DLG1

Protein-coding gene in the species Homo sapiens

DLG1

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
1PDR, 2M3M, 2OQS, 2X7Z, 3RL7, 3RL8, 3W9Y, 4AMH, 4G69

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; OMA:DLG1 - orthologs

Gene location (Human)

Chr.	Chromosome 3 (human)^[1]

Band	3q29	Start	197,042,560 bp^[1]
Band	3q29	End	197,299,330 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 16 (mouse)^[2]

Band	16 B2\|16 22.4 cM	Start	31,482,261 bp^[2]
Band	16 B2\|16 22.4 cM	End	31,693,947 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

endothelial cell

corpus callosum

dorsal motor nucleus of vagus nerve

inferior olivary nucleus

inferior ganglion of vagus nerve

subthalamic nucleus

epithelium of colon

hair follicle

external globus pallidus

Brodmann area 23

Top expressed in

tail of embryo

globus pallidus

medullary collecting duct

vestibular membrane of cochlear duct

primary motor cortex

conjunctival fornix

olfactory tubercle

Paneth cell

utricle

condyle

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	phosphatase binding phosphoprotein phosphatase activity transmembrane transporter binding cytoskeletal protein binding protein C-terminus binding ionotropic glutamate receptor binding kinase binding mitogen-activated protein kinase kinase binding guanylate kinase activity protein binding molecular adaptor activity protein kinase binding L27 domain binding ligand-gated ion channel activity potassium channel regulator activity cadherin binding structural constituent of postsynaptic density
Cellular component	cytoplasm cytosol postsynaptic membrane membrane cell-cell junction bicellular tight junction node of Ranvier synapse perinuclear region of cytoplasm cytoplasmic side of plasma membrane microtubule nucleus cell projection membrane membrane raft ionotropic glutamate receptor complex extracellular exosome Golgi apparatus lateral plasma membrane intercalated disc neuromuscular junction myelin sheath abaxonal region lateral loop endoplasmic reticulum membrane MPP7-DLG1-LIN7 complex sarcolemma postsynaptic density cell junction basolateral plasma membrane plasma membrane endoplasmic reticulum immunological synapse basement membrane apical plasma membrane neuron projection postsynaptic density membrane glutamatergic synapse
Biological process	embryonic skeletal system morphogenesis ureteric bud development positive regulation of actin filament polymerization positive regulation of potassium ion transport negative regulation of p38MAPK cascade amyloid precursor protein metabolic process tissue morphogenesis reproductive structure development membrane raft organization hard palate development endothelial cell proliferation smooth muscle tissue development negative regulation of epithelial cell proliferation regulation of sodium ion transmembrane transport astral microtubule organization actin filament organization mitotic cell cycle checkpoint signaling receptor clustering establishment or maintenance of cell polarity negative regulation of T cell proliferation branching involved in ureteric bud morphogenesis regulation of myelination cortical microtubule organization establishment or maintenance of epithelial cell apical/basal polarity viral process T cell cytokine production T cell activation peristalsis receptor localization to synapse negative regulation of protein kinase B signaling regulation of NIK/NF-kappaB signaling negative regulation of transcription by RNA polymerase II nervous system development regulation of cell shape establishment of centrosome localization immunological synapse formation cortical actin cytoskeleton organization protein localization lens development in camera-type eye bicellular tight junction assembly positive regulation of cell population proliferation negative regulation of ERK1 and ERK2 cascade activation of protein kinase activity negative regulation of mitotic cell cycle regulation of membrane potential protein localization to plasma membrane GDP metabolic process ion transmembrane transport protein dephosphorylation GMP metabolic process chemical synaptic transmission regulation of ventricular cardiac muscle cell action potential regulation of potassium ion import regulation of voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization regulation of potassium ion export across plasma membrane MAPK cascade cell-cell adhesion maintenance of postsynaptic density structure neurotransmitter receptor localization to postsynaptic specialization membrane positive regulation of protein localization to plasma membrane regulation of NMDA receptor activity
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


1739


13383

Ensembl


ENSG00000075711


ENSMUSG00000022770

UniProt


Q12959


Q811D0

RefSeq (mRNA)

NM_001098424 NM_001204386 NM_001204387 NM_001204388 NM_001290983
NM_004087 NM_001363865 NM_001366203 NM_001366204 NM_001366205 NM_001366206 NM_001366207 NM_001366208 NM_001366209 NM_001366210 NM_001366211 NM_001366212 NM_001366213 NM_001366214 NM_001366215 NM_001366216 NM_001366217 NM_001366218 NM_001366219 NM_001366220 NM_001366221 NM_001366222

NM_001252433 NM_001252434 NM_001252435 NM_001252436 NM_007862
NM_001357281 NM_001357282

RefSeq (protein)

NP_001091894 NP_001191315 NP_001191316 NP_001191317 NP_001277912
NP_004078 NP_001350794 NP_001353132 NP_001353133 NP_001353134 NP_001353135 NP_001353136 NP_001353137 NP_001353138 NP_001353139 NP_001353140 NP_001353141 NP_001353142 NP_001353143 NP_001353144 NP_001353145 NP_001353146 NP_001353147 NP_001353148 NP_001353149 NP_001353150 NP_001353151

NP_001239362 NP_001239363 NP_001239364 NP_001239365 NP_031888
NP_001344210 NP_001344211

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.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000075711 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000022770 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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.
^ 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.
^ 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.
^ 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.
^ ^a ^b 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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]}
^ 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.

External links

Drosophila discs large 1 - The Interactive Fly

PDB gallery

1iu0: The first PDZ domain of PSD-95
1iu2: The first PDZ domain of PSD-95
1kef: PDZ1 of SAP90
1pdr: CRYSTAL STRUCTURE OF THE THIRD PDZ DOMAIN FROM THE HUMAN HOMOLOG OF DISCS LARGE PROTEIN
1rgr: Cyclic Peptides Targeting PDZ Domains of PSD-95: Structural Basis for Enhanced Affinity and Enzymatic Stability
1rso: Hetero-tetrameric L27 (Lin-2, Lin-7) domain complexes as organization platforms of supra-molecular assemblies
1zok: PDZ1 Domain Of Synapse Associated Protein 97
2awu: Synapse associated protein 97 PDZ2 domain variant C378G
2aww: Synapse associated protein 97 PDZ2 domain variant C378G with C-terminal GluR-A peptide
2awx: Synapse associated protein 97 PDZ2 domain variant C378S
2g2l: Crystal Structure of the Second PDZ Domain of SAP97 in Complex with a GluR-A C-terminal Peptide
2i0i: X-ray crystal structure of Sap97 PDZ3 bound to the C-terminal peptide of HPV18 E6
2i0l: X-ray crystal structure of Sap97 PDZ2 bound to the C-terminal peptide of HPV18 E6.