The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

DLG1  -  discs, large homolog 1 (Drosophila)

Homo sapiens

Synonyms: DLGH1, Disks large homolog 1, SAP-97, SAP97, Synapse-associated protein 97, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of DLG1

  • As one-third retained the normal brain-splicing pattern, the loss of normal splicing of hDLG1 may not in itself cause formation of tumors, but it might reflect the biological character of individual neuroblastomas [1].
  • The human homologue of Drosophila tumor suppressor dlg, hDLG1, is one of the proteins known to interact with APC, a tumor suppressor for colorectal cancer [1].
  • Our results suggest that (i) besides its well documented role in regulating epithelial polarity, Dlgh1 also regulates smooth muscle orientation, and (ii) human DLG1 mutations may contribute to hereditary forms of hydronephrosis [2].
  • Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma [3].
  • The fact that several different human virus oncoproteins, including adenovirus type 9 E4-ORF1, evolved to target the Dlg1 mammalian homolog of the membrane-associated Drosophila discs-large tumor suppressor has implicated this cellular factor in human cancer [4].

High impact information on DLG1

  • A human Dlg homolog, hDlg, has been implicated in tumorigenic processes via its association with the product of the Adenomatous Polyposis Coli (APC) gene [5].
  • A Dlgh1 mutant incapable of binding p38 failed to activate NFAT [6].
  • Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors [6].
  • Loss of potentiation was correlated with faster turnover of monomeric SAP97 mutants in dendritic spines [7].
  • We also suggest how recently discovered binding interactions could provide a structural readout mechanism: the autophosphorylated state of CaMKII binds tightly to the NMDAR and forms, through CaMKII-actinin-actin-(4.1/SAP97) linkages, additional sites for anchoring AMPARs at synapses [8].

Chemical compound and disease context of DLG1

  • Using a yeast two-hybrid screen, we identified hDlg as a cellular binding partner of a viral membrane integral protein, the envelope glycoprotein (Env) of human T-cell leukemia virus type 1 (HTLV-1) [9].

Biological context of DLG1


Anatomical context of DLG1

  • In contrast, in stably transfected confluent MDCK cells, both hDlg-I2 and -I3 isoforms localized efficiently to the lateral membrane, consistent with the previous notion that the N-terminal domain of hDlg mediates its membrane targeting in polarized epithelial cells [13].
  • 1. Furthermore, we found that Kir4.1 as well as SAP97 distributed not diffusely but clustered in retinal glial cells [14].
  • In epithelial cells, hDlg localizes at the basolateral plasma membrane, but its localization mechanism is unknown [15].
  • These results suggest that hDlg localizes at the plasma membrane through TEM5 and TEM5-like and furthermore scaffolds these GPCRs in endothelial cells during tumor angiogenesis and neoangiogenesis [15].
  • Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia [16].

Associations of DLG1 with chemical compounds

  • In a two-hybrid screen, we identified a 322-aa serine/threonine kinase that binds to the PDZ2 domain of hDlg [11].
  • Threonine phosphorylation of the MMAC1/ PTEN-PDZBD peptide inhibited both microtiter plate binding to the hDLG and hMAST205 PDZ domains and coprecipitation of the Mr 140,000 and > 200,000 proteins, but promoted coprecipitation of proteins of approximately Mr 90,000 and Mr 120,000 from A431 cell lysate [17].
  • Here, green fluorescent protein (GFP)-tagged chimeras and deletion mutants of SAP97 and SAP90 were employed to define the molecular mechanism underlying their differential association with kainate receptors [18].
  • Selective binding of synapse-associated protein 97 to GluR-A alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionate receptor subunit is determined by a novel sequence motif [19].
  • Surface plasmon resonance experiments revealed that mutation of SAP97 Thr(389) to alanine, as with the other PSD-95-like membrane-associated guanylate kinases, induced binding to megalin [20].

Physical interactions of DLG1


Co-localisations of DLG1


Regulatory relationships of DLG1


Other interactions of DLG1

  • We introduced a double mutation (I38A/I40A) into the N-terminal domain of hDlg, which disrupted its interaction with DLG2, a key event in the membrane targeting of hDlg [13].
  • The SAP97 PDZ2 domain differed at four positions from the other members of the PSD-95 subfamily [20].
  • Together, our results demonstrate that in addition to the N-terminal targeting domain, the alternatively spliced I3 insertion plays a critical role in recruiting hDlg to the lateral membrane in epithelial cells via its interaction with protein 4.1R [13].
  • E6AP was required for the in vivo degradation of DLG1 by both HVP-18 E6 and a chimeric HPV-11E6 [28].
  • hDlg, the human homologue of the Drosophila Discs-large (Dlg) tumor suppressor protein, is known to interact with the tumor suppressor protein APC and the human papillomavirus E6 transforming protein [11].

Analytical, diagnostic and therapeutic context of DLG1


  1. Identification of brain-specific splicing variants of the hDLG1 gene and altered splicing in neuroblastoma cell lines. Mori, K., Iwao, K., Miyoshi, Y., Nakagawara, A., Kofu, K., Akiyama, T., Arita, N., Hayakawa, T., Nakamura, Y. J. Hum. Genet. (1998) [Pubmed]
  2. Discs-large homolog 1 regulates smooth muscle orientation in the mouse ureter. Mahoney, Z.X., Sammut, B., Xavier, R.J., Cunningham, J., Go, G., Brim, K.L., Stappenbeck, T.S., Miner, J.H., Swat, W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Somatic mutations and altered expression of the candidate tumor suppressors CSNK1 epsilon, DLG1, and EDD/hHYD in mammary ductal carcinoma. Fuja, T.J., Lin, F., Osann, K.E., Bryant, P.J. Cancer Res. (2004) [Pubmed]
  4. Oncogenic function for the Dlg1 mammalian homolog of the Drosophila discs-large tumor suppressor. Frese, K.K., Latorre, I.J., Chung, S.H., Caruana, G., Bernstein, A., Jones, S.N., Donehower, L.A., Justice, M.J., Garner, C.C., Javier, R.T. EMBO J. (2006) [Pubmed]
  5. Inhibition of patterned cell shape change and cell invasion by Discs large during Drosophila oogenesis. Goode, S., Perrimon, N. Genes Dev. (1997) [Pubmed]
  6. Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors. Round, J.L., Humphries, L.A., Tomassian, T., Mittelstadt, P., Zhang, M., Miceli, M.C. Nat. Immunol. (2007) [Pubmed]
  7. Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. Nakagawa, T., Futai, K., Lashuel, H.A., Lo, I., Okamoto, K., Walz, T., Hayashi, Y., Sheng, M. Neuron (2004) [Pubmed]
  8. A model of synaptic memory: a CaMKII/PP1 switch that potentiates transmission by organizing an AMPA receptor anchoring assembly. Lisman, J.E., Zhabotinsky, A.M. Neuron (2001) [Pubmed]
  9. Human Dlg protein binds to the envelope glycoproteins of human T-cell leukemia virus type 1 and regulates envelope mediated cell-cell fusion in T lymphocytes. Blot, V., Delamarre, L., Perugi, F., Pham, D., Bénichou, S., Benarous, R., Hanada, T., Chishti, A.H., Dokhélar, M.C., Pique, C. J. Cell. Sci. (2004) [Pubmed]
  10. DLG1: chromosome location of the closest human homologue of the Drosophila discs large tumor suppressor gene. Azim, A.C., Knoll, J.H., Marfatia, S.M., Peel, D.J., Bryant, P.J., Chishti, A.H. Genomics (1995) [Pubmed]
  11. Characterization of PDZ-binding kinase, a mitotic kinase. Gaudet, S., Branton, D., Lue, R.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  12. Two independent domains of hDlg are sufficient for subcellular targeting: the PDZ1-2 conformational unit and an alternatively spliced domain. Lue, R.A., Brandin, E., Chan, E.P., Branton, D. J. Cell Biol. (1996) [Pubmed]
  13. Protein 4.1-mediated membrane targeting of human discs large in epithelial cells. Hanada, T., Takeuchi, A., Sondarva, G., Chishti, A.H. J. Biol. Chem. (2003) [Pubmed]
  14. Clustering and enhanced activity of an inwardly rectifying potassium channel, Kir4.1, by an anchoring protein, PSD-95/SAP90. Horio, Y., Hibino, H., Inanobe, A., Yamada, M., Ishii, M., Tada, Y., Satoh, E., Hata, Y., Takai, Y., Kurachi, Y. J. Biol. Chem. (1997) [Pubmed]
  15. Direct binding of the human homologue of the Drosophila disc large tumor suppressor gene to seven-pass transmembrane proteins, tumor endothelial marker 5 (TEM5), and a novel TEM5-like protein. Yamamoto, Y., Irie, K., Asada, M., Mino, A., Mandai, K., Takai, Y. Oncogene (2004) [Pubmed]
  16. Selective reduction of a PDZ protein, SAP-97, in the prefrontal cortex of patients with chronic schizophrenia. Toyooka, K., Iritani, S., Makifuchi, T., Shirakawa, O., Kitamura, N., Maeda, K., Nakamura, R., Niizato, K., Watanabe, M., Kakita, A., Takahashi, H., Someya, T., Nawa, H. J. Neurochem. (2002) [Pubmed]
  17. Threonine phosphorylation of the MMAC1/PTEN PDZ binding domain both inhibits and stimulates PDZ binding. Adey, N.B., Huang, L., Ormonde, P.A., Baumgard, M.L., Pero, R., Byreddy, D.V., Tavtigian, S.V., Bartel, P.L. Cancer Res. (2000) [Pubmed]
  18. Molecular mechanisms regulating the differential association of kainate receptor subunits with SAP90/PSD-95 and SAP97. Mehta, S., Wu, H., Garner, C.C., Marshall, J. J. Biol. Chem. (2001) [Pubmed]
  19. Selective binding of synapse-associated protein 97 to GluR-A alpha-amino-5-hydroxy-3-methyl-4-isoxazole propionate receptor subunit is determined by a novel sequence motif. Cai, C., Coleman, S.K., Niemi, K., Keinänen, K. J. Biol. Chem. (2002) [Pubmed]
  20. Selective interaction of megalin with postsynaptic density-95 (PSD-95)-like membrane-associated guanylate kinase (MAGUK) proteins. Larsson, M., Hjälm, G., Sakwe, A.M., Engström, A., Höglund, A.S., Larsson, E., Robinson, R.C., Sundberg, C., Rask, L. Biochem. J. (2003) [Pubmed]
  21. Identification of SAP97 as an intracellular binding partner of TACE. Peiretti, F., Deprez-Beauclair, P., Bonardo, B., Aubert, H., Juhan-Vague, I., Nalbone, G. J. Cell. Sci. (2003) [Pubmed]
  22. Binding of the human homolog of the Drosophila discs large tumor suppressor protein to the mitochondrial ribosomal protein MRP-S34. Ogawa, F., Adachi, S., Kohu, K., Shige, K., Akiyama, T. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  23. Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells. Laprise, P., Viel, A., Rivard, N. J. Biol. Chem. (2004) [Pubmed]
  24. The APC-hDLG complex negatively regulates cell cycle progression from the G0/G1 to S phase. Ishidate, T., Matsumine, A., Toyoshima, K., Akiyama, T. Oncogene (2000) [Pubmed]
  25. Regulation of the discs large tumor suppressor by a phosphorylation-dependent interaction with the beta-TrCP ubiquitin ligase receptor. Mantovani, F., Banks, L. J. Biol. Chem. (2003) [Pubmed]
  26. Inward rectifier potassium channel Kir2.2 is associated with synapse-associated protein SAP97. Leonoudakis, D., Mailliard, W., Wingerd, K., Clegg, D., Vandenberg, C. J. Cell. Sci. (2001) [Pubmed]
  27. Dual role of CaMKII-dependent SAP97 phosphorylation in mediating trafficking and insertion of NMDA receptor subunit NR2A. Mauceri, D., Gardoni, F., Marcello, E., Di Luca, M. J. Neurochem. (2007) [Pubmed]
  28. Association of E6AP (UBE3A) with human papillomavirus type 11 E6 protein. Brimer, N., Lyons, C., Vande Pol, S.B. Virology (2007) [Pubmed]
  29. Plasma membrane Ca2+-atpase isoforms 2b and 4b interact promiscuously and selectively with members of the membrane-associated guanylate kinase family of PDZ (PSD95/Dlg/ZO-1) domain-containing proteins. DeMarco, S.J., Strehler, E.E. J. Biol. Chem. (2001) [Pubmed]
  30. Human discs large and scrib are localized at the same regions in colon mucosa and changes in their expression patterns are correlated with loss of tissue architecture during malignant progression. Gardiol, D., Zacchi, A., Petrera, F., Stanta, G., Banks, L. Int. J. Cancer (2006) [Pubmed]
  31. Human homologue of the Drosophila discs large tumor suppressor binds to p56lck tyrosine kinase and Shaker type Kv1.3 potassium channel in T lymphocytes. Hanada, T., Lin, L., Chandy, K.G., Oh, S.S., Chishti, A.H. J. Biol. Chem. (1997) [Pubmed]
WikiGenes - Universities