The reference OMIM entry for this protein is 600534

Bone marrow stromal cell antigen 2; bst2
Tetherin
Cd317 antigen; cd317

CLONING

Bone marrow stromal cells regulate B-cell growth and development through their surface molecules and cytokines. Ishikawa et al. (1995) produced a monoclonal antibody that recognized a novel human membrane protein, BST2, which is expressed on bone marrow stromal cell lines and rheumatoid arthritis synovial cell lines. They cloned a cDNA encoding CST2 and showed that it is a 30- to 36-kD type II transmembrane protein consisting of 180 amino acids. BST2 is expressed not only on certain bone marrow stromal cell lines but also on various normal tissues, although its expression pattern is different from that of BST1 (600387). By comparative sequence analysis, Cocka and Bates (2012) identified alternative translation initiation sites in human BST2 that generate long and short tetherin isoforms. The short isoform lacks 12 N-terminal residues present in the long isoform. Western blot and immunoprecipitation analyses showed that the long and short tetherin isoforms assembled into homo- and heterodimers.

MAPPING

Ishikawa et al. (1995) localized the BST2 gene to chromosome 19p13.2 by fluorescence in situ hybridization.

GENE FUNCTION

Ishikawa et al. (1995) found that BST2 surface expression on fibroblast cell lines facilitated the stromal cell-dependent growth of a murine bone marrow-derived pre-B-cell line. The results suggested that BST2 may be involved in pre-B-cell growth. Human cells possess an antiviral activity that inhibits the release of retrovirus particles, and other enveloped virus particles, and is antagonized by the HIV-1 accessory protein, Vpu. This antiviral activity can be constitutively expressed or induced by interferon-alpha (147660), and it consists of protein-based tethers, which Neil et al. (2008) termed 'tetherins,' that cause retention of fully-formed virions on infected cell surfaces. Using deductive constraints and gene expression analyses, Neil et al. (2008) identified CD317 (also called BST2 or HM1.24), a membrane protein of previously unknown function, as a tetherin. Specifically, CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukemia virus particle release. Furthermore, in cells where HIV-1 virion release requires Vpu expression, depletion of CD317 abolished this requirement. CD317 caused retention of virions on cell surfaces, and after endocytosis, in CD317-positive compartments. Neil et al. (2008) suggested that inhibition of Vpu function and consequent mobilization of tetherin's antiviral activity is a potential therapeutic strategy in HIV/AIDS. Using several cell systems, Kuhl et al. (2010) found that tetherin, but not CAML (CAMLG; 601118), restricted Vpu-mediated retroviral release in HIV-1 nonpermissive cells. Sauter et al. (2010) reviewed the structure and function of tetherin, as well as its role as a restriction factor that blocks the release of HIV-1 and other enveloped viruses. Cocka and Bates (2012) found that, in response to HIV-1 Vpu, surface expression of the long tetherin isoform was downregulated more than that of the short isoform, and they observed preferential degradation of the long form. Mutation of serine and threonine residues in the 12-amino acid unique region of the long isoform resulted in resistance to Vpu-mediated degradation. Luciferase analysis indicated that the long isoform, but not the short isoform, induced NFKB (see 1640111) activation. The short isoform was found to inhibit activation mediated by ... More on the omim web site

Subscribe to this protein entry history

Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 600534 was added.