">DLG3</span> Protein-coding gene in humans

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.

<span class="mw-page-title-main">DLG2</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">GRIN2B</span> Protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit epsilon-2, also known as N-methyl D-aspartate receptor subtype 2B, is a protein that in humans is encoded by the GRIN2B gene.

<span class="mw-page-title-main">Brain-specific angiogenesis inhibitor 1</span> Protein-coding gene in the species Homo sapiens

Brain-specific angiogenesis inhibitor 1 is a protein that in humans is encoded by the BAI1 gene. It is a member of the adhesion-GPCR family of receptors.

<span class="mw-page-title-main">GRIN2A</span> Protein-coding gene in the species Homo sapiens

Glutamate [NMDA] receptor subunit epsilon-1 is a protein that in humans is encoded by the GRIN2A gene. With 1464 amino acids, the canonical GluN2A subunit isoform is large. GluN2A-short isoforms specific to primates can be produced by alternative splicing and contain 1281 amino acids.

<span class="mw-page-title-main">GRIA1</span> Mammalian protein found in Homo sapiens

Glutamate receptor 1 is a protein that in humans is encoded by the GRIA1 gene.

<span class="mw-page-title-main">KCNA4</span> Protein-coding gene in the species Homo sapiens

Potassium voltage-gated channel subfamily A member 4 also known as Kv1.4 is a protein that in humans is encoded by the KCNA4 gene. It contributes to the cardiac transient outward potassium current (Ito1), the main contributing current to the repolarizing phase 1 of the cardiac action potential.

<span class="mw-page-title-main">KCNJ4</span> Protein-coding gene in the species Homo sapiens

Potassium inwardly-rectifying channel, subfamily J, member 4, also known as KCNJ4 or Kir2.3, is a human gene.

<span class="mw-page-title-main">MAGI1</span> Protein-coding gene in the species Homo sapiens

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

<span class="mw-page-title-main">DLGAP1</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">MAGI2</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">DLGAP4</span> Protein-coding gene in the species Homo sapiens

Disks large-associated protein 4 (DAP-4) also known as SAP90/PSD-95-associated protein 4 (SAPAP-4) is a protein that in humans is encoded by the DLGAP4 gene.

<span class="mw-page-title-main">LIN7B</span> Protein-coding gene in humans

Lin-7 homolog B is a protein that in humans is encoded by the LIN7B gene.

<span class="mw-page-title-main">DLGAP2</span> Protein-coding gene in the species Homo sapiens

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000075711 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022770 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Müller BM, Kistner U, Veh RW, Cases-Langhoff C, Becker B, Gundelfinger ED, Garner CC (Mar 1995). "Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein". The Journal of Neuroscience. 15 (3 Pt 2): 2354–66. doi:10.1523/JNEUROSCI.15-03-02354.1995. PMC   6578138 . PMID   7891172.
  6. ↑ Sans N, Racca C, Petralia RS, Wang YX, McCallum J, Wenthold RJ (Oct 2001). "Synapse-associated protein 97 selectively associates with a subset of AMPA receptors early in their biosynthetic pathway". The Journal of Neuroscience. 21 (19): 7506–16. doi: 10.1523/JNEUROSCI.21-19-07506.2001 . PMC   6762903 . PMID   11567040.
  7. ↑ Caruana G, Bernstein A (Mar 2001). "Craniofacial dysmorphogenesis including cleft palate in mice with an insertional mutation in the discs large gene". Molecular and Cellular Biology. 21 (5): 1475–83. doi:10.1128/MCB.21.5.1475-1483.2001. PMC   86693 . PMID   11238884.
  8. ↑ Mahoney ZX, Sammut B, Xavier RJ, Cunningham J, Go G, Brim KL, Stappenbeck TS, Miner JH, Swat W (Dec 2006). "Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter". Proceedings of the National Academy of Sciences of the United States of America. 103 (52): 19872–7. Bibcode:2006PNAS..10319872M. doi: 10.1073/pnas.0609326103 . PMC   1750896 . PMID   17172448.
  9. 1 2 Rumbaugh G, Sia GM, Garner CC, Huganir RL (Jun 2003). "Synapse-associated protein-97 isoform-specific regulation of surface AMPA receptors and synaptic function in cultured neurons". The Journal of Neuroscience. 23 (11): 4567–76. doi:10.1523/JNEUROSCI.23-11-04567.2003. PMC   6740810 . PMID   12805297.
  10. ↑ Xu S, Zhou F, Tao J, Song L, Ng SC, Wang X, Chen L, Yi F, Ran Z, Zhou R, Xia B (2014). "Exome sequencing identifies DLG1 as a novel gene for potential susceptibility to Crohn's disease in a Chinese family study". PLOS ONE. 9 (6): e99807. Bibcode:2014PLoSO...999807X. doi: 10.1371/journal.pone.0099807 . PMC   4061034 . PMID   24937328.
  11. ↑ Lee S, Fan S, Makarova O, Straight S, Margolis B (Mar 2002). "A novel and conserved protein-protein interaction domain of mammalian Lin-2/CASK binds and recruits SAP97 to the lateral surface of epithelia". Molecular and Cellular Biology. 22 (6): 1778–91. doi:10.1128/MCB.22.6.1778-1791.2002. PMC   135599 . PMID   11865057.
  12. ↑ Wu H, Nash JE, Zamorano P, Garner CC (Aug 2002). "Interaction of SAP97 with minus-end-directed actin motor myosin VI. Implications for AMPA receptor trafficking". The Journal of Biological Chemistry. 277 (34): 30928–34. doi: 10.1074/jbc.M203735200 . PMID   12050163.
  13. ↑ Osterweil E, Wells DG, Mooseker MS (Jan 2005). "A role for myosin VI in postsynaptic structure and glutamate receptor endocytosis". The Journal of Cell Biology. 168 (2): 329–38. doi:10.1083/jcb.200410091. PMC   2171578 . PMID   15657400.
  14. ↑ Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW (Jul 1998). "SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit". The Journal of Biological Chemistry. 273 (31): 19518–24. doi: 10.1074/jbc.273.31.19518 . PMID   9677374.[ permanent dead link ]
  15. ↑ Cai C, Coleman SK, Niemi K, Keinänen K (Aug 2002). "Selective binding of synapse-associated protein 97 to GluR-A alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionate receptor subunit is determined by a novel sequence motif". The Journal of Biological Chemistry. 277 (35): 31484–90. doi: 10.1074/jbc.M204354200 . PMID   12070168.

Further reading

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