TNR14_MOUSE
ID TNR14_MOUSE Reviewed; 275 AA.
AC Q80WM9;
DT 16-JAN-2019, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 14;
DE AltName: Full=Herpes virus entry mediator A {ECO:0000303|PubMed:19915044, ECO:0000303|PubMed:22801499};
DE Short=Herpesvirus entry mediator A {ECO:0000250|UniProtKB:Q92956};
DE Short=HveA {ECO:0000250|UniProtKB:Q92956};
DE AltName: Full=Tumor necrosis factor receptor-like 2;
DE Short=TR2 {ECO:0000250|UniProtKB:Q92956};
DE AltName: CD_antigen=CD270;
DE Flags: Precursor;
GN Name=Tnfrsf14 {ECO:0000312|MGI:MGI:2675303};
GN Synonyms=hvem {ECO:0000303|PubMed:19915044, ECO:0000303|PubMed:22801499};
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].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
RA Benencia F., Conejo-Garcia J.R., Courreges M.C., Coukos G.;
RT "Light regulation in a murine model of ovarian carcinoma.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH BTLA, AND DOMAIN.
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 [4]
RP SUBUNIT, AND INTERACTION WITH CD160.
RX PubMed=18193050; DOI=10.1038/ni1554;
RA Cai G., Anumanthan A., Brown J.A., Greenfield E.A., Zhu B., Freeman G.J.;
RT "CD160 inhibits activation of human CD4+ T cells through interaction with
RT herpesvirus entry mediator.";
RL Nat. Immunol. 9:176-185(2008).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [6]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=22801499; DOI=10.1038/nature11242;
RA Shui J.W., Larange A., Kim G., Vela J.L., Zahner S., Cheroutre H.,
RA Kronenberg M.;
RT "HVEM signalling at mucosal barriers provides host defence against
RT pathogenic bacteria.";
RL Nature 488:222-225(2012).
RN [7]
RP FUNCTION.
RX PubMed=25711213; DOI=10.1084/jem.20131601;
RA Tu T.C., Brown N.K., Kim T.J., Wroblewska J., Yang X., Guo X., Lee S.H.,
RA Kumar V., Lee K.M., Fu Y.X.;
RT "CD160 is essential for NK-mediated IFN-gamma production.";
RL J. Exp. Med. 212:415-429(2015).
CC -!- FUNCTION: Receptor for four distinct ligands: The TNF superfamily
CC members TNFSF14/LIGHT and homotrimeric LTA/lymphotoxin-alpha and the
CC immunoglobulin superfamily members BTLA and CD160, altogether defining
CC a complex stimulatory and inhibitory signaling network (By similarity).
CC Signals via the TRAF2-TRAF3 E3 ligase pathway to promote immune cell
CC survival and differentiation (PubMed:19915044). Participates in
CC bidirectional cell-cell contact signaling between antigen presenting
CC cells and lymphocytes. In response to ligation of TNFSF14/LIGHT,
CC delivers costimulatory signals to T cells, promoting cell proliferation
CC and effector functions (By similarity). Interacts with CD160 on NK
CC cells, enhancing IFNG production and anti-tumor immune response
CC (PubMed:25711213). In the context of bacterial infection, acts as a
CC signaling receptor on epithelial cells for CD160 from intraepithelial
CC lymphocytes, triggering the production of antimicrobial proteins and
CC pro-inflammatory cytokines (PubMed:22801499). Upon binding to CD160 on
CC activated CD4+ T cells, down-regulates CD28 costimulatory signaling,
CC restricting memory and alloantigen-specific immune response (By
CC similarity). May interact in cis (on the same cell) or in trans (on
CC other cells) with BTLA (PubMed:19915044, PubMed:15568026). In cis
CC interactions, appears to play an immune regulatory role inhibiting in
CC 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 PubMed:15568026). {ECO:0000250|UniProtKB:Q92956,
CC ECO:0000269|PubMed:15568026, ECO:0000269|PubMed:19915044,
CC ECO:0000269|PubMed:22801499, ECO:0000269|PubMed:25711213}.
CC -!- SUBUNIT: Interacts with TRAF2, TRAF3 and TRAF5 (By similarity).
CC Interacts (via CRD1/TNFR-Cys 1) with CD160; this interaction is direct
CC (PubMed:18193050). Interacts (via CRD1/TNFR-Cys 1) with BTLA; this
CC interaction is direct (PubMed:15568026). {ECO:0000250|UniProtKB:Q92956,
CC ECO:0000269|PubMed:15568026, ECO:0000269|PubMed:18193050}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15568026};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q92956}.
CC -!- TISSUE SPECIFICITY: Expressed at mucosal sites including colon and
CC pulmonary epithelial cells (PubMed:22801499). Expressed in naive T
CC cells (PubMed:19915044). {ECO:0000269|PubMed:19915044,
CC ECO:0000269|PubMed:22801499}.
CC -!- DOMAIN: The cysteine rich domain I (CRD1/TNFR-Cys 1) is required for
CC interaction with CD160 and BTLA. {ECO:0000269|PubMed:15568026}.
CC -!- PTM: N-glycosylated. {ECO:0000255|PROSITE-ProRule:PRU00498}.
CC -!- SIMILARITY: Belongs to the tumor necrosis factor receptor superfamily.
CC {ECO:0000305}.
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DR EMBL; AY264405; AAO89081.1; -; mRNA.
DR EMBL; BX004788; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS19017.1; -.
DR RefSeq; NP_849262.1; NM_178931.2.
DR RefSeq; XP_006538894.1; XM_006538831.3.
DR PDB; 7MSJ; X-ray; 2.10 A; A=39-143.
DR PDBsum; 7MSJ; -.
DR AlphaFoldDB; Q80WM9; -.
DR SMR; Q80WM9; -.
DR IntAct; Q80WM9; 2.
DR STRING; 10090.ENSMUSP00000116757; -.
DR GlyGen; Q80WM9; 2 sites.
DR iPTMnet; Q80WM9; -.
DR PhosphoSitePlus; Q80WM9; -.
DR EPD; Q80WM9; -.
DR MaxQB; Q80WM9; -.
DR PaxDb; Q80WM9; -.
DR PRIDE; Q80WM9; -.
DR ProteomicsDB; 330725; -.
DR Antibodypedia; 1626; 804 antibodies from 45 providers.
DR DNASU; 230979; -.
DR Ensembl; ENSMUST00000123514; ENSMUSP00000116757; ENSMUSG00000042333.
DR GeneID; 230979; -.
DR KEGG; mmu:230979; -.
DR UCSC; uc008wcj.1; mouse.
DR CTD; 8764; -.
DR MGI; MGI:2675303; Tnfrsf14.
DR VEuPathDB; HostDB:ENSMUSG00000042333; -.
DR eggNOG; ENOG502S1XZ; Eukaryota.
DR GeneTree; ENSGT00940000162427; -.
DR HOGENOM; CLU_052667_2_0_1; -.
DR InParanoid; Q80WM9; -.
DR OMA; LPWTRCS; -.
DR PhylomeDB; Q80WM9; -.
DR TreeFam; TF331157; -.
DR Reactome; R-MMU-388841; Costimulation by the CD28 family.
DR Reactome; R-MMU-5669034; TNFs bind their physiological receptors.
DR BioGRID-ORCS; 230979; 4 hits in 76 CRISPR screens.
DR ChiTaRS; Tnfrsf14; mouse.
DR PRO; PR:Q80WM9; -.
DR Proteomes; UP000000589; Chromosome 4.
DR Bgee; ENSMUSG00000042333; Expressed in granulocyte and 54 other tissues.
DR ExpressionAtlas; Q80WM9; baseline and differential.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0019955; F:cytokine binding; ISO:MGI.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0035739; P:CD4-positive, alpha-beta T cell proliferation; IDA:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1905675; P:negative regulation of adaptive immune memory response; ISO:MGI.
DR GO; GO:0046642; P:negative regulation of alpha-beta T cell proliferation; IBA:GO_Central.
DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IDA:MGI.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IMP:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:MGI.
DR GO; GO:2000406; P:positive regulation of T cell migration; IMP:MGI.
DR GO; GO:0031295; P:T cell costimulation; ISO:MGI.
DR GO; GO:0072678; P:T cell migration; IMP:MGI.
DR CDD; cd10582; TNFRSF14; 1.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR022332; TNFR_14.
DR InterPro; IPR034031; TNFRSF14/UL144_N.
DR Pfam; PF00020; TNFR_c6; 3.
DR PRINTS; PR01965; TNFACTORR14.
DR SMART; SM00208; TNFR; 4.
DR PROSITE; PS00652; TNFR_NGFR_1; 1.
DR PROSITE; PS50050; TNFR_NGFR_2; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Cell membrane; Disulfide bond;
KW Glycoprotein; Host cell receptor for virus entry; Host-virus interaction;
KW Immunity; Innate immunity; Membrane; Phosphoprotein; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..38
FT /evidence="ECO:0000255"
FT CHAIN 39..275
FT /note="Tumor necrosis factor receptor superfamily member
FT 14"
FT /id="PRO_5015098926"
FT TRANSMEM 211..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REPEAT 41..75
FT /note="TNFR-Cys 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT REPEAT 77..119
FT /note="TNFR-Cys 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT REPEAT 120..162
FT /note="TNFR-Cys 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 197
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 42..53
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 54..67
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 57..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 78..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 96..111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 99..119
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 121..138
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT DISULFID 144..162
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:7MSJ"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:7MSJ"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:7MSJ"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:7MSJ"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:7MSJ"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:7MSJ"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:7MSJ"
SQ SEQUENCE 275 AA; 30171 MW; C4A7EAD8EFC0521D CRC64;
MEPLPGWGSA PWSQAPTDNT FRLVPCVFLL NLLQRISAQP SCRQEEFLVG DECCPMCNPG
YHVKQVCSEH TGTVCAPCPP QTYTAHANGL SKCLPCGVCD PDMGLLTWQE CSSWKDTVCR
CIPGYFCENQ DGSHCSTCLQ HTTCPPGQRV EKRGTHDQDT VCADCLTGTF SLGGTQEECL
PWTNCSAFQQ EVRRGTNSTD TTCSSQVVYY VVSILLPLVI VGAGIAGFLI CTRRHLHTSS
VAKELEPFQE QQENTIRFPV TEVGFAETEE ETASN
