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Q811T9 (DISC1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 69. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein namesRecommended name:
Disrupted in schizophrenia 1 homolog
Gene names
Name:Disc1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length852 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Involved in the regulation of multiple aspects of embryonic and adult neurogenesis. Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus. Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance. Plays a role as a modulator of the AKT-mTOR signaling pathway controlling the tempo of the process of newborn neurons integration during adult neurogenesis, including neuron positioning, dendritic development and synapse formation. Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A. Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development. Plays a role, together with PCNT, in the microtubule network formation. Ref.7 Ref.8 Ref.9 Ref.10

Subunit structure

Interacts with tubulin alpha, ACTN2, ANKHD1, ATF4, ATF5, CEP63, EIF3S3, MAP1A, PAFAH1B1, RANBP9, SPTBN4, SYNE1 and TRAF3IP1. Interaction with microtubules may be mediated in part by TRAF3IP1. Interacts (via C-terminal) with PCNT. Interacts with CHCHD6 By similarity. Interacts with NDEL1. Interacts with CCDC88A (via C-terminus); the interaction is direct. Interacts with GSK3B. Ref.5 Ref.8 Ref.10

Subcellular location

Cytoplasm. Cytoplasm › cytoskeleton. Cytoplasm › cytoskeleton › centrosome. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Note: Colocalizes with PCNT at the centrosome. Colocalizes with NDEL1 in the perinuclear region and the centrosome By similarity. Localizes to punctate cytoplasmic foci which overlap in part with mitochondria. Ref.5 Ref.6 Ref.11

Tissue specificity

Expressed in granule cell precursors within the dentate migratory stream during the first week of postnatal life and in differentiated granule cells of the hippocampus (at protein level). Expressed in dentate gyrus, hippocampus and in the olfactory bulb. Ref.7 Ref.9

Developmental stage

Expressed in neuronal progenitors residing in the ventricular and subventriculare zones and in postmitotic neurons in the cortical plate of the cerebral cortex at 15 dpc. Expressed in granule cell precursors within the dentate migratory stream of the hippocampus at 19 dpc (at protein level). Ref.8 Ref.9

Disruption phenotype

Loss of function of DISC1 in the dentate gyrus of adult mice results in reduced neural progenitor cell proliferation and the appearance of schizophrenic and depressive-like behaviors. Ref.9

Ontologies

Keywords
   Biological processNeurogenesis
Wnt signaling pathway
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoskeleton
Membrane
Microtubule
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processTOR signaling cascade

Inferred from mutant phenotype Ref.10. Source: UniProtKB

canonical Wnt receptor signaling pathway

Inferred from mutant phenotype PubMed 20624590. Source: DFLAT

cell proliferation in forebrain

Inferred from mutant phenotype PubMed 20624590. Source: DFLAT

cerebral cortex radially oriented cell migration

Inferred from mutant phenotype PubMed 20624590. Source: DFLAT

microtubule cytoskeleton organization

Inferred from electronic annotation. Source: Compara

mitochondrial calcium ion homeostasis

Inferred from mutant phenotype PubMed 20880836. Source: MGI

neuron migration

Inferred from mutant phenotype Ref.9. Source: UniProtKB

positive regulation of Wnt receptor signaling pathway

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of neuroblast proliferation

Inferred from mutant phenotype Ref.8. Source: UniProtKB

positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype PubMed 20880836. Source: MGI

protein localization

Inferred from direct assay PubMed 21471969. Source: MGI

regulation of neuron projection development

Inferred from mutant phenotype Ref.7Ref.10. Source: UniProtKB

regulation of synapse maturation

Inferred from mutant phenotype Ref.7. Source: UniProtKB

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

centrosome

Inferred from direct assay PubMed 21471969. Source: MGI

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

mitochondrion

Inferred from electronic annotation. Source: Compara

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-KW

postsynaptic density

Inferred from electronic annotation. Source: UniProtKB-SubCell

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GSK3BP498414EBI-2298259,EBI-373586From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q811T9-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q811T9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-18: MQGGGPRGAPIHSPSHGA → MEAENSSWLTLPCLLY
Note: No experimental confirmation available.
Isoform 3 (identifier: Q811T9-3)

The sequence of this isoform differs from the canonical sequence as follows:
     595-658: GSCFSTAKELTEEIWALSSEREGLEMFLGRLLALSSRNSRRLGIVKEDHLRCRQDLALQDAAHK → E
Note: No experimental confirmation available.
Isoform 4 (identifier: Q811T9-4)

Also known as: ES;

The sequence of this isoform differs from the canonical sequence as follows:
     374-387: AETLRQRLEELEQE → GESKAVRRQFHLSP
     388-852: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 852852Disrupted in schizophrenia 1 homolog
PRO_0000240230

Regions

Region1 – 294294Interaction with MAP1A By similarity
Region295 – 693399Interaction with TRAF3IP1 By similarity
Region437 – 594158Required for localization to punctate cytoplasmic foci By similarity
Region443 – 852410Necessary and sufficient for interaction with PCNT and localization at the centrosome By similarity
Region595 – 852258Interaction with ATF4 and ATF5 By similarity
Region728 – 852125Interaction with NDEL1 and PAFAH1B1 By similarity
Region728 – 852125Interaction with PAFAH1B1 By similarity
Region802 – 83534Interaction with NDEL1 By similarity
Coiled coil367 – 39731 Potential
Coiled coil449 – 49648 Potential

Natural variations

Alternative sequence1 – 1818MQGGG…PSHGA → MEAENSSWLTLPCLLY in isoform 2.
VSP_019318
Alternative sequence374 – 38714AETLR…ELEQE → GESKAVRRQFHLSP in isoform 4.
VSP_019319
Alternative sequence388 – 852465Missing in isoform 4.
VSP_019320
Alternative sequence595 – 65864GSCFS…DAAHK → E in isoform 3.
VSP_019321

Experimental info

Sequence conflict81G → D in AAN77091. Ref.1
Sequence conflict81G → D in AAN77092. Ref.1
Sequence conflict1201S → F in AAO19641. Ref.3
Sequence conflict1201S → F in AAP83943. Ref.3
Sequence conflict1291A → G in AAN77091. Ref.1
Sequence conflict1291A → G in AAN77092. Ref.1
Sequence conflict1411R → K in AAN77091. Ref.1
Sequence conflict1411R → K in AAN77092. Ref.1
Sequence conflict1531F → C in AAN77091. Ref.1
Sequence conflict1531F → C in AAN77092. Ref.1
Sequence conflict1761K → T in AAN77091. Ref.1
Sequence conflict1761K → T in AAN77092. Ref.1
Sequence conflict1901P → S in AAN77091. Ref.1
Sequence conflict1901P → S in AAN77092. Ref.1
Sequence conflict1991A → P in AAN77091. Ref.1
Sequence conflict1991A → P in AAN77092. Ref.1
Sequence conflict2891S → P in AAN77091. Ref.1
Sequence conflict2891S → P in AAN77092. Ref.1
Sequence conflict2951Missing in AAN77091. Ref.1
Sequence conflict2951Missing in AAN77092. Ref.1
Sequence conflict3021G → V in AAN77091. Ref.1
Sequence conflict3021G → V in AAN77092. Ref.1
Sequence conflict3651V → A in AAN77091. Ref.1
Sequence conflict3651V → A in AAN77092. Ref.1
Sequence conflict3901R → H in AAN77091. Ref.1
Sequence conflict3901R → H in AAN77092. Ref.1
Sequence conflict4411A → T in CAD44629. Ref.2
Sequence conflict4611R → Q in AAN77091. Ref.1
Sequence conflict4611R → Q in AAN77092. Ref.1
Sequence conflict4741S → Y in CAD44629. Ref.2
Sequence conflict5331Q → H in AAN77091. Ref.1
Sequence conflict5331Q → H in AAN77092. Ref.1
Sequence conflict6391V → L in AAN77091. Ref.1
Sequence conflict6431H → Y in AAN77091. Ref.1
Sequence conflict7881K → R in AAN77091. Ref.1
Sequence conflict7881K → R in AAN77092. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 13, 2006. Version 2.
Checksum: B55A850B15028E6F

FASTA85292,525
        10         20         30         40         50         60 
MQGGGPRGAP IHSPSHGADS GHGLPPAVAP QRRRLTRRPG YMRSTAGSGI GFLSPAVGMP 

        70         80         90        100        110        120 
HPSSAGLTGQ QSQHSQSKAG QCGLDPGSHC QASLVGKPFL KSSLVPAVAS EGHLHPAQRS 

       130        140        150        160        170        180 
MRKRPVHFAV HSKNDSRQSE RLTGSFKPGD SGFWQELLSS DSFKSLAPSL DAPWNKGSRG 

       190        200        210        220        230        240 
LKTVKPLASP ALNGPADIAS LPGFQDTFTS SFSFIQLSLG AAGERGEAEG CLPSREAEPL 

       250        260        270        280        290        300 
HQRPQEMAAE ASSSDRPHGD PRHLWTFSLH AAPGLADLAQ VTRSSSRQSE CGTVSSSSSD 

       310        320        330        340        350        360 
TGFSSQDASS AGGRGDQGGG WADAHGWHTL LREWEPMLQD YLLSNRRQLE VTSLILKLQK 

       370        380        390        400        410        420 
CQEKVVEDGD YDTAETLRQR LEELEQEKGR LSWALPSQQP ALRSFLGYLA AQIQVALHGA 

       430        440        450        460        470        480 
TQRAGSDDPE APLEGQLRTT AQDSLPASIT RRDWLIREKQ RLQKEIEALQ ARMSALEAKE 

       490        500        510        520        530        540 
KRLSQELEEQ EVLLRWPGCD LMALVAQMSP GQLQEVSKAL GETLTSANQA PFQVEPPETL 

       550        560        570        580        590        600 
RSLRERTKSL NLAVRELTAQ VCSGEKLCSS LRRRLSDLDT RLPALLEAKM LALSGSCFST 

       610        620        630        640        650        660 
AKELTEEIWA LSSEREGLEM FLGRLLALSS RNSRRLGIVK EDHLRCRQDL ALQDAAHKTR 

       670        680        690        700        710        720 
MKANTVKCME VLEGQLSSCR CPLLGRVWKA DLETCQLLMQ SLQLQEAGSS PHAEDEEQVH 

       730        740        750        760        770        780 
STGEAAQTAA LAVPRTPHPE EEKSPLQVLQ EWDTHSALSP HCAAGPWKED SHIVSAEVGE 

       790        800        810        820        830        840 
KCEAIGVKLL HLEDQLLGAM YSHDEALFQS LQGELQTVKE TLQAMILQLQ PTKEAGEASA 

       850 
SYPTAGAQET EA

« Hide

Isoform 2 [UniParc].

Checksum: 04E0133A67BC4B2E
Show »

FASTA85092,681
Isoform 3 [UniParc].

Checksum: C2EE115DF618732D
Show »

FASTA78985,428
Isoform 4 (ES) [UniParc].

Checksum: 066544374E3C8790
Show »

FASTA38741,115

References

[1]"Cloning and characterization of Disc1, the mouse ortholog of DISC1 (Disrupted-in-Schizophrenia 1)."
Ma L., Liu Y., Ky B., Shughrue P.J., Austin C.P., Morris J.A.
Genomics 80:662-672(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3).
Strain: BALB/c.
[2]"Evolutionary constraints on the Disrupted in Schizophrenia locus."
Taylor M.S., Devon R.S., Millar J.K., Porteous D.J.
Genomics 81:67-77(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), NUCLEOTIDE SEQUENCE [MRNA] OF 1-594 (ISOFORM 1).
Strain: C57BL/6.
[3]"Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth."
Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., Okawa M., Yamada N., Hatten M.E., Snyder S.H., Ross C.A., Sawa A.
Proc. Natl. Acad. Sci. U.S.A. 100:289-294(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6J.
[4]Erratum
Ozeki Y., Tomoda T., Kleiderlein J., Kamiya A., Bord L., Fujii K., Okawa M., Yamada N., Hatten M.E., Snyder S.H., Ross C.A., Sawa A.
Proc. Natl. Acad. Sci. U.S.A. 101:13969-13969(2004)
[5]"Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders."
Brandon N.J., Handford E.J., Schurov I., Rain J.-C., Pelling M., Duran-Jimeniz B., Camargo L.M., Oliver K.R., Beher D., Shearman M.S., Whiting P.J.
Mol. Cell. Neurosci. 25:42-55(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NDEL1, SUBCELLULAR LOCATION.
[6]"Subcellular targeting of DISC1 is dependent on a domain independent from the Nudel binding site."
Brandon N.J., Schurov I., Camargo L.M., Handford E.J., Duran-Jimeniz B., Hunt P., Millar J.K., Porteous D.J., Shearman M.S., Whiting P.J.
Mol. Cell. Neurosci. 28:613-624(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"Disrupted-In-Schizophrenia 1 regulates integration of newly generated neurons in the adult brain."
Duan X., Chang J.H., Ge S., Faulkner R.L., Kim J.Y., Kitabatake Y., Liu X.B., Yang C.H., Jordan J.D., Ma D.K., Liu C.Y., Ganesan S., Cheng H.J., Ming G.L., Lu B., Song H.
Cell 130:1146-1158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[8]"Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling."
Mao Y., Ge X., Frank C.L., Madison J.M., Koehler A.N., Doud M.K., Tassa C., Berry E.M., Soda T., Singh K.K., Biechele T., Petryshen T.L., Moon R.T., Haggarty S.J., Tsai L.H.
Cell 136:1017-1031(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GSK3B, DEVELOPMENTAL STAGE.
[9]"Disc1 regulates granule cell migration in the developing hippocampus."
Meyer K.D., Morris J.A.
Hum. Mol. Genet. 18:3286-3297(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[10]"DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212."
Kim J.Y., Duan X., Liu C.Y., Jang M.H., Guo J.U., Pow-anpongkul N., Kang E., Song H., Ming G.L.
Neuron 63:761-773(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH CCDC88A.
[11]"Deletion of densin-180 results in abnormal behaviors associated with mental illness and reduces mGluR5 and DISC1 in the postsynaptic density fraction."
Carlisle H.J., Luong T.N., Medina-Marino A., Schenker L., Khorosheva E., Indersmitten T., Gunapala K.M., Steele A.D., O'Dell T.J., Patterson P.H., Kennedy M.B.
J. Neurosci. 31:16194-16207(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF513723 mRNA. Translation: AAN77091.1.
AF513724 mRNA. Translation: AAN77092.1.
AJ506179 mRNA. Translation: CAD44629.1.
AJ506180 mRNA. Translation: CAD44630.1.
AY177673 mRNA. Translation: AAO19641.1.
AY320287 mRNA. Translation: AAP83943.1.
IPIIPI00229246.
IPI00399803.
IPI00752934.
IPI00760027.
RefSeqNP_777278.2. NM_174853.2.
NP_777279.2. NM_174854.2.
UniGeneMm.233504.

3D structure databases

ProteinModelPortalQ811T9.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-54914N.
IntActQ811T9. 5 interactions.

PTM databases

PhosphoSiteQ811T9.

Proteomic databases

PRIDEQ811T9.

Protocols and materials databases

DNASU244667.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000075730; ENSMUSP00000075145; ENSMUSG00000043051.
ENSMUST00000098311; ENSMUSP00000095914; ENSMUSG00000043051.
ENSMUST00000117658; ENSMUSP00000112757; ENSMUSG00000043051.
ENSMUST00000118942; ENSMUSP00000112410; ENSMUSG00000043051.
ENSMUST00000121953; ENSMUSP00000112929; ENSMUSG00000043051.
ENSMUST00000122389; ENSMUSP00000112593; ENSMUSG00000043051.
GeneID244667.
KEGGmmu:244667.

Organism-specific databases

CTD27185.
MGIMGI:2447658. Disc1.

Phylogenomic databases

eggNOGNOG76097.
GeneTreeENSGT00390000006176.
HOGENOMHOG000056668.
HOVERGENHBG051360.
KOK16534.
OMAEKCEDIG.
OrthoDBEOG4DNF3X.

Gene expression databases

ArrayExpressQ811T9.
BgeeQ811T9.
CleanExMM_DISC1.
GenevestigatorQ811T9.

Family and domain databases

InterProIPR026081. DISC1.
[Graphical view]
PANTHERPTHR14332. PTHR14332. 1 hit.
ProtoNetSearch...

Other

NextBio386371.
SOURCESearch...

Entry information

Entry nameDISC1_MOUSE
AccessionPrimary (citable) accession number: Q811T9
Secondary accession number(s): Q7TQ21 expand/collapse secondary AC list , Q8CF87, Q8CF88, Q8CHP1, Q8CHP2
Entry history
Integrated into UniProtKB/Swiss-Prot: June 13, 2006
Last sequence update: June 13, 2006
Last modified: April 3, 2013
This is version 69 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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