Shank3 SH3 and multiple ankyrin repeat domains 3 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Shank3provided by MGI
Official Full Name: SH3 and multiple ankyrin repeat domains 3provided by MGI
Primary source: MGI:MGI:1930016
See related: Ensembl:ENSMUSG00000022623 AllianceGenome:MGI:1930016
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Spank-2; proSAP2
Summary: Enables ionotropic glutamate receptor binding activity; protein C-terminus binding activity; and scaffold protein binding activity. A structural constituent of postsynaptic density. Involved in several processes, including learning or memory; modulation of chemical synaptic transmission; and postsynapse organization. Acts upstream of or within several processes, including MAPK cascade; negative regulation of actin filament bundle assembly; and regulation of AMPA glutamate receptor clustering. Located in glutamatergic synapse and neuron spine. Is extrinsic component of cytoplasmic side of plasma membrane. Is expressed in brain and cerebral cortex. Used to study Phelan-McDermid syndrome; autism spectrum disorder; and schizophrenia. Human ortholog(s) of this gene implicated in Phelan-McDermid syndrome and schizophrenia 15. Orthologous to human SHANK3 (SH3 and multiple ankyrin repeat domains 3). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Broad expression in lung adult (RPKM 45.6), adrenal adult (RPKM 22.3) and 20 other tissues See more
Orthologs: human all
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Genomic context

Location:: 15 E3; 15 44.96 cM

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	15	NC_000081.7 (89376929..89444464)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	15	NC_000081.6 (89493013..89560261)

Chromosome 15 - NC_000081.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.
Title: Combined expansion and STED microscopy reveals altered fingerprints of postsynaptic nanostructure across brain regions in ASD-related SHANK3-deficiency.
Shank3 deficiency alters midbrain GABAergic neuron morphology, GABAergic markers and synaptic activity in primary striatal neurons.
Title: Shank3 deficiency alters midbrain GABAergic neuron morphology, GABAergic markers and synaptic activity in primary striatal neurons.
Huddling substates in mice facilitate dynamic changes in body temperature and are modulated by Shank3b and Trpm8 mutation.
Title: Huddling substates in mice facilitate dynamic changes in body temperature and are modulated by Shank3b and Trpm8 mutation.
Neuron type-specific proteomics reveals distinct Shank3 proteoforms in iSPNs and dSPNs lead to striatal synaptopathy in Shank3B[-/-] mice.
Title: Neuron type-specific proteomics reveals distinct Shank3 proteoforms in iSPNs and dSPNs lead to striatal synaptopathy in Shank3B(-/-) mice.
An N-terminal and ankyrin repeat domain interactome of Shank3 identifies the protein complex with the splicing regulator Nono in mice.
Title: An N-terminal and ankyrin repeat domain interactome of Shank3 identifies the protein complex with the splicing regulator Nono in mice.
Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.
Title: Transcriptional determinism and stochasticity contribute to the complexity of autism-associated SHANK family genes.
Trans-synaptic Association of Vesicular Zinc Transporter 3 and Shank3 Supports Synapse-Specific Dendritic Spine Structure and Function in the Mouse Auditory Cortex.
Title: Trans-synaptic Association of Vesicular Zinc Transporter 3 and Shank3 Supports Synapse-Specific Dendritic Spine Structure and Function in the Mouse Auditory Cortex.
Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice.
Title: Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice.
Restoring thalamocortical circuit dysfunction by correcting HCN channelopathy in Shank3 mutant mice.
Title: Restoring thalamocortical circuit dysfunction by correcting HCN channelopathy in Shank3 mutant mice.
Shank3 deficiency elicits autistic-like behaviors by activating p38alpha in hypothalamic AgRP neurons.
Title: Shank3 deficiency elicits autistic-like behaviors by activating p38α in hypothalamic AgRP neurons.

Submit: New GeneRIF Correction See all GeneRIFs (121)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (10) 1 citation
Targeted (27) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

AI841104 (e-PCR)
- UniSTS:165960

Shank3 (e-PCR), detects polymorphism
- UniSTS:496557

D7Wox53 (e-PCR)
- UniSTS:518629

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables G protein-coupled receptor binding	ISO Inferred from Sequence Orthology more info
enables SH3 domain binding	ISO Inferred from Sequence Orthology more info
enables SH3 domain binding	ISS Inferred from Sequence or Structural Similarity more info
enables actin binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables ionotropic glutamate receptor binding	IBA Inferred from Biological aspect of Ancestor more info
enables ionotropic glutamate receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables scaffold protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables scaffold protein binding	ISO Inferred from Sequence Orthology more info
enables structural constituent of postsynaptic density	IDA Inferred from Direct Assay more info	PubMed
enables structural constituent of postsynaptic density	IEP Inferred from Expression Pattern more info	PubMed
enables structural constituent of postsynaptic density	IMP Inferred from Mutant Phenotype more info	PubMed
enables structural constituent of postsynaptic density	ISO Inferred from Sequence Orthology more info
enables synaptic receptor adaptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables synaptic receptor adaptor activity	ISO Inferred from Sequence Orthology more info
enables synaptic receptor adaptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables zinc ion binding	ISO Inferred from Sequence Orthology more info
enables zinc ion binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in AMPA glutamate receptor clustering	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within MAPK cascade	IGI Inferred from Genetic Interaction more info	PubMed
involved_in NMDA glutamate receptor clustering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in adult behavior	ISO Inferred from Sequence Orthology more info
involved_in associative learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in brain morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within dendritic spine morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dendritic spine morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within embryonic epithelial tube formation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in exploration behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glial cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in guanylate kinase-associated protein clustering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in learning	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in learning	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within learning or memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in locomotion	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within locomotory behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in locomotory exploration behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in long-term synaptic depression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in long-term synaptic potentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in maintenance of postsynaptic density structure	IEA Inferred from Electronic Annotation more info
involved_in memory	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in modulation of chemical synaptic transmission	IDA Inferred from Direct Assay more info	PubMed
involved_in modulation of chemical synaptic transmission	IEP Inferred from Expression Pattern more info	PubMed
involved_in modulation of chemical synaptic transmission	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within negative regulation of actin filament bundle assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cell volume	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neural precursor cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuromuscular process controlling balance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of dendritic spine development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of excitatory postsynaptic potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glutamate receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glutamate receptor signaling pathway	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of long-term neuronal synaptic plasticity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of long-term synaptic potentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of synapse structural plasticity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of synaptic transmission, glutamatergic	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in postsynaptic density assembly	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of AMPA glutamate receptor clustering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of behavioral fear response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of dendritic spine morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of grooming behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of long-term synaptic depression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of long-term synaptic potentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of postsynapse organization	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of synaptic plasticity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to interleukin-17	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within social behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in social behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in social behavior	ISO Inferred from Sequence Orthology more info
involved_in striatal medium spiny neuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in synapse assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vocal learning	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within vocalization behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vocalization behavior	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in vocalization behavior	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in ciliary membrane	ISO Inferred from Sequence Orthology more info
located_in ciliary membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
is_active_in dendritic spine	IBA Inferred from Biological aspect of Ancestor more info
located_in dendritic spine	IEA Inferred from Electronic Annotation more info
located_in excitatory synapse	IC Inferred by Curator more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IEP Inferred from Expression Pattern more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in neuron projection	IDA Inferred from Direct Assay more info	PubMed
located_in neuron spine	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynaptic density	IBA Inferred from Biological aspect of Ancestor more info
is_active_in postsynaptic density	ISO Inferred from Sequence Orthology more info
located_in postsynaptic density	ISO Inferred from Sequence Orthology more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
is_active_in postsynaptic density, intracellular component	ISO Inferred from Sequence Orthology more info
colocalizes_with postsynaptic membrane	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: SH3 and multiple ankyrin repeat domains protein 3

Names: SH3/ankyrin domain gene 3; proline-rich synapse-associated protein 2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_021423.4 → NP_067398.3 SH3 and multiple ankyrin repeat domains protein 3

Status: VALIDATED

Source sequence(s)

AC122401, AC137513

Consensus CDS

CCDS27754.1

UniProtKB/Swiss-Prot

F8S0X0, F8S0X2, F8S0X3, F8S0X5, F8S0X6, Q4ACU6, Q69ZD8, Q9JJZ3, S6BMD3, S6CCV8

Related

ENSMUSP00000104932.3, ENSMUST00000109309.9

Conserved Domains (8) summary

cd09506
Location:1738 → 1803

SAM_Shank1,2,3; SAM domain of Shank1,2,3 family proteins

COG0666
Location:200 → 392

ANKYR; Ankyrin repeat [Signal transduction mechanisms]

PRK12323
Location:1204 → 1428

PRK12323; DNA polymerase III subunit gamma/tau

cd00992
Location:647 → 736

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

sd00045
Location:257 → 288

ANK; ANK repeat [structural motif]

pfam12796
Location:329 → 410

Ank_2; Ankyrin repeats (3 copies)

cl17036
Location:548 → 599

SH3; Src Homology 3 domain superfamily

cl28922
Location:83 → 169

Ubiquitin_like_fold; Beta-grasp ubiquitin-like fold

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000081.7 Reference GRCm39 C57BL/6J

Range

89376929..89444464

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006521222.4 → XP_006521285.3 SH3 and multiple ankyrin repeat domains protein 3 isoform X1

UniProtKB/Swiss-Prot

F8S0X0, F8S0X2, F8S0X3, F8S0X5, F8S0X6, Q4ACU6, Q69ZD8, Q9JJZ3, S6BMD3, S6CCV8

Conserved Domains (7) summary

COG0666
Location:200 → 392

ANKYR; Ankyrin repeat [Signal transduction mechanisms]

PRK12323
Location:1204 → 1428

PRK12323; DNA polymerase III subunit gamma/tau

cd00992
Location:647 → 736

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

sd00045
Location:257 → 288

ANK; ANK repeat [structural motif]

pfam12796
Location:329 → 410

Ank_2; Ankyrin repeats (3 copies)

cl17036
Location:548 → 599

SH3; Src Homology 3 domain superfamily

cl28922
Location:83 → 169

Ubiquitin_like_fold; Beta-grasp ubiquitin-like fold
XM_017316717.3 → XP_017172206.2 SH3 and multiple ankyrin repeat domains protein 3 isoform X2

Conserved Domains (6) summary

cd11984
Location:548 → 599

SH3_Shank3; Src homology 3 domain of SH3 and multiple ankyrin repeat domains protein 3

COG0666
Location:200 → 392

ANKYR; Ankyrin repeat [Signal transduction mechanisms]

cd00992
Location:647 → 736

PDZ_signaling; PDZ domain found in a variety of Eumetazoan signaling molecules, often in tandem arrangements. May be responsible for specific protein-protein interactions, as most PDZ domains bind C-terminal polypeptides, and binding to internal (non-C-terminal) ...

sd00045
Location:257 → 288

ANK; ANK repeat [structural motif]

cd17177
Location:83 → 169

FERM_F0_SHANK3; FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F0 sub-domain, found in SH3 and multiple ankyrin repeat domains protein 3 (SHANK3)

pfam12796
Location:329 → 410

Ank_2; Ankyrin repeats (3 copies)