TNR4_HUMAN
ID TNR4_HUMAN Reviewed; 277 AA.
AC P43489; Q13663; Q2M312; Q5T7M0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Tumor necrosis factor receptor superfamily member 4;
DE AltName: Full=ACT35 antigen;
DE AltName: Full=OX40L receptor;
DE AltName: Full=TAX transcriptionally-activated glycoprotein 1 receptor;
DE AltName: CD_antigen=CD134;
DE Flags: Precursor;
GN Name=TNFRSF4; Synonyms=TXGP1L;
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].
RX PubMed=7510240; DOI=10.1002/eji.1830240329;
RA Latza U., Duerkop H., Schnittger S., Ringeling J., Eitelbach F., Hummel M.,
RA Fonatsch C., Stein H.;
RT "The human OX40 homolog: cDNA structure, expression and chromosomal
RT assignment of the ACT35 antigen.";
RL Eur. J. Immunol. 24:677-683(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=7704935;
RA Baum P.R., Gayle R.B. III, Ramsdell F., Srinivasan S., Sorensen R.A.,
RA Watson M.L., Seldin M.F., Clifford K.N., Grabstein K., Alderson M.R.;
RT "Identification of OX40 ligand and preliminary characterization of its
RT activities on OX40 receptor.";
RL Circ. Shock 44:30-34(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=10861060; DOI=10.4049/jimmunol.165.1.263;
RA Pankow R., Duerkop H., Latza U., Krause H., Kunzendorf U., Pohl T.,
RA Bulfone-Paus S.;
RT "The HTLV-I protein transcriptionally modulates OX40 antigen expression.";
RL J. Immunol. 165:263-270(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-10.
RG NIEHS SNPs program;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [7]
RP INTERACTION WITH TRAF1; TRAF2 AND TRAF3.
RX PubMed=9418902; DOI=10.1128/mcb.18.1.558;
RA Arch R.H., Thompson C.B.;
RT "4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth
RT factor receptor subfamily that bind TNF receptor-associated factors and
RT activate nuclear factor kappaB.";
RL Mol. Cell. Biol. 18:558-565(1998).
RN [8]
RP INTERACTION WITH TRAF2 AND TRAF5.
RX PubMed=9488716; DOI=10.1074/jbc.273.10.5808;
RA Kawamata S., Hori T., Imura A., Takaori-Kondo A., Uchiyama T.;
RT "Activation of OX40 signal transduction pathways leads to tumor necrosis
RT factor receptor-associated factor (TRAF) 2- and TRAF5-mediated NF-kappaB
RT activation.";
RL J. Biol. Chem. 273:5808-5814(1998).
RN [9]
RP FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH HUMAN
RP HERPESVIRUS-6B/HHV-6B GQ1:GQ2 PROTEINS.
RX PubMed=23674671; DOI=10.1073/pnas.1305187110;
RA Tang H., Serada S., Kawabata A., Ota M., Hayashi E., Naka T., Yamanishi K.,
RA Mori Y.;
RT "CD134 is a cellular receptor specific for human herpesvirus-6B entry.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:9096-9099(2013).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 29-170 IN COMPLEX WITH TNFSF4, AND
RP DISULFIDE BONDS.
RX PubMed=16905106; DOI=10.1016/j.str.2006.06.015;
RA Compaan D.M., Hymowitz S.G.;
RT "The crystal structure of the costimulatory OX40-OX40L complex.";
RL Structure 14:1321-1330(2006).
RN [11]
RP VARIANT IMD16 CYS-65.
RX PubMed=23897980; DOI=10.1084/jem.20130592;
RA Byun M., Ma C.S., Akcay A., Pedergnana V., Palendira U., Myoung J.,
RA Avery D.T., Liu Y., Abhyankar A., Lorenzo L., Schmidt M., Lim H.K.,
RA Cassar O., Migaud M., Rozenberg F., Canpolat N., Aydogan G.,
RA Fleckenstein B., Bustamante J., Picard C., Gessain A., Jouanguy E.,
RA Cesarman E., Olivier M., Gros P., Abel L., Croft M., Tangye S.G.,
RA Casanova J.L.;
RT "Inherited human OX40 deficiency underlying classic Kaposi sarcoma of
RT childhood.";
RL J. Exp. Med. 210:1743-1759(2013).
CC -!- FUNCTION: Receptor for TNFSF4/OX40L/GP34. Is a costimulatory molecule
CC implicated in long-term T-cell immunity. {ECO:0000269|PubMed:7704935}.
CC -!- FUNCTION: (Microbial infection) Acts as a receptor for human
CC herpesvirus 6B/HHV-6B. {ECO:0000269|PubMed:23674671}.
CC -!- SUBUNIT: Interacts with TRAF2, TRAF3 and TRAF5.
CC {ECO:0000269|PubMed:16905106, ECO:0000269|PubMed:9418902,
CC ECO:0000269|PubMed:9488716}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Human herpesvirus 6B/HHV-
CC 6B gQ1:gQ2 proteins. {ECO:0000269|PubMed:23674671}.
CC -!- INTERACTION:
CC P43489; P23510: TNFSF4; NbExp=2; IntAct=EBI-15596193, EBI-11724451;
CC -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
CC -!- DISEASE: Immunodeficiency 16 (IMD16) [MIM:615593]: An autosomal
CC recessive primary immunodeficiency associated with classic Kaposi
CC sarcoma of childhood and poor T-cell recall immune responses due to
CC complete functional OX40 deficiency. {ECO:0000269|PubMed:23897980}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB33944.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/tnfrsf4/";
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DR EMBL; X75962; CAA53576.1; -; mRNA.
DR EMBL; S76792; AAB33944.1; ALT_INIT; mRNA.
DR EMBL; AJ277151; CAB96543.1; -; Genomic_DNA.
DR EMBL; DQ118974; AAZ15374.1; -; Genomic_DNA.
DR EMBL; AL162741; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC105070; AAI05071.1; -; mRNA.
DR EMBL; BC105072; AAI05073.1; -; mRNA.
DR CCDS; CCDS11.1; -.
DR PIR; I37552; I37552.
DR RefSeq; NP_003318.1; NM_003327.3.
DR RefSeq; XP_016857721.1; XM_017002232.1.
DR PDB; 1D0A; X-ray; 2.00 A; G/H/I/J/K/L=262-266.
DR PDB; 2HEV; X-ray; 2.41 A; R=29-170.
DR PDB; 2HEY; X-ray; 2.00 A; R/T=29-170.
DR PDB; 6OGX; X-ray; 2.77 A; G=29-170.
DR PDB; 6OKM; X-ray; 2.10 A; R=29-170.
DR PDB; 6OKN; X-ray; 3.25 A; E/R=29-170.
DR PDBsum; 1D0A; -.
DR PDBsum; 2HEV; -.
DR PDBsum; 2HEY; -.
DR PDBsum; 6OGX; -.
DR PDBsum; 6OKM; -.
DR PDBsum; 6OKN; -.
DR AlphaFoldDB; P43489; -.
DR SMR; P43489; -.
DR BioGRID; 113144; 8.
DR DIP; DIP-3024N; -.
DR ELM; P43489; -.
DR IntAct; P43489; 2.
DR STRING; 9606.ENSP00000368538; -.
DR ChEMBL; CHEMBL3989383; -.
DR GuidetoPHARMACOLOGY; 1873; -.
DR GlyGen; P43489; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; P43489; -.
DR PhosphoSitePlus; P43489; -.
DR BioMuta; TNFRSF4; -.
DR DMDM; 1171933; -.
DR MassIVE; P43489; -.
DR PaxDb; P43489; -.
DR PeptideAtlas; P43489; -.
DR PRIDE; P43489; -.
DR ProteomicsDB; 55637; -.
DR ABCD; P43489; 67 sequenced antibodies.
DR Antibodypedia; 4246; 943 antibodies from 40 providers.
DR DNASU; 7293; -.
DR Ensembl; ENST00000379236.4; ENSP00000368538.3; ENSG00000186827.11.
DR GeneID; 7293; -.
DR KEGG; hsa:7293; -.
DR MANE-Select; ENST00000379236.4; ENSP00000368538.3; NM_003327.4; NP_003318.1.
DR UCSC; uc001ade.4; human.
DR CTD; 7293; -.
DR DisGeNET; 7293; -.
DR GeneCards; TNFRSF4; -.
DR HGNC; HGNC:11918; TNFRSF4.
DR HPA; ENSG00000186827; Tissue enhanced (lymphoid).
DR MalaCards; TNFRSF4; -.
DR MIM; 600315; gene.
DR MIM; 615593; phenotype.
DR neXtProt; NX_P43489; -.
DR OpenTargets; ENSG00000186827; -.
DR Orphanet; 431149; Combined immunodeficiency due to OX40 deficiency.
DR PharmGKB; PA36611; -.
DR VEuPathDB; HostDB:ENSG00000186827; -.
DR eggNOG; ENOG502SB1F; Eukaryota.
DR GeneTree; ENSGT00730000111452; -.
DR HOGENOM; CLU_092451_0_0_1; -.
DR InParanoid; P43489; -.
DR OMA; HFSPGDD; -.
DR OrthoDB; 1081476at2759; -.
DR PhylomeDB; P43489; -.
DR TreeFam; TF330135; -.
DR PathwayCommons; P43489; -.
DR Reactome; R-HSA-5669034; TNFs bind their physiological receptors.
DR SignaLink; P43489; -.
DR SIGNOR; P43489; -.
DR BioGRID-ORCS; 7293; 9 hits in 1069 CRISPR screens.
DR EvolutionaryTrace; P43489; -.
DR GeneWiki; CD134; -.
DR GenomeRNAi; 7293; -.
DR Pharos; P43489; Tchem.
DR PRO; PR:P43489; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P43489; protein.
DR Bgee; ENSG00000186827; Expressed in apex of heart and 92 other tissues.
DR Genevisible; P43489; HS.
DR GO; GO:0009986; C:cell surface; ISS:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005031; F:tumor necrosis factor receptor activity; IBA:GO_Central.
DR GO; GO:0001618; F:virus receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; IBA:GO_Central.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISS:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:BHF-UCL.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:BHF-UCL.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:BHF-UCL.
DR GO; GO:0042098; P:T cell proliferation; ISS:BHF-UCL.
DR CDD; cd13406; TNFRSF4; 1.
DR InterPro; IPR001368; TNFR/NGFR_Cys_rich_reg.
DR InterPro; IPR020445; TNFR_4.
DR InterPro; IPR034022; TNFRSF4_N.
DR PANTHER; PTHR47881; PTHR47881; 1.
DR Pfam; PF00020; TNFR_c6; 3.
DR PRINTS; PR01921; TNFACTORR4.
DR SMART; SM00208; TNFR; 3.
DR PROSITE; PS00652; TNFR_NGFR_1; 2.
DR PROSITE; PS50050; TNFR_NGFR_2; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Disease variant; Disulfide bond; Glycoprotein;
KW Host cell receptor for virus entry; Host-virus interaction; Membrane;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..277
FT /note="Tumor necrosis factor receptor superfamily member 4"
FT /id="PRO_0000034554"
FT TOPO_DOM 29..214
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 215..235
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 236..277
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 30..65
FT /note="TNFR-Cys 1"
FT REPEAT 66..107
FT /note="TNFR-Cys 2"
FT REPEAT 108..126
FT /note="TNFR-Cys 3; truncated"
FT REPEAT 127..167
FT /note="TNFR-Cys 4"
FT REGION 158..209
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 248..277
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 180..205
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 146
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 31..42
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206,
FT ECO:0000269|PubMed:16905106"
FT DISULFID 43..56
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206,
FT ECO:0000269|PubMed:16905106"
FT DISULFID 46..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206,
FT ECO:0000269|PubMed:16905106"
FT DISULFID 67..81
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206,
FT ECO:0000269|PubMed:16905106"
FT DISULFID 84..99
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206,
FT ECO:0000269|PubMed:16905106"
FT DISULFID 87..107
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206,
FT ECO:0000269|PubMed:16905106"
FT DISULFID 109..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206,
FT ECO:0000269|PubMed:16905106"
FT DISULFID 128..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206,
FT ECO:0000269|PubMed:16905106"
FT DISULFID 147..166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00206"
FT VARIANT 10
FT /note="R -> C (in dbSNP:rs35304565)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_025164"
FT VARIANT 65
FT /note="R -> C (in IMD16; dbSNP:rs587777075)"
FT /evidence="ECO:0000269|PubMed:23897980"
FT /id="VAR_070942"
FT STRAND 33..38
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 41..44
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:6OKM"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 77..79
FT /evidence="ECO:0007829|PDB:2HEY"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:6OGX"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 113..116
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:6OKN"
FT TURN 147..151
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 153..156
FT /evidence="ECO:0007829|PDB:2HEV"
FT STRAND 160..162
FT /evidence="ECO:0007829|PDB:2HEY"
FT STRAND 165..167
FT /evidence="ECO:0007829|PDB:2HEV"
SQ SEQUENCE 277 AA; 29341 MW; 49F15525941550BF CRC64;
MCVGARRLGR GPCAALLLLG LGLSTVTGLH CVGDTYPSND RCCHECRPGN GMVSRCSRSQ
NTVCRPCGPG FYNDVVSSKP CKPCTWCNLR SGSERKQLCT ATQDTVCRCR AGTQPLDSYK
PGVDCAPCPP GHFSPGDNQA CKPWTNCTLA GKHTLQPASN SSDAICEDRD PPATQPQETQ
GPPARPITVQ PTEAWPRTSQ GPSTRPVEVP GGRAVAAILG LGLVLGLLGP LAILLALYLL
RRDQRLPPDA HKPPGGGSFR TPIQEEQADA HSTLAKI
