OS9 (gene)

Osteosarcoma amplified 9, endoplasmic reticulum lectin
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3AIH​
Identifiers
Symbols	OS9 ; ERLEC2; OS-9
External IDs	OMIM: 609677 MGI: 1924301 HomoloGene: 31409 GeneCards: OS9 Gene
Gene ontology Molecular function • glycoprotein binding • protease binding • protein binding • carbohydrate binding Cellular component • Hrd1p ubiquitin ligase complex • endoplasmic reticulum lumen • endoplasmic reticulum quality control compartment Biological process • protein targeting • protein retention in ER lumen • protein ubiquitination • ER-associated ubiquitin-dependent protein catabolic process • response to endoplasmic reticulum stress • protein ubiquitination involved in ubiquitin-dependent protein catabolic process • negative regulation of retrograde protein transport, ER to cytosol Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	10956	216440
Ensembl	ENSG00000135506	ENSMUSG00000040462
UniProt	Q13438	Q8K2C7
RefSeq (mRNA)	NM_001017956	NM_001171026
RefSeq (protein)	NP_001017956	NP_001164497
Location (UCSC)	Chr 12: 57.69 – 57.72 Mb	Chr 10: 127.09 – 127.12 Mb
PubMed search

Protein OS-9 is a protein that in humans is encoded by the OS9 gene.^{[1][2][3][4][5]}

Function

This gene encodes a protein that is highly expressed in osteosarcomas. This protein binds to the hypoxia-inducible factor 1 (HIF-1), a key regulator of the hypoxic response and angiogenesis, and promotes the degradation of one of its subunits. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.^[5]

Model organisms

Model organisms have been used in the study of OS9 function. A conditional knockout mouse line called Os9^{tm1a(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute.^[6] Male and female animals underwent a standardized phenotypic screen^[7] to determine the effects of deletion.^{[8][9][10][11]} Additional screens performed: - In-depth immunological phenotyping^[12]

Os9 knockout mouse phenotype

Characteristic	Phenotype
All data available at.[7][12]{
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
General Observations	Abnormal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Anti-nuclear Antibody Assay	Normal
Epidermal Immune Composition	Normal
Influenza Challenge	Normal

References

1. Su YA, Hutter CM, Trent JM, Meltzer PS (Apr 1996). "Complete sequence analysis of a gene (OS-9) ubiquitously expressed in human tissues and amplified in sarcomas". Molecular Carcinogenesis 15 (4): 270–5. doi:10.1002/(SICI)1098-2744(199604)15:4<270::AID-MC4>3.0.CO;2-K. PMID 8634085.
2. Kimura Y, Nakazawa M, Tsuchiya N, Asakawa S, Shimizu N, Yamada M (Dec 1997). "Genomic organization of the OS-9 gene amplified in human sarcomas". Journal of Biochemistry 122 (6): 1190–5. doi:10.1093/oxfordjournals.jbchem.a021880. PMID 9498564.
3. Hosokawa N, Kamiya Y, Kamiya D, Kato K, Nagata K (Jun 2009). "Human OS-9, a lectin required for glycoprotein endoplasmic reticulum-associated degradation, recognizes mannose-trimmed N-glycans". The Journal of Biological Chemistry 284 (25): 17061–8. doi:10.1074/jbc.M809725200. PMC 2719344. PMID 19346256.
4. Christianson JC, Shaler TA, Tyler RE, Kopito RR (Mar 2008). "OS-9 and GRP94 deliver mutant alpha1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD". Nature Cell Biology 10 (3): 272–82. doi:10.1038/ncb1689. PMC 2757077. PMID 18264092.
5. "Entrez Gene: OS9 amplified in osteosarcoma".
6. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
7. "International Mouse Phenotyping Consortium".
8. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
9. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
10. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
11. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
12. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
• Baek JH, Mahon PC, Oh J, Kelly B, Krishnamachary B, Pearson M, Chan DA, Giaccia AJ, Semenza GL (Feb 2005). "OS-9 interacts with hypoxia-inducible factor 1alpha and prolyl hydroxylases to promote oxygen-dependent degradation of HIF-1alpha". Molecular Cell 17 (4): 503–12. doi:10.1016/j.molcel.2005.01.011. PMID 15721254.
• Colland F, Jacq X, Trouplin V, Mougin C, Groizeleau C, Hamburger A, Meil A, Wojcik J, Legrain P, Gauthier JM (Jul 2004). "Functional proteomics mapping of a human signaling pathway". Genome Research 14 (7): 1324–32. doi:10.1101/gr.2334104. PMC 442148. PMID 15231748.
• Vigneron N, Ooms A, Morel S, Degiovanni G, Van Den Eynde BJ (Jul 2002). "Identification of a new peptide recognized by autologous cytolytic T lymphocytes on a human melanoma". Cancer Immunity 2: 9. PMID 12747754.
• Litovchick L, Friedmann E, Shaltiel S (Sep 2002). "A selective interaction between OS-9 and the carboxyl-terminal tail of meprin beta". The Journal of Biological Chemistry 277 (37): 34413–23. doi:10.1074/jbc.M203986200. PMID 12093806.
• Friedmann E, Salzberg Y, Weinberger A, Shaltiel S, Gerst JE (Sep 2002). "YOS9, the putative yeast homolog of a gene amplified in osteosarcomas, is involved in the endoplasmic reticulum (ER)-Golgi transport of GPI-anchored proteins". The Journal of Biological Chemistry 277 (38): 35274–81. doi:10.1074/jbc.M201044200. PMID 12077121.
• Nakayama T, Yaoi T, Kuwajima G, Yoshie O, Sakata T (Jun 1999). "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". FEBS Letters 453 (1-2): 77–80. doi:10.1016/S0014-5793(99)00700-0. PMID 10403379.
• Kimura Y, Nakazawa M, Yamada M (May 1998). "Cloning and characterization of three isoforms of OS-9 cDNA and expression of the OS-9 gene in various human tumor cell lines". Journal of Biochemistry 123 (5): 876–82. doi:10.1093/oxfordjournals.jbchem.a022019. PMID 9562620.
• Elkahloun AG, Krizman DB, Wang Z, Hofmann TA, Roe B, Meltzer PS (Jun 1997). "Transcript mapping in a 46-kb sequenced region at the core of 12q13.3 amplification in human cancers". Genomics 42 (2): 295–301. doi:10.1006/geno.1997.4727. PMID 9192850.