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 24-JAN-2024, entry version 227. 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}; GN 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. 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; 32. DR DIP; DIP-34779N; -. DR ELM; Q92956; -. DR IntAct; Q92956; 31. DR MINT; Q92956; -. DR STRING; 9606.ENSP00000347948; -. DR GlyCosmos; Q92956; 2 sites, No reported glycans. DR GlyGen; Q92956; 3 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q92956; -. DR PhosphoSitePlus; Q92956; -. DR BioMuta; TNFRSF14; -. DR DMDM; 13878821; -. DR CPTAC; CPTAC-5985; -. DR EPD; Q92956; -. DR jPOST; Q92956; -. DR MassIVE; Q92956; -. DR PaxDb; 9606-ENSP00000347948; -. DR PeptideAtlas; Q92956; -. DR ProteomicsDB; 75630; -. [Q92956-1] DR Antibodypedia; 1626; 866 antibodies from 46 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 AGR; HGNC:11912; -. 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; GWELPPW; -. DR OrthoDB; 24515at2759; -. 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; 12 hits in 1154 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 97 other cell types or tissues. DR ExpressionAtlas; Q92956; baseline and differential. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. 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 Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 3. DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg. DR InterPro; IPR022332; TNFR_14. DR InterPro; IPR034031; TNFRSF14/UL144_N. DR PANTHER; PTHR46838; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 14; 1. DR PANTHER; PTHR46838:SF1; TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY MEMBER 14; 1. DR Pfam; PF00020; TNFR_c6; 1. DR PRINTS; PR01965; TNFACTORR14. DR SMART; SM00208; TNFR; 3. DR SUPFAM; SSF57586; TNF receptor-like; 2. DR PROSITE; PS00652; TNFR_NGFR_1; 1. DR PROSITE; PS50050; TNFR_NGFR_2; 2. DR Genevisible; Q92956; HS. 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 //