BST2

Bone marrow stromal cells are involved in the growth and development of B-cells. The specific function of the protein encoded by the bone marrow stromal cell antigen 2 is undetermined; however, this protein may play a role in pre-B-cell growth and in rheumatoid arthritis.

Bone Marrow Stromal Cell Antigen 2

Bone Marrow Stromal Cell Antigen 2; HM1.24 Antigen; TETHERIN; BST-2; Bone Marrow Stromal Antigen 2; CD317 Antigen; NPC-A-7; CD317;

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).

B cell activation Source: UniProtKB-KW
Defense response to virus Source: UniProtKB
Innate immune response Source: UniProtKB
Negative regulation of cell growth Source: UniProtKB
Negative regulation of cell migration Source: UniProtKB
Negative regulation of intracellular transport of viral material Source: UniProtKB
Negative regulation of plasmacytoid dendritic cell cytokine production Source: UniProtKB
Negative regulation of viral genome replication Source: UniProtKB
Neutrophil degranulation Source: Reactome
Positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
Positive regulation of leukocyte proliferation Source: GO_Central
Regulation of actin cytoskeleton organization Source: UniProtKB
Response to interferon-alpha Source: UniProtKB
Response to interferon-beta Source: UniProtKB
Response to interferon-gamma Source: UniProtKB
Response to virus Source: UniProtKB
Type I interferon signaling pathway Source: Reactome

Trans-Golgi network; Cytoplasm; Cell membrane; Apical cell membrane; Membrane raft. Shuttles between the cell membrane, where it is present predominantly in membrane/lipid rafts, and the trans-Golgi network. Forms a complex with MMP14 and localizes to the cytoplasm.
Trans-Golgi network; Late endosome. (Microbial infection) HIV-1 VPU and HIV-2 ENV can target it to the trans-Golgi network thus sequestering it away from virus assembly sites on the cell membrane. Targeted to late endosomes upon KSHV infection and subsequent ubiquitination.

Cytoplasmic: 1-20 aa
Helical: 21-48 aa
Extracellular: 49-161 aa

Monoubiquitinated by KSHV E3 ubiquitin-protein ligase K5, leading to its targeting to late endosomes and degradation.1 Publication
The GPI anchor is essential for its antiviral activity.