P31016

SS
Gene name
Dlg4
Protein name
Disks large homolog 4
Names
Postsynaptic density protein 95, PSD-95, Synapse-associated protein 90, SAP-90, SAP90
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:29495
EC number
Protein Class

Descriptions

Dlg4 is a member of the membrane-associated guanylate kinase (MAGUK) family of PDZ domain-containing proteins and regulates surface expression of NMDA receptors. SH3 domain also interacts with GK domain for regulation. In Drosophila Dlg1 (P31007), PDZ 3 domain is also involved in the autoinhibition of the GK domain.

Autoinhibitory domains (AIDs)

313-393 (PDZ 3 domain) SS

Target domain

534-709 (GK domain)

Relief mechanism

Ligand binding

Assay

486-566 (SH3 domain) SS

Target domain

534-709 (GK domain)

Relief mechanism

Partner binding, Others

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

41 structures for P31016

Entry ID Method Resolution Chain Position Source
1BE9 X-ray 182 A A 302-430 PDB
1BFE X-ray 230 A A 302-402 PDB
1IU0 NMR - A 61-151 PDB
1IU2 NMR - A 61-151 PDB
1JXM X-ray 200 A A 430-724 PDB
1JXO X-ray 230 A A/B 430-724 PDB
1KJW X-ray 180 A A 430-724 PDB
1QLC NMR - A 155-249 PDB
1RGR NMR - A 62-154 PDB
1TP3 X-ray 199 A A 302-402 PDB
1TP5 X-ray 154 A A 302-402 PDB
1TQ3 X-ray 189 A A 302-402 PDB
2KA9 NMR - A 61-249 PDB
2MHO NMR - A 60-155 PDB
2XKX Other 2290 A A/B 1-724 PDB
3GSL X-ray 205 A A/B 61-249 PDB
3WP0 X-ray 204 A A 531-713 PDB
3WP1 X-ray 280 A B 531-713 PDB
5B64 X-ray 270 A A 531-713 PDB
5D13 X-ray 215 A A/B/C/D 302-402 PDB
5GNV X-ray 260 A A 531-713 PDB
5HDY X-ray 180 A A 302-402 PDB
5HEB X-ray 165 A A 302-402 PDB
5HED X-ray 170 A A 302-402 PDB
5HET X-ray 200 A A 302-402 PDB
5HEY X-ray 150 A A 302-402 PDB
5HF1 X-ray 175 A A 302-402 PDB
5HF4 X-ray 175 A A 302-402 PDB
5HFB X-ray 162 A A 302-402 PDB
5HFC X-ray 185 A A 302-402 PDB
5HFD X-ray 160 A A 302-402 PDB
5HFE X-ray 180 A A 302-402 PDB
5HFF X-ray 175 A A 302-402 PDB
5MZ7 X-ray 153 A A/B/C/D 303-402 PDB
5W72 NMR - A 301-402 PDB
5YPO X-ray 229 A A/B 531-713 PDB
5YPR X-ray 235 A A 426-721 PDB
7CQF X-ray 180 A A 309-422 PDB
7F7G X-ray 245 A A/B 531-713 PDB
7F7I X-ray 260 A A/B/C/D/E/F 531-713 PDB
AF-P31016-F1 Predicted AlphaFoldDB

No variants for P31016

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for P31016

No associated diseases with P31016

9 regional properties for P31016

Type Name Position InterPro Accession
domain SH3 domain 428 - 498 IPR001452
domain PDZ domain 65 - 152 IPR001478-1
domain PDZ domain 160 - 247 IPR001478-2
domain PDZ domain 313 - 394 IPR001478-3
domain Guanylate kinase-like domain 534 - 709 IPR008144
domain Guanylate kinase/L-type calcium channel beta subunit 533 - 712 IPR008145
domain Disks large homolog 1-4, PDZ-associated domain 245 - 312 IPR019583
domain Disks large homologue 1, N-terminal PEST domain 10 - 64 IPR019590
conserved_site Guanylate kinase, conserved site 566 - 583 IPR020590

Functions

Description
EC Number
Subcellular Localization
  • Cell membrane ; Lipid-anchor ; Cytoplasmic side
  • Postsynaptic density
  • Synapse
  • Cytoplasm
  • Cell projection, axon
  • Cell projection, dendritic spine
  • Cell projection, dendrite
  • Presynapse
  • High levels in postsynaptic density of neurons in the forebrain
  • Also in presynaptic region of inhibitory synapses formed by cerebellar basket cells on axon hillocks of Purkinje cells
  • Suppression of neuronal activity induces synaptic accumulation and clustering of DLG4 (PubMed:19596852)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

30 GO annotations of cellular component

Name Definition
AMPA glutamate receptor complex An assembly of four or five subunits which form a structure with an extracellular N-terminus and a large loop that together form the ligand binding domain. The C-terminus is intracellular. The ionotropic glutamate receptor complex itself acts as a ligand gated ion channel; on binding glutamate, charged ions pass through a channel in the center of the receptor complex. The AMPA receptors mediate fast synaptic transmission in the CNS and are composed of subunits GluR1-4, products from separate genes. These subunits have an extracellular N-terminus and an intracellular C-terminus.
anchored component of postsynaptic density membrane The component of the postsynaptic density membrane consisting of the gene products that are tethered to the membrane only by a covalently attached anchor, such as a lipid group that is embedded in the membrane. Gene products with peptide sequences that are embedded in the membrane are excluded from this grouping.
cell junction A cellular component that forms a specialized region of connection between two or more cells, or between a cell and the extracellular matrix, or between two membrane-bound components of a cell, such as flagella.
cell periphery The part of a cell encompassing the cell cortex, the plasma membrane, and any external encapsulating structures.
cell-cell junction A cell junction that forms a connection between two or more cells of an organism; excludes direct cytoplasmic intercellular bridges, such as ring canals in insects.
cerebellar mossy fiber An axon arising from cerebellar projecting cells in the cochlea, vestibular nuclei, spinal cord, reticular formation, cerebellar nuclei and basilar pontine nuclei. Mossy fibers enter through all three cerebellar peduncles and send collaterals to the deep cerebellar nuclei, then branch in the white matter and terminate in the granule cell layer. Through this branching, a given mossy fiber can innervate several folia. Mossy fibers synapse on granule cells. The synaptic contacts are made at enlargements along the length of the mossy fiber called mossy fiber rosettes. The enlargements of the rosettes give the axons a mossy-looking appearance in Golgi stained preparations.
cortical cytoskeleton The portion of the cytoskeleton that lies just beneath the plasma membrane.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
dendrite A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body.
dendrite cytoplasm All of the contents of a dendrite, excluding the surrounding plasma membrane.
dendritic spine A small, membranous protrusion from a dendrite that forms a postsynaptic compartment, typically receiving input from a single presynapse. They function as partially isolated biochemical and an electrical compartments. Spine morphology is variable:they can be thin, stubby, mushroom, or branched, with a continuum of intermediate morphologies. They typically terminate in a bulb shape, linked to the dendritic shaft by a restriction. Spine remodeling is though to be involved in synaptic plasticity.
endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
excitatory synapse A synapse in which an action potential in the presynaptic cell increases the probability of an action potential occurring in the postsynaptic cell.
extrinsic component of cytoplasmic side of plasma membrane The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
juxtaparanode region of axon A region of an axon near a node of Ranvier that is between the paranode and internode regions.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
neuromuscular junction The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
neuron projection A prolongation or process extending from a nerve cell, e.g. an axon or dendrite.
neuron projection terminus The specialized, terminal region of a neuron projection such as an axon or a dendrite.
neuron spine A small membranous protrusion, often ending in a bulbous head and attached to the neuron by a narrow stalk or neck.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynapse The part of a synapse that is part of the post-synaptic cell.
postsynaptic density An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components.
postsynaptic density membrane The membrane component of the postsynaptic density. This is the region of the postsynaptic membrane in which the population of neurotransmitter receptors involved in synaptic transmission are concentrated.
postsynaptic membrane A specialized area of membrane facing the presynaptic membrane on the tip of the nerve ending and separated from it by a minute cleft (the synaptic cleft). Neurotransmitters cross the synaptic cleft and transmit the signal to the postsynaptic membrane.
synapse The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.
synaptic membrane A specialized area of membrane on either the presynaptic or the postsynaptic side of a synapse, the junction between a nerve fiber of one neuron and another neuron or muscle fiber or glial cell.
synaptic vesicle A secretory organelle, typically 50 nm in diameter, of presynaptic nerve terminals; accumulates in high concentrations of neurotransmitters and secretes these into the synaptic cleft by fusion with the 'active zone' of the presynaptic plasma membrane.

20 GO annotations of molecular function

Name Definition
acetylcholine receptor binding Binding to an acetylcholine receptor.
beta-1 adrenergic receptor binding Binding to a beta-1 adrenergic receptor.
beta-2 adrenergic receptor binding Binding to a beta-2 adrenergic receptor.
D1 dopamine receptor binding Binding to a D1 dopamine receptor.
frizzled binding Binding to a frizzled (fz) receptor.
glutamate receptor binding Binding to a glutamate receptor.
immunoglobulin binding Binding to an immunoglobulin.
ionotropic glutamate receptor binding Binding to an ionotropic glutamate receptor. Ionotropic glutamate receptors bind glutamate and exert an effect through the regulation of ion channels.
kinase binding Binding to a kinase, any enzyme that catalyzes the transfer of a phosphate group.
kinesin binding Interacting selectively and non-covalently and stoichiometrically with kinesin, a member of a superfamily of microtubule-based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation.
neuroligin family protein binding Binding to a member of the neuroligin protein family, neuronal cell surface proteins that mediate synapse formation.
P2Y1 nucleotide receptor binding Binding to a P2Y1 nucleotide receptor.
PDZ domain binding Binding to a PDZ domain of a protein, a domain found in diverse signaling proteins.
protein C-terminus binding Binding to a protein C-terminus, the end of a peptide chain at which the 1-carboxyl function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
protein phosphatase binding Binding to a protein phosphatase.
protein-containing complex binding Binding to a macromolecular complex.
scaffold protein binding Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes.
signaling receptor binding Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function.
structural constituent of postsynaptic density The action of a molecule that contributes to the structural integrity of a postsynaptic density.

30 GO annotations of biological process

Name Definition
AMPA glutamate receptor clustering The glutamate receptor clustering process in which alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors are localized to distinct domains in the cell membrane.
cell-cell adhesion The attachment of one cell to another cell via adhesion molecules.
cellular response to potassium ion Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a potassium ion stimulus.
chemical synaptic transmission The vesicular release of classical neurotransmitter molecules from a presynapse, across a chemical synapse, the subsequent activation of neurotransmitter receptors at the postsynapse of a target cell (neuron, muscle, or secretory cell) and the effects of this activation on the postsynaptic membrane potential and ionic composition of the postsynaptic cytosol. This process encompasses both spontaneous and evoked release of neurotransmitter and all parts of synaptic vesicle exocytosis. Evoked transmission starts with the arrival of an action potential at the presynapse.
dendritic spine morphogenesis The process in which the anatomical structures of a dendritic spine are generated and organized. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission.
dendritic spine organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a dendritic spine. A dendritic spine is a specialized protrusion from a neuronal dendrite and is involved in synaptic transmission.
establishment of protein localization The directed movement of a protein to a specific location.
locomotory exploration behavior The specific movement from place to place of an organism in response to a novel environment.
negative regulation of receptor internalization Any process that stops, prevents, or reduces the frequency, rate or extent of receptor internalization.
neuromuscular process controlling balance Any process that an organism uses to control its balance, the orientation of the organism (or the head of the organism) in relation to the source of gravity. In humans and animals, balance is perceived through visual cues, the labyrinth system of the inner ears and information from skin pressure receptors and muscle and joint receptors.
neuronal ion channel clustering The process in which voltage-gated ion channels become localized to distinct subcellular domains in the neuron. Specific targeting, clustering, and maintenance of these channels in their respective domains are essential to achieve high conduction velocities of action potential propagation.
neurotransmitter receptor localization to postsynaptic specialization membrane A process in which a neurotransmitter is transported to, or maintained in, a location within the membrane adjacent to a postsynaptic specialization (e.g. postsynaptic density).
positive regulation of AMPA glutamate receptor clustering Any process that activates or increases the frequency, rate or extent of AMPA glutamate receptor clustering.
positive regulation of cytosolic calcium ion concentration Any process that increases the concentration of calcium ions in the cytosol.
positive regulation of excitatory postsynaptic potential Any process that enhances the establishment or increases the extent of the excitatory postsynaptic potential (EPSP) which is a temporary increase in postsynaptic potential due to the flow of positively charged ions into the postsynaptic cell. The flow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC) and makes it easier for the neuron to fire an action potential.
positive regulation of neuron projection arborization Any process that activates or increases the frequency, rate or extent of the process in which the anatomical structures of a neuron projection are generated and organized into branches.
positive regulation of protein tyrosine kinase activity Any process that increases the rate, frequency, or extent of protein tyrosine kinase activity.
positive regulation of synaptic transmission Any process that activates or increases the frequency, rate or extent of synaptic transmission, the process of communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse.
postsynaptic neurotransmitter receptor diffusion trapping The process by which diffusing neurotransmitter receptor becomes trapped at the postsynaptic specialization membrane. This is typically due to interaction with components of the post-synaptic specialization.
protein localization to synapse Any process in which a protein is transported to, and/or maintained at the synapse, the junction between a nerve fiber of one neuron and another neuron or muscle fiber or glial cell.
protein-containing complex assembly The aggregation, arrangement and bonding together of a set of macromolecules to form a protein-containing complex.
receptor clustering The receptor metabolic process that results in grouping of a set of receptors at a cellular location, often to amplify the sensitivity of a signaling response.
receptor localization to synapse Any process in which a receptor is transported to, and/or maintained at the synapse, the junction between a nerve fiber of one neuron and another neuron or muscle fiber or glial cell.
regulation of grooming behavior Any process that modulates the frequency, rate or extent of grooming behavior.
regulation of long-term neuronal synaptic plasticity A process that modulates long-term neuronal synaptic plasticity, the ability of neuronal synapses to change long-term as circumstances require. Long-term neuronal synaptic plasticity generally involves increase or decrease in actual synapse numbers.
regulation of neuronal synaptic plasticity A process that modulates neuronal synaptic plasticity, the ability of neuronal synapses to change as circumstances require. They may alter function, such as increasing or decreasing their sensitivity, or they may increase or decrease in actual numbers.
regulation of NMDA receptor activity Any process that modulates the frequency, rate or extent of N-methyl-D-aspartate selective glutamate receptor activity.
social behavior Behavior directed towards society, or taking place between members of the same species. Occurs predominantly, or only, in individuals that are part of a group.
synaptic vesicle maturation Steps required to form an initiated synaptic vesicle into a fully formed and transmissible synaptic vesicle.
vocalization behavior The behavior in which an organism produces sounds by a mechanism involving its respiratory system.

21 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P31007 dlg1 Disks large 1 tumor suppressor protein Drosophila melanogaster (Fruit fly) EV
Q12959 DLG1 Disks large homolog 1 Homo sapiens (Human) SS
Q92796 DLG3 Disks large homolog 3 Homo sapiens (Human) SS
Q15700 DLG2 Disks large homolog 2 Homo sapiens (Human) SS
Q9BXL7 CARD11 Caspase recruitment domain-containing protein 11 Homo sapiens (Human) EV
P78352 DLG4 Disks large homolog 4 Homo sapiens (Human) SS
Q811D0 Dlg1 Disks large homolog 1 Mus musculus (Mouse) SS
Q8CIS0 Card11 Caspase recruitment domain-containing protein 11 Mus musculus (Mouse) SS
P70175 Dlg3 Disks large homolog 3 Mus musculus (Mouse) SS
Q99KF0 Card14 Caspase recruitment domain-containing protein 14 Mus musculus (Mouse) PR
Q91XM9 Dlg2 Disks large homolog 2 Mus musculus (Mouse) SS
Q62108 Dlg4 Disks large homolog 4 Mus musculus (Mouse) SS
P70587 Lrrc7 Leucine-rich repeat-containing protein 7 Rattus norvegicus (Rat) PR
Q62936 Dlg3 Disks large homolog 3 Rattus norvegicus (Rat) SS
Q62696 Dlg1 Disks large homolog 1 Rattus norvegicus (Rat) SS
Q63622 Dlg2 Disks large homolog 2 Rattus norvegicus (Rat) EV
G5ECY0 dlg-1 Disks large homolog 1 Caenorhabditis elegans SS
Q28C55 dlg1 Disks large homolog 1 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) SS
Q5PYH5 dlg1l Discs large homolog 1-like protein Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q5PYH7 dlg2 Disks large homolog 2 Danio rerio (Zebrafish) (Brachydanio rerio) SS
Q6R005 dlg4 Disks large homolog 4 Danio rerio (Zebrafish) (Brachydanio rerio) SS
10 20 30 40 50 60
MDCLCIVTTK KYRYQDEDTP PLEHSPAHLP NQANSPPVIV NTDTLEAPGY ELQVNGTEGE
70 80 90 100 110 120
MEYEEITLER GNSGLGFSIA GGTDNPHIGD DPSIFITKII PGGAAAQDGR LRVNDSILFV
130 140 150 160 170 180
NEVDVREVTH SAAVEALKEA GSIVRLYVMR RKPPAEKVME IKLIKGPKGL GFSIAGGVGN
190 200 210 220 230 240
QHIPGDNSIY VTKIIEGGAA HKDGRLQIGD KILAVNSVGL EDVMHEDAVA ALKNTYDVVY
250 260 270 280 290 300
LKVAKPSNAY LSDSYAPPDI TTSYSQHLDN EISHSSYLGT DYPTAMTPTS PRRYSPVAKD
310 320 330 340 350 360
LLGEEDIPRE PRRIVIHRGS TGLGFNIVGG EDGEGIFISF ILAGGPADLS GELRKGDQIL
370 380 390 400 410 420
SVNGVDLRNA SHEQAAIALK NAGQTVTIIA QYKPEEYSRF EAKIHDLREQ LMNSSLGSGT
430 440 450 460 470 480
ASLRSNPKRG FYIRALFDYD KTKDCGFLSQ ALSFRFGDVL HVIDAGDEEW WQARRVHSDS
490 500 510 520 530 540
ETDDIGFIPS KRRVERREWS RLKAKDWGSS SGSQGREDSV LSYETVTQME VHYARPIIIL
550 560 570 580 590 600
GPTKDRANDD LLSEFPDKFG SCVPHTTRPK REYEIDGRDY HFVSSREKME KDIQAHKFIE
610 620 630 640 650 660
AGQYNSHLYG TSVQSVREVA EQGKHCILDV SANAVRRLQA AHLHPIAIFI RPRSLENVLE
670 680 690 700 710 720
INKRITEEQA RKAFDRATKL EQEFTECFSA IVEGDSFEEI YHKVKRVIED LSGPYIWVPA
RERL