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Q7Z6A9 (BTLA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
B- and T-lymphocyte attenuator
Alternative name(s):
B- and T-lymphocyte-associated protein
CD_antigen=CD272
Gene names
Name:BTLA
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length289 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3030 Potential
Chain31 – 289259B- and T-lymphocyte attenuator
PRO_0000014523

Regions

Topological domain31 – 157127Extracellular Potential
Transmembrane158 – 17821Helical; Potential
Topological domain179 – 289111Cytoplasmic Potential
Domain31 – 132102Ig-like V-type

Amino acid modifications

Glycosylation751N-linked (GlcNAc...) Potential
Glycosylation941N-linked (GlcNAc...) Potential
Glycosylation1101N-linked (GlcNAc...) Potential
Disulfide bond34 ↔ 63 Ref.9
Disulfide bond58 ↔ 115 Ref.9
Disulfide bond72 ↔ 79 Ref.9

Natural variations

Alternative sequence135 – 18248Missing in isoform 2.
VSP_040305
Natural variant1241I → V.
Corresponds to variant rs16859633 [ dbSNP | Ensembl ].
VAR_056027
Natural variant1571R → S. Ref.1 Ref.5 Ref.6
Corresponds to variant rs2931761 [ dbSNP | Ensembl ].
VAR_027607
Natural variant2671P → L. Ref.1 Ref.2 Ref.3 Ref.5 Ref.6
Corresponds to variant rs9288952 [ dbSNP | Ensembl ].
VAR_027608

Experimental info

Mutagenesis2261Y → 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
Mutagenesis2571Y → 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
Mutagenesis2821Y → 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 conflict1051V → M in AAP44003. Ref.1
Sequence conflict1381S → G in AAP44003. Ref.1
Sequence conflict1481M → V in AAP44003. Ref.1
Sequence conflict1711C → W in AAP44003. Ref.1
Sequence conflict2191L → P in BAD18396. Ref.6
Sequence conflict2231T → A in AAP44003. Ref.1
Sequence conflict2431Y → C in AAP44003. Ref.1

Secondary structure

....................... 289
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 3.
Checksum: F4D1FF775D7D33F3

FASTA28932,834
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 991AFF2495C3F612
Show »

FASTA24127,317

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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.
CCDSCCDS33819.1. [Q7Z6A9-1]
CCDS43130.1. [Q7Z6A9-2]
RefSeqNP_001078826.1. NM_001085357.1. [Q7Z6A9-2]
NP_861445.3. NM_181780.3.
XP_005247193.1. XM_005247136.2. [Q7Z6A9-1]
UniGeneHs.445162.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2AW2X-ray2.80A/X26-137[»]
ProteinModelPortalQ7Z6A9.
SMRQ7Z6A9. Positions 34-137.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid127411. 2 interactions.
DIPDIP-48795N.
IntActQ7Z6A9. 3 interactions.
MINTMINT-8020099.
STRING9606.ENSP00000333919.

PTM databases

PhosphoSiteQ7Z6A9.

Polymorphism databases

DMDM296439425.

Proteomic databases

PaxDbQ7Z6A9.
PRIDEQ7Z6A9.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000334529; ENSP00000333919; ENSG00000186265. [Q7Z6A9-1]
ENST00000383680; ENSP00000373178; ENSG00000186265. [Q7Z6A9-2]
GeneID151888.
KEGGhsa:151888.
UCSCuc003dza.4. human. [Q7Z6A9-1]
uc003dzb.4. human. [Q7Z6A9-2]

Organism-specific databases

CTD151888.
GeneCardsGC03M112182.
HGNCHGNC:21087. BTLA.
HPAHPA047211.
MIM607925. gene.
neXtProtNX_Q7Z6A9.
PharmGKBPA134968341.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42530.
HOGENOMHOG000168895.
HOVERGENHBG080937.
InParanoidQ7Z6A9.
KOK06707.
OMAAAICVRS.
OrthoDBEOG7F513T.
PhylomeDBQ7Z6A9.
TreeFamTF337694.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeQ7Z6A9.
CleanExHS_BTLA.
GenevestigatorQ7Z6A9.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
InterProIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
SMARTSM00409. IG. 1 hit.
[Graphical view]
PROSITEPS50835. IG_LIKE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ7Z6A9.
GeneWikiBTLA.
GenomeRNAi151888.
NextBio86817.
PROQ7Z6A9.
SOURCESearch...

Entry information

Entry nameBTLA_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 103 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries