Q7Z6A9 (BTLA_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	289 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. Ref.1
Subunit structure	Interacts with tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2. Interacts with TNFRSF14/HVEM. Ref.1 Ref.7 Ref.8
Subcellular location	Membrane; Single-pass type I membrane protein Potential.
Post-translational modification	Phosphorylated on Tyr residues by TNFRSF14 and by antigen receptors cross-linking, both inducing association with PTPN6 and PTPN11. Ref.8 N-glycosylated. Ref.1
Sequence similarities	Contains 1 Ig-like V-type (immunoglobulin-like) domain.
Sequence caution	The sequence BAD18396.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Adaptive immunity Immunity
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
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	T cell costimulation Traceable author statement. Source: Reactome immune response-regulating cell surface receptor signaling pathway Inferred from electronic annotation. Source: Compara negative regulation of B cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of alpha-beta T cell proliferation Inferred from electronic annotation. Source: Compara
Cellular_component	external side of plasma membrane Inferred from electronic annotation. Source: Compara integral to plasma membrane Inferred from electronic annotation. Source: Compara plasma membrane Traceable author statement. Source: Reactome
Molecular_function	receptor activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q7Z6A9-1)

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: Q7Z6A9-2)

The sequence of this isoform differs from the canonical sequence as follows:
     135-182: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 30

30

Potential

Chain

31 – 289

259

B- and T-lymphocyte attenuator

PRO_0000014523

Regions

Topological domain

31 – 157

127

Extracellular Potential

Transmembrane

158 – 178

21

Helical; Potential

Topological domain

179 – 289

111

Cytoplasmic Potential

Domain

43 – 134

92

Ig-like V-type

Amino acid modifications

Glycosylation

75

1

N-linked (GlcNAc...) Potential

Glycosylation

94

1

N-linked (GlcNAc...) Potential

Glycosylation

110

1

N-linked (GlcNAc...) Potential

Disulfide bond

34 ↔ 63

Ref.9

Disulfide bond

58 ↔ 115

Ref.9

Disulfide bond

72 ↔ 79

Ref.9

Natural variations

Alternative sequence

135 – 182

48

Missing in isoform 2.

VSP_040305

Natural variant

124

1

I → V.
Corresponds to variant rs16859633 [ dbSNP | Ensembl ].

VAR_056027

Natural variant

157

1

R → S. Ref.1 Ref.5 Ref.6
Corresponds to variant rs2931761 [ dbSNP | Ensembl ].

VAR_027607

Natural variant

267

1

P → L. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6
Corresponds to variant rs9288952 [ dbSNP | Ensembl ].

VAR_027608

Experimental info

Mutagenesis

226

1

Y → F: No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-257 and/or F-282. Ref.1 Ref.7

Mutagenesis

257

1

Y → F: No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-226 and/or F-282. Ref.1 Ref.7

Mutagenesis

282

1

Y → F: No change of phosphorylation implicated in interaction with PTPN6 and PTPN11. Severe reduction of phosphorylation; when associated with F-226 and/or F-257. Ref.1 Ref.7

Sequence conflict

105

1

V → M in AAP44003. Ref.1

Sequence conflict

138

1

S → G in AAP44003. Ref.1

Sequence conflict

148

1

M → V in AAP44003. Ref.1

Sequence conflict

171

1

C → W in AAP44003. Ref.1

Sequence conflict

219

1

L → P in BAD18396. Ref.6

Sequence conflict

223

1

T → A in AAP44003. Ref.1

Sequence conflict

243

1

Y → C in AAP44003. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

289

Helix Strand Turn

Details...

Beta strand

44 – 49

6

Beta strand

54 – 61

8

Beta strand

63 – 65

3

Beta strand

68 – 74

7

Beta strand

79 – 81

3

Beta strand

87 – 91

5

Beta strand

96 – 104

9

Helix

107 – 109

3

Beta strand

111 – 119

9

Beta strand

122 – 125

4

Beta strand

129 – 134

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 3. Checksum: F4D1FF775D7D33F3	FASTA	289	32,834
	10 20 30 40 50 60 MKTLPAMLGT GKLFWVFFLI PYLDIWNIHG KESCDVQLYI KRQSEHSILA GDPFELECPV 70 80 90 100 110 120 KYCANRPHVT WCKLNGTTCV KLEDRQTSWK EEKNISFFIL HFEPVLPNDN GSYRCSANFQ 130 140 150 160 170 180 SNLIESHSTT LYVTDVKSAS ERPSKDEMAS RPWLLYRLLP LGGLPLLITT CFCLFCCLRR 190 200 210 220 230 240 HQGKQNELSD TAGREINLVD AHLKSEQTEA STRQNSQVLL SETGIYDNDP DLCFRMQEGS 250 260 270 280 EVYSNPCLEE NKPGIVYASL NHSVIGPNSR LARNVKEAPT EYASICVRS
	Isoform 2 [UniParc]. Checksum: 991AFF2495C3F612	FASTA	241	27,317
	10 20 30 40 50 60 MKTLPAMLGT GKLFWVFFLI PYLDIWNIHG KESCDVQLYI KRQSEHSILA GDPFELECPV 70 80 90 100 110 120 KYCANRPHVT WCKLNGTTCV KLEDRQTSWK EEKNISFFIL HFEPVLPNDN GSYRCSANFQ 130 140 150 160 170 180 SNLIESHSTT LYVTGKQNEL SDTAGREINL VDAHLKSEQT EASTRQNSQV LLSETGIYDN 190 200 210 220 230 240 DPDLCFRMQE GSEVYSNPCL EENKPGIVYA SLNHSVIGPN SRLARNVKEA PTEYASICVR S

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] (ISOFORM 1), MUTAGENESIS OF TYR-226; TYR-257 AND TYR-282, GLYCOSYLATION, FUNCTION, INTERACTION WITH PTPN6 AND PTPN11, VARIANTS SER-157 AND LEU-267.
[2]	"Point mutations in the BTLA gene in multiple myeloma and other hematologic malignancies." Mao Y., Wang X., Wu H., Chen Y., Ge Y., Chen J., Zhang X. Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-267.
[3]	"Human BTLA mRNA alternate splice transcript lacking transmembrane encoding region." Oaks M.K., Tector M.F., Mewissen G. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANT LEU-267. Tissue: Peripheral blood.
[4]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2-289 (ISOFORM 1), VARIANTS SER-157 AND LEU-267.
[6]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 4-289 (ISOFORM 1), VARIANTS SER-157 AND LEU-267. Tissue: Trachea.
[7]	"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-226; TYR-257 AND TYR-282, INTERACTION WITH PTPN6 AND PTPN11.
[8]	"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.
[9]	"Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex." Compaan D.M., Gonzalez L.C., Tom I., Loyet K.M., Eaton D., Hymowitz S.G. J. Biol. Chem. 280:39553-39561(2005) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-137 IN COMPLEX WITH TNFRSF14, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY293286 mRNA. Translation: AAP44003.1.
AY599411 mRNA. Translation: AAT44901.1.
DQ198368 mRNA. Translation: ABA54407.1.
AC092894 Genomic DNA. No translation available.
BC107091 mRNA. Translation: AAI07092.1.
BC107092 mRNA. Translation: AAI07093.1.
AK131204 mRNA. Translation: BAD18396.1. Different initiation.

IPI

IPI00376243.
IPI00654867.

RefSeq

NP_001078826.1. NM_001085357.1.
NP_861445.3. NM_181780.3.

UniGene

Hs.445162.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2AW2	X-ray	2.80	A/X	26-137	[»]

ProteinModelPortal

Q7Z6A9.

SMR

Q7Z6A9. Positions 34-137.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48795N.

IntAct

Q7Z6A9. 1 interaction.

MINT

MINT-8020099.

STRING

9606.ENSP00000333919.

PTM databases

PhosphoSite

Q7Z6A9.

Polymorphism databases

DMDM

296439425.

Proteomic databases

PaxDb

Q7Z6A9.

PRIDE

Q7Z6A9.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000334529; ENSP00000333919; ENSG00000186265.
ENST00000383680; ENSP00000373178; ENSG00000186265.

GeneID

151888.

KEGG

hsa:151888.

UCSC

uc003dza.4. human.
uc003dzb.4. human.

Organism-specific databases

CTD

151888.

GeneCards

GC03M112182.

HGNC

HGNC:21087. BTLA.

HPA

HPA047211.

MIM

607925. gene.

neXtProt

NX_Q7Z6A9.

PharmGKB

PA134968341.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG42530.

HOGENOM

HOG000168895.

HOVERGEN

HBG080937.

InParanoid

Q7Z6A9.

KO

K06707.

OMA

PNVTWCK.

OrthoDB

EOG4NKBWD.

PhylomeDB

Q7Z6A9.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

Q7Z6A9.

CleanEx

HS_BTLA.

Genevestigator

Q7Z6A9.

GermOnline

ENSG00000186265. Homo sapiens.

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

Q7Z6A9.

GenomeRNAi

151888.

NextBio

86817.

SOURCE

Search...

Entry information

Entry name

BTLA_HUMAN

Accession

Primary (citable) accession number: Q7Z6A9
Secondary accession number(s): Q3B831, Q3HS85, Q6ZNH9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2005
Last sequence update:	May 18, 2010
Last modified:	May 29, 2013
This is version 94 of the entry and version 3 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.