DISC1_HUMAN
ID DISC1_HUMAN Reviewed; 854 AA.
AC Q9NRI5; A6NLH2; C4P091; C4P095; C4P0A1; C4P0A3; C4P0B3; C4P0B6; C4P0C1;
AC C9J6D0; O75045; Q5VT44; Q5VT45; Q8IXJ0; Q8IXJ1; Q9BX19; Q9NRI3; Q9NRI4;
DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2007, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Disrupted in schizophrenia 1 protein {ECO:0000305};
GN Name=DISC1 {ECO:0000312|HGNC:HGNC:2888}; Synonyms=KIAA0457;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), AND VARIANTS GLN-264
RP 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 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 from
RT 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 with
RT 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., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., 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., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., 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., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., 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 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., Juvonen H.,
RA Arajaervi R., Partonen T., Suvisaari J., Loennqvist J., Meyer J.,
RA 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 SUBCELLULAR
RP 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 protein
RT that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of
RT interaction with mutation.";
RL Hum. Mol. Genet. 12:1591-1608(2003).
RN [8]
RP INVOLVEMENT IN 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., Loennqvist J.,
RA Peltonen L., Ekelund J.;
RT "Haplotype transmission analysis provides evidence of association for DISC1
RT 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 binding
RT to NudE-like (NUDEL) and inhibits neurite outgrowth.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:289-294(2003).
RN [10]
RP ERRATUM OF PUBMED:12506198.
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 SCZD9, 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., Lipsky R.H.,
RA 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 LOCATION,
RP 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 major
RT 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., Duran-Jimeniz B.,
RA Hunt P., Millar J.K., Porteous D.J., Shearman M.S., Whiting P.J.;
RT "Subcellular targeting of DISC1 is dependent on a domain independent from
RT the Nudel binding site.";
RL Mol. Cell. Neurosci. 28:613-624(2005).
RN [14]
RP INVOLVEMENT IN 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., Cascio M.B.,
RA Elashvili S., Koizumi H., Takanezawa Y., Dickerson F., Yolken R., Arai H.,
RA Sawa A.;
RT "DISC1-NDEL1/NUDEL protein interaction, an essential component for neurite
RT outgrowth, is modulated by genetic variations of DISC1.";
RL Hum. Mol. Genet. 15:3313-3323(2006).
RN [17]
RP INTERACTION WITH PDE4B.
RX PubMed=17519386; DOI=10.1124/jpet.107.122218;
RA Cheung Y.F., Kan Z., Garrett-Engele P., Gall I., Murdoch H., Baillie G.S.,
RA Camargo L.M., Johnson J.M., Houslay M.D., Castle J.C.;
RT "PDE4B5, a novel, super-short, brain-specific cAMP phosphodiesterase-4
RT variant whose isoform-specifying N-terminal region is identical to that of
RT cAMP phosphodiesterase-4D6 (PDE4D6).";
RL J. Pharmacol. Exp. Ther. 322:600-609(2007).
RN [18]
RP INTERACTION WITH ZNF365.
RX PubMed=17389905; DOI=10.1038/sj.mp.4001945;
RA Hattori T., Baba K., Matsuzaki S., Honda A., Miyoshi K., Inoue K.,
RA Taniguchi M., Hashimoto H., Shintani N., Baba A., Shimizu S., Yukioka F.,
RA Kumamoto N., Yamaguchi A., Tohyama M., Katayama T.;
RT "A novel DISC1-interacting partner DISC1-binding zinc-finger protein:
RT implication in the modulation of DISC1-dependent neurite outgrowth.";
RL Mol. Psychiatry 12:398-407(2007).
RN [19]
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., Katayama T.,
RA Tohyama M.;
RT "DISC1-kendrin interaction is involved in centrosomal microtubule network
RT formation.";
RL Biochem. Biophys. Res. Commun. 377:1051-1056(2008).
RN [20]
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 hippocampus.";
RL Hum. Mol. Genet. 18:3286-3297(2009).
RN [21]
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., Tassa C.,
RA Berry E.M., Soda T., Singh K.K., Biechele T., Petryshen T.L., Moon R.T.,
RA Haggarty S.J., Tsai L.H.;
RT "Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation
RT via modulation of GSK3beta/beta-catenin signaling.";
RL Cell 136:1017-1031(2009).
RN [22]
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).
RN [23] {ECO:0007744|PDB:5V4B}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 193-207 IN COMPLEX WITH FBXW7,
RP DOMAIN, UBIQUITINATION AT LYS-372, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP MUTAGENESIS OF LYS-372.
RX PubMed=28727686; DOI=10.1038/mp.2017.138;
RA Yalla K., Elliott C., Day J.P., Findlay J., Barratt S., Hughes Z.A.,
RA Wilson L., Whiteley E., Popiolek M., Li Y., Dunlop J., Killick R.,
RA Adams D.R., Brandon N.J., Houslay M.D., Hao B., Baillie G.S.;
RT "FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system.";
RL Mol. Psychiatry 23:1278-1286(2018).
CC -!- FUNCTION: Involved in the regulation of multiple aspects of embryonic
CC and adult neurogenesis (PubMed:19502360, PubMed:19303846). Required for
CC neural progenitor proliferation in the ventrical/subventrical zone
CC during embryonic brain development and in the adult dentate gyrus of
CC the hippocampus (By similarity). Participates in the Wnt-mediated
CC neural progenitor proliferation as a positive regulator by modulating
CC GSK3B activity and CTNNB1 abundance (PubMed:19303846). Plays a role as
CC a modulator of the AKT-mTOR signaling pathway controlling the tempo of
CC the process of newborn neurons integration during adult neurogenesis,
CC including neuron positioning, dendritic development and synapse
CC formation (By similarity). Inhibits the activation of AKT-mTOR
CC signaling upon interaction with CCDC88A (By similarity). Regulates the
CC migration of early-born granule cell precursors toward the dentate
CC gyrus during the hippocampal development (PubMed:19502360). Inhibits
CC ATF4 transcription factor activity in neurons by disrupting ATF4
CC dimerization and DNA-binding (By similarity). Plays a role, together
CC with PCNT, in the microtubule network formation (PubMed:18955030).
CC {ECO:0000250|UniProtKB:Q811T9, ECO:0000269|PubMed:18955030,
CC ECO:0000269|PubMed:19303846, ECO:0000269|PubMed:19502360}.
CC -!- SUBUNIT: Interacts with NDEL1 (PubMed:12506198). Interacts with CCDC88A
CC (via C-terminus); the interaction is direct. Interacts with GSK3B (By
CC similarity). Interacts with tubulin alpha, ACTN2, ANKHD1, ATF4, ATF5,
CC CEP63, EIF3S3, MAP1A, NDEL1, PAFAH1B1, RANBP9, SPTBN4, SYNE1 and
CC TRAF3IP1 (PubMed:12812986). Interaction with microtubules may be
CC mediated in part by TRAF3IP1. Interacts (via C-terminal) with PCNT
CC (PubMed:18955030). Interacts with CHCHD6 (PubMed:22228767). Interacts
CC with CCDC141 (By similarity). Interacts with FBXW7, the substrate-
CC recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-
CC protein ligase complex; the interaction targets DISC1 for proteasomal
CC degradation (PubMed:28727686). Interacts with ZNF365 (PubMed:17389905).
CC Interacts with ATF4; inhibiting ATF4 transcription factor activity by
CC disrupting ATF4 dimerization and DNA-binding (By similarity). Interacts
CC with PDE4B (isoform PDE4B5) (PubMed:17519386).
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:17389905,
CC ECO:0000269|PubMed:17519386, ECO:0000269|PubMed:18955030,
CC ECO:0000269|PubMed:22228767, ECO:0000269|PubMed:28727686}.
CC -!- INTERACTION:
CC Q9NRI5; P35609: ACTN2; NbExp=4; IntAct=EBI-529989, EBI-77797;
CC Q9NRI5; Q99996: AKAP9; NbExp=2; IntAct=EBI-529989, EBI-1048311;
CC Q9NRI5; Q8IWZ3-1: ANKHD1; NbExp=6; IntAct=EBI-529989, EBI-1785446;
CC Q9NRI5; P18848: ATF4; NbExp=4; IntAct=EBI-529989, EBI-492498;
CC Q9NRI5; Q9Y2D1: ATF5; NbExp=8; IntAct=EBI-529989, EBI-492509;
CC Q9NRI5; Q6VMQ6: ATF7IP; NbExp=3; IntAct=EBI-529989, EBI-928732;
CC Q9NRI5; Q6ZP82: CCDC141; NbExp=5; IntAct=EBI-529989, EBI-928795;
CC Q9NRI5; Q5SW79: CEP170; NbExp=4; IntAct=EBI-529989, EBI-1104799;
CC Q9NRI5; Q96MT8: CEP63; NbExp=7; IntAct=EBI-529989, EBI-741977;
CC Q9NRI5; P10909: CLU; NbExp=4; IntAct=EBI-529989, EBI-1104674;
CC Q9NRI5; P12110: COL6A2; NbExp=3; IntAct=EBI-529989, EBI-928749;
CC Q9NRI5; Q9NRI5: DISC1; NbExp=4; IntAct=EBI-529989, EBI-529989;
CC Q9NRI5; Q99615: DNAJC7; NbExp=3; IntAct=EBI-529989, EBI-357552;
CC Q9NRI5; P14416: DRD2; NbExp=3; IntAct=EBI-529989, EBI-2928178;
CC Q9NRI5; Q03001: DST; NbExp=4; IntAct=EBI-529989, EBI-310758;
CC Q9NRI5; Q14204: DYNC1H1; NbExp=4; IntAct=EBI-529989, EBI-356015;
CC Q9NRI5; O15372: EIF3H; NbExp=6; IntAct=EBI-529989, EBI-709735;
CC Q9NRI5; Q8WXI9: GATAD2B; NbExp=3; IntAct=EBI-529989, EBI-923440;
CC Q9NRI5; Q4V328: GRIPAP1; NbExp=5; IntAct=EBI-529989, EBI-717919;
CC Q9NRI5; P06396: GSN; NbExp=2; IntAct=EBI-529989, EBI-351506;
CC Q9NRI5; Q16891: IMMT; NbExp=3; IntAct=EBI-529989, EBI-473801;
CC Q9NRI5; Q15811: ITSN1; NbExp=4; IntAct=EBI-529989, EBI-602041;
CC Q9NRI5; Q9Y496: KIF3A; NbExp=5; IntAct=EBI-529989, EBI-1104844;
CC Q9NRI5; O14782: KIF3C; NbExp=3; IntAct=EBI-529989, EBI-1104854;
CC Q9NRI5; Q14974: KPNB1; NbExp=2; IntAct=EBI-529989, EBI-286758;
CC Q9NRI5; Q9UPN3: MACF1; NbExp=4; IntAct=EBI-529989, EBI-522925;
CC Q9NRI5; P78559: MAP1A; NbExp=3; IntAct=EBI-529989, EBI-929047;
CC Q9NRI5; O95819: MAP4K4; NbExp=2; IntAct=EBI-529989, EBI-2511133;
CC Q9NRI5; P43243: MATR3; NbExp=3; IntAct=EBI-529989, EBI-352602;
CC Q9NRI5; Q9NXR1: NDE1; NbExp=4; IntAct=EBI-529989, EBI-941227;
CC Q9NRI5; Q9GZM8: NDEL1; NbExp=12; IntAct=EBI-529989, EBI-928842;
CC Q9NRI5; Q12769: NUP160; NbExp=3; IntAct=EBI-529989, EBI-295715;
CC Q9NRI5; Q8TEM1: NUP210; NbExp=2; IntAct=EBI-529989, EBI-372826;
CC Q9NRI5; P43034: PAFAH1B1; NbExp=2; IntAct=EBI-529989, EBI-720620;
CC Q9NRI5; O95613: PCNT; NbExp=5; IntAct=EBI-529989, EBI-530012;
CC Q9NRI5; Q5VU43: PDE4DIP; NbExp=3; IntAct=EBI-529989, EBI-1105124;
CC Q9NRI5; Q96S59: RANBP9; NbExp=7; IntAct=EBI-529989, EBI-636085;
CC Q9NRI5; Q13813: SPTAN1; NbExp=3; IntAct=EBI-529989, EBI-351450;
CC Q9NRI5; Q01082: SPTBN1; NbExp=4; IntAct=EBI-529989, EBI-351561;
CC Q9NRI5; Q9H254: SPTBN4; NbExp=3; IntAct=EBI-529989, EBI-308543;
CC Q9NRI5; Q8NF91: SYNE1; NbExp=7; IntAct=EBI-529989, EBI-928867;
CC Q9NRI5; Q9UBB9: TFIP11; NbExp=3; IntAct=EBI-529989, EBI-1105213;
CC Q9NRI5; Q9UKE5: TNIK; NbExp=4; IntAct=EBI-529989, EBI-1051794;
CC Q9NRI5; Q9H2K2: TNKS2; NbExp=2; IntAct=EBI-529989, EBI-4398527;
CC Q9NRI5; Q8TDR0: TRAF3IP1; NbExp=9; IntAct=EBI-529989, EBI-928811;
CC Q9NRI5; O75962: TRIO; NbExp=3; IntAct=EBI-529989, EBI-718519;
CC Q9NRI5; Q9H0D6: XRN2; NbExp=3; IntAct=EBI-529989, EBI-372110;
CC Q9NRI5; P62258: YWHAE; NbExp=3; IntAct=EBI-529989, EBI-356498;
CC Q9NRI5; P63104: YWHAZ; NbExp=3; IntAct=EBI-529989, EBI-347088;
CC Q9NRI5; Q6A065: Cep170; Xeno; NbExp=2; IntAct=EBI-529989, EBI-2554140;
CC Q9NRI5; Q8VD04: Gripap1; Xeno; NbExp=2; IntAct=EBI-529989, EBI-7585099;
CC Q9NRI5; Q9Z1B5: Mad2l1; Xeno; NbExp=2; IntAct=EBI-529989, EBI-2552918;
CC Q9NRI5; Q9CZA6: Nde1; Xeno; NbExp=2; IntAct=EBI-529989, EBI-309934;
CC Q9NRI5; Q9ERR1: Ndel1; Xeno; NbExp=2; IntAct=EBI-529989, EBI-646668;
CC Q9NRI5-1; O15372: EIF3H; NbExp=3; IntAct=EBI-15881455, EBI-709735;
CC Q9NRI5-1; Q16891-1: IMMT; NbExp=9; IntAct=EBI-15881455, EBI-11614103;
CC Q9NRI5-1; Q9UPN3: MACF1; NbExp=3; IntAct=EBI-15881455, EBI-522925;
CC Q9NRI5-1; Q9GZM8: NDEL1; NbExp=4; IntAct=EBI-15881455, EBI-928842;
CC Q9NRI5-1; Q99784: OLFM1; NbExp=3; IntAct=EBI-15881455, EBI-1105073;
CC Q9NRI5-2; Q9NYB9-2: ABI2; NbExp=3; IntAct=EBI-11988027, EBI-11096309;
CC Q9NRI5-2; Q96SZ5: ADO; NbExp=3; IntAct=EBI-11988027, EBI-11102284;
CC Q9NRI5-2; Q13155: AIMP2; NbExp=3; IntAct=EBI-11988027, EBI-745226;
CC Q9NRI5-2; A2BDD9: AMOT; NbExp=3; IntAct=EBI-11988027, EBI-17286414;
CC Q9NRI5-2; Q9BXS5: AP1M1; NbExp=3; IntAct=EBI-11988027, EBI-541426;
CC Q9NRI5-2; Q9H6L4: ARMC7; NbExp=3; IntAct=EBI-11988027, EBI-742909;
CC Q9NRI5-2; O95816: BAG2; NbExp=3; IntAct=EBI-11988027, EBI-355275;
CC Q9NRI5-2; Q13515: BFSP2; NbExp=3; IntAct=EBI-11988027, EBI-10229433;
CC Q9NRI5-2; Q96GS4: BORCS6; NbExp=4; IntAct=EBI-11988027, EBI-10193358;
CC Q9NRI5-2; O95696: BRD1; NbExp=3; IntAct=EBI-11988027, EBI-714754;
CC Q9NRI5-2; Q9NX04: C1orf109; NbExp=3; IntAct=EBI-11988027, EBI-8643161;
CC Q9NRI5-2; Q53TS8: C2CD6; NbExp=3; IntAct=EBI-11988027, EBI-739879;
CC Q9NRI5-2; Q9H7E9: C8orf33; NbExp=3; IntAct=EBI-11988027, EBI-715389;
CC Q9NRI5-2; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-11988027, EBI-11530605;
CC Q9NRI5-2; Q68D86: CCDC102B; NbExp=3; IntAct=EBI-11988027, EBI-10171570;
CC Q9NRI5-2; Q8IYE1: CCDC13; NbExp=3; IntAct=EBI-11988027, EBI-10961312;
CC Q9NRI5-2; Q8NCU1: CCDC197; NbExp=3; IntAct=EBI-11988027, EBI-750686;
CC Q9NRI5-2; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-11988027, EBI-10961624;
CC Q9NRI5-2; Q53HC0: CCDC92; NbExp=3; IntAct=EBI-11988027, EBI-719994;
CC Q9NRI5-2; Q8TD31-3: CCHCR1; NbExp=3; IntAct=EBI-11988027, EBI-10175300;
CC Q9NRI5-2; Q9UJX2: CDC23; NbExp=3; IntAct=EBI-11988027, EBI-396137;
CC Q9NRI5-2; Q16543: CDC37; NbExp=3; IntAct=EBI-11988027, EBI-295634;
CC Q9NRI5-2; Q8IVW4: CDKL3; NbExp=3; IntAct=EBI-11988027, EBI-3919850;
CC Q9NRI5-2; Q86XR8-3: CEP57; NbExp=3; IntAct=EBI-11988027, EBI-11752486;
CC Q9NRI5-2; Q8IYR0: CFAP206; NbExp=3; IntAct=EBI-11988027, EBI-749051;
CC Q9NRI5-2; Q9UI47-2: CTNNA3; NbExp=3; IntAct=EBI-11988027, EBI-11962928;
CC Q9NRI5-2; Q2TBE0: CWF19L2; NbExp=3; IntAct=EBI-11988027, EBI-5453285;
CC Q9NRI5-2; P26196: DDX6; NbExp=3; IntAct=EBI-11988027, EBI-351257;
CC Q9NRI5-2; P38919: EIF4A3; NbExp=3; IntAct=EBI-11988027, EBI-299104;
CC Q9NRI5-2; Q7Z589-5: EMSY; NbExp=3; IntAct=EBI-11988027, EBI-11989522;
CC Q9NRI5-2; Q9NWN3: FBXO34; NbExp=3; IntAct=EBI-11988027, EBI-719816;
CC Q9NRI5-2; Q96Q35-2: FLACC1; NbExp=3; IntAct=EBI-11988027, EBI-11533409;
CC Q9NRI5-2; Q9H0R8: GABARAPL1; NbExp=3; IntAct=EBI-11988027, EBI-746969;
CC Q9NRI5-2; Q8NHY3: GAS2L2; NbExp=3; IntAct=EBI-11988027, EBI-7960826;
CC Q9NRI5-2; O95995: GAS8; NbExp=3; IntAct=EBI-11988027, EBI-1052570;
CC Q9NRI5-2; Q96CN9: GCC1; NbExp=3; IntAct=EBI-11988027, EBI-746252;
CC Q9NRI5-2; P55040: GEM; NbExp=3; IntAct=EBI-11988027, EBI-744104;
CC Q9NRI5-2; Q9P2W3: GNG13; NbExp=3; IntAct=EBI-11988027, EBI-11427343;
CC Q9NRI5-2; O95872: GPANK1; NbExp=3; IntAct=EBI-11988027, EBI-751540;
CC Q9NRI5-2; Q4V328: GRIPAP1; NbExp=3; IntAct=EBI-11988027, EBI-717919;
CC Q9NRI5-2; P07910: HNRNPC; NbExp=3; IntAct=EBI-11988027, EBI-357966;
CC Q9NRI5-2; Q8IY31-3: IFT20; NbExp=3; IntAct=EBI-11988027, EBI-9091197;
CC Q9NRI5-2; Q96LB3-2: IFT74; NbExp=3; IntAct=EBI-11988027, EBI-12066130;
CC Q9NRI5-2; Q9HAQ2: KIF9; NbExp=3; IntAct=EBI-11988027, EBI-8472129;
CC Q9NRI5-2; Q9BVG8-5: KIFC3; NbExp=3; IntAct=EBI-11988027, EBI-14069005;
CC Q9NRI5-2; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-11988027, EBI-726510;
CC Q9NRI5-2; Q8NEH6: MNS1; NbExp=3; IntAct=EBI-11988027, EBI-743811;
CC Q9NRI5-2; Q15014: MORF4L2; NbExp=3; IntAct=EBI-11988027, EBI-399257;
CC Q9NRI5-2; O43639: NCK2; NbExp=3; IntAct=EBI-11988027, EBI-713635;
CC Q9NRI5-2; Q9GZM8: NDEL1; NbExp=3; IntAct=EBI-11988027, EBI-928842;
CC Q9NRI5-2; Q8N987: NECAB1; NbExp=3; IntAct=EBI-11988027, EBI-11956853;
CC Q9NRI5-2; Q9Y5B8: NME7; NbExp=3; IntAct=EBI-11988027, EBI-744782;
CC Q9NRI5-2; O43189: PHF1; NbExp=3; IntAct=EBI-11988027, EBI-530034;
CC Q9NRI5-2; Q4G0R1: PIBF1; NbExp=3; IntAct=EBI-11988027, EBI-14066006;
CC Q9NRI5-2; Q92569: PIK3R3; NbExp=3; IntAct=EBI-11988027, EBI-79893;
CC Q9NRI5-2; Q16512: PKN1; NbExp=3; IntAct=EBI-11988027, EBI-602382;
CC Q9NRI5-2; Q9BUI4: POLR3C; NbExp=3; IntAct=EBI-11988027, EBI-5452779;
CC Q9NRI5-2; O75145: PPFIA3; NbExp=3; IntAct=EBI-11988027, EBI-1763225;
CC Q9NRI5-2; Q8WXF1-2: PSPC1; NbExp=3; IntAct=EBI-11988027, EBI-12135327;
CC Q9NRI5-2; P47897: QARS1; NbExp=3; IntAct=EBI-11988027, EBI-347462;
CC Q9NRI5-2; Q96IZ5: RBM41; NbExp=3; IntAct=EBI-11988027, EBI-740773;
CC Q9NRI5-2; Q6P9E2: RECK; NbExp=3; IntAct=EBI-11988027, EBI-10253121;
CC Q9NRI5-2; O75150: RNF40; NbExp=3; IntAct=EBI-11988027, EBI-744408;
CC Q9NRI5-2; Q96GM5: SMARCD1; NbExp=3; IntAct=EBI-11988027, EBI-358489;
CC Q9NRI5-2; Q969G3: SMARCE1; NbExp=3; IntAct=EBI-11988027, EBI-455078;
CC Q9NRI5-2; Q8IY18: SMC5; NbExp=3; IntAct=EBI-11988027, EBI-605405;
CC Q9NRI5-2; Q8NB12: SMYD1; NbExp=3; IntAct=EBI-11988027, EBI-8463848;
CC Q9NRI5-2; Q9H0A9-2: SPATC1L; NbExp=3; IntAct=EBI-11988027, EBI-11995806;
CC Q9NRI5-2; O75558: STX11; NbExp=4; IntAct=EBI-11988027, EBI-714135;
CC Q9NRI5-2; Q9UMX1: SUFU; NbExp=3; IntAct=EBI-11988027, EBI-740595;
CC Q9NRI5-2; Q9Y4C2-2: TCAF1; NbExp=3; IntAct=EBI-11988027, EBI-11974855;
CC Q9NRI5-2; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-11988027, EBI-11955057;
CC Q9NRI5-2; Q9BUZ4: TRAF4; NbExp=3; IntAct=EBI-11988027, EBI-3650647;
CC Q9NRI5-2; Q14134: TRIM29; NbExp=3; IntAct=EBI-11988027, EBI-702370;
CC Q9NRI5-2; Q6AZZ1: TRIM68; NbExp=3; IntAct=EBI-11988027, EBI-2130449;
CC Q9NRI5-2; Q9BZW7: TSGA10; NbExp=3; IntAct=EBI-11988027, EBI-744794;
CC Q9NRI5-2; Q969E8: TSR2; NbExp=3; IntAct=EBI-11988027, EBI-746981;
CC Q9NRI5-2; Q5W5X9-3: TTC23; NbExp=3; IntAct=EBI-11988027, EBI-9090990;
CC Q9NRI5-2; P57075-2: UBASH3A; NbExp=3; IntAct=EBI-11988027, EBI-7353612;
CC Q9NRI5-2; Q8TF42: UBASH3B; NbExp=3; IntAct=EBI-11988027, EBI-1380492;
CC Q9NRI5-2; O75604: USP2; NbExp=3; IntAct=EBI-11988027, EBI-743272;
CC Q9NRI5-2; Q15973: ZNF124; NbExp=3; IntAct=EBI-11988027, EBI-2555767;
CC Q9NRI5-2; P36508: ZNF76; NbExp=3; IntAct=EBI-11988027, EBI-7254550;
CC Q9NRI5-3; A2AST1: Ccdc141; Xeno; NbExp=6; IntAct=EBI-21925300, EBI-20565696;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12506198,
CC ECO:0000269|PubMed:15797709}. Cytoplasm, cytoskeleton
CC {ECO:0000269|PubMed:14962739, ECO:0000269|PubMed:15797709}.
CC Mitochondrion {ECO:0000269|PubMed:12506198,
CC ECO:0000269|PubMed:15797709}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000269|PubMed:12812986,
CC ECO:0000269|PubMed:18955030}. Postsynaptic density
CC {ECO:0000250|UniProtKB:Q811T9}. Note=Colocalizes with NDEL1 in the
CC perinuclear region and the centrosome (By similarity). Localizes to
CC punctate cytoplasmic foci which overlap in part with mitochondria
CC (PubMed:12506198, PubMed:15797709). Colocalizes with PCNT at the
CC centrosome (PubMed:18955030). {ECO:0000250|UniProtKB:Q811T9,
CC ECO:0000269|PubMed:12506198, ECO:0000269|PubMed:15797709,
CC ECO:0000269|PubMed:18955030}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=11;
CC Comment=Additional isoforms seem to exist. More than 50 different
CC 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 gyrus
CC of the hippocampus. Also expressed in the temporal and parahippocampal
CC cortices and cells of the white matter. {ECO:0000269|PubMed:16510495}.
CC -!- DEVELOPMENTAL STAGE: Expression rises within the dentate gyrus and
CC temporal cortex from the neonatal period to infancy, declines markedly
CC in adolescence, and declines further with aging.
CC {ECO:0000269|PubMed:16510495}.
CC -!- PTM: Ubiquitinated. Ubiquitination with 'Lys-48'-linked polyubiquitin
CC chains leads to its proteasomal degradation.
CC {ECO:0000269|PubMed:28727686}.
CC -!- DISEASE: Note=A chromosomal aberration involving DISC1 segregates with
CC schizophrenia and related psychiatric disorders in a large Scottish
CC family. Translocation t(1;11)(q42.1;q14.3). The truncated DISC1 protein
CC produced by this translocation is unable to interact with ATF4, ATF5
CC and NDEL1.
CC -!- DISEASE: Schizophrenia 9 (SCZD9) [MIM:604906]: 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:11468279, ECO:0000269|PubMed:14532331,
CC ECO:0000269|PubMed:15386212, ECO:0000269|PubMed:15939883}. Note=Disease
CC susceptibility is associated with variants affecting the gene
CC represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 1]: Non-canonical donor and acceptor splice
CC sites for the last 2 exons. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 2]: Non-canonical donor and acceptor splice
CC sites for the last 2 exons. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA32302.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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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; AL136171; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161743; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL359543; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL450284; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL445200; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL626763; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL751364; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455159; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; KF455161; -; 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; CCDS53485.1; -. [Q9NRI5-7]
DR CCDS; CCDS59205.1; -. [Q9NRI5-9]
DR CCDS; CCDS59206.1; -. [Q9NRI5-10]
DR CCDS; CCDS59207.1; -. [Q9NRI5-11]
DR CCDS; CCDS86058.1; -. [Q9NRI5-2]
DR CCDS; CCDS86059.1; -. [Q9NRI5-1]
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 PDB; 5V4B; X-ray; 2.60 A; C=193-207.
DR PDBsum; 5V4B; -.
DR AlphaFoldDB; Q9NRI5; -.
DR SASBDB; Q9NRI5; -.
DR SMR; Q9NRI5; -.
DR BioGRID; 118061; 418.
DR CORUM; Q9NRI5; -.
DR DIP; DIP-33828N; -.
DR ELM; Q9NRI5; -.
DR IntAct; Q9NRI5; 949.
DR MINT; Q9NRI5; -.
DR STRING; 9606.ENSP00000355593; -.
DR MoonDB; Q9NRI5; Predicted.
DR iPTMnet; Q9NRI5; -.
DR PhosphoSitePlus; Q9NRI5; -.
DR BioMuta; DISC1; -.
DR DMDM; 160332362; -.
DR EPD; Q9NRI5; -.
DR jPOST; Q9NRI5; -.
DR MassIVE; Q9NRI5; -.
DR MaxQB; Q9NRI5; -.
DR PaxDb; Q9NRI5; -.
DR PeptideAtlas; Q9NRI5; -.
DR PRIDE; Q9NRI5; -.
DR ProteomicsDB; 82365; -. [Q9NRI5-1]
DR ProteomicsDB; 82366; -. [Q9NRI5-2]
DR ProteomicsDB; 82367; -. [Q9NRI5-3]
DR ProteomicsDB; 82368; -. [Q9NRI5-4]
DR ProteomicsDB; 82369; -. [Q9NRI5-5]
DR ProteomicsDB; 82370; -. [Q9NRI5-6]
DR ProteomicsDB; 82371; -. [Q9NRI5-7]
DR ProteomicsDB; 82372; -. [Q9NRI5-8]
DR Antibodypedia; 34687; 653 antibodies from 39 providers.
DR DNASU; 27185; -.
DR Ensembl; ENST00000317586.8; ENSP00000320784.4; ENSG00000162946.23. [Q9NRI5-4]
DR Ensembl; ENST00000366633.7; ENSP00000355593.3; ENSG00000162946.23. [Q9NRI5-5]
DR Ensembl; ENST00000366636.8; ENSP00000355596.4; ENSG00000162946.23. [Q9NRI5-3]
DR Ensembl; ENST00000366637.8; ENSP00000355597.6; ENSG00000162946.23. [Q9NRI5-2]
DR Ensembl; ENST00000439617.8; ENSP00000403888.4; ENSG00000162946.23. [Q9NRI5-1]
DR Ensembl; ENST00000535983.5; ENSP00000443996.1; ENSG00000162946.23. [Q9NRI5-8]
DR Ensembl; ENST00000539444.5; ENSP00000440953.1; ENSG00000162946.23. [Q9NRI5-6]
DR Ensembl; ENST00000602281.5; ENSP00000473425.1; ENSG00000162946.23. [Q9NRI5-9]
DR Ensembl; ENST00000602700.5; ENSP00000473417.1; ENSG00000162946.23. [Q9NRI5-10]
DR Ensembl; ENST00000602713.5; ENSP00000473261.1; ENSG00000162946.23. [Q9NRI5-10]
DR Ensembl; ENST00000602822.5; ENSP00000473586.1; ENSG00000162946.23. [Q9NRI5-10]
DR Ensembl; ENST00000602873.5; ENSP00000473386.1; ENSG00000162946.23. [Q9NRI5-11]
DR Ensembl; ENST00000628350.2; ENSP00000487190.1; ENSG00000162946.23. [Q9NRI5-7]
DR GeneID; 27185; -.
DR KEGG; hsa:27185; -.
DR MANE-Select; ENST00000439617.8; ENSP00000403888.4; NM_018662.3; NP_061132.2.
DR UCSC; uc001hux.1; human. [Q9NRI5-1]
DR CTD; 27185; -.
DR DisGeNET; 27185; -.
DR GeneCards; DISC1; -.
DR HGNC; HGNC:2888; DISC1.
DR HPA; ENSG00000162946; Tissue enhanced (retina).
DR MalaCards; DISC1; -.
DR MIM; 604906; phenotype.
DR MIM; 605210; gene.
DR neXtProt; NX_Q9NRI5; -.
DR OpenTargets; ENSG00000162946; -.
DR Orphanet; 171703; Microcephaly-polymicrogyria-corpus callosum agenesis syndrome.
DR PharmGKB; PA27342; -.
DR VEuPathDB; HostDB:ENSG00000162946; -.
DR eggNOG; ENOG502S3S3; Eukaryota.
DR GeneTree; ENSGT00390000006176; -.
DR HOGENOM; CLU_1514037_0_0_1; -.
DR InParanoid; Q9NRI5; -.
DR OMA; CMEDNHP; -.
DR PhylomeDB; Q9NRI5; -.
DR TreeFam; TF332357; -.
DR PathwayCommons; Q9NRI5; -.
DR SignaLink; Q9NRI5; -.
DR SIGNOR; Q9NRI5; -.
DR BioGRID-ORCS; 27185; 7 hits in 1066 CRISPR screens.
DR GeneWiki; DISC1; -.
DR GenomeRNAi; 27185; -.
DR Pharos; Q9NRI5; Tbio.
DR PRO; PR:Q9NRI5; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9NRI5; protein.
DR Bgee; ENSG00000162946; Expressed in buccal mucosa cell and 123 other tissues.
DR ExpressionAtlas; Q9NRI5; baseline and differential.
DR Genevisible; Q9NRI5; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0090724; C:central region of growth cone; IEA:Ensembl.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; IEA:Ensembl.
DR GO; GO:0097546; C:ciliary base; IDA:SYSCILIA_CCNET.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0030286; C:dynein complex; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IDA:HPA.
DR GO; GO:0005871; C:kinesin complex; IEA:Ensembl.
DR GO; GO:0005874; C:microtubule; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR GO; GO:0014069; C:postsynaptic density; IEA:UniProtKB-SubCell.
DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0019894; F:kinesin binding; IEA:Ensembl.
DR GO; GO:0060090; F:molecular adaptor activity; IEA:Ensembl.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
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:0060271; P:cilium assembly; IBA:GO_Central.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0032091; P:negative regulation of protein binding; ISS:ARUK-UCL.
DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl.
DR GO; GO:0001764; P:neuron migration; IMP:UniProtKB.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:SYSCILIA_CCNET.
DR GO; GO:0045773; P:positive regulation of axon extension; IEA:Ensembl.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IEA:Ensembl.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; IGI:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IEA:Ensembl.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IGI:UniProtKB.
DR GO; GO:0071539; P:protein localization to centrosome; IEA:Ensembl.
DR GO; GO:0021852; P:pyramidal neuron migration to cerebral cortex; IEA:Ensembl.
DR GO; GO:0060998; P:regulation of dendritic spine development; IEA:Ensembl.
DR GO; GO:0090128; P:regulation of synapse maturation; IEA:Ensembl.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IEA:Ensembl.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0031929; P:TOR signaling; IEA:Ensembl.
DR GO; GO:0006511; P:ubiquitin-dependent protein catabolic process; IEA:Ensembl.
DR InterPro; IPR026081; DISC1.
DR PANTHER; PTHR14332; PTHR14332; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosomal rearrangement; Coiled coil;
KW Cytoplasm; Cytoskeleton; Developmental protein; Isopeptide bond;
KW Microtubule; Mitochondrion; Neurogenesis; Reference proteome;
KW Schizophrenia; Synapse; Ubl conjugation; Wnt signaling pathway.
FT CHAIN 1..854
FT /note="Disrupted in schizophrenia 1 protein"
FT /id="PRO_0000079916"
FT REGION 1..292
FT /note="Interaction with MAP1A"
FT /evidence="ECO:0000269|PubMed:12812986"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 179..205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 221..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 278..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 293..696
FT /note="Interaction with TRAF3IP1"
FT /evidence="ECO:0000269|PubMed:12812986"
FT REGION 440..597
FT /note="Required for localization to punctate cytoplasmic
FT foci"
FT REGION 446..854
FT /note="Necessary and sufficient for interaction with PCNT
FT and localization at the centrosome"
FT /evidence="ECO:0000269|PubMed:18955030"
FT REGION 598..854
FT /note="Interaction with ATF4 and ATF5"
FT /evidence="ECO:0000269|PubMed:12812986"
FT REGION 716..739
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 727..854
FT /note="Interaction with PAFAH1B1"
FT /evidence="ECO:0000269|PubMed:14962739"
FT REGION 802..835
FT /note="Interaction with NDEL1"
FT COILED 366..394
FT /evidence="ECO:0000255"
FT COILED 452..505
FT /evidence="ECO:0000255"
FT COILED 602..666
FT /evidence="ECO:0000255"
FT COILED 802..830
FT /evidence="ECO:0000255"
FT MOTIF 197..203
FT /note="Interaction with FBXW7"
FT /evidence="ECO:0000269|PubMed:28727686"
FT CROSSLNK 372
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:28727686"
FT VAR_SEQ 23..372
FT /note="Missing (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_047525"
FT VAR_SEQ 350..369
FT /note="VISLRLKLQKLQEDAVENDD -> LEPIALDPPWKPRHPEPNSY (in
FT isoform 4)"
FT /evidence="ECO:0000303|PubMed:12573262"
FT /id="VSP_019314"
FT VAR_SEQ 350..356
FT /note="VISLRLK -> LRRYNKD (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_047526"
FT VAR_SEQ 357..854
FT /note="Missing (in isoform 10)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_047527"
FT VAR_SEQ 370..854
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12573262"
FT /id="VSP_019315"
FT VAR_SEQ 545..559
FT /note="SLQERIKSLNLSLKE -> RNKCEGKYYEVHGNT (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_043583"
FT VAR_SEQ 545..551
FT /note="SLQERIK -> RKPFLDG (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_047528"
FT VAR_SEQ 552..854
FT /note="Missing (in isoform 11)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_047529"
FT VAR_SEQ 560..579
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_043584"
FT VAR_SEQ 564..579
FT /note="VCMSEKFCSTLRKKVN -> ETISGRLKTSPRRLDH (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_043585"
FT VAR_SEQ 580..854
FT /note="Missing (in isoform 6 and isoform 7)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_043586"
FT VAR_SEQ 661..854
FT /note="ETSVKENTMKYMETLKNKLCSCKCPLLGKVWEADLEACRLLIQSLQLQEARG
FT SLSVEDERQMDDLEGAAPPIPPRLHSEDKRKTPLKVLEEWKTHLIPSLHCAGGEQKEES
FT YILSAELGEKCEDIGKKLLYLEDQLHTAIHSHDEDLIQSLRRELQMVKETLQAMILQLQ
FT PAKEAGEREAAASCMTAGVHEAQA -> DGVSLCRPVWSAVVRSCSLQPLPPEFKQFSC
FT LSLRSSWDYRCPPPCLANFVFLVEMGFYHVDQTGLKLLTSSDPPSSASQSAGITDMSHC
FT AWPLQ (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_043214"
FT VAR_SEQ 661..695
FT /note="ETSVKENTMKYMETLKNKLCSCKCPLLGKVWEADL -> AASVHCLGKCGKL
FT TWKLVDCLSRAYSSRKPGEACL (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_043587"
FT VAR_SEQ 661..678
FT /note="ETSVKENTMKYMETLKNK -> GYKYCDAESWTQRSQQLA (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:12573262"
FT /id="VSP_019316"
FT VAR_SEQ 661..662
FT /note="ET -> GR (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_047530"
FT VAR_SEQ 663..854
FT /note="Missing (in isoform 9)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_047531"
FT VAR_SEQ 679..854
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:12573262"
FT /id="VSP_019317"
FT VAR_SEQ 696..854
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:19805229"
FT /id="VSP_043588"
FT VAR_SEQ 748..769
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:9455484"
FT /id="VSP_003849"
FT VARIANT 5
FT /note="G -> V (in dbSNP:rs3738400)"
FT /evidence="ECO:0000269|PubMed:15386212"
FT /id="VAR_030422"
FT VARIANT 116
FT /note="A -> V (in dbSNP:rs56020408)"
FT /id="VAR_061642"
FT VARIANT 264
FT /note="R -> Q (in dbSNP:rs3738401)"
FT /evidence="ECO:0000269|PubMed:10814723,
FT ECO:0000269|PubMed:12573262, ECO:0000269|PubMed:9455484"
FT /id="VAR_022437"
FT VARIANT 328
FT /note="T -> N (in dbSNP:rs55795950)"
FT /id="VAR_061643"
FT VARIANT 330
FT /note="L -> F (in dbSNP:rs34622148)"
FT /id="VAR_050954"
FT VARIANT 531
FT /note="G -> R (in dbSNP:rs56229136)"
FT /id="VAR_061644"
FT VARIANT 607
FT /note="L -> F (associated with susceptibility to
FT schizoaffective disorder; dbSNP:rs6675281)"
FT /evidence="ECO:0000269|PubMed:15386212"
FT /id="VAR_026704"
FT VARIANT 704
FT /note="S -> C (in dbSNP:rs821616)"
FT /evidence="ECO:0000269|PubMed:10814723,
FT ECO:0000269|PubMed:15939883"
FT /id="VAR_022438"
FT MUTAGEN 372
FT /note="K->R: Reduced ubiquitination."
FT /evidence="ECO:0000269|PubMed:28727686"
FT MUTAGEN 815
FT /note="L->P: Impairs interaction with NDEL1; when
FT associated with P-822."
FT /evidence="ECO:0000269|PubMed:14962739"
FT MUTAGEN 822
FT /note="L->P: Impairs interaction with NDEL1; when
FT associated with P-815."
FT /evidence="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
