InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Shank3

Summary

InnateDB Protein

IDBP-174487.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Shank3

Protein Name

SH3/ankyrin domain gene 3

Synonyms

AI841104; Shank3b; SHANK3c-3; SHANK3c-4;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000048062

InnateDB Gene

IDBG-174485 (Shank3)

Protein Structure

UniProt Annotation

Function

Major scaffold postsynaptic density protein which interacts with multiple proteins and complexes to orchestrate the dendritic spine and synapse formation, maturation and maintenance. Interconnects receptors of the postsynaptic membrane including NMDA-type and metabotropic glutamate receptors via complexes with GKAP/PSD-95 and HOMER, respectively, and the actin-based cytoskeleton. Plays a role in the structural and functional organization of the dendritic spine and synaptic junction through the interaction with Arp2/3 and WAVE1 complex as well as the promotion of the F-actin clusters. By way of this control of actin dynamics, participates in the regulation of developing neurons growth cone motility and the NMDA receptor-signaling. Also modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to control the AMPA and metabotropic glutamate receptor- mediated synaptic transmission and plasticity. May be required at an early stage of synapse formation and be inhibited by IGF1 to promote synapse maturation. {ECO:0000269PubMed:21423165, ECO:0000269PubMed:21558424, ECO:0000269PubMed:23739967, ECO:0000269PubMed:24153177}.

Subcellular Localization

Cytoplasm. Cell junction, synapse. Cell junction, synapse, postsynaptic cell membrane, postsynaptic density. Cell projection, dendritic spine {ECO:0000250}. Note=In neuronal cells, extends into the region subjacent to the postsynaptic density (PSD).

Disease Associations

Tissue Specificity

In brain, highly expressed in striatum, thalamus, hippocampus and granule cells of the cerebellum. {ECO:0000269PubMed:21423165, ECO:0000269PubMed:21558424, ECO:0000269PubMed:24153177}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 9 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.

Experimentally validated
Total	9 [view]
Protein-Protein	9 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	8 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0005515	protein binding
GO:0008022	protein C-terminus binding
GO:0008270	zinc ion binding
GO:0017124	SH3 domain binding
GO:0030160	GKAP/Homer scaffold activity
GO:0035255	ionotropic glutamate receptor binding
GO:0042802	identical protein binding
GO:0043621	protein self-association
GO:0097110	scaffold protein binding

Biological Process

GO:0000165	MAPK cascade
GO:0001838	embryonic epithelial tube formation
GO:0007416	synapse assembly
GO:0007612	learning
GO:0007613	memory
GO:0021773	striatal medium spiny neuron differentiation
GO:0032232	negative regulation of actin filament bundle assembly
GO:0035176	social behavior
GO:0035641	locomotory exploration behavior
GO:0045794	negative regulation of cell volume
GO:0048170	positive regulation of long-term neuronal synaptic plasticity
GO:0048854	brain morphogenesis
GO:0050885	neuromuscular process controlling balance
GO:0051259	protein oligomerization
GO:0051835	positive regulation of synapse structural plasticity
GO:0051968	positive regulation of synaptic transmission, glutamatergic
GO:0060997	dendritic spine morphogenesis
GO:0060999	positive regulation of dendritic spine development
GO:0061001	regulation of dendritic spine morphogenesis
GO:0071625	vocalization behavior
GO:0097107	postsynaptic density assembly
GO:0097113	alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor clustering
GO:0097114	N-methyl-D-aspartate receptor clustering
GO:0097117	guanylate kinase-associated protein clustering
GO:1900271	regulation of long-term synaptic potentiation
GO:1900451	positive regulation of glutamate receptor signaling pathway
GO:1900452	regulation of long term synaptic depression
GO:2000463	positive regulation of excitatory postsynaptic membrane potential
GO:2000821	regulation of grooming behavior
GO:2000822	regulation of behavioral fear response
GO:2000969	positive regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity

Cellular Component

GO:0005737	cytoplasm
GO:0005886	plasma membrane
GO:0030054	cell junction
GO:0043005	neuron projection
GO:0043197	dendritic spine
GO:0044309	neuron spine
GO:0045211	postsynaptic membrane
GO:0060076	excitatory synapse
GO:0060170	ciliary membrane
GO:0097481	neuronal postsynaptic density

Protein Structure and Domains

PDB ID

MGI:1930016

InterPro

IPR001452 SH3 domain
IPR001478 PDZ domain
IPR001660 Sterile alpha motif domain
IPR002110 Ankyrin repeat
IPR011510 Sterile alpha motif, type 2
IPR011511 Variant SH3 domain
IPR013761 Sterile alpha motif/pointed domain
IPR020683 Ankyrin repeat-containing domain
IPR021129 Sterile alpha motif, type 1

PFAM