Q4ACU6 (SHAN3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
SH3 and multiple ankyrin repeat domains protein 3
Short name=Shank3

Alternative name(s):
Proline-rich synapse-associated protein 2
Short name=ProSAP2
SPANK-2

Gene names

Name:	Shank3
Synonyms:	Kiaa1650

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1805 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Seems to be an adapter protein in the postsynaptic density (PSD) of excitatory synapses that 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. May play a role in the structural and functional organization of the dendritic spine and synaptic junction By similarity.
Subunit structure	May homomultimerize via its SAM domain. Interacts with BAIAP2 By similarity. Interacts with DLGAP1/GKAP, MGLUR1A and MGLUR5 C-termini via its PDZ domain. Interacts (via PDZ domain) with PROSAPIP1 (via C-terminus) By similarity. Interacts with HOMER1, HOMER2, HOMER3 and CTTN/cortactin SH3 domain By similarity. Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP By similarity. Interacts with DBNL. Interacts with the GRIA1 subunit of AMPA receptor through the SH3-PDZ domain. Ref.2
Subcellular location	Cytoplasm. Cell junction › synapse. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Note: Postsynaptic density of neuronal cells. Extends into the region subjacent to the PSD.
Sequence similarities	Belongs to the SHANK family. Contains 6 ANK repeats. Contains 1 PDZ (DHR) domain. Contains 1 SAM (sterile alpha motif) domain. Contains 1 SH3 domain.
Caution	It is uncertain whether Met-1 or Met-76 is the initiator.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cytoplasm Membrane Postsynaptic cell membrane Synapse
Domain	ANK repeat Coiled coil Repeat SH3 domain
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Inferred from genetic interaction PubMed 15569713. Source: MGI N-methyl-D-aspartate receptor clustering Inferred from mutant phenotype PubMed 21558424. Source: BHF-UCL alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor clustering Inferred from mutant phenotype PubMed 21558424PubMed 21795692. Source: BHF-UCL brain morphogenesis Inferred from mutant phenotype PubMed 21423165. Source: BHF-UCL dendritic spine morphogenesis Inferred from mutant phenotype PubMed 21167025PubMed 21423165PubMed 21558424. Source: BHF-UCL embryonic epithelial tube formation Inferred from genetic interaction PubMed 15569713. Source: MGI guanylate kinase-associated protein clustering Inferred from mutant phenotype PubMed 21558424. Source: BHF-UCL learning Inferred from mutant phenotype PubMed 21558424. Source: BHF-UCL locomotory exploration behavior Inferred from mutant phenotype PubMed 21423165PubMed 21558424. Source: BHF-UCL memory Inferred from mutant phenotype PubMed 21558424. Source: BHF-UCL negative regulation of actin filament bundle assembly Inferred from direct assay PubMed 19208628. Source: MGI negative regulation of cell volume Inferred from mutant phenotype PubMed 21423165. Source: BHF-UCL neuromuscular process controlling balance Inferred from mutant phenotype PubMed 21558424. Source: BHF-UCL positive regulation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate selective glutamate receptor activity Inferred from mutant phenotype PubMed 21423165. Source: BHF-UCL positive regulation of dendritic spine development Inferred from mutant phenotype PubMed 21795692. Source: BHF-UCL positive regulation of excitatory postsynaptic membrane potential Inferred from mutant phenotype PubMed 21167025PubMed 21423165PubMed 21795692. Source: BHF-UCL positive regulation of glutamate receptor signaling pathway Inferred from mutant phenotype PubMed 21795692. Source: BHF-UCL positive regulation of long-term neuronal synaptic plasticity Inferred from mutant phenotype PubMed 21167025. Source: BHF-UCL positive regulation of synapse structural plasticity Inferred from mutant phenotype PubMed 21167025. Source: BHF-UCL positive regulation of synaptic transmission, glutamatergic Inferred from mutant phenotype PubMed 21167025PubMed 21423165PubMed 21795692. Source: BHF-UCL postsynaptic density assembly Inferred from mutant phenotype PubMed 21423165. Source: BHF-UCL protein oligomerization Inferred from electronic annotation. Source: Compara regulation of behavioral fear response Inferred from mutant phenotype PubMed 21423165. Source: BHF-UCL regulation of dendritic spine morphogenesis Inferred from mutant phenotype PubMed 21795692. Source: BHF-UCL regulation of grooming behavior Inferred from mutant phenotype PubMed 21423165PubMed 21558424. Source: BHF-UCL regulation of long term synaptic depression Inferred from mutant phenotype PubMed 21795692. Source: BHF-UCL regulation of long-term synaptic potentiation Inferred from mutant phenotype PubMed 21558424. Source: BHF-UCL social behavior Inferred from mutant phenotype PubMed 21167025PubMed 21423165PubMed 21558424. Source: BHF-UCL striatal medium spiny neuron differentiation Inferred from mutant phenotype PubMed 21423165. Source: BHF-UCL vocalization behavior Inferred from mutant phenotype PubMed 21167025PubMed 21558424. Source: BHF-UCL
Cellular_component	cell junction Inferred from electronic annotation. Source: UniProtKB-KW cilium membrane Inferred from electronic annotation. Source: Compara cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell excitatory synapse Inferred by curator PubMed 21423165. Source: BHF-UCL plasma membrane Inferred from direct assay Ref.2. Source: BHF-UCL postsynaptic density Inferred from sequence or structural similarity. Source: BHF-UCL postsynaptic membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	GKAP/Homer scaffold activity Inferred from sequence or structural similarity. Source: BHF-UCL zinc ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1805

1805

SH3 and multiple ankyrin repeat domains protein 3

PRO_0000291257

Regions

Repeat

223 – 253

31

ANK 1

Repeat

257 – 286

30

ANK 2

Repeat

290 – 320

31

ANK 3

Repeat

324 – 353

30

ANK 4

Repeat

357 – 386

30

ANK 5

Repeat

390 – 420

31

ANK 6

Domain

545 – 604

60

SH3

Domain

645 – 739

95

PDZ

Domain

1742 – 1805

64

SAM

Coiled coil

1569 – 1589

21

Potential

Motif

1485 – 1491

7

SH3-binding Potential

Compositional bias

6 – 15

10

Poly-Ala

Compositional bias

510 – 537

28

Pro-rich

Compositional bias

752 – 755

4

Poly-Pro

Compositional bias

888 – 1424

537

Pro-rich

Amino acid modifications

Modified residue

197

1

Phosphotyrosine Ref.4

Modified residue

450

1

Phosphoserine Ref.5

Modified residue

469

1

Phosphoserine Ref.6

Modified residue

630

1

Phosphotyrosine Ref.4

Modified residue

639

1

Phosphotyrosine Ref.4

Modified residue

856

1

Phosphoserine Ref.5

Modified residue

1234

1

Phosphoserine By similarity

Modified residue

1238

1

Phosphoserine By similarity

Modified residue

1309

1

Phosphothreonine By similarity

Modified residue

1328

1

Phosphoserine By similarity

Modified residue

1709

1

Phosphoserine Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

1805

Helix Strand Turn

Details...

Beta strand

639 – 649

11

Beta strand

657 – 661

5

Beta strand

676 – 678

3

Beta strand

683 – 687

5

Beta strand

689 – 692

4

Helix

693 – 696

4

Beta strand

703 – 707

5

Helix

718 – 726

9

Turn

727 – 729

3

Beta strand

730 – 740

11

Sequences

	Sequence		Length	Mass (Da)
	Q4ACU6 [UniParc]. Last modified June 12, 2007. Version 2. Checksum: AC678B7C98FCCEC7	FASTA	1,805	192,218
	10 20 30 40 50 60 MQLNRAAVAA AAAPAEPPEP LSPALAPAPA PPGPLPRSAV GGALAGGQGG PGRRAESPCA 70 80 90 100 110 120 PLSAGNSPGP GASTGMDGPG ASAVVVRVGI PDLQQTKCLR LDPTAPVWAA KQRVLCALNH 130 140 150 160 170 180 SLQDALNYGL FQPPSRGRAG KFLDEERLLQ DYPPNLDTPL PYLEFRYKRR VYAQNLIDDK 190 200 210 220 230 240 QFAKLHTKAN LKKFMDYVQL HSTDKVARLL DKGLDPNFHD PDSGECPLSL AAQLDNATDL 250 260 270 280 290 300 LKVLRNGGAH LDFRTRDGLT AVHCATRQRN AGALTTLLDL GASPDYKDSR GLTPLYHSAL 310 320 330 340 350 360 GGGDALCCEL LLHDHAQLGT TDENGWQEIH QACRFGHVQH LEHLLFYGAN MGAQNASGNT 370 380 390 400 410 420 ALHICALYNQ ESCARVLLFR GANKDVRNYN SQTAFQVAII AGNFELAEVI KTHKDSDVVP 430 440 450 460 470 480 FRETPSYAKR RRLAGPSGLA SPRPLQRSAS DINLKGDQPA ASPGPTLRSL PHQLLLQRLQ 490 500 510 520 530 540 EEKDRDRDGE LENDISGPSA GRGGHNKISP SGPGGSGPAP GPGPASPAPP APPPRGPKRK 550 560 570 580 590 600 LYSAVPGRKF IAVKAHSPQG EGEIPLHRGE AVKVLSIGEG GFWEGTVKGR TGWFPADCVE 610 620 630 640 650 660 EVQMRQYDTR HETREDRTKR LFRHYTVGSY DSLTSHSDYV IDDKVAILQK RDHEGFGFVL 670 680 690 700 710 720 RGAKAETPIE EFTPTPAFPA LQYLESVDVE GVAWRAGLRT GDFLIEVNGV NVVKVGHKQV 730 740 750 760 770 780 VGLIRQGGNR LVMKVVSVTR KPEEDGARRR APPPPKRAPS TTLTLRSKSM TAELEELASI 790 800 810 820 830 840 RRRKGEKLDE ILAVAAEPTL RPDIADADSR AATVKQRPTS RRITPAEISS LFERQGLPGP 850 860 870 880 890 900 EKLPGSLRKG IPRTKSVGED EKLASLLEGR FPRSTSMQDT VREGRGIPPP PQTAPPPPPA 910 920 930 940 950 960 PYYFDSGPPP TFSPPPPPGR AYDTVRSSFK PGLEARLGAG AAGLYDPSTP LGPLPYPERQ 970 980 990 1000 1010 1020 KRARSMIILQ DSAPEVGDVP RPAPAATPPE RPKRRPRPSG PDSPYANLGA FSASLFAPSK 1030 1040 1050 1060 1070 1080 PQRRKSPLVK QLQVEDAQER AALAVGSPGP VGGSFAREPS PTHRGPRPGS LDYSSGEGLG 1090 1100 1110 1120 1130 1140 LTFGGPSPGP VKERRLEERR RSTVFLSVGA IEGSPPSADL PSLQPSRSID ERLLGTGATT 1150 1160 1170 1180 1190 1200 GRDLLLPSPV SALKPLVGGP SLGPSGSTFI HPLTGKPLDP SSPLALALAA RERALASQTP 1210 1220 1230 1240 1250 1260 SRSPTPVHSP DADRPGPLFV DVQTRDSERG PLASPAFSPR SPAWIPVPAR REAEKPPREE 1270 1280 1290 1300 1310 1320 RKSPEDKKSM ILSVLDTSLQ RPAGLIVVHA TSNGQEPSRL GAEEERPGTP ELAPAPMQAA 1330 1340 1350 1360 1370 1380 AVAEPMPSPR AQPPGSIPAD PGPGQGSSEE EPELVFAVNL PPAQLSSSDE ETREELARIG 1390 1400 1410 1420 1430 1440 LVPPPEEFAN GILLTTPPPG PGPLPTTVPS PASGKPSSEL PPAPESAADS GVEEADTRSS 1450 1460 1470 1480 1490 1500 SDPHLETTST ISTVSSMSTL SSESGELTDT HTSFADGHTF LLEKPPVPPK PKLKSPLGKG 1510 1520 1530 1540 1550 1560 PVTFRDPLLK QSSDSELMAQ QHHAASTGLA SAAGPARPRY LFQRRSKLWG DPVESRGLPG 1570 1580 1590 1600 1610 1620 PEDDKPTVIS ELSSRLQQLN KDTRSLGEEP VGGLGSLLDP AKKSPIAAAR LFSSLGELST 1630 1640 1650 1660 1670 1680 ISAQRSPGGP GGGASYSVRP SGRYPVARRA PSPVKPASLE RVEGLGAGVG GAGRPFGLTP 1690 1700 1710 1720 1730 1740 PTILKSSSLS IPHEPKEVRF VVRSVSARSR SPSPSPLPSP SPGSGPSAGP RRPFQQKPLQ 1750 1760 1770 1780 1790 1800 LWSKFDVGDW LESIHLGEHR DRFEDHEIEG AHLPALTKED FVELGVTRVG HRMNIERALR QLDGS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6J.
[2]	"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." Uchino S., Wada H., Honda S., Nakamura Y., Ondo Y., Uchiyama T., Tsutsumi M., Suzuki E., Hirasawa T., Kohsaka S. J. Neurochem. 97:1203-1214(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 76-1805, INTERACTION WITH GRIA1.
[3]	"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries." Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H. DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 950-1805. Tissue: Brain.
[4]	"Large-scale identification and evolution indexing of tyrosine phosphorylation sites from murine brain." Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P. J. Proteome Res. 7:311-318(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-197; TYR-630 AND TYR-639, MASS SPECTROMETRY. Tissue: Brain.
[5]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450; SER-856 AND SER-1709, MASS SPECTROMETRY. Tissue: Liver.
[6]	"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry." Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M. J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-469, MASS SPECTROMETRY. Tissue: Melanoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AC122401 Genomic DNA. No translation available.
AC137513 Genomic DNA. No translation available.
AB231013 mRNA. Translation: BAE16756.1.
AK173228 mRNA. Translation: BAD32506.1.

IPI

IPI00351827.

RefSeq

NP_067398.2. NM_021423.3.

UniGene

Mm.146855.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3O5N	X-ray	1.83	A/B/C/D/E/F/G/H	637-744	[»]

ProteinModelPortal

Q4ACU6.

SMR

Q4ACU6. Positions 192-490, 561-603, 637-742, 1739-1802.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q4ACU6. 2 interactions.

PTM databases

PhosphoSite

Q4ACU6.

Proteomic databases

PaxDb

Q4ACU6.

PRIDE

Q4ACU6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000039074; ENSMUSP00000048062; ENSMUSG00000022623.
ENSMUST00000109309; ENSMUSP00000104932; ENSMUSG00000022623.

GeneID

58234.

KEGG

mmu:58234.

UCSC

uc007xha.2. mouse.

Organism-specific databases

CTD

85358.

MGI

MGI:1930016. Shank3.

Rouge

Search...

Phylogenomic databases

eggNOG

COG0666.

GeneTree

ENSGT00510000046474.

HOGENOM

HOG000293276.

HOVERGEN

HBG054027.

InParanoid

Q4ACU6.

KO

K15009.

OMA

KFIAVKA.

OrthoDB

EOG48PMJ9.

Gene expression databases

ArrayExpress

Q4ACU6.

Bgee

Q4ACU6.

CleanEx

MM_SHANK3.

Genevestigator

Q4ACU6.

Family and domain databases

Gene3D

1.10.150.50. 1 hit.
1.25.40.20. 1 hit.

InterPro

IPR002110. Ankyrin_rpt.
IPR020683. Ankyrin_rpt-contain_dom.
IPR001478. PDZ.
IPR001660. SAM.
IPR013761. SAM/pointed.
IPR021129. SAM_type1.
IPR011511. SH3_2.
IPR001452. SH3_domain.
[Graphical view]

Pfam

PF12796. Ank_2. 2 hits.
PF00595. PDZ. 1 hit.
PF00536. SAM_1. 1 hit.
PF07653. SH3_2. 1 hit.
[Graphical view]

SMART

SM00248. ANK. 5 hits.
SM00228. PDZ. 1 hit.
SM00454. SAM. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]

SUPFAM

SSF48403. ANK. 1 hit.
SSF50156. PDZ. 1 hit.
SSF47769. SAM_homology. 1 hit.
SSF50044. SH3. 1 hit.

PROSITE

PS50297. ANK_REP_REGION. 1 hit.
PS50088. ANK_REPEAT. 4 hits.
PS50106. PDZ. 1 hit.
PS50105. SAM_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SHANK3. mouse.

EvolutionaryTrace

Q4ACU6.

NextBio

314265.

SOURCE

Search...

Entry information

Entry name

SHAN3_MOUSE

Accession

Primary (citable) accession number: Q4ACU6
Secondary accession number(s): Q69ZD8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 12, 2007
Last sequence update:	June 12, 2007
Last modified:	May 1, 2013
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program