BST2_HUMAN » Bone marrow stromal antigen 2

BST2_HUMAN » Bone marrow stromal antigen 2
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
BST2_HUMAN » Bone marrow stromal antigen 2 » BST-2; HM1.24 antigen;Tetherin;
Hydrophobic Thickness 38.0 ± 2.2 Å
Tilt Angle 1 ± 0°
ΔGtransfer -54.4 kcal/mol
ΔGfold -27.6 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology In
TM Segments 18-47 (14-51)
Pathways none
PDB 2lk9 (18-47), 3mq7 (A/B...=47-161), 3mq9 (A/B...=66-139), 2x7a (A/B...=87-147), 3nwh (A/B/C/D=47-152), 3mqc (A/B/C/D=47-161), 3mqb (A/B/E/F=47-161), 2xg7 (A/C=51-151), 4p6z (T=1-21)
OPM none
Complexes

BST2:BST2_HUMAN

Interactions

BST2, Complex: Homodimer of bone marrow stromal antigen 2 ectodomain, PDBID: 2XG7

LIRA4, Complex: BST2:LIRA4, PubMed

TFR1, Complex: TFR1:BST2, PubMed

Domains

AA: 49-136, PDBID: 2X7A, Subunit G, Seq Identity:100%, Bone marrow stromal antigen 2

UniProt annotation for BST2_HUMAN » Bone marrow stromal antigen 2
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.

SUBUNIT: Parallel homodimer; disulfide-linked. May form homotetramers under reducing conditions. Isoform 1 and isoform 2 form homodimers and also heterodimers with each other. 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.

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.

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).

UniProt features for BST2_HUMAN » Bone marrow stromal antigen 2
CHAIN 1 161 Bone marrow stromal antigen 2.
PROPEP 162 180 Removed in mature form (Potential).
COILED 68 152
DISULFID 53 53 Interchain.
DISULFID 63 63 Interchain.
DISULFID 91 91 Interchain.
CROSSLNK 18 18 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin).
Amino Acid Sequence for BST2_HUMAN » Bone marrow stromal antigen 2
MASTSYDYCR VPMEDGDKRC KLLLGIGILV LLIIVILGVP LIIFTIKANS EACRDGLRAV MECRNVTHLL QQELTEAQKG FQDVEAQAAT CNHTVMALMA SLDAEKAQGQ KKVEELEGEI TTLNHKLQDA SAEVERLRRE NQVLSVRIAD KKYYPSSQDS SSAAAPQLLI VLLGLSALLQ