ID SHAN3_HUMAN Reviewed; 1731 AA. AC Q9BYB0; D7UT47; Q8TET3; DT 26-JUL-2002, integrated into UniProtKB/Swiss-Prot. DT 19-FEB-2014, sequence version 3. DT 27-MAR-2024, entry version 182. 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; GN Name=SHANK3; Synonyms=KIAA1650, PROSAP2, PSAP2; 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] (ISOFORM 1). RA Uchino S., Waga C., Kohsaka S.; RT "Novel veriants of human SHANK3 gene."; RL Submitted (JUN-2010) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C., RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., RA Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 935-1731 (ISOFORMS 1/2). RX PubMed=11258795; DOI=10.1093/dnares/8.1.1; RA Hirosawa M., Nagase T., Murahashi Y., Kikuno R., Ohara O.; RT "Identification of novel transcribed sequences on human chromosome 22 by RT expressed sequence tag mapping."; RL DNA Res. 8:1-9(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 962-1731 (ISOFORMS 1/2). RC TISSUE=Spleen; RA Ohara O., Nagase T., Kikuno R., Okumura K.; RT "The nucleotide sequence of a long cDNA clone isolated from human spleen."; RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1158 AND SER-1162, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-1234 AND SER-1253, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [7] RP ALTERNATIVE SPLICING (ISOFORM 2), AND INVOLVEMENT IN NEUROPSYCHIATRIC RP DISORDERS. RX PubMed=24186872; DOI=10.1093/hmg/ddt547; RA Zhu L., Wang X., Li X.L., Towers A., Cao X., Wang P., Bowman R., Yang H., RA Goldstein J., Li Y.J., Jiang Y.H.; RT "Epigenetic dysregulation of SHANK3 in brain tissues from individuals with RT autism spectrum disorders."; RL Hum. Mol. Genet. 23:1563-1578(2014). RN [8] RP CHROMOSOMAL TRANSLOCATION WITH APPL2. RX PubMed=11431708; DOI=10.1086/321293; RA Bonaglia M.C., Giorda R., Borgatti R., Felisari G., Gagliardi C., RA Selicorni A., Zuffardi O.; RT "Disruption of the ProSAP2 gene in a t(12;22)(q24.1;q13.3) is associated RT with the 22q13.3 deletion syndrome."; RL Am. J. Hum. Genet. 69:261-268(2001). RN [9] 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 [10] 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 [11] RP INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS. RX PubMed=22922660; DOI=10.1016/j.ejmg.2012.07.009; RA Vucurovic K., Landais E., Delahaigue C., Eutrope J., Schneider A., RA Leroy C., Kabbaj H., Motte J., Gaillard D., Rolland A.C., Doco-Fenzy M.; RT "Bipolar affective disorder and early dementia onset in a male patient with RT SHANK3 deletion."; RL Eur. J. Med. Genet. 55:625-629(2012). RN [12] RP INVOLVEMENT IN PHMDS. RX PubMed=23758760; DOI=10.1186/2040-2392-4-18; RA Soorya L., Kolevzon A., Zweifach J., Lim T., Dobry Y., Schwartz L., RA Frank Y., Wang A.T., Cai G., Parkhomenko E., Halpern D., Grodberg D., RA Angarita B., Willner J.P., Yang A., Canitano R., Chaplin W., Betancur C., RA Buxbaum J.D.; RT "Prospective investigation of autism and genotype-phenotype correlations in RT 22q13 deletion syndrome and SHANK3 deficiency."; RL Mol. Autism 4:18-18(2013). RN [13] RP INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS. RX PubMed=24153177; DOI=10.1038/nature12630; RA Han K., Holder J.L. Jr., Schaaf C.P., Lu H., Chen H., Kang H., Tang J., RA Wu Z., Hao S., Cheung S.W., Yu P., Sun H., Breman A.M., Patel A., Lu H.C., RA Zoghbi H.Y.; RT "SHANK3 overexpression causes manic-like behaviour with unique RT pharmacogenetic properties."; RL Nature 503:72-77(2013). RN [14] RP INVOLVEMENT IN PHMDS, FUNCTION IN SYNAPSE FORMATION, AND SUBCELLULAR RP LOCATION. RX PubMed=24132240; DOI=10.1038/nature12618; RA Shcheglovitov A., Shcheglovitova O., Yazawa M., Portmann T., Shu R., RA Sebastiano V., Krawisz A., Froehlich W., Bernstein J.A., Hallmayer J.F., RA Dolmetsch R.E.; RT "SHANK3 and IGF1 restore synaptic deficits in neurons from 22q13 deletion RT syndrome patients."; RL Nature 503:267-271(2013). RN [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-913; THR-1234; SER-1253; RP SER-1636 AND SER-1638, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP INTERACTION WITH CAMK2A. RX PubMed=28130356; DOI=10.1523/jneurosci.2068-16.2017; RA Stephenson J.R., Wang X., Perfitt T.L., Parrish W.P., Shonesy B.C., RA Marks C.R., Mortlock D.P., Nakagawa T., Sutcliffe J.S., Colbran R.J.; RT "Mutation Disrupts Dendritic Morphology and Synaptic Transmission, and RT Causes ASD-Related Behaviors."; RL J. Neurosci. 37:2216-2233(2017). RN [17] RP VARIANTS ARG-321; LEU-341; SER-970; THR-1173; LEU-1263; VAL-1406; THR-1443; RP SER-1557 AND THR-1654, AND INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS. RX PubMed=17999366; DOI=10.1086/522590; RA Moessner R., Marshall C.R., Sutcliffe J.S., Skaug J., Pinto D., Vincent J., RA Zwaigenbaum L., Fernandez B., Roberts W., Szatmari P., Scherer S.W.; RT "Contribution of SHANK3 mutations to autism spectrum disorder."; RL Am. J. Hum. Genet. 81:1289-1297(2007). RN [18] RP VARIANTS CYS-12; GLY-198; THR-224; CYS-300; GLY-963; VAL-1011; HIS-1231; RP GLY-1566 AND THR-1654, INVOLVEMENT IN NEUROPSYCHIATRIC DISORDERS, AND RP CHARACTERIZATION OF VARIANTS CYS-12 AND CYS-300. RX PubMed=17173049; DOI=10.1038/ng1933; RA Durand C.M., Betancur C., Boeckers T.M., Bockmann J., Chaste P., RA Fauchereau F., Nygren G., Rastam M., Gillberg I.C., Anckarsaeter H., RA Sponheim E., Goubran-Botros H., Delorme R., Chabane N., RA Mouren-Simeoni M.-C., de Mas P., Bieth E., Roge B., Heron D., Burglen L., RA Gillberg C., Leboyer M., Bourgeron T.; RT "Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are RT associated with autism spectrum disorders."; RL Nat. Genet. 39:25-27(2007). RN [19] RP VARIANT SCZD15 TRP-536, AND VARIANTS THR-245; GLN-493; THR-720; THR-952; RP VAL-1010; LYS-1298; GLY-1333; VAL-1546 AND THR-1645. RX PubMed=20385823; DOI=10.1073/pnas.0906232107; RA Gauthier J., Champagne N., Lafreniere R.G., Xiong L., Spiegelman D., RA Brustein E., Lapointe M., Peng H., Cote M., Noreau A., Hamdan F.F., RA Addington A.M., Rapoport J.L., Delisi L.E., Krebs M.O., Joober R., RA Fathalli F., Mouaffak F., Haghighi A.P., Neri C., Dube M.P., Samuels M.E., RA Marineau C., Stone E.A., Awadalla P., Barker P.A., Carbonetto S., RA Drapeau P., Rouleau G.A.; RT "De novo mutations in the gene encoding the synaptic scaffolding protein RT SHANK3 in patients ascertained for schizophrenia."; RL Proc. Natl. Acad. Sci. U.S.A. 107:7863-7868(2010). RN [20] RP VARIANTS PHMDS ALA-141 AND SER-1452. RX PubMed=22892527; DOI=10.1038/ejhg.2012.175; RA Boccuto L., Lauri M., Sarasua S.M., Skinner C.D., Buccella D., Dwivedi A., RA Orteschi D., Collins J.S., Zollino M., Visconti P., Dupont B., Tiziano D., RA Schroer R.J., Neri G., Stevenson R.E., Gurrieri F., Schwartz C.E.; RT "Prevalence of SHANK3 variants in patients with different subtypes of RT autism spectrum disorders."; RL Eur. J. Hum. Genet. 21:310-316(2013). 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:24132240}. 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 (By similarity). Interacts with CAMK2A (PubMed:28130356). CC Interacts with DIP2A (By similarity). {ECO:0000250|UniProtKB:Q4ACU6, CC ECO:0000250|UniProtKB:Q9JLU4, ECO:0000269|PubMed:28130356}. CC -!- INTERACTION: CC Q9BYB0; P12814: ACTN1; NbExp=2; IntAct=EBI-1752330, EBI-351710; CC Q9BYB0; Q14155: ARHGEF7; NbExp=2; IntAct=EBI-1752330, EBI-717515; CC Q9BYB0; P21333: FLNA; NbExp=2; IntAct=EBI-1752330, EBI-350432; CC Q9BYB0; P62993: GRB2; NbExp=2; IntAct=EBI-1752330, EBI-401755; CC Q9BYB0; P07910: HNRNPC; NbExp=2; IntAct=EBI-1752330, EBI-357966; CC Q9BYB0; O75525: KHDRBS3; NbExp=3; IntAct=EBI-1752330, EBI-722504; CC Q9BYB0; P16333: NCK1; NbExp=4; IntAct=EBI-1752330, EBI-389883; CC Q9BYB0; Q99435: NELL2; NbExp=2; IntAct=EBI-1752330, EBI-946274; CC Q9BYB0; Q9NRD5: PICK1; NbExp=2; IntAct=EBI-1752330, EBI-79165; CC Q9BYB0; P19174: PLCG1; NbExp=2; IntAct=EBI-1752330, EBI-79387; CC Q9BYB0; P55036: PSMD4; NbExp=2; IntAct=EBI-1752330, EBI-359318; CC Q9BYB0; Q8IXJ6: SIRT2; NbExp=2; IntAct=EBI-1752330, EBI-477232; CC Q9BYB0-1; Q01668: CACNA1D; NbExp=2; IntAct=EBI-20939234, EBI-9207771; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24132240}. CC Postsynaptic density {ECO:0000269|PubMed:24132240}. Cell projection, CC dendritic spine {ECO:0000250}. Note=In neuronal cells, extends into the CC region subjacent to the postsynaptic density (PSD). {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative promoter usage; Named isoforms=2; CC Comment=Additional isoforms seem to exist. These isoforms may be the CC product of multiple intragenic promoter and/or alternative splicing.; CC Name=1; Synonyms=A; CC IsoId=Q9BYB0-1; Sequence=Displayed; CC Name=2; Synonyms=B; CC IsoId=Q9BYB0-3; Sequence=VSP_053605; CC -!- TISSUE SPECIFICITY: Expressed in the cerebral cortex and the CC cerebellum. 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:0000250}. CC -!- DISEASE: Note=A chromosomal aberration involving SHANK3 is found in CC patients with chromosome 22q13.3 deletion syndrome. Translocation CC t(12;22)(q24.1;q13.3) with APPL2/DIP13B. {ECO:0000269|PubMed:11431708}. CC -!- DISEASE: Note=Defects in SHANK3 are associated with neuropsychiatric CC disorders such as autism spectrum disorders (ASD), bipolar affective CC disorders and early dementia onset. ASD are characterized by CC impairments in reciprocal social interaction and communication as well CC as restricted and stereotyped patterns of interest and activities. ASD CC include forms with moderate to severe cognitive impairment and milder CC forms with higher cognitive ability (Asperger syndrome). Gene CC duplication is associated with hyperkinetic neuropsychiatric disorders CC (PubMed:24153177) such as hyperactivity, auditory overstimulation, CC epilepsy and bipolar affective disorders, among others. CC {ECO:0000269|PubMed:24153177}. CC -!- DISEASE: Phelan-McDermid syndrome (PHMDS) [MIM:606232]: A developmental CC disorder with variable features. Common features include neonatal CC hypotonia, global developmental delay, normal to accelerated growth, CC absent to severely delayed speech, autistic behavior, and minor CC dysmorphic features. {ECO:0000269|PubMed:22892527, CC ECO:0000269|PubMed:23758760, ECO:0000269|PubMed:24132240}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Schizophrenia 15 (SCZD15) [MIM:613950]: A complex, CC multifactorial psychotic disorder or group of disorders characterized CC by disturbances in the form and content of thought (e.g. delusions, CC hallucinations), in mood (e.g. inappropriate affect), in sense of self CC and relationship to the external world (e.g. loss of ego boundaries, CC withdrawal), and in behavior (e.g bizarre or apparently purposeless CC behavior). Although it affects emotions, it is distinguished from mood CC disorders in which such disturbances are primary. Similarly, there may CC be mild impairment of cognitive function, and it is distinguished from CC the dementias in which disturbed cognitive function is considered CC primary. Some patients manifest schizophrenic as well as bipolar CC disorder symptoms and are often given the diagnosis of schizoaffective CC disorder. {ECO:0000269|PubMed:20385823}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- MISCELLANEOUS: [Isoform 1]: Primarily expressed in neurons. CC -!- MISCELLANEOUS: [Isoform 2]: Produced by alternative promoter usage. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AC000050; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC000036; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB051437; BAB33320.1; -; mRNA. DR EMBL; AK074038; BAB84864.1; -; mRNA. DR EMBL; AB569469; BAJ09793.1; -; mRNA. DR RefSeq; NP_277052.1; NM_033517.1. DR PDB; 6CPK; NMR; -; A=471-530. DR PDB; 7C7I; X-ray; 2.28 A; C/D=1-99. DR PDB; 7C7J; X-ray; 2.39 A; C/D=1-99. DR PDBsum; 6CPK; -. DR PDBsum; 7C7I; -. DR PDBsum; 7C7J; -. DR AlphaFoldDB; Q9BYB0; -. DR SMR; Q9BYB0; -. DR BioGRID; 124487; 173. DR CORUM; Q9BYB0; -. DR DIP; DIP-52267N; -. DR IntAct; Q9BYB0; 191. DR MINT; Q9BYB0; -. DR STRING; 9606.ENSP00000489407; -. DR TCDB; 8.A.28.1.7; the ankyrin (ankyrin) family. DR CarbonylDB; Q9BYB0; -. DR iPTMnet; Q9BYB0; -. DR PhosphoSitePlus; Q9BYB0; -. DR BioMuta; SHANK3; -. DR DMDM; 148887434; -. DR jPOST; Q9BYB0; -. DR MassIVE; Q9BYB0; -. DR PeptideAtlas; Q9BYB0; -. DR ProteomicsDB; 79606; -. [Q9BYB0-1] DR ABCD; Q9BYB0; 2 sequenced antibodies. DR AGR; HGNC:14294; -. DR GeneCards; SHANK3; -. DR GeneReviews; SHANK3; -. DR HGNC; HGNC:14294; SHANK3. DR MalaCards; SHANK3; -. DR MIM; 606230; gene. DR MIM; 606232; phenotype. DR MIM; 613950; phenotype. DR neXtProt; NX_Q9BYB0; -. DR Orphanet; 48652; Monosomy 22q13.3. DR Orphanet; 106; NON RARE IN EUROPE: Autism. DR InParanoid; Q9BYB0; -. DR PathwayCommons; Q9BYB0; -. DR Reactome; R-HSA-6794361; Neurexins and neuroligins. DR Reactome; R-HSA-8853659; RET signaling. DR SignaLink; Q9BYB0; -. DR SIGNOR; Q9BYB0; -. DR BioGRID-ORCS; 85358; 13 hits in 309 CRISPR screens. DR ChiTaRS; SHANK3; human. DR GeneWiki; SHANK3; -. DR GenomeRNAi; 85358; -. DR Pharos; Q9BYB0; Tbio. DR PRO; PR:Q9BYB0; -. DR Proteomes; UP000005640; Unplaced. DR RNAct; Q9BYB0; Protein. 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; IBA:GO_Central. DR GO; GO:0043005; C:neuron projection; ISS:BHF-UCL. DR GO; GO:0044309; C:neuron spine; 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:0003779; F:actin binding; IEA:UniProtKB-KW. DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISS:BHF-UCL. DR GO; GO:0043621; F:protein self-association; ISS:BHF-UCL. DR GO; GO:0097110; F:scaffold protein binding; ISS:BHF-UCL. DR GO; GO:0017124; F:SH3 domain binding; ISS:BHF-UCL. DR GO; GO:0030160; F:synaptic receptor adaptor activity; ISS:BHF-UCL. DR GO; GO:0008270; F:zinc ion binding; ISS:BHF-UCL. DR GO; GO:0030534; P:adult behavior; IMP:BHF-UCL. DR GO; GO:0097113; P:AMPA glutamate receptor clustering; ISS:BHF-UCL. DR GO; GO:0048854; P:brain morphogenesis; ISS:BHF-UCL. DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:BHF-UCL. DR GO; GO:0097117; P:guanylate kinase-associated protein clustering; ISS:BHF-UCL. DR GO; GO:0007612; P:learning; IMP:BHF-UCL. 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: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; ISS:BHF-UCL. 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:0061001; P:regulation of dendritic spine morphogenesis; 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:0035176; P:social behavior; IMP: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; IMP:BHF-UCL. DR GO; GO:0071625; P:vocalization behavior; IMP:BHF-UCL. DR CDD; cd17177; FERM_F0_SHANK3; 1. DR CDD; cd00992; PDZ_signaling; 1. DR CDD; cd09506; SAM_Shank1_2_3; 1. DR CDD; cd11984; SH3_Shank3; 1. DR Gene3D; 2.30.42.10; -; 1. DR Gene3D; 1.25.40.20; Ankyrin repeat-containing domain; 2. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 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 PANTHER; PTHR24135; SH3 AND MULTIPLE ANKYRIN REPEAT DOMAINS PROTEIN; 1. DR PANTHER; PTHR24135:SF4; SH3 AND MULTIPLE ANKYRIN REPEAT DOMAINS PROTEIN 3; 1. 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; 5. DR SMART; SM00228; PDZ; 1. DR SMART; SM00454; SAM; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF48403; Ankyrin repeat; 1. DR SUPFAM; SSF50156; PDZ domain-like; 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR SUPFAM; SSF50044; SH3-domain; 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; ANK repeat; KW Autism spectrum disorder; Cell projection; Chromosomal rearrangement; KW Coiled coil; Cytoplasm; Disease variant; Methylation; Phosphoprotein; KW Reference proteome; Repeat; Schizophrenia; SH3 domain; SH3-binding; KW Synapse. FT CHAIN 1..1731 FT /note="SH3 and multiple ankyrin repeat domains protein 3" FT /id="PRO_0000174675" FT REPEAT 148..178 FT /note="ANK 1" FT REPEAT 182..211 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 471..530 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT DOMAIN 571..665 FT /note="PDZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143" FT DOMAIN 1668..1731 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT REGION 1..75 FT /note="Intramolecular interaction with the ANK repeats" FT /evidence="ECO:0000250" FT REGION 407..467 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 665..689 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 678..685 FT /note="Required for interaction with ABI1" FT /evidence="ECO:0000250" FT REGION 760..853 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 871..1021 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1115..1460 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1475..1525 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1546..1584 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1627..1664 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 1494..1514 FT /evidence="ECO:0000255" FT MOTIF 1410..1416 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 439..465 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 779..793 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 810..847 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1175..1193 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1327..1348 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1367..1400 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1495..1509 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1638..1658 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:0000250|UniProtKB:Q4ACU6" FT MOD_RES 388 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 395 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JLU4" FT MOD_RES 483 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 556 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 695 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 782 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 791 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 802 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:0007744|PubMed:24275569" FT MOD_RES 931 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:Q9JLU4" FT MOD_RES 966 FT /note="Asymmetric dimethylarginine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1129 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1133 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1158 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087" FT MOD_RES 1162 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18088087" FT MOD_RES 1165 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1234 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1253 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:24275569" FT MOD_RES 1420 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JLU4" FT MOD_RES 1510 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1521 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1529 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1539 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1634 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q4ACU6" FT MOD_RES 1636 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 1638 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT VAR_SEQ 1..119 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_053605" FT VARIANT 12 FT /note="R -> C (found in patients with neuropsychiatric FT disorders; uncertain significance; disrupts synaptic FT localization; dbSNP:rs1336089966)" FT /evidence="ECO:0000269|PubMed:17173049" FT /id="VAR_032804" FT VARIANT 141 FT /note="P -> A (in PHMDS; dbSNP:rs397514705)" FT /evidence="ECO:0000269|PubMed:22892527" FT /id="VAR_070259" FT VARIANT 198 FT /note="A -> G (in dbSNP:rs1232069989)" FT /evidence="ECO:0000269|PubMed:17173049" FT /id="VAR_032805" FT VARIANT 224 FT /note="A -> T (in dbSNP:rs766856815)" FT /evidence="ECO:0000269|PubMed:17173049" FT /id="VAR_032806" FT VARIANT 245 FT /note="I -> T (in dbSNP:rs9616915)" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_032807" FT VARIANT 300 FT /note="R -> C (found in patients with neuropsychiatric FT disorders; uncertain significance; disrupts synaptic FT localization; dbSNP:rs376862893)" FT /evidence="ECO:0000269|PubMed:17173049" FT /id="VAR_032808" FT VARIANT 321 FT /note="Q -> R (found in a patient with neuropsychiatric FT disorders; uncertain significance)" FT /evidence="ECO:0000269|PubMed:17999366" FT /id="VAR_070260" FT VARIANT 341 FT /note="S -> L (found in patient with neuropsychiatric FT disorders; uncertain significance; dbSNP:rs1314696433)" FT /evidence="ECO:0000269|PubMed:17999366" FT /id="VAR_070261" FT VARIANT 493 FT /note="H -> Q" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065799" FT VARIANT 536 FT /note="R -> W (in SCZD15; dbSNP:rs387906933)" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065800" FT VARIANT 720 FT /note="A -> T" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065801" FT VARIANT 952 FT /note="S -> T (in dbSNP:rs1340094921)" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065802" FT VARIANT 963 FT /note="A -> G" FT /evidence="ECO:0000269|PubMed:17173049" FT /id="VAR_070262" FT VARIANT 970 FT /note="A -> S (found in a patient with neuropsychiatric FT disorders; uncertain significance; dbSNP:rs530255181)" FT /evidence="ECO:0000269|PubMed:17999366" FT /id="VAR_070263" FT VARIANT 1010 FT /note="G -> V" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065803" FT VARIANT 1011 FT /note="G -> V (in dbSNP:rs767058690)" FT /evidence="ECO:0000269|PubMed:17173049" FT /id="VAR_070264" FT VARIANT 1134 FT /note="P -> H (in dbSNP:rs769454362)" FT /id="VAR_065804" FT VARIANT 1173 FT /note="A -> T (found in a patient with neuropsychiatric FT disorders; uncertain significance; dbSNP:rs139686326)" FT /evidence="ECO:0000269|PubMed:17999366" FT /id="VAR_070265" FT VARIANT 1231 FT /note="R -> H (in dbSNP:rs750186589)" FT /evidence="ECO:0000269|PubMed:17173049" FT /id="VAR_070266" FT VARIANT 1263 FT /note="P -> L (found in a patient with neuropsychiatric FT disorders; uncertain significance; dbSNP:rs757572910)" FT /evidence="ECO:0000269|PubMed:17999366" FT /id="VAR_070267" FT VARIANT 1298 FT /note="R -> K (in dbSNP:rs201483867)" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065805" FT VARIANT 1333 FT /note="V -> G (in dbSNP:rs200087210)" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065806" FT VARIANT 1406 FT /note="L -> V (found in a patient with neuropsychiatric FT disorders; uncertain significance; dbSNP:rs201973139)" FT /evidence="ECO:0000269|PubMed:17999366" FT /id="VAR_070268" FT VARIANT 1443 FT /note="M -> T (found in a patient with neuropsychiatric FT disorders; uncertain significance; dbSNP:rs773395828)" FT /evidence="ECO:0000269|PubMed:17999366" FT /id="VAR_070269" FT VARIANT 1452 FT /note="A -> S (in PHMDS)" FT /evidence="ECO:0000269|PubMed:22892527" FT /id="VAR_070270" FT VARIANT 1546 FT /note="I -> V (in dbSNP:rs1389307970)" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065807" FT VARIANT 1557 FT /note="G -> S (found in a patient with neuropsychiatric FT disorders; uncertain significance; dbSNP:rs1224063430)" FT /evidence="ECO:0000269|PubMed:17999366" FT /id="VAR_070271" FT VARIANT 1566 FT /note="S -> G (in dbSNP:rs1481014682)" FT /evidence="ECO:0000269|PubMed:17173049" FT /id="VAR_070272" FT VARIANT 1645 FT /note="P -> T" FT /evidence="ECO:0000269|PubMed:20385823" FT /id="VAR_065808" FT VARIANT 1654 FT /note="P -> T (found in patients with neuropsychiatric FT disorders; uncertain significance; dbSNP:rs749130556)" FT /evidence="ECO:0000269|PubMed:17173049, FT ECO:0000269|PubMed:17999366" FT /id="VAR_070273" FT STRAND 9..15 FT /evidence="ECO:0007829|PDB:7C7I" FT HELIX 16..18 FT /evidence="ECO:0007829|PDB:7C7I" FT STRAND 20..26 FT /evidence="ECO:0007829|PDB:7C7I" FT HELIX 32..42 FT /evidence="ECO:0007829|PDB:7C7I" FT TURN 43..45 FT /evidence="ECO:0007829|PDB:7C7I" FT HELIX 50..52 FT /evidence="ECO:0007829|PDB:7C7I" FT STRAND 53..57 FT /evidence="ECO:0007829|PDB:7C7I" FT STRAND 70..73 FT /evidence="ECO:0007829|PDB:7C7J" FT HELIX 74..76 FT /evidence="ECO:0007829|PDB:7C7I" FT STRAND 81..85 FT /evidence="ECO:0007829|PDB:7C7I" FT STRAND 87..92 FT /evidence="ECO:0007829|PDB:7C7I" FT STRAND 476..478 FT /evidence="ECO:0007829|PDB:6CPK" FT STRAND 486..489 FT /evidence="ECO:0007829|PDB:6CPK" FT STRAND 497..503 FT /evidence="ECO:0007829|PDB:6CPK" FT STRAND 505..513 FT /evidence="ECO:0007829|PDB:6CPK" FT STRAND 516..521 FT /evidence="ECO:0007829|PDB:6CPK" FT HELIX 522..524 FT /evidence="ECO:0007829|PDB:6CPK" FT STRAND 525..527 FT /evidence="ECO:0007829|PDB:6CPK" SQ SEQUENCE 1731 AA; 184667 MW; 781936CE60988D08 CRC64; MDGPGASAVV VRVGIPDLQQ TKCLRLDPAA PVWAAKQRVL CALNHSLQDA LNYGLFQPPS RGRAGKFLDE ERLLQEYPPN LDTPLPYLEF RYKRRVYAQN LIDDKQFAKL HTKANLKKFM DYVQLHSTDK VARLLDKGLD PNFHDPDSGE CPLSLAAQLD NATDLLKVLK NGGAHLDFRT RDGLTAVHCA TRQRNAAALT TLLDLGASPD YKDSRGLTPL YHSALGGGDA LCCELLLHDH AQLGITDENG WQEIHQACRF GHVQHLEHLL FYGADMGAQN ASGNTALHIC ALYNQESCAR VLLFRGANRD VRNYNSQTAF QVAIIAGNFE LAEVIKTHKD SDVVPFRETP SYAKRRRLAG PSGLASPRPL QRSASDINLK GEAQPAASPG PSLRSLPHQL LLQRLQEEKD RDRDADQESN ISGPLAGRAG QSKISPSGPG GPGPAPGPGP APPAPPAPPP RGPKRKLYSA VPGRKFIAVK AHSPQGEGEI PLHRGEAVKV LSIGEGGFWE GTVKGRTGWF PADCVEEVQM RQHDTRPETR EDRTKRLFRH YTVGSYDSLT SHSDYVIDDK VAVLQKRDHE GFGFVLRGAK AETPIEEFTP TPAFPALQYL ESVDVEGVAW RAGLRTGDFL IEVNGVNVVK VGHKQVVALI RQGGNRLVMK VVSVTRKPEE DGARRRAPPP PKRAPSTTLT LRSKSMTAEL EELASIRRRK GEKLDEMLAA AAEPTLRPDI ADADSRAATV KQRPTSRRIT PAEISSLFER QGLPGPEKLP GSLRKGIPRT KSVGEDEKLA SLLEGRFPRS TSMQDPVREG RGIPPPPQTA PPPPPAPYYF DSGPPPAFSP PPPPGRAYDT VRSSFKPGLE ARLGAGAAGL YEPGAALGPL PYPERQKRAR SMIILQDSAP ESGDAPRPPP AATPPERPKR RPRPPGPDSP YANLGAFSAS LFAPSKPQRR KSPLVKQLQV EDAQERAALA VGSPGPGGGS FAREPSPTHR GPRPGGLDYG AGDGPGLAFG GPGPAKDRRL EERRRSTVFL SVGAIEGSAP GADLPSLQPS RSIDERLLGT GPTAGRDLLL PSPVSALKPL VSGPSLGPSG STFIHPLTGK PLDPSSPLAL ALAARERALA SQAPSRSPTP VHSPDADRPG PLFVDVQARD PERGSLASPA FSPRSPAWIP VPARREAEKV PREERKSPED KKSMILSVLD TSLQRPAGLI VVHATSNGQE PSRLGGAEEE RPGTPELAPA PMQSAAVAEP LPSPRAQPPG GTPADAGPGQ GSSEEEPELV FAVNLPPAQL SSSDEETREE LARIGLVPPP EEFANGVLLA TPLAGPGPSP TTVPSPASGK PSSEPPPAPE SAADSGVEEA DTRSSSDPHL ETTSTISTVS SMSTLSSESG ELTDTHTSFA DGHTFLLEKP PVPPKPKLKS PLGKGPVTFR DPLLKQSSDS ELMAQQHHAA SAGLASAAGP ARPRYLFQRR SKLWGDPVES RGLPGPEDDK PTVISELSSR LQQLNKDTRS LGEEPVGGLG SLLDPAKKSP IAAARLFSSL GELSSISAQR SPGGPGGGAS YSVRPSGRYP VARRAPSPVK PASLERVEGL GAGAGGAGRP FGLTPPTILK SSSLSIPHEP KEVRFVVRSV SARSRSPSPS PLPSPASGPG PGAPGPRRPF QQKPLQLWSK FDVGDWLESI HLGEHRDRFE DHEIEGAHLP ALTKDDFVEL GVTRVGHRMN IERALRQLDG S //