DISC1_RAT
ID DISC1_RAT Reviewed; 846 AA.
AC Q810H6;
DT 13-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 13-JUN-2006, sequence version 2.
DT 03-AUG-2022, entry version 120.
DE RecName: Full=Disrupted in schizophrenia 1 homolog {ECO:0000305};
GN Name=Disc1 {ECO:0000312|RGD:631359};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, AND DEVELOPMENTAL STAGE.
RC STRAIN=Sprague-Dawley;
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [4]
RP FUNCTION, INTERACTION WITH NDEL1, INDUCTION, AND SUBCELLULAR LOCATION.
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 [5]
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).
CC -!- FUNCTION: Involved in the regulation of multiple aspects of embryonic
CC and adult neurogenesis (PubMed:17035248). Required for neural
CC progenitor proliferation in the ventrical/subventrical zone during
CC embryonic 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 and
CC CTNNB1 abundance. Plays a role as a modulator of the AKT-mTOR signaling
CC pathway controlling the tempo of the process of newborn neurons
CC integration during adult neurogenesis, including neuron positioning,
CC dendritic development and synapse formation. Inhibits the activation of
CC AKT-mTOR signaling upon interaction with CCDC88A. Regulates the
CC migration of early-born granule cell precursors toward the dentate
CC gyrus during the hippocampal development. Inhibits ATF4 transcription
CC factor activity in neurons by disrupting ATF4 dimerization and DNA-
CC binding (By similarity). Plays a role, together with PCNT, in the
CC microtubule network formation (By similarity).
CC {ECO:0000250|UniProtKB:Q811T9, ECO:0000250|UniProtKB:Q9NRI5,
CC ECO:0000269|PubMed:17035248}.
CC -!- SUBUNIT: Interacts with NDEL1 (PubMed:17035248). 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. Interaction with microtubules may be mediated in part by
CC TRAF3IP1. Interacts (via C-terminal) with PCNT. Interacts with CHCHD6
CC (By similarity). Interacts with CCDC141 (By similarity). Interacts with
CC FBXW7, the substrate-recognition component of a SCF (SKP1-CUL1-F-box
CC protein) E3 ubiquitin-protein ligase complex; the interaction targets
CC DISC1 for proteasomal degradation (By similarity). Interacts with
CC ZNF365 (PubMed:17389905). Interacts with ATF4; inhibiting ATF4
CC transcription factor activity by disrupting ATF4 dimerization and DNA-
CC binding (By similarity). Interacts with PDE4B (By similarity).
CC {ECO:0000250|UniProtKB:Q811T9, ECO:0000250|UniProtKB:Q9NRI5,
CC ECO:0000269|PubMed:17035248, ECO:0000269|PubMed:17389905}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12506198}.
CC Cytoplasm, cytoskeleton {ECO:0000250|UniProtKB:Q9NRI5}. Mitochondrion
CC {ECO:0000269|PubMed:12506198}. Cytoplasm, cytoskeleton, microtubule
CC organizing center, centrosome {ECO:0000250|UniProtKB:Q9NRI5}.
CC Postsynaptic density {ECO:0000250|UniProtKB:Q811T9}. Note=Colocalizes
CC with NDEL1 in the perinuclear region and the centrosome (By
CC similarity). Localizes to punctate cytoplasmic foci which overlap in
CC part with mitochondria (PubMed:12506198). Colocalizes with PCNT at the
CC centrosome (By similarity). {ECO:0000250|UniProtKB:Q811T9,
CC ECO:0000250|UniProtKB:Q9NRI5, ECO:0000269|PubMed:12506198}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q810H6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q810H6-2; Sequence=VSP_019322;
CC -!- TISSUE SPECIFICITY: Expressed in brain, heart, kidney, liver and
CC thymus. Within the brain expression is high in the cerebral cortex,
CC hippocampus and olfactory bulb and is also seen at lower levels in the
CC cerebellum (at protein level). {ECO:0000269|PubMed:12506198}.
CC -!- DEVELOPMENTAL STAGE: Expressed at high levels at 20.5 dpc. Expressed at
CC lower levels at P2 and P6 and in adults (at protein level).
CC {ECO:0000269|PubMed:12506198}.
CC -!- INDUCTION: Up-regulated during neurite outgrowth upon differentiation
CC with NGF. {ECO:0000269|PubMed:17035248}.
CC -!- PTM: Ubiquitinated. Ubiquitination with 'Lys-48'-linked polyubiquitin
CC chains leads to its proteasomal degradation.
CC {ECO:0000250|UniProtKB:Q9NRI5}.
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DR EMBL; AY177674; AAO19642.2; -; mRNA.
DR EMBL; AABR03114003; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03114017; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03114274; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03114520; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03114547; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03114825; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03114846; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03114921; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115035; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115070; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115140; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115229; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115356; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115432; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115751; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03115947; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03116117; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_783186.2; NM_175596.2. [Q810H6-2]
DR RefSeq; XP_008770838.1; XM_008772616.2. [Q810H6-2]
DR AlphaFoldDB; Q810H6; -.
DR SMR; Q810H6; -.
DR BioGRID; 258859; 1.
DR CORUM; Q810H6; -.
DR STRING; 10116.ENSRNOP00000054753; -.
DR PaxDb; Q810H6; -.
DR Ensembl; ENSRNOT00000119995; ENSRNOP00000095161; ENSRNOG00000019779. [Q810H6-1]
DR GeneID; 307940; -.
DR KEGG; rno:307940; -.
DR UCSC; RGD:631359; rat. [Q810H6-1]
DR CTD; 27185; -.
DR RGD; 631359; Disc1.
DR eggNOG; ENOG502S3S3; Eukaryota.
DR GeneTree; ENSGT00390000006176; -.
DR HOGENOM; CLU_016380_1_0_1; -.
DR InParanoid; Q810H6; -.
DR OMA; CMEDNHP; -.
DR OrthoDB; 254709at2759; -.
DR PhylomeDB; Q810H6; -.
DR PRO; PR:Q810H6; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000019779; Expressed in heart and 9 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0044297; C:cell body; IDA:RGD.
DR GO; GO:0090724; C:central region of growth cone; IDA:RGD.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0036064; C:ciliary basal body; ISO:RGD.
DR GO; GO:0097546; C:ciliary base; ISO:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030286; C:dynein complex; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:RGD.
DR GO; GO:0045111; C:intermediate filament cytoskeleton; IBA:GO_Central.
DR GO; GO:0005871; C:kinesin complex; IDA:RGD.
DR GO; GO:0005874; C:microtubule; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0008021; C:synaptic vesicle; ISO:RGD.
DR GO; GO:0008092; F:cytoskeletal protein binding; TAS:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0019894; F:kinesin binding; IDA:RGD.
DR GO; GO:0060090; F:molecular adaptor activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0021846; P:cell proliferation in forebrain; ISO:RGD.
DR GO; GO:0021799; P:cerebral cortex radially oriented cell migration; ISO:RGD.
DR GO; GO:0060271; P:cilium assembly; IMP:RGD.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; ISO:RGD.
DR GO; GO:0051560; P:mitochondrial calcium ion homeostasis; ISO:RGD.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IMP:RGD.
DR GO; GO:0070050; P:neuron cellular homeostasis; IEA:Ensembl.
DR GO; GO:0001764; P:neuron migration; ISO:RGD.
DR GO; GO:1905515; P:non-motile cilium assembly; ISO:RGD.
DR GO; GO:0045773; P:positive regulation of axon extension; IMP:RGD.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:RGD.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISO:RGD.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:RGD.
DR GO; GO:0071539; P:protein localization to centrosome; IMP:GO_Central.
DR GO; GO:0021852; P:pyramidal neuron migration to cerebral cortex; IMP:RGD.
DR GO; GO:0060998; P:regulation of dendritic spine development; IMP:RGD.
DR GO; GO:0010975; P:regulation of neuron projection development; IMP:UniProtKB.
DR GO; GO:0090128; P:regulation of synapse maturation; ISO:RGD.
DR GO; GO:0051966; P:regulation of synaptic transmission, glutamatergic; IMP:MGI.
DR GO; GO:0051602; P:response to electrical stimulus; IEP:RGD.
DR GO; GO:0031929; P:TOR signaling; ISO:RGD.
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 Alternative splicing; Coiled coil; Cytoplasm; Cytoskeleton;
KW Developmental protein; Microtubule; Mitochondrion; Neurogenesis;
KW Reference proteome; Synapse; Ubl conjugation; Wnt signaling pathway.
FT CHAIN 1..846
FT /note="Disrupted in schizophrenia 1 homolog"
FT /id="PRO_0000240231"
FT REGION 1..288
FT /note="Interaction with MAP1A"
FT /evidence="ECO:0000250"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..312
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 289..686
FT /note="Interaction with TRAF3IP1"
FT /evidence="ECO:0000250"
FT REGION 409..436
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 429..587
FT /note="Required for localization to punctate cytoplasmic
FT foci"
FT /evidence="ECO:0000250"
FT REGION 435..846
FT /note="Necessary and sufficient for interaction with PCNT
FT and localization at the centrosome"
FT /evidence="ECO:0000250"
FT REGION 588..846
FT /note="Interaction with ATF4 and ATF5"
FT /evidence="ECO:0000250"
FT REGION 721..846
FT /note="Interaction with NDEL1 and PAFAH1B1"
FT /evidence="ECO:0000250"
FT REGION 721..846
FT /note="Interaction with PAFAH1B1"
FT /evidence="ECO:0000250"
FT REGION 795..828
FT /note="Interaction with NDEL1"
FT /evidence="ECO:0000250"
FT COILED 440..489
FT /evidence="ECO:0000255"
FT COMPBIAS 128..144
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 277..304
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 741..762
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12506198"
FT /id="VSP_019322"
SQ SEQUENCE 846 AA; 92563 MW; 8711C2FFC8494877 CRC64;
MQGAGSRGAW IHSPSHCPGN GHGSPPAVAP QRRRLTRRPG YMRSTASPGI GFLSPAVGMP
RPISAGLTGQ EFYPSQSKAR QCSLDLRSHC QDSLVGNPFL KGSLGPAVTS VGHLHPAQGS
MRERMVHSGV HSGNDRRQSE RLTGDSGCRQ EFLSSDSSKS LASSLDVAWS KGSRGLKTVR
PLVSPASNGP VDIPSLPGFQ DTFTSNFSFI RLSLGAAGER GEAEGCLPSR EAEPLHQSPQ
EMAAEGSGSD RPHGEPRHLW TFSLHAAPGL VDLAQGTRSN RQPECGMVSS SDAGFSSQDA
SPAGGRSDQD GGWADAHGWH ALLREWEPML QDYLLSNRRQ LEVTSLILKL QKLQEKAVED
GDYDMAETLR QRLEDLEQEK GRLPWALPSQ QPALRSFLGY LATQTHAALH GAPQRAGSDD
PEAPLEGQRR TTAQDSLPGL AVTRRDWLMR EKEQLQKEIE ALRARVSVLE AKEQRLSQEL
EDQEMLLRWQ GCDQMALVAQ LSPGQLQEVS KALGETLTSA RWAPFRVEPP ETLRSLRERT
KSLDLAVREL TEQVCSGEKL CSSLRKRLAD LDTRLPALLE AKMLALSGSC FSTAKELAEE
IWAVSSEREG LEMFLGRLLA LSSRNTRRLG SVKEDYLRCR QDLALQEAAH KTRVKANTVK
CTEVLEGQLS CCRCPLLERV WKADLEACQL LMQSLEIQEA GSSSHVEDEK QVHSTGEAAQ
TAALAVPRTP HPEEEKSPLQ VLCEWNTYSA SLPHCAAGLW KEESHVVFAE VGDKCEAIGM
RLLHLEDQLL GAMHGHDEAL FQSLQGELQM VKETLQTMFL QLQPAKEAGG EASASYSTAG
AQEAED
