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BST2

gene
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Also known as CD317tetherinBST-2HM1.24

Summary

BST2 (bone marrow stromal cell antigen 2, HGNC:1119) is a protein-coding gene on chromosome 19p13.11, encoding Bone marrow stromal antigen 2 (Q10589). 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.

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.

Source: NCBI Gene 684 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 34 total
  • GTEx eGene: eQTL in 35 tissues, sQTL in 1 (q < 0.05)
  • Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.97 (unconstrained)
  • MANE Select transcript: NM_004335
  • Interaction hub: 1,732 STRING partners (top 10% of genes corpus-wide)

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1119
Approved symbolBST2
Namebone marrow stromal cell antigen 2
Location19p13.11
Locus typegene with protein product
StatusApproved
AliasesCD317, tetherin, BST-2, HM1.24
Ensembl geneENSG00000130303
Ensembl biotypeprotein_coding
OMIM600534
Entrez684

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 14 protein_coding, 3 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000252593

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2

ENST00000252593, ENST00000527220, ENST00000533098, ENST00000860181, ENST00000860182, ENST00000860183, ENST00000860184, ENST00000860185, ENST00000860186, ENST00000982416, ENST00000982417, ENST00000982418, ENST00001010764, ENST00001100483, ENST00001118800, ENST00001128046, ENST00001131149, ENST00001141971

RefSeq mRNA: 1 — MANE Select: NM_004335 NM_004335

CCDS: CCDS12358

Canonical transcript exons

ENST00000252593 — 5 exons

ExonStartEnd
ENSE000006655911740437117404437
ENSE000012574511740293917403326
ENSE000017285881740529117405630
ENSE000036358451740368017403824
ENSE000036552521740412917404189

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 99.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4462 / max 439.6829, expressed in 1137 samples.

Highest expression (Bgee): adrenal gland, adrenal gland cortex, ovary, adrenal cortex, uterine tube.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BST2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 35 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 36 significant tissue × QTL associations:

TissueQTLq-valueSlopeLead variant
Adipose Subcutaneouseqtl3.5e-20+0.5819:17407483:C:T
Artery Aortaeqtl3.8e-18+0.6119:17395367:T:C
Cells Cultured fibroblastseqtl3.5e-15+0.4019:17395124:A:C
Adipose Visceral Omentumeqtl4.8e-14+0.5919:17405591:A:AGCTGAAAG
Nerve Tibialeqtl1.0e-10+0.6719:17407483:C:T
Esophagus Mucosaeqtl2.6e-09+0.3319:17395367:T:C
Artery Tibialeqtl4.9e-09+0.4719:17405591:A:AGCTGAAAG
Skin Not Sun Exposed Suprapubiceqtl1.4e-08+0.6119:17407483:C:T
Heart Atrial Appendageeqtl6.0e-08+0.7419:17405591:A:AGCTGAAAG
Cells EBV-transformed lymphocyteseqtl2.1e-07+0.4619:17407483:C:T
Colon Transverseeqtl4.1e-07+0.4519:17405591:A:AGCTGAAAG
Colon Sigmoideqtl1.2e-06+0.8419:17405591:A:AGCTGAAAG
Pancreaseqtl1.5e-06+0.7019:17407483:C:T
Skin Sun Exposed Lower legeqtl1.9e-06+0.4319:17407483:C:T
Brain Putamen basal gangliaeqtl1.3e-05-1.3119:17405817:C:T
Esophagus Musculariseqtl1.7e-05+0.5719:17405591:A:AGCTGAAAG
Testiseqtl6.4e-05+0.3219:17405591:A:AGCTGAAAG
Muscle Skeletaleqtl7.3e-05+0.4219:17405591:A:AGCTGAAAG
Spleeneqtl3.0e-04+0.2519:17401421:A:AT
Heart Left Ventricleeqtl1.3e-03+0.3819:17403837:T:TGGG

FANTOM5 promoters

4 alternative TSS:

Promoter IDTPM avgSamples expressed
17986413.32541107
1798650.5942323
1798630.3707192
2087230.155969

Top tissues by expression

showing 100 of 295 tissues by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
right adrenal glandUBERON:000123399.52gold quality
right adrenal gland cortexUBERON:003582799.51gold quality
left adrenal glandUBERON:000123499.49gold quality
left adrenal gland cortexUBERON:003582599.49gold quality
left ovaryUBERON:000211999.47gold quality
adrenal cortexUBERON:000123599.45gold quality
right ovaryUBERON:000211899.44gold quality
adrenal glandUBERON:000236998.93gold quality
left uterine tubeUBERON:000130398.89gold quality
monocyteCL:000057698.74gold quality
granulocyteCL:000009498.62gold quality
spleenUBERON:000210698.49gold quality
right uterine tubeUBERON:000130298.48gold quality
peritoneumUBERON:000235898.44gold quality
omental fat padUBERON:001041498.44gold quality
leukocyteCL:000073898.35gold quality
mononuclear cellCL:000084298.35gold quality
gall bladderUBERON:000211098.07gold quality
adipose tissue of abdominal regionUBERON:000780898.05gold quality
apex of heartUBERON:000209898.02gold quality
right lobe of liverUBERON:000111497.79gold quality
pericardiumUBERON:000240797.69gold quality
mucosa of stomachUBERON:000119997.63gold quality
lymph nodeUBERON:000002997.43gold quality
right lungUBERON:000216797.32gold quality
ovaryUBERON:000099297.21gold quality
upper lobe of left lungUBERON:000895297.05gold quality
descending thoracic aortaUBERON:000234597.03gold quality
thoracic aortaUBERON:000151596.50gold quality
ascending aortaUBERON:000149696.47gold quality
endocervixUBERON:000045896.42gold quality
muscle layer of sigmoid colonUBERON:003580596.28gold quality
upper lobe of lungUBERON:000894896.12gold quality
small intestine Peyer’s patchUBERON:000345496.07gold quality
metanephros cortexUBERON:001053395.71gold quality
olfactory segment of nasal mucosaUBERON:000538695.66gold quality
subcutaneous adipose tissueUBERON:000219095.59gold quality
peripheral nervous systemUBERON:000001095.25gold quality
tibial nerveUBERON:000132395.25gold quality
adipose tissueUBERON:000101395.15gold quality
esophagogastric junction muscularis propriaUBERON:003584195.10gold quality
right coronary arteryUBERON:000162594.79gold quality
vermiform appendixUBERON:000115494.62gold quality
adenohypophysisUBERON:000219694.55gold quality
body of uterusUBERON:000985394.45gold quality
small intestineUBERON:000210894.43gold quality
trigeminal ganglionUBERON:000167594.38gold quality
ectocervixUBERON:001224994.37gold quality
right atrium auricular regionUBERON:000663194.34gold quality
caecumUBERON:000115394.33gold quality
connective tissueUBERON:000238494.29gold quality
liverUBERON:000210794.28gold quality
fundus of stomachUBERON:000116094.15gold quality
coronary arteryUBERON:000162194.08gold quality
left coronary arteryUBERON:000162694.07gold quality
lower esophagus muscularis layerUBERON:003583393.62gold quality
lower esophagusUBERON:001347393.57gold quality
transverse colonUBERON:000115793.55gold quality
colonic epitheliumUBERON:000039793.54gold quality
vena cavaUBERON:000408793.48gold quality
heart left ventricleUBERON:000208493.46gold quality
cortex of kidneyUBERON:000122593.29gold quality
cardiac ventricleUBERON:000208293.28gold quality
right lobe of thyroid glandUBERON:000111993.16gold quality
cardiac atriumUBERON:000208193.08gold quality
C1 segment of cervical spinal cordUBERON:000646993.04gold quality
adrenal tissueUBERON:001830393.04gold quality
bloodUBERON:000017892.84gold quality
mucosa of transverse colonUBERON:000499192.69gold quality
smooth muscle tissueUBERON:000113592.66gold quality
sigmoid colonUBERON:000115992.50gold quality
thymusUBERON:000237092.46gold quality
heartUBERON:000094892.42gold quality
dorsal root ganglionUBERON:000004492.26gold quality
left lobe of thyroid glandUBERON:000112092.22gold quality
bone marrow cellCL:000209292.16gold quality
pituitary glandUBERON:000000792.11gold quality
vaginaUBERON:000099692.06gold quality
putamenUBERON:000187491.92gold quality
adult mammalian kidneyUBERON:000008291.73gold quality
body of stomachUBERON:000116191.71gold quality
colonUBERON:000115591.67gold quality
intestineUBERON:000016091.61gold quality
metanephrosUBERON:000008191.54gold quality
renal glomerulusUBERON:000007491.43gold quality
hindlimb stylopod muscleUBERON:000425291.28gold quality
caudate nucleusUBERON:000187391.24gold quality
large intestineUBERON:000005991.19gold quality
spinal cordUBERON:000224091.16gold quality
amygdalaUBERON:000187691.15gold quality
aortaUBERON:000094791.11gold quality
thyroid glandUBERON:000204690.96gold quality
bone marrowUBERON:000237190.92gold quality
lungUBERON:000204890.88gold quality
stomachUBERON:000094590.82gold quality
metanephric glomerulusUBERON:000473690.74gold quality
prostate glandUBERON:000236790.73gold quality
rectumUBERON:000105290.69gold quality
esophagusUBERON:000104390.55gold quality
muscle of legUBERON:000138389.82gold quality

Single-cell (SCXA)

Detected in 31 experiment(s), a significant marker in 27.

ExperimentMarker?Max mean expression
E-GEOD-114530yes3321.36
E-GEOD-124472yes3199.59
E-HCAD-10yes2837.65
E-HCAD-24yes1563.71
E-ENAD-20yes1004.43
E-MTAB-8559yes845.71
E-HCAD-13yes418.66
E-HCAD-6yes403.04
E-MTAB-10018yes274.59
E-MTAB-10290yes215.14
E-MTAB-6701yes97.79
E-HCAD-4yes79.55
E-MTAB-10287yes71.79
E-MTAB-10553yes59.14
E-HCAD-1yes54.81

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cellAxisnTPMProtein (IHC)
Ovarytissue486.3medium
Adrenal glandtissue261.7high
Placentatissue190.8medium
Livertissue183.5low
Spleentissue173.4medium
Fallopian tubetissue153.3medium
Adipose tissuetissue143.7medium
Lymph nodetissue119.9high
Lungtissue116.9high
Thymustissue115.2
Gallbladdertissue102.5medium
Seminal vesicletissue99.2high
Bone marrowtissue97.9high
Appendixtissue90.1medium
Vaginatissue85.0low
Cervixtissue84.2not detected
Urinary bladdertissue77.6medium
Salivary glandtissue73.1medium
Smooth muscletissue70.9medium
Tonsiltissue61.7high
Breasttissue57.7medium
Heart muscletissue56.7medium
Epididymistissue56.1high
Pituitary glandtissue55.9
Stomach 1tissue51.5medium
Small intestinetissue48.2medium
Tonguetissue47.5
Colontissue45.5medium
Duodenumtissue44.6medium
Skeletal muscletissue43.3low
Prostatetissue42.0medium
Endometrium 1tissue38.7low
Kidneytissue35.5high
Esophagustissue34.1not detected
Rectumtissue31.3medium
Testistissue27.5high
Hippocampustissue22.1low
Pancreastissue20.7medium
Nucleus accumbenstissue18.9
Thyroid glandtissue17.3low
Locus coeruleustissue17.0
Choroid plexustissue15.3
Parathyroid glandtissue12.9
Frontal cortextissue11.5
Postcentral gyrustissue10.9
Skin 1tissue9.9low
Caudate putamentissue9.1
Spinal cordtissue5.7
Superior colliculitissue4.7
Substantia nigratissue3.9
Medulla oblongatatissue3.3
Midbraintissue3.1
Ponstissue2.8
Thalamustissue2.8
Putamentissue2.5
Olfactory bulbtissue2.1
Cerebral cortextissue1.9medium
Retinatissue1.9
Temporal cortextissue1.9
Hypothalamustissue1.8

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (107.6), Nucleus gracilis (57.5), Cervical spinal cord, dorsal horn (47.9), Dorsal motor vagal complex (44.3), Peritrigeminal nucleus (42.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ERCC6, GATA1, STAT1, STAT2, STAT3, TFAP2A

miRNA regulators (miRDB)

Targeting BST2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

6 miRNAs:

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-6756-5P99.8267.972466
HSA-MIR-6766-5P99.6867.702325
HSA-MIR-548AS-3P99.1269.122294
HSA-MIR-451898.1266.821030
HSA-MIR-446997.9365.811319
HSA-MIR-1266-5P97.7166.921052

Functional genomics

gnomAD constraint: pLI 0.0137, LOEUF 0.969, missense Z 1.19 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000252593 — one region, missense o/e 0.80.

Literature-anchored findings (GeneRIF, showing 40)

  • CD317 expression correlated with, and induced, a requirement for Vpu during HIV-1 and murine leukaemia virus particle release (PMID:18200009)
  • CD317, a tetherin, is associated with antiviral activity; tetherin expression correlates with a requirement for the antiviral antagonist Vpu during HIV-1 virus particle release. (PMID:18200009)
  • Interferon-alpha enhances BST2 expression and the antitumor activity of anti-CD317 monoclonal antibody in renal cell carcinoma xenogfraft models. (PMID:19032371)
  • Tetherin inhibits the release of Lassa and Marburg virus from host cells. (PMID:19091864)
  • Thus, CD317 provides a physical link between lipid rafts and the apical actin network in polarized epithelial cells and is crucial for the maintenance of microvilli in such cells. (PMID:19273615)
  • HIV-1 Vpu suppresses the expression of the CD317 antiviral factor in human cells. (PMID:19286137)
  • Results provide novel data indicating the BST2 protein expression is associated with the formation of bone metastases in human breast cancer and that BST2 may be a potential biomarker in breast cancer with bone metastasis. (PMID:19338666)
  • Clathrin-dependent endocytosis of human CD317 from the cell surface lipid rafts is mediated by direct interaction with alpha-adaptin. (PMID:19359243)
  • findings show that SIV Nef overcomes restriction by rhesus macaque & sooty mangabey tetherin, but not human tetherin; HIV-1 Vpu counteracts restriction by human tetherin, but is ineffective against macaque or mangabey tetherin (PMID:19436700)
  • study provides evidence that tetherin is important in protecting against viral infection, and that the HIV-1 Vpu-mediated countermeasure is specifically adapted to act against human tetherin (PMID:19461879)
  • Vpu antagonizes human BST-2 through interacting with the transmembrane domain of BST-2. (PMID:19474106)
  • Vpu co-opts the beta-TrCP/SCF E3 ubiquitin ligase complex to induce endosomal trafficking events that remove BST-2 from its site of action as a virion-tethering factor. (PMID:19478868)
  • hBST-2 has potential to suppress the release of Vpu-deficient HIV-1. hBST-2 can tether HIV-1 particles without the need of additional co-factor(s) that may be expressed exclusively in primates. (PMID:19490609)
  • Vpu appears to interact with BST-2 in the trans-Golgi network or in early endosomes, leading to lysosomal degradation of BST-2. (PMID:19515779)
  • Data show that BST2 directly binds to purified ILT7, initiates signaling via the ILT7-FcepsilonRIgamma complex, and regulates TLR7/9 responses in plasmacytoid dendritic cells. (PMID:19564354)
  • KSHV release is decreased in the absence of K5 in a BST2-dependent manner, suggesting that K5 contributes to the evasion of intracellular antiviral defense programs (PMID:19605472)
  • Analysis of single, double, or triple cysteine mutants revealed that any one of three cysteine residues present in the BST-2 extracellular domain was sufficient for BST-2 dimerization, for inhibition of virus release, and sensitivity to Vpu. (PMID:19737401)
  • HIV-2 envelope glycoprotein antagonism by intracellular sequestration (PMID:19740980)
  • tetherin retains progeny virions on the cell surface by a mechanism other than dimerization (PMID:19742323)
  • Results show that HIV-1 Vpu physically interacts with BST-2 through their mutual transmembrane domains and leads to the degradation of this host factor via a lysosomal, not proteasomal, pathway. (PMID:19837671)
  • These observations emphasize the importance of tetherin in protecting mammals against viral infection and suggest that HIV-1 Vpu inhibitors may select active envelope mutants. (PMID:19864625)
  • Study demonstrates, through mutational analyses and domain replacement experiments, that tetherin configuration rather than primary sequence is critical for antiviral activity. (PMID:19879838)
  • Data show that human tetherin, recently described as an antiviral protein able to inhibit the release of enveloped viruses, and its porcine homologue can inhibit PERV release from producer cells. (PMID:20015985)
  • BCA2 is a co-factor or enhancer for the tetherin-dependent restriction of HIV-1 release from infected cells. (PMID:20019814)
  • The authors show that mutation of serine 52 to alanine (S52A) entirely disrupts Vpu-mediated degradation of CD4 and strongly impairs its ability to antagonize tetherin. (PMID:20078884)
  • Data show that tetherin restricts particle release and does not require CAML for this effect. (PMID:20126395)
  • tetherin is the physical tether linking HIV-1 virions and the plasma membrane. (PMID:20140192)
  • CD317 localizes to the plasma membrane, to early and recycling endosomes, and to the trans-Golgi network and largely relocates to endosomes upon HIV-1 infection (PMID:20147389)
  • These data show that HIV-1 Vpu can efficiently antagonize virion tethering in the absence of CD317 degradation. (PMID:20147395)
  • incorporation of BST-2 into viral envelopes underlies its broad restrictive activity, whereas its relative exclusion from virions and sites of viral assembly by proteins such as HIV-1 Vpu may provide viral antagonism of restriction (PMID:20221443)
  • Tetherin inhibits virus shedding during HIV1 infection. (PMID:20329562)
  • The authors propose that the irregular coiled coil provides conformational flexibility, ensuring that BST-2/tetherin anchoring both in the plasma membrane and in the newly formed virus membrane is maintained during virus budding. (PMID:20399176)
  • These findings suggest that Ebola virus GP uses a novel mechanism to circumvent tetherin restriction. (PMID:20444895)
  • Combined evolutionary and functional studies have allowed reconstruction of the host-pathogen interactions that have shaped Tetherin and its lentivirus-encoded antagonists, including Vpu and Nef. (PMID:20444900)
  • viral proteins such as HIV-1 Vpu, simian immunodeficiency virus Nef, and KSHV K5 counteract BST-2, thereby allowing mature virions to readily escape from infected cells (PMID:20485522)
  • Both HIV-1 Vpu and HIV-2 Env redirect tetherin away from the cell surface and sequester the protein in a perinuclear compartment, which likely blocks the action of this cellular restriction factor. (PMID:20529266)
  • Tetherin restricts productive HIV-1 cell-to-cell transmission. (PMID:20585562)
  • TLR3 acativation by polyI:C resulted in inhibition of HIV infections in macrophages via induction of type 1 interferon antiviral factors, tetherin and APOBEC3G. (PMID:20636339)
  • Elevated cellular levels of BST-2 inhibited the release of virus-like particles consisting of the matrix proteins of multiple highly virulent NIAID Priority Pathogens (PMID:20686043)
  • siRNA-mediated knockdown of CD317 relieved a virion release restriction and markedly enhanced the egress of HIV-1, HIV-2, and simian immunodeficiency virus (SIV) in rat cells, including primary macrophages. (PMID:20702620)

Cross-species orthologs

2 orthologs

OrganismSymbolGene ID
mus_musculusBst2ENSMUSG00000046718
rattus_norvegicusBst2ENSRNOG00000059900

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1916800) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)Records
abnormal liver morphology1
small liver1
enlarged spleen1
enlarged lymph nodes1
abnormal skin morphology1
abnormal kidney morphology1
small kidney1
abnormal cell physiology1
increased susceptibility to Retroviridae infection1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

OrganismUniProtIdentityMethod
Cricetulus griseusQ6WRU050.0%Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

SymbolTypeEntrez
TMEM221protein-coding100130519
BISPRncRNA105221694
NXNL1protein-coding115861
MVB12Aprotein-coding93343
CCDC194protein-coding110806280
PLVAPprotein-coding83483
GTPBP3protein-coding84705

Protein

Protein identifiers

Bone marrow stromal antigen 2 — Q10589 (reviewed: Q10589)

Alternative names: HM1.24 antigen, Tetherin

All UniProt accessions (3): Q10589, A0A024R7H5, A0A7P0T9F9

UniProt curated annotations — full annotation on UniProt →

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, paramyxoviridae: nipah virus, and coronaviridae: SARS-CoV. 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 / interactions. 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. Interacts with MMP14 (via C-terminal cytoplasmic tail). Interacts with LILRA4/ILT7. Interacts with RNF115. (Microbial infection) Interacts with ebola GP protein. (Microbial infection) Interacts (via transmembrane domain) with HIV-1 VPU (via transmembrane domain). (Microbial infection) Interacts with HIV-2 ENV. (Microbial infection) Interacts with SARS-CoV ORF7a protein. (Microbial infection) Interacts with rabies virus protein G.

Subcellular location. Golgi apparatus. trans-Golgi network. Cell membrane. Membrane raft. Cytoplasm. Apical cell membrane Golgi apparatus. Late endosome.

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).

Post-translational modifications. Monoubiquitinated by KSHV E3 ubiquitin-protein ligase K5, leading to its targeting to late endosomes and degradation. The GPI anchor is essential for its antiviral activity. Heavily glycosylated.

Domain organisation. 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.

Induction. By type I interferons. (Microbial infection) Down-regulated by HIV-1 VPU protein. Antagonizes 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. (Microbial infection) Down-regulated by HIV-2 ENV protein. Antagonizes its function by targeting it to the trans-Golgi network, sequestering it away from virus assembly sites on the cell membrane. (Microbial infection) Down-regulated by KSHV K5 protein. K5 ubiquitinates it leading to its targeting to late endosomes and degradation. (Microbial infection) Down-regulated by ebola virus GP protein. (Microbial infection) Made inactive by SARS-CoV ORF7a protein through impairing proper glycosylation. May be down-regulated by SARS-CoV Spike protein through lysosomal degradation pathway.

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. Produced by alternative initiation at Met-13 of isoform 1.

Similarity. Belongs to the tetherin family.

Isoforms (2)

UniProt IDNamesCanonical?
Q10589-11, l-Tetherinyes
Q10589-22, s-Tetherin

RefSeq proteins (1): NP_004326* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR024886BST2Family

Pfam: PF16716

UniProt features (29 total): mutagenesis site 10, disulfide bond 3, topological domain 2, strand 2, glycosylation site 2, chain 1, propeptide 1, cross-link 1, splice variant 1, sequence variant 1, sequence conflict 1, helix 1, transmembrane region 1, coiled-coil region 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

15 structures by resolution:

PDBTitleMethodResolution (Å)
7Q9AMHC Class I A02 Allele presenting LLLGIGILVL, in complex with Mel5 TCRX-RAY DIFFRACTION2.1
3MQ7Crystal Structure of Ectodomain Mutant of BST-2/Tetherin/CD317X-RAY DIFFRACTION2.28
3NWHCrystal structure of BST2/TetherinX-RAY DIFFRACTION2.6
2X7AStructural basis of HIV-1 tethering to membranes by the Bst2-tetherin ectodomainX-RAY DIFFRACTION2.77
3MQ9Crystal Structure of Ectodomain Mutant of BST-2/Tetherin/CD317 Fused to MBPX-RAY DIFFRACTION2.8
3MQCCrystal Structure of Ectodomain of BST-2/Tetherin/CD317 (P21)X-RAY DIFFRACTION2.8
4P6ZCrystal structure of the human BST2 cytoplasmic domain and the HIV-1 Vpu cytoplasmic …X-RAY DIFFRACTION3
3MQBCrystal Structure of Ectodomain of BST-2/Tetherin/CD317 (C2)X-RAY DIFFRACTION3.2
2XG7Crystal Structure of BST2-Tetherin Ectodomain expressed in HEK293T cellsX-RAY DIFFRACTION3.45
6CM9Structure of the cargo bound AP-1:Arf1:tetherin-Nef closed trimer monomeric subunitELECTRON MICROSCOPY3.73
6DFFStructure of the cargo bound AP-1:Arf1:tetherin-Nef monomerELECTRON MICROSCOPY3.9
6D83Structure of the cargo bound AP-1:Arf1:tetherin-Nef (L164A, L165A) dileucine mutant dimer …ELECTRON MICROSCOPY4.27
6D84Structure of the cargo bound AP-1:Arf1:tetherin-Nef (L164A, L165A) dileucine mutant dimerELECTRON MICROSCOPY6.72
6CRIStructure of the cargo bound AP-1:Arf1:tetherin-Nef stable closed trimerELECTRON MICROSCOPY6.8
2LK9Structure of BST-2/Tetherin Transmembrane DomainSOLUTION NMR

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q10589-F185.630.69

Human Protein Atlas

Protein class: CD markers, Transporters, Transporter channels and pores, Predicted membrane proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus; vesicles

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (2)

TypePositions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in ubiquitin)18
Gpi-anchor amidated serine161

Disulfide bonds (3)

TypePositions
Interchain63, 91, 53

Glycosylation sites (2)

TypePositions
N-linked (glcnac…) asparagine65, 92

Mutagenesis-validated functional residues (10)

PositionPhenotype
3–5partial resistance to vpu.
6partial resistance to vpu and significantly reduced activation of nf-kb; when associated with a-8.
8partial resistance to vpu and significantly reduced activation of nf-kb; when associated with a-6.
18abolishes redistribution to late endosomes in cells expressing ksh virus e3 ubiquitin-protein ligase k5.
21no effect on redistribution to late endosomes in cells expressing ksh virus e3 ubiquitin-protein ligase k5.
53prevents homodimerization and inhibition of sars-cov, hcov-229e, and hiv-1 viral particles production ex vivo; when associated with a-63 …
63prevents homodimerization and inhibition of sars-cov, hcov-229e, and hiv-1 viral particles production ex vivo; when associated with a-53 …
65loss of glycosylation site.
91prevents homodimerization and inhibition of sars-cov, hcov-229e, and hiv-1 viral particles production ex vivo; when associated with a-53 …
92loss of glycosylation site. impairs anti-viral activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 curated (TAS) of 13; 7 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

13 pathways:

IDPathwayEvidence
R-HSA-9692916SARS-CoV-1 activates/modulates innate immune responses ⚕curated
R-HSA-909733Interferon alpha/beta signalingcurated
R-HSA-6798695Neutrophil degranulationcurated
R-HSA-1643685Disease ⚕—
R-HSA-5663205Infectious disease ⚕—
R-HSA-9679506SARS-CoV Infections ⚕—
R-HSA-9678108SARS-CoV-1 Infection ⚕—
R-HSA-9692914SARS-CoV-1-host interactions ⚕—
R-HSA-9824446Viral Infection Pathways ⚕—
R-HSA-1280215Cytokine Signaling in Immune system—
R-HSA-168256Immune System—
R-HSA-168249Innate Immune System—
R-HSA-913531Interferon Signaling—

MSigDB gene sets: 431 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, MODULE_92, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, MODULE_151, BECKER_TAMOXIFEN_RESISTANCE_UP, GOBP_NEGATIVE_REGULATION_OF_PRODUCTION_OF_MOLECULAR_MEDIATOR_OF_IMMUNE_RESPONSE, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_CELL_GROWTH, MODULE_64

GO Biological Process (16): negative regulation of plasmacytoid dendritic cell cytokine production (GO:0002737), response to virus (GO:0009615), negative regulation of cell growth (GO:0030308), negative regulation of cell migration (GO:0030336), regulation of actin cytoskeleton organization (GO:0032956), response to type II interferon (GO:0034341), response to interferon-alpha (GO:0035455), response to interferon-beta (GO:0035456), B cell activation (GO:0042113), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), negative regulation of viral genome replication (GO:0045071), innate immune response (GO:0045087), defense response to virus (GO:0051607), positive regulation of leukocyte proliferation (GO:0070665), negative regulation of intracellular transport of viral material (GO:1901253), immune system process (GO:0002376)

GO Molecular Function (5): RNA binding (GO:0003723), metalloendopeptidase inhibitor activity (GO:0008191), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), protein binding (GO:0005515)

GO Cellular Component (12): multivesicular body (GO:0005771), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), cell surface (GO:0009986), membrane (GO:0016020), apical plasma membrane (GO:0016324), azurophil granule membrane (GO:0035577), membrane raft (GO:0045121), extracellular exosome (GO:0070062), side of membrane (GO:0098552), cytoplasm (GO:0005737), late endosome (GO:0005770)

Reactome top-level categories

10 top-level categories:

CategoryPathways
Immune System2
Innate Immune System1
Interferon Signaling1
SARS-CoV-1-host interactions1
Disease1
Cytokine Signaling in Immune system1
SARS-CoV Infections1
Viral Infection Pathways1
SARS-CoV-1 Infection1
Infectious disease1

GO top-level categories

58 GO namespaces:

CategoryTerms
cellular anatomical structure4
response to cytokine3
membrane2
plasmacytoid dendritic cell cytokine production1
negative regulation of dendritic cell cytokine production1
regulation of plasmacytoid dendritic cell cytokine production1
response to other organism1
regulation of cell growth1
cell growth1
negative regulation of growth1
negative regulation of cellular process1
cell migration1
regulation of cell migration1
negative regulation of cell motility1
actin cytoskeleton organization1
regulation of actin filament-based process1
regulation of cytoskeleton organization1
innate immune response1
lymphocyte activation1
canonical NF-kappaB signal transduction1
regulation of canonical NF-kappaB signal transduction1
positive regulation of intracellular signal transduction1
viral genome replication1
regulation of viral genome replication1
negative regulation of viral process1
immune response1
defense response to symbiont1
defense response1
response to virus1
positive regulation of cell population proliferation1
leukocyte proliferation1
regulation of leukocyte proliferation1
intracellular transport of virus1
regulation of intracellular transport of viral material1
negative regulation of viral life cycle1
biological_process1
nucleic acid binding1
metalloendopeptidase activity1
endopeptidase inhibitor activity1
protein binding1
identical protein binding1
protein dimerization activity1
binding1
late endosome1
cytoplasm1
endomembrane system1
intracellular membrane-bounded organelle1
cell periphery1
apical part of cell1
plasma membrane region1
lysosomal membrane1
secretory granule membrane1
azurophil granule1
membrane microdomain1
extracellular vesicle1
leaflet of membrane bilayer1
intracellular anatomical structure1
endosome1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 18 of 33 annotations. The rest are phylogenetic / computational / electronic (IEA).

18 experimentally-supported GO terms:

GO termNSEvidence
defense response to virusBPdirect assay
innate immune responseBPdirect assay
negative regulation of cell growthBPdirect assay
negative regulation of cell migrationBPdirect assay
negative regulation of intracellular transport of viral materialBPdirect assay
negative regulation of plasmacytoid dendritic cell cytokine productionBPdirect assay
negative regulation of viral genome replicationBPdirect assay
response to virusBPdirect assay
Golgi apparatusCCdirect assay
cell surfaceCCmutant phenotype
extracellular exosomeCChigh-throughput assay
membraneCChigh-throughput assay
multivesicular bodyCCmutant phenotype
plasma membraneCCdirect assay
RNA bindingMFhigh-throughput assay
identical protein bindingMFphysical interaction
metalloendopeptidase inhibitor activityMFdirect assay
protein homodimerization activityMFphysical interaction

Protein interactions and networks

STRING

showing 15 of 1,732 interactions by confidence (×1000):

Protein AProtein BPartner UniProtScore
BST2APOBEC3GQ9HC16865
BST2TRIM5Q9C035798
BST2SAMHD1Q9Y3Z3759
BST2PLVAPQ9BX97745
BST2CAMLGP49069725
BST2RIGIO95786713
BST2MX2P20592702
BST2ISG15P05161681
BST2RSAD2Q8WXG1669
BST2MX1P20591655
BST2IFNA13P01562654
BST2CD4P01730651
BST2LILRA4P59901638
BST2IFI35P80217632
BST2SERINC5Q86VE9631

IntAct

Human interaction partners of BST2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

PartnerInteraction typeMIscoreRecords
LILRA4direct interaction0.6803
CD81physical association0.5603
GPphysical association0.5202
RBBP5physical association0.4001
RPL14physical association0.4001
HAGHphysical association0.3701
HARS2physical association0.3701
DPM1association0.3501

BioGRID (76 interactions; top human partners by supporting records): BTRC (Affinity Capture-Western; 2 records), CHMP4B (Affinity Capture-MS; 2 records), ABL1 (Affinity Capture-MS), ABL2 (Affinity Capture-MS), ANLN (Affinity Capture-MS), BMPR1A (Proximity Label-MS), BSG (Proximity Label-MS), CALCOCO2 (Affinity Capture-Western), CAPZA2 (Affinity Capture-MS), CD81 (Two-hybrid), CYB5R3 (Co-fractionation), DONSON (Affinity Capture-MS), DPM1 (Affinity Capture-MS), ECT2 (Affinity Capture-MS), EGFR (Proximity Label-MS)

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

PartnerThis gene’s roleSignaling class
LILRA4ligand

Disease & clinical

Genetic variants

Variant evidence for BST2: 34 ClinVar records (0 pathogenic / likely pathogenic).

ClinVar

34 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance20
Likely benign3
Benign0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 27 predictions of 265):

Position(s)EffectΔscoreSites
19:17405289–17405290donor_loss1.00004
19:17403825–17403826acceptor_loss0.99005
19:17403829acceptor_gain0.9900
19:17404193acceptor_gain0.9900
19:17404198acceptor_gain0.9900
19:17404951donor_gain0.9900
19:17405290donor_loss0.9900
19:17403678–17403679donor_loss0.98005
19:17403830acceptor_gain0.9800
19:17404127–17404129donor_loss0.98007

AlphaMissense

152 missense substitutions predicted likely pathogenic (of 1,160 scored), across 73 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

ResidueLikely-pathogenic substitutionsMean am_pathogenicityMax am_pathogenicity
C5360.7240.840
C6360.7100.845
F8150.8130.888
G5650.7840.878
I12050.7830.942
S5050.7530.810
L12740.8560.986
G3840.8270.938
F4440.8270.893
L11640.7920.963
R13840.7220.815
N6540.7150.757
L12330.8220.920
L9830.8110.946
T6730.7500.925
G2730.7310.754
M9930.7220.722
N14130.6960.809
M6130.6610.661
Q12830.6600.821

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

CancerPrognosticp-value
Testicular Germ Cell Tumor (TCGA)unfavorable0.000645

Disease associations

OMIM: gene MIM:600534 | disease phenotypes:

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6067079 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValue
CHEMBL5653589KD1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
6.67Kd215.9nMCHEMBL3752910
6.67ED50215.9nMCHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide2147961: Binding affinity to human BST2 incubated for 45 mins by Kinobead based pull down assaykd0.2159uM

CTD chemical–gene interactions

73 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Valproic Acidaffects expression, decreases expression, increases expression, increases methylation5
sodium arsenitedecreases expression, increases expression4
Estradioldecreases expression, affects cotreatment, increases expression4
Tretinoinaffects expression, affects cotreatment, increases expression, decreases expression4
(+)-JQ1 compounddecreases expression3
Tetrachlorodibenzodioxinaffects cotreatment, increases expression, decreases expression3
Cyclosporinedecreases expression, increases expression3
mercuric bromidedecreases expression, affects cotreatment2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression, increases expression2
Resveratroldecreases expression, increases expression2
Air Pollutantsincreases abundance, decreases expression2
Benzo(a)pyreneincreases methylation, decreases expression2
Methotrexateaffects response to substance, decreases expression2
Phenylmercuric Acetateaffects cotreatment, decreases expression2
Particulate Matterdecreases expression, increases abundance, affects cotreatment2
GSK-J4decreases expression1
3,19-(2-bromobenzylidene)andrographolidedecreases response to substance, increases expression1
dicrotophosdecreases expression1
methylmercuric chloridedecreases expression1
bisphenol Aaffects expression1
kojic aciddecreases expression1
arseniteaffects binding, increases reaction1
mono-(2-ethylhexyl)phthalatedecreases expression1
tris(1,3-dichloro-2-propyl)phosphatedecreases expression1
nickel chlorideaffects cotreatment, increases expression1
chloroquine diphosphatedecreases expression1
nickel sulfateincreases expression1
hydroquinonedecreases expression1
pentanalincreases expression1
tamibaroteneaffects expression1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL5651003BindingBinding affinity to human BST2 incubated for 45 mins by Kinobead based pull down assayNVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — *ChemMedChem*

Cellosaurus cell lines

5 cell lines: 3 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_B1BTAbcam A-431 BST2 KOCancer cell lineFemale
CVCL_D9ACUbigene HEK293 BST2 KOTransformed cell lineFemale
CVCL_SF88HAP1 BST2 (-) 1Cancer cell lineMale
CVCL_SF89HAP1 BST2 (-) 2Cancer cell lineMale
CVCL_WL54Teth-CRFKSpontaneously immortalized cell lineFemale

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for BST2 across ~30M SureChEMBL compounds — explore on Sugi Predict.

No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.