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Showing Protein Disrupted in schizophrenia 1 protein (HMDBP14447)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 1 metabolite
Identification
HMDB Protein ID HMDBP14447
Secondary Accession Numbers None
Name Disrupted in schizophrenia 1 protein
Synonyms Not Available
Gene Name DISC1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Involved in the regulation of multiple aspects of embryonic and adult neurogenesis (PubMed:19502360, PubMed:19303846). Required for neural progenitor proliferation in the ventrical/subventrical zone during embryonic brain development and in the adult dentate gyrus of the hippocampus (By similarity). Participates in the Wnt-mediated neural progenitor proliferation as a positive regulator by modulating GSK3B activity and CTNNB1 abundance (PubMed:19303846). 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 (By similarity). Inhibits the activation of AKT-mTOR signaling upon interaction with CCDC88A (By similarity). Regulates the migration of early-born granule cell precursors toward the dentate gyrus during the hippocampal development (PubMed:19502360). Inhibits ATF4 transcription factor activity in neurons by disrupting ATF4 dimerization and DNA-binding (By similarity). Plays a role, together with PCNT, in the microtubule network formation (PubMed:18955030).
Pathways Not Available
Reactions Not Available
GO Classification
Biological Process
regulation of neuron projection development
response to electrical stimulus
regulation of dendritic spine development
positive regulation of neuroblast proliferation
positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
neuron migration
positive regulation of axon extension
cilium morphogenesis
positive regulation of neuron projection development
cell proliferation in forebrain
mitochondrial calcium ion homeostasis
non-motile cilium assembly
protein localization to centrosome
pyramidal neuron migration
regulation of synapse maturation
regulation of synaptic transmission, glutamatergic
canonical Wnt receptor signaling pathway
TOR signaling
positive regulation of cell-matrix adhesion
negative regulation of protein binding
microtubule cytoskeleton organization
positive regulation of Wnt receptor signaling pathway
Cellular Component
cytosol
centrosome
endoplasmic reticulum
mitochondrion
perinuclear region of cytoplasm
nucleus
cell body
synaptic vesicle
intermediate filament cytoskeleton
central region of growth cone
ciliary base
dynein complex
kinesin complex
ciliary basal body
postsynaptic density
microtubule
Molecular Function
protein-containing complex binding
molecular adaptor activity
kinesin binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 854
Molecular Weight 93609.585
Theoretical pI 6.36
Pfam Domain Function Not Available
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q9NRI5
UniProtKB/Swiss-Prot Entry Name DISC1_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gregory SG, Barlow KF, McLay KE, Kaul R, Swarbreck D, Dunham A, Scott CE, Howe KL, Woodfine K, Spencer CC, Jones MC, Gillson C, Searle S, Zhou Y, Kokocinski F, McDonald L, Evans R, Phillips K, Atkinson A, Cooper R, Jones C, Hall RE, Andrews TD, Lloyd C, Ainscough R, Almeida JP, Ambrose KD, Anderson F, Andrew RW, Ashwell RI, Aubin K, Babbage AK, Bagguley CL, Bailey J, Beasley H, Bethel G, Bird CP, Bray-Allen S, Brown JY, Brown AJ, Buckley D, Burton J, Bye J, Carder C, Chapman JC, Clark SY, Clarke G, Clee C, Cobley V, Collier RE, Corby N, Coville GJ, Davies J, Deadman R, Dunn M, Earthrowl M, Ellington AG, Errington H, Frankish A, Frankland J, French L, Garner P, Garnett J, Gay L, Ghori MR, Gibson R, Gilby LM, Gillett W, Glithero RJ, Grafham DV, Griffiths C, Griffiths-Jones S, Grocock R, Hammond S, Harrison ES, Hart E, Haugen E, Heath PD, Holmes S, Holt K, Howden PJ, Hunt AR, Hunt SE, Hunter G, Isherwood J, James R, Johnson C, Johnson D, Joy A, Kay M, Kershaw JK, Kibukawa M, Kimberley AM, King A, Knights AJ, Lad H, Laird G, Lawlor S, Leongamornlert DA, Lloyd DM, Loveland J, Lovell J, Lush MJ, Lyne R, Martin S, Mashreghi-Mohammadi M, Matthews L, Matthews NS, McLaren S, Milne S, Mistry S, Moore MJ, Nickerson T, O'Dell CN, Oliver K, Palmeiri A, Palmer SA, Parker A, Patel D, Pearce AV, Peck AI, Pelan S, Phelps K, Phillimore BJ, Plumb R, Rajan J, Raymond C, Rouse G, Saenphimmachak C, Sehra HK, Sheridan E, Shownkeen R, Sims S, Skuce CD, Smith M, Steward C, Subramanian S, Sycamore N, Tracey A, Tromans A, Van Helmond Z, Wall M, Wallis JM, White S, Whitehead SL, Wilkinson JE, Willey DL, Williams H, Wilming L, Wray PW, Wu Z, Coulson A, Vaudin M, Sulston JE, Durbin R, Hubbard T, Wooster R, Dunham I, Carter NP, McVean G, Ross MT, Harrow J, Olson MV, Beck S, Rogers J, Bentley DR, Banerjee R, Bryant SP, Burford DC, Burrill WD, Clegg SM, Dhami P, Dovey O, Faulkner LM, Gribble SM, Langford CF, Pandian RD, Porter KM, Prigmore E: The DNA sequence and biological annotation of human chromosome 1. Nature. 2006 May 18;441(7091):315-21. [PubMed:16710414 ]
  2. Seki N, Ohira M, Nagase T, Ishikawa K, Miyajima N, Nakajima D, Nomura N, Ohara O: Characterization of cDNA clones in size-fractionated cDNA libraries from human brain. DNA Res. 1997 Oct 31;4(5):345-9. [PubMed:9455484 ]
  3. Brandon NJ, Handford EJ, Schurov I, Rain JC, Pelling M, Duran-Jimeniz B, Camargo LM, Oliver KR, Beher D, Shearman MS, Whiting PJ: Disrupted in Schizophrenia 1 and Nudel form a neurodevelopmentally regulated protein complex: implications for schizophrenia and other major neurological disorders. Mol Cell Neurosci. 2004 Jan;25(1):42-55. [PubMed:14962739 ]
  4. Millar JK, Wilson-Annan JC, Anderson S, Christie S, Taylor MS, Semple CA, Devon RS, St Clair DM, Muir WJ, Blackwood DH, Porteous DJ: Disruption of two novel genes by a translocation co-segregating with schizophrenia. Hum Mol Genet. 2000 May 22;9(9):1415-23. doi: 10.1093/hmg/9.9.1415. [PubMed:10814723 ]
  5. Taylor MS, Devon RS, Millar JK, Porteous DJ: Evolutionary constraints on the Disrupted in Schizophrenia locus. Genomics. 2003 Jan;81(1):67-77. doi: 10.1016/s0888-7543(02)00026-5. [PubMed:12573262 ]
  6. Nakata K, Lipska BK, Hyde TM, Ye T, Newburn EN, Morita Y, Vakkalanka R, Barenboim M, Sei Y, Weinberger DR, Kleinman JE: DISC1 splice variants are upregulated in schizophrenia and associated with risk polymorphisms. Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):15873-8. doi: 10.1073/pnas.0903413106. Epub 2009 Sep 2. [PubMed:19805229 ]
  7. Ekelund J, Hovatta I, Parker A, Paunio T, Varilo T, Martin R, Suhonen J, Ellonen P, Chan G, Sinsheimer JS, Sobel E, Juvonen H, Arajarvi R, Partonen T, Suvisaari J, Lonnqvist J, Meyer J, Peltonen L: Chromosome 1 loci in Finnish schizophrenia families. Hum Mol Genet. 2001 Jul 15;10(15):1611-7. doi: 10.1093/hmg/10.15.1611. [PubMed:11468279 ]
  8. Hennah W, Varilo T, Kestila M, Paunio T, Arajarvi R, Haukka J, Parker A, Martin R, Levitzky S, Partonen T, Meyer J, Lonnqvist J, Peltonen L, Ekelund J: Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects. Hum Mol Genet. 2003 Dec 1;12(23):3151-9. doi: 10.1093/hmg/ddg341. Epub 2003 Oct 7. [PubMed:14532331 ]
  9. Ozeki Y, Tomoda T, Kleiderlein J, Kamiya A, Bord L, Fujii K, Okawa M, Yamada N, Hatten ME, Snyder SH, Ross CA, Sawa A: Disrupted-in-Schizophrenia-1 (DISC-1): mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):289-94. doi: 10.1073/pnas.0136913100. Epub 2002 Dec 27. [PubMed:12506198 ]
  10. Hodgkinson CA, Goldman D, Jaeger J, Persaud S, Kane JM, Lipsky RH, Malhotra AK: Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder. Am J Hum Genet. 2004 Nov;75(5):862-72. doi: 10.1086/425586. Epub 2004 Sep 22. [PubMed:15386212 ]
  11. Brandon NJ, Schurov I, Camargo LM, Handford EJ, Duran-Jimeniz B, Hunt P, Millar JK, Porteous DJ, Shearman MS, Whiting PJ: Subcellular targeting of DISC1 is dependent on a domain independent from the Nudel binding site. Mol Cell Neurosci. 2005 Apr;28(4):613-24. doi: 10.1016/j.mcn.2004.11.003. [PubMed:15797709 ]
  12. Callicott JH, Straub RE, Pezawas L, Egan MF, Mattay VS, Hariri AR, Verchinski BA, Meyer-Lindenberg A, Balkissoon R, Kolachana B, Goldberg TE, Weinberger DR: Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8627-32. doi: 10.1073/pnas.0500515102. Epub 2005 Jun 6. [PubMed:15939883 ]
  13. Lipska BK, Peters T, Hyde TM, Halim N, Horowitz C, Mitkus S, Weickert CS, Matsumoto M, Sawa A, Straub RE, Vakkalanka R, Herman MM, Weinberger DR, Kleinman JE: Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs. Hum Mol Genet. 2006 Apr 15;15(8):1245-58. doi: 10.1093/hmg/ddl040. Epub 2006 Mar 1. [PubMed:16510495 ]
  14. Hattori T, Baba K, Matsuzaki S, Honda A, Miyoshi K, Inoue K, Taniguchi M, Hashimoto H, Shintani N, Baba A, Shimizu S, Yukioka F, Kumamoto N, Yamaguchi A, Tohyama M, Katayama T: A novel DISC1-interacting partner DISC1-Binding Zinc-finger protein: implication in the modulation of DISC1-dependent neurite outgrowth. Mol Psychiatry. 2007 Apr;12(4):398-407. doi: 10.1038/sj.mp.4001945. Epub 2007 Jan 23. [PubMed:17389905 ]
  15. Shimizu S, Matsuzaki S, Hattori T, Kumamoto N, Miyoshi K, Katayama T, Tohyama M: DISC1-kendrin interaction is involved in centrosomal microtubule network formation. Biochem Biophys Res Commun. 2008 Dec 26;377(4):1051-6. doi: 10.1016/j.bbrc.2008.10.100. Epub 2008 Oct 26. [PubMed:18955030 ]
  16. Meyer KD, Morris JA: Disc1 regulates granule cell migration in the developing hippocampus. Hum Mol Genet. 2009 Sep 1;18(17):3286-97. doi: 10.1093/hmg/ddp266. Epub 2009 Jun 5. [PubMed:19502360 ]
  17. Mao Y, Ge X, Frank CL, Madison JM, Koehler AN, Doud MK, Tassa C, Berry EM, Soda T, Singh KK, Biechele T, Petryshen TL, Moon RT, Haggarty SJ, Tsai LH: Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation via modulation of GSK3beta/beta-catenin signaling. Cell. 2009 Mar 20;136(6):1017-31. doi: 10.1016/j.cell.2008.12.044. [PubMed:19303846 ]
  18. Yalla K, Elliott C, Day JP, Findlay J, Barratt S, Hughes ZA, Wilson L, Whiteley E, Popiolek M, Li Y, Dunlop J, Killick R, Adams DR, Brandon NJ, Houslay MD, Hao B, Baillie GS: FBXW7 regulates DISC1 stability via the ubiquitin-proteosome system. Mol Psychiatry. 2018 May;23(5):1278-1286. doi: 10.1038/mp.2017.138. Epub 2017 Jul 20. [PubMed:28727686 ]