InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: BST2

Summary

InnateDB Protein

IDBP-36621.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

BST2

Protein Name

bone marrow stromal cell antigen 2

Synonyms

CD317; TETHERIN;

Species

Homo sapiens

Ensembl Protein

ENSP00000252593

InnateDB Gene

IDBG-36619 (BST2)

Protein Structure

UniProt Annotation

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. 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. {ECO:0000269PubMed:18200009, ECO:0000269PubMed:18342597, ECO:0000269PubMed:19036818, ECO:0000269PubMed:19179289, ECO:0000269PubMed:19564354, ECO:0000269PubMed:19879838, ECO:0000269PubMed:20399176, ECO:0000269PubMed:20419159, ECO:0000269PubMed:20686043, ECO:0000269PubMed:20940320, ECO:0000269PubMed:20943977, ECO:0000269PubMed:21529378, ECO:0000269PubMed:21621240, ECO:0000269PubMed:22065321, ECO:0000269PubMed:22520941, ECO:0000269PubMed:23028328}.

Subcellular Localization

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 {ECO:0000250}. 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.

Disease Associations

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). {ECO:0000269PubMed:10329429, ECO:0000269PubMed:16157322}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.

Experimentally validated
Total	11 [view]
Protein-Protein	11 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004871	signal transducer activity
GO:0005515	protein binding
GO:0008191	metalloendopeptidase inhibitor activity
GO:0042803	protein homodimerization activity
GO:0044822	poly(A) RNA binding

Biological Process

GO:0002737	negative regulation of plasmacytoid dendritic cell cytokine production
GO:0006959	humoral immune response
GO:0007165	signal transduction
GO:0007267	cell-cell signaling
GO:0007275	multicellular organismal 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:0045071	negative regulation of viral genome replication
GO:0045087	innate immune response (InnateDB)
GO:0051607	defense response to virus
GO:1901253	negative regulation of intracellular transport of viral material

Cellular Component

GO:0005622	intracellular
GO:0005737	cytoplasm
GO:0005770	late endosome
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005887	integral component of plasma membrane
GO:0009986	cell surface
GO:0016020	membrane
GO:0016324	apical plasma membrane
GO:0031225	anchored component of membrane
GO:0045121	membrane raft
GO:0070062	extracellular vesicular exosome