Q10589 (BST2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bone marrow stromal antigen 2
Short name=BST-2

Alternative name(s):
HM1.24 antigen
Tetherin
CD_antigen=CD317

Gene names

Name:

BST2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	180 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	May be involved in the sorting of secreted proteins By similarity. May be involved in pre-B-cell growth. Antiretroviral defense protein, that blocks release of enveloped virus from the cell surface. Active against at least four virus families: retroviruses, filoviruses, arenaviruses, and herpesviruses. Depleted unpon HIV-1 infection by viral VPU protein through 20S proteasome degradation. Depleted upon infection by human Kaposi's sarcoma-associated herpesvirus (KSHV) through ubiquitination and subsequent degradation. May play a role in B-cell activation in rheumatoid arthritis. Ref.10 Ref.11 Ref.12 Ref.15 Ref.16 Ref.18
Subunit structure	Parralel homodimer; disulfide-linked. May form homotetramers under reducing conditions. Ref.2 Ref.12 Ref.16 Ref.17 Ref.18
Subcellular location	Golgi apparatus › trans-Golgi network. Cell membrane; Single-pass type II membrane protein. Cell membrane; Lipid-anchor › GPI-anchor. Late endosome. Note: Targeted to late endosomes upon KSHV infection and subsequent ubiquitination. Targeted to the trans-Golgi network by viral VPU protein. Ref.9 Ref.12 Ref.15 Ref.16
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). Ref.2 Ref.8
Induction	During B-cell activation (at protein level), or by interferon alpha as part of entiviral state cellular program. Ref.8
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. Ref.16
Post-translational modification	Monoubiquitinated by KSHV E3 ubiquitin-protein ligase K5, leading to its targeting to late endosomes and degradation.
Sequence similarities	Belongs to the tetherin family.

Ontologies

Keywords
Biological process	Antiviral defense B-cell activation Immunity Innate immunity
Cellular component	Cell membrane Endosome Golgi apparatus Membrane
Coding sequence diversity	Polymorphism
Domain	Coiled coil Signal-anchor Transmembrane Transmembrane helix
PTM	Disulfide bond GPI-anchor Glycoprotein Isopeptide bond Lipoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	B cell activation Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Traceable author statement. Source: ProtInc cell-cell signaling Traceable author statement. Source: ProtInc defense response to virus Inferred from direct assay Ref.16. Source: UniProtKB humoral immune response Traceable author statement. Source: ProtInc innate immune response Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Traceable author statement. Source: ProtInc positive regulation of I-kappaB kinase/NF-kappaB cascade Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW integral to plasma membrane Traceable author statement. Source: ProtInc late endosome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	protein homodimerization activity Inferred from physical interaction Ref.16. Source: UniProtKB signal transducer activity Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 161

161

Bone marrow stromal antigen 2

PRO_0000065005

Propeptide

162 – 180

19

Removed in mature form Potential

PRO_0000253552

Regions

Topological domain

1 – 20

20

Cytoplasmic Potential

Transmembrane

21 – 48

28

Helical; Signal-anchor for type II membrane protein; Potential

Topological domain

49 – 161

113

Extracellular Potential

Coiled coil

68 – 152

85

Amino acid modifications

Lipidation

161

1

GPI-anchor amidated serine Potential

Glycosylation

65

1

N-linked (GlcNAc...) Ref.12 Ref.13 Ref.14

Glycosylation

92

1

N-linked (GlcNAc...) Ref.12

Disulfide bond

53

Interchain Ref.12 Ref.16 Ref.17 Ref.18

Disulfide bond

63

Interchain Ref.12 Ref.16 Ref.17 Ref.18

Disulfide bond

91

Interchain Ref.12 Ref.16 Ref.17 Ref.18

Cross-link

18

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.15

Natural variations

Natural variant

143

1

V → F.
Corresponds to variant rs1804402 [ dbSNP | Ensembl ].

VAR_012067

Experimental info

Mutagenesis

18

1

K → R: Abolishes redistribution to late endosomes in cells expressing KSH virus E3 ubiquitin-protein ligase K5. Ref.15

Mutagenesis

21

1

K → R: No effect on redistribution to late endosomes in cells expressing KSH virus E3 ubiquitin-protein ligase K5. Ref.15

Mutagenesis

65

1

N → A: Loss of glycosylation site. Ref.12

Mutagenesis

92

1

N → A: Loss of glycosylation site. Impairs anti-viral activity. Ref.12

Sequence conflict

141

1

N → D in BAD96844. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

180

Helix Strand Turn

Details...

Helix

51 – 54

4

Helix

58 – 78

21

Helix

82 – 107

26

Helix

111 – 116

6

Helix

120 – 149

30

Sequences

	Sequence		Length	Mass (Da)
	Q10589 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: CAF52340D69061EE	FASTA	180	19,769
	10 20 30 40 50 60 MASTSYDYCR VPMEDGDKRC KLLLGIGILV LLIIVILGVP LIIFTIKANS EACRDGLRAV 70 80 90 100 110 120 MECRNVTHLL QQELTEAQKG FQDVEAQAAT CNHTVMALMA SLDAEKAQGQ KKVEELEGEI 130 140 150 160 170 180 TTLNHKLQDA SAEVERLRRE NQVLSVRIAD KKYYPSSQDS SSAAAPQLLI VLLGLSALLQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and chromosomal mapping of a bone marrow stromal cell surface gene, BST2, that may be involved in pre-B-cell growth." Ishikawa J., Kaisho T., Tomizawa H., Lee B.O., Kobune Y., Inazawa J., Oritani K., Itoh M., Ochi T., Ishihara K., Hirano T. Genomics 26:527-534(1995) [PubMed: 7607676] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning and characterization of a surface antigen preferentially overexpressed on multiple myeloma cells." Ohtomo T., Sugamata Y., Ozaki Y., Ono K., Yoshimura Y., Kawai S., Koishihara Y., Ozaki S., Kosaka M., Hirano T., Tsuchiya M. Biochem. Biophys. Res. Commun. 258:583-591(1999) [PubMed: 10329429] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, SUBUNIT.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Blood.
[8]	"Characterization of antibodies submitted to the B cell section of the 8th Human Leukocyte Differentiation Antigens Workshop by flow cytometry and immunohistochemistry." Vidal-Laliena M., Romero X., March S., Requena V., Petriz J., Engel P. Cell. Immunol. 236:6-16(2005) [PubMed: 16157322] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION BY B-CELL ACTIVATION, NOMENCLATURE.
[9]	"Modification-specific proteomics of plasma membrane proteins: identification and characterization of glycosylphosphatidylinositol-anchored proteins released upon phospholipase D treatment." Elortza F., Mohammed S., Bunkenborg J., Foster L.J., Nuehse T.S., Brodbeck U., Peck S.C., Jensen O.N. J. Proteome Res. 5:935-943(2006) [PubMed: 16602701] [Abstract] Cited for: GPI-ANCHOR [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"The interferon-induced protein BST-2 restricts HIV-1 release and is downregulated from the cell surface by the viral Vpu protein." Van Damme N., Goff D., Katsura C., Jorgenson R.L., Mitchell R., Johnson M.C., Stephens E.B., Guatelli J. Cell Host Microbe 3:245-252(2008) [PubMed: 18342597] [Abstract] Cited for: FUNCTION IN HIV-1 INFECTION.
[11]	"Tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu." Neil S.J., Zang T., Bieniasz P.D. Nature 451:425-430(2008) [PubMed: 18200009] [Abstract] Cited for: FUNCTION IN HIV-1 INFECTION.
[12]	"Tetherin inhibits HIV-1 release by directly tethering virions to cells." Perez-Caballero D., Zang T., Ebrahimi A., McNatt M.W., Gregory D.A., Johnson M.C., Bieniasz P.D. Cell 139:499-511(2009) [PubMed: 19879838] [Abstract] Cited for: FUNCTION IN HIV-1 INFECTION, GLYCOSYLATION AT ASN-65 AND ASN-92, SUBCELLULAR LOCATION, DISULFIDE BONDS, SUBUNIT, TOPOLOGY, GPI-ANCHOR, MUTAGENESIS OF ASN-65 AND ASN-92.
[13]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-65, MASS SPECTROMETRY. Tissue: Liver.
[14]	"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins." Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D. Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-65, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"The RING-CH ligase K5 antagonizes restriction of KSHV and HIV-1 particle release by mediating ubiquitin-dependent endosomal degradation of tetherin." Pardieu C., Vigan R., Wilson S.J., Calvi A., Zang T., Bieniasz P., Kellam P., Towers G.J., Neil S.J. PLoS Pathog. 6:E1000843-E1000843(2010) [PubMed: 20419159] [Abstract] Cited for: FUNCTION IN KSHV AND HIV-1 INFECTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-18 AND LYS-21, UBIQUITINATION AT LYS-18 BY KSH VIRUS E3 UBIQUITIN-PROTEIN LIGASE K5.
[16]	"Structural basis of HIV-1 tethering to membranes by the BST-2/tetherin ectodomain." Hinz A., Miguet N., Natrajan G., Usami Y., Yamanaka H., Renesto P., Hartlieb B., McCarthy A.A., Simorre J.P., Gottlinger H., Weissenhorn W. Cell Host Microbe 7:314-323(2010) [PubMed: 20399176] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.77 ANGSTROMS) OF 87-147, FUNCTION, DOMAIN, DISULFIDE BONDS, SUBUNIT, SUBCELLULAR LOCATION, CIRCULAR DICHROISM.
[17]	"Structural and functional studies on the extracellular domain of BST2/tetherin in reduced and oxidized conformations." Schubert H.L., Zhai Q., Sandrin V., Eckert D.M., Garcia-Maya M., Saul L., Sundquist W.I., Steiner R.A., Hill C.P. Proc. Natl. Acad. Sci. U.S.A. 107:17951-17956(2010) [PubMed: 20880831] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 47-152, SUBUNIT, DISULFIDE BONDS.
[18]	"Structural insight into the mechanisms of enveloped virus tethering by tetherin." Yang H., Wang J., Jia X., McNatt M.W., Zang T., Pan B., Meng W., Wang H.W., Bieniasz P.D., Xiong Y. Proc. Natl. Acad. Sci. U.S.A. 107:18428-18432(2010) [PubMed: 20940320] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.28 ANGSTROMS) OF 47-161, SUBUNIT, FUNCTION, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00026241.

PIR

A56836.

RefSeq

NP_004326.1. NM_004335.2.

UniGene

Hs.118110.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LK9	NMR	-	A	18-47	[»]
2X7A	X-ray	2.77	A/B/C/D/E/F/G/H/I/J/K	87-147	[»]
2XG7	X-ray	3.45	A/C	51-151	[»]
3MQ7	X-ray	2.28	A/B/C/D/E/F/G/H/I/J/K/L	47-161	[»]
3MQ9	X-ray	2.80	A/B/C/D/E/F/G/H	66-139	[»]
3MQB	X-ray	3.20	A/B/E/F	47-161	[»]
3MQC	X-ray	2.80	A/B/C/D	47-161	[»]
3NWH	X-ray	2.60	A/B/C/D	47-152	[»]

ProteinModelPortal

Q10589.

SMR

Q10589. Positions 48-152.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-53216N.

IntAct

Q10589. 5 interactions.

STRING

Q10589.

PTM databases

PhosphoSite

Q10589.

Polymorphism databases

DMDM

1705508.

Proteomic databases

PeptideAtlas

Q10589.

PRIDE

Q10589.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000252593; ENSP00000252593; ENSG00000130303.
ENST00000446020; ENSP00000401528; ENSG00000130303.

GeneID

684.

KEGG

hsa:684.

UCSC

uc002ngl.1. human.

Organism-specific databases

CTD

684.

GeneCards

GC19M017502.

H-InvDB

HIX0014891.

HGNC

HGNC:1119. BST2.

HPA

HPA017060.

MIM

600534. gene.

neXtProt

NX_Q10589.

PharmGKB

PA25436.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG20923.

GeneTree

ENSGT00390000013782.

HOVERGEN

HBG004902.

InParanoid

Q10589.

OMA

YPSSQDS.

PhylomeDB

Q10589.

Gene expression databases

ArrayExpress

Q10589.

Bgee

Q10589.

CleanEx

HS_BST2.

Genevestigator

Q10589.

GermOnline

ENSG00000130303. Homo sapiens.

Family and domain databases

InterPro

IPR024886. BST2.
[Graphical view]

KO

K06731.

PANTHER

PTHR15190. PTHR15190. 1 hit.

ProtoNet

Search...

Other

NextBio

2816.

SOURCE

Search...

Entry information

Entry name

BST2_HUMAN

Accession

Primary (citable) accession number: Q10589
Secondary accession number(s): A8K4Y4, Q53G07

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	October 1, 1996
Last modified:	January 25, 2012
This is version 96 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.