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DISC1 Schizophrenia Forum

This was originally intended as a support to an online debate in the Schizophrenia Forum in 2007 Live discussion and again in 2010

As you can see the interactome has grown considerably, confirming the importance of this gene/protein in both Bipolar disorder and Schizophrenia

See also the protein Interactomes and Pathways generated by BioGrid ...CPath ...GenomeNetwork...INTACT ...PSTIING...STRING...HPRD...Reactome

The DISC1 primary interactions are from various two-hybrid and other studies (Camargo et al. 2007 2010 ;Assmann et al. 2006;Miyoshi et al. 2003; 2004

Millar et al. 2003;Morris et al. 2003;Ozeki et al. 2003;Shinoda et al. 2007; Taya et al, 2007 Enomoto et al, 2009). See also Carter 2007a and 2007b Please excuse any omissions.

The subsequent interactions of the DISC1 binding partners are essentially a summary of those found in the ENTREZ Gene interaction section. In some browsers, you should be able to click on the gene to reach this information (This works in Internet explorer but not in Firefox).

Several protein products of genes associated with schizophrenia or bipolar disorder can be directly linked to DISC1 (red lines) while others can be linked in two steps

Red genes have been associated with schizophrenia, yellow genes with bipolar disorder and orange genes with both conditions.



DISC1 as a hub gene 2007


DISC1 Interactome: Update 2010 Schizophrenia

Bipolar Disorder Yellow genes are Bipolar disorder Orange schizophrenia and Bipolar

(Rounded genes are from GWAS studies in both cases)

The DISC1 viral interactome (see below for refs) Proteins in grey boxes are known to bind to viral proteins:

HIV-1 gp120 also binds tyo NMDA receptors


Glutamatergic interactome in Schizophrenia and Bipolar disorder Click here for gene list






Viral binding parters of members of the DISC1 interactome: Data from VirusMint, HSV-1 interaction database and literature survey

DISC1 Partner Gene symbol


Viral binder


Actin, cytoplasmic 2

HIV-1 (1) HSV-1 (2)


Actinin, alpha 2

Hepatitis C (3)


A-kinase anchor protein 9

Epstein-Barr (1)


Cyclic AMP-dependent transcription factor ATF-4

HSV-1 (2)


Cyclic AMP-dependent transcription factor ATF-5

HTLV1 (4)


Protein bicaudal D homolog 1

Cytomegalovirus (5)


Uncharacterized protein C14orf135 precursor

Hepatitis C (6)


Citron kinase

Rubella (7)



HSV-1 (2)


Dynactin subunit 2

Dynactins are involved in the transport of the adenovirus, HSV-1, the hantaan virus, HTLV-1 and the poliovirus (8,9,10,11,12)


DnaJ homolog subfamily C member 7

Part of a complex forming the coxsackie virus receptor (13)


Dynein heavy chain, cytosolic

Adenovirus (in a complex with dynactin and NDEL1) (14)


Elongation factor 2

Epstein Barr (15)


Eukaryotic translation initiation factor 3 subunit 3

Hepatitis C (16)


Fasciculation and elongation protein zeta 1 (zygin I)

JC Polyomavirus (17)


HECT domain and RCC1-like domain-containing protein 2

Papillomavirus 16 (18)


Kinesin-like protein KIF3C

HIV-1 (19)



HSV-1 (2)


Nuclear distribution protein nudE-like 1

Part of a complex involved in Adenovirus transport ( with dynactin and cytoplasmic dynein) (14)


Platelet-activating factor acetylhydrolase IB subunit alpha

Binds to Poliovirus P3 protein and HIV-1 Tat (20,21)



Involved in the microtubular transport of the adenovirus (22)


Phosphoglycerate kinase 1

 Epstein-Barr (23)


SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily E member 1

HSV-1 (1)



 Papillomavirus (23)



 Epstein-Barr (24)


Tubulin beta chain

 Epstein-Barr (23)


Tubulin alpha

Influenza (25)


14-3-3 protein epsilon

Hepatitis C (1)  :L }:Epstein-Barr (23)


14-3-3 protein theta

HIV (1) HSV-1 (2)


14-3-3 protein zeta/delta

HSV-1 (2) :Epstein-Barr (23)

1. Chatr-aryamontri, A., Ceol, A., Peluso, D., Nardozza, A., Panni, S., Sacco, F., Tinti, M., Smolyar, A., Castagnoli, L., Vidal, M., Cusick, M. E., and Cesareni, G.VirusMINT: a viral protein interaction databaseNucleic Acids Res.2009;37:D669-D673. VirusMint

2. Herpes simplex: Host viral protein interactions.

3. Lan, S., Wang, H., Jiang, H., Mao, H., Liu, X., Zhang, X., Hu, Y., Xiang, L., and Yuan, Z.Direct interaction between alpha-actinin and hepatitis C virus NS5BFEBS Lett.20-11-2003;554:289-294.

4. Forgacs, E., Gupta, S. K., Kerry, J. A., and Semmes, O. J.The bZIP transcription factor ATFx binds human T-cell leukemia virus type 1 (HTLV-1) Tax and represses HTLV-1 long terminal repeat-mediated transcriptionJ.Virol.2005;79:6932-6939.

5. Indran, S. V., Ballestas, M. E., and Britt, W. J.Bicaudal D1-dependent trafficking of human cytomegalovirus tegument protein pp150 in virus-infected cellsJ.Virol.2010;84:3162-3177.

6. Huang, Y. P., Cheng, J., Zhang, S. L., Wang, L., Guo, J., Liu, Y., Yang, Y., Zhang, L. Y., Bai, G. Q., Gao, X. S., Ji, D., Lin, S. M., and Shao, Q.Screening of hepatocyte proteins binding to F protein of hepatitis C virus by yeast two-hybrid systemWorld J.Gastroenterol.28-9-2005;11:5659-5665.

7. Atreya, C. D., Kulkarni, S., and Mohan, K. V.Rubella virus P90 associates with the cytokinesis regulatory protein Citron-K kinase and the viral infection and constitutive expression of P90 protein both induce cell cycle arrest following S phase in cell cultureArch.Virol.2004;149:779-789.

8. Radtke, K., Kieneke, D., Wolfstein, A., Michael, K., Steffen, W., Scholz, T., Karger, A., and Sodeik, B.Plus- and minus-end directed microtubule motors bind simultaneously to herpes simplex virus capsids using different inner tegument structuresPLoS.Pathog.8-7-2010;6:e1000991-

9. Bremner, K. H., Scherer, J., Yi, J., Vershinin, M., Gross, S. P., and Vallee, R. B.Adenovirus transport via direct interaction of cytoplasmic dynein with the viral capsid hexon subunitCell Host.Microbe.17-12-2009;6:523-535.

10. Si, H., Verma, S. C., Lampson, M. A., Cai, Q., and Robertson, E. S.Kaposi's sarcoma-associated herpesvirus-encoded LANA can interact with the nuclear mitotic apparatus protein to regulate genome maintenance and segregationJ.Virol.2008;82:6734-6746.

11. Ramanathan, H. N., Chung, D. H., Plane, S. J., Sztul, E., Chu, Y. K., Guttieri, M. C., McDowell, M., Ali, G., and Jonsson, C. B.Dynein-dependent transport of the hantaan virus nucleocapsid protein to the endoplasmic reticulum-Golgi intermediate compartmentJ.Virol.2007;81:8634-8647.

12. Dorweiler, I. J., Ruone, S. J., Wang, H., Burry, R. W., and Mansky, L. M.Role of the human T-cell leukemia virus type 1 PTAP motif in Gag targeting and particle releaseJ.Virol.2006;80:3634-3643.

13. Kobayashi, K., Sueyoshi, T., Inoue, K., Moore, R., and Negishi, M.Cytoplasmic accumulation of the nuclear receptor CAR by a tetratricopeptide repeat protein in HepG2 cellsMol.Pharmacol.2003;64:1069-1075.

14. Bremner, K. H., Scherer, J., Yi, J., Vershinin, M., Gross, S. P., and Vallee, R. B.Adenovirus transport via direct interaction of cytoplasmic dynein with the viral capsid hexon subunitCell Host.Microbe.17-12-2009;6:523-535.

15. Johannsen, E., Luftig, M., Chase, M. R., Weicksel, S., Cahir-McFarland, E., Illanes, D., Sarracino, D., and Kieff, E.Proteins of purified Epstein-Barr virusProc.Natl.Acad.Sci.U.S.A.16-11-2004;101:16286-16291.

16. Collier, A. J., Gallego, J., Klinck, R., Cole, P. T., Harris, S. J., Harrison, G. P., Aboul-Ela, F., Varani, G., and Walker, S.A conserved RNA structure within the HCV IRES eIF3-binding siteNat.Struct.Biol.2002;9:375-380.

17. Sawa, H., Suzuki, T., Orba, Y., Sunden, Y., and Nagashima, K.Recent research on the JC virusBrain Nerve.2007;59:101-108.

18. Vos, R. M., Altreuter, J., White, E. A., and Howley, P. M.The ubiquitin-specific peptidase USP15 regulates human papillomavirus type 16 E6 protein stabilityJ.Virol.2009;83:8885-8892.

19. Konig, R., Zhou, Y., Elleder, D., Diamond, T. L., Bonamy, G. M., Irelan, J. T., Chiang, C. Y., Tu, B. P., De Jesus, P. D., Lilley, C. E., Seidel, S., Opaluch, A. M., Caldwell, J. S., Weitzman, M. D., Kuhen, K. L., Bandyopadhyay, S., Ideker, T., Orth, A. P., Miraglia, L. J., Bushman, F. D., Young, J. A., and Chanda, S. K.Global analysis of host-pathogen interactions that regulate early-stage HIV-1 replicationCell.3-10-2008;135:49-60.

20. Kondratova, A. A., Neznanov, N., Kondratov, R. V., and Gudkov, A. V.Poliovirus protein 3A binds and inactivates LIS1, causing block of membrane protein trafficking and deregulation of cell divisionCell Cycle.2005;4:1403-1410.

21. Epie, N., Ammosova, T., Sapir, T., Voloshin, Y., Lane, W. S., Turner, W., Reiner, O., and Nekhai, S.HIV-1 Tat interacts with LIS1 proteinRetrovirology.7-2-2005;2:6-

22. Verdier, Y. and Penke, B.Binding sites of amyloid beta-peptide in cell plasma membrane and implications for Alzheimer's diseaseCurr.Protein Pept.Sci.2004;5:19-31.

23. Bossis, I., Roden, R. B., Gambhira, R., Yang, R., Tagaya, M., Howley, P. M., and Meneses, P. I.Interaction of tSNARE syntaxin 18 with the papillomavirus minor capsid protein mediates infectionJ.Virol.2005;79:6723-6731.

24. Brunetti, C. R., Dingwell, K. S., Wale, C., Graham, F. L., and Johnson, D. C.Herpes simplex virus gD and virions accumulate in endosomes by mannose 6-phosphate-dependent and -independent mechanismsJ.Virol.1998;72:3330-3339.

25. Mayer, D., Molawi, K., Martinez-Sobrido, L., Ghanem, A., Thomas, S., Baginsky, S., Grossmann, J., Garcia-Sastre, A., and Schwemmle, M.Identification of cellular interaction partners of the influenza virus ribonucleoprotein complex and polymerase complex using proteomic-based approachesJ.Proteome.Res.2007;6:672-682.


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