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O00220

- TR10A_HUMAN

UniProt

O00220 - TR10A_HUMAN

Protein

Tumor necrosis factor receptor superfamily member 10A

Gene

TNFRSF10A

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 141 (01 Oct 2014)
      Sequence version 3 (30 Nov 2010)
      Previous versions | rss
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    Functioni

    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.1 Publication

    GO - Molecular functioni

    1. death receptor activity Source: ProtInc
    2. protease binding Source: UniProtKB
    3. protein binding Source: UniProtKB
    4. receptor activity Source: UniProtKB
    5. TRAIL binding Source: UniProtKB
    6. transcription factor binding Source: UniProtKB

    GO - Biological processi

    1. activation of NF-kappaB-inducing kinase activity Source: UniProtKB
    2. apoptotic process Source: UniProtKB
    3. cellular response to mechanical stimulus Source: UniProtKB
    4. extrinsic apoptotic signaling pathway Source: UniProtKB
    5. extrinsic apoptotic signaling pathway via death domain receptors Source: UniProtKB
    6. signal transduction Source: ProtInc
    7. TRAIL-activated apoptotic signaling pathway Source: ParkinsonsUK-UCL

    Keywords - Molecular functioni

    Receptor

    Keywords - Biological processi

    Apoptosis

    Enzyme and pathway databases

    SignaLinkiO00220.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tumor necrosis factor receptor superfamily member 10A
    Alternative name(s):
    Death receptor 4
    TNF-related apoptosis-inducing ligand receptor 1
    Short name:
    TRAIL receptor 1
    Short name:
    TRAIL-R1
    CD_antigen: CD261
    Gene namesi
    Name:TNFRSF10A
    Synonyms:APO2, DR4, TRAILR1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:11904. TNFRSF10A.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA36597.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 2323Sequence AnalysisAdd
    BLAST
    Chaini24 – 468445Tumor necrosis factor receptor superfamily member 10APRO_0000034579Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi132 ↔ 145PROSITE-ProRule annotation
    Disulfide bondi148 ↔ 164PROSITE-ProRule annotation
    Glycosylationi156 – 1561N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi167 ↔ 180PROSITE-ProRule annotation
    Disulfide bondi170 ↔ 188PROSITE-ProRule annotation
    Disulfide bondi190 ↔ 204PROSITE-ProRule annotation
    Disulfide bondi207 ↔ 221PROSITE-ProRule annotation
    Disulfide bondi211 ↔ 229PROSITE-ProRule annotation
    Modified residuei463 – 4631Phosphoserine1 Publication
    Modified residuei466 – 4661Phosphoserine2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiO00220.
    PaxDbiO00220.
    PRIDEiO00220.

    PTM databases

    PhosphoSiteiO00220.

    Expressioni

    Tissue specificityi

    Widely expressed. High levels are found in spleen, peripheral blood leukocytes, small intestine and thymus, but also in K-562 erythroleukemia cells, MCF-7 breast carcinoma cells and activated T-cells.

    Gene expression databases

    ArrayExpressiO00220.
    BgeeiO00220.
    CleanExiHS_TNFRSF10A.
    GenevestigatoriO00220.

    Organism-specific databases

    HPAiHPA054475.

    Interactioni

    Subunit structurei

    Can interact with TRADD and RIPK1. Interacts with ARAP1.1 Publication

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ARAP1Q96P484EBI-518861,EBI-710003
    CASP8Q147909EBI-518861,EBI-78060
    TNFSF10P505914EBI-518861,EBI-495373

    Protein-protein interaction databases

    BioGridi114325. 14 interactions.
    IntActiO00220. 11 interactions.
    MINTiMINT-99073.
    STRINGi9606.ENSP00000221132.

    Structurei

    3D structure databases

    ProteinModelPortaliO00220.
    SMRiO00220. Positions 131-233.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini24 – 239216ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini263 – 468206CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei240 – 26223HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati107 – 14539TNFR-Cys 1Add
    BLAST
    Repeati147 – 18842TNFR-Cys 2Add
    BLAST
    Repeati189 – 22941TNFR-Cys 3Add
    BLAST
    Domaini365 – 44884DeathPROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi29 – 324Poly-Ala

    Sequence similaritiesi

    Contains 1 death domain.PROSITE-ProRule annotation
    Contains 3 TNFR-Cys repeats.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Signal, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG131298.
    HOGENOMiHOG000142423.
    HOVERGENiHBG061626.
    InParanoidiO00220.
    KOiK04722.
    OMAiNTACQCK.
    OrthoDBiEOG71VSSN.
    PhylomeDBiO00220.
    TreeFamiTF333916.

    Family and domain databases

    Gene3Di1.10.533.10. 1 hit.
    InterProiIPR011029. DEATH-like_dom.
    IPR000488. Death_domain.
    IPR001368. TNFR/NGFR_Cys_rich_reg.
    IPR020465. TNFR_10.
    [Graphical view]
    PfamiPF00531. Death. 1 hit.
    PF00020. TNFR_c6. 2 hits.
    [Graphical view]
    PIRSFiPIRSF037867. CD261_antigen. 1 hit.
    PRINTSiPR01956. TNFACTORR10.
    SMARTiSM00005. DEATH. 1 hit.
    SM00208. TNFR. 2 hits.
    [Graphical view]
    SUPFAMiSSF47986. SSF47986. 1 hit.
    PROSITEiPS50017. DEATH_DOMAIN. 1 hit.
    PS00652. TNFR_NGFR_1. 2 hits.
    PS50050. TNFR_NGFR_2. 2 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    O00220-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAPPPARVHL GAFLAVTPNP GSAASGTEAA AATPSKVWGS SAGRIEPRGG    50
    GRGALPTSMG QHGPSARARA GRAPGPRPAR EASPRLRVHK TFKFVVVGVL 100
    LQVVPSSAAT IKLHDQSIGT QQWEHSPLGE LCPPGSHRSE HPGACNRCTE 150
    GVGYTNASNN LFACLPCTAC KSDEEERSPC TTTRNTACQC KPGTFRNDNS 200
    AEMCRKCSRG CPRGMVKVKD CTPWSDIECV HKESGNGHNI WVILVVTLVV 250
    PLLLVAVLIV CCCIGSGCGG DPKCMDRVCF WRLGLLRGPG AEDNAHNEIL 300
    SNADSLSTFV SEQQMESQEP ADLTGVTVQS PGEAQCLLGP AEAEGSQRRR 350
    LLVPANGADP TETLMLFFDK FANIVPFDSW DQLMRQLDLT KNEIDVVRAG 400
    TAGPGDALYA MLMKWVNKTG RNASIHTLLD ALERMEERHA REKIQDLLVD 450
    SGKFIYLEDG TGSAVSLE 468
    Length:468
    Mass (Da):50,089
    Last modified:November 30, 2010 - v3
    Checksum:i7E96619D0BDC0CD4
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti281 – 2811W → C in BAF83988. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti11 – 111G → V.
    Corresponds to variant rs34737614 [ dbSNP | Ensembl ].
    VAR_052349
    Natural varianti33 – 331T → I.
    Corresponds to variant rs20577 [ dbSNP | Ensembl ].
    VAR_016149
    Natural varianti105 – 1051P → R.
    Corresponds to variant rs11986840 [ dbSNP | Ensembl ].
    VAR_052350
    Natural varianti141 – 1411H → R.2 Publications
    Corresponds to variant rs6557634 [ dbSNP | Ensembl ].
    VAR_016150
    Natural varianti209 – 2091R → T.2 Publications
    Corresponds to variant rs20575 [ dbSNP | Ensembl ].
    VAR_016151
    Natural varianti228 – 2281E → A.
    Corresponds to variant rs20576 [ dbSNP | Ensembl ].
    VAR_016152
    Natural varianti297 – 2971N → H.
    Corresponds to variant rs17088980 [ dbSNP | Ensembl ].
    VAR_052351
    Natural varianti441 – 4411R → K.5 Publications
    Corresponds to variant rs2230229 [ dbSNP | Ensembl ].
    VAR_052352

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U90875 mRNA. Translation: AAC51226.1.
    BT006906 mRNA. Translation: AAP35552.1.
    AK291299 mRNA. Translation: BAF83988.1.
    EF064713 Genomic DNA. Translation: ABK41896.1.
    AC100861 Genomic DNA. No translation available.
    BC012866 mRNA. Translation: AAH12866.1.
    CCDSiCCDS6039.1.
    RefSeqiNP_003835.3. NM_003844.3.
    UniGeneiHs.213467.
    Hs.591834.

    Genome annotation databases

    EnsembliENST00000221132; ENSP00000221132; ENSG00000104689.
    GeneIDi8797.
    KEGGihsa:8797.
    UCSCiuc003xda.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U90875 mRNA. Translation: AAC51226.1 .
    BT006906 mRNA. Translation: AAP35552.1 .
    AK291299 mRNA. Translation: BAF83988.1 .
    EF064713 Genomic DNA. Translation: ABK41896.1 .
    AC100861 Genomic DNA. No translation available.
    BC012866 mRNA. Translation: AAH12866.1 .
    CCDSi CCDS6039.1.
    RefSeqi NP_003835.3. NM_003844.3.
    UniGenei Hs.213467.
    Hs.591834.

    3D structure databases

    ProteinModelPortali O00220.
    SMRi O00220. Positions 131-233.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 114325. 14 interactions.
    IntActi O00220. 11 interactions.
    MINTi MINT-99073.
    STRINGi 9606.ENSP00000221132.

    Chemistry

    BindingDBi O00220.
    ChEMBLi CHEMBL3551.
    GuidetoPHARMACOLOGYi 1879.

    PTM databases

    PhosphoSitei O00220.

    Proteomic databases

    MaxQBi O00220.
    PaxDbi O00220.
    PRIDEi O00220.

    Protocols and materials databases

    DNASUi 8797.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000221132 ; ENSP00000221132 ; ENSG00000104689 .
    GeneIDi 8797.
    KEGGi hsa:8797.
    UCSCi uc003xda.3. human.

    Organism-specific databases

    CTDi 8797.
    GeneCardsi GC08M023048.
    H-InvDB HIX0022944.
    HGNCi HGNC:11904. TNFRSF10A.
    HPAi HPA054475.
    MIMi 603611. gene.
    neXtProti NX_O00220.
    PharmGKBi PA36597.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG131298.
    HOGENOMi HOG000142423.
    HOVERGENi HBG061626.
    InParanoidi O00220.
    KOi K04722.
    OMAi NTACQCK.
    OrthoDBi EOG71VSSN.
    PhylomeDBi O00220.
    TreeFami TF333916.

    Enzyme and pathway databases

    SignaLinki O00220.

    Miscellaneous databases

    GeneWikii TNFRSF10A.
    GenomeRNAii 8797.
    NextBioi 32996.
    PROi O00220.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O00220.
    Bgeei O00220.
    CleanExi HS_TNFRSF10A.
    Genevestigatori O00220.

    Family and domain databases

    Gene3Di 1.10.533.10. 1 hit.
    InterProi IPR011029. DEATH-like_dom.
    IPR000488. Death_domain.
    IPR001368. TNFR/NGFR_Cys_rich_reg.
    IPR020465. TNFR_10.
    [Graphical view ]
    Pfami PF00531. Death. 1 hit.
    PF00020. TNFR_c6. 2 hits.
    [Graphical view ]
    PIRSFi PIRSF037867. CD261_antigen. 1 hit.
    PRINTSi PR01956. TNFACTORR10.
    SMARTi SM00005. DEATH. 1 hit.
    SM00208. TNFR. 2 hits.
    [Graphical view ]
    SUPFAMi SSF47986. SSF47986. 1 hit.
    PROSITEi PS50017. DEATH_DOMAIN. 1 hit.
    PS00652. TNFR_NGFR_1. 2 hits.
    PS50050. TNFR_NGFR_2. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ARG-141; THR-209 AND LYS-441.
    2. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-441.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ARG-141; THR-209 AND LYS-441.
      Tissue: Tongue.
    4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-441.
    5. "DNA sequence and analysis of human chromosome 8."
      Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
      , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
      Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-441.
      Tissue: Ovary.
    7. "Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway."
      Chaudhary P.M., Eby M., Jasmin A., Bookwalter A., Murray J., Hood L.
      Immunity 7:821-830(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    8. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-466, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    9. "Arf and Rho GAP adapter protein ARAP1 participates in the mobilization of TRAIL-R1/DR4 to the plasma membrane."
      Simova S., Klima M., Cermak L., Sourkova V., Andera L.
      Apoptosis 13:423-436(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARAP1.
    10. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463 AND SER-466, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.

    Entry informationi

    Entry nameiTR10A_HUMAN
    AccessioniPrimary (citable) accession number: O00220
    Secondary accession number(s): A8K5I4, Q53Y72, Q96E62
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: September 26, 2001
    Last sequence update: November 30, 2010
    Last modified: October 1, 2014
    This is version 141 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 8
      Human chromosome 8: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3