Description: Homo sapiens bone marrow stromal cell antigen 2 (BST2), mRNA. RefSeq Summary (NM_004335): 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. [provided by RefSeq, Jul 2008]. Transcript (Including UTRs) Position: hg19 chr19:17,513,755-17,516,384 Size: 2,630 Total Exon Count: 5 Strand: - Coding Region Position: hg19 chr19:17,514,504-17,516,384 Size: 1,881 Coding Exon Count: 4
ID:BST2_HUMAN DESCRIPTION: RecName: Full=Bone marrow stromal antigen 2; Short=BST-2; AltName: Full=HM1.24 antigen; AltName: Full=Tetherin; AltName: CD_antigen=CD317; Flags: Precursor; 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, and paramyxoviridae: nipah virus. 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. SUBUNIT: Parallel homodimer; disulfide-linked. May form homotetramers under reducing conditions. Dimerization is essential for its antiviral activity. Interacts (via cytoplasmic domain) with ARHGAP44 (By similarity). Interacts with MMP14 (via C- terminal cytoplasmic tail). Interacts with LILRA4/ILT7. Interacts (via transmembrane domain) with HIV-1 VPU (via transmembrane domain). Interacts with HIV-2 ENV and ebola GP protein. SUBCELLULAR LOCATION: Golgi apparatus, trans-Golgi network. Cell membrane; Single-pass type II membrane protein. Cell membrane; Lipid-anchor, GPI-anchor. Late endosome. Membrane raft. Cytoplasm. Apical cell membrane (By similarity). Note=Shuttles between the cell membrane, where it is present predominantly in membrane/lipid rafts, and the trans-Golgi network. 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. Forms a complex with MMP14 and localizes to the cytoplasm. TISSUE SPECIFICITY: 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). INDUCTION: By type I interferons. Down-regulated by viral antagonistic factors which include: HIV-1 VPU protein, HIV-2 ENV protein, KSHV K5 protein and ebola virus GP protein. VPU and ENV antagonize 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. K5 ubiquitinates it leading to its targeting to late endosomes and degradation. DOMAIN: The extracellular coiled coil domain forms an extended 170 A long semi-flexible rod-like structure important for virion retention at the cell surface and prevention of virus spreading. PTM: Monoubiquitinated by KSHV E3 ubiquitin-protein ligase K5, leading to its targeting to late endosomes and degradation. PTM: The GPI anchor is essential for its antiviral activity. 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). SIMILARITY: Belongs to the tetherin family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q10589
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0003723 RNA binding GO:0005515 protein binding GO:0008191 metalloendopeptidase inhibitor activity GO:0042802 identical protein binding GO:0042803 protein homodimerization activity
Biological Process: GO:0002376 immune system process GO:0002737 negative regulation of plasmacytoid dendritic cell cytokine production GO:0006959 humoral immune response GO:0007267 cell-cell signaling GO:0007275 multicellular organism development GO:0008283 cell proliferation GO:0009615 response to virus GO:0010951 negative regulation of endopeptidase activity GO:0030308 negative regulation of cell growth GO:0030336 negative regulation of cell migration GO:0032956 regulation of actin cytoskeleton organization GO:0034341 response to interferon-gamma GO:0035455 response to interferon-alpha GO:0035456 response to interferon-beta GO:0042113 B cell activation GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling GO:0043312 neutrophil degranulation GO:0045071 negative regulation of viral genome replication GO:0045087 innate immune response GO:0051607 defense response to virus GO:0060337 type I interferon signaling pathway GO:1901253 negative regulation of intracellular transport of viral material