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.
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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
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Viral binding parters of members of the DISC1 interactome: Data from VirusMint, HSV-1 interaction database and literature survey
DISC1 Partner Gene symbol |
PROTEIN NAME |
Viral binder |
|
ACTG1 |
Actin, cytoplasmic 2 |
HIV-1
(1)
HSV-1
(2)
|
|
ACTN2 |
Actinin, alpha 2 |
Hepatitis C
(3)
|
|
AKAP9 |
A-kinase anchor protein 9 |
Epstein-Barr
(1)
|
|
ATF4 |
Cyclic AMP-dependent transcription factor ATF-4 |
HSV-1
(2)
|
|
ATF5 |
Cyclic AMP-dependent transcription factor ATF-5 |
HTLV1
(4)
|
|
BICD1 |
Protein bicaudal D homolog 1 |
Cytomegalovirus
(5)
|
|
C14orf135 |
Uncharacterized protein C14orf135 precursor |
Hepatitis C
(6)
|
|
CIT |
Citron kinase |
Rubella
(7)
|
|
DCTN1 |
Dynactin-1 |
HSV-1
(2)
|
|
DCTN2 |
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)
|
|
DNAJC7 |
DnaJ homolog subfamily C member 7 |
Part of a complex forming the coxsackie virus receptor
(13)
|
|
DYNC1H1 |
Dynein heavy chain, cytosolic |
Adenovirus (in a complex with dynactin and
NDEL1)
(14)
|
|
EEF2 |
Elongation factor 2 |
Epstein Barr
(15)
|
|
EIF3S3 |
Eukaryotic translation initiation factor 3 subunit 3 |
Hepatitis C
(16)
|
|
FEZ1 |
Fasciculation and elongation protein
zeta 1 (zygin I) |
JC Polyomavirus
(17)
|
|
HERC2 |
HECT domain and RCC1-like domain-containing protein 2 |
Papillomavirus
16
(18)
|
|
KIF3C |
Kinesin-like protein KIF3C |
HIV-1
(19)
|
|
MATR3 |
Matrin-3 |
HSV-1
(2)
|
|
NDEL1 |
Nuclear distribution protein nudE-like 1 |
Part of a complex involved in Adenovirus transport ( with dynactin and
cytoplasmic dynein)
(14)
|
|
PAFAH1B1 |
Platelet-activating factor acetylhydrolase IB
subunit alpha |
Binds to Poliovirus P3 protein and
HIV-1 Tat
(20,21)
|
|
PCNT |
Pericentrin |
Involved in the microtubular transport of
the adenovirus
(22)
|
|
PGK1 |
Phosphoglycerate kinase 1 |
Epstein-Barr
(23)
|
|
SMARCE1 |
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin
subfamily E member 1 |
HSV-1
(1)
|
|
STX18 |
Syntaxin-18 |
Papillomavirus
(23)
|
|
TNKS |
Tankyrase-1 |
Epstein-Barr
(24)
|
|
TUBB |
Tubulin beta chain |
Epstein-Barr
(23)
|
|
TUBB2A |
Tubulin alpha |
Influenza
(25)
|
|
YWHAE |
14-3-3 protein epsilon |
Hepatitis C
(1)
:L }:Epstein-Barr
(23)
|
|
YWHAQ |
14-3-3 protein theta |
HIV
(1)
HSV-1
(2)
|
|
YWHAZ |
14-3-3 protein zeta/delta |
HSV-1
(2)
:Epstein-Barr
(23)
|
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4. Forgacs, E., Gupta, S. K., Kerry, J. A., and Semmes, O. J.The bZIP transcription factor ATFx binds human T-cell leukemia virus
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6. Huang,
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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
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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
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and polymerase complex using proteomic-based approachesJ.Proteome.Res.2007;6:672-682.