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Q7Z6A9

- BTLA_HUMAN

UniProt

Q7Z6A9 - BTLA_HUMAN

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Protein
B- and T-lymphocyte attenuator
Gene
BTLA
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Lymphocyte inhibitory receptor which inhibits lymphocytes during immune response.1 Publication

GO - Molecular functioni

  1. receptor activity Source: Ensembl
Complete GO annotation...

GO - Biological processi

  1. T cell costimulation Source: Reactome
  2. immune response-regulating cell surface receptor signaling pathway Source: Ensembl
  3. negative regulation of B cell proliferation Source: Ensembl
  4. negative regulation of alpha-beta T cell proliferation Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Adaptive immunity, Immunity

Enzyme and pathway databases

ReactomeiREACT_19344. Costimulation by the CD28 family.

Names & Taxonomyi

Protein namesi
Recommended name:
B- and T-lymphocyte attenuator
Alternative name(s):
B- and T-lymphocyte-associated protein
CD_antigen: CD272
Gene namesi
Name:BTLA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 3

Organism-specific databases

HGNCiHGNC:21087. BTLA.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini31 – 157127Extracellular Reviewed prediction
Add
BLAST
Transmembranei158 – 17821Helical; Reviewed prediction
Add
BLAST
Topological domaini179 – 289111Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. external side of plasma membrane Source: Ensembl
  2. integral component of plasma membrane Source: Ensembl
  3. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi226 – 2261Y → 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. 2 Publications
Mutagenesisi257 – 2571Y → 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. 2 Publications
Mutagenesisi282 – 2821Y → 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. 2 Publications

Organism-specific databases

PharmGKBiPA134968341.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3030 Reviewed prediction
Add
BLAST
Chaini31 – 289259B- and T-lymphocyte attenuator
PRO_0000014523Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi34 ↔ 631 Publication
Disulfide bondi58 ↔ 1151 Publication
Disulfide bondi72 ↔ 791 Publication
Glycosylationi75 – 751N-linked (GlcNAc...) Reviewed prediction
Glycosylationi94 – 941N-linked (GlcNAc...) Reviewed prediction
Glycosylationi110 – 1101N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

Phosphorylated on Tyr residues by TNFRSF14 and by antigen receptors cross-linking, both inducing association with PTPN6 and PTPN11.1 Publication
N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiQ7Z6A9.
PRIDEiQ7Z6A9.

PTM databases

PhosphoSiteiQ7Z6A9.

Expressioni

Gene expression databases

BgeeiQ7Z6A9.
CleanExiHS_BTLA.
GenevestigatoriQ7Z6A9.

Organism-specific databases

HPAiHPA047211.

Interactioni

Subunit structurei

Interacts with tyrosine phosphatases PTPN6/SHP-1 and PTPN11/SHP-2. Interacts with TNFRSF14/HVEM.3 Publications

Protein-protein interaction databases

BioGridi127411. 2 interactions.
DIPiDIP-48795N.
IntActiQ7Z6A9. 3 interactions.
MINTiMINT-8020099.
STRINGi9606.ENSP00000333919.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi44 – 496
Beta strandi54 – 618
Beta strandi63 – 653
Beta strandi68 – 747
Beta strandi79 – 813
Beta strandi87 – 915
Beta strandi96 – 1049
Helixi107 – 1093
Beta strandi111 – 1199
Beta strandi122 – 1254
Beta strandi129 – 1346

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2AW2X-ray2.80A/X26-137[»]
ProteinModelPortaliQ7Z6A9.
SMRiQ7Z6A9. Positions 34-137.

Miscellaneous databases

EvolutionaryTraceiQ7Z6A9.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini31 – 132102Ig-like V-type
Add
BLAST

Sequence similaritiesi

Keywords - Domaini

Immunoglobulin domain, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG42530.
HOGENOMiHOG000168895.
HOVERGENiHBG080937.
InParanoidiQ7Z6A9.
KOiK06707.
OMAiAAICVRS.
OrthoDBiEOG7F513T.
PhylomeDBiQ7Z6A9.
TreeFamiTF337694.

Family and domain databases

Gene3Di2.60.40.10. 1 hit.
InterProiIPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view]
SMARTiSM00409. IG. 1 hit.
[Graphical view]
PROSITEiPS50835. IG_LIKE. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q7Z6A9-1) [UniParc]FASTAAdd to Basket

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.

« Hide

MKTLPAMLGT GKLFWVFFLI PYLDIWNIHG KESCDVQLYI KRQSEHSILA    50
GDPFELECPV KYCANRPHVT WCKLNGTTCV KLEDRQTSWK EEKNISFFIL 100
HFEPVLPNDN GSYRCSANFQ SNLIESHSTT LYVTDVKSAS ERPSKDEMAS 150
RPWLLYRLLP LGGLPLLITT CFCLFCCLRR HQGKQNELSD TAGREINLVD 200
AHLKSEQTEA STRQNSQVLL SETGIYDNDP DLCFRMQEGS EVYSNPCLEE 250
NKPGIVYASL NHSVIGPNSR LARNVKEAPT EYASICVRS 289
Length:289
Mass (Da):32,834
Last modified:May 18, 2010 - v3
Checksum:iF4D1FF775D7D33F3
GO
Isoform 2 (identifier: Q7Z6A9-2) [UniParc]FASTAAdd to Basket

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

Show »
Length:241
Mass (Da):27,317
Checksum:i991AFF2495C3F612
GO

Sequence cautioni

The sequence BAD18396.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti124 – 1241I → V.
Corresponds to variant rs16859633 [ dbSNP | Ensembl ].
VAR_056027
Natural varianti157 – 1571R → S.3 Publications
Corresponds to variant rs2931761 [ dbSNP | Ensembl ].
VAR_027607
Natural varianti267 – 2671P → L.5 Publications
Corresponds to variant rs9288952 [ dbSNP | Ensembl ].
VAR_027608

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei135 – 18248Missing in isoform 2.
VSP_040305Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti105 – 1051V → M in AAP44003. 1 Publication
Sequence conflicti138 – 1381S → G in AAP44003. 1 Publication
Sequence conflicti148 – 1481M → V in AAP44003. 1 Publication
Sequence conflicti171 – 1711C → W in AAP44003. 1 Publication
Sequence conflicti219 – 2191L → P in BAD18396. 1 Publication
Sequence conflicti223 – 2231T → A in AAP44003. 1 Publication
Sequence conflicti243 – 2431Y → C in AAP44003. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS33819.1. [Q7Z6A9-1]
CCDS43130.1. [Q7Z6A9-2]
RefSeqiNP_001078826.1. NM_001085357.1. [Q7Z6A9-2]
NP_861445.3. NM_181780.3.
XP_005247193.1. XM_005247136.2. [Q7Z6A9-1]
UniGeneiHs.445162.

Genome annotation databases

EnsembliENST00000334529; ENSP00000333919; ENSG00000186265. [Q7Z6A9-1]
ENST00000383680; ENSP00000373178; ENSG00000186265. [Q7Z6A9-2]
GeneIDi151888.
KEGGihsa:151888.
UCSCiuc003dza.4. human. [Q7Z6A9-1]
uc003dzb.4. human. [Q7Z6A9-2]

Polymorphism databases

DMDMi296439425.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSi CCDS33819.1. [Q7Z6A9-1 ]
CCDS43130.1. [Q7Z6A9-2 ]
RefSeqi NP_001078826.1. NM_001085357.1. [Q7Z6A9-2 ]
NP_861445.3. NM_181780.3.
XP_005247193.1. XM_005247136.2. [Q7Z6A9-1 ]
UniGenei Hs.445162.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2AW2 X-ray 2.80 A/X 26-137 [» ]
ProteinModelPortali Q7Z6A9.
SMRi Q7Z6A9. Positions 34-137.
ModBasei Search...

Protein-protein interaction databases

BioGridi 127411. 2 interactions.
DIPi DIP-48795N.
IntActi Q7Z6A9. 3 interactions.
MINTi MINT-8020099.
STRINGi 9606.ENSP00000333919.

PTM databases

PhosphoSitei Q7Z6A9.

Polymorphism databases

DMDMi 296439425.

Proteomic databases

PaxDbi Q7Z6A9.
PRIDEi Q7Z6A9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000334529 ; ENSP00000333919 ; ENSG00000186265 . [Q7Z6A9-1 ]
ENST00000383680 ; ENSP00000373178 ; ENSG00000186265 . [Q7Z6A9-2 ]
GeneIDi 151888.
KEGGi hsa:151888.
UCSCi uc003dza.4. human. [Q7Z6A9-1 ]
uc003dzb.4. human. [Q7Z6A9-2 ]

Organism-specific databases

CTDi 151888.
GeneCardsi GC03M112182.
HGNCi HGNC:21087. BTLA.
HPAi HPA047211.
MIMi 607925. gene.
neXtProti NX_Q7Z6A9.
PharmGKBi PA134968341.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG42530.
HOGENOMi HOG000168895.
HOVERGENi HBG080937.
InParanoidi Q7Z6A9.
KOi K06707.
OMAi AAICVRS.
OrthoDBi EOG7F513T.
PhylomeDBi Q7Z6A9.
TreeFami TF337694.

Enzyme and pathway databases

Reactomei REACT_19344. Costimulation by the CD28 family.

Miscellaneous databases

EvolutionaryTracei Q7Z6A9.
GeneWikii BTLA.
GenomeRNAii 151888.
NextBioi 86817.
PROi Q7Z6A9.
SOURCEi Search...

Gene expression databases

Bgeei Q7Z6A9.
CleanExi HS_BTLA.
Genevestigatori Q7Z6A9.

Family and domain databases

Gene3Di 2.60.40.10. 1 hit.
InterProi IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
[Graphical view ]
SMARTi SM00409. IG. 1 hit.
[Graphical view ]
PROSITEi PS50835. IG_LIKE. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. 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.

Entry informationi

Entry nameiBTLA_HUMAN
AccessioniPrimary (citable) accession number: Q7Z6A9
Secondary accession number(s): Q3B831, Q3HS85, Q6ZNH9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 19, 2005
Last sequence update: May 18, 2010
Last modified: September 3, 2014
This is version 104 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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