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Protein

Bone marrow stromal antigen 2

Gene

BST2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 2.16 Publications

GO - Molecular functioni

  • metalloendopeptidase inhibitor activity Source: UniProtKB
  • poly(A) RNA binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • signal transducer activity Source: UniProtKB

GO - Biological processi

  • B cell activation Source: UniProtKB-KW
  • cell-cell signaling Source: ProtInc
  • cell proliferation Source: ProtInc
  • defense response to virus Source: UniProtKB
  • humoral immune response Source: ProtInc
  • innate immune response Source: UniProtKB
  • multicellular organism development Source: ProtInc
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell migration Source: UniProtKB
  • negative regulation of intracellular transport of viral material Source: UniProtKB
  • negative regulation of plasmacytoid dendritic cell cytokine production Source: UniProtKB
  • negative regulation of viral genome replication Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • regulation of actin cytoskeleton organization Source: UniProtKB
  • response to interferon-alpha Source: UniProtKB
  • response to interferon-beta Source: UniProtKB
  • response to interferon-gamma Source: UniProtKB
  • response to virus Source: UniProtKB
  • type I interferon signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Biological processi

Antiviral defense, B-cell activation, Immunity, Innate immunity

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130303-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
R-HSA-909733. Interferon alpha/beta signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Bone marrow stromal antigen 2
Short name:
BST-2
Alternative name(s):
HM1.24 antigen
Tetherin
CD_antigen: CD317
Gene namesi
Name:BST2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

HGNCiHGNC:1119. BST2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 20CytoplasmicSequence analysisAdd BLAST20
Transmembranei21 – 48Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST28
Topological domaini49 – 161ExtracellularSequence analysisAdd BLAST113

GO - Cellular componenti

  • anchored component of membrane Source: UniProtKB-KW
  • apical plasma membrane Source: UniProtKB
  • cell surface Source: UniProtKB
  • cytoplasm Source: HPA
  • extracellular exosome Source: UniProtKB
  • Golgi apparatus Source: HPA
  • integral component of plasma membrane Source: ProtInc
  • membrane Source: UniProtKB
  • membrane raft Source: UniProtKB-SubCell
  • multivesicular body Source: CACAO
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi3 – 5STS → AAA: Partial resistance to Vpu. 1 Publication3
Mutagenesisi6Y → A: Partial resistance to Vpu and significantly reduced activation of NF-kB; when associated with A-8. 1 Publication1
Mutagenesisi8Y → A: Partial resistance to Vpu and significantly reduced activation of NF-kB; when associated with A-6. 1 Publication1
Mutagenesisi18K → R: Abolishes redistribution to late endosomes in cells expressing KSH virus E3 ubiquitin-protein ligase K5. 1 Publication1
Mutagenesisi21K → R: No effect on redistribution to late endosomes in cells expressing KSH virus E3 ubiquitin-protein ligase K5. 1 Publication1
Mutagenesisi65N → A: Loss of glycosylation site. 1 Publication1
Mutagenesisi92N → A: Loss of glycosylation site. Impairs anti-viral activity. 1 Publication1

Organism-specific databases

DisGeNETi684.
OpenTargetsiENSG00000130303.
PharmGKBiPA25436.

Polymorphism and mutation databases

DMDMi1705508.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000650051 – 161Bone marrow stromal antigen 2Add BLAST161
PropeptideiPRO_0000253552162 – 180Removed in mature formSequence analysisAdd BLAST19

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki18Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Disulfide bondi53Interchain
Disulfide bondi63Interchain
Glycosylationi65N-linked (GlcNAc...)4 Publications1
Disulfide bondi91Interchain
Glycosylationi92N-linked (GlcNAc...)2 Publications1
Lipidationi161GPI-anchor amidated serineSequence analysis1

Post-translational modificationi

Monoubiquitinated by KSHV E3 ubiquitin-protein ligase K5, leading to its targeting to late endosomes and degradation.1 Publication
The GPI anchor is essential for its antiviral activity.

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Isopeptide bond, Lipoprotein, Ubl conjugation

Proteomic databases

EPDiQ10589.
MaxQBiQ10589.
PaxDbiQ10589.
PeptideAtlasiQ10589.
PRIDEiQ10589.

PTM databases

iPTMnetiQ10589.
PhosphoSitePlusiQ10589.
SwissPalmiQ10589.

Expressioni

Tissue specificityi

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).2 Publications

Inductioni

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.5 Publications

Gene expression databases

BgeeiENSG00000130303.
CleanExiHS_BST2.
ExpressionAtlasiQ10589. baseline and differential.
GenevisibleiQ10589. HS.

Organism-specific databases

HPAiHPA017060.

Interactioni

Subunit structurei

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.By similarity12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Ap1m1P355852EBI-2476339,EBI-1040251From a different organism.
vpuP696997EBI-2476339,EBI-10757638From a different organism.

GO - Molecular functioni

  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi107149. 16 interactors.
DIPiDIP-53216N.
IntActiQ10589. 13 interactors.
MINTiMINT-8402291.
STRINGi9606.ENSP00000252593.

Structurei

Secondary structure

1180
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi23 – 44Combined sources22
Helixi52 – 148Combined sources97
Beta strandi152 – 154Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LK9NMR-A18-47[»]
2X7AX-ray2.77A/B/C/D/E/F/G/H/I/J/K87-147[»]
2XG7X-ray3.45A/C51-151[»]
3MQ7X-ray2.28A/B/C/D/E/F/G/H/I/J/K/L47-161[»]
3MQ9X-ray2.80A/B/C/D/E/F/G/H66-139[»]
3MQBX-ray3.20A/B/E/F47-161[»]
3MQCX-ray2.80A/B/C/D47-161[»]
3NWHX-ray2.60A/B/C/D47-152[»]
4P6ZX-ray3.00T1-21[»]
ProteinModelPortaliQ10589.
SMRiQ10589.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ10589.

Family & Domainsi

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili68 – 152Add BLAST85

Domaini

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.1 Publication

Sequence similaritiesi

Belongs to the tetherin family.Curated

Keywords - Domaini

Coiled coil, Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410JE1U. Eukaryota.
ENOG41115GP. LUCA.
GeneTreeiENSGT00390000013782.
HOGENOMiHOG000013084.
HOVERGENiHBG004902.
InParanoidiQ10589.
KOiK06731.
OMAiFFIIKAN.
OrthoDBiEOG091G1B7U.
PhylomeDBiQ10589.
TreeFamiTF338345.

Family and domain databases

InterProiIPR024886. BST2.
[Graphical view]
PANTHERiPTHR15190. PTHR15190. 1 hit.
PfamiPF16716. BST2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q10589-1) [UniParc]FASTAAdd to basket
Also known as: l-Tetherin

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MASTSYDYCR VPMEDGDKRC KLLLGIGILV LLIIVILGVP LIIFTIKANS
60 70 80 90 100
EACRDGLRAV MECRNVTHLL QQELTEAQKG FQDVEAQAAT CNHTVMALMA
110 120 130 140 150
SLDAEKAQGQ KKVEELEGEI TTLNHKLQDA SAEVERLRRE NQVLSVRIAD
160 170 180
KKYYPSSQDS SSAAAPQLLI VLLGLSALLQ
Length:180
Mass (Da):19,769
Last modified:October 1, 1996 - v1
Checksum:iCAF52340D69061EE
GO
Isoform 2 (identifier: Q10589-2) [UniParc]FASTAAdd to basket
Also known as: s-Tetherin

The sequence of this isoform differs from the canonical sequence as follows:
     1-12: Missing.

Note: Produced by alternative initiation at Met-13 of isoform 1.
Show »
Length:168
Mass (Da):18,394
Checksum:i965DC8B8EC416C94
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti141N → D in BAD96844 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_012067143V → F.Corresponds to variant rs1804402dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0532501 – 12Missing in isoform 2. CuratedAdd BLAST12

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28137 mRNA. Translation: BAA05679.1.
AK223124 mRNA. Translation: BAD96844.1.
AK291099 mRNA. Translation: BAF83788.1.
AC010319 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84602.1.
BC033873 mRNA. Translation: AAH33873.1.
CCDSiCCDS12358.1. [Q10589-1]
PIRiA56836.
RefSeqiNP_004326.1. NM_004335.3. [Q10589-1]
UniGeneiHs.118110.

Genome annotation databases

EnsembliENST00000252593; ENSP00000252593; ENSG00000130303. [Q10589-1]
GeneIDi684.
KEGGihsa:684.
UCSCiuc060vid.1. human. [Q10589-1]

Keywords - Coding sequence diversityi

Alternative initiation, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D28137 mRNA. Translation: BAA05679.1.
AK223124 mRNA. Translation: BAD96844.1.
AK291099 mRNA. Translation: BAF83788.1.
AC010319 Genomic DNA. No translation available.
CH471106 Genomic DNA. Translation: EAW84602.1.
BC033873 mRNA. Translation: AAH33873.1.
CCDSiCCDS12358.1. [Q10589-1]
PIRiA56836.
RefSeqiNP_004326.1. NM_004335.3. [Q10589-1]
UniGeneiHs.118110.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2LK9NMR-A18-47[»]
2X7AX-ray2.77A/B/C/D/E/F/G/H/I/J/K87-147[»]
2XG7X-ray3.45A/C51-151[»]
3MQ7X-ray2.28A/B/C/D/E/F/G/H/I/J/K/L47-161[»]
3MQ9X-ray2.80A/B/C/D/E/F/G/H66-139[»]
3MQBX-ray3.20A/B/E/F47-161[»]
3MQCX-ray2.80A/B/C/D47-161[»]
3NWHX-ray2.60A/B/C/D47-152[»]
4P6ZX-ray3.00T1-21[»]
ProteinModelPortaliQ10589.
SMRiQ10589.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107149. 16 interactors.
DIPiDIP-53216N.
IntActiQ10589. 13 interactors.
MINTiMINT-8402291.
STRINGi9606.ENSP00000252593.

PTM databases

iPTMnetiQ10589.
PhosphoSitePlusiQ10589.
SwissPalmiQ10589.

Polymorphism and mutation databases

DMDMi1705508.

Proteomic databases

EPDiQ10589.
MaxQBiQ10589.
PaxDbiQ10589.
PeptideAtlasiQ10589.
PRIDEiQ10589.

Protocols and materials databases

DNASUi684.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000252593; ENSP00000252593; ENSG00000130303. [Q10589-1]
GeneIDi684.
KEGGihsa:684.
UCSCiuc060vid.1. human. [Q10589-1]

Organism-specific databases

CTDi684.
DisGeNETi684.
GeneCardsiBST2.
HGNCiHGNC:1119. BST2.
HPAiHPA017060.
MIMi600534. gene.
neXtProtiNX_Q10589.
OpenTargetsiENSG00000130303.
PharmGKBiPA25436.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410JE1U. Eukaryota.
ENOG41115GP. LUCA.
GeneTreeiENSGT00390000013782.
HOGENOMiHOG000013084.
HOVERGENiHBG004902.
InParanoidiQ10589.
KOiK06731.
OMAiFFIIKAN.
OrthoDBiEOG091G1B7U.
PhylomeDBiQ10589.
TreeFamiTF338345.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000130303-MONOMER.
ReactomeiR-HSA-6798695. Neutrophil degranulation.
R-HSA-909733. Interferon alpha/beta signaling.

Miscellaneous databases

ChiTaRSiBST2. human.
EvolutionaryTraceiQ10589.
GeneWikiiTetherin.
GenomeRNAii684.
PROiQ10589.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000130303.
CleanExiHS_BST2.
ExpressionAtlasiQ10589. baseline and differential.
GenevisibleiQ10589. HS.

Family and domain databases

InterProiIPR024886. BST2.
[Graphical view]
PANTHERiPTHR15190. PTHR15190. 1 hit.
PfamiPF16716. BST2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiBST2_HUMAN
AccessioniPrimary (citable) accession number: Q10589
Secondary accession number(s): A8K4Y4, Q53G07
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 146 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

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).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.