SHAN2_HUMAN
ID SHAN2_HUMAN Reviewed; 1849 AA.
AC Q9UPX8; C0SPG8; C0SPG9; Q3Y8G9; Q52LK2; Q9UKP1;
DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 4.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=SH3 and multiple ankyrin repeat domains protein 2;
DE Short=Shank2;
DE AltName: Full=Cortactin-binding protein 1;
DE Short=CortBP1;
DE AltName: Full=Proline-rich synapse-associated protein 1;
GN Name=SHANK2; Synonyms=CORTBP1, KIAA1022, PROSAP1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
RA Akahane T., Hosoda F., Arai Y., Fujisawa N., Kitabayashi I., Ohta T.,
RA Aoyagi K., Sasaki H., Nakanishi Y., Hirohashi S., Ohki M.;
RT "A molecular scaffolding protein, Shank2, is a potent tumor suppressor in
RT esophageal squamous cell carcinoma.";
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 380-707 (ISOFORM 3), AND TISSUE SPECIFICITY.
RX PubMed=16293618; DOI=10.1074/jbc.m509786200;
RA Han W., Kim K.H., Jo M.J., Lee J.H., Yang J., Doctor R.B., Moe O.W.,
RA Lee J., Kim E., Lee M.G.;
RT "Shank2 associates with and regulates Na+/H+ exchanger 3.";
RL J. Biol. Chem. 281:1461-1469(2006).
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [6]
RP PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RX PubMed=10506216; DOI=10.1074/jbc.274.41.29510;
RA Lim S., Naisbitt S., Yoon J., Hwang J.-I., Suh P.-G., Sheng M., Kim E.;
RT "Characterization of the shank family of synaptic proteins. Multiple genes,
RT alternative splicing, and differential expression in brain and
RT development.";
RL J. Biol. Chem. 274:29510-29518(1999).
RN [7]
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 [8]
RP INTERACTION WITH DNM2.
RX PubMed=11583995; DOI=10.1074/jbc.m104927200;
RA Okamoto P.M., Gamby C., Wells D., Fallon J., Vallee R.B.;
RT "Dynamin isoform-specific interaction with the shank/ProSAP scaffolding
RT proteins of the postsynaptic density and actin cytoskeleton.";
RL J. Biol. Chem. 276:48458-48465(2001).
RN [9]
RP INTERACTION WITH BAIAP2.
RX PubMed=12504591; DOI=10.1006/mcne.2002.1201;
RA Soltau M., Richter D., Kreienkamp H.-J.;
RT "The insulin receptor substrate IRSp53 links postsynaptic shank1 to the
RT small G-protein cdc42.";
RL Mol. Cell. Neurosci. 21:575-583(2002).
RN [10]
RP INTERACTION WITH PDE4D, AND TISSUE SPECIFICITY.
RX PubMed=17244609; DOI=10.1074/jbc.m610857200;
RA Lee J.H., Richter W., Namkung W., Kim K.H., Kim E., Conti M., Lee M.G.;
RT "Dynamic regulation of cystic fibrosis transmembrane conductance regulator
RT by competitive interactions of molecular adaptors.";
RL J. Biol. Chem. 282:10414-10422(2007).
RN [11]
RP INVOLVEMENT IN AUTS17.
RX PubMed=20473310; DOI=10.1038/ng.589;
RA Berkel S., Marshall C.R., Weiss B., Howe J., Roeth R., Moog U., Endris V.,
RA Roberts W., Szatmari P., Pinto D., Bonin M., Riess A., Engels H.,
RA Sprengel R., Scherer S.W., Rappold G.A.;
RT "Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum
RT disorder and mental retardation.";
RL Nat. Genet. 42:489-491(2010).
RN [12]
RP VARIANT THR-1101.
RX PubMed=30500825; DOI=10.1371/journal.pgen.1007671;
RA Hiatt S.M., Neu M.B., Ramaker R.C., Hardigan A.A., Prokop J.W.,
RA Hancarova M., Prchalova D., Havlovicova M., Prchal J., Stranecky V.,
RA Yim D.K.C., Powis Z., Keren B., Nava C., Mignot C., Rio M.,
RA Revah-Politi A., Hemati P., Stong N., Iglesias A.D., Suchy S.F.,
RA Willaert R., Wentzensen I.M., Wheeler P.G., Brick L., Kozenko M.,
RA Hurst A.C.E., Wheless J.W., Lacassie Y., Myers R.M., Barsh G.S.,
RA Sedlacek Z., Cooper G.M.;
RT "De novo mutations in the GTP/GDP-binding region of RALA, a RAS-like small
RT GTPase, cause intellectual disability and developmental delay.";
RL PLoS Genet. 14:e1007671-e1007671(2018).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
CC -!- FUNCTION: Seems to be an adapter protein in the postsynaptic density
CC (PSD) of excitatory synapses that interconnects receptors of the
CC postsynaptic membrane including NMDA-type and metabotropic glutamate
CC receptors, and the actin-based cytoskeleton. May play a role in the
CC structural and functional organization of the dendritic spine and
CC synaptic junction.
CC -!- SUBUNIT: Is part of a complex with DLG4/PSD-95 and DLGAP1/GKAP.
CC Interacts with CTTN/cortactin SH3 domain, DLGAP1/GKAP and alpha-
CC latrotoxin receptor 1. Interacts with DNM2, DBNL, GRID2, BAIAP2,
CC SLC9A3, PLCB3 and CFTR. Interacts (via proline-rich region) with PDE4D.
CC Interacts with ABI1 (via SH3 domain). {ECO:0000269|PubMed:11583995,
CC ECO:0000269|PubMed:12504591, ECO:0000269|PubMed:17244609}.
CC -!- INTERACTION:
CC Q9UPX8; P46108: CRK; NbExp=2; IntAct=EBI-1570571, EBI-886;
CC Q9UPX8; P62993: GRB2; NbExp=2; IntAct=EBI-1570571, EBI-401755;
CC Q9UPX8; P16333: NCK1; NbExp=6; IntAct=EBI-1570571, EBI-389883;
CC Q9UPX8; P27986: PIK3R1; NbExp=2; IntAct=EBI-1570571, EBI-79464;
CC Q9UPX8; P19174: PLCG1; NbExp=4; IntAct=EBI-1570571, EBI-79387;
CC Q9UPX8-4; Q8IWW6-4: ARHGAP12; NbExp=3; IntAct=EBI-11959011, EBI-11959591;
CC Q9UPX8-4; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-11959011, EBI-9092016;
CC Q9UPX8-4; Q86YM7: HOMER1; NbExp=3; IntAct=EBI-11959011, EBI-746815;
CC Q9UPX8-4; Q08209-2: PPP3CA; NbExp=3; IntAct=EBI-11959011, EBI-11959013;
CC Q9UPX8-4; Q96MK2: RIPOR3; NbExp=3; IntAct=EBI-11959011, EBI-12010512;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Synapse {ECO:0000250}. Postsynaptic density
CC {ECO:0000250}. Cell projection, growth cone {ECO:0000250}. Cell
CC projection, dendritic spine {ECO:0000250}. Note=Colocalizes with
CC cortactin in growth cones in differentiating hippocampal neurons.
CC Colocalized with PDE4D to the apical membrane of colonic crypt cells
CC (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=3; Synonyms=E;
CC IsoId=Q9UPX8-3; Sequence=Displayed;
CC Name=1; Synonyms=A;
CC IsoId=Q9UPX8-1; Sequence=VSP_061471;
CC Name=2; Synonyms=C;
CC IsoId=Q9UPX8-2; Sequence=VSP_061470, VSP_061473, VSP_061474;
CC Name=4; Synonyms=B;
CC IsoId=Q9UPX8-4; Sequence=VSP_061470, VSP_061472;
CC -!- TISSUE SPECIFICITY: Isoform 3 is present in epithelial colonic cells
CC (at protein level). {ECO:0000269|PubMed:16293618,
CC ECO:0000269|PubMed:17244609}.
CC -!- DOMAIN: The PDZ domain is required for interaction with GRID2, PLCB3,
CC CFTR and SLC9A3. {ECO:0000250}.
CC -!- DISEASE: Autism 17 (AUTS17) [MIM:613436]: A complex multifactorial,
CC pervasive developmental disorder characterized by impairments in
CC reciprocal social interaction and communication, restricted and
CC stereotyped patterns of interests and activities, and the presence of
CC developmental abnormalities by 3 years of age. Most individuals with
CC autism also manifest moderate intellectual disability.
CC {ECO:0000269|PubMed:20473310}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: Contains 6 ANK repeats at positions 196-
CC 226, 230-259, 263-293, 297-326, 330-359, 363-393. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the SHANK family. {ECO:0000305}.
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DR EMBL; AB208025; BAH37016.1; -; mRNA.
DR EMBL; AB208026; BAH37017.1; -; mRNA.
DR EMBL; AP000590; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP003783; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP005401; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC093885; AAH93885.1; -; mRNA.
DR EMBL; BC112097; AAI12098.1; -; mRNA.
DR EMBL; DQ152234; AAZ77790.1; -; mRNA.
DR EMBL; AB028945; BAA82974.1; -; mRNA.
DR EMBL; AF141901; AAF02496.1; -; mRNA.
DR RefSeq; NP_036441.2; NM_012309.4. [Q9UPX8-3]
DR RefSeq; NP_573573.2; NM_133266.4.
DR RefSeq; XP_005277989.1; XM_005277932.3.
DR RefSeq; XP_016872876.1; XM_017017387.1. [Q9UPX8-3]
DR RefSeq; XP_016872877.1; XM_017017388.1. [Q9UPX8-3]
DR AlphaFoldDB; Q9UPX8; -.
DR SMR; Q9UPX8; -.
DR BioGRID; 116598; 33.
DR DIP; DIP-52255N; -.
DR IntAct; Q9UPX8; 21.
DR MINT; Q9UPX8; -.
DR STRING; 9606.ENSP00000469689; -.
DR GlyGen; Q9UPX8; 4 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; Q9UPX8; -.
DR PhosphoSitePlus; Q9UPX8; -.
DR BioMuta; SHANK2; -.
DR DMDM; 254763402; -.
DR EPD; Q9UPX8; -.
DR jPOST; Q9UPX8; -.
DR MassIVE; Q9UPX8; -.
DR MaxQB; Q9UPX8; -.
DR PaxDb; Q9UPX8; -.
DR PeptideAtlas; Q9UPX8; -.
DR PRIDE; Q9UPX8; -.
DR ProteomicsDB; 85467; -. [Q9UPX8-1]
DR ProteomicsDB; 85468; -. [Q9UPX8-2]
DR ProteomicsDB; 85469; -. [Q9UPX8-3]
DR ProteomicsDB; 85470; -. [Q9UPX8-4]
DR ABCD; Q9UPX8; 2 sequenced antibodies.
DR Antibodypedia; 2161; 312 antibodies from 28 providers.
DR DNASU; 22941; -.
DR Ensembl; ENST00000601538.6; ENSP00000469689.2; ENSG00000162105.21. [Q9UPX8-3]
DR Ensembl; ENST00000656230.1; ENSP00000499561.1; ENSG00000162105.21. [Q9UPX8-1]
DR GeneID; 22941; -.
DR KEGG; hsa:22941; -.
DR MANE-Select; ENST00000601538.6; ENSP00000469689.2; NM_012309.5; NP_036441.2.
DR UCSC; uc058etm.1; human. [Q9UPX8-3]
DR CTD; 22941; -.
DR DisGeNET; 22941; -.
DR GeneCards; SHANK2; -.
DR HGNC; HGNC:14295; SHANK2.
DR HPA; ENSG00000162105; Tissue enhanced (choroid).
DR MalaCards; SHANK2; -.
DR MIM; 603290; gene.
DR MIM; 613436; phenotype.
DR neXtProt; NX_Q9UPX8; -.
DR OpenTargets; ENSG00000162105; -.
DR Orphanet; 106; NON RARE IN EUROPE: Autism.
DR PharmGKB; PA37867; -.
DR VEuPathDB; HostDB:ENSG00000162105; -.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG4375; Eukaryota.
DR GeneTree; ENSGT00940000153561; -.
DR HOGENOM; CLU_001824_2_0_1; -.
DR InParanoid; Q9UPX8; -.
DR OMA; HASVCCQ; -.
DR OrthoDB; 36120at2759; -.
DR PhylomeDB; Q9UPX8; -.
DR PathwayCommons; Q9UPX8; -.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; Q9UPX8; -.
DR SIGNOR; Q9UPX8; -.
DR BioGRID-ORCS; 22941; 10 hits in 222 CRISPR screens.
DR ChiTaRS; SHANK2; human.
DR GeneWiki; SHANK2; -.
DR GenomeRNAi; 22941; -.
DR Pharos; Q9UPX8; Tbio.
DR PRO; PR:Q9UPX8; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9UPX8; protein.
DR Bgee; ENSG00000162105; Expressed in Brodmann (1909) area 23 and 164 other tissues.
DR ExpressionAtlas; Q9UPX8; baseline and differential.
DR Genevisible; Q9UPX8; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0016324; C:apical plasma membrane; ISS:BHF-UCL.
DR GO; GO:0031526; C:brush border membrane; ISS:BHF-UCL.
DR GO; GO:0060170; C:ciliary membrane; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; ISS:BHF-UCL.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0030426; C:growth cone; ISS:BHF-UCL.
DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; ISS:BHF-UCL.
DR GO; GO:0043025; C:neuronal cell body; ISS:BHF-UCL.
DR GO; GO:0001917; C:photoreceptor inner segment; ISS:BHF-UCL.
DR GO; GO:0001750; C:photoreceptor outer segment; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; ISS:BHF-UCL.
DR GO; GO:0014069; C:postsynaptic density; ISS:BHF-UCL.
DR GO; GO:0048786; C:presynaptic active zone; IEA:Ensembl.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISS:BHF-UCL.
DR GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0098919; F:structural constituent of postsynaptic density; IEA:Ensembl.
DR GO; GO:0030160; F:synaptic receptor adaptor activity; IBA:GO_Central.
DR GO; GO:0030534; P:adult behavior; IMP:BHF-UCL.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0008306; P:associative learning; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:0007612; P:learning; IMP:BHF-UCL.
DR GO; GO:0060292; P:long-term synaptic depression; ISS:BHF-UCL.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISS:BHF-UCL.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IMP:FlyBase.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:FlyBase.
DR GO; GO:0050807; P:regulation of synapse organization; IEA:Ensembl.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0035176; P:social behavior; IMP:BHF-UCL.
DR GO; GO:0007416; P:synapse assembly; ISS:BHF-UCL.
DR GO; GO:0071625; P:vocalization behavior; IMP: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; 2.
DR Pfam; PF17820; PDZ_6; 1.
DR Pfam; PF00536; SAM_1; 1.
DR Pfam; PF07653; SH3_2; 1.
DR SMART; SM00248; ANK; 6.
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; 2.
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 Alternative splicing; ANK repeat; Autism; Autism spectrum disorder;
KW Cell membrane; Cell projection; Cytoplasm; Glycoprotein; Membrane;
KW Phosphoprotein; Reference proteome; Repeat; SH3 domain; SH3-binding;
KW Synapse.
FT CHAIN 1..1849
FT /note="SH3 and multiple ankyrin repeat domains protein 2"
FT /id="PRO_0000174673"
FT REPEAT 196..226
FT /note="ANK 1"
FT /evidence="ECO:0000255"
FT REPEAT 230..259
FT /note="ANK 2"
FT /evidence="ECO:0000255"
FT REPEAT 263..293
FT /note="ANK 3"
FT /evidence="ECO:0000255"
FT REPEAT 297..326
FT /note="ANK 4"
FT /evidence="ECO:0000255"
FT REPEAT 330..359
FT /note="ANK 5"
FT /evidence="ECO:0000255"
FT REPEAT 363..393
FT /note="ANK 6"
FT /evidence="ECO:0000255"
FT DOMAIN 526..585
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 626..720
FT /note="PDZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 1786..1849
FT /note="SAM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184"
FT REGION 1..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 451..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..808
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 878..910
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1013..1293
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1328..1371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1432..1526
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1574..1594
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1678..1776
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1327..1333
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 1..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 884..908
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1035..1055
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1170..1199
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1272..1293
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1328..1343
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1440..1469
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1503..1526
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1576..1590
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1678..1716
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1725..1745
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1760..1776
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 831
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z38"
FT MOD_RES 860
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z38"
FT MOD_RES 960
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z38"
FT MOD_RES 1099
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z38"
FT MOD_RES 1278
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z38"
FT MOD_RES 1709
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z38"
FT MOD_RES 1713
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80Z38"
FT CARBOHYD 1667
FT /note="O-linked (GlcNAc) threonine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..617
FT /note="MPRSPTSSEDEMAQSFSDYSVGSESDSSKEETIYDTIRATAEKPGGARTEES
FT QGNTLVIRVVIHDLQQTKCIRFNPDATVWVAKQRILCTLTQSLKDVLNYGLFQPASNGR
FT DGKFLDEERLLREYPQPVGEGVPSLEFRYKKRVYKQASLDEKQLAKLHTKTNLKKCMDH
FT IQHRLVEKITKMLDRGLDPNFHDPETGETPLTLAAQLDDSVEVIKALKNGGAHLDFRAK
FT DGMTALHKAARARNQVALKTLLELGASPDYKDSYGLTPLYHTAIVGGDPYCCELLLHEH
FT ATVCCKDENGWHEIHQACRYGHVQHLEHLLFYGADMSAQNASGNTALHICALYNQDSCA
FT RVLLFRGGNKELKNYNSQTPFQVAIIAGNFELAEYIKNHKETDIVPFREAPAYSNRRRR
FT PPNTLAAPRVLLRSNSDNNLNASAPDWAVCSTATSHRSLSPQLLQQMPSKPEGAAKTIG
FT SYVPGPRSRSPSLNRLGGAGEDGKRPQPLWHVGSPFALGANKDSLSAFEYPGPKRKLYS
FT AVPGRLFVAVKPYQPQVDGEIPLHRGDRVKVLSIGEGGFWEGSARGHIGWFPAECVEEV
FT QCKPRDSQAETRADRSKKLFRHYTVGSYDSFDTS -> MMMNVPGGGAAAVMMTGYNNG
FT RCPRNSLY (in isoform 2 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:10470851,
FT ECO:0000303|PubMed:10506216, ECO:0000303|PubMed:15489334"
FT /id="VSP_061470"
FT VAR_SEQ 1..391
FT /note="MPRSPTSSEDEMAQSFSDYSVGSESDSSKEETIYDTIRATAEKPGGARTEES
FT QGNTLVIRVVIHDLQQTKCIRFNPDATVWVAKQRILCTLTQSLKDVLNYGLFQPASNGR
FT DGKFLDEERLLREYPQPVGEGVPSLEFRYKKRVYKQASLDEKQLAKLHTKTNLKKCMDH
FT IQHRLVEKITKMLDRGLDPNFHDPETGETPLTLAAQLDDSVEVIKALKNGGAHLDFRAK
FT DGMTALHKAARARNQVALKTLLELGASPDYKDSYGLTPLYHTAIVGGDPYCCELLLHEH
FT ATVCCKDENGWHEIHQACRYGHVQHLEHLLFYGADMSAQNASGNTALHICALYNQDSCA
FT RVLLFRGGNKELKNYNSQTPFQVAIIAGNFELAEYIKNHKETDI -> MKSLLNAFTKK
FT E (in isoform 1)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_061471"
FT VAR_SEQ 763..769
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10470851"
FT /id="VSP_061472"
FT VAR_SEQ 851..869
FT /note="DSRIFLSGITEEERQFLAP -> GKKCGTPPQKLPLGFQTQP (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:10506216,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_061473"
FT VAR_SEQ 870..1849
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10506216,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_061474"
FT VARIANT 1101
FT /note="A -> T (found in a child with developmental
FT disabilities; unknown pathological significance;
FT dbSNP:rs868939163)"
FT /evidence="ECO:0000269|PubMed:30500825"
FT /id="VAR_085767"
SQ SEQUENCE 1849 AA; 201261 MW; 45550DC5D5701399 CRC64;
MPRSPTSSED EMAQSFSDYS VGSESDSSKE ETIYDTIRAT AEKPGGARTE ESQGNTLVIR
VVIHDLQQTK CIRFNPDATV WVAKQRILCT LTQSLKDVLN YGLFQPASNG RDGKFLDEER
LLREYPQPVG EGVPSLEFRY KKRVYKQASL DEKQLAKLHT KTNLKKCMDH IQHRLVEKIT
KMLDRGLDPN FHDPETGETP LTLAAQLDDS VEVIKALKNG GAHLDFRAKD GMTALHKAAR
ARNQVALKTL LELGASPDYK DSYGLTPLYH TAIVGGDPYC CELLLHEHAT VCCKDENGWH
EIHQACRYGH VQHLEHLLFY GADMSAQNAS GNTALHICAL YNQDSCARVL LFRGGNKELK
NYNSQTPFQV AIIAGNFELA EYIKNHKETD IVPFREAPAY SNRRRRPPNT LAAPRVLLRS
NSDNNLNASA PDWAVCSTAT SHRSLSPQLL QQMPSKPEGA AKTIGSYVPG PRSRSPSLNR
LGGAGEDGKR PQPLWHVGSP FALGANKDSL SAFEYPGPKR KLYSAVPGRL FVAVKPYQPQ
VDGEIPLHRG DRVKVLSIGE GGFWEGSARG HIGWFPAECV EEVQCKPRDS QAETRADRSK
KLFRHYTVGS YDSFDTSSDC IIEEKTVVLQ KKDNEGFGFV LRGAKADTPI EEFTPTPAFP
ALQYLESVDE GGVAWQAGLR TGDFLIEVNN ENVVKVGHRQ VVNMIRQGGN HLVLKVVTVT
RNLDPDDTAR KKAPPPPKRA PTTALTLRSK SMTSELEELV DKASVRKKKD KPEEIVPASK
PSRAAENMAV EPRVATIKQR PSSRCFPAGS DMNSVYERQG IAVMTPTVPG SPKAPFLGIP
RGTMRRQKSI DSRIFLSGIT EEERQFLAPP MLKFTRSLSM PDTSEDIPPP PQSVPPSPPP
PSPTTYNCPK SPTPRVYGTI KPAFNQNSAA KVSPATRSDT VATMMREKGM YFRRELDRYS
LDSEDLYSRN AGPQANFRNK RGQMPENPYS EVGKIASKAV YVPAKPARRK GMLVKQSNVE
DSPEKTCSIP IPTIIVKEPS TSSSGKSSQG SSMEIDPQAP EPPSQLRPDE SLTVSSPFAA
AIAGAVRDRE KRLEARRNSP AFLSTDLGDE DVGLGPPAPR TRPSMFPEEG DFADEDSAEQ
LSSPMPSATP REPENHFVGG AEASAPGEAG RPLNSTSKAQ GPESSPAVPS ASSGTAGPGN
YVHPLTGRLL DPSSPLALAL SARDRAMKES QQGPKGEAPK ADLNKPLYID TKMRPSLDAG
FPTVTRQNTR GPLRRQETEN KYETDLGRDR KGDDKKNMLI DIMDTSQQKS AGLLMVHTVD
ATKLDNALQE EDEKAEVEMK PDSSPSEVPE GVSETEGALQ ISAAPEPTTV PGRTIVAVGS
MEEAVILPFR IPPPPLASVD LDEDFIFTEP LPPPLEFANS FDIPDDRAAS VPALSDLVKQ
KKSDTPQSPS LNSSQPTNSA DSKKPASLSN CLPASFLPPP ESFDAVADSG IEEVDSRSSS
DHHLETTSTI STVSSISTLS SEGGENVDTC TVYADGQAFM VDKPPVPPKP KMKPIIHKSN
ALYQDALVEE DVDSFVIPPP APPPPPGSAQ PGMAKVLQPR TSKLWGDVTE IKSPILSGPK
ANVISELNSI LQQMNREKLA KPGEGLDSPM GAKSASLAPR SPEIMSTISG TRSTTVTFTV
RPGTSQPITL QSRPPDYESR TSGTRRAPSP VVSPTEMNKE TLPAPLSAAT ASPSPALSDV
FSLPSQPPSG DLFGLNPAGR SRSPSPSILQ QPISNKPFTT KPVHLWTKPD VADWLESLNL
GEHKEAFMDN EIDGSHLPNL QKEDLIDLGV TRVGHRMNIE RALKQLLDR
