Biomarker: BST2

Histology type: endometrial carcinoma

Followed up time :

Conclusion: Plasma membrane proteomics identifies bone marrow stromal antigen 2 as a potential therapeutic target in endometrial cancer

Sample type : tissue

Sample method: immunohistochemisty

Expression pattern : Overexpression

Expression elevation: Immunostainings were scored according to the intensity of the staining (no staining = 0, weak staining = 1, moderate staining = 2, strong staining= 3) and the extent of stained cells (0–9% = 0, 10–40% = 1, 41–70% = 2, 71–100% = 3). The final immunohistochemistry (IHC) score was determined by multiplying the intensity score (0, 1, 2, or 3) with the positivity score (0, 1, 2, or 3), resulting in a maximum score of 9.

Funtion description: The therapeutic effect of an anti-BST2 antibody was studied both in vitro and in vivo. An anti-BST2 monoclonal antibody showed in vitro cytotoxicity in BST2-positive endometrial cancer cells via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. In an in vivo xenograft model, anti-BST2 antibody treatment significantly inhibited tumor growth of BST2-positive endometrial cancer cells in an NK cell-dependent manner. The anti-BST2 antibody had a potent antitumor effect against endometrial cancer both in vitro and in vivo, indicating a strong potential for clinical use of anti-BST2 antibody for endometrial cancer treatment. The combination of biotinylation-based enrichment of cell-surface proteins and iTRAQ analysis should be a useful screening method for future discovery of potential therapeutic targets.

Funtion Uniprot: IFN-induced antiviral host restriction factor which efficiently blocks the release of diverse mammalian enveloped viruses by directly tethering nascent virions to the membranes of infected cells. Acts as a direct physical tether, holding virions to the cell membrane and linking virions to each other. The tethered virions can be internalized by endocytosis and subsequently degraded or they can remain on the cell surface. In either case, their spread as cell-free virions is restricted (PubMed:22520941, PubMed:21529378, PubMed:20940320, PubMed:20419159, PubMed:20399176, PubMed:19879838, PubMed:19036818, PubMed:18342597, PubMed:18200009). Its target viruses belong to diverse families, including retroviridae: human immunodeficiency virus type 1 (HIV-1), human immunodeficiency virus type 2 (HIV-2), simian immunodeficiency viruses (SIVs), equine infectious anemia virus (EIAV), feline immunodeficiency virus (FIV), prototype foamy virus (PFV), Mason-Pfizer monkey virus (MPMV), human T-cell leukemia virus type 1 (HTLV-1), Rous sarcoma virus (RSV) and murine leukemia virus (MLV), flavivirideae: hepatitis C virus (HCV), filoviridae: ebola virus (EBOV) and marburg virus (MARV), arenaviridae: lassa virus (LASV) and machupo virus (MACV), herpesviridae: kaposis sarcoma-associated herpesvirus (KSHV), rhabdoviridae: vesicular stomatitis virus (VSV), orthomyxoviridae: influenza A virus, paramyxoviridae: nipah virus, and coronaviridae: SARS-CoV (PubMed:22520941, PubMed:21621240, PubMed:21529378, PubMed:20943977, PubMed:20686043, PubMed:20419159, PubMed:20399176, PubMed:19879838, PubMed:19179289, PubMed:18342597, PubMed:18200009, PubMed:26378163, PubMed:31199522). Can inhibit cell surface proteolytic activity of MMP14 causing decreased activation of MMP15 which results in inhibition of cell growth and migration (PubMed:22065321). Can stimulate signaling by LILRA4/ILT7 and consequently provide negative feedback to the production of IFN by plasmacytoid dendritic cells in response to viral infection (PubMed:19564354, PubMed:26172439). Plays a role in the organization of the subapical actin cytoskeleton in polarized epithelial cells. Isoform 1 and isoform 2 are both effective viral restriction factors but have differing antiviral and signaling activities (PubMed:23028328, PubMed:26172439). Isoform 2 is resistant to HIV-1 Vpu-mediated degradation and restricts HIV-1 viral budding in the presence of Vpu (PubMed:23028328, PubMed:26172439). Isoform 1 acts as an activator of NF-kappa-B and this activity is inhibited by isoform 2 (PubMed:23028328).19 Publications

UniProt ID: Q10589

UniProt Link: https://www.uniprot.org/uniprotkb/Q10589/entry

Biological function from UniProt: #Antiviral defense #B-cell activation #Host-virus interaction #Immunity #Innate immunity

Molecular function from UniProt:

Tissue specificity from UniProt: Predominantly expressed in liver, lung, heart and placenta. Lower levels in pancreas, kidney, skeletal muscle and brain. Overexpressed in multiple myeloma cells. Highly expressed during B-cell development, from pro-B precursors to plasma cells. Highly expressed on T-cells, monocytes, NK cells and dendritic cells (at protein level).

Subcellular UniProt: #Cell membrane #Cytoplasm #Endosome #Golgi apparatus #Membrane

Alternative name from UniProt:

Miscellaneous: Tetherin shows evidence of positive (adaptive) selection, presumably as a result of evolutionary pressure applied by antagonistic viral proteins that counteract its inhibitiory activity and this has led to the species-specific tetherin sensitivity to viral countermeasures. For example, Tantalus monkey tetherin cannot be abrogated by HIV-1 VPU due to variation in the tetherin transmembrane region. Similarly, SIV Nefs are able to overcome simian tetherins, but not human tetherin, due to a unique 5-amino-acid deletion in the cytoplasmic tail domain of human tetherin (PubMed:19917491).

Recommended name: Bone marrow stromal antigen 2

Gene name from HGNC: BST2 (CD317, tetherin)

CD antigen name: CD317

HPA class: CD markers Plasma proteins Transporters

AlphaFold DB: Q10589

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q10589

Induction: By type I interferons.2 Publications (Microbial infection) Down-regulated by HIV-1 VPU protein. Antagonizes its function by targeting it to the trans-Golgi network, sequestering it away from virus assembly sites on the cell membrane. VPU also acts as an adapter molecule linking it to BTRC, a substrate recognition subunit of the Skp1/Cullin/F-box protein E3 ubiquitin ligase, inducing its ubiquitination and subsequent proteasomal degradation.3 Publications (Microbial infection) Down-regulated by HIV-2 ENV protein. Antagonizes its function by targeting it to the trans-Golgi network, sequestering it away from virus assembly sites on the cell membrane.1 Publication (Microbial infection) Down-regulated by KSHV K5 protein. K5 ubiquitinates it leading to its targeting to late endosomes and degradation.1 Publication (Microbial infection) Down-regulated by ebola virus GP protein.1 Publication (Microbial infection) Made inactive by SARS-CoV ORF7a protein through impairing proper glycosylation (PubMed:26378163). May be down-regulated by SARS-CoV Spike protein through lysosomal degradation pathway (PubMed:31199522).2 Publications

HPA link: https://www.proteinatlas.org/ENSG00000130303-BST2

Tissue specificity RNA from HPA: Tissue enhanced (ovary)

Tissue expression from HPA: General cytoplasmic expression.

Single cell type specificity Cell type enhanced (Adipocytes, Theca cells, Hepatic stellate cells)

Immune cell specificity: Low immune cell specificity

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable), testis cancer (unfavorable) and breast cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000130303-BST2/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000130303-BST2/pathology/endometrial+cancer

OMIM: 600534

OMIM link2: https://www.omim.org/entry/600534

HGNC ID: HGNC:1119

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:1119