TNR14_HUMAN
ID TNR14_HUMAN Reviewed; 283 AA.
AC Q92956; B3KW30; B9DI89; Q6IB95; Q8N634; Q8WXR1; Q96J31; Q9UM65;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 3.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 14;
DE AltName: Full=Herpes virus entry mediator A {ECO:0000303|PubMed:9696799};
DE Short=Herpesvirus entry mediator A {ECO:0000303|PubMed:9696799};
DE Short=HveA {ECO:0000303|PubMed:11511370};
DE AltName: Full=Tumor necrosis factor receptor-like 2;
DE Short=TR2 {ECO:0000303|PubMed:9162061};
DE AltName: CD_antigen=CD270;
DE Flags: Precursor;
GN Name=TNFRSF14 {ECO:0000312|HGNC:HGNC:11912};
GN Synonyms=HVEA, HVEM {ECO:0000303|PubMed:18193050}; ORFNames=UNQ329/PRO509;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION AS A RECEPTOR FOR
RP HHV-1.
RC TISSUE=Cervix adenocarcinoma;
RX PubMed=8898196; DOI=10.1016/s0092-8674(00)81363-x;
RA Montgomery R.I., Warner M.S., Lum B.J., Spear P.G.;
RT "Herpes simplex virus-1 entry into cells mediated by a novel member of the
RT TNF/NGF receptor family.";
RL Cell 87:427-436(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9162061; DOI=10.1074/jbc.272.22.14272;
RA Kwon B.S., Tan K.B., Ni J., Oh K.-O., Lee Z.H., Kim K.K., Kim Y.-J.,
RA Wang S., Gentz R., Yu G.-L., Harrop J., Lyn S.D., Silverman C.,
RA Porter T.G., Truneh A., Young P.R.;
RT "A newly identified member of the tumor necrosis factor receptor
RT superfamily with a wide tissue distribution and involvement in lymphocyte
RT activation.";
RL J. Biol. Chem. 272:14272-14276(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Zhang W., Wan T., Cao X.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS ARG-17 AND ILE-241.
RX PubMed=11756979; DOI=10.1086/338116;
RA Struyf F., Posavad C.M., Keyaerts E., Van Ranst M., Corey L., Spear P.G.;
RT "Search for polymorphisms in the genes for herpesvirus entry mediator,
RT Nectin-1, and Nectin-2 in immune seronegative individuals.";
RL J. Infect. Dis. 185:36-44(2002).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ARG-17.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-17; THR-117; GLU-174
RP AND ILE-241.
RG NIEHS SNPs program;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Skin;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP PROTEIN SEQUENCE OF 39-53.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [13]
RP INTERACTION WITH TRAF2 AND TRAF5.
RX PubMed=9153189; DOI=10.1074/jbc.272.21.13471;
RA Hsu H., Solovyev I., Colombero A., Elliott R., Kelley M., Boyle W.J.;
RT "ATAR, a novel tumor necrosis factor receptor family member, signals
RT through TRAF2 and TRAF5.";
RL J. Biol. Chem. 272:13471-13474(1997).
RN [14]
RP INTERACTION WITH TRAF3 AND TRAF5.
RX PubMed=9162022; DOI=10.1074/jbc.272.22.14029;
RA Marsters S.A., Ayres T.M., Skubatch M., Gray C.L., Rothe M., Ashkenazi A.;
RT "Herpesvirus entry mediator, a member of the tumor necrosis factor receptor
RT (TNFR) family, interacts with members of the TNFR-associated factor family
RT and activates the transcription factors NF-kappaB and AP-1.";
RL J. Biol. Chem. 272:14029-14032(1997).
RN [15]
RP FUNCTION, SUBUNIT, INTERACTION WITH LTA, AND INTERACTION WITH TNFSF14.
RX PubMed=9462508; DOI=10.1016/s1074-7613(00)80455-0;
RA Mauri D.N., Ebner R., Montgomery R.I., Kochel K.D., Cheung T.C., Yu G.-L.,
RA Ruben S., Murphy M., Eisenberg R.J., Cohen G.H., Spear P.G., Ware C.F.;
RT "LIGHT, a new member of the TNF superfamily, and lymphotoxin alpha are
RT ligands for herpesvirus entry mediator.";
RL Immunity 8:21-30(1998).
RN [16]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN HERPESVIRUS
RP 1/HHV-1 AND HUMAN HERPESVIRUS 2/HHV-2 GLYCOPROTEIN D.
RX PubMed=9696799; DOI=10.1128/jvi.72.9.7064-7074.1998;
RA Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W., Lambris J.D.,
RA Geraghty R.J., Spear P.G., Cohen G.H., Eisenberg R.J.;
RT "Herpes simplex virus glycoprotein D can bind to poliovirus receptor-
RT related protein 1 or herpesvirus entry mediator, two structurally unrelated
RT mediators of virus entry.";
RL J. Virol. 72:7064-7074(1998).
RN [17]
RP FUNCTION.
RX PubMed=10754304; DOI=10.4049/jimmunol.164.8.4105;
RA Tamada K., Shimozaki K., Chapoval A.I., Zhai Y., Su J., Chen S.F.,
RA Hsieh S.L., Nagata S., Ni J., Chen L.;
RT "LIGHT, a TNF-like molecule, costimulates T cell proliferation and is
RT required for dendritic cell-mediated allogeneic T cell response.";
RL J. Immunol. 164:4105-4110(2000).
RN [18]
RP FUNCTION, TISSUE SPECIFICITY, SUBUNIT, INTERACTION WITH CD160, AND DOMAIN.
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 [19]
RP FUNCTION, TISSUE SPECIFICITY, SUBUNIT, INTERACTION WITH BTLA, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF TYR-61.
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 [20]
RP FUNCTION, SUBUNIT, AND INTERACTION WITH CD160.
RX PubMed=23761635; DOI=10.4049/jimmunol.1300894;
RA Sedy J.R., Bjordahl R.L., Bekiaris V., Macauley M.G., Ware B.C.,
RA Norris P.S., Lurain N.S., Benedict C.A., Ware C.F.;
RT "CD160 activation by herpesvirus entry mediator augments inflammatory
RT cytokine production and cytolytic function by NK cells.";
RL J. Immunol. 191:828-836(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-240, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 39-200 IN COMPLEX WITH HUMAN
RP HERPESVIRUS 1 GLYCOPROTEIN, AND FUNCTION (MICROBIAL INFECTION).
RX PubMed=11511370; DOI=10.1016/s1097-2765(01)00298-2;
RA Carfi A., Willis S.H., Whitbeck J.C., Krummenacher C., Cohen G.H.,
RA Eisenberg R.J., Wiley D.C.;
RT "Herpes simplex virus glycoprotein D bound to the human receptor HveA.";
RL Mol. Cell 8:169-179(2001).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-137 IN COMPLEX WITH BTLA,
RP GLYCOSYLATION AT ASN-110, AND DISULFIDE BOND.
RX PubMed=16169851; DOI=10.1074/jbc.m507629200;
RA Compaan D.M., Gonzalez L.C., Tom I., Loyet K.M., Eaton D., Hymowitz S.G.;
RT "Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM
RT complex.";
RL J. Biol. Chem. 280:39553-39561(2005).
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 (PubMed:9462508,
CC PubMed:10754304, PubMed:18193050, PubMed:23761635). Signals via the
CC TRAF2-TRAF3 E3 ligase pathway to promote immune cell survival and
CC differentiation (PubMed:19915044, PubMed:9153189, PubMed:9162022).
CC Participates in bidirectional cell-cell contact signaling between
CC antigen presenting cells and lymphocytes. In response to ligation of
CC TNFSF14/LIGHT, delivers costimulatory signals to T cells, promoting
CC cell proliferation and effector functions (PubMed:10754304). Interacts
CC with CD160 on NK cells, enhancing IFNG production and anti-tumor immune
CC response (PubMed:23761635). In the context of bacterial infection, acts
CC as a signaling receptor on epithelial cells for CD160 from
CC intraepithelial lymphocytes, triggering the production of antimicrobial
CC proteins and pro-inflammatory cytokines (By similarity). Upon binding
CC to CD160 on activated CD4+ T cells, down-regulates CD28 costimulatory
CC signaling, restricting memory and alloantigen-specific immune response
CC (PubMed:18193050). May interact in cis (on the same cell) or in trans
CC (on other cells) with BTLA (PubMed:19915044) (By similarity). 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) (By
CC similarity). {ECO:0000250|UniProtKB:Q80WM9,
CC ECO:0000269|PubMed:10754304, ECO:0000269|PubMed:18193050,
CC ECO:0000269|PubMed:19915044, ECO:0000269|PubMed:23761635,
CC ECO:0000269|PubMed:9153189, ECO:0000269|PubMed:9162022,
CC ECO:0000269|PubMed:9462508}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Herpes simplex
CC virus 1/HHV-1. {ECO:0000269|PubMed:11511370,
CC ECO:0000269|PubMed:9696799}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for Herpes simplex
CC virus 2/HHV-2. {ECO:0000269|PubMed:11511370,
CC ECO:0000269|PubMed:9696799}.
CC -!- SUBUNIT: Interacts with TRAF2, TRAF3 and TRAF5 (PubMed:9153189,
CC PubMed:9162022). Interacts (via CRD1/TNFR-Cys 1) with CD160; this
CC interaction is direct (PubMed:18193050, PubMed:23761635). Interacts
CC with LTA and TNFSF14 (PubMed:9462508). Interacts (via CRD1/TNFR-Cys 1)
CC in cis and trans with BTLA; the cis interactions inhibits the trans
CC interactions (PubMed:19915044, PubMed:16169851).
CC {ECO:0000269|PubMed:16169851, ECO:0000269|PubMed:18193050,
CC ECO:0000269|PubMed:19915044, ECO:0000269|PubMed:23761635,
CC ECO:0000269|PubMed:9153189, ECO:0000269|PubMed:9162022,
CC ECO:0000269|PubMed:9462508}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus
CC 1/HHV-1 envelope glycoprotein D. {ECO:0000269|PubMed:11511370,
CC ECO:0000269|PubMed:9696799}.
CC -!- SUBUNIT: (Microbial infection) Interacts with herpes simplex virus
CC 2/HHV-2 envelope glycoprotein D. {ECO:0000269|PubMed:11511370,
CC ECO:0000269|PubMed:9696799}.
CC -!- INTERACTION:
CC Q92956; Q3SYB3: FOXD4L6; NbExp=3; IntAct=EBI-1056653, EBI-6425864;
CC Q92956; O43557: TNFSF14; NbExp=5; IntAct=EBI-1056653, EBI-524131;
CC Q92956; Q12933: TRAF2; NbExp=2; IntAct=EBI-1056653, EBI-355744;
CC Q92956; Q12933-2: TRAF2; NbExp=4; IntAct=EBI-1056653, EBI-355760;
CC Q92956; O00463: TRAF5; NbExp=5; IntAct=EBI-1056653, EBI-523498;
CC Q92956-2; Q13148: TARDBP; NbExp=6; IntAct=EBI-25985089, EBI-372899;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:19915044};
CC Single-pass type I membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92956-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92956-2; Sequence=VSP_054186;
CC -!- TISSUE SPECIFICITY: Widely expressed, with the highest expression in
CC lung, spleen and thymus. Expressed in a subpopulation of B cells and
CC monocytes (PubMed:18193050). Expressed in naive T cells
CC (PubMed:19915044). {ECO:0000269|PubMed:18193050,
CC ECO:0000269|PubMed:19915044}.
CC -!- DOMAIN: The cysteine rich domain I (CRD1/TNFR-Cys 1) is required for
CC interaction with BY55 and BTLA. {ECO:0000269|PubMed:18193050}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:16169851}.
CC -!- SIMILARITY: Belongs to the tumor necrosis factor receptor superfamily.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tnfrsf14/";
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DR EMBL; U70321; AAB58354.1; -; mRNA.
DR EMBL; U81232; AAD00505.1; -; mRNA.
DR EMBL; AF153978; AAF75588.1; -; mRNA.
DR EMBL; AF373877; AAL47717.1; -; mRNA.
DR EMBL; AF373878; AAL47718.1; -; mRNA.
DR EMBL; AY358879; AAQ89238.1; -; mRNA.
DR EMBL; AK124010; BAG53992.1; -; mRNA.
DR EMBL; CR456909; CAG33190.1; -; mRNA.
DR EMBL; AY466111; AAR23264.1; -; Genomic_DNA.
DR EMBL; AL139246; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471183; EAW56089.1; -; Genomic_DNA.
DR EMBL; CH471183; EAW56090.1; -; Genomic_DNA.
DR EMBL; BC002794; AAH02794.1; -; mRNA.
DR EMBL; BC029848; AAH29848.1; -; mRNA.
DR CCDS; CCDS44046.1; -. [Q92956-1]
DR RefSeq; NP_003811.2; NM_003820.3. [Q92956-1]
DR RefSeq; XP_016858209.1; XM_017002720.1. [Q92956-2]
DR PDB; 1JMA; X-ray; 2.65 A; B=39-199.
DR PDB; 2AW2; X-ray; 2.80 A; B/Y=39-142.
DR PDB; 4FHQ; X-ray; 2.25 A; A=39-162.
DR PDB; 4RSU; X-ray; 2.30 A; D/E/F/J/K/L=39-162.
DR PDB; 5T2Q; X-ray; 1.90 A; A/B=39-142.
DR PDB; 5T2R; X-ray; 2.10 A; A/B=39-142.
DR PDB; 6NG3; X-ray; 2.88 A; A=39-143.
DR PDB; 7MSG; X-ray; 3.50 A; D/E/F=39-143.
DR PDBsum; 1JMA; -.
DR PDBsum; 2AW2; -.
DR PDBsum; 4FHQ; -.
DR PDBsum; 4RSU; -.
DR PDBsum; 5T2Q; -.
DR PDBsum; 5T2R; -.
DR PDBsum; 6NG3; -.
DR PDBsum; 7MSG; -.
DR AlphaFoldDB; Q92956; -.
DR SMR; Q92956; -.
DR BioGRID; 114298; 31.
DR DIP; DIP-34779N; -.
DR ELM; Q92956; -.
DR IntAct; Q92956; 31.
DR MINT; Q92956; -.
DR STRING; 9606.ENSP00000347948; -.
DR GlyGen; Q92956; 2 sites.
DR iPTMnet; Q92956; -.
DR PhosphoSitePlus; Q92956; -.
DR BioMuta; TNFRSF14; -.
DR DMDM; 13878821; -.
DR EPD; Q92956; -.
DR jPOST; Q92956; -.
DR MassIVE; Q92956; -.
DR PaxDb; Q92956; -.
DR PeptideAtlas; Q92956; -.
DR PRIDE; Q92956; -.
DR ProteomicsDB; 75630; -. [Q92956-1]
DR Antibodypedia; 1626; 804 antibodies from 45 providers.
DR CPTC; Q92956; 3 antibodies.
DR DNASU; 8764; -.
DR Ensembl; ENST00000355716.5; ENSP00000347948.4; ENSG00000157873.18. [Q92956-1]
DR Ensembl; ENST00000621877.3; ENSP00000478308.1; ENSG00000273936.4. [Q92956-1]
DR GeneID; 8764; -.
DR KEGG; hsa:8764; -.
DR MANE-Select; ENST00000355716.5; ENSP00000347948.4; NM_003820.4; NP_003811.2.
DR UCSC; uc001ajr.4; human. [Q92956-1]
DR CTD; 8764; -.
DR DisGeNET; 8764; -.
DR GeneCards; TNFRSF14; -.
DR HGNC; HGNC:11912; TNFRSF14.
DR HPA; ENSG00000157873; Low tissue specificity.
DR MIM; 602746; gene.
DR neXtProt; NX_Q92956; -.
DR OpenTargets; ENSG00000157873; -.
DR PharmGKB; PA36605; -.
DR VEuPathDB; HostDB:ENSG00000157873; -.
DR eggNOG; ENOG502S1XZ; Eukaryota.
DR GeneTree; ENSGT00940000162427; -.
DR InParanoid; Q92956; -.
DR OMA; LPWTRCS; -.
DR PhylomeDB; Q92956; -.
DR TreeFam; TF331157; -.
DR PathwayCommons; Q92956; -.
DR Reactome; R-HSA-388841; Costimulation by the CD28 family.
DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors.
DR SignaLink; Q92956; -.
DR SIGNOR; Q92956; -.
DR BioGRID-ORCS; 8764; 10 hits in 1066 CRISPR screens.
DR ChiTaRS; TNFRSF14; human.
DR EvolutionaryTrace; Q92956; -.
DR GeneWiki; TNFRSF14; -.
DR GenomeRNAi; 8764; -.
DR Pharos; Q92956; Tbio.
DR PRO; PR:Q92956; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q92956; protein.
DR Bgee; ENSG00000157873; Expressed in granulocyte and 95 other tissues.
DR ExpressionAtlas; Q92956; baseline and differential.
DR Genevisible; Q92956; HS.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0019955; F:cytokine binding; IPI:UniProtKB.
DR GO; GO:0005031; F:tumor necrosis factor receptor activity; TAS:ProtInc.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
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:0007166; P:cell surface receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IBA:GO_Central.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:1905675; P:negative regulation of adaptive immune memory response; IDA:UniProtKB.
DR GO; GO:0046642; P:negative regulation of alpha-beta T cell proliferation; IBA:GO_Central.
DR GO; GO:0002720; P:positive regulation of cytokine production involved in immune response; IBA:GO_Central.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IBA:GO_Central.
DR GO; GO:2000406; P:positive regulation of T cell migration; IBA:GO_Central.
DR GO; GO:0031295; P:T cell costimulation; IDA:UniProtKB.
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; 1.
DR PRINTS; PR01965; TNFACTORR14.
DR SMART; SM00208; TNFR; 3.
DR PROSITE; PS00652; TNFR_NGFR_1; 1.
DR PROSITE; PS50050; TNFR_NGFR_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Adaptive immunity; Alternative splicing; Cell membrane;
KW Direct protein sequencing; Disulfide bond; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Immunity;
KW Innate immunity; Membrane; Phosphoprotein; Receptor; Reference proteome;
KW Repeat; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..38
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 39..283
FT /note="Tumor necrosis factor receptor superfamily member
FT 14"
FT /id="PRO_0000034590"
FT TOPO_DOM 39..202
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 224..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 42..75
FT /note="TNFR-Cys 1"
FT REPEAT 78..119
FT /note="TNFR-Cys 2"
FT REPEAT 121..162
FT /note="TNFR-Cys 3"
FT MOD_RES 240
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT CARBOHYD 110
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16169851"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..53
FT /evidence="ECO:0000269|PubMed:16169851"
FT DISULFID 54..67
FT /evidence="ECO:0000269|PubMed:16169851"
FT DISULFID 57..75
FT /evidence="ECO:0000269|PubMed:16169851"
FT DISULFID 78..93
FT /evidence="ECO:0000269|PubMed:16169851"
FT DISULFID 96..111
FT /evidence="ECO:0000269|PubMed:16169851"
FT DISULFID 99..119
FT /evidence="ECO:0000269|PubMed:16169851"
FT DISULFID 121..138
FT /evidence="ECO:0000269|PubMed:16169851"
FT DISULFID 127..135
FT /evidence="ECO:0000269|PubMed:16169851"
FT VAR_SEQ 1..100
FT /note="MEPPGDWGPPPWRSTPKTDVLRLVLYLTFLGAPCYAPALPSCKEDEYPVGSE
FT CCPKCSPGYRVKEACGELTGTVCEPCPPGTYIAHLNGLSKCLQCQMCD -> MVSRPPR
FT TPLSPSSWT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_054186"
FT VARIANT 17
FT /note="K -> R (in dbSNP:rs4870)"
FT /evidence="ECO:0000269|PubMed:11756979,
FT ECO:0000269|PubMed:12975309, ECO:0000269|Ref.8"
FT /id="VAR_013007"
FT VARIANT 117
FT /note="A -> T (in dbSNP:rs2234163)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_018955"
FT VARIANT 174
FT /note="G -> E (in dbSNP:rs11573986)"
FT /evidence="ECO:0000269|Ref.8"
FT /id="VAR_018956"
FT VARIANT 241
FT /note="V -> I (in dbSNP:rs2234167)"
FT /evidence="ECO:0000269|PubMed:11756979, ECO:0000269|Ref.8"
FT /id="VAR_013440"
FT MUTAGEN 61
FT /note="Y->A: Abolishes cis interactions with BTLA."
FT /evidence="ECO:0000269|PubMed:19915044"
FT MUTAGEN 61
FT /note="Y->F: Does not affect cis interactions with BTLA."
FT /evidence="ECO:0000269|PubMed:19915044"
FT CONFLICT 135
FT /note="C -> R (in Ref. 10; AAH29848)"
FT /evidence="ECO:0000305"
FT STRAND 46..49
FT /evidence="ECO:0007829|PDB:5T2Q"
FT STRAND 52..55
FT /evidence="ECO:0007829|PDB:5T2Q"
FT STRAND 61..65
FT /evidence="ECO:0007829|PDB:5T2Q"
FT STRAND 69..71
FT /evidence="ECO:0007829|PDB:4RSU"
FT STRAND 74..77
FT /evidence="ECO:0007829|PDB:5T2Q"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:4RSU"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:5T2Q"
FT STRAND 105..109
FT /evidence="ECO:0007829|PDB:5T2Q"
FT STRAND 113..115
FT /evidence="ECO:0007829|PDB:4FHQ"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:5T2Q"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:5T2Q"
FT STRAND 134..139
FT /evidence="ECO:0007829|PDB:5T2Q"
SQ SEQUENCE 283 AA; 30392 MW; 46CE13C2C70242C1 CRC64;
MEPPGDWGPP PWRSTPKTDV LRLVLYLTFL GAPCYAPALP SCKEDEYPVG SECCPKCSPG
YRVKEACGEL TGTVCEPCPP GTYIAHLNGL SKCLQCQMCD PAMGLRASRN CSRTENAVCG
CSPGHFCIVQ DGDHCAACRA YATSSPGQRV QKGGTESQDT LCQNCPPGTF SPNGTLEECQ
HQTKCSWLVT KAGAGTSSSH WVWWFLSGSL VIVIVCSTVG LIICVKRRKP RGDVVKVIVS
VQRKRQEAEG EATVIEALQA PPDVTTVAVE ETIPSFTGRS PNH
