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Gene Review

OS9  -  osteosarcoma amplified 9, endoplasmic...

Homo sapiens

Synonyms: Amplified in osteosarcoma 9, ERLEC2, OS-9, Protein OS-9

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OS-9 was originally identified as gene that is amplified in osteosarcomas [1] [2], and was later found to bind N- copine and to be involved in the ER-to-Golgi transport of meprin-beta [3]. Interestingly, OS-9 is also involved in the TLR-regulated ER-to-Golgi translocation of DC-STAMP, an ER-resident four- to seven-transmembrane protein preferentially expressed in antigen-presenting dendritic cells [4]. OS-9 also binds LUMAN, an ER-resident transciption factor that also interacts with DC-STAMP and is activated upon TLR signaling [5]. Taken together, these data indicate that OS-9 is generally involved in ER-to-Golgi transport and may be involved in a pathway linking TLR signaling and intracellular transport.

Other data suggest that OS-9 is a lectin in the Endoplasmic Reticulum Quality Control Compartment (ERQC) that bind proteins with major folding defect and targets them to translocation to the cytosol and degradation through ubiquitinalation. Proteins with folding defect accumulate in the ERQC [6] where they interact with various lectines and mannosidases, that determine whether the folding defect can be corrected or not. The proteins targeted for degradation are modified with a particular N-glycan composed by 5 or 6 mannoses (it could be useful to remind that almost all the proteins in the ER are N-glycosylated), which is recognized by OS9.


Disease relevance of OS9


High impact information on OS9

  • These data indicate that OS-9 is an essential component of a multiprotein complex that regulates HIF-1alpha levels in an O2-dependent manner [9].
  • We characterized OS-9 and found that it is associated with ER membranes and that it is exposed to the cytoplasm [3].
  • OS-9 is involved in the ER-to-Golgi transport of DC-STAMP in response to TLR signaling in dendritic cells, the professional antigen presenting cell of our immune system [4].
  • OS-9 interacts with, and possibly regulates, transcription factor LUMAN, which also interacts with DC-STAMP; LUMAN resides in the ER of dendritic cells when inactive, but translocates to the nucleus upon proteolytic activation during innate immune signaling [5].
  • These results reveal that OS-9 is a potential target of N-copine [10].
  • We further revealed that the second C2 domain of N-copine bound with the carboxy-terminal region of OS-9 [10].
  • OS-9 was co-amplified with CDK4 in three of five sarcoma tissues [2].

Chemical compound and disease context of OS9


Biological context of OS9

  • We now report further characterization of the full-length OS-9 cDNA sequence consists of 2785 bp from which an open reading frame (ORF) with 667 amino-acid residues was deduced, The predicted polypeptide was water soluble and acidic [2].
  • Possible involvement of the OS-9 gene in cell growth is discussed [1].
  • We have identified another antigen of LG2-MEL as a peptide presented by HLA-B*4403 and resulting from a point mutation in gene OS-9 [8].
  • The mutation we have identified in gene OS-9 might therefore participate in the oncogenic process by affecting the function of this potential tumor-suppressor gene [8].

Anatomical context of OS9


Associations of OS9 with chemical compounds

  • The mutation, a C-to-T transition, changes a proline residue into a leucine at position 446 of the OS-9 protein [8].
  • OS-9 activity does not require an intact mannose 6-P homology domain [11].

Physical interactions of OS9

  • By using yeast two-hybrid assays, we identified OS-9 as a protein capable of interacting with N-copine [10].
  • OS-9 interacts with the cytoplasmic tail of DC-STAMP, as determined by yeast two-hybrid assays and co-immunoprecipitation analysis [4]
  • OS-9 interacts with the cytoplasmic part of the transcription factor LUMAN, as determined by co-immunoprecipitation analysis [5]

Other interactions of OS9

  • Here, we demonstrate that OS-9, the protein product of a widely expressed gene, interacts with both HIF-1alpha and HIF-1alpha prolyl hydroxylases [9].

Analytical, diagnostic and therapeutic context of OS9


  1. Cloning and characterization of three isoforms of OS-9 cDNA and expression of the OS-9 gene in various human tumor cell lines. Kimura, Y., Nakazawa, M., Yamada, M. J. Biochem. (1998) [Pubmed]
  2. Complete sequence analysis of a gene (OS-9) ubiquitously expressed in human tissues and amplified in sarcomas. Su, Y.A., Hutter, C.M., Trent, J.M., Meltzer, P.S. Mol. Carcinog. (1996) [Pubmed]
  3. A selective interaction between OS-9 and the carboxyl-terminal tail of meprin beta. Litovchick, L., Friedmann, E., Shaltiel, S. J. Biol. Chem. (2002) [Pubmed]
  4. OS9 interacts with DC-STAMP and modulates its intracellular localization in response to TLR ligation. Jansen, B.J., Eleveld-Trancikova, D., Sanecka, A., van Hout-Kuijer, M., Hendriks, I.A., Looman, M.G., Leusen, J.H., Adema, G.J. Mol. Immunol. (2009) [Pubmed]
  5. DC-STAMP interacts with ER-resident transcription factor LUMAN which becomes activated during DC maturation. Eleveld-Trancikova, D., Sanecka, A., van Hout-Kuijer, M.A., Looman, M.W., Hendriks, I.A., Jansen, B.J., Adema, G.J. Mol. Immunol. (2010) [Pubmed]
  6. Endoplasmic reticulum (ER) mannosidase I is compartmentalized and required for N-glycan trimming to Man5-6GlcNAc2 in glycoprotein ER-associated degradation. Avezov, E., Frenkel, Z., Ehrlich, M., Herscovics, A., Lederkremer, G.Z. Mol. Biol. Cell. (2008) [Pubmed]
  7. YOS9, the putative yeast homolog of a gene amplified in osteosarcomas, is involved in the endoplasmic reticulum (ER)-Golgi transport of GPI-anchored proteins. Friedmann, E., Salzberg, Y., Weinberger, A., Shaltiel, S., Gerst, J.E. J. Biol. Chem. (2002) [Pubmed]
  8. Identification of a new peptide recognized by autologous cytolytic T lymphocytes on a human melanoma. Vigneron, N., Ooms, A., Morel, S., Degiovanni, G., Van Den Eynde, B.J. Cancer Immun. (2002) [Pubmed]
  9. OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha. Baek, J.H., Mahon, P.C., Oh, J., Kelly, B., Krishnamachary, B., Pearson, M., Chan, D.A., Giaccia, A.J., Semenza, G.L. Mol. Cell (2005) [Pubmed]
  10. Ca2(+)-dependent interaction of N-copine, a member of the two C2 domain protein family, with OS-9, the product of a gene frequently amplified in osteosarcoma. Nakayama, T., Yaoi, T., Kuwajima, G., Yoshie, O., Sakata, T. FEBS Lett. (1999) [Pubmed]
  11. A dual task for the Xbp1-responsive OS-9 variants in the mammalian endoplasmic reticulum: inhibiting secretion of misfolded protein conformers and enhancing their disposal. Bernasconi, R., Pertel, T., Luban, J., Molinari, M. J. Biol. Chem. (2008) [Pubmed]
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