BTLA_MOUSE
ID BTLA_MOUSE Reviewed; 306 AA.
AC Q7TSA3;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 25-MAY-2022, entry version 132.
DE RecName: Full=B- and T-lymphocyte attenuator {ECO:0000303|PubMed:14652006};
DE AltName: Full=B- and T-lymphocyte-associated protein;
DE AltName: CD_antigen=CD272;
DE Flags: Precursor;
GN Name=Btla {ECO:0000303|PubMed:12796776, ECO:0000312|MGI:MGI:2658978};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), MUTAGENESIS OF TYR-245;
RP TYR-274 AND TYR-299, GLYCOSYLATION, TISSUE SPECIFICITY, INTERACTION WITH
RP PTPN6 AND PTPN11, DISRUPTION PHENOTYPE, VARIANTS GLU-41; 45-ASN--LYS-47;
RP HIS-52; TRP-55; GLU-63; TRP-85; GLY-91 AND ARG-102, FUNCTION, AND
RP SUBCELLULAR LOCATION.
RC STRAIN=129/SvEv;
RX PubMed=12796776; DOI=10.1038/ni944;
RA Watanabe N., Gavrieli M., Sedy J.R., Yang J., Fallarino F., Loftin S.K.,
RA Hurchla M.A., Zimmerman N., Sim J., Zang X., Murphy T.L., Russell J.H.,
RA Allison J.P., Murphy K.M.;
RT "BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and
RT PD-1.";
RL Nat. Immunol. 4:670-679(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND VARIANT THR-143.
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP MUTAGENESIS OF TYR-245; TYR-274 AND TYR-299, INTERACTION WITH PTPN6 AND
RP PTPN11, AND FUNCTION.
RX PubMed=14652006; DOI=10.1016/j.bbrc.2003.11.070;
RA Gavrieli M., Watanabe N., Loftin S.K., Murphy T.L., Murphy K.M.;
RT "Characterization of phosphotyrosine binding motifs in the cytoplasmic
RT domain of B and T lymphocyte attenuator required for association with
RT protein tyrosine phosphatases SHP-1 and SHP-2.";
RL Biochem. Biophys. Res. Commun. 312:1236-1243(2003).
RN [4]
RP INTERACTION WITH TNFRSF14, AND PHOSPHORYLATION.
RX PubMed=15568026; DOI=10.1038/ni1144;
RA Sedy J.R., Gavrieli M., Potter K.G., Hurchla M.A., Lindsley R.C.,
RA Hildner K., Scheu S., Pfeffer K., Ware C.F., Murphy T.L., Murphy K.M.;
RT "B and T lymphocyte attenuator regulates T cell activation through
RT interaction with herpesvirus entry mediator.";
RL Nat. Immunol. 6:90-98(2005).
RN [5]
RP TISSUE SPECIFICITY, AND POLYMORPHISM.
RX PubMed=15749870; DOI=10.4049/jimmunol.174.6.3377;
RA Hurchla M.A., Sedy J.R., Gavrieli M., Drake C.G., Murphy T.L., Murphy K.M.;
RT "B and T lymphocyte attenuator exhibits structural and expression
RT polymorphisms and is highly induced in anergic CD4+ T cells.";
RL J. Immunol. 174:3377-3385(2005).
RN [6]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH TNFRSF14.
RX PubMed=19915044; DOI=10.4049/jimmunol.0902490;
RA Cheung T.C., Oborne L.M., Steinberg M.W., Macauley M.G., Fukuyama S.,
RA Sanjo H., D'Souza C., Norris P.S., Pfeffer K., Murphy K.M., Kronenberg M.,
RA Spear P.G., Ware C.F.;
RT "T cell intrinsic heterodimeric complexes between HVEM and BTLA determine
RT receptivity to the surrounding microenvironment.";
RL J. Immunol. 183:7286-7296(2009).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 30-150, MUTAGENESIS OF LEU-44;
RP ARG-48; PRO-65 AND HIS-136, INTERACTION WITH TNFRSF14/HVEM, AND DISULFIDE
RP BONDS.
RX PubMed=18178834; DOI=10.4049/jimmunol.180.2.940;
RA Nelson C.A., Fremont M.D., Sedy J.R., Norris P.S., Ware C.F., Murphy K.M.,
RA Fremont D.H.;
RT "Structural determinants of herpesvirus entry mediator recognition by
RT murine B and T lymphocyte attenuator.";
RL J. Immunol. 180:940-947(2008).
CC -!- FUNCTION: Inhibitory receptor on lymphocytes that negatively regulates
CC antigen receptor signaling via PTPN6/SHP-1 and PTPN11/SHP-2
CC (PubMed:12796776, PubMed:14652006). May interact in cis (on the same
CC cell) or in trans (on other cells) with TNFRSF14 (PubMed:19915044). In
CC cis interactions, appears to play an immune regulatory role inhibiting
CC in trans interactions in naive T cells to maintain a resting state. In
CC trans interactions, can predominate during adaptive immune response to
CC provide survival signals to effector T cells (PubMed:19915044).
CC {ECO:0000269|PubMed:12796776, ECO:0000269|PubMed:14652006,
CC ECO:0000269|PubMed:19915044}.
CC -!- SUBUNIT: Interacts with tyrosine phosphatases PTPN6/SHP-1 and
CC PTPN11/SHP-2 (PubMed:12796776, PubMed:14652006). Interacts with
CC TNFRSF14/HVEM (via cysteine-rich domain 1) (PubMed:19915044).
CC {ECO:0000269|PubMed:12796776, ECO:0000269|PubMed:14652006,
CC ECO:0000269|PubMed:15568026, ECO:0000269|PubMed:18178834,
CC ECO:0000269|PubMed:19915044}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12796776};
CC Single-pass type I membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q7TSA3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TSA3-2; Sequence=VSP_014836;
CC Name=3;
CC IsoId=Q7TSA3-3; Sequence=VSP_014837;
CC -!- TISSUE SPECIFICITY: Expressed in splenic T- and B-cells as well as
CC lymph node tissues but very weakly in somatic tissues. Also expressed
CC in macrophages, NK cells and dendritic cells. A polymorphic tissue
CC distribution between several strains is seen.
CC {ECO:0000269|PubMed:12796776, ECO:0000269|PubMed:15749870}.
CC -!- PTM: Phosphorylated on Tyr residues by TNFRSF14 and by antigen
CC receptors cross-linking, both inducing association with PTPN6 and
CC PTPN11. {ECO:0000269|PubMed:15568026}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:12796776}.
CC -!- DISRUPTION PHENOTYPE: Mice exhibit no developmental defects in T- or B-
CC cells in thymus or bone marrow, but increased antibody responses and
CC sensitivity to antigen-induced 'experimental autoimmune
CC encephalomyelitis'. T-cells lacking Btla show increased proliferation
CC with a heightened response to anti-CD3 and a slightly greater response
CC to stimulation with anti-IgM. {ECO:0000269|PubMed:12796776}.
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DR EMBL; AY293285; AAP44002.1; -; mRNA.
DR EMBL; AK041334; BAC30910.1; -; mRNA.
DR CCDS; CCDS28195.1; -. [Q7TSA3-1]
DR CCDS; CCDS28196.1; -. [Q7TSA3-3]
DR RefSeq; NP_001032808.2; NM_001037719.2.
DR RefSeq; NP_808252.1; NM_177584.3.
DR PDB; 1XAU; X-ray; 1.80 A; A=30-150.
DR PDBsum; 1XAU; -.
DR AlphaFoldDB; Q7TSA3; -.
DR SMR; Q7TSA3; -.
DR BioGRID; 228954; 3.
DR STRING; 10090.ENSMUSP00000099866; -.
DR GlyGen; Q7TSA3; 6 sites.
DR iPTMnet; Q7TSA3; -.
DR PhosphoSitePlus; Q7TSA3; -.
DR PaxDb; Q7TSA3; -.
DR PRIDE; Q7TSA3; -.
DR ProteomicsDB; 265317; -. [Q7TSA3-1]
DR ProteomicsDB; 265318; -. [Q7TSA3-2]
DR ProteomicsDB; 265319; -. [Q7TSA3-3]
DR ABCD; Q7TSA3; 9 sequenced antibodies.
DR GeneID; 208154; -.
DR KEGG; mmu:208154; -.
DR UCSC; uc007zik.1; mouse. [Q7TSA3-3]
DR CTD; 151888; -.
DR MGI; MGI:2658978; Btla.
DR eggNOG; ENOG502SGTG; Eukaryota.
DR InParanoid; Q7TSA3; -.
DR OrthoDB; 1342267at2759; -.
DR PhylomeDB; Q7TSA3; -.
DR TreeFam; TF337694; -.
DR Reactome; R-MMU-388841; Costimulation by the CD28 family.
DR BioGRID-ORCS; 208154; 1 hit in 76 CRISPR screens.
DR EvolutionaryTrace; Q7TSA3; -.
DR PRO; PR:Q7TSA3; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q7TSA3; protein.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0038023; F:signaling receptor activity; IGI:MGI.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IDA:MGI.
DR GO; GO:0002768; P:immune response-regulating cell surface receptor signaling pathway; IMP:MGI.
DR GO; GO:0046642; P:negative regulation of alpha-beta T cell proliferation; IMP:MGI.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:MGI.
DR GO; GO:0042130; P:negative regulation of T cell proliferation; IMP:MGI.
DR Gene3D; 2.60.40.10; -; 1.
DR InterPro; IPR039257; BTLA.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR PANTHER; PTHR37996; PTHR37996; 1.
DR SMART; SM00409; IG; 1.
DR SUPFAM; SSF48726; SSF48726; 1.
DR PROSITE; PS50835; IG_LIKE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane;
KW Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Membrane;
KW Phosphoprotein; Receptor; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT CHAIN 30..306
FT /note="B- and T-lymphocyte attenuator"
FT /id="PRO_0000014524"
FT TOPO_DOM 30..183
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 205..306
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 37..139
FT /note="Ig-like V-type"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 101
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 148
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 165
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..69
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:18178834"
FT DISULFID 64..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:18178834"
FT DISULFID 78..85
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114,
FT ECO:0000269|PubMed:18178834"
FT VAR_SEQ 37..142
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12796776"
FT /id="VSP_014836"
FT VAR_SEQ 156..157
FT /note="TV -> I (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014837"
FT VARIANT 41
FT /note="P -> E (in strain: 129/SvEv; requires 2 nucleotide
FT substitutions)"
FT /evidence="ECO:0000269|PubMed:12796776"
FT VARIANT 45..47
FT /note="TIT -> NIK (in strain: 129/SvEv)"
FT VARIANT 52
FT /note="Q -> H (in strain: 129/SvEv)"
FT /evidence="ECO:0000269|PubMed:12796776"
FT VARIANT 55
FT /note="R -> W (in strain: 129/SvEv)"
FT /evidence="ECO:0000269|PubMed:12796776"
FT VARIANT 63
FT /note="Q -> E (in strain: 129/SvEv)"
FT /evidence="ECO:0000269|PubMed:12796776"
FT VARIANT 85
FT /note="C -> W (in strain: 129/SvEv)"
FT /evidence="ECO:0000269|PubMed:12796776"
FT VARIANT 91
FT /note="S -> G (in strain: 129/SvEv)"
FT /evidence="ECO:0000269|PubMed:12796776"
FT VARIANT 102
FT /note="Q -> R (in strain: 129/SvEv)"
FT /evidence="ECO:0000269|PubMed:12796776"
FT VARIANT 143
FT /note="R -> T (in strain: C57BL/6J)"
FT /evidence="ECO:0000269|PubMed:16141072"
FT MUTAGEN 44
FT /note="L->H: Loss of interaction with TNFRSF14."
FT /evidence="ECO:0000269|PubMed:18178834"
FT MUTAGEN 48
FT /note="R->D: Loss of interaction with TNFRSF14."
FT /evidence="ECO:0000269|PubMed:18178834"
FT MUTAGEN 65
FT /note="P->A: Loss of interaction with TNFRSF14."
FT /evidence="ECO:0000269|PubMed:18178834"
FT MUTAGEN 136
FT /note="H->D: Loss of interaction with TNFRSF14."
FT /evidence="ECO:0000269|PubMed:18178834"
FT MUTAGEN 245
FT /note="Y->F: No change of phosphorylation implicated in
FT interaction with PTPN6 and PTPN11. Severe reduction of
FT phosphorylation; when associated with F-274 and/or F-299."
FT /evidence="ECO:0000269|PubMed:12796776,
FT ECO:0000269|PubMed:14652006"
FT MUTAGEN 274
FT /note="Y->F: No change of phosphorylation implicated in
FT interaction with PTPN6 and PTPN11. Severe reduction of
FT phosphorylation; when associated with F-245 and/or F-299."
FT /evidence="ECO:0000269|PubMed:12796776,
FT ECO:0000269|PubMed:14652006"
FT MUTAGEN 299
FT /note="Y->F: No change of phosphorylation implicated in
FT interaction with PTPN6 and PTPN11. Severe reduction of
FT phosphorylation; when associated with F-245 and/or F-274."
FT /evidence="ECO:0000269|PubMed:12796776,
FT ECO:0000269|PubMed:14652006"
FT STRAND 50..55
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 60..67
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 75..80
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 94..99
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 101..104
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 106..111
FT /evidence="ECO:0007829|PDB:1XAU"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 120..128
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 131..134
FT /evidence="ECO:0007829|PDB:1XAU"
FT STRAND 138..143
FT /evidence="ECO:0007829|PDB:1XAU"
SQ SEQUENCE 306 AA; 34337 MW; A5B4584BAC882B93 CRC64;
MKTVPAMLGT PRLFREFFIL HLGLWSILCE KATKRNDEEC PVQLTITRNS KQSARTGELF
KIQCPVKYCV HRPNVTWCKH NGTICVPLEV SPQLYTSWEE NQSVPVFVLH FKPIHLSDNG
SYSCSTNFNS QVINSHSVTI HVRERTQNSS EHPLITVSDI PDATNASGPS TMEERPGRTW
LLYTLLPLGA LLLLLACVCL LCFLKRIQGK EKKPSDLAGR DTNLVDIPAS SRTNHQALPS
GTGIYDNDPW SSMQDESELT ISLQSERNNQ GIVYASLNHC VIGRNPRQEN NMQEAPTEYA
SICVRS
