Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Gene: OS9 - amplified in osteosarcoma

Homo sapiens

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

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Nakayama, T., Kimura, Y., Vigneron, N., Su, Y.A., Baek, J.H., et al.

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Disease relevance of OS9

The OS-9 gene maps to a region (q13-15) of chromosome 12 that is highly amplified in human osteosarcomas and encodes a protein of unknown function [1].
Complete sequence analysis of a gene (OS-9) ubiquitously expressed in human tissues and amplified in sarcomas [2].
We isolated and characterized three isoforms of OS-9 cDNA found in a myeloid leukemia HL-60 cDNA library [3].
Interestingly, some of the melanoma sublines of LG2-MEL have lost the wild-type allele of gene OS-9 [4].

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 [5].
We characterized OS-9 and found that it is associated with ER membranes and that it is exposed to the cytoplasm [6].
These results reveal that OS-9 is a potential target of N-copine [7].
We further revealed that the second C2 domain of N-copine bound with the carboxy-terminal region of OS-9 [7].
OS-9 was co-amplified with CDK4 in three of five sarcoma tissues [2].

Chemical compound and disease context of OS9

Isoform 1 consisted of 2,700 bp, from which a 667 amino acid sequence was deduced and found to be identical with that of OS-9 cDNA from osteosarcoma cells [Su et al. (1996) Mol. Carcinogen. 15, 270-275] [3].

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 [3].
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 [4].
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 [4].

Anatomical context of OS9

Northern blotting revealed similar levels of expression of OS-9 gene in various tumor cell lines of sarcoma cells, carcinoma cells and myeloid leukemia cells, but 3-4 times higher expression in OsA-CL cells and Rh30 cells containing a homogeneously staining region of 12q13-15 [3].
OS-9 expression decreased in differentiation-induced HL-60 cells [3].

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 [4].

Physical interactions of OS9

By using yeast two-hybrid assays, we identified OS-9 as a protein capable of interacting with N-copine [7].

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 [5].

Analytical, diagnostic and therapeutic context of OS9

By Northern blot analysis, N-copine and OS-9 were co-expressed in the same regions of human brain [7].
Their interaction in vivo was also confirmed by co-immunoprecipitation from 293E cells co-expressing transfected N-copine and OS-9 [7].

References

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)
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)
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)
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)
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)
A selective interaction between OS-9 and the carboxyl-terminal tail of meprin beta. Litovchick, L., Friedmann, E., Shaltiel, S. J. Biol. Chem. (2002)
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)