Q7TSA3 (BTLA_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
B- and T-lymphocyte attenuator

Alternative name(s):
B- and T-lymphocyte-associated protein
CD_antigen=CD272

Gene names

Name:

Btla

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	306 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	Lymphocyte inhibitory receptor which inhibits lymphocytes during immune response.
Subunit structure	Interacts with tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2. Interacts with TNFRSF14/HVEM. Ref.1 Ref.3 Ref.4 Ref.6
Subcellular location	Membrane; Single-pass type I membrane protein Potential.
Tissue specificity	Expressed in splenic T- and B-cells as well as lymph node tissues but very weakly in somatic tissues. Also expressed in macrophages, NK cells and dendritic cells. A polymorphic tissue distribution between several strains is seen. Ref.1 Ref.5
Post-translational modification	Phosphorylated on Tyr residues by TNFRSF14 and by antigen receptors cross-linking, both inducing association with PTPN6 and PTPN11. Ref.4 N-glycosylated. Ref.1
Disruption phenotype	Mice exhibit no developmental defects in T- or B-cells in thymus or bone marrow, but increased antibody responses and sensitivity to antigen-induced 'experimental autoimmune encephalomyelitis'. T-cells lacking Btla show increased proliferation with a heightened response to anti-CD3 and a slightly greater response to stimulation with anti-IgM. Ref.1
Sequence similarities	Contains 1 Ig-like V-type (immunoglobulin-like) domain.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Immunoglobulin domain Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	immune response-regulating cell surface receptor signaling pathway Inferred from mutant phenotype Ref.4. Source: MGI negative regulation of B cell proliferation Inferred from mutant phenotype Ref.1. Source: MGI negative regulation of alpha-beta T cell proliferation Inferred from mutant phenotype Ref.4. Source: MGI
Cellular_component	external side of plasma membrane Inferred from direct assay Ref.4. Source: MGI integral to plasma membrane Inferred from direct assay Ref.1. Source: MGI
Molecular_function	receptor activity Inferred from genetic interaction PubMed 12920180. Source: MGI
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7TSA3-1)

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.

Isoform 2 (identifier: Q7TSA3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     37-142: Missing.

Isoform 3 (identifier: Q7TSA3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     156-157: TV → I

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 29

29

Potential

Chain

30 – 306

277

B- and T-lymphocyte attenuator

PRO_0000014524

Regions

Topological domain

30 – 183

154

Extracellular Potential

Transmembrane

184 – 204

21

Helical; Potential

Topological domain

205 – 306

102

Cytoplasmic Potential

Domain

49 – 143

95

Ig-like V-type

Amino acid modifications

Glycosylation

74

1

N-linked (GlcNAc...) Potential

Glycosylation

81

1

N-linked (GlcNAc...) Potential

Glycosylation

101

1

N-linked (GlcNAc...) Potential

Glycosylation

119

1

N-linked (GlcNAc...) Potential

Glycosylation

148

1

N-linked (GlcNAc...) Potential

Glycosylation

165

1

N-linked (GlcNAc...) Potential

Disulfide bond

40 ↔ 69

Ref.6

Disulfide bond

64 ↔ 124

Ref.6

Disulfide bond

78 ↔ 85

Ref.6

Natural variations

Alternative sequence

37 – 142

106

Missing in isoform 2.

VSP_014836

Alternative sequence

156 – 157

2

TV → I in isoform 3.

VSP_014837

Natural variant

41

1

P → E in strain: 129/SvEv; requires 2 nucleotide substitutions. Ref.1

Natural variant

45 – 47

3

TIT → NIK in strain: 129/SvEv.

Natural variant

52

1

Q → H in strain: 129/SvEv. Ref.1

Natural variant

55

1

R → W in strain: 129/SvEv. Ref.1

Natural variant

63

1

Q → E in strain: 129/SvEv. Ref.1

Natural variant

85

1

C → W in strain: 129/SvEv. Ref.1

Natural variant

91

1

S → G in strain: 129/SvEv. Ref.1

Natural variant

102

1

Q → R in strain: 129/SvEv. Ref.1

Natural variant

143

1

R → T in strain: C57BL/6J. Ref.2

Experimental info

Mutagenesis

44

1

L → H: Loss of interaction with TNFRSF14. Ref.6

Mutagenesis

48

1

R → D: Loss of interaction with TNFRSF14. Ref.6

Mutagenesis

65

1

P → A: Loss of interaction with TNFRSF14. Ref.6

Mutagenesis

136

1

H → D: Loss of interaction with TNFRSF14. Ref.6

Mutagenesis

245

1

Y → F: No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-274 and/or F-299. Ref.1 Ref.3

Mutagenesis

274

1

Y → F: No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-245 and/or F-299. Ref.1 Ref.3

Mutagenesis

299

1

Y → F: No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-245 and/or F-274. Ref.1 Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

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.

.

.

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.

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.

.

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306

Helix Strand Turn

Details...

Beta strand

50 – 55

6

Beta strand

60 – 67

8

Beta strand

69 – 71

3

Beta strand

75 – 80

6

Beta strand

82 – 87

6

Beta strand

94 – 99

6

Beta strand

101 – 104

4

Beta strand

106 – 111

6

Helix

116 – 118

3

Beta strand

120 – 128

9

Beta strand

131 – 134

4

Beta strand

138 – 143

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 19, 2005. Version 2. Checksum: A5B4584BAC882B93	FASTA	306	34,337
	10 20 30 40 50 60 MKTVPAMLGT PRLFREFFIL HLGLWSILCE KATKRNDEEC PVQLTITRNS KQSARTGELF 70 80 90 100 110 120 KIQCPVKYCV HRPNVTWCKH NGTICVPLEV SPQLYTSWEE NQSVPVFVLH FKPIHLSDNG 130 140 150 160 170 180 SYSCSTNFNS QVINSHSVTI HVRERTQNSS EHPLITVSDI PDATNASGPS TMEERPGRTW 190 200 210 220 230 240 LLYTLLPLGA LLLLLACVCL LCFLKRIQGK EKKPSDLAGR DTNLVDIPAS SRTNHQALPS 250 260 270 280 290 300 GTGIYDNDPW SSMQDESELT ISLQSERNNQ GIVYASLNHC VIGRNPRQEN NMQEAPTEYA SICVRS
	Isoform 2 [UniParc]. Checksum: 94A167B779171DF0	FASTA	200	22,326
	10 20 30 40 50 60 MKTVPAMLGT PRLFREFFIL HLGLWSILCE KATKRNRERT QNSSEHPLIT VSDIPDATNA 70 80 90 100 110 120 SGPSTMEERP GRTWLLYTLL PLGALLLLLA CVCLLCFLKR IQGKEKKPSD LAGRDTNLVD 130 140 150 160 170 180 IPASSRTNHQ ALPSGTGIYD NDPWSSMQDE SELTISLQSE RNNQGIVYAS LNHCVIGRNP 190 200 RQENNMQEAP TEYASICVRS
	Isoform 3 [UniParc]. Checksum: 14C51F126F2F519A	FASTA	305	34,250
	10 20 30 40 50 60 MKTVPAMLGT PRLFREFFIL HLGLWSILCE KATKRNDEEC PVQLTITRNS KQSARTGELF 70 80 90 100 110 120 KIQCPVKYCV HRPNVTWCKH NGTICVPLEV SPQLYTSWEE NQSVPVFVLH FKPIHLSDNG 130 140 150 160 170 180 SYSCSTNFNS QVINSHSVTI HVRERTQNSS EHPLIISDIP DATNASGPST MEERPGRTWL 190 200 210 220 230 240 LYTLLPLGAL LLLLACVCLL CFLKRIQGKE KKPSDLAGRD TNLVDIPASS RTNHQALPSG 250 260 270 280 290 300 TGIYDNDPWS SMQDESELTI SLQSERNNQG IVYASLNHCV IGRNPRQENN MQEAPTEYAS ICVRS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1." Watanabe N., Gavrieli M., Sedy J.R., Yang J., Fallarino F., Loftin S.K., Hurchla M.A., Zimmerman N., Sim J., Zang X., Murphy T.L., Russell J.H., Allison J.P., Murphy K.M. Nat. Immunol. 4:670-679(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF TYR-245; TYR-274 AND TYR-299, GLYCOSYLATION, TISSUE SPECIFICITY, INTERACTION WITH PTPN6 AND PTPN11, DISRUPTION PHENOTYPE, VARIANTS GLU-41; 45-ASN--LYS-47; HIS-52; TRP-55; GLU-63; TRP-85; GLY-91 AND ARG-102. Strain: 129/SvEv.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), VARIANT THR-143. Strain: C57BL/6J. Tissue: Thymus.
[3]	"Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B and T lymphocyte attenuator required for association with protein tyrosine phosphatases SHP-1 and SHP-2." Gavrieli M., Watanabe N., Loftin S.K., Murphy T.L., Murphy K.M. Biochem. Biophys. Res. Commun. 312:1236-1243(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF TYR-245; TYR-274 AND TYR-299, INTERACTION WITH PTPN6 AND PTPN11.
[4]	"B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator." Sedy J.R., Gavrieli M., Potter K.G., Hurchla M.A., Lindsley R.C., Hildner K., Scheu S., Pfeffer K., Ware C.F., Murphy T.L., Murphy K.M. Nat. Immunol. 6:90-98(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TNFRSF14, PHOSPHORYLATION.
[5]	"B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly induced in anergic CD4+ T cells." Hurchla M.A., Sedy J.R., Gavrieli M., Drake C.G., Murphy T.L., Murphy K.M. J. Immunol. 174:3377-3385(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY, POLYMORPHISM.
[6]	"Structural determinants of herpesvirus entry mediator recognition by murine B and T lymphocyte attenuator." Nelson C.A., Fremont M.D., Sedy J.R., Norris P.S., Ware C.F., Murphy K.M., Fremont D.H. J. Immunol. 180:940-947(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 30-150, MUTAGENESIS OF LEU-44; ARG-48; PRO-65 AND HIS-136, INTERACTION WITH TNFRSF14/HVEM, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY293285 mRNA. Translation: AAP44002.1.
AK041334 mRNA. Translation: BAC30910.1.

IPI

IPI00380719.
IPI00607941.
IPI00608090.

RefSeq

NP_001032808.2. NM_001037719.2.
NP_808252.1. NM_177584.3.

UniGene

Mm.38199.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XAU	X-ray	1.80	A	30-150	[»]

ProteinModelPortal

Q7TSA3.

SMR

Q7TSA3. Positions 40-143.

ModBase

Search...

Protein-protein interaction databases

STRING

10090.ENSMUSP00000067877.

PTM databases

PhosphoSite

Q7TSA3.

Proteomic databases

PRIDE

Q7TSA3.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000102802; ENSMUSP00000099866; ENSMUSG00000052013.

GeneID

208154.

KEGG

mmu:208154.

Organism-specific databases

CTD

151888.

MGI

MGI:2658978. Btla.

Phylogenomic databases

eggNOG

NOG42530.

GeneTree

ENSGT00390000017390.

HOGENOM

HOG000168895.

HOVERGEN

HBG080937.

InParanoid

Q7TSA3.

KO

K06707.

OrthoDB

EOG4NKBWD.

Gene expression databases

ArrayExpress

Q7TSA3.

Bgee

Q7TSA3.

CleanEx

MM_BTLA.

Genevestigator

Q7TSA3.

GermOnline

ENSMUSG00000052013. Mus musculus.

Family and domain databases

Gene3D

2.60.40.10. 1 hit.

InterPro

IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]

SMART

SM00409. IG. 1 hit.
[Graphical view]

PROSITE

PS50835. IG_LIKE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q7TSA3.

NextBio

372176.

SOURCE

Search...

Entry information

Entry name

BTLA_MOUSE

Accession

Primary (citable) accession number: Q7TSA3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	July 19, 2005
Last modified:	April 3, 2013
This is version 80 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program