MOUSE:SHAN3

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Species (Taxon ID)	Mus musculus (Mouse). ([1])
Gene Name(s)	Shank3 (synonyms: Kiaa1650)
Protein Name(s)	SH3 and multiple ankyrin repeat domains protein 3 Shank3 Proline-rich synapse-associated protein 2 ProSAP2 SPANK-2
External Links
EMBL	AC122401 AC137513 AB231013 AK173228
IPI	IPI00351827
RefSeq	NP_067398.2
UniGene	Mm.146855
PDB	3O5N
PDBsum	3O5N
ProteinModelPortal	Q4ACU6
SMR	Q4ACU6
IntAct	Q4ACU6
STRING	Q4ACU6
PhosphoSite	Q4ACU6
PRIDE	Q4ACU6
Ensembl	ENSMUST00000039074 ENSMUST00000109309
GeneID	58234
KEGG	mmu:58234
UCSC	uc007xha.2
CTD	85358
MGI	MGI:1930016
eggNOG	roNOG12929
GeneTree	ENSGT00510000046474
HOGENOM	HBG715321
HOVERGEN	HBG054027
InParanoid	Q4ACU6
OMA	GRFPRST
OrthoDB	EOG48PMJ9
NextBio	314265
ArrayExpress	Q4ACU6
Bgee	Q4ACU6
CleanEx	MM_SHANK3
Genevestigator	Q4ACU6
GO	GO:0030054 GO:0005737 GO:0060076 GO:0005886 GO:0014069 GO:0045211 GO:0030160 GO:0035255 GO:0008022 GO:0097110 GO:0048854 GO:0060997 GO:0001838 GO:0035641 GO:0045794 GO:2000969 GO:2000463 GO:0048170 GO:0051835 GO:0051968 GO:0097107 GO:2000822 GO:2000821 GO:0035176 GO:0021773 GO:0071625
InterPro	IPR002110 IPR020683 IPR001478 IPR001660 IPR013761 IPR021129 IPR011511 IPR001452
Gene3D	G3DSA:1.25.40.20 G3DSA:1.10.150.50
KO	K15009
Pfam	PF12796 PF00595 PF00536 PF07653
SMART	SM00248 SM00228 SM00454 SM00326
SUPFAM	SSF48403 SSF50156 SSF47769 SSF50044
PROSITE	PS50297 PS50088 PS50106 PS50105 PS50002

Annotations

Qualifier	GO ID	GO term name	Reference	Evidence Code	with/from	Aspect	Notes	Status
	GO:0001838	embryonic epithelial tube formation	PMID:15569713^[1]	IGI: Inferred from Genetic Interaction	MGI:MGI:97902	P	Seeded From UniProt
	GO:0005515	protein binding	PMID:15569713^[1]	IPI: Inferred from Physical Interaction	UniProtKB:P35546-2	F	Seeded From UniProt
	GO:0005515	protein binding	PMID:15569713^[1]	IPI: Inferred from Physical Interaction	UniProtKB:Q60631	F	Seeded From UniProt
	GO:0005737	cytoplasm	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-0963	C	Seeded From UniProt
	GO:0005737	cytoplasm	GO_REF:0000023	IEA: Inferred from Electronic Annotation	SP_SL:SL-0086	C	Seeded From UniProt
	GO:0005886	plasma membrane	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-1003	C	Seeded From UniProt
	GO:0005886	plasma membrane	PMID:16606358^[2]	IDA: Inferred from Direct Assay		C	Seeded From UniProt
	GO:0007416	synapse assembly	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0008022	protein C-terminus binding	GO_REF:0000019	IEA: Inferred from Electronic Annotation	Ensembl:ENSRNOP00000040444	F	Seeded From UniProt
	GO:0008022	protein C-terminus binding	PMID:16606358^[2]	IPI: Inferred from Physical Interaction	UniProtKB:P23818	F	Seeded From UniProt
	GO:0008270	zinc ion binding	GO_REF:0000019	IEA: Inferred from Electronic Annotation	Ensembl:ENSRNOP00000040444	F	Seeded From UniProt
	GO:0014069	postsynaptic density	GO_REF:0000019	IEA: Inferred from Electronic Annotation	Ensembl:ENSRNOP00000040444	C	Seeded From UniProt
	GO:0014069	postsynaptic density	GO_REF:0000023	IEA: Inferred from Electronic Annotation	SP_SL:SL-0297	C	Seeded From UniProt
	GO:0014069	postsynaptic density	GO_REF:0000024	ISS: Inferred from Sequence or Structural Similarity	UniProtKB:Q9JLU4	C	Seeded From UniProt
	GO:0016020	membrane	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-0472	C	Seeded From UniProt
	GO:0017124	SH3 domain binding	GO_REF:0000019	IEA: Inferred from Electronic Annotation	Ensembl:ENSRNOP00000040444	F	Seeded From UniProt
	GO:0021773	striatal medium spiny neuron differentiation	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0030054	cell junction	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-0965	C	Seeded From UniProt
	GO:0030160	GKAP/Homer scaffold activity	GO_REF:0000024	ISS: Inferred from Sequence or Structural Similarity	UniProtKB:Q9JLU4	F	Seeded From UniProt
	GO:0035176	social behavior	PMID:21167025^[4]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0035176	social behavior	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0035255	ionotropic glutamate receptor binding	PMID:16606358^[2]	IPI: Inferred from Physical Interaction	UniProtKB:P23818	F	Seeded From UniProt
	GO:0035641	locomotory exploration behavior	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0043621	protein self-association	GO_REF:0000019	IEA: Inferred from Electronic Annotation	Ensembl:ENSRNOP00000040444	F	Seeded From UniProt
	GO:0044309	neuron spine	PMID:16606358^[2]	IDA: Inferred from Direct Assay		C	Seeded From UniProt
	GO:0045202	synapse	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-0770	C	Seeded From UniProt
	GO:0045202	synapse	GO_REF:0000019	IEA: Inferred from Electronic Annotation	Ensembl:ENSRNOP00000040444	C	Seeded From UniProt
	GO:0045202	synapse	GO_REF:0000023	IEA: Inferred from Electronic Annotation	SP_SL:SL-0258	C	Seeded From UniProt
	GO:0045211	postsynaptic membrane	GO_REF:0000004	IEA: Inferred from Electronic Annotation	SP_KW:KW-0628	C	Seeded From UniProt
	GO:0045794	negative regulation of cell volume	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0048170	positive regulation of long-term neuronal synaptic plasticity	PMID:21167025^[4]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0048854	brain morphogenesis	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0051259	protein oligomerization	GO_REF:0000019	IEA: Inferred from Electronic Annotation	Ensembl:ENSRNOP00000040444	P	Seeded From UniProt
	GO:0051835	positive regulation of synapse structural plasticity	PMID:21167025^[4]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0051968	positive regulation of synaptic transmission, glutamatergic	PMID:21167025^[4]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0051968	positive regulation of synaptic transmission, glutamatergic	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0060076	excitatory synapse	PMID:21423165^[3]	IC: Inferred by Curator	GO:0051966	C	Seeded From UniProt
	GO:0060997	dendritic spine morphogenesis	PMID:21167025^[4]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0060997	dendritic spine morphogenesis	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0071625	vocalization behavior	PMID:21167025^[4]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0097107	postsynaptic density assembly	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0097110	scaffold protein binding	PMID:16606358^[2]	IPI: Inferred from Physical Interaction	UniProtKB:Q62108	F	Seeded From UniProt
	GO:2000463	positive regulation of excitatory postsynaptic membrane potential	PMID:21167025^[4]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:2000463	positive regulation of excitatory postsynaptic membrane potential	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:2000821	regulation of grooming behavior	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:2000822	regulation of behavioral fear response	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:2000969	positive regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity	PMID:21423165^[3]	IMP: Inferred from Mutant Phenotype		P	Seeded From UniProt
	GO:0019717	synaptosome	PMID:21795692^[5]	IMP: Inferred from Mutant Phenotype		C	Mouse hippocampal neurons, figure 1C and D, there was reduction of shank3 protein in synaptosomes in hippocampal culture.	complete
	GO:0061001	regulation of dendritic spine morphogenesis	PMID:21795692^[5]	IMP: Inferred from Mutant Phenotype		P	Figure 2C and 2D showed reduction in spinal number and width, also there was an increase in length in knockout Shank3 mouse hippocampal neurons.	complete
	GO:0043406	positive regulation of MAP kinase activity	PMID:21795692^[5]	IMP: Inferred from Mutant Phenotype		P	Figure 3A, B shows that knockout Shank3 mice impaired ERK1/2 phosphorylation in neurons.	complete
	GO:0032793	positive regulation of CREB transcription factor activity	PMID:21795692^[5]	IMP: Inferred from Mutant Phenotype		P	Figure 3A, B shows that knockout Shank3 mice impaired CREB phosphorylation in neurons.	complete
	GO:2000463	positive regulation of excitatory postsynaptic membrane potential	PMID:21795692^[5]	IMP: Inferred from Mutant Phenotype		P	Figure 5A-F, Knockdown Shank3 reduced mEPSC frequency	complete
	GO:0051968	positive regulation of synaptic transmission, glutamatergic	PMID:21795692^[5]	IMP: Inferred from Mutant Phenotype		P	Figure 5A-F, Knockdown Shank3 reduced mEPSC frequency. Figure 6A-D showed LTD mediated through mGluR5 impaired in Shank3 mutant mice.	complete
	GO:0060292	long term synaptic depression	PMID:21795692^[5]	IMP: Inferred from Mutant Phenotype		P	Figure 6A-d shows that when DHPG is used to induce LTD in mEPSC in neurons with Shank3 expression but LTD was impaired when Shank3 was knocked down.	complete
	GO:0097113	alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor clustering	PMID:21795692^[5]	IMP: Inferred from Mutant Phenotype		P	Figure 6E and F, showed decrease in mutant Shank3 mice of GluR1 subunit of AMPA receptor cluster at plasma membrane of dendrites.	complete
	GO:0035176	social behavior	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Control mice showed more affiliation with novel social stimulus than mutant Shank3 mice, figure 2A and B. Also when mice given choice of interacting with social or non-social stimulus, mutant Shank3 mice failed to show social affiliation compared to control. Similar results seen in figure 2C, mutant mice did not initiate the first social interaction.	complete
	GO:0071625	vocalization behavior	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Ultrasonic vocalization investigated. Control Shank3 mice showed more vocal (figure 2G) and complex calls than mutant mice (figure 2H). Control mice showed more long duration calls than mutant Shank3 mice but the opposite was seen in mutant Shank3 where more short duration calls were made compared to wild type (figure 2I and J)	complete
	GO:0050885	neuromuscular process controlling balance	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	To test motor coordination, foot misplacement test was done where there is a arena comprised of 16 parallel stainless-steel rods spaced 6 mm apart. A touch-sensor is used to record when the mouse foot slipped (losing balance) between the bars and was recorded as a foot-fault. Figure 3A showed mutant mice had more foot faults than control. A possible new GO term can be 'motor behaviour' as a child term for 'behaviour' and then a child term for 'motor behaviour' can be 'motor coordination behaviour' to represent this evidence better.	complete
	GO:0040011	locomotion	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Locomotion was decreased in mutant Shank3 mice compared to control (figure 3C)	complete
	GO:0007612	learning	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Figure 3D and E showed that control increase in latency to fall off an accelerating rotorod compared to mutant male Shank3 mice where the latency did not change indicating no learning was taking place. New GO term can be ‘motor learning’ as child term of learning.	complete
	GO:2000821	regulation of grooming behavior	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Shank3 mutant mice showed more self grooming behaviour compared to control, figure 3H	complete
	GO:0035640	exploration behavior	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Novel object exploration was investigated from inside and outside the nest. Shank3 control mice made contact with novel object more often from outside than inside the nest whereas mutant Shank3 mice made contact with novel object more from inside the nest than outside the nest. Indicating less exploration behaviour in mutant mice compared to control. Similar results seen in figure 3G mutant mice made same location of contact against novel object where as control mice made contact as different locations of the novel object.	complete
	GO:0007613	memory	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Morse water maze, mutant Shank3 mice showed more circular search swim patterns to the platform than control mice (supplementary material figure S4F top right). Also figure 4A right, when platform was changed, swim distance was the same for both control and mutant on day 7 but swim distance decreased after that for control but not for mutants. Figure 4A left showed that decline in swim distance over the first 3 day was less rapid in mutant Shank3 mice compared to control. Similar result seen in figure 4D, E G, H.	complete
	GO:0060997	dendritic spine morphogenesis	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Figure 5C shows mutant Shank3 mice had longer dendritic spine compared to control. Figure 5I and J showed spine density was reduced and length was increased in CA1 hippocampus in four week old mice. Similar result seen in week 10 mice (figure 5K and L)	complete
	GO:0097117	guanylate kinase-associated protein clustering	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Figure 6A and C, A decrease of PSD proteins in postsynaptic density fraction. There was a decrease in GKAP protein.	complete
	GO:0097113	alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor clustering	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Figure 6B and D, A decrease of receptor subunit in synaptosome membrane fraction. There was a decrease in GluA1 subunit in mutant Shank3 mice compared to control. Similar results was seen in figure 6E, confirmed by quantitative analyses.	complete
	GO:0097114	N-methyl-D-aspartate receptor clustering	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Figure 6B and D, A decrease of receptor subunit in synaptosome membrane fraction. There was a decrease in NR2A subunit in mutant Shank3 mice compared to control.	complete
	GO:0060291	long-term synaptic potentiation	PMID:21558424^[6]	IMP: Inferred from Mutant Phenotype		P	Figure 7A, mutant Shank3 mice showed reduced hippocampal long term potentiation compared to control.	complete
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Notes

References

See Help:References for how to manage references in GONUTS.

↑ ^1.0 ^1.1 ^1.2 Schuetz G et al. (2004) The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells. J Cell Biol 167: 945-52 PubMed GONUTS page
↑ ^2.0 ^2.1 ^2.2 ^2.3 ^2.4 Uchino S et al. (2006) Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. J Neurochem 97: 1203-14 PubMed GONUTS page
↑ ^3.00 ^3.01 ^3.02 ^3.03 ^3.04 ^3.05 ^3.06 ^3.07 ^3.08 ^3.09 ^3.10 ^3.11 ^3.12 ^3.13 Peça J et al. (2011) Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472: 437-42 PubMed GONUTS page
↑ ^4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 Bozdagi O et al. (2010) Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism 1: 15 PubMed GONUTS page
↑ ^5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 ^5.6 ^5.7 Verpelli C et al. (2011) Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses. J Biol Chem 286: 34839-50 PubMed GONUTS page
↑ ^6.00 ^6.01 ^6.02 ^6.03 ^6.04 ^6.05 ^6.06 ^6.07 ^6.08 ^6.09 ^6.10 ^6.11 ^6.12 Wang X et al. (2011) Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet 20: 3093-108 PubMed GONUTS page

[PMID:15569713-0] 1.0 ^1.1 ^1.2 Schuetz G et al. (2004) The neuronal scaffold protein Shank3 mediates signaling and biological function of the receptor tyrosine kinase Ret in epithelial cells. J Cell Biol 167: 945-52 PubMed GONUTS page

[PMID:16606358-1] 2.0 ^2.1 ^2.2 ^2.3 ^2.4 Uchino S et al. (2006) Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. J Neurochem 97: 1203-14 PubMed GONUTS page

[PMID:21423165-2] 3.00 ^3.01 ^3.02 ^3.03 ^3.04 ^3.05 ^3.06 ^3.07 ^3.08 ^3.09 ^3.10 ^3.11 ^3.12 ^3.13 Peça J et al. (2011) Shank3 mutant mice display autistic-like behaviours and striatal dysfunction. Nature 472: 437-42 PubMed GONUTS page

[PMID:21167025-3] 4.0 ^4.1 ^4.2 ^4.3 ^4.4 ^4.5 ^4.6 Bozdagi O et al. (2010) Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Mol Autism 1: 15 PubMed GONUTS page

[PMID:21795692-4] 5.0 ^5.1 ^5.2 ^5.3 ^5.4 ^5.5 ^5.6 ^5.7 Verpelli C et al. (2011) Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses. J Biol Chem 286: 34839-50 PubMed GONUTS page

[PMID:21558424-5] 6.00 ^6.01 ^6.02 ^6.03 ^6.04 ^6.05 ^6.06 ^6.07 ^6.08 ^6.09 ^6.10 ^6.11 ^6.12 Wang X et al. (2011) Synaptic dysfunction and abnormal behaviors in mice lacking major isoforms of Shank3. Hum Mol Genet 20: 3093-108 PubMed GONUTS page

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MOUSE:SHAN3

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