SHAN3_RAT
ID SHAN3_RAT Reviewed; 1740 AA.
AC Q9JLU4; Q9WUY7; Q9WV47;
DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 19-FEB-2014, sequence version 3.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=SH3 and multiple ankyrin repeat domains protein 3;
DE Short=Shank3;
DE AltName: Full=Proline-rich synapse-associated protein 2;
DE Short=ProSAP2;
DE AltName: Full=SPANK-2;
GN Name=Shank3; Synonyms=Prosap2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH DLGAP1 AND DLG4,
RP AND TISSUE SPECIFICITY.
RX PubMed=10527873; DOI=10.1006/bbrc.1999.1489;
RA Boeckers T.M., Winter C., Smalla K.-H., Kreutz M.R., Bockmann J.,
RA Seidenbecher C., Garner C.C., Gundelfinger E.D.;
RT "Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with
RT synaptic proteins of the SAPAP/GKAP family.";
RL Biochem. Biophys. Res. Commun. 264:247-252(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH DLGAP1 AND CTTN,
RP AND OLIGOMERIZATION.
RC STRAIN=Sprague-Dawley; TISSUE=Hippocampus;
RX PubMed=10433268; DOI=10.1016/s0896-6273(00)80809-0;
RA Naisbitt S., Kim E., Tu J.C., Xiao B., Sala C., Valtschanoff J.,
RA Weinberg R.J., Worley P.F., Sheng M.;
RT "Shank, a novel family of postsynaptic density proteins that binds to the
RT NMDA receptor/PSD-95/GKAP complex and cortactin.";
RL Neuron 23:569-582(1999).
RN [3]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Brain;
RX PubMed=10958799; DOI=10.1074/jbc.m006448200;
RA Tobaben S., Suedhof T.C., Stahl B.;
RT "The G protein-coupled receptor CL1 interacts directly with proteins of the
RT Shank family.";
RL J. Biol. Chem. 275:36204-36210(2000).
RN [4]
RP INTERACTION WITH HOMER1; HOMER2; HOMER3; DLGAP1; MGLUR1A AND MGLUR5, AND
RP MUTAGENESIS OF PRO-1311 AND PHE-1314.
RX PubMed=10433269; DOI=10.1016/s0896-6273(00)80810-7;
RA Tu J.C., Xiao B., Naisbitt S., Yuan J.P., Petralia R.S., Brakeman P.,
RA Doan A., Aakalu V.K., Lanahan A.A., Sheng M., Worley P.F.;
RT "Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of
RT postsynaptic density proteins.";
RL Neuron 23:583-592(1999).
RN [5]
RP REVIEW.
RX PubMed=10806096; DOI=10.1242/jcs.113.11.1851;
RA Sheng M., Kim E.;
RT "The Shank family of scaffold proteins.";
RL J. Cell Sci. 113:1851-1856(2000).
RN [6]
RP INTERACTION WITH DBNL, AND TISSUE SPECIFICITY.
RX PubMed=15014124; DOI=10.1523/jneurosci.5479-03.2004;
RA Qualmann B., Boeckers T.M., Jeromin M., Gundelfinger E.D., Kessels M.M.;
RT "Linkage of the actin cytoskeleton to the postsynaptic density via direct
RT interactions of Abp1 with the ProSAP/Shank family.";
RL J. Neurosci. 24:2481-2495(2004).
RN [7]
RP INTERACTION WITH LZTS3, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16522626; DOI=10.1074/jbc.m601101200;
RA Wendholt D., Spilker C., Schmitt A., Dolnik A., Smalla K.H., Proepper C.,
RA Bockmann J., Sobue K., Gundelfinger E.D., Kreutz M.R., Boeckers T.M.;
RT "ProSAP-interacting protein 1 (ProSAPiP1), a novel protein of the
RT postsynaptic density that links the spine-associated Rap-Gap (SPAR) to the
RT scaffolding protein ProSAP2/Shank3.";
RL J. Biol. Chem. 281:13805-13816(2006).
RN [8]
RP INTERACTION WITH ABI1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF PRO-677; PRO-678; PRO-679; PRO-680 AND PRO-684.
RX PubMed=17304222; DOI=10.1038/sj.emboj.7601569;
RA Proepper C., Johannsen S., Liebau S., Dahl J., Vaida B., Bockmann J.,
RA Kreutz M.R., Gundelfinger E.D., Boeckers T.M.;
RT "Abelson interacting protein 1 (Abi-1) is essential for dendrite
RT morphogenesis and synapse formation.";
RL EMBO J. 26:1397-1409(2007).
RN [9]
RP FUNCTION IN MGLUR5 SIGNALING REGULATION, AND TISSUE SPECIFICITY.
RX PubMed=21795692; DOI=10.1074/jbc.m111.258384;
RA Verpelli C., Dvoretskova E., Vicidomini C., Rossi F., Chiappalone M.,
RA Schoen M., Di Stefano B., Mantegazza R., Broccoli V., Boeckers T.M.,
RA Dityatev A., Sala C.;
RT "Importance of Shank3 protein in regulating metabotropic glutamate receptor
RT 5 (mGluR5) expression and signaling at synapses.";
RL J. Biol. Chem. 286:34839-34850(2011).
RN [10]
RP FUNCTION, AND MUTAGENESIS OF ARG-12; ARG-300 AND GLN-321.
RX PubMed=23100419; DOI=10.1523/jneurosci.2215-12.2012;
RA Arons M.H., Thynne C.J., Grabrucker A.M., Li D., Schoen M., Cheyne J.E.,
RA Boeckers T.M., Montgomery J.M., Garner C.C.;
RT "Autism-associated mutations in ProSAP2/Shank3 impair synaptic transmission
RT and neurexin-neuroligin-mediated transsynaptic signaling.";
RL J. Neurosci. 32:14966-14978(2012).
RN [11]
RP FUNCTION, ACTIN-BINDING, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-12;
RP ARG-300 AND GLN-321.
RX PubMed=21606927; DOI=10.1038/mp.2011.57;
RA Durand C.M., Perroy J., Loll F., Perrais D., Fagni L., Bourgeron T.,
RA Montcouquiol M., Sans N.;
RT "SHANK3 mutations identified in autism lead to modification of dendritic
RT spine morphology via an actin-dependent mechanism.";
RL Mol. Psychiatry 17:71-84(2012).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-375; SER-387; SER-394;
RP TYR-931; THR-1131; SER-1135; SER-1160; SER-1167; THR-1235; SER-1254;
RP SER-1421; SER-1511 AND SER-1644, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [13]
RP FUNCTION, DOMAIN, INTERACTION WITH SHARPIN AND SPTAN1, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LEU-68; ARG-300 AND GLN-321.
RX PubMed=23897824; DOI=10.1074/jbc.m112.424747;
RA Mameza M.G., Dvoretskova E., Bamann M., Hoenck H.H., Gueler T.,
RA Boeckers T.M., Schoen M., Verpelli C., Sala C., Barsukov I., Dityatev A.,
RA Kreienkamp H.J.;
RT "SHANK3 gene mutations associated with autism facilitate ligand binding to
RT the Shank3 ankyrin repeat region.";
RL J. Biol. Chem. 288:26697-26708(2013).
RN [14]
RP FUNCTION IN NMDA RECEPTOR SIGNALING REGULATION.
RX PubMed=24089484; DOI=10.1523/jneurosci.1175-13.2013;
RA Duffney L.J., Wei J., Cheng J., Liu W., Smith K.R., Kittler J.T., Yan Z.;
RT "Shank3 deficiency induces NMDA receptor hypofunction via an actin-
RT dependent mechanism.";
RL J. Neurosci. 33:15767-15778(2013).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 1674-1740.
RX PubMed=16439662; DOI=10.1126/science.1118995;
RA Baron M.K., Boeckers T.M., Vaida B., Faham S., Gingery M., Sawaya M.R.,
RA Salyer D., Gundelfinger E.D., Bowie J.U.;
RT "An architectural framework that may lie at the core of the postsynaptic
RT density.";
RL Science 311:531-535(2006).
CC -!- FUNCTION: Major scaffold postsynaptic density protein which interacts
CC with multiple proteins and complexes to orchestrate the dendritic spine
CC and synapse formation, maturation and maintenance. Interconnects
CC receptors of the postsynaptic membrane including NMDA-type and
CC metabotropic glutamate receptors via complexes with GKAP/PSD-95 and
CC HOMER, respectively, and the actin-based cytoskeleton. Plays a role in
CC the structural and functional organization of the dendritic spine and
CC synaptic junction through the interaction with Arp2/3 and WAVE1 complex
CC as well as the promotion of the F-actin clusters. By way of this
CC control of actin dynamics, participates in the regulation of developing
CC neurons growth cone motility and the NMDA receptor-signaling. Also
CC modulates GRIA1 exocytosis and GRM5/MGLUR5 expression and signaling to
CC control the AMPA and metabotropic glutamate receptor-mediated synaptic
CC transmission and plasticity. May be required at an early stage of
CC synapse formation and be inhibited by IGF1 to promote synapse
CC maturation. {ECO:0000269|PubMed:21606927, ECO:0000269|PubMed:21795692,
CC ECO:0000269|PubMed:23100419, ECO:0000269|PubMed:23897824,
CC ECO:0000269|PubMed:24089484}.
CC -!- SUBUNIT: May homomultimerize via its SAM domain. Interacts with BAIAP2,
CC DBNL and SLC17A7/VGLUT1. Interacts with DLGAP1/GKAP, GRM1/MGLUR1,
CC GRM5/MGLUR5 and LZTS3 C-termini via its PDZ domain. Interacts with
CC ABI1, HOMER1, HOMER2, HOMER3 and CTTN/cortactin SH3 domain. Is part of
CC a complex with DLG4/PSD-95 and DLGAP1/GKAP. Interacts (via PDZ domain)
CC with the GRIA1 subunit of the AMPA receptor (via PDZ-binding motif).
CC Interacts with WASF1 and CYFIP2; the interactions mediate the
CC association of SHANK3 with the WAVE1 complex. Interacts with ARPC2; the
CC interaction probably mediates the association of SHANK3 with the Arp2/3
CC complex. Interacts (via ANK repeats) with SHARPIN and SPTAN1. Interacts
CC (via PDZ domain) with ARHGAP44 (probably via PDZ-binding motif); the
CC interaction takes place in dendritic spines and promotes GRIA1
CC exocytosis. Interacts with CAMK2A (By similarity). Interacts with DIP2A
CC (By similarity). {ECO:0000250|UniProtKB:Q4ACU6,
CC ECO:0000250|UniProtKB:Q9BYB0, ECO:0000269|PubMed:10433268,
CC ECO:0000269|PubMed:10433269, ECO:0000269|PubMed:10527873,
CC ECO:0000269|PubMed:15014124, ECO:0000269|PubMed:16522626,
CC ECO:0000269|PubMed:17304222, ECO:0000269|PubMed:23897824}.
CC -!- INTERACTION:
CC Q9JLU4; Q9QZM5: Abi1; NbExp=7; IntAct=EBI-6271152, EBI-920097;
CC Q9JLU4; Q9JLU4: Shank3; NbExp=2; IntAct=EBI-6271152, EBI-6271152;
CC Q9JLU4; Q9ES28-2: Arhgef7; Xeno; NbExp=2; IntAct=EBI-6271152, EBI-8620514;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Postsynaptic density. Cell projection,
CC dendritic spine. Note=In neuronal cells, extends into the region
CC subjacent to the PSD.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=3;
CC Comment=Additional isoforms seem to exist. These isoforms may be the
CC product of multiple intragenic promoter and/or alternative splicing.;
CC Name=2;
CC IsoId=Q9JLU4-1; Sequence=Displayed;
CC Name=1; Synonyms=A;
CC IsoId=Q9JLU4-2; Sequence=VSP_006089;
CC Name=3;
CC IsoId=Q9JLU4-3; Sequence=VSP_006087, VSP_006088;
CC -!- TISSUE SPECIFICITY: Widely expressed in brain (at protein level).
CC {ECO:0000269|PubMed:10527873, ECO:0000269|PubMed:15014124,
CC ECO:0000269|PubMed:16522626, ECO:0000269|PubMed:17304222,
CC ECO:0000269|PubMed:21795692}.
CC -!- DOMAIN: In isoform 1, the N-terminal region preceding the ANK repeats
CC interacts with the 6 ANK repeats in an intramolecular manner, thereby
CC restricting access to ligands, such as SHARPIN and SPTAN1.
CC {ECO:0000269|PubMed:23897824}.
CC -!- SIMILARITY: Belongs to the SHANK family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD42976.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF133301; AAF61375.1; -; mRNA.
DR EMBL; AJ133120; CAB45688.1; -; mRNA.
DR EMBL; AF159047; AAD42976.1; ALT_FRAME; mRNA.
DR RefSeq; NP_067708.1; NM_021676.1.
DR PDB; 2F3N; X-ray; 2.10 A; A/B/C=1674-1740.
DR PDB; 2F44; X-ray; 2.40 A; A/B/C=1674-1740.
DR PDB; 5G4X; X-ray; 2.17 A; A=1-348.
DR PDB; 5O99; X-ray; 0.87 A; A/B=470-528.
DR PDB; 5OVA; X-ray; 2.30 A; A/B=570-664.
DR PDB; 5OVC; X-ray; 1.55 A; A=570-664.
DR PDB; 5OVP; X-ray; 1.50 A; A=570-664.
DR PDB; 5OVV; X-ray; 1.40 A; A=570-664.
DR PDB; 6EXJ; X-ray; 1.80 A; A/C=570-664.
DR PDBsum; 2F3N; -.
DR PDBsum; 2F44; -.
DR PDBsum; 5G4X; -.
DR PDBsum; 5O99; -.
DR PDBsum; 5OVA; -.
DR PDBsum; 5OVC; -.
DR PDBsum; 5OVP; -.
DR PDBsum; 5OVV; -.
DR PDBsum; 6EXJ; -.
DR AlphaFoldDB; Q9JLU4; -.
DR SASBDB; Q9JLU4; -.
DR SMR; Q9JLU4; -.
DR BioGRID; 248756; 16.
DR IntAct; Q9JLU4; 10.
DR MINT; Q9JLU4; -.
DR STRING; 10116.ENSRNOP00000041083; -.
DR iPTMnet; Q9JLU4; -.
DR PhosphoSitePlus; Q9JLU4; -.
DR PaxDb; Q9JLU4; -.
DR PRIDE; Q9JLU4; -.
DR ABCD; Q9JLU4; 4 sequenced antibodies.
DR GeneID; 59312; -.
DR KEGG; rno:59312; -.
DR CTD; 85358; -.
DR RGD; 69264; Shank3.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG4375; Eukaryota.
DR InParanoid; Q9JLU4; -.
DR OrthoDB; 98033at2759; -.
DR Reactome; R-RNO-6794361; Neurexins and neuroligins.
DR Reactome; R-RNO-8853659; RET signaling.
DR EvolutionaryTrace; Q9JLU4; -.
DR PRO; PR:Q9JLU4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0060170; C:ciliary membrane; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; ISS:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0043005; C:neuron projection; ISS:BHF-UCL.
DR GO; GO:0044309; C:neuron spine; ISS:BHF-UCL.
DR GO; GO:0014069; C:postsynaptic density; IDA:UniProtKB.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; IDA:SynGO.
DR GO; GO:0045202; C:synapse; IDA:RGD.
DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISS:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:BHF-UCL.
DR GO; GO:0043621; F:protein self-association; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IPI:RGD.
DR GO; GO:0098919; F:structural constituent of postsynaptic density; IDA:SynGO.
DR GO; GO:0030160; F:synaptic receptor adaptor activity; IDA:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:RGD.
DR GO; GO:0030534; P:adult behavior; ISO:RGD.
DR GO; GO:0097113; P:AMPA glutamate receptor clustering; ISS:BHF-UCL.
DR GO; GO:0008306; P:associative learning; ISO:RGD.
DR GO; GO:0048854; P:brain morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:BHF-UCL.
DR GO; GO:0001838; P:embryonic epithelial tube formation; ISO:RGD.
DR GO; GO:0035640; P:exploration behavior; ISO:RGD.
DR GO; GO:0010467; P:gene expression; ISO:RGD.
DR GO; GO:0014009; P:glial cell proliferation; ISO:RGD.
DR GO; GO:0097117; P:guanylate kinase-associated protein clustering; ISS:BHF-UCL.
DR GO; GO:0007612; P:learning; ISS:BHF-UCL.
DR GO; GO:0007611; P:learning or memory; ISO:RGD.
DR GO; GO:0040011; P:locomotion; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0035641; P:locomotory exploration behavior; ISS:BHF-UCL.
DR GO; GO:0060292; P:long-term synaptic depression; ISO:RGD.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0099562; P:maintenance of postsynaptic density structure; IC:SynGO.
DR GO; GO:0000165; P:MAPK cascade; ISS:BHF-UCL.
DR GO; GO:0007613; P:memory; ISS:BHF-UCL.
DR GO; GO:0032232; P:negative regulation of actin filament bundle assembly; ISS:BHF-UCL.
DR GO; GO:0045794; P:negative regulation of cell volume; ISS:BHF-UCL.
DR GO; GO:0061351; P:neural precursor cell proliferation; ISO:RGD.
DR GO; GO:0050885; P:neuromuscular process controlling balance; ISS:BHF-UCL.
DR GO; GO:0097114; P:NMDA glutamate receptor clustering; ISS:BHF-UCL.
DR GO; GO:2000969; P:positive regulation of AMPA receptor activity; ISS:BHF-UCL.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; ISS:BHF-UCL.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISS:BHF-UCL.
DR GO; GO:1900451; P:positive regulation of glutamate receptor signaling pathway; IMP:RGD.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; ISS:BHF-UCL.
DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISS:BHF-UCL.
DR GO; GO:0051835; P:positive regulation of synapse structural plasticity; ISS:BHF-UCL.
DR GO; GO:0051968; P:positive regulation of synaptic transmission, glutamatergic; ISS:BHF-UCL.
DR GO; GO:0097107; P:postsynaptic density assembly; ISS:BHF-UCL.
DR GO; GO:1904717; P:regulation of AMPA glutamate receptor clustering; ISO:RGD.
DR GO; GO:2000822; P:regulation of behavioral fear response; ISS:BHF-UCL.
DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; ISS:BHF-UCL.
DR GO; GO:2000821; P:regulation of grooming behavior; ISS:BHF-UCL.
DR GO; GO:1900452; P:regulation of long-term synaptic depression; ISS:BHF-UCL.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISS:BHF-UCL.
DR GO; GO:0050807; P:regulation of synapse organization; IDA:SynGO.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISO:RGD.
DR GO; GO:0097396; P:response to interleukin-17; ISO:RGD.
DR GO; GO:0035176; P:social behavior; ISS:BHF-UCL.
DR GO; GO:0021773; P:striatal medium spiny neuron differentiation; ISS:BHF-UCL.
DR GO; GO:0007416; P:synapse assembly; ISS:BHF-UCL.
DR GO; GO:0042297; P:vocal learning; ISO:RGD.
DR GO; GO:0071625; P:vocalization behavior; ISS:BHF-UCL.
DR Gene3D; 1.10.150.50; -; 1.
DR Gene3D; 1.25.40.20; -; 2.
DR Gene3D; 2.30.42.10; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR041489; PDZ_6.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR001660; SAM.
DR InterPro; IPR013761; SAM/pointed_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF17820; PDZ_6; 1.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF07653; SH3_2; 1.
DR SMART; SM00248; ANK; 5.
DR SMART; SM00228; PDZ; 1.
DR SMART; SM00454; SAM; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF47769; SSF47769; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF50156; SSF50156; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 4.
DR PROSITE; PS50106; PDZ; 1.
DR PROSITE; PS50105; SAM_DOMAIN; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Actin-binding; Alternative promoter usage;
KW Alternative splicing; ANK repeat; Cell projection; Coiled coil; Cytoplasm;
KW Methylation; Phosphoprotein; Reference proteome; Repeat; SH3 domain;
KW SH3-binding; Synapse.
FT CHAIN 1..1740
FT /note="SH3 and multiple ankyrin repeat domains protein 3"
FT /id="PRO_0000174676"
FT REPEAT 148..181
FT /note="ANK 1"
FT REPEAT 182..214
FT /note="ANK 2"
FT REPEAT 215..245
FT /note="ANK 3"
FT REPEAT 249..278
FT /note="ANK 4"
FT REPEAT 282..311
FT /note="ANK 5"
FT REPEAT 315..345
FT /note="ANK 6"
FT DOMAIN 470..529
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 570..664
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1677..1740
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..75
FT /note="Intramolecular interaction with the ANK repeats"
FT REGION 354..466
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 664..687
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 677..684
FT /note="Required for interaction with ABI1"
FT /evidence="ECO:0000269|PubMed:17304222"
FT REGION 759..855
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 868..1053
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1115..1199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1211..1463
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1476..1518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1556..1594
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1637..1673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 1495..1515
FT /evidence="ECO:0000255"
FT MOTIF 1411..1417
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 402..418
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 440..464
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 778..792
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 813..847
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1177..1195
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1322..1344
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1368..1401
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1434..1458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1496..1510
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1648..1662
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 122
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 375
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 387
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 394
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 482
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 555
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 694
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 781
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 790
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 801
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 891
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 898
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 913
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYB0"
FT MOD_RES 931
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 966
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1131
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1135
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1160
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1164
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYB0"
FT MOD_RES 1167
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1235
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1254
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1421
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1511
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1522
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1530
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1549
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4ACU6"
FT MOD_RES 1644
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 1646
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYB0"
FT MOD_RES 1648
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9BYB0"
FT VAR_SEQ 1129..1136
FT /note="SPTPVHSP -> PRRRAGMV (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_006087"
FT VAR_SEQ 1137..1740
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_006088"
FT VAR_SEQ 1537..1545
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:10433268,
FT ECO:0000303|PubMed:10527873"
FT /id="VSP_006089"
FT MUTAGEN 12
FT /note="R->C: Disrupts postsynaptic AMPA and NMDA receptor-
FT mediated synaptic transmission as well as transsynaptic
FT signaling and spine maturation."
FT /evidence="ECO:0000269|PubMed:21606927,
FT ECO:0000269|PubMed:23100419"
FT MUTAGEN 68
FT /note="L->P: Slightly increases interaction with SHARPIN
FT and SPTAN1. No effect on localization."
FT /evidence="ECO:0000269|PubMed:23897824"
FT MUTAGEN 300
FT /note="R->C: Disrupts postsynaptic AMPA and NMDA receptor-
FT mediated synaptic transmission as well as transsynaptic
FT signaling and spine maturation. Slightly decreases
FT interaction with SHARPIN and SPTAN1. No effect on
FT localization."
FT /evidence="ECO:0000269|PubMed:21606927,
FT ECO:0000269|PubMed:23100419, ECO:0000269|PubMed:23897824"
FT MUTAGEN 321
FT /note="Q->R: Disrupts postsynaptic AMPA and NMDA receptor-
FT mediated synaptic transmission as well as transsynaptic
FT signaling and spine maturation. Disrupts axonal growth cone
FT motility. Slightly increases interaction with SHARPIN and
FT SPTAN1. No effect on localization."
FT /evidence="ECO:0000269|PubMed:21606927,
FT ECO:0000269|PubMed:23100419, ECO:0000269|PubMed:23897824"
FT MUTAGEN 677
FT /note="P->A: Strongly decreases interaction with ABI1."
FT /evidence="ECO:0000269|PubMed:17304222"
FT MUTAGEN 678
FT /note="P->A: Almost abolishes interaction with ABI1."
FT /evidence="ECO:0000269|PubMed:17304222"
FT MUTAGEN 679
FT /note="P->A: Abolishes interaction with ABI1."
FT /evidence="ECO:0000269|PubMed:17304222"
FT MUTAGEN 680
FT /note="P->A: Abolishes interaction with ABI1."
FT /evidence="ECO:0000269|PubMed:17304222"
FT MUTAGEN 684
FT /note="P->A: Abolishes interaction with ABI1."
FT /evidence="ECO:0000269|PubMed:17304222"
FT MUTAGEN 1311
FT /note="P->L: Abolishes interaction with HOMER1 isoform 3."
FT /evidence="ECO:0000269|PubMed:10433269"
FT MUTAGEN 1314
FT /note="F->C: Abolishes interaction with HOMER1 isoform 3."
FT /evidence="ECO:0000269|PubMed:10433269"
FT CONFLICT 397
FT /note="H -> L (in Ref. 3; AAD42976)"
FT /evidence="ECO:0000305"
FT CONFLICT 706
FT /note="R -> G (in Ref. 3; AAD42976)"
FT /evidence="ECO:0000305"
FT CONFLICT 827..832
FT /note="YYFDSG -> ILRLR (in Ref. 3; AAD42976)"
FT /evidence="ECO:0000305"
FT CONFLICT 837..842
FT /note="FSPPPP -> SHHGHQ (in Ref. 3; AAD42976)"
FT /evidence="ECO:0000305"
FT CONFLICT 846
FT /note="R -> G (in Ref. 3; AAD42976)"
FT /evidence="ECO:0000305"
FT CONFLICT 888
FT /note="R -> G (in Ref. 3; AAD42976)"
FT /evidence="ECO:0000305"
FT CONFLICT 1040
FT /note="S -> N (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1087
FT /note="S -> N (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1092
FT /note="G -> S (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1262
FT /note="S -> N (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1270
FT /note="G -> S (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1273
FT /note="S -> N (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1279
FT /note="E -> K (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1294
FT /note="S -> N (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1432
FT /note="D -> G (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT CONFLICT 1640
FT /note="V -> A (in Ref. 2; AAF61375)"
FT /evidence="ECO:0000305"
FT STRAND 9..15
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:5G4X"
FT STRAND 20..26
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 32..43
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 50..52
FT /evidence="ECO:0007829|PDB:5G4X"
FT STRAND 53..57
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 74..76
FT /evidence="ECO:0007829|PDB:5G4X"
FT STRAND 87..92
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 104..110
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 113..124
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 128..136
FT /evidence="ECO:0007829|PDB:5G4X"
FT TURN 146..148
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 152..156
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 163..171
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 186..192
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 196..204
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 219..226
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 231..238
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 253..260
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 263..271
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 286..293
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 296..304
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 319..325
FT /evidence="ECO:0007829|PDB:5G4X"
FT HELIX 329..337
FT /evidence="ECO:0007829|PDB:5G4X"
FT STRAND 474..479
FT /evidence="ECO:0007829|PDB:5O99"
FT STRAND 496..502
FT /evidence="ECO:0007829|PDB:5O99"
FT STRAND 507..512
FT /evidence="ECO:0007829|PDB:5O99"
FT STRAND 515..520
FT /evidence="ECO:0007829|PDB:5O99"
FT HELIX 521..523
FT /evidence="ECO:0007829|PDB:5O99"
FT STRAND 524..526
FT /evidence="ECO:0007829|PDB:5O99"
FT STRAND 570..574
FT /evidence="ECO:0007829|PDB:5OVV"
FT STRAND 582..587
FT /evidence="ECO:0007829|PDB:5OVV"
FT HELIX 594..596
FT /evidence="ECO:0007829|PDB:5OVV"
FT STRAND 601..603
FT /evidence="ECO:0007829|PDB:5OVA"
FT STRAND 605..612
FT /evidence="ECO:0007829|PDB:5OVV"
FT HELIX 617..620
FT /evidence="ECO:0007829|PDB:5OVV"
FT STRAND 628..632
FT /evidence="ECO:0007829|PDB:5OVV"
FT HELIX 642..651
FT /evidence="ECO:0007829|PDB:5OVV"
FT TURN 652..654
FT /evidence="ECO:0007829|PDB:5OVV"
FT STRAND 655..662
FT /evidence="ECO:0007829|PDB:5OVV"
FT HELIX 1674..1676
FT /evidence="ECO:0007829|PDB:2F3N"
FT HELIX 1679..1688
FT /evidence="ECO:0007829|PDB:2F3N"
FT HELIX 1692..1694
FT /evidence="ECO:0007829|PDB:2F3N"
FT HELIX 1695..1700
FT /evidence="ECO:0007829|PDB:2F3N"
FT HELIX 1705..1710
FT /evidence="ECO:0007829|PDB:2F3N"
FT HELIX 1713..1718
FT /evidence="ECO:0007829|PDB:2F3N"
FT HELIX 1724..1735
FT /evidence="ECO:0007829|PDB:2F3N"
SQ SEQUENCE 1740 AA; 186376 MW; A9F486E893EA5AA0 CRC64;
MDGPGASAVV VRVGIPDLQQ TKCLRLDPTA PVWAAKQRVL CALNHSLQDA LNYGLFQPPS
RGRAGKFLDE ERLLQDYPPN LDTPLPYLEF RYKRRVYAQN LIDDKQFAKL HTKANLKKFM
DYVQLHSTDK VARLLDKGLD PNFHDPDSGE CPLSLAAQLD NATDLLKVLR NGGAHLDFRT
RDGLTAVHCA TRQRNAGALT TLLDLGASPD YKDSRGLTPL YHSALGGGDA LCCELLLHDH
AQLGTTDENG WQEIHQACRF GHVQHLEHLL FYGANMGAQN ASGNTALHIC ALYNQESCAR
VLLFRGANKD VRNYNSQTAF QVAIIAGNFE LAEVIKTHKD SDVVPFRETP SYAKRRRLAG
PSGLASPRPL QRSASDINLK GDQPAASPGP TLRSLPHQLL LQRLQEEKDR DRDGEQENDI
SGPSAGRGGH SKISPSGPGG SGPAPGPGPA SPAPPAPPPR GPKRKLYSAV PGRKFIAVKA
HSPQGEGEIP LHRGEAVKVL SIGEGGFWEG TVKGRTGWFP ADCVEEVQMR QYDTRHETRE
DRTKRLFRHY TVGSYDSLTS HSDYVIDDKV AILQKRDHEG FGFVLRGAKA ETPIEEFTPT
PAFPALQYLE SVDVEGVAWK AGLRTGDFLI EVNGVNVVKV GHKQVVGLIR QGGNRLVMKV
VSVTRKPEED SARRRAPPPP KRAPSTTLTL RSKSMTAELE ELASIRRRKG EKLDEILAVA
AEPTLRPDIA DADSRAATVK QRPTSRRITP AEISSLFERQ GLPGPEKLPG SLRKGIPRTK
SVGEDEKLAS LLEGRFPRST SMQDTVREGR GIPPPPQTAP PPPPAPYYFD SGPPPTFSPP
PPPPGRAYDT VRSSFKPGLE ARLGAGAAGL YDSGTPLGPL PYPERQKRAR SMIILQDSAP
EVGDVPRPAP AATPPERPKR RPRPSGPDSP YANLGAFSAS LFAPSKPQRR KSPLVKQLQV
EDAQERAALA VGSPGPVGGS FAREPSPTHR GPRPGGLDYS SGEGLGLTFG GPSPGPVKER
RLEERRRSTV FLSVGAIEGS PPSADLPSLQ PSRSIDERLL GTGATTGRDL LLPSPVSALK
PLVGGPSLGP SGSTFIHPLT GKPLDPSSPL ALALAARERA LASQTPSRSP TPVHSPDADR
PGPLFVDVQT RDSERGPLAS PAFSPRSPAW IPVPARREAE KPTREERKSP EDKKSMILSV
LDTSLQRPAG LIVVHATSNG QEPNRLGAEE ERPGTPELAP TPMQAAAVAE PMPSPRAQPP
GSIPADPGPG QGSSEEEPEL VFAVNLPPAQ LSSSDEETRE ELARIGLVPP PEEFANGILL
ATPPPGPGPL PTTVPSPASG KPSSELPPAP ESAADSGVEE ADTRSSSDPH LETTSTISTV
SSMSTLSSES GELTDTHTSF ADGHTFLLEK PPVPPKPKLK SPLGKGPVTF RDPLLKQSSD
SELMAQQHHA TSTGLTSAAG PARPRYLFQR RSKLWGDPVE SRGLPGPEDD KPTVISELSS
RLQQLNKDTR SLGEEPVGGL GSLLDPAKKS PIAAARCAVV PSAGWLFSSL GELSTISAQR
SPGGPGGGAS YSVRPSGRYP VARRAPSPVK PASLERVEGL GAGVGGAGRP FGLTPPTILK
SSSLSIPHEP KEVRFVVRSV SARSRSPSPS PLPSPSPGSG PSAGPRRPFQ QKPLQLWSKF
DVGDWLESIH LGEHRDRFED HEIEGAHLPA LTKEDFVELG VTRVGHRMNI ERALRQLDGS
