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UniProtKB/Swiss-Prot entry O14763


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name TR10B_HUMAN
Primary accession number O14763
Secondary accession numbers O14720 O15508 O15517 O15531 Q6UXM8 Q9BVE0
Integrated into Swiss-Prot on September 26, 2001
Sequence was last modified on January 1, 1998 (Sequence version 1)
Annotations were last modified on    July 22, 2008 (Entry version 98)
Name and origin of the protein
Protein name Tumor necrosis factor receptor superfamily member 10B [Precursor]
Synonyms Death receptor 5
TNF-related apoptosis-inducing ligand receptor 2
TRAIL receptor 2
TRAIL-R2
CD262 antigen
Gene name
Name: TNFRSF10B
Synonyms: DR5, KILLER, TRAILR2, TRICK2, ZTNFR9
ORFNames: UNQ160/PRO186
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), AND PROTEIN SEQUENCE OF N-TERMINUS.
TISSUE=Foreskin fibroblast;
DOI=10.1093/emboj/16.17.5386; PubMed=9311998 [NCBI, ExPASy, EBI, Israel, Japan]
Walczak H., Degli-Esposti M.A., Johnson R.S., Smolak P.J., Waugh J.Y., Boiani N., Timour M.S., Gerhart M.J., Schooley K.A., Smith C.A., Goodwin R.G., Rauch C.T.;
"TRAIL-R2: a novel apoptosis-mediating receptor for TRAIL.";
EMBO J. 16:5386-5397(1997).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), ALTERNATIVE SPLICING, AND VARIANTS LEU-32 AND VAL-67.
DOI=10.1016/S0960-9822(06)00297-1; PubMed=9285725 [NCBI, ExPASy, EBI, Israel, Japan]
Screaton G.R., Mongkolsapaya J., Xu X.-N., Cowper A.E., McMichael A.J., Bell J.I.;
"TRICK2, a new alternatively spliced receptor that transduces the cytotoxic signal from TRAIL.";
Curr. Biol. 7:693-696(1997).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG), CHARACTERIZATION, AND VARIANTS LEU-32 AND VAL-67.
TISSUE=Liver, and Spleen;
DOI=10.1016/S0014-5793(97)01231-3; PubMed=9373179 [NCBI, ExPASy, EBI, Israel, Japan]
Schneider P., Bodmer J.-L., Thome M., Hofmann K., Holler N., Tschopp J.;
"Characterization of two receptors for TRAIL.";
FEBS Lett. 416:329-334(1997).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
TISSUE=Ovary;
DOI=10.1038/ng1097-141; PubMed=9326928 [NCBI, ExPASy, EBI, Israel, Japan]
Wu G.S., Burns T.F., McDonald E.R. III, Jiang W., Meng R., Krantz I.D., Kao G., Gan D.D., Zhou J.Y., Muschel R., Hamilton S.R., Spinner N.B., Markowitz S., Wu G., el-Deiry W.S.;
"KILLER/DR5 is a DNA damage-inducible p53-regulated death receptor gene.";
Nat. Genet. 17:141-143(1997).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
DOI=10.1126/science.277.5327.815; PubMed=9242610 [NCBI, ExPASy, EBI, Israel, Japan]
Pan G., Ni J., Wei Y.-F., Yu G.-L., Gentz R., Dixit V.M.;
"An antagonist decoy receptor and a death domain-containing receptor for TRAIL.";
Science 277:815-818(1997).
[6]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND VARIANTS LEU-32 AND VAL-67.
DOI=10.1074/jbc.272.41.25417; PubMed=9325248 [NCBI, ExPASy, EBI, Israel, Japan]
MacFarlane M., Ahmad M., Srinivasula S.M., Fernandes-Alnemri T., Cohen G.M., Alnemri E.S.;
"Identification and molecular cloning of two novel receptors for the cytotoxic ligand TRAIL.";
J. Biol. Chem. 272:25417-25420(1997).
[7]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND VARIANTS LEU-32 AND VAL-67.
DOI=10.1016/S1074-7613(00)80400-8; PubMed=9430227 [NCBI, ExPASy, EBI, Israel, Japan]
Chaudhary P.M., Eby M., Jasmin A., Bookwalter A., Murray J., Hood L.;
"Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway.";
Immunity 7:821-830(1997).
[8]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND VARIANT LEU-32.
DOI=10.1126/science.277.5327.818; PubMed=9242611 [NCBI, ExPASy, EBI, Israel, Japan]
Sheridan J.P., Marsters S.A., Pitti R.M., Gurney A., Skubatch M., Baldwin D.T., Ramakrishnan L., Gray C.L., Baker K., Wood W.I., Goddard A.D., Godowski P.J., Ashkenazi A.;
"Control of TRAIL-induced apoptosis by a family of signaling and decoy receptors.";
Science 277:818-821(1997).
[9]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND VARIANTS LEU-32 AND VAL-67.
DOI=10.1016/S0304-3835(98)00230-4; PubMed=10072170 [NCBI, ExPASy, EBI, Israel, Japan]
Arai T., Akiyama Y., Okabe S., Saito K., Iwai T., Yuasa Y.;
"Genomic organization and mutation analyses of the DR5/TRAIL receptor 2 gene in colorectal carcinomas.";
Cancer Lett. 133:197-204(1998).
[10]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
Cao X., Zhang W., Wan T.;
Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
[11]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND VARIANTS LEU-32 AND VAL-67.
Farrah T., Vu T., Gilbert T., Gross J., O'Hara P.;
"Homo sapiens homolog of tumor necrosis factor receptor.";
Submitted (OCT-1999) to the EMBL/GenBank/DDBJ databases.
[12]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM SHORT), AND VARIANT LEU-32.
DOI=10.1101/gr.1293003; PubMed=12975309 [NCBI, ExPASy, EBI, Israel, Japan]
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.";
Genome Res. 13:2265-2270(2003).
[13]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG), AND VARIANT LEU-32.
TISSUE=Cervix;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[14]
SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
DOI=10.1186/gb-2004-5-2-r8; PubMed=14759258 [NCBI, ExPASy, EBI, Israel, Japan]
Hillman R.T., Green R.E., Brenner S.E.;
"An unappreciated role for RNA surveillance.";
Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004).
[15]
X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 54-183.
DOI=10.1016/S1097-2765(00)80207-5; PubMed=10549288 [NCBI, ExPASy, EBI, Israel, Japan]
Hymowitz S.G., Christinger H.W., Fuh G., Ultsch M., O'Connell M., Kelley R.F., Ashkenazi A., de Vos A.M.;
"Triggering cell death: the crystal structure of Apo2L/TRAIL in a complex with death receptor 5.";
Mol. Cell 4:563-571(1999).
[16]
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 69-184.
DOI=10.1038/14935; PubMed=10542098 [NCBI, ExPASy, EBI, Israel, Japan]
Mongkolsapaya J., Grimes J.M., Chen N., Xu X.-N., Stuart D.I., Jones E.Y., Screaton G.R.;
"Structure of the TRAIL-DR5 complex reveals mechanisms conferring specificity in apoptotic initiation.";
Nat. Struct. Biol. 6:1048-1053(1999).
Comments
  • FUNCTION: Receptor for the cytotoxic ligand TNFSF10/TRAIL. The adapter molecule FADD recruits caspase-8 to the activated receptor. The resulting death-inducing signaling complex (DISC) performs caspase-8 proteolytic activation which initiates the subsequent cascade of caspases (aspartate-specific cysteine proteases) mediating apoptosis. Promotes the activation of NF-kappa-B.
  • SUBUNIT: Homotrimer. Can interact with TRADD and RIP.
  • SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    NameLong
    SynonymsTRICK2B
    Isoform IDO14763-1
    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
    This is the isoform sequence displayed in this entry.
    NameShort
    SynonymsTRICK2A
    Isoform IDO14763-2
    Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
    Features which should be applied to build the isoform sequence: VSP_006490.
  • TISSUE SPECIFICITY: Widely expressed in adult and fetal tissues; very highly expressed in tumor cell lines such as HeLa S3, K562, HL-60, SW480, A549 and G361; highly expressed in heart, peripheral blood lymphocytes, liver, pancreas, spleen, thymus, prostate, ovary, uterus, placenta, testis, esophagus, stomach and throughout the intestinal tract; not detectable in brain.
  • INDUCTION: TNFRSF10B is regulated by the tumor suppressor p53.
  • DISEASE: Defects in TNFRSF10B may be a cause of squamous cell carcinoma of the head and neck (HNSCC) [MIM:275355].
  • SIMILARITY: Contains 1 death domain.
  • SIMILARITY: Contains 3 TNFR-Cys repeats.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF016849; AAC51778.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF018657; AAB70577.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF018658; AAB70578.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF016266; AAB81180.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF022386; AAB71949.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF012628; AAB67109.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF020501; AAB71412.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF016268; AAC01565.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF012535; AAB67103.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB014718; BAA33723.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF153687; AAF75587.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AF192548; AAF07175.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AY358277; AAQ88644.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC001281; AAH01281.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
RefSeq NP_003833.3; -.
NP_671716.1; -.
UniGene Hs.521456
3D structure databases
PDB
1D0G; X-ray; 2.40 A; R/S/T=54-183.[ExPASy / RCSB / EBI]
1D4V; X-ray; 2.20 A; A=69-184.[ExPASy / RCSB / EBI]
1DU3; X-ray; 2.20 A; A/B/C/G/H/I=54-183.[ExPASy / RCSB / EBI]
1ZA3; X-ray; 3.35 A; R/S=54-183.[ExPASy / RCSB / EBI]
2H9G; X-ray; 2.32 A; R/S=54-183.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1D0G; -.
1D4V; -.
1DU3; -.
1ZA3; -.
2H9G; -.
SMR O14763; 69-184.
ModBase O14763.
Protein-protein interaction databases
IntAct O14763; -.
Enzyme and pathway databases
Reactome REACT_578; Apoptosis.
Organism-specific databases
H-InvDB HIX0021066; -.
HGNC HGNC:11905; TNFRSF10B.
GenAtlas TNFRSF10B.
MIM 275355; phenotype. [NCBI / EBI]
603612; gene. [NCBI / EBI]
Orphanet 67037; Squamous cell carcinoma of head and neck.
PharmGKB PA36598; -.
GeneCards O14763.
Gene expression databases
ArrayExpress O14763; -.
CleanEx HS_TNFRSF10B; -.
GermOnline ENSG00000120889; Homo sapiens.
Ontologies
GO
GO:0016021; Cellular component: integral to membrane (inferred by curator from UniProtKB).
GO:0005886; Cellular component: plasma membrane (inferred from experiment from Reactome).
GO:0008656; Molecular function: caspase activator activity (non-traceable author statement from UniProtKB).
GO:0004872; Molecular function: receptor activity (non-traceable author statement from UniProtKB).
GO:0045569; Molecular function: TRAIL binding (non-traceable author statement from UniProtKB).
GO:0007250; Biological process: activation of NF-kappaB-inducing kinase activity (non-traceable author statement from UniProtKB).
GO:0008633; Biological process: activation of pro-apoptotic gene products (inferred from experiment from Reactome).
GO:0006919; Biological process: caspase activation (non-traceable author statement from UniProtKB).
GO:0007166; Biological process: cell surface receptor linked signal transduction (traceable author statement from ProtInc).
GO:0008625; Biological process: induction of apoptosis via death domain receptors (non-traceable author statement from UniProtKB).
GO:0043123; Biological process: positive regulation of I-kappaB kinase/NF-kappaB cascade (inferred from expression pattern from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR000488; Death.
IPR011029; DEATH_like.
IPR017301; TNF-rel_apoptosis-ind_lig_rcpt.
IPR001368; TNFR_c6.
Graphical view of domain structure.
Gene3D G3DSA:1.10.533.10; DEATH_like; 1.
Pfam PF00531; Death; 1.
PF00020; TNFR_c6; 2.
Pfam graphical view of domain structure.
PIRSF PIRSF037867; CD261_antigen; 1.
SMART SM00005; DEATH; 1.
SM00208; TNFR; 2.
SMART graphical view of domain structure.
PROSITE PS50017; DEATH_DOMAIN; 1.
PS00652; TNFR_NGFR_1; 2.
PS50050; TNFR_NGFR_2; 2.
PROSITE graphical view of domain structure (profiles).
BLOCKS O14763.
Genome annotation databases
Ensembl ENSG00000120889; Homo sapiens. [Contig view]
GeneID 8795; -.
KEGG hsa:8795; -.
Phylogenomic databases
HOGENOM O14763; -.
HOVERGEN O14763; -.
Other
LinkHub O14763; -.
SOURCE TNFRSF10B; Homo sapiens.
ProtoNet O14763.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; Apoptosis; Direct protein sequencing; Membrane; Polymorphism; Receptor; Repeat; Signal; Transmembrane.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
SIGNAL   1    55  55      
CHAIN   56   440  385     Tumor necrosis factor receptor superfamily member 10B. PRO_0000034580
TOPO_DOM   56   210  155     Extracellular (Potential). 
TRANSMEM   211   231  21     Potential. 
TOPO_DOM   232   440  209     Cytoplasmic (Potential). 
REPEAT   57    94  38     TNFR-Cys 1. 
REPEAT   97   137  41     TNFR-Cys 2. 
REPEAT   138   178  41     TNFR-Cys 3. 
REPEAT   192   206  15     TAPE. 
DOMAIN   339   422  84     Death. 
COMPBIAS   250   253  4     Poly-Gly. 
DISULFID   81    94         
DISULFID   97   113         
DISULFID   116   129         
DISULFID   119   137         
DISULFID   139   153         
DISULFID   156   170         
DISULFID   160   178         
VAR_SEQ   185   213        Missing (in isoform Short). VSP_006490
VARIANT   32    32  1     P -> L (in dbSNP:rs1129424 [NCBI]). VAR_016153 
VARIANT   67    67  1     A -> V (in dbSNP:rs1047266 [NCBI]). VAR_016154 
CONFLICT   439   439        M -> L (in Ref. 8; AAB67103 and 12; AAQ88644). 
STRAND   85    87  3      
STRAND   89    92  4      
STRAND   94    96  3      
TURN   99   101  3      
STRAND   106   108  3      
STRAND   123   127  5      
STRAND   131   133  3      
STRAND   136   139  4      
STRAND   143   146  4      
STRAND   149   155  7      
STRAND   165   168  4      
STRAND   177   179  3      
Sequence information
Length: 440 AA [This is the length of the unprocessed precursor] Molecular weight: 47850 Da [This is the MW of the unprocessed precursor] CRC64: 603005AF2A8B4870 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MEQRGQNAPA ASGARKRHGP GPREARGARP GPRVPKTLVL VVAAVLLLVS AESALITQQD 

        70         80         90        100        110        120 
LAPQQRAAPQ QKRSSPSEGL CPPGHHISED GRDCISCKYG QDYSTHWNDL LFCLRCTRCD 

       130        140        150        160        170        180 
SGEVELSPCT TTRNTVCQCE EGTFREEDSP EMCRKCRTGC PRGMVKVGDC TPWSDIECVH 

       190        200        210        220        230        240 
KESGTKHSGE APAVEETVTS SPGTPASPCS LSGIIIGVTV AAVVLIVAVF VCKSLLWKKV 

       250        260        270        280        290        300 
LPYLKGICSG GGGDPERVDR SSQRPGAEDN VLNEIVSILQ PTQVPEQEME VQEPAEPTGV 

       310        320        330        340        350        360 
NMLSPGESEH LLEPAEAERS QRRRLLVPAN EGDPTETLRQ CFDDFADLVP FDSWEPLMRK 

       370        380        390        400        410        420 
LGLMDNEIKV AKAEAAGHRD TLYTMLIKWV NKTGRDASVH TLLDALETLG ERLAKQKIED 

       430        440 
HLLSSGKFMY LEGNADSAMS 

O14763 in FASTA format

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