ID TNR14_HUMAN Reviewed; 283 AA.
AC Q92956; B9DI89; Q6IB95; Q8WXR1; Q96J31; Q9UM65;
DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-APR-2001, sequence version 3.
DT 01-MAY-2013, entry version 148.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 14;
DE AltName: Full=Herpes virus entry mediator A;
DE Short=Herpesvirus entry mediator A;
DE Short=HveA;
DE AltName: Full=Tumor necrosis factor receptor-like 2;
DE Short=TR2;
DE AltName: CD_antigen=CD270;
DE Flags: Precursor;
GN Name=TNFRSF14; Synonyms=HVEA, HVEM; ORFNames=UNQ329/PRO509;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION AS A RECEPTOR FOR 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
RT the TNF/NGF receptor family.";
RL Cell 87:427-436(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
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
RT lymphocyte activation.";
RL J. Biol. Chem. 272:14272-14276(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Zhang W., Wan T., Cao X.;
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA], 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.,
RA 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], 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.,
RA Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J.,
RA Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J.,
RA Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A.,
RA Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H.,
RA Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D.,
RA Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale
RT effort to identify novel human secreted and transmembrane proteins: a
RT bioinformatics assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-17; THR-117;
RP GLU-174 AND ILE-241.
RG NIEHS SNPs program;
RL Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
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.,
RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
RA 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.,
RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
RA 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.,
RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
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
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [12]
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 [13]
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.,
RA Ashkenazi A.;
RT "Herpesvirus entry mediator, a member of the tumor necrosis factor
RT receptor (TNFR) family, interacts with members of the TNFR-associated
RT factor family and activates the transcription factors NF-kappaB and
RT AP-1.";
RL J. Biol. Chem. 272:14029-14032(1997).
RN [14]
RP INTERACTION WITH HHV-1 AND HHV-2 GLYCOPROTEIN D.
RX PubMed=9696799;
RA Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W.,
RA Lambris J.D., 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
RT unrelated mediators of virus entry.";
RL J. Virol. 72:7064-7074(1998).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 39-200 IN COMPLEX WITH HUMAN
RP HERPESVIRUS 1 GLYCOPROTEIN.
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
RT HveA.";
RL Mol. Cell 8:169-179(2001).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 26-137 IN COMPLEX WITH BTLA,
RP AND GLYCOSYLATION AT ASN-110.
RX PubMed=16169851; DOI=10.1074/jbc.M507629200;
RA Compaan D.M., Gonzalez L.C., Tom I., Loyet K.M., Eaton D.,
RA Hymowitz S.G.;
RT "Attenuating lymphocyte activity: the crystal structure of the BTLA-
RT HVEM complex.";
RL J. Biol. Chem. 280:39553-39561(2005).
CC -!- FUNCTION: Receptor for BTLA. Receptor for TNFSF14/LIGHT and
CC homotrimeric TNFSF1/lymphotoxin-alpha. Involved in lymphocyte
CC activation. Plays an important role in HSV pathogenesis because it
CC enhanced the entry of several wild-type HSV strains of both
CC serotypes into CHO cells, and mediated HSV entry into activated
CC human T-cells.
CC -!- SUBUNIT: Interacts with TRAF2, TRAF3 and TRAF5. Interacts with
CC herpes simplex virus 1 (HHV-1) and herpes simplex virus 1 (HHV-2)
CC envelope glycoprotein D; functions as an entry receptor for these
CC viruses.
CC -!- INTERACTION:
CC O43557:TNFSF14; NbExp=2; IntAct=EBI-1056653, EBI-524131;
CC Q12933-2:TRAF2; NbExp=4; IntAct=EBI-1056653, EBI-355760;
CC O00463:TRAF5; NbExp=5; IntAct=EBI-1056653, EBI-523498;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC protein (Probable).
CC -!- TISSUE SPECIFICITY: Widely expressed, with the highest expression
CC in lung, spleen and thymus.
CC -!- PTM: N-glycosylated.
CC -!- SIMILARITY: Contains 3 TNFR-Cys repeats.
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; CR456909; CAG33190.1; -; mRNA.
DR EMBL; AY466111; AAR23264.1; -; Genomic_DNA.
DR EMBL; AL139246; CAX30824.1; -; Genomic_DNA.
DR EMBL; CH471183; EAW56089.1; -; Genomic_DNA.
DR EMBL; BC002794; AAH02794.1; -; mRNA.
DR IPI; IPI00024331; -.
DR RefSeq; NP_003811.2; NM_003820.2.
DR UniGene; Hs.512898; -.
DR PDB; 1JMA; X-ray; 2.65 A; B=39-200.
DR PDB; 2AW2; X-ray; 2.80 A; B/Y=39-142.
DR PDB; 4FHQ; X-ray; 2.25 A; A=39-162.
DR PDBsum; 1JMA; -.
DR PDBsum; 2AW2; -.
DR PDBsum; 4FHQ; -.
DR ProteinModelPortal; Q92956; -.
DR DIP; DIP-34779N; -.
DR DIP; DIP-6233N; -.
DR IntAct; Q92956; 16.
DR MINT; MINT-208002; -.
DR STRING; 9606.ENSP00000347948; -.
DR DMDM; 13878821; -.
DR PaxDb; Q92956; -.
DR PRIDE; Q92956; -.
DR DNASU; 8764; -.
DR Ensembl; ENST00000355716; ENSP00000347948; ENSG00000157873.
DR GeneID; 8764; -.
DR KEGG; hsa:8764; -.
DR UCSC; uc001ajr.3; human.
DR CTD; 8764; -.
DR GeneCards; GC01P002487; -.
DR HGNC; HGNC:11912; TNFRSF14.
DR HPA; CAB026150; -.
DR HPA; CAB030007; -.
DR HPA; HPA006404; -.
DR MIM; 602746; gene.
DR neXtProt; NX_Q92956; -.
DR PharmGKB; PA36605; -.
DR eggNOG; NOG40150; -.
DR HOGENOM; HOG000065766; -.
DR HOVERGEN; HBG072084; -.
DR InParanoid; Q92956; -.
DR KO; K05152; -.
DR OMA; GHFCIVQ; -.
DR PhylomeDB; Q92956; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; TNFRSF14; human.
DR EvolutionaryTrace; Q92956; -.
DR GenomeRNAi; 8764; -.
DR NextBio; 32872; -.
DR ArrayExpress; Q92956; -.
DR Bgee; Q92956; -.
DR CleanEx; HS_TNFRSF14; -.
DR Genevestigator; Q92956; -.
DR GermOnline; ENSG00000157873; Homo sapiens.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Compara.
DR GO; GO:0005887; C:integral to plasma membrane; IC:ProtInc.
DR GO; GO:0005031; F:tumor necrosis factor-activated receptor activity; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0046642; P:negative regulation of alpha-beta T cell proliferation; IEA:Compara.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IEA:Compara.
DR GO; GO:0031295; P:T cell costimulation; TAS:Reactome.
DR GO; GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR022332; TNFR_14.
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; Complete proteome; Direct protein sequencing;
KW Disulfide bond; Glycoprotein; Host cell receptor for virus entry;
KW Host-virus interaction; Membrane; Polymorphism; Receptor;
KW Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1 38
FT CHAIN 39 283 Tumor necrosis factor receptor
FT superfamily member 14.
FT /FTId=PRO_0000034590.
FT TOPO_DOM 39 202 Extracellular (Potential).
FT TRANSMEM 203 223 Helical; (Potential).
FT TOPO_DOM 224 283 Cytoplasmic (Potential).
FT REPEAT 42 75 TNFR-Cys 1.
FT REPEAT 78 119 TNFR-Cys 2.
FT REPEAT 121 162 TNFR-Cys 3.
FT CARBOHYD 110 110 N-linked (GlcNAc...).
FT CARBOHYD 173 173 N-linked (GlcNAc...) (Potential).
FT DISULFID 42 53
FT DISULFID 54 67
FT DISULFID 57 75
FT DISULFID 78 93
FT DISULFID 96 111
FT DISULFID 99 119
FT DISULFID 121 138
FT DISULFID 127 135
FT VARIANT 17 17 K -> R (in dbSNP:rs4870).
FT /FTId=VAR_013007.
FT VARIANT 117 117 A -> T (in dbSNP:rs2234163).
FT /FTId=VAR_018955.
FT VARIANT 174 174 G -> E (in dbSNP:rs11573986).
FT /FTId=VAR_018956.
FT VARIANT 241 241 V -> I (in dbSNP:rs2234167).
FT /FTId=VAR_013440.
FT STRAND 46 49
FT STRAND 52 55
FT STRAND 61 65
FT STRAND 69 71
FT STRAND 74 77
FT STRAND 86 88
FT HELIX 101 103
FT STRAND 105 109
FT STRAND 113 115
FT STRAND 118 121
FT STRAND 125 131
FT STRAND 134 140
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
//
