SHANK2
Encyclopedia
SH3 and multiple ankyrin repeat domains protein 2 is a protein
that in humans is encoded by the SHANK2 gene
. Two alternative splice variants, encoding distinct isoforms, are reported. Additional splice variants exist but their full-length nature has not been determined.
(PSD). Shank proteins contain multiple domains for protein-protein interaction, including ankyrin repeat
s, an SH3 domain
, a PSD-95
/Dlg/ZO-1 domain, a sterile alpha motif domain, and a proline-rich region. This particular family member contains a PDZ domain
, a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. The alternative splicing
demonstrated in Shank genes has been suggested as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the PSDs of adult and developing brain.
It is thought that SHANK2 might play a role in synaptogenesis
by attaching metabotropic glutamate receptor
s (mGluRs) to an existing pool of NMDA receptor
s (NMDA-R), bylinking to the NMDA-R through PSD-95, and the mGluRs through HOMER1
. An alternative hypothesis is that the Homer/Shank/GKAP/PSD-95 assembly mediates physical association of the NMDAR with IP3R/RYR and intracellular Ca2+ stores.
with:
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 SHANK2 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...
. Two alternative splice variants, encoding distinct isoforms, are reported. Additional splice variants exist but their full-length nature has not been determined.
Function
This gene encodes a protein that is a member of the Shank family of synaptic proteins that may function as molecular scaffolds in the postsynaptic densityPostsynaptic density
The postsynaptic density is a protein dense specialization attached to the postsynaptic membrane. PSDs were originally identified by electron microscopy as an electron-dense region at the membrane of a postsynaptic neuron...
(PSD). Shank proteins contain multiple domains for protein-protein interaction, including ankyrin repeat
Ankyrin repeat
The ankyrin repeat is a 33-residue motif in proteins consisting of two alpha helices separated by loops, first discovered in signaling proteins in yeast Cdc10 and Drosophila Notch. Ankyrin repeats mediate protein–protein interactions and are among the most common structural motifs in known proteins...
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...
, a PSD-95
DLG4
PSD-95 also known as SAP-90 is a protein that in humans is encoded by the DLG4 gene....
/Dlg/ZO-1 domain, a sterile alpha motif domain, and a proline-rich region. This particular family member contains a PDZ domain
PDZ 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...
, a consensus sequence for cortactin SH3 domain-binding peptides and a sterile alpha motif. The alternative splicing
Alternative splicing
Alternative splicing is a process by which the exons of the RNA produced by transcription of a gene are reconnected in multiple ways during RNA splicing...
demonstrated in Shank genes has been suggested as a mechanism for regulating the molecular structure of Shank and the spectrum of Shank-interacting proteins in the PSDs of adult and developing brain.
It is thought that SHANK2 might play a role in synaptogenesis
Synaptogenesis
Synaptogenesis is the formation of synapses. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development...
by attaching metabotropic glutamate receptor
Metabotropic glutamate receptor
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs...
s (mGluRs) to an existing pool of NMDA receptor
NMDA receptor
The NMDA receptor , a glutamate receptor, is the predominant molecular device for controlling synaptic plasticity and memory function....
s (NMDA-R), bylinking to the NMDA-R through PSD-95, and the mGluRs through HOMER1
HOMER1
Homer protein homolog 1 or Homer1 is a neuronal protein that in humans is encoded by the HOMER1 gene. Other names are Vesl and PSD-Zip45.-Domain structure:...
. An alternative hypothesis is that the Homer/Shank/GKAP/PSD-95 assembly mediates physical association of the NMDAR with IP3R/RYR and intracellular Ca2+ stores.
Interactions
SHANK2 has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with:
- ARHGEF7ARHGEF7Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.-Interactions:ARHGEF7 has been shown to interact with GIT1, SHANK3, Cbl gene, SHANK1 and SHANK2.-External links:* Info with links in the...
, - CortactinCortactinCortactin is a monomeric protein located in the cytoplasm of cells that can be activated by external stimuli to promote polymerization and rearrangement of the actin cytoskeleton, especially the actin cortex around the cellular periphery. It is present in all cell types...
, - DLG4DLG4PSD-95 also known as SAP-90 is a protein that in humans is encoded by the DLG4 gene....
, - DLGAP1DLGAP1Disks large-associated protein 1 , also known as guanylate kinase-associated protein 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 This gene encodes the protein...
, and - DNM2DNM2Dynamin-2 is a protein that in humans is encoded by the DNM2 gene.-Interactions:DNM2 has been shown to interact with SNX9, SHANK1 and SHANK2.-External Links:* -Further reading:...
.