ID DISC1_HUMAN Reviewed; 854 AA. AC Q9NRI5; O75045; Q5VT44; Q5VT45; Q8IXJ0; Q8IXJ1; Q9BX19; Q9NRI3; AC Q9NRI4; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 16-NOV-2001, sequence version 2. DT 23-JAN-2007, entry version 42. DE 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 VARIANT RP CYS-704. RX MEDLINE=20275630; 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 schizophrenia-linked RT translocation."; RL Hum. Mol. Genet. 9:1415-1423(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), AND VARIANT ARG-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). RC TISSUE=Brain; RX MEDLINE=98116662; 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 [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-264. 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., Hubbard T., Wooster R., Dunham I., RA Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., RA Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] 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 [6] RP INTERACTION WITH NDEL1, AND SUBCELLULAR LOCATION. RX MEDLINE=22406307; 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 [7] 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 [8] 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 [9] 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 [10] 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). CC -!- SUBUNIT: Interacts with tubulin alpha, ACTN2, ANKHD1, ATF4, ATF5, CC CEP63, EIF3S3, MAP1A, NDEL1, PAFAH1B1, RANBP9, SPTBN4, SYNE1 and CC TRAF3IP1. Interaction with microtubules may be mediated in part by CC TRAF3IP1. CC -!- INTERACTION: CC Q59EN1:-; NbExp=2; IntAct=EBI-529989, EBI-1104844; CC Q7Z586:-; NbExp=6; IntAct=EBI-529989, EBI-928720; CC Q9NRD6:-; NbExp=6; IntAct=EBI-529989, EBI-928811; CC Q5VXF1:ACTN2; NbExp=3; IntAct=EBI-529989, EBI-928705; CC P18848:ATF4; NbExp=3; IntAct=EBI-529989, EBI-492498; CC Q9Y2D1:ATF5; NbExp=7; IntAct=EBI-529989, EBI-492509; CC Q96JB5:CDK5RAP3; NbExp=2; IntAct=EBI-529989, EBI-718818; CC Q96MT8:CEP63; NbExp=7; IntAct=EBI-529989, EBI-741977; CC P12110:COL6A2; NbExp=3; IntAct=EBI-529989, EBI-928749; CC Q13561:DCTN2; NbExp=2; IntAct=EBI-529989, EBI-715074; CC Q5HYC1:DKFZp686L07235; NbExp=2; IntAct=EBI-529989, EBI-1104674; CC Q14204:DNCH1; NbExp=2; IntAct=EBI-529989, EBI-356015; CC O94833-2:DST; NbExp=2; IntAct=EBI-529989, EBI-1019345; CC O15372:EIF3S3; NbExp=7; IntAct=EBI-529989, EBI-709735; CC Q8N8H3:FLJ39502; NbExp=5; IntAct=EBI-529989, EBI-928795; CC Q16891:IMMT; NbExp=2; IntAct=EBI-529989, EBI-473801; CC Q15811:ITSN1; NbExp=3; IntAct=EBI-529989, EBI-602041; CC Q9P2H0:KIAA1377; NbExp=2; IntAct=EBI-529989, EBI-473176; CC Q9UPN3:MACF1; NbExp=2; IntAct=EBI-529989, EBI-522925; CC P78559:MAP1A; NbExp=3; IntAct=EBI-529989, EBI-929047; CC Q86XW5:MCAF; NbExp=3; IntAct=EBI-529989, EBI-928732; CC Q9GZM8:MITAP1; NbExp=9; IntAct=EBI-529989, EBI-928842; CC P12883:MYH7; NbExp=2; IntAct=EBI-529989, EBI-519141; CC Q99784:OLFM1; NbExp=2; IntAct=EBI-529989, EBI-1105073; CC O95613:PCNT; NbExp=3; IntAct=EBI-529989, EBI-530012; CC Q96S59:RANBP9; NbExp=6; IntAct=EBI-529989, EBI-636085; CC Q02833:RASSF7; NbExp=2; IntAct=EBI-529989, EBI-929013; CC Q969G3:SMARCE1; NbExp=2; IntAct=EBI-529989, EBI-455078; CC Q9UNH7:SNX6; NbExp=2; IntAct=EBI-529989, EBI-949294; CC Q9H254:SPTBN4; NbExp=3; IntAct=EBI-529989, EBI-308543; CC Q8NF91:SYNE1; NbExp=6; IntAct=EBI-529989, EBI-928867; CC P63104:YWHAZ; NbExp=2; IntAct=EBI-529989, EBI-347088; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Centrosome. Note=Localizes to CC neurites (By similarity). Localizes to punctate cytoplasmic foci CC which overlap in part with mitochondria. Also localizes to the CC centrosome. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; 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 -!- 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 -!- 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 -!- DISEASE: A chromosomal aberration involving DISC1 segregates with CC 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 --------------------------------------------------------------------------- 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; AL626763; CAH70955.1; -; 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; -; 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; -; 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; -; 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; -; 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; -; 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 IntAct; Q9NRI5; -. DR Ensembl; ENSG00000162946; Homo sapiens. DR KEGG; hsa:27185; -. DR H-InvDB; HIX0022179; -. DR HGNC; HGNC:2888; DISC1. DR MIM; 605210; gene. DR ArrayExpress; Q9NRI5; -. DR GermOnline; ENSG00000162946; Homo sapiens. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR InterPro; IPR009079; 4_helix_cytokine. KW Alternative splicing; Chromosomal rearrangement; Coiled coil; KW Cytoskeleton; Microtubule; Polymorphism. 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 598 854 Interaction with ATF4 and ATF5. FT REGION 727 854 Interaction with NDEL1 and PAFAH1B1. FT COILED 366 394 Potential. FT COILED 452 505 Potential. FT COILED 602 666 Potential. FT COILED 802 830 Potential. FT VAR_SEQ 350 369 VISLRLKLQKLQEDAVENDD -> LEPIALDPPWKPRHPEP FT NSY (in isoform 4). FT /FTId=VSP_019314. FT VAR_SEQ 370 854 Missing (in isoform 4). FT /FTId=VSP_019315. FT VAR_SEQ 661 678 ETSVKENTMKYMETLKNK -> GYKYCDAESWTQRSQQLA FT (in isoform 3). FT /FTId=VSP_019316. FT VAR_SEQ 679 854 Missing (in isoform 3). FT /FTId=VSP_019317. FT VAR_SEQ 748 769 Missing (in isoform 2). FT /FTId=VSP_003849. FT VARIANT 264 264 Q -> R (in dbSNP:rs3738401). FT /FTId=VAR_022437. FT VARIANT 607 607 L -> F (in dbSNP:rs6675281). FT /FTId=VAR_026704. FT VARIANT 704 704 S -> C (in dbSNP:rs821616). FT /FTId=VAR_022438. FT MUTAGEN 815 815 L->P: Impairs interaction with NDEL1; FT when associated with P-822. FT MUTAGEN 822 822 L->P: Impairs interaction with NDEL1; FT when associated with P-815. FT CONFLICT 809 809 Q -> H (in Ref. 4). SQ SEQUENCE 854 AA; 93583 MW; C74903867F83A06A 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 CLSQPFSLLA 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 //