ID DISC1_HUMAN Reviewed; 854 AA. AC Q9NRI5; A6NLH2; C4P091; C4P095; C4P0A1; C4P0A3; C4P0B3; C4P0B6; AC C4P0C1; C9J6D0; O75045; Q5VT44; Q5VT45; Q8IXJ0; Q8IXJ1; Q9BX19; AC Q9NRI3; Q9NRI4; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 13-NOV-2007, sequence version 3. DT 07-JAN-2015, entry version 124. DE RecName: Full=Disrupted in schizophrenia 1 protein; GN Name=DISC1; Synonyms=KIAA0457; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANTS RP GLN-264 AND CYS-704. RX PubMed=10814723; DOI=10.1093/hmg/9.9.1415; RA Millar J.K., Wilson-Annan J.C., Anderson S., Christie S., Taylor M.S., RA Semple C.A.M., Devon R.S., St Clair D.M., Muir W.J., Blackwood D.H.R., RA Porteous D.J.; RT "Disruption of two novel genes by a translocation co-segregating with RT schizophrenia."; RL Hum. Mol. Genet. 9:1415-1423(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), AND VARIANT GLN-264. RC TISSUE=Fetal heart; RX PubMed=12573262; DOI=10.1016/S0888-7543(02)00026-5; RA Taylor M.S., Devon R.S., Millar J.K., Porteous D.J.; RT "Evolutionary constraints on the Disrupted in Schizophrenia locus."; RL Genomics 81:67-77(2003). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT RP GLN-264. RC TISSUE=Brain; RX PubMed=9455484; DOI=10.1093/dnares/4.5.345; RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., RA Nomura N., Ohara O.; RT "Characterization of cDNA clones in size-fractionated cDNA libraries RT from human brain."; RL DNA Res. 4:345-349(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5; 6; 7; 8; 9; 10 AND 11), AND RP ALTERNATIVE SPLICING. RC TISSUE=Brain; RX PubMed=19805229; DOI=10.1073/pnas.0903413106; RA Nakata K., Lipska B.K., Hyde T.M., Ye T., Newburn E.N., Morita Y., RA Vakkalanka R., Barenboim M., Sei Y., Weinberger D.R., Kleinman J.E.; RT "DISC1 splice variants are upregulated in schizophrenia and associated RT with risk polymorphisms."; RL Proc. Natl. Acad. Sci. U.S.A. 106:15873-15878(2009). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] RP INVOLVEMENT IN SUSCEPTIBILITY TO SCZD9. RX PubMed=11468279; DOI=10.1093/hmg/10.15.1611; RA Ekelund J., Hovatta I., Parker A., Paunio T., Varilo T., Martin R., RA Suhonen J., Ellonen P., Chan G., Sinsheimer J.S., Sobel E., RA Juvonen H., Arajaervi R., Partonen T., Suvisaari J., Loennqvist J., RA Meyer J., Peltonen L.; RT "Chromosome 1 loci in Finnish schizophrenia families."; RL Hum. Mol. Genet. 10:1611-1617(2001). RN [7] RP INTERACTION WITH ACTN2; ANKHD1; ATF4; ATF5; CEP63; EIF3S3; MAP1A; RP MICROTUBULES; NDEL1; RANBP9; SPTBN4; SYNE1 AND TRAF3IP1, AND RP SUBCELLULAR LOCATION. RX PubMed=12812986; DOI=10.1093/hmg/ddg162; RA Morris J.A., Kandpal G., Ma L., Austin C.P.; RT "DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated RT protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation RT and loss of interaction with mutation."; RL Hum. Mol. Genet. 12:1591-1608(2003). RN [8] RP INVOLVEMENT IN SUSCEPTIBILITY TO SCZD9. RX PubMed=14532331; DOI=10.1093/hmg/ddg341; RA Hennah W., Varilo T., Kestilae M., Paunio T., Arajaervi R., Haukka J., RA Parker A., Martin R., Levitzky S., Partonen T., Meyer J., RA Loennqvist J., Peltonen L., Ekelund J.; RT "Haplotype transmission analysis provides evidence of association for RT DISC1 to schizophrenia and suggests sex-dependent effects."; RL Hum. Mol. Genet. 12:3151-3159(2003). RN [9] RP INTERACTION WITH NDEL1, AND SUBCELLULAR LOCATION. RX PubMed=12506198; DOI=10.1073/pnas.0136913100; RA Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., RA Okawa M., Yamada N., Hatten M.E., Snyder S.H., Ross C.A., Sawa A.; RT "Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents RT binding to NudE-like (NUDEL) and inhibits neurite outgrowth."; RL Proc. Natl. Acad. Sci. U.S.A. 100:289-294(2003). RN [10] RP ERRATUM. RA Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., RA Okawa M., Yamada N., Hatten M.E., Snyder S.H., Ross C.A., Sawa A.; RL Proc. Natl. Acad. Sci. U.S.A. 101:13969-13969(2004). RN [11] RP INVOLVEMENT IN SUSCEPTIBILITY TO SCZD, AND VARIANTS VAL-5 AND PHE-607. RX PubMed=15386212; DOI=10.1086/425586; RA Hodgkinson C.A., Goldman D., Jaeger J., Persaud S., Kane J.M., RA Lipsky R.H., Malhotra A.K.; RT "Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, RT schizoaffective disorder, and bipolar disorder."; RL Am. J. Hum. Genet. 75:862-872(2004). RN [12] RP INTERACTION WITH TUBULIN ALPHA; NDEL1 AND PAFAH1B1, SUBCELLULAR RP LOCATION, AND MUTAGENESIS OF LEU-815 AND LEU-822. RX PubMed=14962739; DOI=10.1016/j.mcn.2003.09.009; RA Brandon N.J., Handford E.J., Schurov I., Rain J.-C., Pelling M., RA Duran-Jimeniz B., Camargo L.M., Oliver K.R., Beher D., Shearman M.S., RA Whiting P.J.; RT "Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally RT regulated protein complex: implications for schizophrenia and other RT major neurological disorders."; RL Mol. Cell. Neurosci. 25:42-55(2004). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=15797709; DOI=10.1016/j.mcn.2004.11.003; RA Brandon N.J., Schurov I., Camargo L.M., Handford E.J., RA Duran-Jimeniz B., Hunt P., Millar J.K., Porteous D.J., Shearman M.S., RA Whiting P.J.; RT "Subcellular targeting of DISC1 is dependent on a domain independent RT from the Nudel binding site."; RL Mol. Cell. Neurosci. 28:613-624(2005). RN [14] RP INVOLVEMENT IN SUSCEPTIBILITY TO SCZD9, AND VARIANT CYS-704. RX PubMed=15939883; DOI=10.1073/pnas.0500515102; RA Callicott J.H., Straub R.E., Pezawas L., Egan M.F., Mattay V.S., RA Hariri A.R., Verchinski B.A., Meyer-Lindenberg A., Balkissoon R., RA Kolachana B., Goldberg T.E., Weinberger D.R.; RT "Variation in DISC1 affects hippocampal structure and function and RT increases risk for schizophrenia."; RL Proc. Natl. Acad. Sci. U.S.A. 102:8627-8632(2005). RN [15] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=16510495; DOI=10.1093/hmg/ddl040; RA Lipska B.K., Peters T., Hyde T.M., Halim N., Horowitz C., Mitkus S., RA Weickert C.S., Matsumoto M., Sawa A., Straub R.E., Vakkalanka R., RA Herman M.M., Weinberger D.R., Kleinman J.E.; RT "Expression of DISC1 binding partners is reduced in schizophrenia and RT associated with DISC1 SNPs."; RL Hum. Mol. Genet. 15:1245-1258(2006). RN [16] RP INTERACTION WITH NDEL1. RX PubMed=17035248; DOI=10.1093/hmg/ddl407; RA Kamiya A., Tomoda T., Chang J., Takaki M., Zhan C., Morita M., RA Cascio M.B., Elashvili S., Koizumi H., Takanezawa Y., Dickerson F., RA Yolken R., Arai H., Sawa A.; RT "DISC1-NDEL1/NUDEL protein interaction, an essential component for RT neurite outgrowth, is modulated by genetic variations of DISC1."; RL Hum. Mol. Genet. 15:3313-3323(2006). RN [17] RP FUNCTION, INTERACTION WITH PCNT, AND SUBCELLULAR LOCATION. RX PubMed=18955030; DOI=10.1016/j.bbrc.2008.10.100; RA Shimizu S., Matsuzaki S., Hattori T., Kumamoto N., Miyoshi K., RA Katayama T., Tohyama M.; RT "DISC1-kendrin interaction is involved in centrosomal microtubule RT network formation."; RL Biochem. Biophys. Res. Commun. 377:1051-1056(2008). RN [18] RP FUNCTION. RX PubMed=19502360; DOI=10.1093/hmg/ddp266; RA Meyer K.D., Morris J.A.; RT "Disc1 regulates granule cell migration in the developing RT hippocampus."; RL Hum. Mol. Genet. 18:3286-3297(2009). RN [19] RP FUNCTION. RX PubMed=19303846; DOI=10.1016/j.cell.2008.12.044; RA Mao Y., Ge X., Frank C.L., Madison J.M., Koehler A.N., Doud M.K., RA Tassa C., Berry E.M., Soda T., Singh K.K., Biechele T., RA Petryshen T.L., Moon R.T., Haggarty S.J., Tsai L.H.; RT "Disrupted in schizophrenia 1 regulates neuronal progenitor RT proliferation via modulation of GSK3beta/beta-catenin signaling."; RL Cell 136:1017-1031(2009). RN [20] RP INTERACTION WITH CHCHD6. RX PubMed=22228767; DOI=10.1074/jbc.M111.277103; RA An J., Shi J., He Q., Lui K., Liu Y., Huang Y., Sheikh M.S.; RT "CHCM1/CHCHD6, a novel mitochondrial protein linked to regulation of RT mitofilin and mitochondrial cristae morphology."; RL J. Biol. Chem. 287:7411-7426(2012). CC -!- FUNCTION: Involved in the regulation of multiple aspects of CC embryonic and adult neurogenesis. Required for neural progenitor CC proliferation in the ventrical/subventrical zone during embryonic CC brain development and in the adult dentate gyrus of the CC hippocampus. Participates in the Wnt-mediated neural progenitor CC proliferation as a positive regulator by modulating GSK3B activity CC and CTNNB1 abundance. Plays a role as a modulator of the AKT-mTOR CC signaling pathway controlling the tempo of the process of newborn CC neurons integration during adult neurogenesis, including neuron CC positioning, dendritic development and synapse formation. Inhibits CC the activation of AKT-mTOR signaling upon interaction with CC CCDC88A. Regulates the migration of early-born granule cell CC precursors toward the dentate gyrus during the hippocampal CC development. Plays a role, together with PCNT, in the microtubule CC network formation. {ECO:0000269|PubMed:18955030, CC ECO:0000269|PubMed:19303846, ECO:0000269|PubMed:19502360}. CC -!- SUBUNIT: Interacts with NDEL1 (PubMed:12506198). Interacts with CC CCDC88A (via C-terminus); the interaction is direct. Interacts CC with GSK3B (By similarity). Interacts with tubulin alpha, ACTN2, CC ANKHD1, ATF4, ATF5, CEP63, EIF3S3, MAP1A, NDEL1, PAFAH1B1, RANBP9, CC SPTBN4, SYNE1 and TRAF3IP1 (PubMed:12812986). Interaction with CC microtubules may be mediated in part by TRAF3IP1. Interacts (via CC C-terminal) with PCNT (PubMed:18955030). Interacts with CHCHD6 CC (PubMed:22228767). Interacts with CCDC141 (By similarity). CC {ECO:0000250|UniProtKB:Q811T9, ECO:0000269|PubMed:12506198, CC ECO:0000269|PubMed:12812986, ECO:0000269|PubMed:14962739, CC ECO:0000269|PubMed:17035248, ECO:0000269|PubMed:18955030, CC ECO:0000269|PubMed:22228767}. CC -!- INTERACTION: CC P35609:ACTN2; NbExp=3; IntAct=EBI-529989, EBI-77797; CC Q8IWZ3-1:ANKHD1; NbExp=6; IntAct=EBI-529989, EBI-1785446; CC P18848:ATF4; NbExp=3; IntAct=EBI-529989, EBI-492498; CC Q9Y2D1:ATF5; NbExp=8; IntAct=EBI-529989, EBI-492509; CC Q6VMQ6:ATF7IP; NbExp=3; IntAct=EBI-529989, EBI-928732; CC Q6ZP82:CCDC141; NbExp=5; IntAct=EBI-529989, EBI-928795; CC Q96MT8:CEP63; NbExp=7; IntAct=EBI-529989, EBI-741977; CC P10909:CLU; NbExp=4; IntAct=EBI-529989, EBI-1104674; CC P12110:COL6A2; NbExp=3; IntAct=EBI-529989, EBI-928749; CC Q13561:DCTN2; NbExp=3; IntAct=EBI-529989, EBI-715074; CC Q03001:DST; NbExp=5; IntAct=EBI-529989, EBI-310758; CC Q14204:DYNC1H1; NbExp=3; IntAct=EBI-529989, EBI-356015; CC O15372:EIF3H; NbExp=8; IntAct=EBI-529989, EBI-709735; CC Q15811:ITSN1; NbExp=3; IntAct=EBI-529989, EBI-602041; CC Q9Y496:KIF3A; NbExp=3; IntAct=EBI-529989, EBI-1104844; CC Q9UPN3:MACF1; NbExp=5; IntAct=EBI-529989, EBI-522925; CC P78559:MAP1A; NbExp=3; IntAct=EBI-529989, EBI-929047; CC Q9GZM8:NDEL1; NbExp=13; IntAct=EBI-529989, EBI-928842; CC Q99784:OLFM1; NbExp=3; IntAct=EBI-529989, EBI-1105073; CC O95613:PCNT; NbExp=5; IntAct=EBI-529989, EBI-530012; CC Q96S59:RANBP9; NbExp=6; IntAct=EBI-529989, EBI-636085; CC Q01082:SPTBN1; NbExp=3; IntAct=EBI-529989, EBI-351561; CC Q9H254:SPTBN4; NbExp=3; IntAct=EBI-529989, EBI-308543; CC Q8NF91:SYNE1; NbExp=6; IntAct=EBI-529989, EBI-928867; CC Q8TDR0:TRAF3IP1; NbExp=10; IntAct=EBI-529989, EBI-928811; CC O75962:TRIO; NbExp=3; IntAct=EBI-529989, EBI-718519; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasm, cytoskeleton. CC Cytoplasm, cytoskeleton, microtubule organizing center, CC centrosome. Cell junction, synapse, postsynaptic cell membrane, CC postsynaptic density {ECO:0000250}. Note=Colocalizes with NDEL1 in CC the perinuclear region and the centrosome (By similarity). CC Localizes to punctate cytoplasmic foci which overlap in part with CC mitochondria. Colocalizes with PCNT at the centrosome. CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=11; CC Comment=Additional isoforms seem to exist. More than 50 CC different isoforms are produced in the brain.; CC Name=1; Synonyms=L; CC IsoId=Q9NRI5-1; Sequence=Displayed; CC Name=2; Synonyms=LV; CC IsoId=Q9NRI5-2; Sequence=VSP_003849; CC Name=3; Synonyms=S; CC IsoId=Q9NRI5-3; Sequence=VSP_019316, VSP_019317; CC Name=4; Synonyms=ES; CC IsoId=Q9NRI5-4; Sequence=VSP_019314, VSP_019315; CC Name=5; Synonyms=26; CC IsoId=Q9NRI5-5; Sequence=VSP_043214; CC Name=6; CC IsoId=Q9NRI5-6; Sequence=VSP_043585, VSP_043586; CC Name=7; CC IsoId=Q9NRI5-7; Sequence=VSP_043583, VSP_043584, VSP_043586; CC Name=8; CC IsoId=Q9NRI5-8; Sequence=VSP_043587, VSP_043588; CC Name=9; CC IsoId=Q9NRI5-9; Sequence=VSP_047530, VSP_047531; CC Name=10; CC IsoId=Q9NRI5-10; Sequence=VSP_047526, VSP_047527; CC Name=11; CC IsoId=Q9NRI5-11; Sequence=VSP_047525, VSP_047528, VSP_047529; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in the dentate CC gyrus of the hippocampus. Also expressed in the temporal and CC parahippocampal cortices and cells of the white matter. CC {ECO:0000269|PubMed:16510495}. CC -!- DEVELOPMENTAL STAGE: Expression rises within the dentate gyrus and CC temporal cortex from the neonatal period to infancy, declines CC markedly in adolescence, and declines further with aging. CC {ECO:0000269|PubMed:16510495}. CC -!- DISEASE: Note=A chromosomal aberration involving DISC1 segregates CC with schizophrenia and related psychiatric disorders in a large CC Scottish family. Translocation t(1;11)(q42.1;q14.3). The truncated CC DISC1 protein produced by this translocation is unable to interact CC with ATF4, ATF5 and NDEL1. CC -!- DISEASE: Schizophrenia 9 (SCZD9) [MIM:604906]: A complex, CC multifactorial psychotic disorder or group of disorders CC characterized by disturbances in the form and content of thought CC (e.g. delusions, hallucinations), in mood (e.g. inappropriate CC affect), in sense of self and relationship to the external world CC (e.g. loss of ego boundaries, withdrawal), and in behavior (e.g CC bizarre or apparently purposeless behavior). Although it affects CC emotions, it is distinguished from mood disorders in which such CC disturbances are primary. Similarly, there may be mild impairment CC of cognitive function, and it is distinguished from the dementias CC in which disturbed cognitive function is considered primary. Some CC patients manifest schizophrenic as well as bipolar disorder CC symptoms and are often given the diagnosis of schizoaffective CC disorder. {ECO:0000269|PubMed:11468279, CC ECO:0000269|PubMed:14532331, ECO:0000269|PubMed:15939883}. CC Note=Disease susceptibility is associated with variations CC affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAA32302.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305}; CC Sequence=CAH70955.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=CAI15677.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=CAI17204.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=CAI21886.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=CAI22543.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC Sequence=CAI23013.1; Type=Erroneous gene model prediction; Evidence={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; AF222983; AAF73874.1; -; Genomic_DNA. DR EMBL; AF222987; AAF73877.1; -; Genomic_DNA. DR EMBL; AF222980; AAF73889.1; -; mRNA. DR EMBL; AJ506178; CAD44628.1; -; mRNA. DR EMBL; AJ506177; CAD44631.1; -; mRNA. DR EMBL; AB007926; BAA32302.1; ALT_INIT; mRNA. DR EMBL; FJ804174; ACR40040.1; -; mRNA. DR EMBL; FJ804178; ACR40044.1; -; mRNA. DR EMBL; FJ804180; ACR40046.1; -; mRNA. DR EMBL; FJ804182; ACR40048.1; -; mRNA. DR EMBL; FJ804184; ACR40050.1; -; mRNA. DR EMBL; FJ804186; ACR40052.1; -; mRNA. DR EMBL; FJ804190; ACR40056.1; -; mRNA. DR EMBL; FJ804191; ACR40057.1; -; mRNA. DR EMBL; FJ804196; ACR40062.1; -; mRNA. DR EMBL; FJ804197; ACR40063.1; -; mRNA. DR EMBL; FJ804199; ACR40065.1; -; mRNA. DR EMBL; FJ804200; ACR40066.1; -; mRNA. DR EMBL; FJ804203; ACR40069.1; -; mRNA. DR EMBL; FJ804204; ACR40070.1; -; mRNA. DR EMBL; FJ804205; ACR40071.1; -; mRNA. DR EMBL; FJ804208; ACR40074.1; -; mRNA. DR EMBL; FJ804212; ACR40078.1; -; mRNA. DR EMBL; AL626763; CAH70955.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL136171; CAH70955.1; JOINED; Genomic_DNA. DR EMBL; AL161743; CAH70955.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAH70955.1; JOINED; Genomic_DNA. DR EMBL; AL445200; CAH70955.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAH70955.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAH70956.1; -; Genomic_DNA. DR EMBL; AL136171; CAH70956.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAH70956.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAH70956.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAH70957.1; -; Genomic_DNA. DR EMBL; AL359543; CAH70957.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAI15677.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL136171; CAI15677.1; JOINED; Genomic_DNA. DR EMBL; AL161743; CAI15677.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAI15677.1; JOINED; Genomic_DNA. DR EMBL; AL445200; CAI15677.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAI15677.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAI15679.1; -; Genomic_DNA. DR EMBL; AL136171; CAI15679.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAI15679.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAI15679.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAI17204.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL136171; CAI17204.1; JOINED; Genomic_DNA. DR EMBL; AL161743; CAI17204.1; JOINED; Genomic_DNA. DR EMBL; AL445200; CAI17204.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAI17204.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAI17204.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAI17206.1; -; Genomic_DNA. DR EMBL; AL136171; CAI17206.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAI17206.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAI17206.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAI17207.1; -; Genomic_DNA. DR EMBL; AL626763; CAI17207.1; JOINED; Genomic_DNA. DR EMBL; AL136171; CAI21886.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL161743; CAI21886.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAI21886.1; JOINED; Genomic_DNA. DR EMBL; AL445200; CAI21886.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAI21886.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAI21886.1; JOINED; Genomic_DNA. DR EMBL; AL136171; CAI21888.1; -; Genomic_DNA. DR EMBL; AL359543; CAI21888.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAI21888.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAI21888.1; JOINED; Genomic_DNA. DR EMBL; AL161743; CAI22543.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL136171; CAI22543.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAI22543.1; JOINED; Genomic_DNA. DR EMBL; AL445200; CAI22543.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAI22543.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAI22543.1; JOINED; Genomic_DNA. DR EMBL; AL445200; CAI23013.1; ALT_SEQ; Genomic_DNA. DR EMBL; AL136171; CAI23013.1; JOINED; Genomic_DNA. DR EMBL; AL161743; CAI23013.1; JOINED; Genomic_DNA. DR EMBL; AL359543; CAI23013.1; JOINED; Genomic_DNA. DR EMBL; AL450284; CAI23013.1; JOINED; Genomic_DNA. DR EMBL; AL626763; CAI23013.1; JOINED; Genomic_DNA. DR EMBL; AL751364; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR CCDS; CCDS31055.1; -. [Q9NRI5-3] DR CCDS; CCDS31056.1; -. [Q9NRI5-4] DR CCDS; CCDS53482.1; -. [Q9NRI5-5] DR CCDS; CCDS53483.1; -. [Q9NRI5-8] DR CCDS; CCDS53484.1; -. [Q9NRI5-6] DR CCDS; CCDS59205.1; -. [Q9NRI5-9] DR CCDS; CCDS59206.1; -. [Q9NRI5-10] DR CCDS; CCDS59207.1; -. [Q9NRI5-11] DR PIR; T00071; T00071. DR RefSeq; NP_001012975.1; NM_001012957.1. [Q9NRI5-2] DR RefSeq; NP_001012976.1; NM_001012958.1. [Q9NRI5-4] DR RefSeq; NP_001012977.1; NM_001012959.1. [Q9NRI5-3] DR RefSeq; NP_001158011.1; NM_001164539.1. [Q9NRI5-5] DR RefSeq; NP_001158013.1; NM_001164541.1. [Q9NRI5-8] DR RefSeq; NP_001158016.1; NM_001164544.1. [Q9NRI5-9] DR RefSeq; NP_001158017.1; NM_001164545.1. [Q9NRI5-6] DR RefSeq; NP_001158018.1; NM_001164546.1. [Q9NRI5-7] DR RefSeq; NP_001158019.1; NM_001164547.1. [Q9NRI5-7] DR RefSeq; NP_001158027.1; NM_001164555.1. [Q9NRI5-10] DR RefSeq; NP_001158028.1; NM_001164556.1. [Q9NRI5-11] DR RefSeq; NP_061132.2; NM_018662.2. [Q9NRI5-1] DR UniGene; Hs.13318; -. DR ProteinModelPortal; Q9NRI5; -. DR BioGrid; 118061; 117. DR DIP; DIP-33828N; -. DR IntAct; Q9NRI5; 100. DR PhosphoSite; Q9NRI5; -. DR DMDM; 160332362; -. DR MaxQB; Q9NRI5; -. DR PaxDb; Q9NRI5; -. DR PRIDE; Q9NRI5; -. DR Ensembl; ENST00000317586; ENSP00000320784; ENSG00000162946. [Q9NRI5-4] DR Ensembl; ENST00000366633; ENSP00000355593; ENSG00000162946. [Q9NRI5-5] DR Ensembl; ENST00000366636; ENSP00000355596; ENSG00000162946. [Q9NRI5-3] DR Ensembl; ENST00000535983; ENSP00000443996; ENSG00000162946. [Q9NRI5-8] DR Ensembl; ENST00000539444; ENSP00000440953; ENSG00000162946. [Q9NRI5-6] DR Ensembl; ENST00000602281; ENSP00000473425; ENSG00000162946. [Q9NRI5-9] DR Ensembl; ENST00000602700; ENSP00000473417; ENSG00000162946. [Q9NRI5-10] DR Ensembl; ENST00000602713; ENSP00000473261; ENSG00000162946. [Q9NRI5-10] DR Ensembl; ENST00000602822; ENSP00000473586; ENSG00000162946. [Q9NRI5-10] DR Ensembl; ENST00000602873; ENSP00000473386; ENSG00000162946. [Q9NRI5-11] DR GeneID; 27185; -. DR KEGG; hsa:27185; -. DR UCSC; uc001hux.1; human. [Q9NRI5-4] DR UCSC; uc001huy.3; human. [Q9NRI5-3] DR UCSC; uc001huz.3; human. [Q9NRI5-1] DR UCSC; uc001hva.3; human. [Q9NRI5-2] DR UCSC; uc010pwf.2; human. DR UCSC; uc010pwg.1; human. DR UCSC; uc010pwk.1; human. [Q9NRI5-6] DR UCSC; uc010pwu.1; human. DR UCSC; uc010pww.2; human. [Q9NRI5-5] DR UCSC; uc010pxc.1; human. [Q9NRI5-7] DR UCSC; uc010pxf.2; human. [Q9NRI5-8] DR CTD; 27185; -. DR GeneCards; GC01P231762; -. DR HGNC; HGNC:2888; DISC1. DR HPA; CAB013016; -. DR MIM; 181500; phenotype. DR MIM; 604906; phenotype. DR MIM; 605210; gene. DR neXtProt; NX_Q9NRI5; -. DR Orphanet; 3140; Schizophrenia. DR PharmGKB; PA27342; -. DR eggNOG; NOG76097; -. DR GeneTree; ENSGT00390000006176; -. DR HOGENOM; HOG000056668; -. DR HOVERGEN; HBG051360; -. DR InParanoid; Q9NRI5; -. DR KO; K16534; -. DR PhylomeDB; Q9NRI5; -. DR TreeFam; TF332357; -. DR GeneWiki; DISC1; -. DR GenomeRNAi; 27185; -. DR NextBio; 50024; -. DR PRO; PR:Q9NRI5; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; Q9NRI5; -. DR ExpressionAtlas; Q9NRI5; baseline and differential. DR Genevestigator; Q9NRI5; -. DR GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0036064; C:ciliary basal body; IEA:Ensembl. DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW. DR GO; GO:0005739; C:mitochondrion; IDA:MGI. DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell. DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-KW. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0021846; P:cell proliferation in forebrain; IEA:Ensembl. DR GO; GO:0034613; P:cellular protein localization; IEA:Ensembl. DR GO; GO:0021799; P:cerebral cortex radially oriented cell migration; IEA:Ensembl. DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB. DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IEA:Ensembl. DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB. DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IGI:UniProtKB. DR GO; GO:2000060; P:positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process; IEA:Ensembl. DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IGI:UniProtKB. DR GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0090128; P:regulation of synapse maturation; IEA:Ensembl. DR GO; GO:0031929; P:TOR signaling; IEA:Ensembl. DR InterPro; IPR026081; DISC1. DR InterPro; IPR009053; Prefoldin. DR PANTHER; PTHR14332; PTHR14332; 1. DR SUPFAM; SSF46579; SSF46579; 1. PE 1: Evidence at protein level; KW Alternative splicing; Cell junction; Cell membrane; KW Chromosomal rearrangement; Coiled coil; Complete proteome; Cytoplasm; KW Cytoskeleton; Developmental protein; Membrane; Microtubule; KW Neurogenesis; Polymorphism; Postsynaptic cell membrane; KW Reference proteome; Schizophrenia; Synapse; Wnt signaling pathway. FT CHAIN 1 854 Disrupted in schizophrenia 1 protein. FT /FTId=PRO_0000079916. FT REGION 1 292 Interaction with MAP1A. FT REGION 293 696 Interaction with TRAF3IP1. FT REGION 440 597 Required for localization to punctate FT cytoplasmic foci. FT REGION 446 854 Necessary and sufficient for interaction FT with PCNT and localization at the FT centrosome. FT REGION 598 854 Interaction with ATF4 and ATF5. FT REGION 727 854 Interaction with PAFAH1B1. FT REGION 802 835 Interaction with NDEL1. FT COILED 366 394 {ECO:0000255}. FT COILED 452 505 {ECO:0000255}. FT COILED 602 666 {ECO:0000255}. FT COILED 802 830 {ECO:0000255}. FT VAR_SEQ 23 372 Missing (in isoform 11). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_047525. FT VAR_SEQ 350 369 VISLRLKLQKLQEDAVENDD -> LEPIALDPPWKPRHPEP FT NSY (in isoform 4). FT {ECO:0000303|PubMed:12573262}. FT /FTId=VSP_019314. FT VAR_SEQ 350 356 VISLRLK -> LRRYNKD (in isoform 10). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_047526. FT VAR_SEQ 357 854 Missing (in isoform 10). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_047527. FT VAR_SEQ 370 854 Missing (in isoform 4). FT {ECO:0000303|PubMed:12573262}. FT /FTId=VSP_019315. FT VAR_SEQ 545 559 SLQERIKSLNLSLKE -> RNKCEGKYYEVHGNT (in FT isoform 7). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_043583. FT VAR_SEQ 545 551 SLQERIK -> RKPFLDG (in isoform 11). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_047528. FT VAR_SEQ 552 854 Missing (in isoform 11). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_047529. FT VAR_SEQ 560 579 Missing (in isoform 7). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_043584. FT VAR_SEQ 564 579 VCMSEKFCSTLRKKVN -> ETISGRLKTSPRRLDH (in FT isoform 6). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_043585. FT VAR_SEQ 580 854 Missing (in isoform 6 and isoform 7). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_043586. FT VAR_SEQ 661 854 ETSVKENTMKYMETLKNKLCSCKCPLLGKVWEADLEACRLL FT IQSLQLQEARGSLSVEDERQMDDLEGAAPPIPPRLHSEDKR FT KTPLKVLEEWKTHLIPSLHCAGGEQKEESYILSAELGEKCE FT DIGKKLLYLEDQLHTAIHSHDEDLIQSLRRELQMVKETLQA FT MILQLQPAKEAGEREAAASCMTAGVHEAQA -> DGVSLCR FT PVWSAVVRSCSLQPLPPEFKQFSCLSLRSSWDYRCPPPCLA FT NFVFLVEMGFYHVDQTGLKLLTSSDPPSSASQSAGITDMSH FT CAWPLQ (in isoform 5). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_043214. FT VAR_SEQ 661 695 ETSVKENTMKYMETLKNKLCSCKCPLLGKVWEADL -> AA FT SVHCLGKCGKLTWKLVDCLSRAYSSRKPGEACL (in FT isoform 8). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_043587. FT VAR_SEQ 661 678 ETSVKENTMKYMETLKNK -> GYKYCDAESWTQRSQQLA FT (in isoform 3). FT {ECO:0000303|PubMed:12573262}. FT /FTId=VSP_019316. FT VAR_SEQ 661 662 ET -> GR (in isoform 9). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_047530. FT VAR_SEQ 663 854 Missing (in isoform 9). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_047531. FT VAR_SEQ 679 854 Missing (in isoform 3). FT {ECO:0000303|PubMed:12573262}. FT /FTId=VSP_019317. FT VAR_SEQ 696 854 Missing (in isoform 8). FT {ECO:0000303|PubMed:19805229}. FT /FTId=VSP_043588. FT VAR_SEQ 748 769 Missing (in isoform 2). FT {ECO:0000303|PubMed:9455484}. FT /FTId=VSP_003849. FT VARIANT 5 5 G -> V (in dbSNP:rs3738400). FT {ECO:0000269|PubMed:15386212}. FT /FTId=VAR_030422. FT VARIANT 116 116 A -> V (in dbSNP:rs56020408). FT /FTId=VAR_061642. FT VARIANT 264 264 R -> Q (in dbSNP:rs3738401). FT {ECO:0000269|PubMed:10814723, FT ECO:0000269|PubMed:12573262, FT ECO:0000269|PubMed:9455484}. FT /FTId=VAR_022437. FT VARIANT 328 328 T -> N (in dbSNP:rs55795950). FT /FTId=VAR_061643. FT VARIANT 330 330 L -> F (in dbSNP:rs34622148). FT /FTId=VAR_050954. FT VARIANT 531 531 G -> R (in dbSNP:rs56229136). FT /FTId=VAR_061644. FT VARIANT 607 607 L -> F (associated with susceptibility to FT schizoaffective disorder; FT dbSNP:rs6675281). FT {ECO:0000269|PubMed:15386212}. FT /FTId=VAR_026704. FT VARIANT 704 704 S -> C (in dbSNP:rs821616). FT {ECO:0000269|PubMed:10814723, FT ECO:0000269|PubMed:15939883}. FT /FTId=VAR_022438. FT MUTAGEN 815 815 L->P: Impairs interaction with NDEL1; FT when associated with P-822. FT {ECO:0000269|PubMed:14962739}. FT MUTAGEN 822 822 L->P: Impairs interaction with NDEL1; FT when associated with P-815. FT {ECO:0000269|PubMed:14962739}. SQ SEQUENCE 854 AA; 93611 MW; 63C3FDF2F59830C6 CRC64; MPGGGPQGAP AAAGGGGVSH RAGSRDCLPP AACFRRRRLA RRPGYMRSST GPGIGFLSPA VGTLFRFPGG VSGEESHHSE SRARQCGLDS RGLLVRSPVS KSAAAPTVTS VRGTSAHFGI QLRGGTRLPD RLSWPCGPGS AGWQQEFAAM DSSETLDASW EAACSDGARR VRAAGSLPSA ELSSNSCSPG CGPEVPPTPP GSHSAFTSSF SFIRLSLGSA GERGEAEGCP PSREAESHCQ SPQEMGAKAA SLDGPHEDPR CLSRPFSLLA TRVSADLAQA ARNSSRPERD MHSLPDMDPG SSSSLDPSLA GCGGDGSSGS GDAHSWDTLL RKWEPVLRDC LLRNRRQMEV ISLRLKLQKL QEDAVENDDY DKAETLQQRL EDLEQEKISL HFQLPSRQPA LSSFLGHLAA QVQAALRRGA TQQASGDDTH TPLRMEPRLL EPTAQDSLHV SITRRDWLLQ EKQQLQKEIE ALQARMFVLE AKDQQLRREI EEQEQQLQWQ GCDLTPLVGQ LSLGQLQEVS KALQDTLASA GQIPFHAEPP ETIRSLQERI KSLNLSLKEI TTKVCMSEKF CSTLRKKVND IETQLPALLE AKMHAISGNH FWTAKDLTEE IRSLTSEREG LEGLLSKLLV LSSRNVKKLG SVKEDYNRLR REVEHQETAY ETSVKENTMK YMETLKNKLC SCKCPLLGKV WEADLEACRL LIQSLQLQEA RGSLSVEDER QMDDLEGAAP PIPPRLHSED KRKTPLKVLE EWKTHLIPSL HCAGGEQKEE SYILSAELGE KCEDIGKKLL YLEDQLHTAI HSHDEDLIQS LRRELQMVKE TLQAMILQLQ PAKEAGEREA AASCMTAGVH EAQA //