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Gene Review

GEMIN4  -  gem (nuclear organelle) associated protein 4

Homo sapiens

Synonyms: Component of gems 4, DKFZP434B131, DKFZP434D174, Gem-associated protein 4, Gemin-4, ...
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Disease relevance of GEMIN4


Psychiatry related information on GEMIN4


High impact information on GEMIN4

  • Here we provide evidence that the soluble form of the iron binding protein p97 is found in elevated amounts in the serum of Alzheimer's patients compared with healthy controls [4].
  • In an in vitro model of retrotranslocation, the AAA ATPase p97, an enzyme critical for ERAD, was the only cytosolic cofactor required for protein export from isolated phagosomes [5].
  • Gemin4 is associated in vivo with the SMN complex through a direct interaction with Gemin3 [6].
  • Monoclonal antibodies against Gemin4 efficiently immunoprecipitate the spliceosomal U snRNAs U1 and U5 from Xenopus oocytes cytoplasm [6].
  • Interestingly, Gemin4 is also detected in the nucleoli, suggesting that the SMN complex may also function in preribosomal RNA processing or ribosome assembly [6].

Biological context of GEMIN4


Anatomical context of GEMIN4

  • Inasmuch as SMN-containing complexes have been implicated in the delivery of snRNPs to the H-complex, these results provide strong evidence that galectin-1 and galectin-3, by interacting with Gemin4, play a role in spliceosome assembly in vivo [11].
  • Gemin4 is one component of a macromolecular complex containing approximately 15 polypeptides, including SMN (survival of motor neuron) protein [11].
  • This protein, designated p97, was present in both cultured cells and biopsy material from melanomas and certain other tumors, but it was not detected in eight different samples of normal adult epithelial or mesenchymal tissues obtained from five donors [12].
  • Tumor-infiltrating lymphocytes (TIL) were obtained from a mouse melanoma cell line (CL 62) transfected with the gene for the human melanoma Ag p97 [13].
  • Two of the cell surface proteins, p80 and p97, were not detected in autologous fibroblasts [14].

Associations of GEMIN4 with chemical compounds

  • By two-dimensional gel electrophoresis and partial proteolytic mapping, these new proteins, which are induced by anaerobic exposures exceeding 12 hr, are identical to 76 and 97 kDa (p76 and p97, respectively) proteins induced by extended periods of glucose deprivation (greater than 14 hr) when oxygen is present [15].
  • Upon infection of tissue culture cells, v-p97NY expressed high levels of a membrane-bound glycoprotein immunoreactive with a p97-specific monoclonal antibody [2].

Physical interactions of GEMIN4

  • Association of galectin-1 and galectin-3 with Gemin4 in complexes containing the SMN protein [11].
  • We also found that galectin-3 interacted with Gemin4 and that it constituted one component of the complex co-immunoprecipitated with galectin-1 [11].

Other interactions of GEMIN4


Analytical, diagnostic and therapeutic context of GEMIN4

  • Since several of the transfected clones were found to express a stable level of p97 and have consistent in vivo growth behavior, they provide a useful model for various forms of antigen-specific active and passive immunotherapy with the same agents as those intended for human application [17].
  • Molecular cloning of cDNA for a new regulatory subunit, designated p97, of the human 26S proteasome showed that the polypeptide consists of 908 amino acid residues with a calculated molecular mass of 100184 Da and an isoelectric point of 4.94 [18].
  • Expression of the human melanoma-associated antigens, 250-Kd glycoprotein/proteoglycan and p97, was examined quantitatively by flow cytometry on fresh cell suspensions of human melanoma [19].
  • Autoantibodies to a full-length recombinant p97/VCP were assayed by immunoprecipitation [20].


  1. A unique antigenic epitope of human melanoma is carried on the common melanoma glycoprotein gp95/p97. Furukawa, K.S., Furukawa, K., Real, F.X., Old, L.J., Lloyd, K.O. J. Exp. Med. (1989) [Pubmed]
  2. Characterization of a recombinant vaccinia virus expressing human melanoma-associated antigen p97. Hu, S.L., Plowman, G.D., Sridhar, P., Stevenson, U.S., Brown, J.P., Estin, C.D. J. Virol. (1988) [Pubmed]
  3. Expression level of valosin-containing protein (p97) is correlated with progression and prognosis of non-small-cell lung carcinoma. Yamamoto, S., Tomita, Y., Hoshida, Y., Iizuka, N., Monden, M., Yamamoto, S., Iuchi, K., Aozasa, K. Ann. Surg. Oncol. (2004) [Pubmed]
  4. Serum levels of the iron binding protein p97 are elevated in Alzheimer's disease. Kennard, M.L., Feldman, H., Yamada, T., Jefferies, W.A. Nat. Med. (1996) [Pubmed]
  5. A Role for the Endoplasmic Reticulum Protein Retrotranslocation Machinery during Crosspresentation by Dendritic Cells. Ackerman, A.L., Giodini, A., Cresswell, P. Immunity (2006) [Pubmed]
  6. Gemin4. A novel component of the SMN complex that is found in both gems and nucleoli. Charroux, B., Pellizzoni, L., Perkinson, R.A., Yong, J., Shevchenko, A., Mann, M., Dreyfuss, G. J. Cell Biol. (2000) [Pubmed]
  7. HCC-associated protein HCAP1, a variant of GEMIN4, interacts with zinc-finger proteins. Di, Y., Li, J., Zhang, Y., He, X., Lu, H., Xu, D., Ling, J., Huo, K., Wan, D., Li, Y.Y., Gu, J. J. Biochem. (2003) [Pubmed]
  8. Two variants of the human hepatocellular carcinoma-associated HCAP1 gene and their effect on the growth of the human liver cancer cell line Hep3B. Wan, D., He, M., Wang, J., Qiu, X., Zhou, W., Luo, Z., Chen, J., Gu, J. Genes Chromosomes Cancer (2004) [Pubmed]
  9. Nucleotide-specific interaction of Ran/TC4 with nuclear transport factors NTF2 and p97. Paschal, B.M., Delphin, C., Gerace, L. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  10. Isolation of a cDNA encoding the chicken p50B/p97 (Lyt-10) transcription factor. Ikeda, T., Hirota, Y., Onodera, T. Gene (1994) [Pubmed]
  11. Association of galectin-1 and galectin-3 with Gemin4 in complexes containing the SMN protein. Park, J.W., Voss, P.G., Grabski, S., Wang, J.L., Patterson, R.J. Nucleic Acids Res. (2001) [Pubmed]
  12. Identification of a cell surface protein, p97, in human melanomas and certain other neoplasms. Woodbury, R.G., Brown, J.P., Yeh, M.Y., Hellström, I., Hellström, K.E. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  13. Enhancement of in vitro tumor-infiltrating lymphocyte cytotoxicity by heteroconjugated antibodies. Reid, I., Lundy, J., Donohue, J.H. J. Immunol. (1992) [Pubmed]
  14. Protein antigens of normal and malignant human cells identified by immunoprecipitation with monoclonal antibodies. Brown, J.P., Wright, P.W., Hart, C.E., Woodbury, R.G., Hellström, K.E., Hellström, I. J. Biol. Chem. (1980) [Pubmed]
  15. Induction of glucose-regulated proteins during anaerobic exposure and of heat-shock proteins after reoxygenation. Sciandra, J.J., Subjeck, J.R., Hughes, C.S. Proc. Natl. Acad. Sci. U.S.A. (1984) [Pubmed]
  16. Gemin5, a novel WD repeat protein component of the SMN complex that binds Sm proteins. Gubitz, A.K., Mourelatos, Z., Abel, L., Rappsilber, J., Mann, M., Dreyfuss, G. J. Biol. Chem. (2002) [Pubmed]
  17. Transfected mouse melanoma lines that express various levels of human melanoma-associated antigen p97. Estin, C.D., Stevenson, U., Kahn, M., Hellström, I., Hellström, K.E. J. Natl. Cancer Inst. (1989) [Pubmed]
  18. cDNA cloning and functional analysis of the p97 subunit of the 26S proteasome, a polypeptide identical to the type-1 tumor-necrosis-factor-receptor-associated protein-2/55.11. Tsurumi, C., Shimizu, Y., Saeki, M., Kato, S., Demartino, G.N., Slaughter, C.A., Fujimuro, M., Yokosawa, H., Yamasaki, M., Hendil, K.B., Toh-e, A., Tanahashi, N., Tanaka, K. Eur. J. Biochem. (1996) [Pubmed]
  19. Human melanoma-associated antigens: analysis of antigenic heterogeneity by molecular, serologic and flow-cytometric approaches. Morgan, A.C., Woodhouse, C., Bartholemew, R., Schroff, R. Mol. Immunol. (1986) [Pubmed]
  20. Anti-p97/VCP Antibodies: An Autoantibody Marker for a Subset of Primary Biliary Cirrhosis Patients with Milder Disease? Miyachi, K., Hosaka, H., Nakamura, N., Miyakawa, H., Mimori, T., Shibata, M., Matsushima, S., Chinoh, H., Horigome, T., Hankins, R.W., Zhang, M., Fritzler, M.J. Scand. J. Immunol. (2006) [Pubmed]
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