Protein: Bone marrow stromal antigen 2 (BST-2) (HM1.24 antigen) (Tetherin) (CD antigen CD317) (Q10589)
Organism: Homo sapiens (Human)
Function: 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. 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. Can inhibit cell surface proteolytic activity of MMP14 causing decreased activation of MMP15 which results in inhibition of cell growth and migration. 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. 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. Isoform 2 is resistant to HIV-1 Vpu-mediated degradation and restricts HIV-1 viral budding in the presence of Vpu. Isoform 1 acts as an activator of NF-kappa-B and this activity is inhibited by isoform 2.
Subcellular location: Golgi apparatus, trans-Golgi network. Cell membrane {ECO:0000269|PubMed:26172439}; Single-pass type II membrane protein. Cell membrane {ECO:0000269|PubMed:19879838, ECO:0000269|PubMed:26172439, ECO:0000269|PubMed:37922253}; Lipid-anchor, GPI-anchor {ECO:0000269|PubMed:19879838, ECO:0000305|PubMed:26172439}. Membrane raft. Cytoplasm. Apical cell membrane {ECO:0000250}. Note=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.; SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network {ECO:0000269|PubMed:26172439}. Late endosome {ECO:0000269|PubMed:20419159}. Note=(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. {ECO:0000269|PubMed:20419159, ECO:0000269|PubMed:26172439}.
Interaction partners:
- Leukocyte immunoglobulin-like receptor subfamily A member 4
- RING-type E3 ubiquitin transferase
- DNA dC->dU-editing enzyme APOBEC-3G
- Deoxynucleoside triphosphate triphosphohydrolase SAMHD1
- Agrin
- Tripartite motif-containing protein 5
- Ubiquitin-like protein ISG15
- Interferon-induced 35 kDa protein
- Interferon regulatory factor 9
- Signal transducer and activator of transcription 1-alpha/beta
Sequence:
MASTSYDYCRVPMEDGDKRCKLLLGIGILVLLIIVILGVPLIIFTIKANSEACRDGLRAVMECRNVTHLLQQELTEAQKGFQDVEAQAATCNHTVMALMASLDAEKAQGQKKVEELEGEITTLNHKLQDASAEVERLRRENQVLSVRIADKKYYPSSQDSSSAAAPQLLIVLLGLSALLQ